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Background: Colorectal cancer (CRC) is considered the fourth type of cancer that causes death in the world. Changes in levels of Zinc (Zn), Copper (Cu), and Selenium (Se) as well as low glutathione peroxidase (GPx) activity can lead to CRC and this study was aimed to evaluate their possible use as diagnostic markers. Methods: CRC patients (n=90) were divided into three groups; newly diagnosed, before surgery, and after surgery. These groups were compared to healthy subjects (n=30); the mean age ±SD was 50.63±9.26 and 49.97 ±10.85 for CRC patients and healthy subjects, respectively. Biochemical study for serum levels of Zn and Cu were measured by FAAS, Se was measured by HGAAS, and ELISA for GPx. Results: Zn, Cu, Se and GPx were significantly lower in all CRC patient groups, except for the after surgery group which showed no differences for Zn and GPx as compared to the healthy subjects. Positive correlations were found between Se and Zn and between Se and GPx (r = 0.71, r = 0.42; P < 0.01, respectively) in all CRC patient groups. A receiver operating characteristic (ROC) curve analysis applied for the newly diagnostic group showed that all parameters can be used as diagnostic markers for CRC. Conclusion: The present results conclude that Zn, Cu Se, and GPx can be used as diagnostic markers for CRC, where the decrease of these parameters may be associated with an increased risk of CRC and as indicators of the response to therapy.
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Caspian J Intern Med 2020; 11(4):384-390
DOI: 10.22088/cjim.11.4.384
Original Article
Copyright © 2020, Babol University of Medical Sciences
This open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0
Raghad F. Al-ansari (MSc) 1
Abdulnasser M. AL-Gebori
(PhD) 1
Ghassan M. Sulaiman (PhD) 2*
1. Applied Chemistry Division,
Applied Science Department,
University of Technology,
Baghdad, Iraq
2. Biotechnology Division, Applied
Science Department, University of
Technology, Baghdad, Iraq
* Correspondence:
Ghassan M. Sulaiman,
Biotechnology Division, Applied
Science Department, University of
Technology, Baghdad, Iraq
Tel: 0096 49702781890
Received: 15 Sep 2019
Revised: 9 Feb 2020
Accepted: 16 Feb 2020
Serum levels of zinc, copper, selenium and glutathione
peroxidase in the different groups of colorectal cancer patients
Background: Colorectal cancer (CRC) is considered the fourth type of cancer that causes
death worldwide. Changes in the levels of zinc (Zn), copper (Cu), and selenium (Se) as well
as low glutathione peroxidase (GPx) activity can lead to CRC and this study was aimed to
evaluate their possible use as diagnostic markers.
Methods: CRC patients (n=90) were divided into three groups; newly diagnosed, before
surgery, and after surgery. These groups were compared to healthy subjects (n=30); the
mean age ±SD was 50.63±9.26 and 49.97±10.85 for CRC patients and healthy subjects,
respectively. Biochemical study for serum levels of Zn and Cu was measured by FAAS, Se
was measured by HGAAS, and ELISA for GPx.
Results: Zn, Cu, Se and GPx were significantly lower in all CRC patient groups, except for
the after surgery group which showed no differences for Zn and GPx as compared to the
healthy subjects. Positive correlations were found between Se and Zn and between Se and
GPx (r=0.71, r=0.42; P<0.01, respectively) in all CRC patient groups. A receiver operating
characteristic (ROC) curve analysis was applied for the newly diagnostic group showing all
the parameters that can be used as diagnostic markers for CRC.
Conclusion: The present results conclude that Zn, Cu Se, and GPx can be used as diagnostic
markers for CRC, where the decrease of these parameters may be associated with an
increased risk of CRC and as indicators of the response to therapy.
Keywords: Colorectal cancer, Zn, Cu, Se, GPx, Serum.
Al-ansari R, Al-Gebori A, Sulaiman G. Serum levels of zinc, copper, selenium and glutathione
peroxidase in the different groups of colorectal cancer patients. Caspian J Intern Med 2020; 11(4):
Colorectal cancer (CRC) is considered as the fourth cause of death among types of
cancer globally. It is also ranked third among the most commonly diagnosed types of cancer
(1). CRC refers to malignant epithelial neoplasms that occur in the colon and/or the rectum
by transforming epithelial cells into adenocarcinoma cells (2). Zinc (Zn), copper (Cu), and
selenium (Se) are essential dietary nutrients for the body and are implicated in cancer risk, where
they act as anti-oxidant agents. Zn catalyzes the activity of more than 300 enzymes and has roles
in the immune function, DNA synthesis, protein synthesis, and cell division. It is also
responsible for the maintenance of the structure of DNA and its binding to more than 1000
transcription factors that are required for gene expression of many proteins. Cu plays an
important function in preserving the integrity of DNA by preventing oxidative DNA damage.
Many enzymes and proteins in humans depend on Zn, Cu and Se. Both Zn and Cu play the
main role in the activity of the antioxidant enzyme known as copper-zinc superoxide dismutase.
Se also contributes to the formation of some enzymes such as glutathione peroxidase (GPx),
thioredoxin reductase (TrxR) and iodothyronine deiodinases (IDD) which act as anti-oxidant
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 385
It has also an important role in the protection against
oxidative stress through the action of antioxidant
selenoproteins against reactive oxygen species (ROS) and
reactive nitrogen species (NOS). Together, H2O2, O2−, and OH
radicals form the ROS, the excessive generation of which
causes oxidative stress. Many diseases, such as cancer, can
develop as a result of oxidative stress, if there is an imbalance
between the defense antioxidant system of the cell and the
generation of ROS species (3-8).
A previous study on CRC patients showed that the serum
level of Se decreased while Zn level increased, while it
showed no difference in the level of Cu (9). Zn deficiency
appeared in colon cancer patients, whereas Cu showed no
difference compared with the healthy controls in a Saudi
population (10). Iraqi patients with colon cancer also showed
a decrease in Zn and an increase in Cu levels (11). The same
findings were also reported in CRC patients in Brazil (12).
Another recent study has reported that both Zn and Cu
decreased in Iranian CRC patients (13).
GPx (EC is an enzyme that is classified as
oxidoreductase which catalyzes the reduction of the organic
hydroperoxides or H2O2 to corresponding alcohols or water
using reduced glutathione. Some GPx isozymes are described
as selenium-dependent (14). Previous studies reported that
GPx activity in colon cancer patients was lower in the plasma
and serum as compared to the control (15, 16).
Several factors are involved in the process of CRC
treatment, including the disease stage; about 95% of stage I
and 65-80% of stage II patients can only be treated via
surgery. However, several types of treatment such as chemo-
and radiotherapy can be applied to patients in stages III and
IV before having to undergo surgery (17). The ability of
cancer cells to spread to other tissues, including lymph nodes,
was well documented, while the rate of this process as well as
the speed of cancer cells growth are correlated with the
disease grades that are classified into G1, G2, and G3
according to severity (18).
Hence, the previous investigations conducted on the
relationships between Zn and Cu with CRC are controversial
as to whether these elements increased or decreased in the
serum of the patients. Also, the cutoff values of these
parameters were not defined by previous studies. In this study,
we assessed the levels of these parameters in different groups
of CRC patients and determined the cutoff values that could
be applied for newly diagnostic patients. Also, we analyzed
the correlations among the investigated elements.
Study population: This research involved 30 healthy subjects
(males and females) and 90 patients who were diagnosed as
primary colorectal adenocarcinoma patients. The mean age
was 49.97 ±10.85 years for healthy subjects and 50.63±9.26
years for CRC patients. Healthy subjects matched the patients
in the gender ratio. Tumor lymph node metastasis (TNM)
system was used for staging. CRC patients were divided into
three equal groups; newly diagnosed (no treatment, no
surgery, all stages of disease), before surgery (chemo- and
radiotherapy-treated, stages III and IV), and after surgery (No
treatment before and after surgery, stages I and II). Patients
with diabetes, heart diseases, kidney failure, familial history
for CRC, intestinal polyposis, chronic digestive problems, and
those who are alcoholic and smokers were excluded. The
diagnosis for CRC patient was performed by consultant
doctors who identified tumor location, whereas tumor type,
grade, and stage were identified by pathologists. The ethics
committee of the Medical City in Baghdad, Iraq approved this
research. The number of CRC patients within stage I was 23
(25.55%), stage II was 23 (25.55%), stage III was 22
(24.44%), and stage IV was 22 (24.44%). The number of
patients with grade 1 was 22 (22.22%), grade 2 was 58 (64.44
%), and grade 3 was 12 (13.33%). Tumor location was
determined using the International Classification of Diseases
(ICD- version 10). Patients with colon and those with rectal
cancers were both included, where the number of patients who
had a primary tumor in the cecum was 4 (4.44%), in the
ascending colon,11 (12.22%), in the hepatic flexure,5
(5.55%), in the transverse colon, 8 (8.88%), in the splenic
flexure, 6 (6.66%), in the descending colon, 15 (16.66%), in
the sigmoid colon, 12 (13.33%), in the recto-sigmoid junction,
10 (11.11%), and in the rectum was 19 (21.11%).
Materials: Chemicals used for preparing standard solutions
of Zn, Cu and Se element were purchased from Merck KGaA,
Germany. Enzyme linked immunosorbent assay research kit
(type sandwich ELISA) was used to assay glutathione
peroxidase activity purchased from MyBioSource-U.S.A.
Laboratory assessment: Specimens were taken from healthy
subjects and CRC patients; Blood (10 mL) was collected from
each person, then the serum was stored at -40º C after being
separated by centrifugation. Atomic absorption spectroscopy
(AAS; novAA 300, Analytik Jena, Germany) was used to
assay Zn, Cu and Se, whereas flame atomic absorption
spectroscopy (FAAS) was used for Zn and Cu assay, using
acetyleneair as a flame and hollow cathode lamps as a
Caspian J Intern Med 2020; 11(4): 384-390
386 Al-ansari RF, et al.
radiation source. Burner height and gas flow rates were
adjusted to achieve the highest absorbance signal of each
element. Slit width used to isolate wavelength was 1 nm.
Absorbance was read at 213.9 nm and 324.7 nm, respectively,
for Zn and Cu. Hydride generation atomic absorption
spectroscopy (HGAAS) was used for Se assay. Hydride
generation system was heated to 950º C. Absorbance was read
at 196.0 nm. Carrier gas was argon. For hydride generation,
NaBH4 0.6% solution (98% Sigma, Germany) in 0.6% NaOH
(HiMedia Laboratories Pvt. Ltd., India) was prepared.
Samples were prepared by adding 3 mL of HNO3 70%
(HiMedia Laboratories Pvt. Ltd., India) to 1 mL of serum,
followed by decomposition by microwave according to a
specific program for decomposition. Samples were then left
for 10 min before adding deionized water to a defined volume.
These steps were applied to all samples. 5 mL of HCl 37%
(Sigma, Germany) was also added to samples prepared for the
Se assay which were heated at 85º C for 30 min (9).
Statistical analysis: IBM SPSS statistics Version 24 was used
to analyze the data by Windows 10. The parameters were
expressed as mean±SD, for normal distribution Shapiro- Wilk
test was used and for homogeneity of variance, Levene test
was used, One-way ANOVA test was used to find the
differences in the means between the groups also t-test. The
cutoff values and diagnostic markers were estimated by
receiving operating characteristic (ROC) curve. The Pearson
correlation coefficient was used to find the correlations among
the parameters. Differences at p<0.05 were considered to be
The values of all the tested parameters (Zn, Cu, Se and
GPx) were significantly lower in all CRC patient groups as
compared to healthy subjects, except for the after surgery
group which showed no significant difference for Zn and GPx
table 1. Age (years) showed no differences between CRC
patient groups, newly diagnosed, before and after surgery,
(50.75±11.93, 52.00±12.79, and 49.16±12.08; respectively)
compared with healthy subjects (49.97±10.85). Body mass
index (Kg/m2) also showed no differences between CRC
patient groups (23.94±3.50, 24.18±4.55, and 24.02±4.03;
respectively) compared with healthy subjects (24.12±2.34).
The correlations among the parameters are shown in table 2,
while the positive correlations between Se and Zn and
between Se and GPx are shown in figures 1 and 2.
ROC curve analysis was applied for the newly diagnostic
group and showed that Zn, Cu, Se, and GPx can be used as
diagnostic markers for CRC disease; the area under the curve
(AUC) explains the ability of using these parameters as
markers. The analysis showed that all the differences in the
AUC values were significant (p<0.01). For each parameter,
95%-confidence interval (95%-CI) and standard error (SE) for
the AUC were calculated. The cutoff values were assessed at
the maximum of both sensitivity and specificity, as shown in
table 3.
Correlations between both BMI and age with the
parameters in healthy subjects and CRC patients are shown in
table 4. The associations of clinical features for CRC patients
and the parameters are shown in table 5.
Table 1. Total mean serum levels of Zn, Cu, and Se, with GPx activity in the sera of healthy subjects and CRC patients
Zn (μg/dL)
Cu (μg/dL)
Se (μg/dL)
GPx (U/L)
Healthy subjects
Newly diagnosed
Before surgery
After surgery
*P<0.05, **P<0.01
Table 2 .Correlations between parameters in serum for CRC patients
Correlation between
r (P-value)
Zn and Cu
-0.16 (>0.05)
Zn and Se
0.71 (<0.01)
Zn and GPx
0.24 (>0.05)
Cu and Se
0.01 (>0.05)
Cu and GPx
-0.07 (>0.05)
Se and GPx
0.42 (<0.01)
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 387
Figure 1: Positive correlation between Se and Zn in
CRC patients.
Figure 2: Positive correlation between Se and GPx in
CRC patients.
Table 3. ROC curve analysis findings for parameters.
Sensitivity (%)
Specificity (%)
95% - CI
Cutoff value
0.91 *
0.82- 1.00
84.45 (μg/dL)
1.00 *
1.00- 1.00
55.24 (μg/dL)
1.00 *
1.00- 1.00
5.40 (μg/dL)
0.91 *
0.80- 1.00
113.37 (U/L)
* P<0.01
Table 4. Correlations between both BMI and age with parameters in serum for healthy subjects and CRC patients
Correlation between
CRC Patients
r (p value)
Healthy subjects
r (P-value)
Zn and Age
0.03 (0.75)
-0.14 (0.53)
Cu and Age
-0.09 (0.43)
0.08 (0.73)
Se and Age
-0.005 (0.96)
0.18 (0.44)
GPx and Age
0.02 (0.87)
-0.29 (0.20)
Zn and BMI
-0.01 (0.93)
-0.22 (0.33)
Cu and BMI
-0.08 (0.50)
-0.03 (0.10)
Se and BMI
0.25 (0.04)
0.27 (0.26)
GPx and BMI
-0.01 (0.90)
0.04 (0.86)
Table 5. Association of clinical features for all CRC patients and serum levels of Zn, Cu, Se, and GPx
Case (%)
Zn (μg/dL)
Cu (μg/dL)
Se (μg/dL)
GPx (U/L)
*Only between two groups of CRC patients (the newly diagnosed and the before surgery). N.S: Non-significant
Caspian J Intern Med 2020; 11(4): 384-390
388 Al-ansari RF, et al.
Alterations of trace element levels adversely affect many
biological processes and they could also promote
carcinogenesis. The results of our study showed that Zn, Cu,
Se and GPx were significantly lower in all groups of CRC
patients, while the patients in the after surgery group showed
no significant difference for both Zn and GPx, as shown in
table 1.
In the present study, all groups of CRC patients were
deficient in Cu and Se, as it was observed, for example, in the
newly diagnosed group in all stages as well as in the patients
before surgery who received radiotherapy and chemotherapy
in advanced stages. In the after surgery group, the early
surgical intervention in the patients with eral stage disease
could not restore normal levels of the studied elements, even
after 21 days of post-surgical blood collection. This indicates
that tumor removal was not efficient in bringing these
parameters to normal levels. A recent study on males and
female patients with thyroid cancer has demonstrated that
serum levels of Se significantly decreased in the pre- and post-
operative patients, an effect that was suggested to be
associated with thyroid cancer pathogenesis (19).
The rise in the levels of free radicals was related to cancer
etiology because such a rise can damage DNA, cause
destruction of proteins, and ultimately lead to tumor growth.
Copper-restricted diet in humans leads to elevated fecal free
radicals, and causes cytotoxicity which is one of the putative
colon cancer’s risk factors (20-23).
Moreover, experiments in animals indicated that low Cu
intake is considered as a risk factor for 3,2’-dimethyl-4-
aminobiphenyl (DMABP)-induced colon tumor development
in rats, whereas the activities of ceruloplasmin and Cu,Zn-
SOD enzymes were reduced in rats fed on low Cu intake (24).
Se is engaged in a number of biochemical pathways where it
can be found in many forms. Anticarcinogenic pathways of
Se include the prevention of oxidative damage, regulation of
immune responses, repair of DNA damage, and regulation of
apoptosis and cell cycle (25, 26). Selenomethionine is a major
component of Se diet that modulates the redox status
(reduction/oxidation) (20, 27). Besides that, it induces the
P53-mediated cell cycle arrest and programmed cell death in
human colon cancer cells (28). Se significantly induces
apoptosis and its relatively high doses were related to
overexpression of p53 in rat hepatocytes (29). A previous
study reported that low serum levels of Se were strongly
correlated with CRC risk (30). Zn level and GPx activity
significantly decreased in the newly diagnosed and before
surgery groups, but the levels showed non-significant
differences in the after surgery group as compared with
healthy subjects. This may be attributed to the stage and
differentiation grade of the disease. Our study with the after
surgery group involved patients in G1 and G2 grades only,
that showed non-significant difference in these parameters as
compared to the control group.
In a study conducted on colon and rectal cancer patients of
all stages of the disease who did not undergo surgical
intervention or treatment, the authors reported that the levels
of serum Zn significantly decreased but only in advanced
stages (31).
Another study in patients with colon and stomach cancer
demonstrated that high grade differentiated (G3; poorly
differentiated) stomach tissue has lower Zn level comparing
with the normal tissue and with the tissues from moderately
differentiated carcinoma G2 and well-differentiated
carcinoma G1 grades. Also, the study reported the inverse
association between Zn levels in the tissues and the advanced
stages of carcinoma in both colon and stomach cancer patients
(32). In our study, ROC curve analysis for the newly
diagnosed group was used to illustrate the association of these
parameters with CRC. The findings in table 3 indicate that the
parameters can be used as diagnostic markers, where a very
highly significant difference in AUC is shown. These values
can be used to predict people's health when the levels of these
parameters are less than the cutoff values, then the individuals
are at risk or already having CRC. A previous study noted that
the progression to colon cancer was associated with low levels
of Zn and decreased Cu,Zn-SOD activity in the plasma of rats
(33). P53 folding and misfolding is modulated by Zn, which
is one of the reasons that causes cancer (34). A previous study
about colorectal cancer showed that the serum levels of both
Zn and Cu were significantly lower as compared to healthy
people (13). Human CRC patients had lower serum
concentrations of Cu, Zn, and Se according to a review
published in 2019 (35). Our results are consistent with these
studies. Cu and Zn deficiencies have recently increased in
different regions of the world for unknown reasons. The total
prevalence of Cu deficiency in populations in Iran and Spain
was 32.1 % (age 15-65 years old) and 30.1 % (age over 60
years old), respectively. The Spanish study also reported that
the total prevalence of Zn deficiency was 66.8% (36, 37). The
positive correlation between Zn and Se that we found can be
explained by the results of a previous report which found that
Caspian J Intern Med 2020; 11(4): 384-390
Trace elements and glutathione peroxidase in serum of colorectal cancer patients 389
Zn can induce a decrease in Se urinary excretion (38). In a
previous study on humans, two significant positive
correlations between Zn and Se were found in two biological
media (urine and feces) from healthy people. The study also
found a significant positive correlation between dietary Zn
intake and Se levels in blood (39). Hence, Zn deficiency may
contribute to Se deficiency. Hypothetically, Zn may influence
the status of Se by modulating one of the phases of Se
homeostasis, represented by absorption, excretion or
retention. We also found another correlation between Se and
GPx, where Se deficiency led to decreased GPx activity,
which was previously shown to result in the accumulation of
H2O2, leading to destruction of the cells (14,5). In studies
conducted on colon cancer patients, the GPx activity was
reported to decrease in the plasma and serum (15, 16). Our
results have been consistent with these recent studies.
In our study, BMI was positively associated with serum Se
levels in CRC patients. A previous study found that high Se
diet causes a subclinical hypothyroid response which leads to
weight gain and decreases energy expenditure. But a low Se
diet causes a subclinical hyperthyroid response which leads to
weight loss and increases energy expenditure. Therefore,
dietary Se intake alters the energy metabolism of humans
(40). Other parameters showed no association with BMI for
all CRC patients groups, including patients under treatment.
In a previous study on breast cancer, the patients showed a
BMI that was not affected by therapy (41).
In conclusions our findings indicate the involvement of
low levels of Zn, Cu, and Se as well as the low activity of GPx
in the pathogenicity of CRC. Zn level and GPx activity
significantly decreased in the newly diagnosed and before
surgery groups, but not in the after surgery group. This may
be attributed to the stage and differentiation grade of the
disease. Such low levels were not observed in the control
subjects, while the applied exclusion criteria could probably
exclude other possible sources of such declined levels, which
confirm the strict association between CRC and these
parameters. Thus, we conclude that Zn, Cu Se, and GPx can
be used as diagnostic markers for CRC, where the decrease of
these parameters may be associated with an increased risk of
CRC and as indicators of the response to therapy.
We thank the patients and healthy volunteers for their
support and participation in this research study and the staff
of the Medical City-Ministry of Health and Environment,
Baghdad, Iraq for their assistance.
Conflicts of interest: There are no conflicts of interest.
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... The study also showed that boiling does not have much effect on the concentration of Fe in S. torvum. Copper, as a trace mineral is a component of the antioxidant enzyme glutathione peroxidase ( [31][32][33][34]. Copper is essential but in high doses it affect biological processes, cause anaemia, liver and kidney damage, stomach and intestinal irritation [34,35]. ...
... Copper, as a trace mineral is a component of the antioxidant enzyme glutathione peroxidase ( [31][32][33][34]. Copper is essential but in high doses it affect biological processes, cause anaemia, liver and kidney damage, stomach and intestinal irritation [34,35]. The estimated average requirement (EAR) per day ranges from 260 μg/day in children to 900 μg/day in men and women with an upper limit of 10 mg/day [28]. ...
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The fruits and leaves of Solanum torvum are good sources of nutrients and minerals for the prevention of nutrient deficiencies. However, there is limited information on the effect of boiling on the nutrients, minerals and phytochemicals in the fruits and leaves. This study sought to assess the mineral, macronutrient and phytochemical compositions of fresh and boiled fruits and leaves of S. torvum. Fresh unripe fruit and leaf samples of S. torvum were collected from six communities, boiled, and pulverized for mineral, proximate and phytochemical analyses. The data obtained was subjected to ANOVA and t-test. Solanum torvum was found to contain Fe, Zn, Cu, Mn, Ca, Mg, Na, K, protein, crude fat, carbohydrate, fibre, saponins, tannins, flavanols, terpenoids/steroids and glycosides making it nutritious. The results revealed almost equal concentrations of minerals in fresh and boiled leaves and fruits. A similar observation was made in the case of carbohydrate, crude fat and ash. However, there were significant differences in moisture, protein and crude fibre concentrations in the samples. Phytochemical analysis revealed the presence of saponin, tannin, flavonoids, terpenoids/steroids and glycosides in all leaf samples no matter the treatment. There were no flavonoids and terpenoids/steroids in fruits. Boiling nominally reduced and in a few cases, increased concentration of the nutrient composition but did not have significant effect on the concentration of the macro- and micro- minerals in the fruits and leaves. This study suggests that boiling could affects the concentration of nutrients that could be accessed in fruits and leaves of S. torvum.
... A significant association between high Cu level and occurrence of colorectal cancer has been reported in other case control studies [18,[23][24][25][26], but these were much smaller in size (Table 15). There are two small studies with results in contrast to our observations. ...
... A significantly lower (<0.001) serum Cu level in CRC patient groups (0.47 mg/L) was observed in a retrospective study of 90 CRC patients and 30 healthy persons (mean serum Cu level: 0.80 mg/L) from Iraq [25]. In a small case-control study from the Moravian region of the Czech Republic, conducted on 17 CRC patients and 7 control subjects, a higher (although not significantly) serum Cu level was found among controls (Cu level 0.95 mg/L vs 1.21 mg/L respectively; p = 0.899) [26]. ...
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There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls. Cases and controls were matched for sex, smoking status (yes/no) and year of birth. Among the cases, the mean blood copper level was 1031 µg/L (range 657 µg/L to 2043 µg/L) and among the controls, the mean blood copper level was 864 µg/L (range 589 µg/L to 1433 µg/L). The odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98–32.3; p < 0.001). Of the patients with stage I–II colon cancer, 62% had a copper level in the highest quartile. A blood copper level in excess of 930 µg/L is associated with an increase in the prevalence of colorectal cancer in the Polish population and its potential use in early detection programs should be considered.
... Zinc (Zn) is an essential dietary component for the body linked to cancer risk. It requires the production and activation of several enzymes, catalyzes their actions, and has a role in preserving a healthy immune system, DNA synthesis, protein synthesis, and cell division 6,7 . In addition to calcium, Zn is one of two metals that bind to a leukocyte protein called calprotectin, the main biomarker of IBD that can develop in axSpA patients and is associated with disease activity 8,9 . ...
Axial spondyloarthritis (axSpA) is a chronic rheumatic inflammatory disease affecting mainly the spine and sacroiliac joints. Since the copper-to-zinc ratio (Cu/Zn) indicates an inflammatory response, the change in ratio is expected to correlate with axSpA. This study compared levels of Cu/Zn in the serum of axSpA patients. Serum samples were obtained from 53 patients with axSpA divided according to biological treatment into cohorts A and B, and 28 healthy control as cohort C. Serum levels of Cu and Zn were determined first by a fully automated chemistry analyzer TC-Matrix Plus, then the ratio was obtained. The elevated serum Cu concentration means of cohort B (189.32 ± 13.808 µg/dL) compared to cohort A (168.85 ± 7.244 µg/dL) and cohort C (155.68 ± 3.707 µg/dL) with 0.029 p-values. Reduced Zn concentration means of cohort B (79.74 ± 4.344 µg/dL) compared to cohort A (91.26 ± 4.159 µg/dL) and cohort C (100.93 ± 6.161 µg/dL) with 0.031 p-values. The Cu/Zn mean of cohort B was (2.54 ± 0.25) compared to the Cu/Zn mean of cohort A (1.968 ± 0.125) and cohort C (1.679 ± 0.104) with 0.002 p-values. Due to the results suggesting that the differences between cohorts were associated with inflammatory responses since there was a similar change in ESR levels; however, the differences between cohorts A and B are due to the anti-inflammatory therapy (TNF inhibitor) that cohort A was treated with. Keywords: Axial spondyloarthritis; copper-to-zinc ratio; copper; zinc; inflammation.
... Whenever cells are exposed to high levels of oxidative stress, GSSG accumulates, and the ratio of GSH to GSSG decreases. Therefore, the redox ratio, [GSH]/[GSSG], is also used as a measure of the extent of oxidative stress [24,25]. In our study, the GSH/GSSG ratio was significantly decreased in individuals with colon cancer compared to healthy individuals. ...
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Colon cancer (CC) is accepted as the third type of cancer that causes death in the world. Oxidative stress and low glutathione peroxidase (GPx) activity can cause CC. This study aims to show whether GPx and Oxidized (GSSG)/ reduced glutathione (GSH) levels, which are considered oxidative stress markers, are effective in the etiopathogenesis of CC. Erythrocyte isolation was performed in 3 ml blood sample taken from volunteers aged 18-75 years. Hemoglobin amounts were determined from the standard graph drawn by monitoring the conversion of methemoglobin to cyanmethemoglobin in the presence of cyanide at 540 nm. Glutathione peroxidase activity was determined by spectrophotometric monitoring of NADPH+H+ (reduced nicotinamide adenine dinucleotide phosphate) oxidation at a wavelength of 340 nm. The amounts of oxidized and reduced glutathione were determined by using the standard graph drawn by following the 412 nm wavelength of the formation of 2-nitro-5-thiobenzoic acid, which has a yellow color. GPx activity of individuals with CC is 5.64 ± 1.49 U/gHb, GSH concentration is 6.96 ± 1.45 nmol/gHb, and GSH/GSSG ratio is 1.04 ± 0.49, GPx activity of healthy individuals is 10.52 ± 2.22 U/gHb, GSH concentration 11.43 ± 1.90 nmol/gHb, and GSH/GSSG: 3.86 ± 1.30, that is, the values of the patient group were significantly lower than the control group. Current results suggest that GPx activity, GSH concentration and GSH/GSSG ratio can be used as CC markers in the diagnosis and monitoring of disease course, and that the decrease in these parameters may be associated with an increased risk of CC.
... Cancer remains a life-threatening disease that accounts for high mortality rates worldwide [8]. Recently, announced data from Iraq's national cancer registry indicate that over 31,500 cancer and tumour-related cases existed in Iraq in 2017-2018. ...
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Nanoparticles (NPs) have biological activities like antibacterial, antifungal, drug delivery, immunomodu-lation and antitumor activities. The aim of the current study was to investigate some of biomedical applications of silver NP synthesis using extracts from leaves of Eriobotrya japonica. Colour changes, UV-visible spectroscopy, SEM, zeta potential, dynamic light scattering, FTIR and XRD were used to confirm AgNPs formation. The UV-vis spectrum absorption band was observed at almost 430 nm. The SEM image shows quasi-spherical shape of AgNPs. The zeta potential demonstrated the negative surface charge of NPs. FTIR results showed the functional groups of AgNPs. Crystalline nature of AgNPs was confirmed by XRD pattern. MTT assay was used to study the anti-proliferative activity against MCF-7 and HeLa cells. Apoptosis was tested using a DNA-fragmentation test, and expression of P 53. AgNPs inhibited the proliferation of MCF-7 and HeLa cells, and reduced inflammation. Treatment with AgNPs significantly decreased allergic disorder. AgNPs stimulated the phagocytosis process in BMDMs. The results suggested that AgNPs could be a promising therapy for future and preventing inflammation, reduce allergic disorders and prevent bacterial infection through the up-regulation of phagocytosis. Hence, future work such as developed and improved NPs as adjuvants, immune-modulating substances and nano-drug delivery system is needed. ARTICLE HISTORY
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Periodontal disease is a common disease and may affect 90% of people, and is classified into gingivitis and periodontitis. The objective of this study was if the deficiency of some vitamins and trace elements affects the increase in exposure to periodontal diseases or to find out whether the periodontal disease can cause changes in the blood level of some nutrients and their role in reducing periodontal diseases. For this purpose, samples were taken from the University of Baghdad, College of Dentistry, Department of Periodontics, in the Periodontics clinic, including a group of 40 patients’ periodontitis, as well as another 40 patients’ gingivitis, and 40 healthy periodontium as control. There was no overall sickness in any of the groups. Periodontal clinical data were recorded, and serum parameter levels were assessed. The findings showed that plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss were significantly greater (P< 0.01) in patients compared to the control. Levels of vitamin C and D were significantly decreased in patients compared with control (P
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Background: Over the past few years, research into the pathogenesis of colon cancer has progressed rapidly, and cuproptosis is an emerging mode of cellular apoptosis. Exploring the relationship between colon cancer and cuproptosis benefits in identifying novel biomarkers and even improving the outcome of the disease. Aim: To look at the prognostic relationship between colon cancer and the genes associated with cuproptosis and the immune system in patients. The main purpose was to assess whether reasonable induction of these biomarkers reduces mortality among patients with colon cancers. Method: Data obtained from The Cancer Genome Atlas and Gene Expression Omnibus and the Genotype-Tissue Expression were used in differential analysis to explore differential expression genes associated with cuproptosis and immune activation. The least absolute shrinkage and selection operator and Cox regression algorithm was applied to build a cuproptosis- and immune-related combination model, and the model was utilized for principal component analysis and survival analysis to observe the survival and prognosis of the patients. A series of statistically meaningful transcriptional analysis results demonstrated an intrinsic relationship between cuproptosis and the micro-environment of colon cancer. Results: Once prognostic characteristics were obtained, the CDKN2A and DLAT genes related to cuproptosis were strongly linked to colon cancer: The first was a risk factor, whereas the second was a protective factor. The finding of the validation analysis showed that the comprehensive model associated with cuproptosis and immunity was statistically significant. Within the component expressions, the expressions of HSPA1A, CDKN2A, and UCN3 differed markedly. Transcription analysis primarily reflects the differential activation of related immune cells and pathways. Furthermore, genes linked to immune checkpoint inhibitors were expressed differently between the subgroups, which may reveal the mechanism of worse prognosis and the different sensitivities of chemotherapy. Conclusion: The prognosis of the high-risk group evaluated in the combined model was poorer, and cuproptosis was highly correlated with the prognosis of colon cancer. It is possible that we may be able to improve patients' prognosis by regulating the gene expression to intervene the risk score.
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Oxidative stress has been linked to the development of a variety of malignancies, including leukemia. Furthermore, the incidence of leukemia increases with age due to an increase in the number of free radicals reacting with age and a lower ability of the immune system to detoxify those free radicals. This study aims to investigate the levels of antioxidant activity and their relationship with various types of leukemia. The current study was carried out in the Hematology section of Baghdad Teaching Hospital/Medical City from November 2020 to January 2021. Patients with leukemia (n = 60) were divided into four groups based on their leukemia type: Acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic lymphoid leukemia (CLL), and chronic myeloid leukemia (CML). These groups were compared to 30 healthy subjects. In this study, serum levels of superoxide dismutase (SOD) and vitamin E were measured using an enzyme-linked immunosorbent assay. The findings revealed that (Mean±SE) SOD levels were observed to be raised with age, but (Mean±SE) vitamin E levels decreased with age in leukemia patients. There were no statistically significant differences in gender (males and females). Compared with healthy subjects, the results showed a significant increase in SOD levels in ALL, AML, CLL, and CML (P < 0.01). There were no statistically significant differences observed in vitamin E levels in ALL, AML, and CML except for the CLL group, which showed a significant decrease compared to the healthy subjects. Positive correlations were found between SOD and age (r = 0.367 P < 0.01). These results suggest that SOD and vitamin E levels play a critical role as an indicator of acute and chronic leukemia.
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Given the importance of trace elements in the human body and their strong relationship to the incidence of many diseases such as cancerous diseases, so many studies have been conducted on these elements to reduce such diseases. Through our study, 30 samples of healthy blood serum were taken from the blood bank in Najaf Governorate and 47 samples of blood serum from patients with colon cancer, which were divided between males and females for the elements copper and zinc from the Middle Euphrates Cancer Center, using atomic absorption spectroscopy, the concentrations of the two studied elements were measured. The values of copper concentrations for healthy and patients were lower than the internationally recommended normal values (0.7-1.4), and through the results that we also obtained for healthy males and females, zinc was higher than the recommended normal, and the result was the opposite for colon patients. There was no statistical significance for the copper concentration between healthy people and patients for the male and female (p-value > 0.05), to calculate the increase in the average levels of copper concentrations for colon patients.
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In this study, mycelial filtrate of Aspergillus terreus BA6 was used to reduce AgNO3 to form silver nanoparticles (AgNPs). The effect of seven independent variables on the diameter of AgNPs was studied by applying design of experiments (DOE). At optimal conditions, the diameter of AgNPs was reduced by approximately 26.7% compared to the basal culture condition and AgNO3 concentration was found to be the most significant factor affecting the diameter of AgNPs. A. terreus nano-Ag was characterized using UV-visible spectroscopy, transmission electron microscopy, energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zeta potential. The maximum UV absorption was obtained at 420 nm and the microscopic results showed particles with narrow size distribution ranging from 7 to 23 nm. XRD pattern of AgNPs revealed four diffraction peaks of metallic silver and the EDX spectrum showed a strong signal attributed to Ag nano-crystals. AgNPs mycofabricated by A. terreus showed potent minimum inhibitory concentration (MIC) and broad minimum bactericidal/fungicidal concentration (MBC/MFC) against 12 reference microorganisms. The MIC and MBC/MFC values of AgNPs were 0.312 to 1.25 μg/ml and 0.625 to 10 μg/ml, respectively. Nevertheless, AgNPs did not demonstrate any antagonistic activity against Coxsackie B virus. The in vitro cytotoxicity of the mycosynthesized AgNPs showed significant antitumor activity against adenocarcinoma epithelial cells from human breast cancer (Mcf-7) cell line with an inhibitory concentration (IC50) of 87.5 μg/ml.
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Background Trace elements play a pivotal role in Colorectal Cancer (CRC) inhibition and development process. This systematic review provides the basic comparison of case-control studies focusing on concentration of trace elements between those with CRC and controls Methods The systematic review searched through two databases of Medline and Cochrane up to 24th June 2017. The search strategy focused on Population, Intervention, Comparison, and Outcomes (PICO). We searched the role of trace elements in cancer and focusing on case-control studies in CRC to obtain an insight into the differences in trace element concentrations between those with and without cancer. Results The serum concentrations of Ca, Cu, Mg, Mn, Se, Si, and Zn were lower in CRC patients but for Co and S the levels were higher in CRC patients. The concentrations of Cd, Cr, Cu, Mg, Mn, Pb, and Zn were increased in patients with metastasis, but not in Se. As for colon tissue specimens, inconsistent levels were reported between studies, notably in Cu, Se, and Zn. No changes were reported for B and Ca levels. Most of the trace elements in the tissue specimens showed higher concentrations of Cr, Fe, K, Mg, P, Rb, S, and Si compared to Br. Conclusion With the growing interest to understand the link between trace elements in carcinogenesis and the possible interactions, multi assessment analysis of a larger cohort of samples is necessary.
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2018AbstractRecent researchon herbal field reportsvarious ailmentsassociated with free radicals. The risk of ailments because of oxidative stress increasesdue toundesirable way of life, exposure of natural and synthetic chemicals, cigarette smoking, medications, stress and so on. Cancer prevention agents are the substances which can search free radicals and help diminish the frequency of oxidative pressure induced harm. The main sources of antioxidants are vitamins, fruits, minerals, plants and vegetables. The functionsof antioxidants areto neutralize the effect of reactive oxygen species(ROS)and preventvarious diseases such as cancer, diabetes and cardiovascular diseases. The presence of antioxidants can be evaluated by various methods but the cheapest and easiest available methods are 1, 1-diphenyl-2-picrylhydrazyl (DPPH), total antioxidants capacity (TAC), total phenolic contents (TPC), reducing power (RP) and ferric reducing antioxidant potential (FRAP) methods. Thisreviewgenerally discussesthe information related to the antioxidantsand their role in changing the free radicals into neutral or less reactive species. It also discusses therole of antioxidant enrich sources in decreasing the risk of different human diseases.
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Colon cancer is still one of the leading causes of cancer death worldwide and the second most common cause of mortality from cancer. It is linked to numerous reasons such as socioeconomic status, the dramatic change in dietary habits, the presence of refrigeration, chemical preservatives, and the environmental changes. Our study involved the estimation of Ceruloplasmin activity (Cp), copper and zinc levels in patient with colon cancer. Serum samples were collected from 50 patient with colon cancer from Al-Hussain hospital / Kerbala , digestive and liver disease education hospital medical city in Bagdad/ Iraq and teaching oncology hospital Bagdad medical city/Iraq .The results showed decrease in the Cp activity but not significant in patients with colon cancer comparing with the control, whereas Cu concentration was significant increase (p< 0.0001) in patients so there was significant decrease (p< 0.0001) in Zn concentration in patients with colon cancer compared with the control group. Also the patients were divided into four groups according to the stage of cancer, the results revealed no any significant differences (p > 0.05) between the stages in the concentrations of parameters under study except there was significant differences (p<0.05) in concentration of copper when comparing stage 3 versus stage 4. The aim of this study is to find the relation between ceruloplasmin and related elements in patients with colon cancer.
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Background Breast cancer is the most common serious disease around the world. The trace elements have a vital role in the metabolism and chemotherapy may change the level of metal ions. Due to the ambiguity of the existence in this regard, the study examined the trace element serum levels in women with breast cancer before and after chemotherapy . Methods Sixty patients were studied undergoing specialist. First sampling was taken before chemotherapy (after 4 weeks of surgery) and second sampling was taken after the completion of 3 courses of chemotherapy, approximately 9 weeks after the first chemotherapy. The patients took Adriamycin 60mg/m² Cytoxan 600mg/m². Serum zinc and iron levels were measured using standard spectrophotometric method. Measurement of serum copper was done by atomic absorption spectroscopy. Results Serum zinc and iron levels in women after chemotherapy significantly decreased (p<0.001), however, the serum level of copper increased but was not significant (P=0.676). Conclusions Our findings demonstrate significant decrease in zinc and iron levels in breast cancer patients after 3 courses of Adriamycin and Cytoxan chemotherapy. Prescribing zinc supplements can be useful after chemotherapy.
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Aim: Free radicals play a key role in the development of degenerative diseases, none the less, effects of harmful reactive species can be controlled by natural defense mechanisms in the body. In this study, we aimed to investigate enzyme activities of superoxide dismutase (SOD), glutathione (GSH) reductase, glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in blood serum samples of patients with colon cancer. Material and Method: This retrospective study included patients diagnosed with colon cancer (n=25) and age- and sex-matched healthy individuals as the control group (n=25). Serum levels of SOD, GSH, GSH-Px, and MDA were analyzed using the spectrophotometric method. Results: Enzyme levels of SOD, GSH, GSH-Px, and MDA were found to be statistically significantly (p<0.05), compared to the control group. There was a significant increase in the MDA levels (p<0.05), whereas the SOD, GSH, and GSH-Px levels decreased in the patients with colon cancer, compared to the control group (p<0.05). MDA levels were significantly higher in the patients with colon cancer, while antioxidant enzymes including SOD, GSH, and GSH-Px activities were significantly lower in these patients, compared to the control group (p< 0.05). Discussion: Our study, for the first time, suggests a relationship between colon cancer, oxidative stress, and antioxidant parameters. This is also the first study to investigate the levels of oxidative stress levels and antioxidant enzymes such as SOD, GSH, and GSH-Px activities in the literature. Also, decreased GSH-Px activity may increase MDA production, suggesting that serum SOD, GSH, GSH-Px and MDA levels can affect the etiopathogenesis of colon cancer.
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Despite significant improvements in the technical aspects of cancer diagnosis and management, it is still a leading cause of mortality worldwide. Although, the development of a variety of therapeutic strategies with effective mechanisms of action is increasing, the advanced understanding of molecular mechanisms of cancer initiation and progression is still the important consequence. Reactive oxygen species (ROS) with great concern due to the ability to modulate cell survival and cell death signaling pathways are could be considered to design the effective anti-cancer strategies. Several anti-cancer agents used for the treatment of various cancers regulates ROSs generation which subsequently modulate the pro-apoptotic molecules, expression of various transcription factors including Sp1, AP1, NF-kβ, and other pro-oncogenic genes that are engaged in cancer cell proliferation, survival and metastasis. Concentration dependent ROS has distinct role in different cancer processes like in apoptosis, cancer survival, autophagy, angiogenesis, metastasis, and inflammation. Radiation and potent agents used in chemotherapy are working on the phenomenon of ROS generation that inhibit cancer process. With the intense understanding of ROS’s role in the particular cancer process which is inevitable in cancer, may be used in health care to improve patient’s survival rate. The current review presents all the proposed molecular interactions of ROS with their known cellular targets in cancer cell.
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The present study aims to examine the changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. The study registered 50 individuals, of whom 25 were female and 25 were male. The patients were allocated to four groups: group 1: male thyroid cancer patients group (n = 15), group 2: female thyroid cancer patients group (n = 15), group 3: male control group (n = 10), group 4: female control group (n = 10). The subjects in groups 1 and 2 were the patients who were post-operatively diagnosed with a pathological malignancy in the thyroid tissue samples. Blood samples were collected from all subjects before the operation, immediately after the operation, and on the post-operative day 15. Additionally, thyroid tissue samples were taken from all subjects post-operatively. Some elements in the blood and tissue samples were determined using the atomic emission method. Zinc and selenium levels of groups 1 and 2 in the pre- and post-operative measurements were significantly lower than those in the control groups (p < 0.05), but were higher in the thyroid tissue (p < 0.05). Serum zinc and selenium levels measured in the subjects on the post-operative day 15 were similar to those measured in the controls. Our study show that changes in the serum and thyroid tissue levels of trace elements like zinc and selenium, which play a critical role in thyroid function, might be associated with the pathogenesis of thyroid cancer.
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PURPOSE : This study aimed to determine Cu/Zn ratio, nutritional and inflammatory status in patients during the perioperative period for colorectal cancer. METHODS: The study included patients with histological diagnosis of colorectal adenocarcinoma (Cancer Group, n=46) and healthy volunteers (Control Group, n=28). We determined habitual food intake, body composition, laboratory data of nutritional status, serum calprotectin and plasma Cu and Zn concentrations. Mann-Whitney U-test was performed between-group comparisons and Spearman correlation test for correlations between the variables. RESULTS: Individuals in the Cancer Group presented significantly lower BMI, fat mass, plasma hemoglobin, total protein and albumin as compared with the Control Group. Serum calprotectin[70.1 ng/mL (CI95% 55.8-84.5) vs.53.3 ng/mL (40.3-66.4), p=0.05], plasma Cu concentrations [120 µg/dL(CI95% 114-126) vs. 106 µg/dL(CI95% 98-114), p<0.01] and the Cu/Zn ratio [1.59 (CI95% 1.48-1.71)vs. 1.35 (CI95% 1.23-1.46), p=0.01]were higher in patients with colorectal cancer than in controls. Additionally, the Cancer Group showed negative correlations between the Cu/Zn ratio and Zn intake, hemoglobin, serum albumin, and positive correlation between the Cu/Zn ratio and serum calprotectin. CONCLUSION: These results indicate that an increased plasma Cu/Zn ratio and serum calprotectin, and decreased protein values may be a result of the systemic inflammatory response to the tumor process.
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Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O-2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established.
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In recent years spectral histopathology (SHP) is established as label free method, to identify cancer within tissue. Here, this approach is extended. It is not only used to identify tumour tissue with a sensitivity of 94 % and a specificity of 100 %, but in addition the tumour grading is determined. Grading is a measure how much the tumour cells differ from the healthy cells. The grading refers to G1 (well differentiated) over G2 (moderately differentiated) to G3 (poorly differentiated) and in rare cases to G4 (anaplastic). The grading is prognostic and is needed for the therapeutic decision of the clinician. The presented results showed a nice agreement between the annotation by the SHP and by the pathologists. A correlation matrix is presented. The presented results show, that SHP provide prognostic values in colon cancer, which are obtained label free and automated. It might become an important automated diagnostic tool at the bedside in precision medicine.