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Anti-Cancer Activity of Cow Urine: Current Status and Future Directions

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Abstract

Cow urine has a unique place in Ayurveda and has been described in ‘Sushrita Samhita’ and ‘Ashtanga Sangraha’ to be the most effective substance/secretion of animal origin with innumerable therapeutic values. It has been recognized as water of life or “Amrita” (beverages of immotality), the nector of the God. In India, drinking of cow urine has been practiced for thousands of years. It is an important ingredient of panchgavya, a term used to describe five major substances (urine, milk, ghee, curd and dung), obtained from cow. All the five products possess medicinal properties, and are used singly or in combination with some other herbs against many diseases, even those not curable by allopathic treatments. This kind of alternative treatment, termed as ‘panchgavya therapy’ or ‘cowpathy’, has been reported to be beneficial even for dreaded diseases like cancer, AIDS and diabetes. Practitioners of Ayurvedic medicine from India routinely use cow urine as a remedy and the medicines made from it are used to cure several diseases. Improvements have been shown or reported with those suffering from flu, allergies, colds, rheumatoid arthritis, bacterial/viral infections, tuberculosis, chicken pox, hepatitis, leucorrhoea, leprosy, ulcer, heart disease, asthma, skin infections, aging, chemical intoxication etc. Cow urine can kill the number of drug resistant bacteria and viruses. Recently the cow urine has been granted U.S. Patents (No. 6896907 and 6,410,059) for its medicinal properties, particularly for its use along with antibiotics for the control of bacterial infection and fight against cancers. Through extensive research studies a cow urine distillate fraction, popularly known as ‘ark’, has been identified as a bioenhancer of the activities of commonly used antibiotics, anti- fungal and anti-cancer drugs. Thus it can promote and augment the bioactivity or bioavailability or the uptake of drugs in combination therapy and reduce the dose and duration of treatment. These milestone achievements highlight the beneficial role of cow urine in treating bacterial infections and cancers and that cow urine enhances the efficacy and potency of therapeutic drugs. During the past few years cow urine therapy has provided promising and authentic results for the treatment of cancer, a deadly malady which is being faced by the mankind and the incidences of which are ever increasing in the current scenario of changed lifestyle and food habbits along with exposure to predisposing factors of carcinogens such as tobacco chewing, smoking, alcohol intake, environmental pollutants, occupational health hazards etc. Anti-cancer potential of cow urine therapy has been reflected by several case reports, success stories and practical feed back of patients for the treatment of cancer. Cow urine enhances the immunocompetence and improves general health of an individual; prevent the free radicals formation and act as anti-aging factor; reduces apoptosis in lymphocytes and helps them to survive; and efficiently repairs the damaged DNA, thus is effective for the cancer therapy. Experimentally it has been proved that among all sorts of urines, the urine of the Indian cows is most effective. Seeing the potential use of indigenous cow urine in several ailments including even the cancer, the use of Gomutra (cow urine) of indigenous breeds of cattle should be promoted extensively. However, scientific validation of cow urine therapy is required for its worldwide acceptance and popularity. This review highlights the anti-cancer activity of cow urine and the strategies for promoting its vital medicinal potential and prospectives for the benefit of mankind with the view that cow urine therapy needs immediate attention, promotion, and wide popularity and proper support of the scientists, researchers and clinicians to strengthen this alternate low cost therapy having no side effects, as generally observed with chemotherapy and radiation therapy being followed for curing cancers, and thus inspire confidence in the public about its good virtues.
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International Journal of Cow Science, 1(2): 1-25
REVIEW ARTICLE
© 2005, Cow Therapy Society, Pantnagar, India. 0973-2241/05/$5.0
ANTI-CANCER ACTIVITY OF COW URINE: CURRENT STATUS
AND FUTURE DIRECTIONS
K. DHAMA
1
, R.S. CHAUHAN
2
AND LOKESH SINGHAL
2
Indian Veterinary Research Institute, Izatnagar (U.P.)- 243 122, INDIA
Abstract
Cow urine has a unique place in Ayurveda and has been described in ‘Sushrita Samhita’ and
‘Ashtanga Sangraha’ to be the most effective substance/secretion of animal origin with innumerable
therapeutic values. It has been recognized as water of life or “Amrita” (beverages of immotality), the
nector of the God. In India, drinking of cow urine has been practiced for thousands of years. It is an
important ingredient of panchgavya, a term used to describe five major substances (urine, milk,
ghee, curd and dung), obtained from cow. All the five products possess medicinal properties, and
are used singly or in combination with some other herbs against many diseases, even those not
curable by allopathic treatments. This kind of alternative treatment, termed as ‘panchgavya therapy’
or ‘cowpathy’, has been reported to be beneficial even for dreaded diseases like cancer, AIDS and
diabetes. Practitioners of Ayurvedic medicine from India routinely use cow urine as a remedy and
the medicines made from it are used to cure several diseases. Improvements have been shown or
reported with those suffering from flu, allergies, colds, rheumatoid arthritis, bacterial/viral infections,
tuberculosis, chicken pox, hepatitis, leucorrhoea, leprosy, ulcer, heart disease, asthma, skin infections,
aging, chemical intoxication etc. Cow urine can kill the number of drug resistant bacteria and viruses.
Recently the cow urine has been granted U.S. Patents (No. 6896907 and 6,410,059) for its medicinal
properties, particularly for its use along with antibiotics for the control of bacterial infection and fight
against cancers. Through extensive research studies a cow urine distillate fraction, popularly known
as ‘ark’, has been identified as a bioenhancer of the activities of commonly used antibiotics, anti-
fungal and anti-cancer drugs. Thus it can promote and augment the bioactivity or bioavailability or
the uptake of drugs in combination therapy and reduce the dose and duration of treatment. These
milestone achievements highlight the beneficial role of cow urine in treating bacterial infections and
cancers and that cow urine enhances the efficacy and potency of therapeutic drugs. During the past
few years cow urine therapy has provided promising and authentic results for the treatment of
cancer, a deadly malady which is being faced by the mankind and the incidences of which are ever
increasing in the current scenario of changed lifestyle and food habbits along with exposure to
predisposing factors of carcinogens such as tobacco chewing, smoking, alcohol intake, environmental
pollutants, occupational health hazards etc. Anti-cancer potential of cow urine therapy has been
reflected by several case reports, success stories and practical feed back of patients for the treatment
of cancer. Cow urine enhances the immunocompetence and improves general health of an individual;
prevent the free radicals formation and act as anti-aging factor; reduces apoptosis in lymphocytes
and helps them to survive; and efficiently repairs the damaged DNA, thus is effective for the cancer
therapy. Experimentally it has been proved that among all sorts of urines, the urine of the Indian
cows is most effective. Seeing the potential use of indigenous cow urine in several ailments including
even the cancer, the use of Gomutra (cow urine) of indigenous breeds of cattle should be promoted
extensively. However, scientific validation of cow urine therapy is required for its worldwide acceptance
and popularity. This review highlights the anti-cancer activity of cow urine and the strategies for
promoting its vital medicinal potential and prospectives for the benefit of mankind with the view that
cow urine therapy needs immediate attention, promotion, and wide popularity and proper support
of the scientists, researchers and clinicians to strengthen this alternate low cost therapy having no
side effects, as generally observed with chemotherapy and radiation therapy being followed for
curing cancers, and thus inspire confidence in the public about its good virtues.
Key words: Cow urine, cancer, tumor, cowpathy, panchgavya, treatment
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1
Division of Avian Diseases,
2
Centre for Animal Disease Research and Diagnosis (CADRAD),
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INTRODUCTION
“Panchagavya” is a combination of cow urine, milk,
dung, ghee and curd. Indian cow breeds are unique and
distinct species, popularly known as “Kamdhenu” and
“Gaumata, has high socio-cultural values, plays
significant role in rural economy, represent cattle wealth
and bio-diversity. The ancient Indian system of medicine,
Ayurveda, has detail mentions of importance of
panchgavya in the treatment of various human diseases.
Apart from high medicinal values, panchgavya has many
beneficial implications in agriculture, organic farming
as good quality natural manure and biopesticides, bio-
fertilizer, pest repellants and as alternate energy
resources (biogas, fuel and electricity) (Charaka-
Samhita, 1981, Susruta Samhita, 1985; Tietze, 1996;
Chauhan, 2000, 2001, 2002 a,b, 2004a,b, 2005; Fulzele
et al., 2001, 2003; Joshi, 2002; Nautiyal, 2002; Garg
and Chauhan, 2003a,b; Achliya et al., 2004; Saxena et
al., 2004, Singh and Chauhan, 2004, Dhama et al.,
2005). These can provide food free from health hazards
of chemical fertilizers and pesticides. Scientists /
clinicians are facing problem in modern allopathic
treatments due to the development of multiple drug
resistance in microorganisms, presence of antibiotic
residues in food chain and/or associated allergies and
autoimmune disorders in humans. Immunity is reducing
drastically as a result of the environmental pollution,
use of agrochemicals in agriculture and presence of
pesticides, heavy metals, fungal toxins etc. in the food
chain. This has lead to the inefficacy of antibiotic drugs,
development of resistance in bacteria, recurrent
infections, and/or decreased immune status of an
individual. As per WHO, the twentieth century wonder
drugs “antibiotics” will not remain useful and become
almost ineffective by the year 2020. Also the incidences
of human sufferings from cancer, a deadly malady, are
ever increasing in the current scenario of changed
lifestyle and food habbits along with dangers of
carcinogen in the form of tobacco chewing, smoking,
alcohol intake, environmental pollutants, occupational
health hazards etc. The methodologies like
chemotherapy, radiotherapy and surgery are available
for treating the cancer, but the success rate is low
particularly with malignant tumors, and moreover, these
therapies produce severe side effects adding to the
physical and mental agony of the patient and are costly,
and even some of the tumors are incurable. In all these
circumstances mentioned above one has to think over
the alternative therapeutic approaches to control the
infections, save mankind from different ailments and
fight diseases such as cancer (Garg and Chauhan, 2003;
Chauhan, 2005).
Utilizing the beneficial properties of cow’s urine,
milk, ghee, curd and dung, the kind of treatment is called
panchgavya therapy or cowpathy, a system of
naturopathy. Panchgavya products have been found to
be beneficial in curing several human ailments and
enhance the body’s immunity and resistance to fight
the infections. This kind of alternative treatment has
been reported to be beneficial even for dreaded diseases
like cancer, AIDS and diabetes. Of these, the cow urine
recently has received worldwide attention. Two US
patents have been granted to Indian scientists on
establishing the bioenhancing properties of cow urine,
its use in tuberculous patients and fight cancers, thus
opening a new era in medical science. Cow urine along
with the antibiotics can also prevent the development
of resistance in microorganisms against the antibiotics.
Several scientists from different laboratories of Council
of Scientific and Industrial Research (CSIR), All India
Institute of Medical Sciences (AIIMS), G.B. Pant
University of Agriculture and Technology, Pantnagar, and
Indian Veterinary Research Institute (IVRI), besides Non-
Government Organizations (NGOs) and other Institutes
are working on different medicinal properties of cow
urine and other panchgavya products. Several students
of M.Sc., M.V.Sc., M.D. and/or Ph.D. are working on
the medicinal properties of cow urine and other
panchgavya products (Chauhan, 2005).
The people frustrated from the heavy medication
of allopathy are now using cowpathy drugs and being
benefited by the panchgavya products for several
diseases. Cow urine is an important element of
panchgavya, and the cow urine therapy has been
successful in relieving human sufferings from flu,
allergies, colds, rheumatoid arthritis, bacterial/viral
infections, hepatitis, leucorrhoea, leprosy, asthma, skin
infections etc. However, scientific validation of cow urine
is required for its worldwide acceptance and popularity
in terms of medicinal applications so as to exploit its
optimal power for the service of mankind. Regardless of
scientific validation, people are using and getting benefits
of it. The present review focuses the anti-cancer activity
of cow urine, well supported by the known scientific facts
and case reports, success stories and feedback of cancer
patients treated with cow urine therapy. The authors have
compiled this information with ultimate goal of
popularizing “Cow Urine Therapy / Chikitsa” as an
alternate prophylactic / therapeutic approach, which is
safer, cheaper and without any side effects for fighting
cancer, the most dreaded and incurable malady. Many a
good virtues of cow urine need proper attention and
promotional campaigns and judicious support of the
scientists, researchers and clinicians so as to strengthen
2 Dhama et al.
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the miraculous cow urine therapy which can inspire
confidence in the physicians as well as the public that
deadly diseases like cancer could be treated.
CANCER
Cancer is the term used to describe the
uncontrolled growth of abnormal cells that have
changed, or mutated, from normal cells, it is also known
as neoplasm or tumor It is a group of cells, usually
derived from a single cell, that has lost its normal control
mechanisms and thus has unregulated growth.
Cancerous (malignant) cells can develop from any tissue
within any organ. As cancerous cells grow and multiply,
they form a mass of cancerous tissue, called a tumor,
which invades and destroys adjacent healthy tissue.
Tumors generally provide no useful function and grow
at the expense of healthy tissues. This growth prevents
normal function of vital organs and can cause organ
failure. Cancerous cells from the primary (initial) site
can spread (metastasize) throughout the body. The
growth of tumour persists in the same excess even after
cessation of the stimuli/etiology. Oncology is branch of
science which deals with the study of tumours
(Oncos=tumour, logos=study) (Ezra, 2002; Stephen,
2004; Merck Source.htm).
Neoplasm is a general term for a tumor, whether
cancerous or non-cancerous. The word neoplasm has
been derived from Greek language means “New
formations or new growth” (Neo=new, plasm=growth).
It can be defined as “A mass of tissue formed as a result
of abnormal, excessive, uncoordinated, autonomous and
purpose less proliferation of cells” and is characterized
by key features of continuous growth, resemblance to
embryonic cells, no structural/orderly arrangement, no
useful function and no clear etiology. A neoplastic growth
does not obey the laws of the healing or normal tissue
growth, and its cells continue to multiply indefinitely
irrespective of any structural or functional requirements
and form an ever increasing mass of tissue.
CLASSIFICATION
Tumors are classified as either benign or
malignant.
Benign: These are slow-growing and often
harmless depending on the location. It is non-cancerous
in nature. In Benign tumours, the cells are of adult type.
These neoplams are well differentiated, grow slowly by
expansion and do not invade below basement
membrane. They remain localized, encapsulated and
can be removed by surgery. They are classified with
addition of a suffix-oma to the cell type. e.g. Fibroma,
Chondroma, Adenoma, Papilloma.
Malignant: Malignant tumors are what we call
cancer. These are faster-growing and likely to spread
to other parts of the body and cause severe problems.
The invasive capacity of a cancer to infiltrate and destroy
surrounding tissue affects its spread. Cancerous cells
spread to a completely new location by metaplasia. In
malignant tumors the cells are having characteristics
of embryonic stages. This reversion towards cells to a
more primitive or embryonic and less differentiated type
is also known as anaplasia. The more anaplastic cells
we see in a tumour more malignancy will be there. It
will depend on the degree of anaplasia in which
malignant cells characteristically show enlargement of
nucleus, multiple nuclei, (tumour giant cells),
enlargement of nucleolus, increase number of mitotic
figures, hyperchromasia and embryonic type features.
Thus, the neoplastic cells are anaplastic, metastasize
and invade the adjacent tissues and destroy normal
tissue. They are also called as cancer meaning “like
crab”. They can adhere to any part of body. They are
classified with suffix as carcinoma or sarcoma.
Ectodermal origin- Carcinoma, Mesodermal origin-
Sarcoma. e.g. Lymphosarcoma, Adenocarcinoma,
Squamous cell carcinoma. Some tumors are highly
undifferentiated they are referred as “undifferentiated
malignant tumours”.
NEOPLASTIC CELL STRUCTURE
Anaplasia: More anaplasia represents more
undifferentiated neoplasm.
Loss of contact: Neoplastic cells loss contact with
neighbouring cells due to decreased adhesiveness. It
helps in invasion and metastasis.
Neoplastic cell lack contact inhibition: It helps
in the growth/spread of tumours.
Abnormal cytoskeleton of cells: Its unstable
chromosome movements cause abnormality in
cytoskeleton.
Chromosomal defects: Malignant cells are
usually aneuploid i.e. cells having more or less than
diploid number of chromosomes. This gives a pathologic
karyotype in the form of chromosomal breaks or
translocations. e.g.. Plasmacytoma (tumour of B-
lymphocytes) in which translocation of segments of
chromosome 15 occurs to chromosome 12.
ETIOLOGY AND RISK FACTORS
In general, tumors appear to be caused by
abnormal regulation of cell division. Typically, the
division of cells in the body is strictly controlled and
regulated. New cells are created to replace older ones
or to perform new functions. Cells that are damaged or
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no longer needed die to make room for healthy
replacements. If the balance of cell division and death
is disturbed, a tumor may form. Carcinogen is an agent
that causes cancer and includes many chemicals
(arsenic, asbestos, aromatic amines, benzene,
chromates, nickel, vinyl chloride, mineral oil, diesel
exhaust), medicinal/therapeutic agents (alkylating
agents, chemotherapy drugs such as topoisomerase
inhibitors, diethylstilbestrol, radiation therapy), betel
nuts, tobacco, certain viruses, poisonous mushrooms,
aflatoxins etc. The time between exposure to the
chemicals and development of the cancer may be many
years. Other factors include genetic abnormalities,
radiation, excessive sunlight exposure, alcoholism,
obesity and sedentary lifestyle. Tobacco causes more
deaths from cancer than any other environmental agent.
Abnormalities of the immune system, which usually
detects and blocks aberrant growth, can also lead to
tumors.
Instrinsic or Predisposing Factors
Family History and Genetic/Heredity factors:
History of genetic abnormalities and an extra or
abnormal chromosome may increase the risk of cancer.
Some chicken are susceptible for leucosis while others
are resistant for leucosis. Pigmentation also effects the
cancer development. In white horses Melanosarcoma
is common. Squamous cell carcinoma is common in
hereford cattle.
Sex and Age: Some tumors are more common
in one sex than the other, some are more common
among children or the elderly. However, most cancers
are more common in older people. The increased cancer
rate is probably due to a combination of increased and
prolonged exposure to carcinogens and weakening of
the body’s immune system. Tumors of genital tract are
common in females.
Extrinsic Factors
Physical factors: Extended exposure to
ultraviolet radiation (UV-rays), X-rays, radium, ionizing
radiation primarily from sunlight, causes skin cancer.
Ionizing radiation is particularly carcinogenic.
Chemical factors: Many chemicals are known to
cause cancer and many others are suspected of doing
so. Initiators: Coal-tar, Aflatoxins, Actinomycin D,
Mitomycin, Alkylating agents (Cyclophosphamide,
Nitrosourea), Polycyclic aromatic hydrocarbons
(Tobacco, Smoke, Pollutants), Benzanthracene, Arsenic,
Metals (Nickel, Lead, Cobalt, Chromium), Insecticides
(Aldrin, Dieldrin, Chlordane). Promoters: Phenols,
Hormones (Estrogen), Drugs (Phenobarbital), Artificial
sweetners (saccharine, colouring/flavouring agents and
preservatives.
Environmental Factors: Pollution in the air,
whether from industrial wastes or cigarette smoke, can
increase the cancer risk. For example, asbestos
exposure may cause lung cancer. Smoking cigarettes
produces carcinogens that substantially increase the risk
of developing cancers of the lung, mouth, larynx, kidney,
and bladder.
Viral Infections: Several viruses are known to
cause cancer in humans, and several others are
suspected of causing cancer. The papillomavirus (which
causes genital warts) is one cause of cervical cancer in
women. Hepatitis B virus can cause liver cancer. Some
human retroviruses cause lymphomas and other cancers
of the blood system. Epstein-Barr virus causes Burkitt’s
lymphoma. Other viruses causing cancers include
Polyoma virus, Adeno virus, Poxvirus, Hepdna virus
(Hepatitis B virus – hepatocellular carcinoma),
Retrovirus and Herpes virus.
Other factors
Geography: The geographic variation in cancer
risk is probably multifactorial: a combination of genetics,
diet and environment.
Diet: A diet high in fat has been linked to an
increased risk of colon, breast, and possibly prostate
cancer. People who drink large amounts of alcohol are
at much higher risk of developing esophageal cancer. A
diet high in smoked and pickled foods or in barbecued
meats increases the risk of developing stomach cancer.
Inflammatory Diseases: Ulcerative colitis can
result in colon cancer. Infection with the parasite
Schistosoma (Bilharzia) may cause bladder cancer by
chronically irritating the bladder.
DEVELOPMENT AND SPREAD
Cancer occurs when cell division gets out of
control. Usually, the timing of cell division is under strict
constraint, involving a network of signals that work
together to say when a cell can divide, how often it
should happen and how errors can be fixed. Mutations
in one or more of the nodes in this network can trigger
cancer, be it through exposure to some environmental
factor (e.g. tobacco smoke) or because of a genetic
predisposition, or both. Usually, several cancer-
promoting factors have to add up before a person will
develop a malignant growth. The predominant
mechanisms for the cancers development are (i)
impairment of a DNA repair pathway (ii) the
transformation of a normal gene into an oncogene and
(iii) the malfunction of a tumor supressor gene.
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Neoplastic cell genesis (Carcinogenesis)
Cell differentiation: Specialized cells derived
from less specialized cells (embryonic cells) are
controlled by specific gene. Cells become differentiated
so that the genes that control embryonic characters are
switched off and genes for more differentiated
characters are activated. In neoplastic cells, the
presence of abnormal genes (genetic mechanisms) or
normal genes expressed at abnormal level (epigenetic
mechanism) favour proliferation over differentiation.
Genetic mechanisms: Mutation in a somatic cell
nucleic acid occurs to provide a stable and monoclonal
population of cells.
Epigenetic mechanism: Genome is normal in
cancer cell but transcription and translation is abnormal
which is responsible for abnormal growth of cells.
In most tumors genetic mutation or genetic
rearrangement occurs like DNA transcribe to mRNA and
mRNA translated to protein (enzymes) which direct cells
for proliferation. Changes occur in DNA as a result of
direct chemical or radiation damage or there is insertion
of viral genes to host DNA that induces cell proliferation
through neutralizing normal growth controlling gene.
Tumors do not arise from completely differentiated cells
such as neurons or keratinized epithelial cells, but stem
cells (pluripotential) must be present for the growth of
tumour. Neoplastic cells do not “dedifferentiate” but fail
to respond to normal signals for differentiation.
Cancerous cells develop from healthy cells in a complex
process called transformation. The first step in the
process is initiation, in which a change in the cell’s
genetic material, in the DNA and sometimes in the
chromosome structure, primes the cell to become
cancerous. This change in the cell’s genetic material
may occur spontaneously or be brought on by an agent
that causes cancer (a carcinogen). However, not all cells
are equally susceptible to carcinogens. A genetic flaw
in a cell may make it more susceptible. Even chronic
physical irritation may make a cell more susceptible to
carcinogens. The second step in the development of
cancer is called promotion. Agents that cause promotion
are called promoters, which may be substances in the
environment or even some drugs (such as barbiturates).
Unlike carcinogens, promoters do not cause cancer by
themselves. Instead, promoters allow a cell that has
undergone initiation to become cancerous. Promotion
has no effect on non-initiated cells. Thus, several factors,
often the combination of a susceptible cell and a
carcinogen, are needed to cause cancer. Some
carcinogens are sufficiently powerful to be able to cause
cancer without the need for promotion. For example,
ionizing radiation, used in X-rays and produced in
nuclear power plants and atomic bomb explosions can
cause a variety of cancers, particularly sarcomas,
leukemia, thyroid cancer and breast cancer.
Viral Oncogenesis: Oncogenes are the trans-
forming genes present in most tumor cells of animal and
man. It is also present in certain viruses. Experimentally,
when they are incorporated in cells in culture, the cells
get transformed to multiply. When such genes are present
in normal cells that are known as cellular oncogenes (c-
oncs) or proto-oncogenes, which are present in a wide
range of cells and has a physiological role of proliferation
of cells through protein product. Proto-oncogenes are
converted into active oncogenes through mechanisms
of point mutation, translocation, gene amplification,
inappropriate expression of proto-oncogenes and
integration of viral DNA into host cell DNA. The
integration of viral DNA into host cell DNA causes
adjacent gene activated for growth of the cell without
control. Some of the viral oncogenes (v-oncs) are: src
(Rous sarcoma Virus), myc, myb, erb-B, erb-A (Avian
leucosis virus), pim-1, myc (Feline leukemia Virus), src,
raf, myc (Papilloma virus), hap (Hepadna virus), rel
(Reticuloendotheliosis), yes, ros (Avian sarcoma virus)
and fes, fms (Feline sarcoma virus).
Antioncogenes are genes that suppresses the
cellular proliferation. So neoplastic growth occurs either
as a result of activation of oncogene or due to
inactivation of antioncogene.
Telomeres: These are unique DNA-protein
structures that contain noncoding TTAGGG repeats and
telomere-associated proteins, which are essential for
maintaining genomic integrity. Alterations that lead to
the disruption of telomere maintenance result in
chromosome end-to-end fusions and/or ends being
recognized as double-stranded breaks. It is suggested
that cell responds to dysfunctional telomeres by
undergoing senescence, apoptosis, or genomic
instability. In conjunction with other predisposing
mechanisms, the genomic instability encountered in
preimmortal cells due to dysfunctional or uncapped
telomeres might lead to cancer. Genomic instability is
one of the earliest neoplastic changes known to occur
in most cancers and leads to mis-regulation of genes
involved in growth control, ultimately resulting in
tumorigenesis. Telomere dysfunction has been proposed
to play critical roles in aging as well as cancer
progression. The greatest risk factor for cancer in
humans is growing older. Genetic alterations must occur
within multiple growth control pathways before normal
cells are converted into cancer cells. Inducing short
telomeres or loss of capping can sensitize cells to death
via DNA damaging reagents or ionizing radiation.
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Neoplastic Cell Metabolism
Normal regulation of programmed protein
synthesis is lost in neoplastic cells. Gene expression
and mRNA translation is being directed towards purine
synthesis to meet the requirements of mitosis; defective
sodium pump (ATPase) due to abnormal receptor
molecules and glycoproteins on neoplastic cells; and
increased glycolysis due to damage in self replicating
DNA of moitochondria, overproduction of inorganic
phosphorous due to high rate of ATP hydrolysis and
abnormal enzymes on cell surface.
Spread of Neoplasms
Expansion: Benign tumors are encapsulated and
surrounded by fibrous tissue and hence they do not
infiltrate in neighbouring tissue. However, they expand
as their growth increases.
Distant spread/metastasis: Metastasis is the
movement or spreading of cancer cells from one organ
or tissue to another. Cancer cells usually spread via the
bloodstream or the lymph system. It is the spread of
tumors by invasion in such a way that detached tumor
mass may form secondary tumor at the site of lodgment.
They can grow directly into surrounding tissue or spread
to tissues or organs, nearby or distant. Cancer spreads
throughout the body shortly after the tumor cells develop
the ability to invade blood and lymph vessels. Such
spread may be overt, in the form of visible metastases,
or undetectable, in the form of micrometastasis.
Carcinomas typically spread through the lymphatic
system. For example, breast cancer usually spreads
first to the nearby lymph nodes and then it spreads more
extensively throughout the body. Sarcomas spread via
the bloodstream. Most of the malignant tumors
metastasize except malignant tumor of central nervous
system and basal cell carcinoma of skin. The process
of metastasis includes 5 steps viz. penetration
(invasion), separation, dissemination, establishment and
subsequent proliferation.
There are several methods of metastasis, which
are as under:
Infiltration: Neoplastic cells infiltrate or invade
the surrounding tissue. Various factors responsible for
invasion are growth of new cells, lack of contact
inhibition, motility of malignant cells, secretion of lytic
enzymes, role of chemotactic factors and activation of
complement.
Lymphatic spread: Epithelial tumors like
carcinomas spread through lymphatic route. Cancer
cells invade the wall of lymphatics which is known as
lymphatic permeation and form tumor emboli. These
cells are lodged in subcapsular sinus of lymph node
and may grow. Nearest lymph node initially act as barrier
filter and kill the tumor cells but later it provides fertile
environment for growth of tumor cells. Obstruction of
lymphatics by tumor cells also disturbs the lymphatic
flow and is responsible for metastasis at unusual sites.
Hematogenous spread: Metastasis through
blood is common route for most of the sarcomas
(connective tissue tumors). Some carcinomas (lung,
mammary gland, thyroid, kidney) may spread through
blood. Common sites of lodgment of tumor cells are
liver, lungs, kidneys, brain and bones. Cancer cell invade
the wall of capillaries to form tumor emboli. Blood borne
metastasis appear as multiple and rounded nodules
scattered in the organ.
Transcoelomic spread: The tumor cells invade
serosal wall and enters in coelomic cavity and then
tumor cells implant at another place, e.g. Peritoneal
cavity- carcinoma of stomach/ovary.
Spread along epithelial lined surfaces: The
neoplasms of epithelium spread along the line of
basement membrane without damaging it, e.g. spread
of tumor through fallopian tube from ovaries to
endometrium, and spread of tumor through bronchus
to alveoli.
Spread via cerebrospinal fluid (CSF): Tumor
of meninges may spread through cerebrospinal fluid as
the detached tumor cells metastasize at other sites in
central nervous system through CSF.
Implantation: It is a very rare method of spread
of tumors. In this the tumor cells are implanted at another
site inadvertently, e.g. Surgeon’s scalpel, needle, sutures
may transfer tumor cells from one to another place in
body; Cancer of lower lip may metastasize to upper lip.
Cancer is more likely to progress in people whose
immune system is altered or impaired, as in people with
acquired immunodeficiency syndrome (AIDS), those
receiving immunosuppressive drugs, those with certain
autoimmune diseases, and older people, in whom the
immune system works less well than in younger people.
However, even when a person’s immune system is
functioning normally, cancer can escape the immune
system’s protective surveillance.
SYMPTOMS AND SIGNS
Cancer can produce many different symptoms but
some tumors produce no symptom. Symptoms depend
on the type and location of the tumor. Some symptoms
occur with many or almost all cancers, and others are
specific to the type of cancer and where it is growing.
For example, lung tumors can cause coughing,
shortness of breath, or chest pain while tumors of the
colon can cause weight loss, diarrhea, constipation and
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blood in the stool. At first, cancer, as a tiny mass of
cells, produces no symptoms whatsoever. When cancer
grows in an area with a lot of space, such as in the wall
of the large intestine, it may not cause any symptoms
until it becomes quite large. In contrast, a cancer growing
in a more restricted space, such as on a vocal cord,
may cause symptoms (such as hoarseness) when it is
relatively small. Cancers produce symptoms by growing
into and thus irritating or destroying other tissues, putting
pressure on other tissues, producing toxic substances,
and using energy and nutrients normally available for
other bodily functions. It may cause one set of symptoms
as it grows in its initial site and cause different symptoms
as it spreads (metastasizes) to other parts of the body.
Some symptoms develop early in the course of cancer
and are therefore important warning signs that should
be evaluated by a doctor. Other symptoms develop only
after the cancer progresses and are therefore not helpful
in the early detection of cancer. General symptoms that
often accompany tumors (warning signs of cancer)
include: fevers, recurrent fever, chills, night sweating,
persistent pain, recurrent nausea, weight loss, loss of
appetite, sudden depression, fatigue, malaise, vomiting,
a recent change in bowel habits (constipation or
diarrhea), blood in urine/stool (either visible or detectable
by special tests), chronic cough, changes in the size or
color of a mole or changes in a skin ulcer that does not
heal, enlarged lymph nodes etc.
Cancers are typically painless at first. However,
as they grow, the first symptom is often a mild
discomfort, which may steadily worsen into increasingly
severe pain as the cancer enlarges. The pain may result
from the cancer compressing or eroding into nerves or
other structures. This may cause several neurological
and muscular symptoms, including a change in
sensations (such as tingling sensations) or muscle
weakness. As the cancer enlarges and invades
surrounding tissues, it may grow into a nearby blood
vessel, causing bleeding. The bleeding may be slight
and undetectable or detectable only with testing.
Particularly with advanced cancer, the bleeding may
be massive and even life threatening. As a cancer begins
to spread, it may first spread to nearby lymph nodes,
which become swollen and may be felt as hard or
rubbery. Cancer can compress or block structures, such
as the airways in the lungs, causing shortness of breath
or pneumonia and the inability to cough up secretions.
When a cancer grows in the brain, symptoms may be
hard to pinpoint but can include confusion, dizziness,
headaches, nausea, changes in vision, and seizures.
People with advanced stage cancer are often may find
that they feel very tired or become short of breath when
exerting themselves, fatigued and loose weight. They
sleep many hours a day. Depression can be related to
the symptoms of the illness, a fear of dying, and a loss
of independence. Cancer produces both direct and
indirect effects on bone health. Bone metastases cause
considerable morbidity, including severe pain, impaired
mobility, symptoms of hypercalcemia, pathologic
fractures due to reduced load-bearing capabilities, and
spinal cord compression. Cord compression can lead
to paralysis or death. Hypercalcemia is potentially lethal
and may cause dysfunction of the gastrointestinal tract,
kidneys, and central nervous system. Pain is often the
first indication that the tumor has metastasized to the
bone, which in turn has a detrimental affect on a patient’s
quality of life, interfering with daily activities and limiting
a patient’s capabilities. These effects often lead to
feelings of anger, fear, and depression.
The size of a tumour varies from one mm to
several centimeter diameter. The common warts/
papilloma over skin have smaller size while certain
tumors have many centimeter diameter such as uterine
tumors etc. The weight of tumor also varies from few
milligram to several kg. The consistency of a tumour
depends on the type of tissue involved. The tumour of
bone is hard while connective tissue tumors are firm
and dense or sclerotic. Brain tumors are mostly soft.
Microscopically, the tumour is composed of cells, which
resembles the type of tissue/organ involved. The
appearance of cells vary on degree of malignancy.
CLINICOPATHOLOGICAL EFFECTS OF
NEOPLASMS
Malignant neoplastic cells kill humans and animals
through many effects which are categorized into local
and systemic effects.
Local effects: The main local effect is pressure
on surrounding tissue. The tumor causes pain, ischemia,
oedema and lymphatic blockade in surrounding tissue.
The lumen of ducts are obstructed due to pressure from
outside tumors. e.g. squamous cell carcinoma of
respiratory tract causes dyspnoea and hypoxia due to
obstruction in pharynx. Tumors which cause obstruction
in urinary tract or obstruction in bile ducts may lead to
death.
Systemic effects
Cachexia: Cachexia is main characteristic feature
of malignant tumors. In later stages, anorexia occurs in
leading to loss of weight and letharginess. Anorexia
occurs due to depression of appetite centre in brain. A
humoral factor is released by tumour cells that causes
suppression of appetite centre in brain. Cytokines
secreted by tumor cells or by altered macrophages
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(affected by neoplastic cell) are known as cachectin
which causes suppression of gene that produces
lipogenic enzymes responsible for fat deposition.
Neoplastic cells act as amino acid trap and thus, drain
out the essential amino acids leading to regression of
skeletal muscles, liver, pancreas and other organs.
Hepatocytes become atrophied.
Hypoglycemia: It is characteristic feature of
tumors of pancreas and other epithelial tumors. It is
characterized by restlessness, weakness, tremors,
episodes of collapse and seizures.
Anemia: Anemia is a common feature in all
metastatic tumors. It is caused by haemorrhage through
invasion by cancer cells, decreased erythropoiesis due
to invasion of tumour cells in bone marrow, increased
erythrocyte fragmentation as many blood vessels pass
though tumors. In highly vascular tumor, there are more
chances of anemia. In hyperspleenism, there is
spleenomegaly due to excessive removal of RBC from
circulation. Iron deficiency due to tumor may also lead
to anemia. Due to anticancer therapy there is non
regeneration of stem cells. It causes death of stem cells
or dividing cells of bone marrow leading to anemia.
Autoimmune anemia occurs in lymphoid neoplasms and
there is suppression of erythropoitin by kidneys.
Thrombocytopenia: In tumor patients
thrombocyte production is reduced. e.g. in viral
leukemia, platelet survival rate is reduced from 40-80%
in dogs.
Thrombosis: Tumor cells produce procoagulants
which are responsible for intra vascular coagulation and
thrombi formation.
Hypercalcemia: In most of the malignant
neoplasms, hypercalcemia occurs through two
mechanism. In solid tumors due to osteolytic metastasis
excessive bone resorption occurs leading to calcium
release. Tumour cell also secrete proteins that increases
parathyroid hormone leading to increase in calcium level
in blood. Pseudohyperpara-thyroidism is associated with
mammary gland cancer, fibrosarcoma, lymphosarcoma
and adenocarcinoma in dogs and gastric carcinoma in
horses.
Diarrhoea: Prolonged diarrhoea occurs in
malignant neoplasms which is unresponsive to therapy
and non associated with microorganisms. Neoplastic
cell secretes vasoactive intestinal peptides that cause
diarrhoea leading to death of the affected individual.
Fever: Some tumor cells release pyrogens that
increases body temperature which is anti neoplastic in
nature. In late stage of metastatic tumors fever is a
characteristic feature.
TUMOR COMPLICATIONS
Complications can occur if a tumor is located in a
region of the body where it compromises the function
of the normal organ. When a malignant tumor grows
and spreads throughout the body, a number of
complications can result, depending on the degree to
which a tumor grows and spreads i.e. its aggressiveness.
The diagnosis of cancer often causes a lot of anxiety
and can affect one’s entire life. Some of these
complications can be serious and require emergency
treatment. Paraneoplastic syndromes occur when a
cancer produces one or more substances that circulate
in the bloodstream, such as hormones, cytokines (a type
of protein), or other proteins and thus spread throughout
the body. These substances can affect the function of
other tissues and organs. Some substances damage
organs or tissues by causing an autoimmune reaction.
Others directly interfere with the function of different
organs or actually destroy tissues. Symptoms such as
low blood sugar, diarrhea, and high blood pressure can
result. Cardiac temponade occurs when fluid
accumulates in the baglike structure surrounding the
heart (pericardium, or pericardial sac), when a cancer
invades the pericardium and irritates it and which puts
pressure on the heart and interferes with its ability to
pump blood. This can be observed with lung cancer,
breast cancer, and lymphoma. Pleural effusion occurs
when fluid accumulates in the pleural sac of lungs,
causing shortness of breath. Superior vena cava
syndrome occurs when cancer partially or completely
blocks the superior vena cava causing the veins in the
upper part of the chest and neck to swell, resulting in
swelling of the face, neck, and upper part of the chest.
Spinal cord compression occurs when cancer
compresses the spinal cord or the spinal cord nerves,
resulting in pain and loss of function.
Brain dysfunction occurs when the brain functions
abnormally as a result of a cancer growing within it,
either as a brain cancer or more commonly as a
metastasis from a cancer elsewhere in the body. Many
different symptoms can occur, including confusion,
sedation, agitation, headaches, abnormal vision,
abnormal sensations, weakness, nausea, vomiting, and
seizures. Polyneuropathy occurs as a dysfunction of
peripheral nerves, resulting in weakness, loss of
sensation, reduced reflexes and incoordination.
Subacute cerebellar degeneration occurs in women with
breast or ovarian cancer, due to an autoantibody that
destroys the cerebellum. Symptoms are unsteadiness
in walking, incoordination of the arms and legs, difficulty
in speaking, dizziness, and double vision, which may
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appear weeks, months, or even years before the cancer
is detected and often result in severe disability. Spasms
of the eye and muscles and lack of coordination of
movements can occur in some children with neuro-
blastoma. Hypertrophic osteoarthropathy can also occur
in people with lung cancer, in which the shape of the
fingers and toes and causes changes at the ends of
long bones. Squamous cell carcinoma may secrete a
hormone like substance that leads to very high calcium
levels in the blood (hypercalcemic syndrome). This may
also be the result if the cancer directly invades bone,
thereby releasing calcium into the bloodstream, which
can progress to coma and even death. Other problems
include breast enlargement in men (gynecomastia), an
excess of thyroid hormone (hyperthyroidism), and skin
changes, including darkening of the skin in the armpits.
People with cancer are at risk for developing nutritional
deficiencies. The deficiencies may be the result of the
cancer itself, or the side effects of common cancer
treatments such as surgery, chemotherapy, and radiation
therapy. Malignancies directly compromise nutritional
status by altering metabolism and causing loss of
appetite. There are also individual alterations in
carbohydrate, protein, and fat metabolism. These
changes contribute to the loss of skeletal muscle and
adipose tissue (fat) stores. Cancer-associated anorexia
is probably the result of physiological changes but may
also be due to a psychological response to the disease.
Malignancy can adversely affect food and nutrient
ingestion, tolerance, and utilization.
DIAGNOSIS
Diagnosis of cancer/neoplasms can be done on
the basis of symptoms and lesions, clinicopathological
effects, immunological methods by using tumor markers
and gross and microscopic features (histopathological
examination) and employing recent diagnostic tools and
technologies. The symptoms and signs of tumors vary
based on their site and type. Some symptoms may give
early warning of cancer and should, therefore, trigger a
person to seek medical care. Fortunately, most of the
symptoms are usually caused by far less serious
conditions. Nonetheless, the development of any of the
warning signs of cancer should not be ignored. Diagnosis
encompasses screening, testing, and a physical
examination. For diagnosing and staging cancers and
to determine whether the cancer has spread in the body
the tests include: Computed tomography (CT) scan,
magnetic resonance imaging (MRI), positron emission
tomography (PET) scan, complete blood count (CBC),
blood chemistries, biopsy of the tumor, bone marrow
biopsy (most often for lymphoma or leukemia),
endoscopy usually guided by a CT scan, barium X-ray,
chest X-ray, mammogram, bone scans, ultrasound,
blood tests for liver enzymes, sputum cytology,
radioisotope scan, exploratory surgery, barium enema
examination and testing for tumor markers/antigens.
These tests vary with the location of the tumor in the
body. When a tumor is found, a biopsy is performed to
determine if the tumor is benign or malignant, which is
important in both diagnosis and staging. Depending on
the location of the tumor, the biopsy may be a simple
procedure or a serious operation. Biopsies are often
needed to be sure that an abnormality discovered on
an imaging test is cancer. Many kinds of biopsies can
be performed with a needle and do not require surgery.
Sometimes, however, surgery is needed to obtain a
sample of tissue. Physical examination and whole-body
photography is done for skin cancer, stool examination
for occult blood, rectal examination for rectal and colon
cancer, pelvic examination and Pa panicolaou (Pap)
test for cervical cancer, physical examination and
mammography for breast cancer. Most patients with
tumors undergo CT scans or MRI to determine the exact
location of the tumor and its extent. In MRI, a very
powerful magnetic field generates and exquisitely
detailed anatomic images are obtained. MRI is of
particular value in detecting cancers of the brain, bone
and spinal cord. More recently, PET scans have been
used to visualize tumors, by measuring biochemical
processes within it. Monoclonal (one-cell type)
antibodies, which can selectively bind to unique tumor
antigens can be used diagnostically when linked with
low-intensity radionuclides. The patient is then “scanned”
with a gamma counter, and any areas of localized
radiation emission (possible cancer lesions) can be
identified.
Screening programs allow early detection and
diagnosis of cancer and serve to detect the possibility
that a cancer is present before symptoms occur.
Screening for cancers can help prevent tumors or detect
them at their earliest and most treatable stages. Because
cancer is more likely to be cured if treated early, it is
critical that cancer be discovered early. These usually
are not definitive; results are confirmed or disproved
with further examinations and tests. Although screening
tests can help save lives, they can be costly and
sometimes have psychologic or physical repercussions.
In women, two of the most widely used screening tests
are the Papanicolaou (Pap) test to detect cervical cancer
and mammography to detect breast cancer. In men, a
common screening test involves measuring the level
of prostate-specific antigen (PSA) in the blood. PSA
levels are high in men with prostate cancer, but levels
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are also elevated in men with noncancerous (benign)
enlargement of the prostate. Finding occult blood in the
stool in older people is an indication that something is
wrong in the colon. The problem may be cancer,
although many other disorders can also cause small
amounts of blood to leak into the stool. Some screening
tests can be done at home. For example, monthly breast
self-examinations are valuable in helping women detect
breast cancer. Periodically examining the testes can help
men detect testicular cancer, one of the most curable
forms of cancer, especially when diagnosed early.
Periodically checking the mouth for sores can help
detect mouth cancer in an early stage.
When cancer is diagnosed, staging tests help
determine how advanced the cancer is in terms of its
location, size, growth into nearby structures, and spread
to other parts of the body. Staging allows doctors to
determine the most appropriate treatment as well as
helping to determine prognosis.
Tumor Markers/Antigens:
Tumor markers are substances secreted into the
bloodstream by certain tumors and can be detected with
blood tests. These are fetal antigens and alpha
fetoproteins produced by embryonic cells. It is produced
by liver cells but after birth it’s production is stopped
normally. It is a differentiation antigen as in normal cells
or viral antigens on cell surface., e.g.. Retrovirus. Tumor
antigens have been identified in several types of cancer,
including malignant melanoma, bone cancer
(osteosarcoma), and some cancers of the digestive tract.
Sometimes these are used for diagnosis and sometimes
to evaluate the person’s response to treatment.
Measurements of some of the tumor markers can be
used as screening tests in people who have no
symptoms of cancer. However, tumor markers
sometimes are present in the blood of people who do
not have cancer. Thus, finding a tumor marker does not
necessarily mean a person has cancer. But, in people
who do have cancer, tumor markers can be used to
monitor the effectiveness of treatment and to detect
possible recurrence of the cancer. If the tumor marker
was present before treatment but no longer appears in
a blood sample after treatment, the treatment has
probably been successful. If the tumor marker
disappears after treatment then later reappears, the
cancer has probably returned i.e. the level of a tumor
marker increases if the cancer recurs.
Carcinoembryonic antigen (CEA): Levels are
raised in the blood of people with cancer of the colon,
breast, pancreas, bladder, ovary, or cervix. Levels may
also be raised in people who are heavy cigarette
smokers and in those who have cirrhosis of the liver or
ulcerative colitis.
Alpha-fetoprotein (AFP): Normally produced by
fetal liver cells, AFP is found in the blood of people with
liver cancer (hepatoma). AFP is often also found in
people with certain cancers of the ovary or testis and in
children and young adults with pineal gland tumors.
Beta-human chorionic gonadotropin (ß-HCG):
This hormone is produced during pregnancy but also
occurs in women who have a cancer originating in the
placenta and in men with various types of testicular
cancer.
Prostate-specific antigen (PSA): Levels are
raised in men with noncancerous (benign) enlargement
of the prostate and are considerably higher in men with
prostate cancer.
Carbohydrate antigen 125 (CA-125): Levels are
raised in women with a variety of ovarian diseases,
including cancer.
Carbohydrate antigen 15-3 (CA 15-3): Levels
are raised in people with breast cancer.
Carbohydrate antigen 19-9 (CA 19-9): Levels
are raised in people with cancers of the digestive tract,
particularly pancreatic cancer.
Beta
2
2
)-microglobulin: Levels are raised in
people with multiple myeloma, chronic lymphocytic
leukemia, and in many forms of lymphoma.
Lactate dehydrogenase: Levels can be raised
for a variety of reasons, and particularly in people with
testicular cancer, melanomas, and lymphomas.
IMMUNE MECHANISMS:
In some individuals the growth of neoplasm is very
fast that leads to early death. In others, tumor growth is
slow and the individual may survive several years. When
malignant tumor is clinically manifested it takes 6 month
to 1 year to cause death. There are many systems/
functions in the body which works together to fight with
neoplastic cells.
Nonspecific lysis and phagocytosis: Most
tumor cells are phagocytosed by polymorphonuclear
cells and macrophages. On contact, macrophages insert
cytoplasmic processes into the tumor cells and transfer
lysosomal enzymes into the cytoplasm of cancer cell
leading to death of cell. Because in cancer cell
decreased catalase and glutathione contents makes
them susceptible to oxidative injury by macrophages.
On the contrary reactive oxygen metabolites of
neutrophils “respiratory burst” are mutagenic and may
act as tumor promoter.
Natural killer cell: It is a population of immature
lymphocytes which bears Fc receptor that causes lysis
of neoplastic cells or virus infected cells.
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Antibodies: Antibodies against tumor antigens
also restrain the growth of tumor.
Tumour antigens: Tumour cells develop certain
biochemical alterations on their surface (protein change)
that makes the “tumour” antigens”. These are useful in
differentiating between neoplastic or preneoplastic cell.
These antigens may evoke immune response in body
by humoral or cell mediated mechanism which may
inhibit the tumour cell growth. Tumour antigens induced
selective CMI response which destroys the malignant
cells. During cytological or histological examination of
biopsy material, if one finds lymphocytes along with
cancer cells, the prognosis is considered as good.
Propionibacterium acnes (Corynebacterium parvum),
BCG and filterate of G-ve
bacterial cultures are used to
stimulate the reticulo-endothelial system against tumors.
Macrophages attract and attach on tumor growth and
remove it through phagocytosis. e.g. in ocular squamous
cell carcinoma, intra tumor injection of BCG reduces
growth by 71%. In early tumor growth, tumor cells
excrete some products that inhibits the macrophages,
e.g. macrophages also release certain soluble factors
that are having anti-tumour activities, such as tumour
necrosis factor (TNF) which causes necrosis of tumor
cells. It needs to be activated by P. acnes or LPS of G-
ve bacteria. It affects subcutaneous transplantation of
tumor.
Escape of neoplastic cells from immunological
destruction
Delayed immunostimulation: The tumor
antigens appear late on the anaplastic/neoplastic cell
surface causing delayed immune response.
Antigenic modulation: Frequent change in
antigenic determinants over neoplastic cell surface may
escape the cell from immune response.
Antigenic overload: There are too many
antigenic determinants on the neoplastic cell surface
that leads to immune tolerance.
General immunodeficiency Neoplasia, in
general, causes immunosuppression in body.
Specific immunodeficiency: There is lack of
recognition of tumor antigens on neoplastic cells by the
immunocytes that leads to suppression of specific
immune response.
Humoral antibodies: Antibodies binds with tumor
antigens and blocks the effect of more potent anti-
neoplastic action by another source.
TREATMENT:
Treating cancer is one of the most complex
aspects of medical care. Successful treatment of cancer
requires elimination of all cancer cells, whether at the
primary site, extended to local-regional areas, or
metastatic to other regions of the body, and with the
result that the specific cancer will not grow back.
Treatment also varies based on the type of tumor,
whether it is benign or malignant, and its location. If the
tumor is benign and is located in a “safe” area where it
will not cause symptoms or disturb the proper functioning
of the organ, sometimes no treatment is needed.
Sometimes benign tumors may be removed for cosmetic
reasons. A variety of approaches are used to treat cancer
that has spread beyond the regional place like
application of surgery, radiation, chemotherapy,
hormone therapy, and immunotherapy using biologic
response modifiers. If all of the cancer cannot be
removed with surgery, the options for treatment include
radiation and chemotherapy, or both. Some patients
require a combination of surgery, radiation and
chemotherapy.
Cancer therapy involves a team that encompasses
many types of doctors working together (for example,
primary care doctors, gynecologists, oncologists,
surgeons, radiotherapists, and pathologists) and many
other types of health care workers (for example, nurses,
physiotherapists, social workers, and pharmacists).
Treatment decisions take into account many factors,
including the likelihood of cure or of prolonging life when
cure is not possible, the effect of treatment on
symptoms, the side effects of treatment, and reduce
the chance of spread (metastases). People undergoing
cancer treatment hope for the best outcome and the
longest survival with the highest quality of life. Even
when a cure is impossible, symptoms resulting from
the cancer can often be relieved with treatment that
improves the quality and length of life (palliative
therapy). However, people who are candidates for
radiation therapy or anti-cancer drugs must understand
the risks involved with treatment. Therefore it should
be ensured that people receive the most effective care
with the fewest side effects (Groenwald et al., 1997).
Surgery: Historically, until the advent of
radiotherapy and chemotherapy, surgery was the only
available technique for treating cancer. It still is the
primary method for curing about one-third of cancer
patients with localized tumors i.e. the cancer confined
to one location. Cancer is most curable surgically when
the lesion is small and has not metastasized. If the lesion
and a small margin of surrounding healthy tissue are
removed, the chance of curing most tumor types, if no
metastases are present, is good. If it has spread to local
lymph nodes only, sometimes can also be removed.
Patients with distant metastases are not curable
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surgically, although palliative resection is sometimes
indicated. Premalignant, also called precancerous,
lesions can also be cured by surgical removal. These
tend to progress to malignant lesions, if not properly
treated. Surgery may be performed for palliative reasons
to reduce the tumor burden and/or to relieve symptoms.
Decreasing the tumor mass (debulking) may increase
the response to chemotherapy and/or radiotherapy in
some tumors, such as ovarian cancer. Surgery is also
used for diagnosis and/or staging, as in Hodgkin’s
disease and ovarian cancer, wherein the extent of
treatment is dictated by the stage of disease. Surgery
is used in the cancers such as all cancers of the
gastrointestinal tract and accessory structures,
gallbladder, bone, breast, endometrium (the lining of
the uterus), eye, genitalia, cervix, ovary, larynx, lung,
melanomas, many head and neck cancers, most skin
cancers, renal (kidney) cancer, salivary gland, sarcomas
(cancer of the connective tissue), some brain tumors
and thyroid tumors. Surgery is never curative in
disseminated cancer (Sabiston, 1991).
Radiotherapy: It is a treatment approach that
uses radiation (x-rays or related radiation) to destroy
cancer cells. Radiation preferentially kills cells that
divide rapidly. Cancer cells usually multiply faster than
other cells in the body and therefore are more likely
than most normal cells to be killed by radiation. Radiation
prevents the cancerous cells from continuing to
reproduce and thus prevents the tumor from growing
further. Cancer cells differ in how easily they are killed
by radiation, some are very resistant and thus cannot
be effectively treated. Radiation therapy is thought to
stop the growth of malignant lesions by damaging the
DNA within the cancer cells. It involves a field of intense
energy focused on a certain area or organ of the body.
Commonly used radioactive substances are Cesium
(
137
Cs), Cobalt (
60
Co), Iodine (
131
I), Phosphorus (
32
P),
Gold (
198
Au), Iridium (
192
Ir), Yttrium (
90
Y), Palladium
(
103
Pa). The units of measurement for radiation include
the roentgen, radiation absorbed dose (rad), the
generation of oxygen free radicals, which degrade tumor
DNA. Other units of radiation are the gray (Gy) and the
Sievert (SV). Two general techniques of radiation
delivery are used: brachytherapy and teletherapy. With
brachytherapy, the radiation source is placed close to
or within the target tissue. Teletherapy delivers radiation
from a device outside the body. The accuracy of delivery
is also enhanced by supervoltage radiation. A radioactive
substance may be injected into a vein to travel to the
cancer, for example radioactive iodine, which is used
in treatment of thyroid cancer, or radioactive implants,
which may be placed directly into the cancer. A linear
accelerator directs the radiation to the tumor, while
normal tissue is shielded as much as possible. A doctor
tries to accurately target the radiation therapy to protect
normal cells. For treating superficial skin lesions, the
electron beam is used. Cells with low sensitivity are
more resistant to the effects of radiation, but can, with
sufficiently high dosage, be killed. However, high
radiation doses may damage adjacent normal tissue.
Therefore, radiation therapy is divided into a series of
doses with moderate doses of radiotherapy or multiple
beam paths over a prolonged period of time, which
increases the lethal effects of the radiation on tumor
cells, while decreasing the toxic effects of the radiation
on normal cells, thus reducing the acute toxicity without
compromising anti-tumor efficacy. Also normal cells
have the capacity to repair themselves quickly after
being exposed to radiation (Dow and Hilderley, 1992;
Milenic and Brechbiel, 2004).
Physicians evaluate four factors when considering
the treatment of cancer with radiotherapy: 1) tumor
location - radiation may pose problems if a tumor is
located on or near a vital organ that is particularly
sensitive to radiation (eg, spinal cord), 2) extent of the
tumor- benefit from radiotherapy may be limited if a
tumor is too large or widespread, 3) patient health- a
debilitated patient may be a poor risk for radiotherapy,
and 4) therapeutic ratio (TR) - defined as the relationship
between normal tissue tolerance dose and the tumor
lethal dose. Radiation therapy plays a key role in curing
many cancers particularly localized tumors, including
Hodgkin’s disease, squamous cell cancer of the head
and neck, cancer of the skin, cervix, endometrium,
breast, larynx, seminoma (a testicular cancer), prostate
cancer, early-stage breast cancer, lung cancer, and
medulloblastoma (a brain or spinal cord tumor). One
could not effectively control numerous sites of
metastases, because one would not be able to safely
radiate such large areas. Lymphoma is usually not
treated with surgery and chemotherapy, the radiation
therapy is the treatment of choice. It may also be used
to provide temporary relief of symptoms particularly in
advanced cancer, or to treat malignancies (cancers) that
cannot be removed with surgery as in multiple myeloma
and advanced lung, esophageal, head and neck, and
stomach cancers. It can be given as palliative therapy
to relieve symptoms caused by spread of cancer to bone
or brain. Often it is used to shrink the tumor as much as
possible before surgery to remove the cancer. After
surgery it is used to prevent the cancer from coming
back. New techniques of intense and highly focused
radiation therapy, such as proton radiation, can
effectively treat certain tumors in areas where damage
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to normal tissue is a worry, such as the eye, brain, or
spinal cord. Radiation may be preferred in patients who
are high-risk surgical candidates. It is also the treatment
of choice for most tumors of the CNS, because of the
inaccessibility of these lesions to surgical procedures.
In conjunction with surgery, radiation should be used
when it can improve the local and regional control rate
or the overall cure rate. In this respect, as in the case of
many head and neck cancers, radiotherapy is used pre-
operatively to reduce the tumor mass, or post-
operatively to destroy residual cells. This approach has
led to significant improvement in local control and cure
of soft-tissue sarcomas.
Chemotherapy or drug therapy: Chemotherapy
involves the use of drugs (chemical agents), that kill
rapidly growing cells, to destroy cancer cells. It is
followed for cancers of systemic sites. Those cancers
that are the most rapidly growing (Burkitt’s lymphoma,
acute leukemia, germ cell cancer, and several others)
may be cured by chemotherapy in many cases.
Effectiveness of chemotherapy depends on that a tumor
consists of rapidly dividing cancer cells and these cells
are more sensitive to anticancer drugs than non-dividing,
normal cells. Although an ideal chemotherapy drug
would destroy cancer cells without harming normal cells,
few such drugs exist. Cancer chemotherapy kills or
arrests the growth of cancer cells by targeting specific
parts of the cell growth cycle. However, normal healthy
cells share some of these pathways, and thus are also
injured or killed by chemotherapy. Thus toxicities occur
with chemotherapeutic drug treatment, which tend to
harm dividing normal cells, such as those found in the
bone marrow or the lining of the gastrointestinal tract.
Most chemotherapeutic agents act by damaging
deoxyribonucleic acid (DNA), the cellular genetic
material. In many cases, it is likely that drug cytotoxicity
involves multiple intracellular sites of action and may
not be linked to specific cell cycle events. Therapeutic
index of a drug reflects the difference between its
efficacy (tumor cell killing) versus its toxicity to normal
cells. Classic chemotherapeutic drugs such as alkylating
agents can be quite toxic and the number of cycles that
may be administered is limited. Not all cancers respond
to chemotherapy. The type of cancer determines which
drugs are used, in what combination, and at what dose.
Chemotherapy may be used as the sole treatment or
combined with radiation therapy and surgery (Crowell,
2005).
Chemotherapy may be administered with curative
or palliative intent, depending on the type and stage of
the tumor. For example, testicular cancer, Hodgkin’s
disease, certain leukemias, diffuse non-Hodgkin’s
lymphomas, Ewing’s sarcoma, and Wilms’ tumor are
now curable with chemotherapy alone. However, in
patients with other types of advanced incurable diseases
(eg. disseminated breast cancer), chemotherapy
(including hormonal therapy) may provide years of
effective palliation. Just as bacteria may develop
resistance to antibiotics, cancer cells may become
resistant to chemotherapeutic agents (Gatti and Zunino,
2005). Using several drugs at the same time
(combination chemotherapy) is one way to minimize
such resistance. Dose-intensity chemotherapy is a new
but risky approach in which especially high doses of
drugs are used. This therapy is used for a few types of
cancer (including some types of myeloma, lymphoma,
and leukemia) that have recurred even though the
person had a good response when first treated with
drugs. The strategy is to markedly increase the drug
dose to kill more cancer cells and thus prolong the
person’s survival. However, it can cause life-threatening
injury to the bone marrow. Therefore, it is commonly
combined with bone marrow rescue strategies, in which
marrow cells are harvested before the chemotherapy
and returned to the person after chemotherapy.
Goal of cancer drug development is to find agents
that are effective at killing tumor cells while sparing
normal cells in the process. An exciting and very
promising new area of cancer drug development is the
identification of molecular targeted therapies (Thiery-
Vuillemin et al., 2003). Driven by increased knowledge
of cancer cell biology, new agents are being designed
to inhibit specific cellular proteins and signal transduction
pathways. These are more specifically targeted at growth
pathways that are only found in cancer cells and may
be more effective while also being less toxic. These
“molecularly targeted” drugs can enter cancerous
(malignant) cells and interrupt important pathways of
information flow in the cell, and thus render the cells
defective, and they die, while avoiding undesirable
toxicity. Imatinibsome, the first such drug, alters the
energy site in the malignant cell and is highly effective
in chronic myelocytic leukemia and certain tumors of
the digestive tract. Other such drugs target cell surface
receptors in nonsmall cell lung cancer and colon cancer.
Some of these new targeted drugs have shown
remarkable activity such as Gleevec for chronic myeloid
leukemia (CML) and bevacizumab, which inhibits tumor
blood vessel formation (angiogenesis). Further
development of targeted therapies will be acheived as
the knowledge continue to be explored that which
pathways and systems are dysregulated in each type of
cancer. These insights will usher in a new age of cancer
treatment based on “individualized” therapy. These new
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molecules have anticancer activity when used alone,
but are often more effective when combined with
traditional, cytotoxic chemotherapy.
Chemotherapy Drugs
Alkylating agents: Cyclophosphamide,
Chlorambucil, Melphalan : Forms chemical bond with
DNA, causing breaks in DNA and errors in replication
of DNA.
Antimetabolites: Methotrexate, Cytarabine,
Fludarabine, 6-Mercaptopurine, 5-Fluorouracil : Block
synthesis of DNA.
Antimitotics: Vincristine, Paclitaxel, Vinorelbine:
Block division of cancer cells.
Topoisomerase inhibitors: Doxorubicin,
Irinotecan : Prevent DNA synthesis and repair through
blockage of enzymes called topoisomerases.
Platinum derivatives: Cisplatin, Carboplatin :
Form bonds with DNA causing breaks.
Biotherapy: Biotherapy includes immunotherapy
and biologic response modifier (BRM) therapy to
enhance endogenous immune cell killing and tumor
vaccines (Rieger, 1995; Rosenberg, 1997).
Immunotherapy: Even when a cell becomes
cancerous, the immune system is thought to be able to
recognize it as abnormal and destroy it before it
replicates or spreads. So, the purpose of immunotherapy
is to stimulate the body’s immune system against cancer.
Several approaches are used to stimulate the immune
system to recognize and attack tumor cells. These
include: 1) the use of vaccines developed from tumor
cell fragments to “immunize” patients against their own
tumors; 2) general (nonspecific) stimulation or
restoration of immune function, as with interferon,
levamisole, or the Mycobacterium BCG; and 3) the
injection of the patient’s own cytotoxic lymphocytes
cultured for enhanced antitumor effects in vitro (adoptive
biotherapy). Thus, a number of different approaches are
being developed to utilize biotherapy in the treatment
of human cancer. Use of vaccines is composed of
antigens derived from tumor cells to boost the body’s
production of antibodies or immune cells (T
lymphocytes). Its basis is that cancer cells possess
distinct surface protein antigens that are potential targets
for antibody-directed or cell-mediated immunity. When
a cell becomes cancerous, new antigens, unfamiliar to
the immune system, appear on the cell’s surface (tumor
antigens). The immune system may regard these new
antigens as foreign and may be able to contain or destroy
the cancerous cells by the immune mechanism and is
often able to destroy cancerous cells before they can
become established. However, even a fully functioning
immune system cannot always destroy all cancerous
cells. And, once cancerous cells reproduce and form a
mass of cancerous cells (tumor), the body’s immune
system is highly unlikely to be able to destroy it. Thus,
antibodies against the tumor antigens can be produced,
but are usually not powerful enough to control the cancer.
Substances such as extracts of weakened tuberculosis
bacteria, which are known to boost the immune
response, have been successful when applied locally
to bladder cancers. Marek’s disease virus (MDV), caused
by a Herpesvirus, which causes polyneuritis and
malignant lymphoma in poultry, is the only virus for
which a vaccine is available to control cancer. To date,
other vaccines have not proven useful in the treatment
of cancer. Monoclonal antibody therapy involves the use
of experimentally produced antibodies to specific
proteins on the cell surface. These are administered to
the cancer patient in an attempt to destroy tumor tissue.
The monoclonal antibodies (MoAbs) can be used
therapeutically when linked to cancer drugs, therapeutic
radionuclides or potent plant toxins, such as ricin. The
antibody binds to the cancer cell, selectively delivering
the cancer drug or toxin to the tumor, called the magic
bullets. Antibodies linked to a radioactive isotope can
be used to deliver radiation directly to the cancer cells.
This area of research is certain to expand, especially
with the emerging availability of non-rodent (humanized)
antibodies, which have much lower sensitizing side
effects (i.e., fewer human anti-mouse antibody or
“HAMA” reactions). Approaches for stimulating the host
immune response is often used in patients with
advanced cancer, which have depressed immune
responses (Reiche et al., 2004; Li et al., 2005; Stern
and Herrmann, 2005).
Biologic response modifiers: These are used to
improve the immune system’s ability to find and destroy
cancer cells, such as by stimulating normal cells to
produce chemical messengers (mediators). Interferon
(of which there are several types) is the best-known and
most widely used biologic response modifier. Almost all
human cells produce interferon naturally, but it can also
be made artificially using recombinant technology. With
interferons measurable responses have occurred in
people with Kaposi’s sarcoma, chronic myelocytic
leukemia, renal cell carcinoma and malignant melanoma.
Two of the most frequently used biotherapy agents are
α-IFN (alfa interferon) and interleukin-2 (IL-2). α -IFN
produces antitumor effects by several mechanisms: 1)
inhibition of protein synthesis (one of its main antiviral
effects), 2) enhanced antigenicity of tumors by up-
regulation of the major histocompatibility complex (MHC)
on the cell surface, and 3) general immune stimulation
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to increase the activity of effector cells such as cytotoxic
T-lymphocytes (CTL). α -IFN is given by self-
administered subcutaneous injection, usually three times
weekly. IL-2 is a polypeptide growth factor for T
lymphocytes, Its normal function is to increase T cells
following antigen presentation on a macrophage. In
cancer therapy, IL-2 has been shown to increase the
numbers and activity of specialized cytotoxic T-cells
called lymphokine activated killer (LAK) cells. These cells
mediate direct tumor cell lysis by releasing toxins next
to the target tumor cell. A more specialized type of LAK
cell is the tumor-infiltrating lymphocyte or TIL, which is
found within tumor masses. This cell has even greater
tumor-lytic activity. When cultured in vitro with a patient’s
own lymphocytes, IL-2 has been used as a stimulant of
LAK cell formation. These cells can then be reinfused
into the patient, a process called “adoptive transfer” or
adoptive nonspecific biotherapy.
Hormonal/Endocrine Therapy: The rationale for
hormonal therapy is that some cancers arise from
tissues sensitive to hormonal growth control (eg. breast,
prostate, endometrium and liver) and retain this
sensitivity, even after malignant changes. Endocrine
therapy deprives the tumour
cell of hormones either by
reducing local and systemic hormone
concentrations or
by blocking its receptor. Whether a tumor will respond
to a hormone depends on the presence of receptors for
that hormone in the tumor tissue. For example, breast
cancers with high estrogen receptor content have a high
likelihood of responding to anti-estrogen therapy with
tamoxifen. Other agents are like progestins (megestrol),
estrogens (diethylstilbestrol), glucocorticosteroids
(prednisone), Imatinib etc. These agents tend to reduce
symptoms (palliation), but not complete shrinkage or
eradication of disease. Nonetheless these responses
can be long lasting. The growth of a hormone-sensitive
tumor often may be “turned off” for many months by
hormonal therapy. Because
of its relative lack of toxicity,
endocrine therapy is widely
used to treat advanced
disease as adjuvant and preoperative
therapy, and is
now being assessed for disease prevention. Hormonal
agents may be natural or synthetic. Several of the newer
hormonal agents are synthetic peptides which mimic
endogenous peptide hormones. For example, there are
several analogs of gonadotropin releasing hormone
(GnRH) which act at the pituitary to reduce the release
of sex hormones, FSH and LH. This deprives the
prostate gland of its androgen stimulation (a medical
castration) without the need for surgery. A number of
tumors have been shown to be responsive to biotherapy,
although complete responses are rare and overall
response rates are low. Hormone-responsive tumors are
breast cancer, prostrate cancer, neuroendocrine gut
tumors, lymphocytic leukemia and lymphomas,
endometrium and liver cancers.
Thermotherapy: It utilizes the principles of
cryotherapy and heat.
Recent evidence has shown cancer cell growth
and viability is dependent upon proper telomere
maintenance, which contributes towards the indefinite
proliferation of cancers and that targeting telomere
maintenance mechanisms and inducing telomere
dysfunction in cancer cells by inhibiting telomerase can
lead to catastrophic events including rapid cell death
and increased sensitivity to other cancer therapeutics.
Therefore, preventing the maintenance of telomeres,
such as via telomerase inhibition or loss of t-loop, and
thus the immortal phenotype of cancer might be a useful
mode of therapy. This might provide a mechanism or a
window of opportunity to specifically target and inhibit
the growth of cancer cells. The differences in telomerase
length, coupled with the much more rapid rate of cell
division in cancer cells, make the inhibition of
telomerase a potential cancer therapeutic target. Thus
the limitless proliferative potential of cancer could be
blocked. Short telomeres have been recently suggested
to be a potential cancer predisposition factor.
Ascertaining the telomere length status may be useful
in screening patients for telomerase inhibitor therapies.
Thus, it might be possible to use telomere lengths to
identify high-risk groups for preventative cancer
therapies. Combining telomerase inhibitors with
conventional cancer therapies or using inhibitors to
prevent tumor re-population might prove to be a useful
cancer treatment regimen. By allowing critically short
or uncapped telomeres to be recognized as DNA breaks,
additional DNA damage signals in the mitotically
unstable cancer cells can trigger the ultimate mitotic
catastrophe of apoptosis or terminal growth arrest. It
will be necessary to see their positive potential translated
into clinical trials (Gilley et al., 2005).
Each treatment method has a unique place and
value in the treatment of cancer. For example, surgery
can control or cure tumors that can be entirely removed
from surrounding normal tissues; radiation therapy can
control or cure certain cancers confined to a limited area,
sometimes avoiding deforming surgery; chemotherapy
can be used to cure or control metastatic malignancies;
biotherapy is used to manipulate the immune system to
help the body fight cancer or to administer biotherapeutic
agents in an attempt to destroy tumor tissue. Frequently,
combinations of these methods are used because some
cancers are more effectively treated by combinations
than by any one of these methods alone.
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Combined-Modality Therapy: Multimodality
therapy combines the assets of various modes of cancer
treatment. For some cancers, the best approach is a
combination of surgery, radiation, and chemotherapy.
Surgery or radiation therapy treats cancer that is
confined locally, while chemotherapy also kills cancer
cells that may have spread. Sometimes radiation or
chemotherapy is given before surgery to shrink a tumor,
thereby making the complete removal of the tumor using
surgery more likely, or after surgery to destroy any
remaining cancer cells. The stage of the cancer often
determines whether single therapy or a combination is
needed. For example, early-stage breast cancer may
be treated with surgery alone or surgery combined with
radiation therapy, chemotherapy, or with all three
treatments, depending on the size of the tumor and the
risk of recurrence. Locally advanced breast cancer is
usually treated with chemotherapy, radiation therapy,
and surgery. Sometimes combination chemotherapy is
used not to cure but to reduce symptoms and prolong
life. This can be useful for people with advanced cancers
that are not suitable for irradiation or surgical treatment,
for example, those with nonsmall cell lung cancer,
esophageal cancer, or bladder cancer. Commonly
several chemotherapy drugs are combined (combination
chemotherapy), so as to use drugs that work on different
parts of the cancer cell’s life cycle, thereby increasing
the likelihood that more cancer cells will be killed. Here
each drug can be used at its optimal dose, helping avoid
intolerable side effects. Drugs that kill tumor cells may
be combined with antibodies or with drugs that stimulate
the body’s immune system against cancer (biologic
response modifiers). Adjuvant chemotherapy is used
following or in conjunction with some other primary
therapy. It is designed to eradicate disseminated
micrometastases that remain after surgery and/or
irradiation of the primary tumor. It is practised in patients
with breast cancer, osteogenic sarcoma, large bowel
cancer, ovarian cancer, head and neck cancer,
pancreatic cancer, melanoma, and nonsmall cell lung
cancer.
The goals and progress of cancer therapy can be
clarified by observing the success of cure. For a potential
cure, a complete remission or complete response must
be achieved, which requires disappearance of clinically
evident disease. Absence of all evidence of a cancer
after treatment is termed as remission. Such patients
may appear to be cured but may still have viable
neoplastic cells that will, in time, cause relapse or
recurrence of cancer, where the cancerous cells return
after treatment, either in the primary location or as
metastases (spread). A partial response is a > 50%
reduction in the size of a tumor mass or masses, which
may lead to significant palliation and prolongation of
life, but tumor regrowth is inevitable. A patient may also
have no response. The interval between disappearance
of cancer and relapse is termed the disease-free interval
or disease-free survival.
Side Effects of Cancer Therapy:
Almost everyone who receives cancer treatment
experiences side effects, which vary according to the
treatment and the area of the body undergoing
treatment. Chemotherapeutic agents, sometimes called
cytotoxic agents because they kill cells, produce toxic
side effects on rapidly dividing host tissues such as bone
marrow and intestinal mucosa. Some normal cells,
including blood cells, hair, and cells lining the
gastrointestinal tract are also rapidly dividing, and are
most likely to be damaged. All chemotherapy drugs
affect normal cells and cause side effects, varying
according to the type of drug. Chemotherapy commonly
causes nausea, vomiting, loss of appetite (anorexia),
weight loss, fatigue, and low blood cell counts that lead
to anemia and risk of infections. People often lose their
hair. Cytopenia, a deficiency of one or more types of
blood cell like abnormally low numbers of red blood cells
(anemia), white blood cells (neutropenia or leukopenia),
or platelets (thrombocytopenia), can develop because
of the toxic effect of drugs on bone marrow. These drugs
also can cause nerve dysfunction, heart and kidney
damage, hearing loss, bone marrow suppression, injure
lining of stomach and decreased fertility. Cytotoxic
chemotherapy has an independently negative effect on
bone cells (primarily osteoblasts) and can induce
premature ovarian failure in patients with breast cancer,
which leads to estrogen deprivation, which in turn leads
to loss of bone mineral density (BMD). Radiation therapy
is also associated with a significant number of adverse
reactions, which depend on the part of the body being
irradiated, how large an area is being treated, the dose
and schedule given, and the tumor’s proximity to
sensitive tissues. It can damage normal tissues adjacent
to the tumor, especially tissues in which cells normally
divide rapidly such as skin, the bone marrow, hair
follicles, and the lining of the mouth, esophagus, and
intestines. Radiation can also damage the ovaries or
testes. Skin and hair are most noticeably affected by
radiation treatment, resulting in skin lesions, burning,
redness, and possibly hair loss. The most common
complaints are fatigue, malaise, anorexia, decreased
libido, hair loss, mucositis, and bone marrow depression.
Others are low blood counts, difficult or painful
swallowing, erythema, edema, desquamation (shedding
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or sloughing-off of the outer layer of skin), increased
skin pigment (hyperpigmentation), atrophy, skin itching
(pruritus), skin pain, changes in taste, lack of appetite,
nausea, vomiting, gastritis/enteritis, diarrhea. fetal
damage (in a pregnant woman) and increased
susceptibility to infection. Acute adverse reactions occur
within the first few weeks of treatment and subside after
a few weeks. These effects are more severe with higher
doses or the concomitant use of chemotherapy.
Subacute adverse reactions develop within weeks to 6
months after radiotherapy, like the radiation pneumonitis.
Late adverse reactions appear months or even years
after therapy, depending on the total radiation dose, and
are usually caused by damage to vascular or connective
tissue, like fistulas, fibrosis, necrosis, edema, and
secondary neoplasms. Late complications are not
usually spontaneously reversible and they do not
generally respond to treatment.
Hormonal therapies can cause endometrial
cancer, blood clots, hot flashes, erectile dysfunction
(impotence), abnormal liver function test and fluid
retention. These therapies, such as selective estrogen
replacement modulators (SERMs) and aromatase
inhibitors have been shown to cause bone loss in
premenopausal women with breast cancer. Androgen
deprivation therapy may cause hypogonadism, which
increases risk for fracture. Monoclonal antibodies can
cause allergic reaction. Biologic response modifiers can
also show toxicity, alpha-IFN produces a flu-like
syndrome (headache, fever, chills, respiratory distress,
myalgia and bone marrow suppression. The toxicities
of IL-2 are more serious and include a flu-like syndrome
along with significant fluid accumulation, which can lead
to renal or cardiac insufficiency. Cancer therapy can
also cause lactose intolerance and mouth ulcers. Some
cancer treatments cause “dumping syndrome” i.e. food
is “dumped” into the jejunum (small intestine) 10 or 15
minutes after being swallowed and the presence of
undigested food in the jejunum leads to abdominal
fullness, nausea and crampy abdominal pain. Other
symptoms include feeling warm, dizzy, and faint and
there can be rapid pulse and cold sweats immediately
after eating. Bone loss also can be caused by cytotoxic
therapy directed toward the tumor or by surgical or
hormonal therapy leading to estrogen or androgen
depletion. This is referred to as treatment-related
osteoporosis or cancer-treatment–induced bone loss
(CTIBL). So it can be caused by glucocorticoids, gonadal
ablation or suppression (ovarian and testicular), and
radiation therapy to bone (causing osteonecrosis and
reduced function and number of osteoblasts). Surgically
induced menopause by oophorectomy will decline
estrogen levels and produce negative bone health.
Seeing the several side effects of cancer
therapies, preventive and corrective measures should
be followed in cancer treatment. Careful doses of
treatment modalities are required in well monitored
hospital settings. Relieving side effects is an important
part of treatment. Symptomatic treatment can be given
for some of the side effects. A registered dietitian, which
is a trained health professional in the area of nutrition,
can assist in nutritional planning for people with cancer.
PREVENTIVE MEASURES
Reducing the risks of certain cancers may be
possible through certain dietary and other lifestyle
changes. The risk of malignant tumors can be reduced
by not smoking or chewing tobacco, avoiding heavy
alcohol consumption, eating a healthy diet, exercising
regularly, maintaining a healthy weight, reducing sun
exposure if you burn easily, and minimizing exposure
to radiation and toxic chemicals. The idea is that tumors
can be prevented by avoiding things that cause cancer.
Not smoking and avoiding exposure to tobacco smoke
can greatly reduce the risk of lung, kidney, bladder, and
head and neck cancer. Avoiding the use of smokeless
tobacco (snuff, chew) decreases the risk of cancer of
the mouth and tongue. Avoiding sun exposure
(especially during the middle of the day) can reduce
the risk of skin cancer. Covering exposed skin and using
sunscreen lotion with a high sun protection factor (SPF)
against ultraviolet light also helps reduce the risk of skin
cancer. A reduced intake of fat, particularly from animal
sources, in the diet appears to decrease the risk of breast
and colon cancer. Use of aspirin and other non-steroidal
anti-inflammatory drugs (NSAIDs) reduces the risk of
colon cancer. Avoiding occupational carcinogens (for
example, asbestos), increasing intake of fruits and
vegetables, being physically active and maintaining a
healthy weight are good preventives measures.
COMPLEMENTARY / ALTERNATIVE MEDICINE
(CAM)
As the popularity of complementary/alternative
medicine (CAM) grows, patients are incorporating more
CAM therapies into their conventional cancer care.
Some people turn to alternative medicine including
certain medicinal herbs to treat their cancer, instead of
or in addition to standard treatment. However, most
types of alternative medicine have not been subjected
to careful scientific studies. Very little is known about
the effectiveness of alternative medicine in treating
cancer. It is generally believed that the use of alternative
medicine may be toxic, may interact with standard
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treatment, thus reducing the effectiveness of
chemotherapy, it may be costly, reducing the person’s
ability to afford standard treatment. Therefore these
points have to be clarified via scientific basis and
practical implications / clinical trials. Of these Ayurvedic
medicine, herbal products, homeopathy and cow urine
therapy can share the high standards of medicine. In
the next section of this review, cow urine therapy will
be discussed in details (Treasure, 2005).
COW URINE THERAPY
Cow urine has been described in ‘Sushrita
Samhita’ and ‘Ashtanga Sangraha’ to be the most
effective substance/secretion of animal origin with
innumerable therapeutic values. The medicines made
from cow urine are used to cure several diseases. Taken
in measured quantities, cow urine or gaumutra has a
unique place in Ayurveda and is suggested for improving
general health. Exploring its antimicrobial activities, it
is being used to produce a whole range of Ayurvedic
drugs. Cow urine therapy has a long history. It is
recognized as ‘water of life’ or “Amrita” (beverages of
immotality), the nector of the God in Vedas, sacred
Hindu writing, which is said to be the oldest books in
Asia. In India, drinking of cow urine has been practiced
for thousands of years. It is an important ingredient of
panchgavya, which has been tested by various workers
for its immunomodulatory properties and have been
reported that it enhances both cellular and humoral
immune response (Kumar, 2001; Chauhan et al., 2004).
It has also been experimentally proved that among all
sorts of urines, the urine of the Indian cows is most
effective and interestingly almost nil or few medicinal
properties with regards to immunomodulation are
present in the urine of crossbred, exotic cows and
buffaloes. The immunomodulatory property of
indigenous cow urine is due to the presence of a
“Rasayan” which has been found absent in urine of other
animals on HPLC analysis
Cow urine singularly has got all such chemical
properties, potentialities and constituents that are
capable of removing all the ill effects, imbalances in
the body (Bartnett, 1988; Chauhan et al., 2001;
Chauhan, 2003a). Cow urine contains 24 types of salts.
Its main contents are water 95%, urea 2.5%, minerals,
salt, hormones, and enzymes-2.5%. It contains iron,
calcium, phosphorus, carbonic acid, potash, nitrogen,
ammonia, manganese, iron, sulphur, phosphates,
potassium, urea, uric acid, amino acids, enzymes,
cytokine and lactose etc. (Bhadauria, 2002). Copper has
the power to destroy diseases and act as an antidote.
Cytokines and amino acids might play a role in immune
enhancement. Since the urine of the cow contains all
beneficial elements in it, hence it is natural and universal
medicine that fulfills the deficiency of elements and
reduces the increased elements in the body. It is the
unique quality of the urine, which helps in curing even
the most incurable diseases. There is evidence that the
urine of the cow works as the best appetizer. It
smoothens and nourishes the heart and adds to the
power of wisdom of man, and increases their physical
strength as well. It increases life span and purifies blood
from all sorts of impurities. Cow urine is entirely sterile
after secretion and has antiseptic effect. It acts like a
disinfectant and prophylactic agent and thus purifies
atmosphere.
Practitioners of Ayurvedic medicine (from India)
routinely use urine as a remedy. A number of ailments
could be treated by cow urine therapy. Most of the
medicines are made by distilling urine and collecting
vapours termed as ‘ark’ (distillate). Improvements have
been shown or reported with those suffering from flu,
sinus, allergies, colds, ear infection, rheumatoid arthritis,
bacterial/viral infections, tuberculosis, chicken pox,
hepatitis, leprosy, asthma, gastric ulcer, heart disease,
depression, hypertension, fatigue, burns, skin infections,
eczema, tetanus, morning sickness, fever, obesity, etc.
It is also used as a diuretic, laxative and for treatment
of chronic malaria, enteritis, constipation, edema,
baldness, headaches, fever, chemical intoxication, aging
etc. It is proved as a universal curer of blood disorders,
leucorrhoea and even leprosy. The urine of the cow
cleans the intestines and removes the deposited
material. Hence diseases like fever, mouth and skin
diseases menstruation disorders, asthma, giddiness,
increase of cough and urinary irregularities in humans
are cured by its regular use without any side effects. It
is non-toxic in nature. Cow urine can kill the number of
drug resistant bacteria and viruses. Even this therapy
has been reported to be beneficial for dreaded diseases
like cancer, AIDS and diabetes.
Cow Urine as Immunostimulant
Cow’s urine has immunostimulant activity in plants
and animals. Recent researches showed that cow urine
enhances the immune status of an individual through
activating the macrophages and augmenting their
engulfment power as well as bactericidal activity. In
poultry, cow urine has been reported to enhance the
immunocompetence of birds and provide better
protection along with vaccination and increases egg
production and egg quality. In-vivo cow urine treatment
to developing chicks marginally upregulated the
lymphocyte proliferation activity (Prabhakar et. al.,
18 Dhama et al.
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2004). Chauhan et al. (2001) and Kumar et al. (2004)
reported the cow urine (Kamdhenu ark’ / cow urine
distillate) to be a potent and safe immunomodulator,
which increases both humoral and cell mediated
immunity in mice. It was observed that cow urine
enhances both T and B cell proliferation and also
increases the titre level of IgG, IgA and IgM antibodies.
Chauhan et al. (2004) observed that it increases the
secretion of interleukin-1 and 2 also. The level of both
IL-1 and 2 in mice got increased by 30.9 and 11.0%,
respectively and in rats these levels were increased
significantly by 14.75 and 33.6%, respectively.
Prabhakar (2004) reported that the cow urine had
protective effect on lymphocytes of birds undergoing
apoptosis and suggested the exploitation through
experimental trails for specific use of cow urine as an
adjunct to vaccination. Thus the cow urine not only
maintains the immunity of body but also modulate it in
the positive direction to an optimum level. Garg et al.
(2004) reported beneficial effects of cow urine on serum
biochemical profile (total serum protein, glucose,
calcium and cholesterol of laying birds. Its usefulness
as antimicrobial agent, positive effect on body weight
gain and haematological profiles have also been
reported. Garg et al. (2004) suggested that cow urine
can be used as a feed additive for layer birds in order to
get good quality eggs and immune-enhancer.
Cow urine as Bioenhancer
A cow urine distillate fraction (ark) has been
identified as a bioenhancer of the activities of commonly
used antibiotics, anti-fungal and anti-cancer drugs.
Recently the cow urine has been granted U.S. Patents
(No. 6896907 and 6410059) for its medicinal properties,
particularly for its use along with antibiotics for the control
of bacterial infection and fight against cancers. The
activity of Rifampicin, a front-line anti-tubercular drug
used against tuberculosis, increases by about 5-7 folds
against E. coli and 3-11 folds against Gram-positive
bacteria (The Hindu, 4 July, 2002; The Indian Express,
4 July, 2002). Bioenhancers are substances, which do
not possess drug activity of their own but promote and
augment the bioactivity or bioavailability or the uptake
of drugs in combination therapy. Such bioenhancers
have been earlier isolated only from plant sources. It
has now been found that cow urine also acts as a
bioenhancer and increases the efficacy of the antibiotics
against infectious agents. The molecule of invention
helps in the absorption of antibiotics across the cell
membrane in the animal cells, gram positive and gram
negative bacteria. Bioenhancement has also been
observed with other drugs viz. Ampicillin, Isoniazid,
Clotrimazole, Cyanocobalamine etc. Bioenhancer
activity has been found to reduce the antibiotic dose
per day and duration of treatment in tuberculosis patients
(Joshi, 2002). The Indigenous cow urine contains
“Rasayan” tatva, which is responsible to modulate
immune system and act as bioenhancer.
ANTI-CANCER PROPERTIES OF COW -URINE
Cow urine possesses anti-cancer properties.
Research works carried out by Go-Vigyan Anusandhan
Kendra (Cow Science Research Center) at Nagpur
revealed the beneficial properties of cow urine in the
treatment of cancers. Further extensive research on cow
urine therapy against fighting cancer carried out by
Scientists of Central Institute of Medicinal and Aromatic
Plants (CIMAP), CSIR Center at Lucknow, along with
collaboration with Go-Vigyan Anusandhan Kendra,
Nagpur confirmed this milestone achievement. Studies
highlight the role of cow urine in curing cancers and
that cow urine enhances the efficacy and potency of
anti-cancer drugs. Recently, this significant achievement
has been validated by the grant of U.S. Patent (No.
6896907) in the field of treatment of cancers (Amar
Ujala, July, 19, 2005).
Scientists have proved that the pesticides even
at very low doses cause apoptosis (cell suicide) in
lymphocytes of blood and tissues through fragmentation
of DNA. Distilled cow urine protects DNA and repairs it
rapidly as observed after damage due to pesticides
(Ambwani, 2004). It protects chromosomal aberrations
by mitocycin in human leukocyte (Datta, 2001). Cow
urine helps the lymphocytes to survive and not to commit
suicide (apoptosis). Kumar et al. (2004) reported the
prevention of pathogenic effect of free radicals through
cow urine therapy. These radicals cause damage to
various tissues and attack enzymes, fat and proteins
disrupting normal cell activities or cell membranes,
producing a chain reaction of destruction leading to the
ageing process of a person. By regular use of cow urine
one can get the charm of a youth as it prevents the free
radicals formation.
Thus, the cow urine therapy is suggested to
possess potent anti-cancer abilities by the virtues of
the following properties –
Antimicrobial capability: Cow urine can kill the
number of drug resistant bacteria and viruses, thus can
reduce the incidences of cancer since many a viruses
have been reported to cause cancer.
Bioenhancing property: It can promote and
augment the bioactivity or bioavailability or the uptake
of cancerous drugs, thus could enhance the efficacy
and potency of the chemotherapy drugs, and reduce
Anti-Cancer activity of cow urine 19
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their dose and duration of treatment, which could also
help reduce the cost and side effects of chemotherapy.
So in combination therapy cow urine can be used
efficiently.
Immunomodulating activity: Cow urine
enhances the immunocompetence and improves
general health of an individual. It has vital potential to
enhance the activity of macrophages and lymphocytes
(both T and B cells), and has been reported to increase
the humoral and cellular mediated immunity. Increased
immunocompetece of an individual is a very essential
parameter to prevent the development of cancers by
several mechanisms, of which the upregulation of
lymphocyte proliferation and stimulation activity,
increased macrophage activity, higher antibody
production and increased synthesis and secretion of
cytokines (IL-1, Il-2) plays significant role by enhancing
the recognition of tumor cells by the immune cells of
the body and cytotoxic activities of the tumor killing cells,
the lymphocytes.
Anti-aging factor: It is an efficient anti-aging
factor, since prevents the free radicals formation, which
could help preventing cancers as the incidences of
cancer increases as the one progresses towards old age.
DNA repairing potential: Cow urine efficiently
repairs the damaged DNA, thus can be very effective
for the cancer prevention and therapy, and can also
reduce the spread of malignant cancers and help fighting
tumors.
Apoptosis inhibitor: Cow urine can tremendously
reduce apoptosis in lymphocytes and helps them to
survive, thus the body can avail the tumor fighting
abilities of the lymphoctyes at their optimum activity
and survivabability.
US Patent for Cow urine in the field of cancer:
Recently a pharmaceutical composition comprising an
effective amount of bioactive fraction from cow urine
distillate (CUD) as a pharmaceutically acceptable
additive was tested and applied for a US patent. The
invention relates to an absolutely novel use of CUD as
an activation enhancer and availability facilitator for
bioactive molecules such as anti-infective and anti-
cancer drugs. It was found that the urine distillate
effectively reduced the dosage of drug needed for the
therapies. The applicants (Khanuja et al., 2002) obtained
the ‘Kamadhenu Arka’ (CUD) from Go-Vigyan
Anusandhan Kendra, Nagpur, India and studied its effect
and of the dried fraction (GM-IV). A pharmaceutical
composition comprising of at least one anticancer agent
(‘Taxol’- Peclitaxel) and a cow urine distillate or a dried
fraction (GM-IV) obtained from cow urine distillate was
studied. Cow urine was distillated around 40-50°C to
obtain the distillate and the distillate concentrate
obtained by lyophilization. The cow urine distillate was
used in a concentration range of 0.001µl/ml to 100µl/
ml, and at a concentration 1µl/ml was found to enhance
the cell division inhibitory activity of the drug ‘Taxol’ in
breast cancer cell line, MCF-7 (NCCS, Pune) by 2-20
folds. The GM-IV which was obtained in the range of
10-20 grams/100ml of the distillate showed the same
effect at 0.001-10µg/ml and was found to be more stable
and devoid of unpleasant smell of urine and hence
considered as the advanced product of the invention.
Thus the potency of ‘Taxol’ (paclitaxel) was observed to
get increase against MCF-7, a human breast cancer
cell line in in-vitro assays.
Table showing the effect of Cow urine distillate as
activation enhancer of ‘Taxol’
Taxol Initial titre Final titre Final titre of
(
µµ
µµ
µg/ml) of cancer of cancer viable cancer
cells cells with cells with
Taxol Taxol and Cow
urine distillate
0.001 0.9x10
6
0.059 x10
6
0.039 x10
6
0.005 0.9x10
6
0.042 x10
6
0.032 x10
6
0.01 0.9x10
6
0.036 x10
6
0.012 x10
6
The most important feature of this invention is the
finding that the enhancement action and effectiveness
of the ‘Arka’ is achievable in the very low concentration
(nano to micro molar levels), thus a very low dose of
ark can be helpful in curing cancer, which can reduce
the cost of the treatment.
Thus encouraging results were observed with cow
urine treatment for the antibiotics as well as cancer
therapy. The findings have reflected a direct implication
in reducing the effective dose of drugs as well as acting
as a bio-enhancer. Therefore, the future of cow urine
therapy is encouraging especially in cancer therapy, and
it may very well reduce the harmful side effects of
radiation treatments. The above two U.S. Patents have
attracted global attention. US Patents honored to Indian
Scientists on Cow urine therapy also made realize that
the traditional practices from Indian systems of medicine
have a strong scientific base.
During the past few years cow urine therapy has
provided promising and authentic results for the
treatment of cancer, a deadly malady which is being
faced by the mankind and the incidences of which are
ever increasing in the current scenario of changed
lifestyle and food habbits along with exposure to
predisposing factors of carcinogens such as tobacco
chewing, smoking, alcohol intake, environmental
20 Dhama et al.
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pollutants, occupational health hazards etc. Anti-cancer
potential of cow urine therapy has been reflected by
several case reports, success stories and practical feed
back of patients for the treatment of cancer.
CASE REPORTS, FEEDBACK AND SUCCESS
STORIES
Cow Urine Cancer Cure: Oro-Pharyngeal
Carcinoma- A Case Report: A patient (63 old women)
from Kasargod district of Kerala state in November 2003
was presented to Kasargod Institute of Medical
Sciences, Kasragod, Kerala, with stage IV squamous
cell carcinoma of tonsil, and was treated with
radiotherapy. Even though the carcinoma of tonsil is
highly sensitive to radiations, it is unable to cure the
IV
th
stage. The presented patient showed nasal
regurgitation, dysphagia, dyspnoea and was spitting
blood at times. The patient was supposed to succumb
to the tonsilar neoplasia as evinced by the cachetic
appearance and the severity of the symptoms
suggesting a poor prognosis. She was later adviced to
take 15 ml of ‘Amrutha Sara’ (cow urine distillate) twice
a day and was asked to come after 2 weeks for the
follow up. On the first follow up visit the patient had
shown improvement in the symptoms and was able to
take small quantities of liquid food without the help of
feeding tube. The same therapy was continued for a
period of 10 months with which the patient was
completely cured of the disease. After the cow urine
therapy, the physical examination revealed no visible
oropharyngeal lesions and no cervical palpable lymph
glands. The malignant lesions in tonsils and secondary
lesions in lymph glands were effectively controlled. The
surface of the tosillar fossa and fauces were smooth
and showed no evidence of tumor growth. The tonsillar
malignancy disappeared completely which suggested
the antineoplastic effects of cow urine distillate. This
points to the possibility of the role of the ‘Amrutha Sara’
as an effective antineoplastic drug, clearly evinced by
the dramatic recovery of the patient from stage IV of
the cancer to normalcy. The antineoplastic effects of
cow urine may possibly be due to the antioxidant
properties of vitamins A, E, C and the volatile fatty acids,
both of which acted together to elicit a favorable
response.
Other Case Reports And Success Stories: In
other case reports and feed back obtained from persons
treated for cancer using processed cow urine in the form
of ‘Ark’, it has been observed that cow urine therapy
was successful in fighting the cancer as reflected by
the absence of cancerous cells/tissue, decrease in the
size of tumor, clinical and biochemical picture of the
patient. Mr Kamlesh kumar Agarwal, a native of Kareli
Dist. Narsinghpur (MP) suffered from a cancer near the
kidney due to which his kidney became nearly non-
functional and inspite of different known cancer-
therapies, there was no improvement in his health. After
the use of ‘Kamdhenu Ark’ prescribed by the Cowpathy
physicians, Nagpur, 98% improvement was reported in
his cancer. Mr. Ram Sagar Singh, a native of Begusaray,
north bihar got 80% improvement in the throat cancer
after cow urine therapy. Smt. Seema Verma , resident
of Jainagar (north Bihar), was completely cured from
brest cancer by taking kamdhenu ark. Mr. Babulal
Rungta, got affected with cancer suffered from chronic
renal failure, with serum creatinine and urea level being
10.4 and 107, respectively, and was kept on dialysis
twice a week. After cow urine therapy (Kamdhenu Ark)
his serum creatinine and urea levels were dropped down
to 5.3 and 63, respectively with a drastic improvement
in the functioning of kidneys and relieving of cancer.
Mr. Nanak Bhosray Dhingra, a patient suffering from
multiple myeloma and severe waist pain showed
improvement with the cow urine therapy.
However, scientific validation of cow urine therapy
for the prevention and treatment of cancer, as reflected
in the above practical cases and reports, is required for
its worldwide acceptance and popularity. The unique
anti-cancer activity of cow urine needs immediate
attention and the strategies for promoting its vital
medicinal potential and perspectives for the benefit of
mankind should be planned appropriately. For this proper
support of the scientists, researchers and clinicians/
physicians is needed by which authentic research data
and practical implications of cow urine therapy in the
field of treatment of cancers can be generated, which
can further strengthen this alternate low cost therapy
having no side effects, generally observed with
chemotherapy and radiation therapy being followed for
curing cancers, and thus confidence can also be inspired
in the public about its good virtues.
STRATEGIES TO PROMOTE COW-URINE THERAPY
l Comparative chemical, microbiological and
immunological analysis of urine of various
indigenous cattle breeds with special
reference to their medicinal and nutritional
significance should be evaluated
scientifically.
l Integrated and coordinated approach should
be made for promoting scientific outlook,
research and applications of cow urine in the
field of medicine through information sharing
by organizing conferences, seminars,
Anti-Cancer activity of cow urine 21
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workshops, exhibitions and orientation
programmes.
l A sound data-base or data-collection system
should be developed for further scientific
evaluation of cow urine in the treatment of
cancer and other diseases including the
incurable diseases like AIDS. There should
be a drive for the verification of clinical and
medicinal claims made in ancient literature
related to medicinal properties of cowpathy.
l Applications of cow urine need to be testified
in clinical trials in Veterinary Colleges,
Research Institutes, Universities and
Hospitals. Research programmes should be
undertaken, encouraged and supported in
national institutions, universities and non-
government organizations (NGOs).
l Special R&D fund should be created to
encourage both public and private sector
institutions to undertake result-oriented and
time-bound projects on cow urine.
l The drug control authorities should, after
thorough examination, include such products
in Indian pharmacopia so that their
production and quality may be suitably
standardized.
l Wide publicity by mass communication is
needed by publishing literature, research/
popular articles, and launching web-site(s)
on the implications of cow urine for treating
several diseases and as a potent anti-cancer
therapy. Centers should be established and
recognized for promotion of the innovations
in the field of utility of cow urine in treating
cancer.
l Encouragements, rewards and honors
should be given to research in cow urine
therapy such as that done by the Govigyan
Anusandan Kendra, Nagpur and CSIR at
Lucknow and other centers, which led to the
grant of U.S. Patents, and which may also
help in generating alternative treatment
methodologies.
l Proper attention should be given on cow
urine and panchgavya therapy for inducing
protection against several diseases in the
livestock/poultry populations. The role of cow
urine in enhancing the immunity and general
health needs to be explored in the right
directions.
l Subsidies should be given for production of
cow urine distillate or ark in bulk quantities
and its wide availability should be facilitated
and strengthened.
l As source of medicinal benefits apart from
mechanical, thermal, and electrical energy
along with agricultural benefits, the cattle
wealth should be promoted in the country.
By providing proper funds, infrastructure and
needful promotional campaigns of publicity (adverti-
sements, mass media awareness) and generating
scientific data for the support of cow urine therapy in
curing cancers, this alternative can come out to share
shoulders with the allopathy and multi-national drug
companies.
CONCLUSION
Cancer is a dreaded malady to the mankind, which
though can be treated by following various therapy
procedures of surgery, chemotherapy, radiotherapy and
immunotherapy along with recent molecular approaches
of gene therapy, but the success rate and cost of these
therapy modalities is not very high and moreover, their
well known side effects puts burden on the patients to
be treated. Alternate therapies including of herbs,
homeopathy and ayurvedic medicines have also been
claimed to be helpful in the prevention and control of
cancer. Cow urine therapy has also been claimed to
possess anti-cancer properties and has been supported
recently by the grant of US patent in the field of cancer
treatment by its virtues of bioenhancing the activity of
anti-cancer drugs. The hypothesis of cow urine therapy
in curing cancer has also been supported in the last few
years by the case reports, feed backs and success
stories of the patients treated by this novel alternate
therapy for cancer. The area of cow urine therapy has
tremendous potential in the field of medicine and has
not been exploited to the extremes. Efforts need to be
made for public awareness about the vital virtues of
cow urine therapy. Though, the end user claims are
many but scientific validation of those claims is required.
Most of the tested practices of cowpathy or cow urine
therapy are rejected as myth or mythological
adventures. Now people need information and data
based on research. It is therefore necessary to blend
science, spirituality and wisdom. Such a blending has
resulted in US patents for the cow urine in possessing
anti-cancer and bio-enhancing properties. These
approaches and their potential applications should be
widely promoted. Modulating into the right channels the
research on cow urine and other panchgavya elements,
may be many more patents are awaiting ahead. Grant
of U.S. Patents to cow urine has given the ultimate
stamp of approval for Indian Systems of Medicine and
22 Dhama et al.
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the panchgavya products, particularly the cow urine,
since they have passed through the high standards of
modern scientific testifying methodologies.
Establishment of research and development centers in
this medicinal utility of cow urine and generation of
authentic data for the support and of cow urine therapy
in the treatment of cancer by physicians, clinicians,
scientists and researchers should be given priority, which
can strengthen and promote this unique and natural
alternate therapy in fighting against the cancer, which
would provide a great relief to the human sufferings.
Cow urine is a universal medicine and can be the best
therapy for mankind in curing various sorts of disorders.
It is non-toxic and can be obtained free of cost trough
domestication of indigenous cow. The cow urine therapy
should gain popularity not only in traditional families
but also in highly educated and scientific societies. Thus
an integrated approach is necessary to promote the
highly valuable virtues and wide applications of
Cowpathy, a new version of ancient science, which is
definitely a promising formulation in the years to come
by following the desired promotional strategies. Utilizing
the beneficial properties of cow urine, day may not be
far away when the incurable diseases like cancer, AIDS
and other deadly maladies can be treated successfully.
The role of cow urine in curing the cancer needs further
attention as they can serve as a reliable treatment
alternative without side effects. Further case studies
involving the successful use of ‘Go-muthra Ark’ or
‘Kamdhenu Ark’ are to be brought to medical attention
and should be passed on to the masses.
ACKNOWLEDGEMENT
Authors are thankful to Sri Suneel Mansinhka,
Director, Go-Vigyan Anusandhan Kendra, Nagpur for
providing clinical case histories, success stories and
feed-backs from patients to compile this article.
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Anti-Cancer activity of cow urine 25
... Some evidences of cow urine benefits in cancer treatment are also available. Dhama et al. (2005) reported few case studies related to effect of Re-distillate Cow Urine Distillate (RCUD) as anticancer agent. A female from Kerala with age of 63 years had oropharyngeal carcinoma, who was completely recovered with the intake of Amurtha Sara, made from cow urine. ...
... Different case studies suggesting anticancer activities of cow urine distillate(Dhama et al., 2005) ...
... Cow urine after addition of neem leaves is a wonderful bio pesticide. Such bio pesticides are safe to use, do not accumulate in the food chain and as such do not have the harmful effects like chemical pesticides (Dhama et al., 2005) CONCLUSION Cattle urine having potency in pest infestation control and it improves the nutrient availability for boro rice plant growth, follicle development ultimately it improve boro rice production which is economically comparable with chemical fertilizers and pesticides. Elaborate filed trial and research is necessary for identifying cattle urine potency introduction in coming future. ...
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This study focused on cattle urine utilization as bio-fertilizer and bio-pesticide and its effectiveness on boro rice production comparing with chemical fertilizer and chemical pesticides. Three groups were divided into completely randomized design (CRD) to conduct the experiment. No chemical/bio pesticides and/or fertilizers is being applied in the control group (T0).The second group (T1) is being applied by chemical fertilizer and pesticides in recommended dose. The third group (T2) is being applied by cattle urine as biofertilizer and bio-pesticides in calculative dose. The germinated rice plant BINA boro rice (variety 28) was transferred to a well-prepared rice field after 21 days. The rice field was prepared using cow urine as bio fertilizer. The bio fertilizer solution prepared from mixing cow dung with cow urine (1:1) and then the solution was diluted into1: 9 with water. One kg of fresh neem leaves were kept in 10 L (liters) container with cow urine and allowed 28 days for fermentation. Meanwhile, one liter of the solution extracted from neem leaves was mixed with 10L of fresh water in a ratio of 1:10 to produce a bio pesticide. Cow urine as bio-fertilizer was applied one thousand liters per hectare in boro rice production which was repeated every 28 days from transplant to harvest. Bio pesticide was applied one thousand two hundred liters per hectare by nozzle spraying at 15-day intervals from planting to flowering in boro rice production. Likewise the chemical pesticide was being applied at seven-day intervals. Plant height, chlorophyll content, number of the tiller/hill and grain yield was observed as growth and yield parameter respectively. The tallest plant height and chlorophyll content were 76 cm and 46.5 from T2 on day 45 and 30 respectively, but number of effective tiller per hill, the maximum final score was 14 fromT1.For all treatments, the mean production became identical. However, T2 delivered the highest grain yield at 5.85 t/ha. In yield parameter chemical fertilizer and chemical pesticide (T1) and bio fertilizer and biopesticide (T2) group was non-significant, but in pest infestationbio fertilizer and biopesticide (T2) group was lower. Vol. 9, No. 2, August 2022: 165-169
... Research carried out on indigenous cow urine showed various positive health effects like immunomodulatory, anti-cancer, bioenhancer, anti-infection and it plays an important role in DNA repair Chauhan, 2013;Chauhan, 2017;Chauhan and Malik, 2022). Cow urine improve the human wisdom and act as universal medicine (Dhama et al., 2005). The information on indigenous cow urine on hemogram is scanty and specially there is no report of Badri cow urine. ...
... As a result, regular usage of cow urine helps to maintain the balance of these elements in the human biological system, so aiding in the maintenance of good health and the treatment of various ailments (Singh, 2019). Cow urine increases an individual's immunocompetence and overall health; prevents the creation of free radicals and acts as an anti-aging agent; decreases lymphocyte apoptosis and helps them survive; and efficiently repairs damaged DNA, making it an effective cancer therapy (Dhama et al., 2005). Cow urine has been shown to have anti-hepatotoxic, anti-diabetic, anti-bacterial, immunomodulatory, wound healing, neuroprotective, and geno-protective properties (Sushma et al., 2021). ...
... Cow's milk is a rich source of vitamin K which prevents hemorrhagic disease of newborn, as folic acid present in the milk protects against anaemia. 21,22 Cow milk has anti-aging properties. It has also got fungicidal properties against powdery mildew (Sphaerotheca fuliginea) and can be used as a fungicidal. ...
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Cow urine has many beneficial properties particularly in the area of agriculture and therapeutics. Indigenous cattle or zebu cattle is considered as sacred in Indian literature because it’s products like urine, dung, milk, curd and butter has many wonderful medicinal properties. Among these products cow urine has recently caught the attention of the researchers and a lot of work is going on its medicinal properties. Cow urine is found to have bioenhancing properties, i.e. it adds to the effect of the antibiotics when used in combination. It is can be used as an alternative to the antibiotics in feed additives. Cow urine concoction is believed to have anticonvulsant and hypoglycaemic effects; and is also useful for treating liver disorders and fever; inflammations and anaemia. Practitioners of Ayurvedic medicine from India routinely use cow urine as a remedy and the medicines made from it are used to cure several diseases. Improvements have been shown or reported with those suffering from flu, allergies, colds, rheumatoid arthritis, bacterial/viral infections, tuberculosis, chicken pox, hepatitis, leucorrhoea, leprosy, ulcer, heart disease, asthma, skin infections, aging, chemical intoxication etc. Cow urine can kill the number of drug resistant bacteria and viruses. Recently the cow urine has been granted U.S. Patents (No. 6896907 and 6,410,059) for its medicinal properties, particularly for its use along with antibiotics for the control of bacterial infection and fight against cancers. Cow urine contains 24 types of salts and the medicines made from cow urine are capable of curing even the most incurable diseases. Cow urine contains 95% water, 2.5% urea, and 2.5% minerals, salts, hormones and enzymes. It contains iron, calcium, phosphorus, salts, carbonic acid, potash, nitrogen, ammonia, manganese, sulphur, phosphate, potassium, urea, uric acid, amino acids, enzymes, cytokines, lactose etc. Cytokines and amino acids may play a role in immunoenhancement. Cow urine has antioxidant properties; it can prevent the damage to DNA caused by the environmental stress. And interestingly these properties have been found only in the urine of indigenous cow not in the urine of other species like buffalo, goat or not even in cross bred cows.
... Radiation therapy, surgery, and chemotherapy are all used in combination or separately to treat cancer, yet it may go undetected and untreated for many years [2]. The urgent need for novel anticancer treatments that are less expensive and have fewer side effects is obvious [3]. Numerous therapies have been approved, including selective cyclooxygenase-2 (COX-2) inhibitors and epidermal growth factor receptor (EGFR) monoclonal antibodies. ...
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For most researchers, discovering new anticancer drugs to avoid the adverse effects of current ones, to improve therapeutic benefits and to reduce resistance is essential. Because the COX-2 enzyme plays an important role in various types of cancer leading to malignancy enhancement, inhibition of apoptosis, and tumor-cell metastasis, an indispensable objective is to design new scaffolds or drugs that possess combined action or dual effect, such as kinase and COX-2 inhibition. The start compounds A1 to A6 were prepared through the diazo coupling of 3-aminoacetophenone with a corresponding phenol and then condensed with two new chalcone series, C7-18. The newly synthesized compounds were assessed against both COX-2 and epidermal growth factor receptor (EGFR) for their inhibitory effect. All novel compounds were screened for cytotoxicity against five cancer cell lines. Compounds C9 and G10 exhibited potent EGFR inhibition with IC50 values of 0.8 and 1.1 µM, respectively. Additionally, they also displayed great COX-2 inhibition with IC50 values of 1.27 and 1.88 µM, respectively. Furthermore, the target compounds were assessed for their cyto-toxicity against pancreatic ductal cancer (Panc-1), lung cancer (H-460), human colon cancer (HT-29), human malignant melanoma (A375) and pancreatic cancer (PaCa-2) cell lines. Interestingly, compounds C10 and G12 exhibited the strongest cytotoxic effect against PaCa-2 with average IC50 values of 0.9 and 0.8 µM, respectively. To understand the possible binding modes of the compounds under investigation with the receptor cites of EGFR and COX-2, a virtual docking study was conducted.
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Ghee, the clarifed butter fat is one of the principal dairy products in India. In some places of India, cotton seed is fed extensively to dairy animals which changes the physico-chemical constants and fatty acid profle of the milk fat. Ghee is often adulterated with cotton seed oil and is marketed as cotton tract area ghee. Physico-chemical constants like RM value, Polenske value, BR reading, saponifcation value, iodine value and colorimetric tests i.e., Halphen and DPPH radical test were employed to diferentiate ghee adulterated with cotton seed oil and that from cotton tract area. Chromatographic techniques like HPLC and GC-MS were also explored. Physico-chemical constants were not useful to diferentiate the two types of ghee. Cyclopropenoic acids were observed only in ghee adulterated with cotton seed oil and not in cotton tract ghee. The RP-HPLC could able to distinguish the cotton tract area ghee from ghee adulterated with cotton seed oil on the basis of presence of β-sitosterol in the latter. Halphen test was positive for cotton tract ghee, but not for the cotton seed oil adulterated ghee. Methylene blue reduction and DPPH radical test were also found to be useful to distinguish both types of ghee.
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Ovarian cancer is characterized by the establishment of tolerance, the recurrence of disease, as well as a poor prognosis. Gene signatures in ovarian cancer cells enable cancer medicine research, therapy, prevention, & management problematic. Notwithstanding advances in tumor puncture surgery, novel combinations regimens, and abdominal radiation, which can provide outstanding reaction times, the bulk of gynecological tumor patients suffer from side effects & relapse. As a consequence, more therapy alternatives for individuals with ovarian cancer must always be studied to minimize side effects and improve progression-free and total response rates. The development of cancer medications is presently undergoing a renaissance in the quest for descriptive and prognostic ovarian cancer biomarkers. Nevertheless, abnormalities in the BRCA2 or BRCA1 genes, a variety of hereditary predispositions, unexplained onset and progression, molecular tumor diversity, and illness staging can all compromise the responsiveness and accuracy of such indicators. As a result, current ovarian cancer treatments must be supplemented with broad-spectrum & customized targeted therapeutic approaches. The objective of this review is to highlight recent contributions to the knowledge of the interrelations between selected ovarian tumor markers, various perception signs, and biochemical and molecular signaling processes, as well as one's interpretation of much more targeted and effective treatment interventions.
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In India, cow dung is a low-cost and widely available bioresource used for a variety of traditional purposes, including fire, insect repellent and cleaning. Cow dung contains a varied array of bacteria that, due to their ability to produce a variety of metabolites, may be helpful to humans. Many cow dung microbes have proven inherent potential to boost soil fertility by phosphate solubilization, in addition to producing unique compounds. Nowadays, there is a growing interest in researching applications of cow dung microbes for biofuel generation and environmental pollution management. Anaerobic digestion is a process that converts organic wastes such as cattle manure, dairies solid wastes, etc. into methane and agricultural residues as a sustainable bioresource (biogas and biomethane). The composition of biogas produced by anaerobic digestion varies, but it primarily consists of methane and carbon dioxide, with a small amount of trace gases. The type of substrate being digested, operating temperature, pH, hydraulic retention duration, organic loading rate and digester design are all elements that influence biogas composition. As a result, the goal of this review study is to provide a complete examination of cattle organic waste (cow dung) that has been utilized as a substrate for the long-term production of biogas and/or biomethane, as well as its subsequent applications.KeywordsCow manureBiogasBiomethaneAnaerobic digestionMicroorganism
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Targeted therapies for cancer are discussed. Research into the molecular biology of cancer has revealed critical differences between normal and tumor cells and has pinpointed key processes that regulate the growth and progression of cancers. This, has in turn allowed for the development of agents that specifically target these molecules and pathways, particularly those regulating the signaling transduction pathway that controls cell replication, differentiation, tumor metastasis, and apoptosis. Such novel targeted therapies include those that can inhibit the function of cellular growth factors or their receptors essential for signal transduction, block angiogenesis required for tumor growth and metastasis, and antisense strategies designed to suppress the expression of specific genes. These approaches have resulted in clinical benefit for selected tumor types, yet challenges remain such as determining the optimal dose and administration of these agents, alone or in combination with standard cytotoxic chemotherapy, and at what stage of disease they might have the greatest influence.
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A panchagavya Ayurvedic formulation containing E. officinalis, G. glabra, and cow's ghee was evaluated for its effect on pentobarbital-induced sleeping time, pentylenetetrazol-induced seizures, maximal electroshock-induced seizures, spontaneous motor activity, rota-rod performance (motor coordination) and antagonism to amphetamine in mice. The formulation (300, 500 mg/kg, po) produced a significant prolongation of pentobarbital-induced sleeping time and reduced spontaneous locomotor activity. The formulation also significantly antagonised the amphetamine induced hyper-locomotor activity (500, 750 mg/kg, po) and protected mice against tonic convulsions induced by maximal electroshock (500, 750 mg/kg, po). The formulation slightly prolonged the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. The formulation did not show neurotoxicity. The results suggest that the panchagavya formulation is sedative in nature.