Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus

The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: >or= 2(12)) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/10(5) person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45-74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC.     

Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells

OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation in tumor cells. The effect of the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not been well studied. In this study, we examined cell viability and gene expression profile in hepatoma cell lines treated with TSA. METHODS: To study cell growth inhibition and induction of apoptosis by TSA on human hepatoma cell lines including HuH7, Hep3B, HepG2, and PLC/PRF/5, cells were treated with TSA at various concentrations and analyzed by the 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively. Changes in gene expression profile after exposure to TSA were assessed using a cDNA microarray consisting of 557 distinct cDNA of cancer-related genes. The levels of acetylated histones were examined by the chromatin immunoprecipitation (ChIP) assay using anti-acetylated histone H3 or H4 antibody. RESULTS: The MTT assay demonstrated that TSA showed cell growth inhibition not only in a concentration-dependent but also a time-dependent manner on all cell lines studied. The TUNEL assay also revealed the potential of TSA to induce apoptosis. The microarray analysis revealed that 8 genes including collagen type 1, alpha2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), integrin, alpha7 (ITGA7), basigin (BSG), quiescin Q6 (QSCN6), superoxide dismutase 3, extracellular (SOD3), nerve growth factor receptor (NGFR), and p53-induced protein (PIG11) exhibited substantial induction (ratio >2.0) after TSA treatment in multiple cell lines. ChIP assay, in general, showed a good correlation between the expression level of mRNA and levels of acetylated histones in these upregulated genes. CONCLUSIONS: This study showed cell growth inhibition and the gene expression profile in hepatoma cell lines exposed to TSA. The alteration in levels of acetylated histones was closely associated with expression of specific cancer-related genes in hepatoma cells.     

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level 相似文献   

Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non-small-cell lung cancer

OBJECTIVE: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2). Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was recommended for a phase II study.     

The use of artificial neural network analysis to improve the predictive accuracy of prostate biopsy in the Japanese population

OBJECTIVE: We examined the efficacy of an artificial neural network analysis (ANNA) based on parameters available from previously existing examinations for improving the predictive accuracy of prostate cancer screening in the Japanese population. METHODS: Two hundred and twenty-eight patients with prostate-specific antigen (PSA) of 2-10 ng/ml were enrolled in this study. Two artificial neural network analysis (ANNA) models were constructed: ANNA1 with patient age, total PSA, free to total PSA ratio, prostate volume, transition zone volume (TZ), PSA density (PSAD) and PSA-TZ density (PSATZ) as input variables, and ANNA2 with presumed circle area ratio (PCAR), digital rectal examination (DRE) findings and chief complaint added as variables. The predictive accuracies of the ANNA models were compared with conventional PSA and volume-related parameters and a logistic regression (LR) model by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 228 patients, 58 (25.5%) were diagnosed with prostate cancer. While ANNA2 had a slightly larger area under the curve (AUC) than ANNA1 (0.782 versus 0.793, P = 0.8477), the AUC of ANNA2 was significantly greater than those of ln(PSA), PSAD, PSATZ and free to total PSA ratio (P = 0.0004, 0.0230, 0.0304, and 0.0037, respectively). The accuracy of ANNA2 was significantly better than that of LR analysis at 90 and 95% sensitivity levels (P = 0.0051 and P < 0.0001, respectively). At 95% sensitivity level, ANNA2 reduced unnecessary biopsies by 40.0% with a negative predictive value of 95.7%. CONCLUSIONS: To determine the indication of prostate biopsy for PSA value in the range of 2-10 ng/ml, the ANNA model has the possibility to reduce unnecessary biopsies without missing many cases of cancers.     

A case of advanced gastric cancer successfully treated with neoadjuvant chemotherapy of combined weekly paclitaxel and doxifluridine (5'-DFUR)

We report a case of advanced gastric cancer with metastasis to the paraaortic lymph nodes that showed a remarkable response to treatment with a combination of weekly paclitaxel and doxifluridine (5'-DFUR). The patient was a 72-year-old man. Oral chemotherapy of TS-1 was discontinued due to drug induced eruption. Alternatively, we administered weekly paclitaxel/5'-DFUR combination therapy. Paclitaxel was infused at a dose of 100-130 mg after short premedication and continued for 2-3 weeks with a 1 week rest. 5'-DFUR was administered orally at a dose of 800 mg/day for 14-21 consecutive days. After 4 courses of this therapy, the primary carcinoma and lymph nodes decreased in size (PR). Consequently, the patient underwent a total gastrectomy with paraaortic lymph node dissection, which resulted in a curative resection of the cancer cells macroscopically. Except for afebrile neutropenia (grade 4), no major adverse reactions were observed. Histological examination revealed that the cancer cells were degenerated to a moderate extent. Weekly paclitaxel/5'-DFUR combination may be a promising regimen for patients with advanced gastric cancer as preoperative chemotherapy.     

Effect of Cepharanthin to prevent radiation induced xerostomia in head and neck cancer

We retrospectively examined the effect of Cepharanthin to prevent radiation xerostomia in 37 cases of head and neck cancer. In the Cepharanthin group, the degree of xerostomia was milder than in the non-Cepharanthin group in spite of higher normal tissue complication probability (NTCP) and mean dose (MD) of parotid glands. In the non-Cepharanthin group, the degree of xerostomia was significantly correlated with NTCP and MD of parotid glands. MD of parotid glands and use of Cepharanthin were significantly related to more severe xerostomia by multivariate analysis with logistic regression. Cepharanthin may prevent radiation xerostomia after radiotherapy for head and neck cancer.     

A case of 10-year survival after combination chemotherapy of 5'-deoxy-5-fluorouridine and cisplatin and adjuvant surgery for gastric cancer with liver metastasis

A 36-year-old woman was diagnosed with type 3 advanced gastric cancer with multiple liver metastases in March 1992. The patient was treated with systemic chemotherapy of 5'-deoxy-5-fluorouridine and cisplatin. After 4 courses of chemotherapy, the primary lesion responded and the multiple liver metastases disappeared. Therefore, total gastrectomy with perigastric lymphadenectomy and splenic preservation was performed. Two additional courses of the same chemotherapy were administered after the surgery. The patient has been alive without recurrence for 10 years after the curative resection.     

Myelodysplastic syndrome associated with intestinal tract-type Behçet disease characterized by an esophageal ulcer

A 55-year-old man with advanced myelodysplastic syndrome was hospitalized prior to undergoing an allogeneic bone marrow transplantation. Immediately before hospitalization, he had suffered from phlegmon in both lower extremities and right forearm as well as genital and oral ulcers. After admission, he developed an esophageal ulcer and was thus diagnosed as having intestinal tract-type Beh?et disease. HLA-B51 was not present. Within a month, he died of pulmonary hemorrhage associated with pneumonia, possibly because of a low platelet count, and vasculoendothelial damage related to Beh?et disease. This is a rare case of myelodysplastic syndrome that developed Beh?et disease with a severe esophageal ulcer.     

Calcium intake and osteoporosis

It has been well known that calcium (Ca) deficiency is a major risk factor for osteoporosis. However, few reliable evidences were available regarding the beneficial effect of increased dietary Ca in osteoporosis. Meta-analysis of the recently reported randomized clinical trials revealed that the beneficial effect of increased dietary Ca on BMD and/or fracture prevention was very small, if any.