Alcohol consumption and lung cancer mortality in Japanese men: results from Japan collaborative cohort (JACC) study

BACKGROUND: The relationship between alcohol consumption and increased risk of lung cancer is controversial. This study was set up to investigate the association between alcohol consumption and death from lung cancer in a large Japanese cohort. METHODS: The subjects comprised 28,536 males, aged 40-79 years, living throughout Japan. During 268,464 person-years of follow-up, 377 lung cancer deaths were recorded. The hazard ratio (HR) of alcohol consumption for lung cancer mortality was calculated using the Cox proportional hazards model after adjustment for age, smoking and family history of lung cancer. RESULTS: There was no association between increased mortality from lung cancer and alcohol consumption among current drinkers. Compared with subjects who had never drunk alcohol, the HRs (95% confidence interval [CI]) of death from lung cancer for light (consuming <25.0 g ethanol per day), moderate (25.0-49.9 g per day) and heavy (>or=50 g per day) drinkers were 0.81 (95% CI=0.61-1.07), 0.82 (0.61-1.11) and 0.97 (0.66-1.43), respectively. Further adjustment for fruit and vegetable intake did not change the results, and there was no change in HR materially after excluding those patients who died during the first 5 years of follow-up. CONCLUSIONS: These findings indicate that alcohol consumption was not associated with increased lung cancer mortality in this population of Japanese men.     

Analysis of complications and prognosis for different types of stroke patients registered between 1993 and 2000 in Aichi Prefecture

PURPOSE: This study was designed to analyze complications and prognosis for different types of stroke patients registered in Aichi Prefecture between 1993 and 2000. METHODS: A total of 23,979 out of 27,304 registered patients in the Aichi stroke patient registration program with 4 type of strokes (cerebral thrombosis (CRT), cerebral embolism (CRE), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)) were analyzed for complications and prognosis (survival, disability, dementia), with reference to gender, age-groups, and types of stroke. RESULTS: A total of 13,365 (55.7%) male (65.5 +/- 12.2 yr: Mean +/- SD) and 10,614 (44.3%) female (69.7 +/- 13.3 yr) patients were registered. As the type of stroke, CRT comprised the highest percentage, both in males (49.5%) and females (41.1%), followed by ICH (males: 30.4%, females: 29.8%). The percentage of SAH in females (17.3%) was found to be about twice as high as that in males (8.3%). Analyses of complications revealed hypertension to be the greatest risk factor in both sexes (about 50%), followed by history of stroke (males: 20.1%, females: 16.2%). Male patients had a significantly higher overall survival rate (84.7%) than females (81.0%) (P <0.001). SAH was associated with the lowest survival rate in both sexes (about 60%), with statistical significance (P<0.001). Development of disability or/and dementia as sequela of stroke was higher in females (disability: 54.5%, dementia: 21.1%) than in males (44.2%, 15.1%, respectively) (P< 0.001). Logistic regression analyses revealed that the factors most contributing to death were advanced age, a history of stroke, heart disease, and renal insufficiency. For the development of disability and dementia, being femal, of advanced age, with a history of stroke, heart disease, and renal insufficiency were important. Abnormal lipid metabolism appeared to be a protection factor regarding prognosis (survival, disability, dementia). CONCLUSIONS: This study demonstrated that hypertension is the most frequently reported complication for all types of stroke except CRE, and logistic regression analyses revealed that the factor contributing most to prognosis (survival, disability, dementia) was a history of stroke. The results suggested the importance of: i) removing hypertansion as the most significant risk factor, as well as diabetes and heart disease in order to prevent strokes; and ii) preventing re-attack(s) of stroke in order to improve the prognosis.     

Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis

Cap43 has been identified as a nickel- and calcium-induced gene, and is also known as N-myc downstream-regulated gene 1 (NDRG1), Drg-1 and rit42. It is also reported that overexpression of Cap43 suppresses metastasis of some malignancies, but its precise role remains unclear. In this study, we asked how Cap43 could modulate the tumor growth of pancreatic cancer. Stable Cap43 cDNA transfectants of pancreatic cancer cells with Cap43 overexpression showed similar growth rates in culture as their control counterparts with low Cap43 protein level. By contrast, Cap43 overexpression showed a marked decrease in tumor growth rates in vivo. Moreover, a marked reduction in tumor-induced angiogenesis was observed. Gelatinolytic activity by matrix metalloproteinase-9 and invasive ability in Matrigel invasion activity were markedly decreased in pancreatic cancer cell lines with high Cap43 expression. Cellular expression of matrix metalloproteinase-9 and two major angiogenic factors, vascular endothelial growth factor and interleukin-8, were also significantly decreased in cell lines with Cap43 overexpression as compared with their parental counterparts. Immunohistochemical analysis of specimens from 65 patients with pancreatic ductal adenocarcinoma showed a significant association between Cap43 expression and tumor microvascular density (P = 0.0001) as well as depth of invasion (P = 0.0003), histopathologic grading (P = 0.0244), and overall survival rates for patients with pancreatic cancer (P = 0.0062). Thus, Cap43 could play a key role in the angiogenic on- or off-switch of tumor stroma in pancreatic ductal adenocarcinoma.     

Far lateral extraforaminal facet cyst causing L5 radiculopathy

Most synovial cysts of the lumbar spine appear as intraspinal extradural masses adjacent to the facet joint. Almost all symptomatic synovial cysts are located within the spinal canal and or the neural foramen. To our knowledge, only 6 cases of symptomatic extraspinal synovial cysts have been described in the literature. The authors report a case of lumbar radiculopathy caused by a synovial cyst located in the far lateral extraforaminal area. The patient underwent decompression of the L5 nerve root with recapping right isthmectomy and facetectomy. Postoperative recovery was uneventful, and the patient was totally pain free with no motor deficit. Symptomatic synovial cysts are uncommon lesions that are associated with degenerative disease of the spine. Juxtafacet cysts should be considered in the differential diagnosis of space-occupying lesions at the extraforaminal areas. Recapping isthmectomy and facetectomy are useful procedures for a synovial cyst located in the far lateral extraforaminal area.     

Thin-layer chromatography of bile lipids

A simple and rapid method of evaluating bile lipid components has been developed using thin-layer chromatography. The method can be adapted to routine bile analysis as well as in experiments on small animals. Bile lipids including lecithin, lysolecithin, glycine- and taurine-conjugated cholic and dihydroxycholanic acids, free bile acids, cholesterol and its ester, triglycerides, and fatty acids have been separated on a single plate with successive developments, using as little as 0.5 μl of bile, and making a direct comparison between the single bile lipid components possible.     

ELECTROENCEPHALOGRAPHIC STUDIES OF TIME ESTIMATION PART III: EFFECT OF FREQUENCY OF FLICKERING LIGHT ON TIME ESTIMATION

SUMMARY
We examined the relation between changes in time estimation by various frequencies of flickering lights, that is, 1.5, 3, 6, 10, and 16 cps in the experiment 1, and
Main results are following:
Spearman's rank correlation coefficients between mean PD and mean PA's of δ₁, 5th, α, and β₁ frequency-bands were.70,.60, -.90, and.60 respectively in the experiment 1, -.20,.82, -.50, and.60 respectively in the experiment 2. And for almost all subjects there were low negative correlations between PD and PA of α band.
Thus we believe that a-rhythm plays an important role in estimation of short time, in a way that, as the amplitude of α frequency-band increases in a given time period, it is felt subjectively longer.     

Obesity and risk of cancer in Japan

We conducted a population-based prospective cohort study in Japan to examine the relationship between body mass index (BMI) and the risk of incidence of any cancer and of cancer at individual sites. Body mass index was calculated from self-administered body weight and height at baseline. Relative risks (RR) and 95% confidence intervals (CI) were calculated in multivariate proportional-hazards models. Among 27,539 persons (15,054 women and 12,485 men) aged 40 years or older who were free of cancer at enrollment in 1984, 1,672 (668 women and 1,004 men) developed cancer during 9 years of follow-up. In women, after adjustment for potential confounders, the RR of all cancers associated with different BMI, relative to a BMI of 18.5-24.9, were 1.04 (95% CI = 0.85-1.27) for BMI = 25.0-27.4, 1.29 (1.00-1.68) for BMI = 27.5-29.9 and 1.47 (1.06-2.05) for BMI >/=30.0 (p for trend = 0.007). Higher BMI was also significantly associated with higher risk of cancers of the colorectum, breast (postmenopausal), endometrium and gallbladder in women. In men, we observed significantly increased all-cancer risk among only never-smokers. Overweight and obesity could account for 4.5% (all subjects) or 6.2% (never-smokers) of the risk of any cancer in women and -0.2% (all subjects) or 3.7% (never-smokers) in men. The value for women was within the range among women reported from Western populations (3.2%-8.8%). Our data demonstrate that excess weight is a major cancer risk among Japanese women.     

HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells

Gefitinib (Iressa), an epidermal growth factor receptor targeting drug, has been clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). Gefitinib is currently being applied in clinical studies as either a monotherapy, or as part of a combination therapy against prostate, head and neck, gastric, breast, and colorectal tumors. However, success rates vary between different tumor types, and thus it is important to understand which molecular target(s) are responsible for limiting the therapeutic efficacy of the drug. In this study, we ask whether expression of HER2 affects sensitivity to gefitinib in human lung cancer cells. We established two clones, LK2/HER2-32 and LK2/HER2-57, by transfecting HER2 cDNA into LK2, a NSCLC line with a low expression level of HER2. We observed no mutations in exons 18, 19, and 21 of EGFR gene in LK2, LK2/mock- and two HER2-trasfectants when we observed in-frame deletion mutations (E746-A750) adjacent to K745 in a gefitinib-sensitive NSCLC cell line, PC9. These LK2/HER2-32 and LK2/HER2-57 were much more sensitive to the cytotoxic effects of gefitinib than the parental LK2 lines. Treatment with 0.5 to 1 micromol/L gefitinib specifically blocked Akt activation in both HER2-transfectant lines, but not in the parental LK2 cells. Extracellular signal-regulated kinase-1/2 activation, however, was not blocked by gefitinib up to 10 micromol/L in either the parent or transfectant lines. Gefitinib was also shown to induce cell cycle arrest in the G1-S phase, and an accompanying increase of p27Kip1 was observed. LK2/HER2 transfectants showed constitutive formation of HER2/HER3 heterodimer, which were seen to associate with a regulatory subunit of phosphoinositide-3-kinase, p85alpha, when active. Treatment of LK2/HER2 cells with gefitinib markedly decreased the formation of HER2/HER3 heterodimers, HER3 basal phosphorylation, and the association of p85alpha with HER3. This study is the first to show that under basal growth conditions, HER2 sensitizes low-EGFR NSCLC cell lines to growth inhibition by gefitinib.     

Coffee consumption and the risk of primary liver cancer: pooled analysis of two prospective studies in Japan

Although case-control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self-administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow-up with 170,640 person-years) and Cohort 2 (7 years of follow-up with 284,948 person-years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46-1.09) and 0.58 (0.36-0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high-risk population are needed.