Significance of working environment improvement based on determination of source of harmful substance--example of an endoscope syringe room using glutaraldehyde

Because a worker complained of irritated eyes and throat due to glutaraldehyde (GA) in an endoscope syringe room, the automated endoscope washers and GA liquid stored in reserve were isolated in a separate room. A ventilation system was installed in this room, and the packing of the automated endoscope washers was changed. However, since the obnoxious smell of GA still remained in the endoscope syringe room, we had to determine the source of the smell. A plastic bucket with a cap was found to be filled with GA for disinfection of the endoscope apparatus. GA had evaporated when dispersed around the bucket, resulting in the obnoxious smell. The plastic bucket was replaced with a different type of container. Moreover, GA from the separate room did not affect the concentration of GA in the working area because the separate room for the automated endoscope washers had twice the ventilation volume proposed by the guidelines of the Society of Gastroenterology Nurses and Associates of the USA and the Healthcare Engineering Association of Japan. Consequently, we reconfirmed the significance of working environment improvement after clarifying the source of the harmful substance.     

The frequency of going outdoors, and physical, psychological and social functioning among community-dwelling older adults

PURPOSES: This cross-sectional study examined the relationship between the frequency of going outdoors and physical, psychological, and social functioning among community-dwelling older people. METHODS: Out of all residents aged 65 and over residing in Yoita town, Niigata prefecture (n = 1,673), 1,544 living at home participated in an interview survey held in November 2000. Physical, psychological, and social functioning were compared among four groups defined by the frequency of going outdoors: (1) at least once a day, (2) about once per 2-3 days, (3) about once a week, and (4) seldom. To examine the independent association between the frequency of going outdoors and potential factors, we used multiple logistic regression analysis. RESULTS: Overall distribution of the frequency of going outdoors among the subjects was 76.3% for at least once a day, 13.1% for about once per 2 or 3 days, 3.7% for about once a week, and 6.9% for seldom. The frequency of going outdoors did not differ between genders, but showed significant decrease with advancing age in both sexes. Elderly going outdoors more often were less functionally impaired, scored less for depression and were more socially active than their counterparts going outdoors less often. Multiple logistic regression analysis with the forced entry method identified walking difficulty and fear of falls as the most powerful independent factors associated with going outdoors less than or equal to once a week, while low social activity and a more depressed score were important factors associated with going outdoors about once per 2-3 days. CONCLUSIONS: The frequency of going outdoors may be regarded as a generic health indicator among community-dwelling elderly people.     

Enhancement of apoptosis in salivary gland cancer cells by the combination of oral fluoropyrimidine anticancer agent (S-1) and radiation

S-1 is a new oral antineoplastic agent which can inhibit cell growth and induces apoptosis in certain types of cancer cells including gastric carcinomas, colorectal cancers and salivary gland cancers, but its effect on response of tumor cells to radiation has not been clarified yet. We have reported that S-1 can sensitize human oral cancer cells to radiation, and that S-1 in combination with radiation can exert remarkable effects on decreasing clonogenic survival and in vivo tumor growth. Here, we demonstrate the mechanism of apoptosis enhancing activity by the combination treatment of S-1 and radiation in salivary gland cancer cells. S-1 in combination with radiation have a remarkable effect on decreasing in vitro cell growth. In addition, the combined treatment of S-1 and radiation resulted in an increased DNA fragmentation by detecting Hoechst 33258 staining. Moreover, apoptosis of the cells by combined treatment of S-1 and radiation was associated with reactive oxygen/nitrogen species generation and the activation of caspase-8, -9 and -3. These results indicate that S-1 in combination with radiation can markedly enhance apoptosis of salivary gland cancer cells, and the combined therapy of S-1 and radiation are currently leading to the design of clinical studies.     

Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer

90K/Mac-2 Binding Protein (M2BP) plays a role in regulation of immune responses and cell adhesive ability in patients with cancer and infectious diseases. We previously reported that M2BP was highly expressed in lung cancer and that immune responses to M2BP were increased in many patients with lung cancer. To determine the involvement of M2BP in metastatic processes of cancer progression, we examined the ability of M2BP DNA-transduced lung carcinoma cell lines to adhere to extracellular matrices. Although expressions of cell-surface integrins were not modulated in the M2BP transfectants, they showed increased adhesiveness to fibronectin and collagen IV. We next analyzed the serum levels of M2BP in patients with lung cancer and normal donors and the relationships between M2BP expression and clinicopathological factors in the patients. The M2BP level was markedly elevated in the patients and was strongly correlated with nodal involvement and clinical staging. To determine whether expression of M2BP by cancer cells is modulated in the environment of tumor-bearing hosts, M2BP expression in M2BP-positive QG56 cells following exposure of the cells to pro-inflammatory cytokines was examined. The M2BP expression in QG56 cells was up-regulated by many of the cytokines that activate host protective immunity. The findings in this study suggest that M2BP plays a role in cancer metastasis by increased adhesiveness of cancer cells and that M2BP is increasingly produced even in a state of exposure to the host immune system. This molecule may be useful as a predictive factor of disease progression in lung cancer.     

Surgical resection deteriorates gemcitabine-induced leukopenia in pancreatic cancer

Background Gemcitabine hydrochloride (GEM) is one of the most effective chemotherapeutic agents for pancreatic cancer; however, factors affecting GEM-induced leukopenia have not been clarified yet. In the present study, we analyzed the relationship between patients backgrounds and GEM-induced leukopenia.Methods Thirty-eight patients with pancreatic cancer were analyzed for correlation between the dose of GEM and the blood leukocyte number. Moreover, we compared leukopenia in resected and non-resected patients.Results The incidence of grade 3 or 4 leukopenia was 25% in the non-resected patients, whereas equivalent leukopenia was observed in 57% of the resected patients (P = 0.048 by the ² test). The relative decrease in blood leukocytes induced by GEM administration was more severe in resected patients (41.3 ± 9.9%), as compared to non-resected patients (52.6 ± 16.0%; P = 0.023 by t-test).Conclusion In the present study, we found that the administration of GEM to patients after surgical resection caused more severe leukopenia, as compared to findings in non-resected patients. These data suggested that more frequent monitoring of the leukocyte count and prolonged intervals between GEM administrations are necessary for resected patients with pancreatic cancer.     

Intratumoral injection of IL-2-activated NK cells enhances the antitumor effect of intradermally injected paraformaldehyde-fixed tumor vaccine in a rat intracranial brain tumor model

Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at the basal ganglia of the right hemisphere (intracranial tumor model). Rats were intradermally injected three times with vaccine comprising fixed 9L cells, IL-2- and GMCSF-microparticles, and tuberculin prior to (protective studies) or after (therapeutic studies) challenge with live 9L cells. In the protective studies, the vaccine alone achieved significant tumor growth inhibition and elongation of mean life span in both the subcutaneous and intracranial tumor models. No therapeutic effect was observed in the intracranial tumor model with the vaccine alone. However, intratumoral injection of rat NK cells strongly assisted the therapeutic effect of the vaccine in the brain tumor model and resulted in a statistically significant elongation of life span. We propose that intratumoral injection of NK cells may not only kill brain tumor cells directly, but also trigger a strong immune response in the focal lesion of the brain after vaccination. (Cancer Sci 2004; 95: 98–103)     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies.     

A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.     

Cloning of a G-protein-coupled receptor that shows an activity to transform NIH3T3 cells and is expressed in gastric cancer cells

The present study was directed towards the identification of novel factors involved in the transformation process leading to the formation of gastric cancer. A cDNA library from human gastric cancer cells was constructed using a retroviral vector. Functional cloning was performed by screening for transformation activity in transduced NIH3T3 cells. Six cDNA clones were isolated, including one encoding the elongation factor 1asubunit, which was already known to play a role in tumorigenesis. One cDNA (clone 56.2), which was repeatedly isolated during the course of screening, encoded a protein identical to a G-protein-coupled receptor protein, GPR35. In addition, another cDNA clone (72.3) was found to be an alternatively spliced product of the GPR35 gene, whereby 31 amino acids were added to the N-terminus of GPR35. Hence, the proteins encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively. RT-PCR experiments revealed that GPR35 gene expression is low or absent in surrounding non-cancerous regions, while both mRNAs were present in all of the gastric cancers examined. The level of 72.3-encoded mRNA was consistently significantly higher than that of 56.2 encoded mRNA. An expression pattern similar to that observed in gastric cancers was detected in normal intestinal mucosa. Based on the apparent transformation activities of the two GPR35 clones in NIH3T3 cells, and the marked up-regulation of their expression levels in cancer tissues, it is speculated that these two novel isoforms of GPR35 are involved in the course of gastric cancer formation.     

Eradication of Helicobacter pylori induces apoptosis and inhibits proliferation of heterotopic proliferative glands in infected Mongolian gerbils

Mongolian gerbils infected with Helicobacter pylori (H. pylori ) develop heterotopic proliferative glands (HPGs) in the glandular stomach submucosa. To investigate the effects of H. pylori eradication on cell turnover in HPGs, three antibiotics, lansoprazole, amoxicillin and clarithromycin, were administered at 50 or 75 weeks after inoculation of H. pylori, and the stomachs were excised for histological examination at 1, 2, 4, 8 or 25 weeks thereafter. The HPGs were classified into gastric type (G-type) and others (GI + I-type), which included both pure intestinal (I-type) and gastric-and-intestinal mixed type (GI-type). Apoptosis and cell proliferation were evaluated by means of TUNEL assay and BrdU labeling, respectively. At 8 weeks post-eradication, apoptotic indices were significantly increased in the eradication group (G-type: 2.5%; GI + I-type: 7.2%) compared to the non-eradication group (G-type: 0.6%; GI + I-type: 2.1%: P < 0.01), while BrdU labeling indices were significantly decreased (G-type: 1.9%; GI + I-type: 6.8% as compared with 4.3% and 13.2%, respectively, P < 0.01 for both). At 25 weeks, the apoptotic indices were similarly higher [G-type: 0.4 (eradication group) vs. 0.2% (non-eradication group); GI + I-type: 5.8 vs. 1.1%, both P < 0.01], and the BrdU labeling indices (G-type: 0.8 vs. 2.2%, P < 0.01; GI + I-type: 5.1 vs. 11%, P < 0.05) continued to be lower in HPGs. Furthermore, there were highly significant reductions in the areas of HPGs at 8 and 25 weeks post-eradication. These findings demonstrated that eradication results in apoptosis and reduction of proliferation of HPGs in H. pylori-infected gerbils, these lesions thus being apparently reversible through regulation of cell kinetics.