Role of Helicobacter pylori infection and chronic inflammation in gastric cancer in the cardia

BACKGROUND: Helicobacter pylori-induced gastritis is an important factor for gastric carcinogenesis. However, it is still controversial whether it is also applicable for cardiac cancer development. Recently, we reported that H. pylori is an important factor for the induction of cardiac inflammation. We examined the status of H. pylori-induced gastritis in patients with cardiac cancer. METHODS: Seventy-five Japanese patients (58 men; mean age, 64.2 years) with cardiac cancer were studied. Cardiac cancer was defined as that mainly located within 2 cm from the squamo-columnar junction (SCJ). Histological gastritis including the cardiac region was evaluated using the biopsy or surgically resected sections. Cardiac inflammation was evaluated at 1 cm distal from SCJ in lesser curvature. Sera were collected and several markers were evaluated. The status of H. pylori infection was evaluated by histology and serum antibodies. Expressions of cytokeratins were examined by immunohistochemical analysis. RESULTS: Out of 75 patients with cardiac cancer, H. pylori was positive in 71 (95%) patients. The cardiac inflammation was examined in 30 patients (26 with H. pylori and four without H. pylori infection) and we found cardiac inflammation was present in all cases with H. pylori infection. Histologically, H. pylori-related gastritis was also found in the gastric corpus and antrum. Serological data were consistent with the presence of chronic atrophic gastritis. Intestinal metaplasia was found in 18 cases in the cardiac mucosa, and their cytokeratin 7/20 pattern was judged as a gastric pattern in all cases. CONCLUSION: H. pylori infection is closely associated with cardiac cancer.     

A case of advanced breast cancer leading to DIC after chemotherapy

We reported a case of DIC who was administered FEC90 (5-FU 1,000 mg/body, epirubicin 170 mg/body, cyclophosphamide 1,000 mg/body) for advanced breast cancer. A 55-year-old woman was referred to our hospital with lumbago. There was a huge tumor in her left breast (10x10 cm) and bone scintigraphy showed multiple bone metastasis, so she was treated with FEC90. Before the third course, DIC occurred. The patient was then treated with FOY and heparin, and the DIC was resolved. We think the DIC of this case was related with tumor lysis syndrome. Febrile neutropenia has been occasionally emphasized during chemotherapy, but due care must be taken for lymphocyte depletion during treatment.     

Identification of neovasculature using nestin in colorectal cancer

CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.     

Early development of histiocytic sarcomas in p53 knockout mice treated with N-bis(2-hydroxypropyl)nitrosamine

p53 knockout mice have been utilized for the functional analysis of p53 in carcinogenic processes and for the evaluation of the carcinogenic potential of chemicals. In this study, we established that p53 knockout mice have an elevated susceptibility to the induction of histiocytic sarcoma (HS) by N-bis(2-hydroxy-propyl)nitrosamine (BHP). p53 heterozygous (+/-) and wild-type (+/+) mice were treated with 20 or 200 ppm BHP in their drinking water for 15 weeks or with 20 ppm BHP for 40 weeks. An additional group of p53 nullizygous (-/-) mice were treated with 20 ppm BHP for 15 weeks. In a 15-week experiment, hepatic HSs were unexpectedly observed in BHP-treated p53 (-/-) mice (30.8%) but not in p53 (+/-) and (+/+) mice and untreated (-/-) mice, indicating that a complete loss of p53 dramatically accelerates the genesis of HS. In a 40-week experiment, HSs were significantly increased in female p53 (+/-) mice (37.5%) as compared with female (+/+) mice (5.0%). Additionally, PCR-SSCP and sequencing analysis revealed a high frequency of p53 gene mutations in HSs, demonstrating the involvement of p53 gene mutations in HS development. Our data add to the understanding of the carcinogenic susceptibility of p53 knockout mice, and may help to elucidate the pathogenesis of HS development.     

Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model

BACKGROUND: The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage. We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction. METHODS: We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Subsequently, we induced selective liver injury to recipient mice by DT administration. We then evaluated the engraftment of the transplanted cells and their effect on survivorship. RESULTS: The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice. The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes. They continued to proliferate, forming clusters. The survival rate at 25 days after transplantation of the cell-transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%). CONCLUSIONS: The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation.     

Seasonal changes in symptom score and uroflowmetry in patients with lower urinary tract symptoms

OBJECTIVE: To determine whether subjective or objective seasonal changes occur in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A total of 31 patients with LUTS were observed for >5 years. Their International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), voided volume (VV) a nd post-void residual (PVR) we re measured every month. RESULTS: Total IPSS, QOL, VV or PVR did not show any seasonal changes between the three seasons: summer (hot season: June to September); winter (cold season: December to March); and spring and fall (comfortable season: April, May, October and November). Furthermore, when the IPSS was examined by dividing it into storage symptoms (frequency, urgency and nocturia) and voiding symptoms (incomplete emptying, intermittency, weak stream and straining), no significant seasonal changes were detected. Only Qmax showed a significant seasonal change, being higher in both the cold season (median 10.4 ml/s) and the comfortable season (median 10.1 ml/s) than in the hot season (median 9.4 ml/s). CONCLUSIONS: It has generally been thought that LUTS worsen in winter. Our results indicate that the IPSS and the QOL score remain nearly constant if they are determined regularly over an extended period of time. Qmax may however be influenced by seasonal changes in temperature.     

Antibacterial activity of ciprofloxacin against clinical strains of Vibrio cholerae O139 recently isolated from India

We determined the in vitro antibacterial activity of ciprofloxacin against Vibrio cholerae O139 recently isolated from cholera patients in India. Ciprofloxacin showed excellent antibacterial activity against the O139 strains, and ciprofloxacin-resistant O139 strains were not observed. The lack of incidence of ciprofloxacin resistance in O139 strains may be because O139 strains appeared comparatively recently and have not been extensively treated with antibacterial agents including fluoroquinolones.