• Radiation Oncology Journal
• /
• 제34권2호
• /
• pp.113-120
• /
• 2016

Purpose: The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). Materials and Methods: We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2-3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ${\geq}25kg/m^2$) in local control was evaluated. Results: The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of $25.6kg/m^2$ as a cutoff value. Conclusion: Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted.

• Molecules and Cells
• /
• 제44권10호
• /
• pp.710-722
• /
• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• Journal of Gastric Cancer
• /
• 제21권3호
• /
• pp.279-297
• /
• 2021

Purpose: Various changes in nutrition, metabolism, immunity, and psychological status occur through multiple mechanisms after gastrectomy. The purpose of this study was to predict disease status after gastrectomy by analyzing diseases pattern that occur or change after gastrectomy. Materials and Methods: A retrospective cohort study was conducted using nationwide claims data. Patients with gastric cancer who underwent gastrectomy or endoscopic resection were included in the study. Eighteen target diseases were selected and categorized based on their underlying mechanism. The incidence of each target disease was compared by dividing the study sample into those who underwent gastrectomy (cases) and those who underwent endoscopic resection for early gastric cancer (controls). The cases were matched with controls using propensity score matching. Thereafter, Cox proportional hazard models were used to evaluate intergroup differences in disease incidence after gastrectomy. Results: A total of 97,634 patients who underwent gastrectomy (84,830) or endoscopic resection (12,804) were included. The incidence of cholecystitis (P<0.0001), pancreatitis (P=0.034), acute kidney injury (P=0.0083), anemia (P<0.0001), and inguinal hernia (P=0.0007) were higher after gastrectomy, while incidence of dyslipidemia (P<0.0001), vascular diseases (ischemic heart disease, stroke, and atherosclerosis; P<0.0001, P<0.0001, and P=0.0005), and Parkinson's disease (P=0.0093) were lower after gastrectomy. Conclusions: This study identifies diseases that may occur after gastrectomy in patients with gastric cancer.

• 한국임상약학회지
• /
• 제31권2호
• /
• pp.115-124
• /
• 2021

Background: With an increase in the number of breast cancer survivors, greater importance is attached to health-related quality of life, particularly pain and symptom control. This study aimed to identify the factors that are associated with pain in cancer patients based on the patterns of prescribing opioid, non-opioid, and adjuvant analgesics. Methods: This analysis included new patients who had developed breast cancer between 2003 and 2012. The degree of pain was analyzed based on the socio-demographic (age, income quintile, number of hospitalizations, and duration of disease), indicator (Body Mass Index; BMI, Charlson Comorbidity Index; CCI, Cumulative Analgesic Consumption Score; CACS), operation (mastectomy, lymph node dissection), and therapy (chemotherapy, radiation therapy), as well as complication-related variable (lymphedema). Results: As for the patterns of prescribing analgesics by stages, non-opioid and opioid analgesics constituted 30.7 and 69.3%, respectively. The mean value and variance of CACS were 5.596 and 12.567, respectively. The factors that significantly affected the degree of pain were age (≥50; IRR: 1.848, 95% CI 1.564-2.184, p=0.000), income quintile (IRR: 0.964, 95% CI 0.938-0.991, p=0.008), BMI (≥ 25; IRR: 1.479, 95% CI 1.222-1.795, p=0.000), CCI (≥ 4; IRR: 1.649, 95% CI 1.344-2.036, p=0.000), and lymphedema (yes; IRR: 1.267, 95% CI 1.006-1.610, p=0.047). Conclusions: It is necessary to develop systematic and comprehensive pain control measures to improve the quality of life for breast cancer survivors, especially for those who are 50 years or older, lie in the lower-income quintile, have BMI of ≥25 and CCI score ≥ 4, or have lymphedema.

• 한국환경보건학회지
• /
• 제36권1호
• /
• pp.1-13
• /
• 2010

Evidences supporting gene-environment interaction are accumulating in terms of environmental exposure including lifestyle factors and related genetic variants. One form of defense mechanism against cancer development involves a series of genes whose role is to metabolize (activation/detoxification) and excrete potentially toxic compounds and to repair subtle mistakes in DNA. The purpose of this article is to provide a brief review of the notion of gene-environment interaction, environmental/occupational carcinogens and related cancers, and previous studies of gene-environment interaction on cancers caused by exposure to carcinogenesis. With a number of studies on the interaction between lifestyle factors (e.g., smoking and diet) and genetic polymorphisms in genes involved in xenobiotic metabolism and DNA repair excluded, only several studies have been conducted on the interactive effects between polymorphisms of CYPs, GSTs, ERCCs, XRCCs and environmental/occupational carcinogens such as vinyl chloride, benzo[a]pyrene, and chloroform on carcinogenesis or genotoxicity. Future studies may need to be conducted with sufficient number of subjects and based on occupational cohorts to provide useful information in terms of advanced risk assessment and regulation of exposure level.

• 한국식품영양학회지
• /
• 제28권5호
• /
• pp.880-893
• /
• 2015

Taurine is an abundant amino acid in many animals, including humans. Relatively large amounts of taurine are found in leukocytes, heart, muscles, retinas, kidneys, bones, and liver. Taurine has antioxidant effects; it reacts with hydrogen peroxide to prevent oxidation of the cell membrane. Taurine enhances the effects of anticancer drugs, while also reducing side effects, and taurolidine, a taurine derivative, has been shown to exhibit anti-cancer effects without notable side effects in several types of cancer. Taurine aids in cholesterol metabolism by increasing the rate of synthesis of bile acids, and, thus, reduces triglyceride levels. In addition, taurine is involved in the growth and differentiation of nerve cells and is associated with some neurological disorders. Taurine aids in bone formation and prevents bone dissolution. Moreover, taurine prevents liver damage from a variety of drugs and, thus, protects the liver. Taurine is involved in the development and function of the retina and lens. It also has anti-atherosclerotic and anti-thrombotic effects that protect against cardiovascular disease. Taurine may have additional physiological functions, and warrants further investigation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권6호
• /
• pp.2711-2715
• /
• 2012

Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to pose carcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its real significance for cancer development. Methods: We therefore studied BPA-induced proteomic alterations in immune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water). We performed 2D-gel analyses of samples, considering differences in spleen, exposure levels, sex, and ages. Results: From proteomic analyses, we found various proteins were up- or down-regulated by BPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly down-regulated in a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blot and real time PCR analyses. From gene network analysis, SET is predicted to communicate with other genes including CYP17, which is involved in biosynthesis and metabolism of sex-hormones. Conclusions: This study provided evidence that SET can be applied as a new biomarker for prenatal BPA exposure and suggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.

• Nuclear Medicine and Molecular Imaging
• /
• 제40권4호
• /
• pp.233-236
• /
• 2006

A 67-year-old man with a history of chronic obstructive pulmonary disease (COPD) underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging of gastric cancer. The projection images of F-18 FDG PET/CT showed intensely increased F-18 FDG uptake in the anterior neck, chest wall, and upper abdomen. We suspected distant metastases of cervical lymph nodes, ribs, and peritoneum in gastric canter. However, the transaxial images of F-18 FDG PET/CT showed abnormal F-18 FDG uptake in scalene muscles of anterior neck, intercostal muscles of chest wall, and diaphragm of upper abdomen. Patients with COPD use respiratory muscles extensively on the resting condition. These excessive physiologic use of respiratory muscles causes increased F-18 FDG uptake as a result of increased glucose metabolism. The F-18 FDG uptake in respiratory muscles of gastric cancer patient with COPD mimicked distant metastases in cervical lymph nodes, ribs, and peritoneum.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3509-3514
• /
• 2013

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

• BMB Reports
• /
• 제36권1호
• /
• pp.1-11
• /
• 2003

The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention of chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria:i.adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined.iii. sources of inter- and intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAH-exposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurement may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. Biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurement as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.