Role of TGF-β1 and its Receptors in Breast Carcinogenesis： Evaluation of Gene Expression Pattems and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.     

Cigarette smoking and gastric cancer risk in a community-based cohort study in Korea]

OBJECTIVES: Gastric cancer is the most common incident cancer in Korea. Although Helicobacter pylori infection is the most important risk factor for the development of gastric cancer, cigarette smoking has also been suggested to play an important role in the development of gastric cancer. The objective of this study is to evaluate the relationship between cigarette smoking and gastric cancer risk in a Korean population. METHODS: The study population consisted of 13,785 subjects who had been enrolled in the Korean Multi-Center Cancer Cohort between 1993 and 2002. As of December 2002, 139 incident gastric cancer cases were ascertained through the Korea Central Cancer Registry and the National Death Certificate Database. Relative risks (RR) and 95% confidence intervals (CI) for gastric cancer were estimated using Cox's proportional hazard model adjusted for age, education, alcohol drinking status and history of gastritis or ulcer. RESULTS: Significant dose-response relationships were observed between the duration of smoking and the risk of gastric cancer among the male subjects in comparison to non-smokers: men who smoked for 20-39 years had a 2.09- fold (95% CI 1.00-4.38) increase, and those who smoked for more than 40 years had a 3.13-fold (95% CI 1.59-6.17) increase in the risk of gastric cancer (P trend<0.01). CONCLUSIONS: This study suggests that a longer duration of cigarette smoking may increase the risk of gastric cancer development in a dose-response manner in Korean men. The association between smoking and gastric cancer risk in women should be verified in future studies with a larger number of cases.     

Prevalence and risk factors of distal radius and calcaneus bone mineral density in Korean population

To estimate the prevalence and the related risk factors of low bone mineral density of the calcaneus and the distal radius, a community-based study was conducted in three rural areas of Korea. A total of 1420 women and 732 men aged 40 years and older participated in this study. Information on sociodemographic characteristics and the potential risk factors for osteoporosis were collected by an interviewer-administered standardized questionnaire. Bone mineral density (BMD) of the calcaneus and the distal radius were measured by dual-energy X-ray absorptiometry (DXA). Three hundred and seventeen women and 183 men aged 20–29 years who participated in a regular health check-up were used as a reference population. Osteoporosis was defined using WHO criteria. Odds ratios of the risk factors of osteoporosis were calculated by the unconditional logistic regression model. The standardized prevalence of osteoporosis of the calcaneus was 8.4% for males and 27.3% for females using the Korean population of year 2000 as a standard population. The standardized prevalence of osteoporosis of the distal radius was 4.2% for males and 18.8% for females. Older age and lower body mass index (BMI) were related with low BMD in both the calcaneus and distal radius in males and females. The duration after menopause and the number of live births were an independent risk factor for osteoporosis of the calcaneus (OR=1.1, 95% CI=1.00–1.11; the duration after menopause; OR=2.0, 95% CI=1.20–3.35, the number of live birth) and a familial history of non-traumatic fractures or osteoporosis among the first-degree relatives was significantly related to a increased risk of osteoporosis of the distal radius in females (OR=2.9, 95% CI=1.36–6.31).     

Synthesis and anticonvulsant activities ofN-Cbz-α-aminoglutarimidooxy carboxylate derivatives

Previous studies on the anticonvulsant activity of N-Cbz-alpha-aminoglutarimides have shown that the derivatives of N-Cbz-alpha-amino-N-alkoxy glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of N-Cbz-alpha-amino-glutarimidooxy carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of N-Cbz-alpha-amino-glutarimidooxy acetic acid 3a (ED50 = 42.9 mg/kg).     

Associations of cigarette smoking and alcohol consumption with advanced or multiple colorectal adenoma risks: a colonoscopy-based case-control study in Korea

The associations between alcohol consumption and cigarette smoking habits and the risk for colorectal adenomatous polyps according to the detailed clinical information about polyps were assessed in a large colonoscopy-based study. The study enrolled participants who visited the National Cancer Center of the Republic of Korea for cancer screening between April 2007 and April 2009. In 1,242 newly diagnosed colorectal adenoma patients and 3,019 polyp-free controls, past smokers (odds ratio (OR) = 1.31, 95% confidence interval (CI): 1.04, 1.65) and current smokers (OR = 1.70, 95% CI: 1.37, 2.11) had increased risks for adenomas compared with nonsmokers. Cigarette smoking conferred an even higher risk for advanced adenomas and 3 or more adenomas than for low-risk adenomas or a single adenoma. Dose-response relations were observed among the daily number of cigarettes smoked, the duration of smoking, the pack-years of smoking, and the risk for adenomas. A longer duration of alcohol consumption was associated with a higher risk for advanced adenomas (for >28 years of consumption: OR = 2.0, 95% CI: 1.10, 3.64) and 3 or more adenomas (OR = 2.19, 95% CI: 1.27, 3.76). In conclusion, cigarette smoking and alcohol consumption play roles in colorectal carcinogenesis, and the association differs by the clinical features of the adenomas.     

Associations among dietary seaweed intake,c-MYC rs6983267 polymorphism,and risk of colorectal cancer in a Korean population: a case–control study

The effects of seaweed compounds have been studied in relation to colorectal cancer (CRC) based on their ability to modulate carcinogen metabolism in vivo     

Synthesis and hypnotic activities of <Emphasis Type="Italic">N</Emphasis>-Cbz-α-aminoglutarimidooxy carboxylate derivatives

Typical hypnotic drugs, such as barbitals and glutethimide, have a cyclic imide (-CO-NH-CO-) moiety. The N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives, which we previously showed exhibit moderate anticonvulsant activities, also have a cyclic imide (-CO-N-CO-) moiety. This structural similarity prompted us to examine the hypnotic activities of the N-Cbz-alpha-aminoglutarimidooxy carboxylate derivatives, and we describe their moderate hypnotic activities here.