Koyamangalath Krishnan

• MD
• Chair at East Tennessee State University

PGI Textbook of Laboratory and Clinical Hematology was compiled by an international group of authors and editors. The editorial team led by Koyamangalath Krishnan and ably supported by Bakul Dalal, Amar Dasgupta, Pankaj Malhotra, Neelam Varma, and Subhash Varma have successfully brought together the experience of a team of international PGI-trained...

With special properties such as excellent fluoresce features, low toxicity, good biocompatibility, permeability, and easy clearance from the body, carbon dot (CD)-based nanoparticles (NPs) have the potential to deliver drugs and use in vivo diagnostics through molecular imaging. In this work, folic acid-CD (FA-CD) NPs were prepared to deliver doxor...

Burkitt lymphoma is a highly aggressive B cell non-Hodgkin’s lymphoma characterised by translocation of MYC gene on chromosome 8. This translocation is usually detected by fluorescent in-situ hybridisation (FISH) studies as part of routine diagnostic work-up and prognostication. FISH testing is commonly done with the break-apart probe (BAP). This c...

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer. It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here...

Metformin and γ-tocotrienol (GT3) are promising chemopreventative agents with studies showing improved patient outcomes with metformin use in several cancer types, including prostate cancer. However, the cellular mechanisms underlying the improved survival rates in cancer patients treated with these drugs are incompletely understood. Inhibition of...

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promot...

Cancer management is no longer solely based on the anatomical site of the tumor and is rapidly evolving to take into account the individual differences giving rise to a tumor’s set of phenotypes, i.e., precision oncology (NCI dictionary 2019). Nevertheless, most cancer treatments still rely on a “one size fits all” or a “few sizes” fits all approac...

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote...

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote...

Background: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote...

Qualitative disorders of platelets are often missed at clinical evaluation. Hermansky-Pudlak (HPS) syndrome is a rare genetic metabolic disorder with subtype specific clinical associations most prevalent in Puerto Rico with strong link to consanguinity. HPS is usually associated with albinism, visual impairment and a qualitative platelet dysfunctio...

Background: Lymphoid blast crisis, one of the two major forms of chronic myeloid leukemia (CML) blast crisis (BC), is comprised of lymphoblasts and occurs in about 30% of BC patients. These individuals often respond to the same treatment strategies used in Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Blinatumomab, a bisp...

Heřmanský–Pudlák syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS‐6) is an uncommon subtype generally associated with mild disease. A Caucasian adult female present...

Metformin and γ-tocotrienol (GT3) are promising non-cytotoxic drugs for prostate cancer chemoprevention and as adjunctive treatment options for prostate cancer. Multiple mechanistic pathways may be modulated. Studies suggest that GT3, a member of the vitamin E family, and the antidiabetic agent metformin have antineoplastic properties but their eff...

Background: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in cerami...

This chapter focuses on the role of antioxidant vitamins in protecting the gastrointestinal (GI) tract from oxidative stress. A systems medicine approach is used since it alone is sufficiently comprehensive to capture the broad range of relevant complexities and interrelationships relevant to GI protection. Systems medicine utilizes and integrates...

Introduction: Colorectal cancer is 3rd most common cancer and is the 2nd leading cause of cancer-related deaths in the United States. Type-2 diabetes mellitus increases the risk for several types of cancers including the liver, pancreas, colon, endometrium, and breast. Insulin resistance, hyperinsulinemia, oxidative stress, and proinflammation have...

Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand–foot sk...

The cumulative evidence presented above supports the protective role of some antioxidants and the causative role of prooxidants in many GI disorders. Tocotrienols look particularly promising as protective antioxidants. The use of genomic and metagenomic information is poised to make major contributions to understanding the mechanisms of many GI dis...

Background: A goal of precision chemoprevention is to prevent or delay cancer progression by using minimally toxic agents guided by knowledge of alterations in oncogenic molecular pathways and signaling cascades. Indolent prostate cancer can benefit from chemopreventive agents by delaying growth. Vitamin E is not a single compound and refers to fou...

A goal of precision chemoprevention is to prevent or delay cancer progression by using minimally toxic agents guided by knowledge of alterations in oncogenic molecular pathways and signaling cascades. Indolent prostate cancer is usually a slowly progressing cancer and chemopreventive agents could be useful in further delaying cancer progression. Vi...

Despite major advances in treatment, pediatric cancers in the 5-16 age group remain the most common cause of disease death, and one out of eight children with cancer will not survive. Among children that do survive, some 60% suffer from late effects such as cancer recurrence and increased risk of obesity. This paper will provide a broad overview of...

AKT activation is often associated with resistance to chemotherapeutic agents. We hypothesize that this drug resistance could be caused by the induction of Prdx1 by activated AKT1. Inhibitors of Prdx could, therefore, be effective in overcoming the resistance to pro-oxidant chemotherapeutics. As proof of concept we have found that: (1) inhibition o...

Objective: This study tested the effectiveness of a brief, learner-centered, breaking bad news (BBN) communication skills training module using objective evaluation measures. Methods: This randomized control study (N=66) compared intervention and control groups of students (n=28) and residents' (n=38) objective structured clinical examination (O...

Peroxiredoxins (PRDXs) are highly abundant antioxidant enzymes overexpressed in many cancers, e.g., breast cancer, prostate cancer, lung cancer. About 90% of cellular peroxides are reduced by PRDXs. Melanoma cells, and cancer cells in general, often have a high level of oxidative stress which is thought to drive the expression of many cancer phenot...

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA The antidiabetic drug, Metformin, may possess anti-cancer properties. Metformin has been shown to suppress proliferation of breast cancer cells primarily through activation of AMP-activated protein kinase (AMPK) and its suppression of downstream signaling pathways, suc...

Targeting the mutant BRAF protein is an accepted approach to the treatment of metastatic melanoma. Potent and specific BRAF inhibitors like vemurafenib and dabrafenib are superior to chemotherapy in treatment of BRAF mutant melanomas which represent nearly 50% of all melanomas. Previous studies have shown that certain isoforms of vitamin E and stat...

The predicted structure of oxidized protein hydrolase and its role as a prodrug target for a novel pro-oxidant chemotherapeutic agent

Metformin, an anti-diabetic biguanide, has been shown to have cytotoxic and chemopreventive properties in in vitro and epidemiological studies, respectively. Metformin's predominant cytotoxic functions may be through activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) with subsequent cell apoptosis. Ceramides, a group of waxy l...

The mevalonate pathway plays an important role in cancer biology and has been targeted with farnesyl transferase inhibitors, although their efficacy is limited due to significant adverse effects. Statins and bisphosphonates inhibit the mevalonate pathway at different steps, thus having negative effects at various levels on cancer cells. A combinati...

Background Cancer cell esterases are often overexpressed and can have chiral specificities different from that of the corresponding normal cells and can, therefore, be useful targets for activating chemotherapeutic prodrug esters. Prodrug esters are inactive compounds that can be preferentially activated by esterase enzymes. Moreover, cancer cells...

A patient is diagnosed with chronic lymphocytic leukemia 6 months after he was diagnosed with chronic myeloid leukemia for which he initially received imatinib.

Oxidative stress is a documented factor in the pathogenesis of inflammation and cancer. Vitamin E with its antioxidant properties holds promise for use in clinical practice. There are two main forms of vitamin E, tocopherols and tocotrienols. Palm oil contains almost 70% of tocotrienols. Tocotrienols exerts its antiproliferative activity against ma...

This review focuses on the roles antioxidants and pro-oxidants in colorectal cancer (CRC). Considerable evidence suggests that environmental factors play key roles in the incidence of sporadic CRC. If pro-oxidant factors play an etiological role in CRC it is reasonable to expect causal interconnections between the well-characterized risk factors fo...

Esterases are often overexpressed in cancer cells and can have chiral specificities different from that of the corresponding normal tissues. For this reason, ester prodrugs could be a promising approach in chemotherapy. In this study, we focused on the identification and characterization of differentially expressed esterases between non-tumorigenic...

Cancer is the second leading cause of death in the United States and is expected to become the primary cause of disease-related death within the next decade. There are significant country-to-country variations in cancer incidence, which suggests that nutrition and dietary factors are important to the carcinogenesis process. An increased risk of can...

Cancer cells often exhibit a high level of intrinsic oxidative stress due to an increased formation of reactive oxygen species and a decreased expression of enzymatic antioxidants. Prodrugs inducing additional oxidative stress can selectively induce apoptosis in cancer cells already having a high level of intrinsic oxidative stress. This study focu...

Introduction Statins and tocotrienols modulate the cholesterol biosynthesis pathway by inhibiting the 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. Tocotrienols modulate HMG-CoA reductase by post-transcriptional downregulation. In addition, tocotrienols contain a farnesol moiety in its side-chain that triggers degradation of HMG-CoA r...

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Treatment options are limited and novel therapeutic agents that can inhibit signaling pathways implicated in the proliferation and survival of pancreatic cancer cells are of interest. Tocotrienols are members of the vitamin E family but, unlike tocopherols,...

Chemical differences in gamma-tocotrienol including the presence of an isoprenoid side chain are responsible for differences in cytotoxic potency of gamma-tocotrienol compared to alpha-tocopherol. Alpha-tocopherol has been shown to be ineffective in prostate cancer chemoprevention in the SELECT trial; in fact, there was an increased incidence of pr...

Chronic myeloid leukemia is characterized by a unique reciprocal translocation between chromosomes 9 and 22 resulting in deregulated tyrosine kinase activity. Tyrosine kinase inhibitors, such as imatinib, dasatinib, and nilotinib have revolutionized treatment of Chronic myeloid leukemia. However, tyrosine kinase inhibitors' use has presented new ch...

SESSION TYPE: Critical Care Student/Resident Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PMINTRODUCTION: Isolated paradoxical renal embolism has been reported rarely in literature. We report a case of paradoxical unilateral renal embolus due to patent foramen ovale (PFO) in an otherwise healthy Caucasian female...

Prostate cancer is the most common noncutaneous malignancy in men. It is an excellent target for primary prevention. Vitamin E trials conducted for prevention of prostate cancer have had conflicting results with a lower incidence of prostate cancer in the ATBC trial and a higher incidence in the vitamin E arm of the SELECT trial. Most of the clinic...

Over the last two decades an enormous amount of scientific effort has been devoted to studying the relationship between vitamin E and prostate cancer. This effort is well justified since prostate cancer remains the most common cancer in American men after skin cancer and is the second leading cause of cancer deaths: over 220,000 men will develop pr...

Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic...

We propose a new chemotherapy paradigm for treating cancer based on novel N-acetylated alanyl ester prodrugs that are activated by the esterase activity of oxidized protein hydrolase (OPH) and subsequently promote oxidative stress-induced apoptosis in cancer cells with hyperactive Akt kinase. Cancer cells often exhibit a high level of intrinsic oxi...

This chapter will review the current literature linking vitamin E to prostate cancer with the overall goal of providing a rationale for the design of potential future large-scale clinical chemoprevention studies. Vitamin E is not a single organic compound and refers to at least four tocopherols (alpha-, beta-, gamma- and delta-) and four correspond...

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established risk-benefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influ...

The mevalonate pathway plays an important role in cancer biology and has been targeted previously with farnesyl transferase inhibitors, although their efficacy is limited due to significant adverse effects. We hypothesize that combination of Simvastatin with Alendronate may have significant synergistic anti-carcinogenic potential in prostate cancer...

Tocotrienols are members of the vitamin E family but, unlike tocopherols, possess an unsaturated isoprenoid side chain that confers superior anti-cancer properties. The ability of tocotrienols to selectively inhibit the HMG-CoA reductase pathway through posttranslational degradation and to suppress the activity of transcription factor NF-κB could b...

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Alternate strategies to treat and prevent this cancer are urgently required. In this regard, novel therapeutic agents that can inhibit signaling pathways implicated in the proliferation and survival of pancreatic cancer cells are of immense interest. Tocotrienols are...

Religion and spirituality may influence outcomes in cancer prevention and therapy and contribute to cancer disparities in deeply religious communities like the Appalachian region of the United States. Finding a method to bridge this division is essential to reduce cancer health disparities in this population. Religious beliefs may lead patients to...

Regions along the Mediterranean and in southern Asia have lower prostate cancer incidence compared to the rest of the world. It has been hypothesized that one of the potential contributing factors for this low incidence includes a higher intake of tocotrienols. Here we examine the potential of γ-tocotrienol (GT3) to reduce prostate cancer prolifera...

Chronic inflammation and dietary fat consumption correlates with an increase in prostate cancer. Our previous studies in the colon have demonstrated that gamma-tocopherol treatment could upregulate the expression of peroxisome proliferator-activated preceptors (PPAR) gamma, a nuclear receptor involved in fatty acid metabolism as well modulation of...

Green tea consumption has been shown to exhibit cancer-preventive activities in preclinical studies. Polyphenon E (Poly E) is a well-defined green tea-derived catechin mixture. This study was designed to determine the effects of Poly E on the growth of human Barrett's and aerodigestive adenocarcinoma cells and the mechanisms involved in growth regu...

Dietary vitamin E, highly expressed in palm oil, exists as either tocopherols or tocotrienols. Evidence indicates that vitamin Es maybe potent cancer preventive agents. In this study, the y- and O- isoforms of vitamin E were found to he the most effective at cancer cell growth inhibition, with the tocotrienols being more effective than the tocopher...

Vitamin E is a fat-soluble vitamin that exists in eight different isoforms: four tocopherols (alpha, beta-, gamma- and delta-), and four tocotrienols (also alpha-, beta-, gamma- and delta-). Studies are underway to determine whether vitamin E, through its ability to limit production of free radicals, might help prevent or delay the development of c...

The Appalachian region of the United States has long been recognized for its poor economic and social indicators. Only during the past decade have multi-state data become more accessible to describe the regions' poor health status and resulting outcomes. A recent community-based participatory study engaged rural Appalachians to describe "what makes...

Unlike the tocopherols, the tocotrienols, also members of the vitamin E family, have an unsaturated isoprenoid side chain. In contrast to extensive studies on tocopherol, very little is known about tocotrienol. Because the nuclear factor-kappaB (NF-kappaB) pathway has a central role in tumorigenesis, we investigated the effect of gamma-tocotrienol...

Mediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in the gut and prevent DNA damage, but signal transduction activities can occur independent of the antioxidant function. The...

In this study we demonstrated that vitamin E isoforms, tocopherols and tocotrienols, have variable growth inhibitory effects on both types of prostate cancer cell line models. The gamma isoforms are more effective than the alpha isoforms and the tocotrienols are more effective than the tocopherols. This study further showed that the vitamin E-media...

Prostate cancer has the greatest country-to-country variation in incidence of any reportable cancer suggesting the importance of nutrition and environmental factors [1-3]. Some evidence supports the protective effects of tomato products (lycopene), soy products (isoflavonoids) and fruits. Secondary endpoint analysis of recent intervention trials fo...

Unlabelled: Colorectal cancer is the second most common cause of cancer deaths in the United States. Vitamin E (VE) and other antioxidants may help prevent colon cancer by decreasing the formation of mutagens arising from the free radical oxidation of fecal lipids or by "non-antioxidant" mechanisms. VE is not a single molecule, but refers to at le...

Vitamin E, the main lipid soluble antioxidant, exists in eight different forms, of which α-tocopherol and γ-tocopherol are the two major forms. Previous experiments showed vitamin E uptake by macrophages that contribute to inflammation and immunity. On the other hand, vitamin E has structural similarity to the thiazolidinedione, troglitazone, a per...

Epidemiological, experimental, and clinical observations provide support for a colorectal cancer chemopreventive role for aspirin. We have evaluated the effects of aspirin on proliferation biomarkers in normal-risk and high-risk human subjects for colorectal cancer. Colorectal biopsies were obtained at baseline and at 24h after 28 daily doses of 81...

The purpose of this review is to provide an oversight into the relationship between oxidants, antioxidants and the etiology of colon cancer. Although considerable evidence supports the hypothesis that antioxidant factors protect against colon cancer and proxidant factors promote colon cancer, the overall picture is far from complete. Nevertheless,...

Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of gamma-tocopherol is higher than alpha-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used alpha-toco...

Nutritional factors play an important role in the prevention and promotion of colorectal cancer. Vitamin E is a generic term that describes a group of lipid-soluble chain-breaking antioxidants that includes tocopherols and tocotrienols. Vitamin E occurs in nature as eight structurally related forms that include four tocopherols and four tocotrienol...

A 65-year-old man with a 3-month history of intractable back pain had previously received cytotoxic curative chemotherapy for non-Hodgkin's lymphoma. His postchemotherapy course had been complicated by febrile neutropenia, recurrent coagulase-negative staphylococcal bacteremia, and gastrostomy site infections. He was admitted with severe intractabl...

We report here the first case of severe immune thrombocytopenia induced by a second-generation cephalosporin antibiotic, Loracarbef. A 56-year old white female developed acute severe thrombocytopenia associated with acute respiratory symptoms following administration of Loracarbef. She responded to Loracarbef withdrawal and systemic corticosteroid...

Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Chemoprevention can either prevent DNA damage that init...