HIF1A C1772T polymorphism leads to HIF-1α mRNA overexpression in prostate cancer patients

Hypoxia-inducible factor 1α (HIF-1α) gene polymorphisms have been investigated for a possible role in mediating genetic predisposition to cancer. Our previous data show that men homozygous to C1772T polymorphism had 4-fold risk to develop prostate cancer. Therefore, we studied the effects of C1772T polymorphism on HIF-1α expression. HIF-1α mRNA expression levels were significantly higher in peripheral blood leukocytes of prostate cancer patients with the TT genotype compared with the CC genotype. Expression of C1772T HIF-1α in HIF-1α knockout cancer cells showed higher expression levels and stabilization of HIF-1α mRNA compared with the wild-type. Mutated HIF-1α protein half-life was similar to that of the wild-type. Hence, our data provide evidence that C1772T polymorphism causes activation of HIF-1α as a gain-of-function mechanism driven by stabilization of HIF-1α mRNA. These findings may also explain the increased risk of men homozygous to this mutation to develop prostate cancer.     

The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway

Cyclooxygenase-2 (COX-2) is frequently overexpressed in human malignancies and plays a crucial role in tumorigenesis and cancer progression. The present study aimed to investigate the expression and clinical significance of COX-2 and survivin (SUV) in human osteosarcomas (OS), and explore the effects and molecular mechanisms of a selective COX-2 inhibitor NS-398 and SUV on tumor proliferation and apoptosis. Fifty cases of human OS and osteochondromas (OC) were collected. The expression of COX-2 and SUV was assessed using immunohistochemical assays in biopsy samples. MG-63 human OS cells were treated with different concentrations of NS-398, used to investigate their effects on cell proliferation and apoptosis. The recombinant small hairpin RNA adenovirus vector rAd5-SUV was constructed, and the effects and molecular mechanisms of knockdown of SUV on proliferation and apoptosis were evaluated in MG-63 cells. A subcutaneous xenograft tumor model was established, validating the effects of rAd5-SUV on tumor growth in vivo. Based on the results, the expression of COX-2 and SUV in OS showed a higher strong reactivity rate compared with OC (73.3 vs. 25.0%, P=0.001; 63.3 vs. 30.0%, P=0.02), but it did not correlate with the clinicopathological characteristics of OS. NS-398 inhibited proliferation, induced apoptosis and decreased the mRNA expression of COX-2 and SUV in MG-63 cells. Furthermore, adenovirus-mediated knockdown of SUV inhibited proliferation, induced apoptosis, reduced the expression of proliferating cell nuclear antigen (PCNA), increased the expression of caspase-3 (CAS-3) and slowed the growth of xenograft tumors in MG-63 cells. Taken together, the expression of COX-2 and SUV is closely correlated with human OS, and inhibition of COX-2 or knockdown of SUV suppresses tumor proliferation and induces apoptosis, suggesting that COX-2 may be involved in OS cell proliferation and apoptosis through SUV-mediated regulation of PCNA and CAS-3 expression, and provides a potential therapeutic strategy for the treatment of cancer.     

The -938A/A genotype of BCL2 gene is associated with esophageal cancer

Perturbations in the apoptotic genes have been implicated in human malignancies. The purpose of the present study was to investigate the polymorphisms of -938C/A, Thr43Ala in anti-apoptotic B-cell lymphoma 2 gene (BCL2) and -248G/A in pro-apoptotic B-cell lymphoma 2-associated X protein gene (BAX) and to explore their role in influencing the susceptibility for development of esophageal cancer. A total of 205 esophageal cancer patients and 224 controls were enrolled in the present study. The genotype and allele distributions of -938C/A, ala43thr in BCL2 and -248G/A in BAX were analyzed in patients and controls, as well as the association of -938C/A genotype with clinical characteristics in patients. We found that homozygous -938A/A genotype of BCL2 gene was significantly associated with risk of developing esophageal cancer (χ² = 9.269, P = 0.002, OR = 2.585, 95%CI = 1.380–4.842). Association with clinical characteristics showed that the patients with BCL2 -938A/A genotype were more likely to develop into poor differentiation compared with the AC and CC carriers (χ² = 5.796, P = 0.016, OR = 4.039, 95%CI = 1.200–13.596), and we found smokers were more present in the -938A/A genotype subgroup (χ² = 5.095, P = 0.024, OR = 2.679, 95%CI = 0.893–8.025). The present study revealed that the -938A/A genotype of BCL2 gene is associated with susceptibility of esophageal cancer. There appeared to be an impact of BCL2 -938A/A genotype on tumor differentiation and smoking. Further studies are needed in a larger population.     

Prevalence, intensity and risk factors for clonorchiasis and possible use of questionnaires to detect individuals at risk in northern Vietnam

A high prevalence of the liver flukes Clonorchis sinensis and Opisthorchis viverrini has been reported in a number of provinces in Vietnam. Knowledge about C. sinensis infection gained from Thailand over the past decade suggests that the habit of eating raw freshwater fish is a major risk factor for infection. However, further information to confirm this is needed. In the present study 1155 villagers in two communes in northern Vietnam were interviewed and their stools were examined for the presence of liver flukes. The prevalence of infection was 26% and was 3.6 times higher in males than in females. The habit of eating raw fish increased the risk of C. sinensis infection 53-fold. These results provide evidence of a strong correlation between the intensity of C. sinensis infection and the cumulative quantity of freshwater fish consumed in a lifetime and suggest that simple questionnaires could be used in endemic areas to quickly identify populations at risk and enable targeted treatment.     

Prevalence of patch test results from 1970 to 2002 in a multi-centre population in North America (NACDG)

Background:  The North American Contact Dermatitis Group (NACDG) has members who assess subjects with suspected allergic contact dermatitis (ACD) and patch tests them with the same screening allergens using a standardized procedure permitting analysis of long-term trends in patch test reactions.
Objective:  This study reports the trends in prevalence patch test positivity of allergens by pooling data collected by the NACDG between 1970 and 2002.
Patients/Methods:  Patients were tested with the screening series of allergens, using a standardized technique. Data from these patients were recorded on a standard computer entry form and analysed. More than 100 allergens were tested on over 34 000 patients during several patch studies between the period. The Cochran-Armitage test of trend is used to evaluate changes in prevalence over time.
Results:  4 trends are noticed: (1) The incidence of presumed allergic nickel ( P < 0.0001) and quaternium-15 ( P < 0.0001) reactions rose with consistency over the years. (2) While that of cinnamic aldehyde ( P = 0.21) and p -phenylenediamine ( P < 0.0001) decreased. (3) The prevalence of positive reactions for potassium dichromate ( P < 0.0001) shows an initial steady decrease but then a sharp increase starting from the 1996 period. (4) In contrast, thiuram ( P = 0.0008) and neomycin ( P < 0.0001) show an initial general increase, with a sharp decrease between 1998 and 2002.
Conclusion:  Implications for opportunities to prevent ACD by utilizing less-allergenic alternatives appear robust; however, we do not wish to over generalize interpretations because of important limitations.     

工作时间过长与工伤事故

工作时间过长是全球化经济和24 h工作社会的一个突出特点,尤其是生产和服务行业,从业人员长时间轮班工作.工作时间过长对员工健康和安全有所威胁,可能导致生产安全的负性事件,造成生产中断、医疗费用增加,还会影响到社会公共利益,对从业人员家庭生活也有负面影响.