• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5675-5680
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• 2013

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3993-3996
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• 2014

Background: Diabetes is a chronic disease characterized by impaired fasting blood glucose that leads to disturbances in various organs. In this study, we evaluated relationships between tumor size and grade in a population of diabetic and non-diabetic patients with renal cell carcinoma. Materials and Methods: Between 2007-2013, in our clinic radical nephrectomy performed to 310 patients for renal tumors and pathology reported renal cell carcinoma cases were enrolled in the study. Patients with and without a history of diabetes regarding fasting glucose and HgA1c levels were evaluated during surgery for tumor size and Fuhrman grade. Results: Diabetes was found in 95 patients. The mean age of the patients with and without diabetes mellitus was 64.3 (40-79) and 58.4 (31-87) years, respectively. In the diabetes group 51% of patients had a tumor size over 7 cm and 54% a tumor grade over Fuhrman 3. The respective figures in the non-diabetes group were 35% and 30% (p<0.05 in both cases). Conclusions: Renal cancer appears more aggressive in patients with diabetes. In this study lifestyle and risk factors with diabetes regulation were observed to be important for renal cancer patients. Multicenter studies are needed in larger series for more accurate results.

• 한국임상약학회지
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• 제25권3호
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• pp.131-137
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• 2015

Background: The protective effect of metformin against breast cancer is inconclusive. Objective: To evaluate the effect of metformin on breast cancer risk and mortality in patients with type 2 diabetes. Method: A comprehensive literature search was performed for pertinent articles published prior to June 30, 2014, using PubMed and EMBASE. Study heterogeneity was estimated with $I^2$ statistic. The data from the included studies were pooled and weighted by random-effects model. The quality of each included study was assessed on the basis of the 9-star Newcastle-Ottawa Scale and publication bias was evaluated by visual inspection of a funnel plot. Results: Ten studies were included in the meta-analysis of the association of metformin and breast cancer risk. By synthesizing the data from the studies, the pooled odds ratio (OR) was 0.72 (95% CI: 0.59, 0.87) (p = 0.0005). Three cohort studies were included for meta-analysis of the association between metformin and breast cancer-related mortality. Metformin was associated with a significant decrease in mortality (Risk ratio: 0.68; 95% CI: 0.51, 0.90, p = 0.007). Conclusion: The present meta-analysis suggests that metformin appears to be associated with a lower risk of breast cancer incidence and mortality in patients with type 2 diabetes.

• BMB Reports
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• 제35권1호
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• pp.54-60
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• 2002

The effects of individual cytokine on apoptosis have been extensively studied. However, the effect of the cytokine combination, or the synergistic effect of cytokines on cell death, has not been widely studied, though synergism between cytokines has been documented in a variety of biological situations. In our effort to identify the final death effector molecule(s) in autoimmune diabetes, we inadvertently became interested in the cytokine synergism. We discovered that $IFN{\gamma}/TNF{\alpha}$ synergism, rather than the Fas ligand as currently believed, is responsible for the apoptosis of pancreatic islet cells both in vitro and in vivo. We also studied similar cytokine synergism in cancer cell deaths, and noted the similarities and dissimilarities between cancer cell death and islet cell death.

• 한국임상약학회지
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• 제29권3호
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• pp.186-192
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• 2019

Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ${\geq}30$ years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31-0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.

• Journal of Ginseng Research
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• 제36권2호
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• pp.135-145
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• 2012

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

• BMB Reports
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• 제44권10호
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• pp.619-634
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• 2011

Bone morphogenetic protein (BMP) signaling in diseases is the subject of an overwhelming array of studies. BMPs are excellent targets for treatment of various clinical disorders. Several BMPs have already been shown to be clinically beneficial in the treatment of a variety of conditions, including BMP-2 and BMP-7 that have been approved for clinical application in nonunion bone fractures and spinal fusions. With the use of BMPs increasingly accepted in spinal fusion surgeries, other therapeutic approaches targeting BMP signaling are emerging beyond applications to skeletal disorders. These approaches can further utilize next-generation therapeutic tools such as engineered BMPs and ex vivo-conditioned cell therapies. In this review, we focused to provide insights into such clinical potentials of BMPs in metabolic and vascular diseases, and in cancer.

• 통합자연과학논문집
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• 제6권1호
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• pp.57-63
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• 2013

Histone deacetylase (HDACs) is an enzyme family that deacetylates histones and non-histones protein. Availability of crystal structure of HDAC8 has been a boosting factor to generate target based inhibitors. Hydroxamic class is the most studied one to generate potent inhibitors. HDAC class I and class II enzymes are emerging as a therapeutic target for cancer, diabetes, inflammation and other diseases. DNA methylation and histone modification are epigenetic mechanism, is important for the regulation of cellular functions. HDACs enzymes play essential role in gene transcription to regulate cell proliferation, migration and death. The aim of this article is to provide a comprehensive overview about structure and function of HDACs enzymes, histone deacetylase inhibitors (HDACi) and HDACs enzymes as a therapeutic target for cancer, inflammation and diabetes.

• Nutrition Research and Practice
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• 제8권4호
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• pp.347-351
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• 2014

Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4571-4573
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• 2014

Diabetes, a comprehensive genetic disease, is principally due to the deregulation of glucose levels in the blood. In addition to contemporary epidemiological studies, systematic substantiation suggests that long-term diabetes leads to cancers due to a variety of reasons. In this study, blood samples were collected with informed consent from confirmed type I diabetic (T1DM, n=25) and type II Diabetic patients (T2DM, n=25) with equal numbers of controls. Further depending on the lifestyle habits they were subdivided into smokers/non-smokers and alcoholics/non-alcoholics. Chromosomal assays were performed for these cases and it was found that there was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM). On the other hand, patient groups who were non-smoking and non-alcoholics also showed higher chromosomal aberrations when compared to that of controls. While the mechanisms for these increased chromosomal aberrations in diabetic groups are not clear, they may be due to increased oxidative stress leading to oxidative damage and resulting in genomic instability, which in turn may contribute to an increased risk for cancer.