• Journal of Applied Biological Chemistry
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• v.66
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• pp.159-164
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• 2023

Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8093-8100
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• 2016

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3861-3864
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• 2016

Background: Adipokines are bioactive proteins that mediate metabolism, inflammation and angiogenesis. Changes in the secretion of key serum adipokines - adiponectin and letpin - may be associated with obesity, cancer and metabolic disorders. Thyroid cancer is one of the most important types of endocrine cancer. Therefore, investigating the association between serum levels of adiponectin and leptin and thyroid cancer might be important. The purpose of this study was to assess adiponectin and leptin levels in medullary thyroid carcinoma (MTC) cases in order to identify novel tumor markers. Materials and Methods: This research was based on a case-control study, including 45 patients with medullary thyroid cancer (21 men and 24 women) and 45 healthy controls (24 males and 21 females). Adiponectin and leptin levels were measured by ELISA in both groups. Height and weight were measured and body mass index (kg/m2) was calculated. Results: Adiponectin and leptin levels were not significantly different between medullary thyroid carcinomas and the control group. Also, there was no correlation among age and body mass index and the disease. Conclusions: These results suggest that changes in serum adiponectin and leptin levels do not play an important role in the diagnosis or could act as as biomarkers for medullary thyroid cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3691-3696
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• 2015

Background: Cancer loci comprise heterogeneous cell populations with diverse cellular secretions. Therefore, disseminating cancer-specific or cancer-associated protein antigens from tissue lysates could only be marginally correct, if otherwise not validated against precise standards. Materials and Methods: In this study, 2DE proteomic profiles were examined from lysates of 13 lung-adenocarcinoma tissue samples and matched against the A549 cell line proteome. A549 matched-cancer-specific hits were analyzed and characterized by MALDI-TOF/MS. Results: Comparative analysis identified a total of 13 protein spots with differential expression. These proteins were found to be involved in critical cellular functions regulating pyrimidine metabolism, pentose phosphate pathway and integrin signaling. Gene ontology based analysis classified majority of protein hits responsible for metabolic processes. Among these, only a single non-predictive protein spot was found to be a cancer cell specific hit, identified as Armadillo repeat-containing protein 8 (ARMC8). Pathway reconstruction studies showed that ARMC8 lies at the centre of cancer metabolic pathways. Conclusions: The findings in this report are suggestive of a regulatory role of ARMC8 in control of proliferation and differentiation in lung adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7701-7705
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• 2015

Background: Thyroid hormones (TH) are regulated by the hypothalamic-pituitary axis, which plays an important role in cell growth, differentiation, development and other aspects of metabolism. It is believed that an active hypothalamic-pituitary axis increases the susceptibility of thyroid dysfunction during systemic chemotherapy. In order to investigate the relation between thyroid function and chemotherapy the present study was designed to investigate TH in breast cancer patients receiving at least three cycles of chemotherapy. The levels of TH were measured at the baseline and before each cycle of chemotherapy. Materials and Methods: Blood samples for estimation of TH levels were collected from 80 (pre-menopausal-40; post-menopausal-40) breast cancer patients just before they were undergoing - $1^{st}$, $2^{nd}$, $3^{rd}$ and $4^{th}$ cycle of chemotherapy. The serum was separated and $T_3$, $T_4$ and TSH levels were determined by chemiluminescence method. Results: $T_3$ and $T_4$ were found significantly decreased and TSH was found significantly increased after $1^{st}$ (p<0.001), $2^{nd}$ (p<0.0001) and $3^{rd}$ cycle of chemotherapy (p<0.0001). The variation of $T_3$ levels (decreased) and TSH levels (increased) was found more in post-menopausal (p<0.0001) women then in pre-menopausal women after $3^{rd}$ cycle of chemotherapy as compared to baseline (p<0.001). Conclusions: TH were remarkably altered after each cycle of chemotherapy leading to decline in thyroid function of breast cancer patients. Further, the results also indicated that post-menopausal women were more prone towards decline in thyroid function then pre-menopausal women. The present study proposes the monitoring of TH after each cycle of chemotherapy in breast cancer patients.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.99-108
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• 2003

Recently, the proportion of the population older has increased rapidly. As the aged population is increasing, the prevalence of malignancy rises with age, too. We believe that the potential benefits of approach to cancer care in the elderly are self-evident. In order to investigate the characteristics of cancer in the elderly, we reviewed literature related with the biology of the aged with cancer. The elderly undergo age-related changes in their physiology which may result in altered tolerance to disease and to the requirements of the management of illness. The possible reasons for the increased prevalence of cancer in the elderly are a longer potential duration of exposure to carcinogens, a reduced ability of repair DNA and reduced host defences against malignancy. In general, cancer patients in the elderly have a shorter survival. Because it is impossible to offer the active treatment of cancer in the elderly. Also, they have the problems that the psychosocial change and reduce of physiological function such as absorption, metabolism and excretion. We hope that other groups will further research cancer in the elderly in future.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.521-525
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• 2012

Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8067-8073
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• 2016

Background: Long non-coding RNAs (lncRNAs) are emerging as key players in gene expression that govern cell developmental processes, and thus contributing to diseases, especially cancers. Many studies have suggested that aberrant expression of lncRNAs is responsible for drug resistance, a substantial obstacle for cancer therapy. Drug resistance not only results from individual variations in patients, but also from genetic and epigenetic differences in tumors. It is reported that drug resistance is tightly modulated by lncRNAs which change the stability and translation of mRNAs encoding factors involved in cell survival, proliferation, and drug metabolism. In this review, we summarize recent advances in research on lncRNAs associated with drug resistance and underlying molecular or cellular mechanisms, which may contribute helpful approaches for the development of new therapeutic strategies to overcome treatment failure.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.87-89
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• 2013

Glutathione S-transferases (GSTs) constitute a multigene family of multifunctional phase II metabolic enzymes. GSTT1, an important member of this group has a wide range of substrates including carcinogens. Total homozygous deletion or null genotype resulting in total lack of enzyme activity exists in populations for this enzyme. Since the null genotype may contribute to lower detoxification of carcinogens, this genotype is expected to increase cancer risk. The frequency of the GSTT1 null genotype is known to vary significantly among populations. However, little is known about its distribution in the hilly Kumaun region of northern India. Therefore, in this study, we determined the prevalence of the GSTT1 null polymorphism in the Kumaun popilation by conducting duplex PCR in 365 voluntary healthy individuals. The GSTT1 null genotype was detected in 18.4% of the individuals. Since GSTs play significant role in xenobiotic metabolism, the present data on GSTT1 genotype distribution should contribute in understanding genetic association with cancer risk in this understudied population.

• Animal cells and systems
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• v.15 no.1
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• pp.1-8
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• 2011

Perturbation of metabolism with increased expression of lipogenic enzymes is a common characteristic of human cancers, including prostate cancer. In the present work the overexpression of stearoyl-CoA desaturase (SCD) in LNCaP cells led to increased mRNA levels of fatty acid synthase (FAS) and acetyl-CoA-carboxylase-a, whereas micro RNA-mediated silencing of SCD inhibited the expression of these lipogenic genes in LNCaP cells. Treatment with the FAS-specific inhibitor cerulenin inhibited SCD induction of LNCaP cell proliferation. In addition, a transient transfection assay revealed the capability of cerulenin to suppress SCD and dihydrotestosterone induction of androgen receptor transcriptional activity. Furthermore, overexpression of SCD in LNCaP cells produced marked resistance to ceramide-induced cell death with reduced poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, silencing of SCD expression increased Bax protein in LNCaP cells. Furthermore, addition of ceramide to SCD knockdown LNCaP cells increased cell death and caspase-3 activity with drastic increase of PARP cleavage. Together, the data indicate that SCD may provide resistance of prostate cancer cells to ceramide-induced cell death.