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BACKGROUND: Colorectal cancer in Korea has become more prevalent over the few last decades, and calcium is considered a preventive factor for colorectal cancer development. We examined the associations between total and dietary calcium intake and the prevalence of colorectal adenoma in Korean adults. METHODS: This cross-sectional study included 112 colorectal adenoma cases and 252 adenoma-free non-cases, aged 45 to 71 years, who underwent colonoscopies at the Daegu Catholic University Medical Center from August 2011 to September 2012. Participants were asked about their diet using a validated food frequency questionnaire and about supplement use through interviews. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between total and dietary calcium intake and the prevalence of colorectal adenomas using multivariable logistic regression models. RESULTS: Increasing total calcium intake from foods and supplements was significantly associated with a decreased prevalence of colorectal adenoma in women; comparing the highest quartile with the lowest quartile, the OR (95% CI) was 0.35 (0.15-0.85; P for trend = 0.03). Likewise, high dietary calcium intake from foods was associated with a lower prevalence of colorectal adenoma in women; compared with the lowest quartile, the ORs (95% CIs) were 0.32 (0.13-0.82) for the 3rd quartile and 0.44 (0.19-1.03; P for trend = 0.13) for the 4th quartile. However, the association was not clear for either total or dietary calcium intake among men. CONCLUSIONS: A higher intake of calcium was associated with a reduction of colorectal adenoma prevalence in Korean women.
Academic Medical Centers ; Adenoma* ; Adult* ; Calcium ; Calcium, Dietary* ; Colonoscopy ; Colorectal Neoplasms ; Cross-Sectional Studies ; Daegu ; Diet ; Female ; Humans ; Korea ; Logistic Models ; Male ; Odds Ratio ; Prevalence

BACKGROUND: The present study aimed to examine the association between cigarette smoking, alcohol consumption and colorectal cancer risk among Korean adults. METHODS: Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 18,707 subjects aged older than 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 11.2 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals of cigarette smoking and alcohol consumption for colorectal cancer risk. RESULTS: In men, longer duration and higher average amount of alcohol consumption were associated with elevated risk of colorectal cancer (HR 1.93 [1.17-3.18] for > or = 30 years of consumption compared to non-drinkers; HR 2.24 [1.31-3.84] for > or = 30 g/d). Former smokers showed a non-significantly elevated risk of colorectal cancer in men. There was no apparent association between alcohol consumption or cigarette smoking and colorectal cancer risk among women. CONCLUSIONS: Alcohol consumption was associated with increased colorectal cancer risk among Korean men, and both a longer duration and a higher amount of consumption were associated with elevated risk.
Adult ; Alcohol Drinking* ; Cohort Studies* ; Colorectal Neoplasms* ; Female ; Follow-Up Studies ; Humans ; Male ; Proportional Hazards Models ; Prospective Studies ; Smoking* ; Tobacco Products*

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. The objective of this study is to investigate the protective effect of Sasa quelpaertensis leaf extract (SQE) against oxidative stress in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were treated with SQE (100 mg/kg or 300 mg/kg body weight) by gavage in advance two weeks before inflammation was induced. Then, the mice were administered with 2.5% DSS in drinking water for 7 days and normal drinking water for 7 days between two DSS treatment. Disease activity index values, gut motility, and severity of the resulting oxidative DNA damage were analyzed. The antioxidant effect of SQE was evaluated by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) activity in plasma samples. Catalase activity and expressions levels of glutathione peroxidase 1 (Gpx1), SOD1, and SOD2 were also detected in colon tissues. RESULTS: Administration of SQE significantly reduced the severity of DSS-induced colitis compared to the control (Ctrl) group. Levels of 8-oxo-dG, an oxidative DNA damage marker, were significantly lower in the SQE group compared to the untreated DSS Ctrl group. In the SQE (300 mg/kg) group, MDA levels were significantly lower, while SOD and catalase activity levels in the plasma samples were significantly higher compared with the DSS Ctrl group. The expression levels of the antioxidant enzymes, SOD2 and Gpx1, were significantly higher, while the levels of SOD 1 expression were lower, in the colon tissues of the DSS Ctrl group compared with those of the Ctrl group. In contrast, administration of SQE significantly down-regulated SOD2 and Gpx1 expressions and up-regulated SOD1 expression. CONCLUSIONS: These results indicate that SQE efficiently suppresses oxidative stress in DSS-induced colitis in mice, and its action is associated with the regulation of antioxidant enzymes.
Animals ; Antioxidants ; Catalase ; Colitis* ; Colon ; Dextran Sulfate* ; Dextrans* ; DNA Damage ; Drinking Water ; Glutathione Peroxidase ; Inflammation ; Inflammatory Bowel Diseases ; Malondialdehyde ; Mice* ; Oxidative Stress ; Plasma ; Sasa* ; Superoxide Dismutase

BACKGROUND: While the majority of angiogenesis studies have focused on the late stages of cancer, the emergence of neovascularization in colon tumorigenesis has been observed an earlier stage than expected. Recent reports implied that early angiogenesis might be a defense mechanism to stimulate the natural clearance of microadenomas during colon tumorigenesis. However, little is known about how early angiogenesis affects the natural clearance of tumors. METHODS: Spontaneous colon tumors were developed in adenomatous polyposis coli conditional knockout mice with Cre recombinase adenovirus administration. Vascular endothelial growth factor (VEGF) antagonist, DC101, was administrated to determine the effect of early angiogenesis and then infiltration of immune cells into tumor and concentration of cytokines were evaluated. RESULTS: The continuous administration of the VEGF receptor 2 antagonist DC101 in the mouse models impeded the infiltration by CD4+ and CD8+ cells into the tumor region. Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10. CONCLUSIONS: We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells. Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.
Adenomatous Polyposis Coli ; Adenoviridae ; Animals ; Carcinogenesis ; Chemoprevention ; Colon* ; Cytokines ; Interleukin-10 ; Interleukins ; Mice ; Mice, Knockout ; Receptors, Vascular Endothelial Growth Factor ; Recombinases ; Vascular Endothelial Growth Factor A

BACKGROUND: Tumor growth and invasion are interconnected with the tumor microenvironment. Overexpression of genes that regulate cancer cell invasion by growth factors, cytokines, and lipid factors can affect cancer aggressiveness. A comparative gene expression analysis between highly invasive and low invasive cells revealed that various genes are differentially expressed in association with invasive potential. In this study, we selected variant PC-3 prostate cancer cell sublines and discovered critical molecules that contributed to their invasive potential. METHODS: The high invasive and low invasive variant PC-3 cell sublines were obtained by serial selection following Matrigel-coated Transwell invasion and were characterized by Transwell invasion, luciferase reporter assay, and Rhotekin pull-down assay. Lysophosphatidic acid (LPA) was added to the cultures to observe the response to this extracellular stimulus. The essential molecules related with cancer invasiveness were detected with Northern blotting, quantitative reverse transcription-polymerase chain reaction, and cDNA microarray. RESULTS: Highly invasive PC-3 cells showed higher nuclear factor kappa B (NF-kappaB), activator protein 1 (AP-1) and RhoA activities than of low invasive PC-3 cells. LPA promoted cancer invasion through NF-kappaB, AP-1, and RhoA activities. Thrombospondin-1, interleukin-8, kallikrein 6, matrix metalloproteinase-1, and tissue factor were overexpressed in the highly invasive PC-3 variant cells and further upregulated by LPA stimulation. CONCLUSIONS: The results suggest that the target molecules are involved in invasiveness of prostate cancer. These molecules may have clinical value for anti-invasion therapy by serving as biomarkers for the prediction of aggressive cancers and the detection of pharmacological inhibitors.
Biomarkers ; Blotting, Northern ; Cytokines ; Gene Expression ; Intercellular Signaling Peptides and Proteins ; Interleukin-8 ; Kallikreins ; Luciferases ; Matrix Metalloproteinase 1 ; NF-kappa B ; Oligonucleotide Array Sequence Analysis ; Prostate* ; Prostatic Neoplasms* ; Thromboplastin ; Transcription Factor AP-1 ; Tumor Microenvironment

BACKGROUND: Multiple myeloma SET domain (MMSET)/nuclear receptor binding SET domain 2 (NSD2) is a lysine histone methyltransferase (HMTase) and bona fide oncoprotein found aberrantly expressed in several cancers, suggesting potential role for novel therapeutic strategies. In particular, MMSET/NSD2 is emerging as a target for therapeutic interventions against multiple myeloma, especially t(4;14) myeloma that is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma and remains an incurable malignancy. Thus, effective therapeutic strategies are greatly needed. HMTases inhibitors are scarce and no NSDs inhibitors have been isolated. METHODS: We used homology modeling, molecular modeling simulations, virtual ligand screening, computational chemistry software for structure-activity relationship and performed in vitro H3K36 histone lysine methylation inhibitory assay using recombinant human NSD2-SET and human H3.1 histone. RESULTS: Here, we report the discovery of LEM-06, a hit small molecule inhibitor of NSD2, with an IC50 of 0.8 mM against H3K36 methylation in vitro. CONCLUSIONS: We propose LEM-06 as a hit inhibitor that is useful to further optimize for exploring the biology of NSD2. LEM-06 derivatives may pave the way to specific NSD2 inhibitors suitable for therapeutic efforts against malignancies.
Biology ; Chemistry ; Drug Design ; Epigenomics* ; Hematologic Neoplasms ; Histone-Lysine N-Methyltransferase ; Histones ; Humans ; Inhibitory Concentration 50 ; Lymphoma, Non-Hodgkin ; Lysine ; Mass Screening ; Methylation ; Models, Molecular ; Multiple Myeloma ; Prognosis ; Structure-Activity Relationship ; United States

BACKGROUND: Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells. METHODS: We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4\',6-diamidino-2-phenylindole staining and Western blotting. RESULTS: Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells. CONCLUSIONS: Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti-proliferative agent that induces apoptotic cell death in G361 HMM cells.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Death ; Cyclin D1 ; Humans* ; Melanoma* ; Sp1 Transcription Factor

The incidence trends of colorectal cancer have varied over time, and there is wide geographical variation across the world. Regarding colorectal cancer, diverse modifiable environmental or intrinsic risk factors have been investigated. This review summarizes the effects of both dietary intake of vitamin D and calcium in particular and diet-associated genetic factors on colorectal cancer risk. We searched the electronic database PubMed for articles published between January 2000 and March 2015. We reviewed case-control studies that included dietary factors, genetic polymorphisms, and gene-diet interactions in association with colorectal cancer risk. Overall, 21 studies were selected as eligible studies. These studies demonstrated that dietary consumption of vitamin D and calcium may decrease the risk of colorectal cancer or adenoma. Colorectal carcinogenesis was discussed in conjunction with dietary factors and mediating genetic factors. The epidemiological findings suggested that the gene-diet interactions may possibly alter the associations between dietary intake, genetic polymorphisms, and the risk of colorectal cancer. However, the reported effects of the same potential factors on colorectal cancer risk were inconsistent, depending on the study population and geographical location. This finding may imply the necessity of considering the environmental differences and genetic variations existing between individuals or specified populations. Therefore, further studies are required to investigate modifiable risk factors in diverse locations to derive useful implications for colorectal neoplasia.
Adenoma ; Calcium* ; Carcinogenesis ; Case-Control Studies ; Colorectal Neoplasms ; Gene-Environment Interaction ; Genetic Variation ; Incidence ; Negotiating ; Polymorphism, Genetic* ; Risk Factors ; Vitamin D* ; Vitamins*

Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies.
Carcinogenesis* ; Carotenoids ; DNA Damage ; Eating ; Helicobacter pylori ; Incidence ; Oxidative Stress ; Reactive Oxygen Species ; Risk Factors ; Smoke ; Smoking ; Stomach Neoplasms