[Bi-weekly docetaxel and doxifluridine combination therapy in pretreated patients with unresectable and/or advanced gastric cancer].

We report an investigation of the therapeutic efficacy and safety of combination chemotherapy with docetaxel (DOC) and doxifluridine (5'-DFUR) administered as second-line or third-line chemotherapy in 23 cases of unresectable and/or advanced gastric cancer. Treatment consisted of intravenous DOC (40mg/m/2) on day 1 and 15, and oral 5'-DFUR (600mg/body) on days 1 to 28 every 4 weeks. The response rate for its antitumor efficacy was 17.4 %, with partial response in 4 cases, no change in 6 cases, progressive disease in 12 cases, and one case not evaluable. By site, the response rate was 11. 8% for primary tumors (2/17), 33.3% for lymph nodes (3/9) , and 26.9% for liver metastasis (1/7). Median time to treatment failure was 2.6 months, median overall survival was 4.6 months. The one-year survival rate was 26.1 %, and the two-year survival rate was 13.0%. The most common grade 3 to 4 toxicities were neutropenia( 4.3%), fatigue (8.7%), stomatitis (8.7%), anorexia(4.3% ), and rash (4.3%). Our data suggest that the combination of docetaxel and 5'-DFUR has a promising therapeutic index in patients with unresectable advanced gastric cancer as second-line or third-line chemotherapy.

Three multi-allelic gene pairs are responsible for self-sterility in the ascidian Ciona intestinalis.

Many hermaphroditic organisms possess a self-incompatibility system to avoid inbreeding. Although the mechanisms of self-incompatibility in flowering plants are well known, little is known about the mechanisms of self-sterility in hermaphroditic marine invertebrates. Ascidians are hermaphroditic sessile marine invertebrates that release sperm and eggs into the surrounding seawater. Several species, including Ciona intestinalis type A (Ciona robusta), exhibit strict self-sterility. In a previous study, we found that the candidate genes responsible for self-sterility in Ciona reside in chromosome 2q (locus A) and chromosome 7q (locus B). Two pairs of multi-allelic genes, named s(sperm)-Themis-A and v(vitelline-coat)-Themis-A in locus A and s-Themis-B and v-Themis-B in locus B, are responsible for self-sterility. In this study, we identified a third multi-allelic gene pair, s-Themis-B2 and v-Themis-B2, within locus B that is also involved in this system. Genetic analysis revealed that the haplotypes of s/v-Themis-A, s/v-Themis-B and s/v-Themis-B2 play essential roles in self-sterility. When three haplotypes were matched between s-Themis and v-Themis, fertilization never occurred even in nonself crossing. Interestingly, gene targeting of either s/v-Themis-B/B2 or s/v-Themis-A by genome editing enabled self-fertilization. These results indicate that s/v-Themis-A, -B and -B2 are S-determinant genes responsible for self-sterility in the ascidian C. intestinalis type A.

Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, complementary alternative medicine is actively performed for cancer therapy. We investigated the effectiveness of supplementary food containing superfine dispersed lentinan (beta-1,3-glucan) in patients with unresectable or recurrent hepatocellular carcinoma in a multi-center study. METHODOLOGY: Peripheral blood was collected prior to the test food ingestion and was incubated with fluorescein-labeled lentinan. The rates of lentinan-binding CD14+ monocytes were determined by flow cytometry. Patient survival times were followed up for 3 years. RESULTS: Thirty-six patients were eligible among 40 enrolled patients. Median survival time of eligible patients was 13.6 months (95% confidence interval, 8.7-18.9 months). Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks (p < 0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3 months) of lentinan-high-binding group were significantly longer than those (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05). CONCLUSIONS: A superfine dispersed lentinan-containing supplementary food is effective for hepatocellular carcinoma patients' survival. Long-time ingestion is preferable. Assessment of lentinan-binding CD14+ monocytes is a promising prognostic predictor.

Suppressive effect of oral administration of branched-chain amino acid granules on oxidative stress and inflammation in HCV-positive patients with liver cirrhosis.

AIM: In chronic hepatitis C virus (HCV) infection, it is thought that both chronic persistent inflammation and oxidative stress contribute to the development of hepatocellular carcinoma (HCC), and it has been reported that long-term oral supplementation with branched-chain amino acid (BCAA) granules could inhibit liver carcinogenesis. However, the extent of the involvement of these factors remains obscure. METHODS: To clarify the involvement of inflammation and oxidative stress in the inhibition of liver carcinogenesis, we evaluated the effect of oral administration of BCAA granules on oxidative stress and inflammation in HCV-positive patients with liver cirrhosis. RESULTS: Twenty-seven patients were enrolled in the study: 18 of the patients were treated with BCAA granules (administered group) and nine were observed without BCAA granules (non-administered group). In the non-administered group, the production of oxidative stress, as indicated by urine 8-hydroxydeoxyguanosine (8-OHdG) and 15-F2t-Isoprostane (8-IsoPs), significantly increased with time, while in the administered group the levels of ferritin and 8-OHdG decreased significantly. Comparison of the two groups demonstrated that highly sensitive CRP, ferritin, 8-OHdG and 8-IsoPs were significantly reduced by taking BCAA granules. The time-course analysis showed that ferritin and highly sensitive CRP seemed to decrease first, followed by a decrease of 8-OHdG and 8-IsoPs. CONCLUSION: These findings indicated that the administration of BCAA granules influenced microinflammation and the metabolism of iron in HCV-positive patients with liver cirrhosis, and subsequently seemed to reduce the production of oxidative stress, possibly leading to a decrease in the occurrence of HCC.

Accidental exposure to HCV antibody-positive blood in hospital and pre-emptive one-shot interferon alpha-2b treatment.

AIMS: Infection with hepatitis viruses following blood exposure accidents, such as needle stick injuries, is a serious issue for medical staff. In particular, although accidental exposure to hepatitis C virus (HCV) occurs frequently, postexposure prophylactic measures have not been established yet. In this study we investigate the efficacy of recombinant alpha-2b interferon (IFN) as a single, 10 MU intramuscular injection for preventing transmission. METHODS: 264 incidents of accidental blood to HCV antibody-positive blood, occurring between 1993 and 2003 in the Social Insurance Chukyo Hospital, were surveyed. Accident reports, which described in detail the circumstances and the presence or absence of infectious disease in the blood, and accidental exposure to HCV antibody-positive blood was investigated. RESULTS: Pre-emptive IFN treatment was given in 115 out of 157 cases occurring between 1993 and 1998. One case developed acute HCV. Phylogenetic analysis provided evidence that the accident caused the infection and the patient was cured by immediate IFN therapy. Between 1999 and 2003, the exposed were in principle followed-up without IFN treatment; IFN treatment was only given when requested. As a result, IFN was given in 14 of 107 cases. During this period, no transmission was observed. CONCLUSION: Taken together, the benefits of pre-emptive IFN treatment were considered unremarkable and a follow-up without treatment, or immediate IFN therapy after confirmation of the onset, was recommended.

[An investigation of TS-1 single-agent therapy administered as first-line therapy for unresectable advanced gastric cancer].

We report an investigation of the therapeutic efficacy and safety of TS-1 single-agent therapy administered as first-line therapy in 23 cases of unresectable advanced gastric cancer treated at our institution. TS-1 was administered at 80 mg-120 mg (divided into two doses) per day for 28 days followed by a 14-day rest interval, making up a single cycle. The response rate for its antitumor efficacy was 39.1%, with partial response in nine cases, no change in seven cases, progressive disease in five cases, and two cases not evaluable (9 5% confidence interval: 19.7%-61.5%). By site, the response rate was 43.5% for primary tumors (10/23), 33.3% for lymph nodes (3/9), and 16.7% for liver metastasis (1/6). In 1 patient, the carcinomatous ascites disappeared,and in 3 patients they decreased remarkably. No significant differences were observed with regard to age (70 and over/under 70) or histological type (differentiated/undifferentiated). The one-year survival rate was 32.8%, and the 50% survival period was 29 9 days. The most common side effect was leucopenia in seven cases (30.4%), followed by decreased hemoglobin, loss of appetite, hepatic dysfunction and the like. Most side effects, however, were mild and did not exceed grade 2; grade 3 side effects were seen only in two cases (8.7%) of leucopenia and two (8.7%) of hepatic dysfunction, a low rate of occurrence. The outpatient follow-up ratio(outpatient period/total treatment period) was high at 69.6%, meaning that first-line single-agent therapy with TS-1 is beneficial in terms not only of efficacy but also in maintaining quality of life.

Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.

There have been reports of relapse after cessation of lamivudine monotherapy for hepatitis B virus (HBV) infection. The aim of this study was to examine factors that predict posttreatment relapse. Comparison 22 patients who experienced relapse with 11 who did not after cessation of therapy showed that predictive factors for nonrelapse were hepatitis B e antigen seroconversion and duration of undetectable HBV DNA load (<0.7 log IU/mL), as determined by HBV real-time detection direct testing. However, 7 of 12 patients with seroconversion experienced relapse after cessation of therapy. Multivariate analysis revealed that the duration of an undetectable HBV DNA load was the only independent predictive factor for nonrelapse (odds ratio, 0.50; 95% confidence interval, 0.27-0.9). More-prolonged lamivudine therapy is required after seroconversion, and persistent duration of an HBV DNA level of <0.7 log IU/mL for >6 months can more accurately aid in the decision of when to stop lamivudine therapy.

A randomized controlled trial of consensus interferon with or without lactoferrin for chronic hepatitis C patients with genotype 1b and high viral load.

Recently, lactoferrin has been reported to have anti-HCV effects. The aim of this study was to investigate the effect of combination therapy using consensus interferon (CIFN) and lactoferrin in patients with chronic hepatitis C. Twenty-one patients with chronic HCV infection, who were positive for HCV-RNA genotype 1b with serum viral loads from 100 to 700KIU/ml, were randomly assigned to two groups; the CIFN + Lac group received CIFN with lactoferrin and the CIFN group received CIFN alone. Nine patients in each group completed this trial; the other patients dropped out because of side effects. Three, two and four patients were categorized as complete responders, relapsers and non-responders, respectively, in the CIFN + Lac group, and four, one and four in the CIFN group, respectively. There was no statistically significant difference in virologic response between the two groups. During the follow up after CIFN therapy with continued lactoferrin, there were two relapsers in the CIFN + Lac group and their HCV-RNA titers before treatment were over 400KIU/ml. In conclusion, the combination therapy of CIFN and lactoferrin did not increase the response rate or prevent relapse after discontinuation of IFN.

[Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients].

The relationship between Helicobacter pylori (H. pylori) and gastric diseases (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted. Recent studies have also suggested an association between H. pylori infection and idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori eradication treatment was administered to 20 ITP patients and elucidated for its effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17 (85%) through a C14 urea breath test, a rapid urease test, or a culture examination of a biopsied sample obtained by gastrointestinal endoscopy. Although the other 3 were negative to H. pylori, the H. pylori eradication treatment was also attempted because no other effective treatments had been established at the time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60 mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were given to each patient for 7 days. For 4 cases, CAM was replaced with metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not eradicated after the first treatment received the re-eradication treatment with LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the treatments, the success of eradicating H. pylori was confirmed in all 17 H. pylori positive patients. In addition, platelet recovery was obtained in 11/20 patients (55%), which included 2 H. pylori negative patients and 2 patients whose H. pylori eradication was not successful after the first treatment. No relationship was found between the eradication effectiveness and the following clinical parameters: age, gender, previous therapies, disease duration, presence of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of antibiotics used for the treatment. These results support the efficacy of an H. pylori eradication treatment for ITP patients. A noteworthy result of this study was that an increase of platelet count was observed not only in H. pylori positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients after H. pylori eradication. Further studies are required to elucidate the efficacy of H. pylori eradication therapy in the patients negative for H. pylori.