• Asian Pacific Journal of Cancer Prevention
• /
• 제15권12호
• /
• pp.4745-4751
• /
• 2014

Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

• International journal of thyroidology
• /
• 제11권2호
• /
• pp.88-91
• /
• 2018

After introducing tyrosine kinase inhibitors (TKIs) as promising treatments for radioactive iodine refractory advanced thyroid cancer patients, we more often meet patients with TKI-related hormone and electrolyte imbalances in clinics. Hypocalcemia associated with TKI is associated with an imbalance in calcium-vitamin D metabolism. TKI-related hypothyroidism is related to the metabolic rate of thyroid hormones. The two side effects usually occur in the early stages of TKI treatment, and if the imbalance is corrected appropriately, the effects are minor, but in severe cases, the TKI should be discontinued. The authors reported a case of severe hypocalcemia and thyroid dysfunction after TKI treatment. A 56-year-old man suffered from symptomatic hypocalcemia during TKI treatment, which was resolved after he stopped taking the TKI medication. Although calcium and vitamin D replacement have increased, hypocalcemia was recurred and TKI treatments have been permanently stopped due to serious weight loss in grade 3. After the interruption, his calcium levels normalized.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2193-2197
• /
• 2012

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. Method: We performed a meta-analysis of all relevant case-control studies that examined any association between the C677T polymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess links. Results: Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls were included. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associated with the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TT vs. CC, OR = 1.37, 95%CI 1.00-1.87, P = 0.050; for TT vs. TC+CC: OR = 1.34, 95%CI 1.01-1.77, P = 0.039). However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer risk in the other populations. Conclusion: The MTHFR C677T polymorphism is associated with cervical cancer risk in Asians, while any possible link in the Caucasian population needs further studies.

• 대한한의학회지
• /
• 제26권1호
• /
• pp.76-84
• /
• 2005

Objective: The purpose of this study was to examine the protective efficacy of GHT on alcoholic liver injury. Methods: We measured the rate of alcohol oxidation, serum level of liver enzyme, lipid peroxidation level in liver tissue, and inflammatory related cytokine expressions in the liver. Results : GHT showed liver protective effects, lowered the levels of AST and LDH in serum and inhibited lipid peroxidation in liver tissue, and enhanced alcohol oxidation. GHT treatment up-regulated IL-10 in the liver, whereas it down­regulated $TNF-\alpha,\;TGF-\beta$, and Fas ligand. Conclusion : From these results, GHT is presumed to work in the liver in protective roles not through the pathway of alcohol metabolism but mainly by anti-inflammation activity in our model.

• The Korean Journal of Physiology and Pharmacology
• /
• 제27권1호
• /
• pp.21-29
• /
• 2023

The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin's efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin's efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6249-6256
• /
• 2013

One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin $B_6$ intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin $B_2$, vitamin $B_6$, and vitamin $B_{12}$ with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin $B_{12}$ intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin $B_6$. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.

• 생명과학회지
• /
• 제33권6호
• /
• pp.512-522
• /
• 2023

전세계적으로 인류를 위협하는 가장 큰 질병은 악성종양 혹은 암이다. 이에 따라, 수술적 요법, 항암제를 사용한 항암 요법, 방사선 요법, 면역 요법을 포함한 여러 다양한 방법이 다양한 암의 진단과 치료를 위해 단독 혹은 혼용하여 현재까지 적용되고 있으나, 지금까지 가장 흔히 적용되는 항암 요법은 심각한 부작용이나 특정한 암에 제한적으로 적용되기도 하는 문제점을 가지고 있어, 좀 더 부작용이 낮은 새로운 치료 방법이 절실한 실정이다. 일반적으로 무한 증식을 하는 줄기세포는 세포 분화 후 세포의 성장이 정지되는 것으로 알려져 있다. 이에 이 총설에서는 거의 모든 암세포에서 공통적으로 나타나는 높은 포도당 대사 과정을 가진 암세포에 지방세포로의 분화를 유도하여, 분화된 암세포가 성장 억제 효과가 일어날 수 있는지 조사하였다. 여러 선행 연구에서, 당뇨병의 치료제로 사용되는 TDZs 계열의 약물을 여러 조직 기원의 암세포에 체외 투여하였을 때, 많은 조직 기원의 암세포주는 지방세포로 분화가 되는 것으로 알려줬으며, 분화된 암세포주는 세포의 성장이 점점 억제되는 것을 알 수 있었다. 이러한 결과들을 종합해 볼 때, 거의 모든 암세포에서 공통적으로 나타내는 높은 포도당 대사를 이용하여, 암세포를 지방세포로 분화를 유도하는 방법으로 암의 치료를 위한 한 요법 혹은 보조 요법으로 적용이 가능할 것으로 생각된다. 그러나, 체내에서 임상적으로 적용을 위해서는 지방세포 분화를 위한 약물이 성상 체세포 및 우리 몸의 재생을 위해 존재하는 줄기세포에 미치는 영향과 여러 체내 부작용을 면밀하게 조사하는 것이 필요할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권2호
• /
• pp.957-961
• /
• 2014

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluated genetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1). Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled in this case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results: In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRC and the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants and CRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC, and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledge has not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesis need to be further investigated.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권2호
• /
• pp.863-866
• /
• 2016

Background: Extensive efforts have been made to investigate c-KIT expression in lung cancer specimens and its correlation with clinical outcomes, but the issue remains unresolved. Thus, this study will be conducted to clarify the prognostic value of c-KIT expression in lung cancer patients. Materials and Methods: We will search Pubmed, SCOPUS, and ISI web of sciences with no restriction of language. Studies with any design (except case reports or case series) evaluating correlations of c-KIT expression with survival or outcome in patients with lung cancer will be included. The outcome measures will include all types of survival indexes, including overall survival rate and disease free survival using Kaplan-Meier analysis and hazard ratios. Study selection and data extraction will be performed by two independent researchers. Quality assessment (assessment of risk of bias) and data synthesis will be implemented using Stata software version 11.1. Results: No ethical issues are predicted. These findings will be published in a peer-reviewed journal and presented at national and international conferences. Conclusions: This systematic review protocol is registered in the PROSPERO International Prospective Register of Systematic Reviews, registration number = CRD42015023391.

• Journal of Gastric Cancer
• /
• 제21권3호
• /
• pp.319-324
• /
• 2021

The abscopal effect refers to the phenomenon in which local radiotherapy is associated with the regression of metastatic cancer that is distantly located from the irradiated site. Here, we present a case of a patient with advanced gastric cancer and brain metastases who was successfully treated with brain radiotherapy and anti-programmed death-1 (PD-1) therapy-induced abscopal effect. Although anti-PD-1 therapy alone could not prevent disease progression, the metastatic lesions in the brain and also in the abdominal lymph node showed a drastic response after brain radiotherapy and anti-PD-1 therapy. To our knowledge, this is the first reported case of successful treatment of advanced gastric cancer with multiple brain and abdominal lymph node metastases, possibly through anti-PD-1 therapy combined with brain radiotherapy-induced abscopal effect. We suggest that the combination of brain radiotherapy and anti-PD-1 therapy may be considered as a therapeutic option for advanced gastric cancer, especially when there is brain metastasis.