Biomedical subjects

Hideki Ueno

Publications and source records attributed to Hideki Ueno.

65 records · Page 4Linked to original sources

PubMed2002

Prognostic factors in patients with small hepatocellular carcinoma treated by percutaneous ethanol injection.

BACKGROUND: Percutaneous ethanol injection (PEI) has been widely performed and is now accepted as a viable alternative to hepatic resection in patients with small hepatocellular carcinomas (HCC). However, only a few extensive investigations have been conducted regarding the prognostic factors for HCC patients treated with PEI. METHODS: We investigated the prognostic factors in 100 patients with small HCC who had undergone PEI. Univariate analysis and multivariate analysis with Cox's proportional hazards model were used to determine the factors potentially related to survival. For clinical application, a prognostic index was calculated based on the regression coefficients of the independent variables identified from the multivariate analysis. RESULTS: Median survival time and 1, 3 and 5 year survival rates were 71 months and 100, 84 and 62%, respectively. Among the 15 potential prognostic variables investigated, only three variables, namely a serum albumin level < or = 3.5 g/dL, the presence of tumor stain and a serum glutamic oxaloacetic transaminase level > 66 IU/L, were identified as factors independently associated with a shorter survival. A prognostic index based on the regression coefficients of these three factors was proposed to classify patients into three groups, those with a good (5 year survival rate 91%), intermediate (64%) and poor prognosis (22%). CONCLUSIONS: The results of the present study may be useful in predicting the survival of HCC patients treated with PEI and in the design and analysis of future clinical trials of PEI for HCC.

Carcinoma, Hepatocellular↗

PubMed2002

Prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization.

BACKGROUND: Transcatheter arterial embolization induces marked antitumor response in patients with hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization remains to be determined. This study investigated prognostic factors in patients with advanced hepatocellular carcinoma treated by transcatheter arterial embolization. METHODS: A total of 128 consecutive patients with non-resectable hepatocellular carcinoma, who had undergone transcatheter arterial embolization between May 1990 and August 1998, were analyzed to investigate prognostic factors. RESULTS: Median survival time and survival proportions at 1, 3 and 5 years were 3.3 years, 92.0, 54.6 and 23.4%, respectively. By multivariate analysis using the accelerated failure time model, age <60 years, hepatitis C virus antibody positivity, serum albumin >3.5 g/dl, absence of portal vein invasion and serum alpha-fetoprotein level <400 ng/ml were significantly associated with favorable survival. For clinical application, we also propose a prognostic equation with combination of specific prognostic factors, by which survival curves of each patient could be predicted directly. CONCLUSION: The findings of the current study may be helpful in predicting the life expectancy of hepatocellular carcinoma patients treated by transcatheter arterial embolization and in designing future clinical trials of transcatheter arterial embolization for hepatocellular carcinoma.

Adult↗

PubMed2002

Dose-response trial of lactoferrin in patients with chronic hepatitis C.

Hepatitis C virus (HCV) is one of the most common causes of chronic hepatitis. Interferon is presently the only effective treatment for chronic hepatitis C (CH-C), though its effectiveness is limited. Lactoferrin (LF), which is an 80-kDa, iron-binding glycoprotein, has several biological activities including anti-viral activity, and it was recently reported to inhibit HCV infection in cultured human hepatocytes. The present trial was designed to assess the relationship between the dose of bovine LF (bLF) and the effect of bLF on serum alanine aminotransaminase (ALT) and HCV RNA levels in patients with CH-C. Forty-five patients entered at each of the three dose levels (bLF of 1.8, 3.6, and 7.2 g/day) received orally an 8-week course of bLF. There was no significant relation between the dose of bLF and the effect of bLF on serum ALT or HCV RNA levels. Biochemical (a 50% or greater decrease in the serum ALT level) and virological (a 50% or greater decrease in HCV RNA level) responses were observed in two and four patients, respectively, but all responders relapsed during the follow-up period after bLF treatment. The bLF treatment was generally well tolerated, and no patient had any serious adverse event. In conclusion, the excellent tolerance and potential anti-HCV activity of bLF shown in this trial suggest that further trials using a large number of patients are mandatory. We are currently conducting a double-blind randomized controlled trial comparing bLF with placebo to clarify the anti-HCV activity of bLF in patients with CH-C.

Adult↗

PubMed2002

Phase II study of uracil-tegafur in patients with metastatic pancreatic cancer.

OBJECTIVE: Uracil-tegafur (UFT) has been reported to have a broad anti-tumor activity in a variety of malignancies including colorectal cancer and breast cancer. However, its activity in pancreatic cancer has not been fully evaluated. The aim of the present study was to evaluate the anti-tumor activity and toxicity of UFT in patients with metastatic pancreatic cancer. METHODS: All patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. A dose of 360 mg/m2/day of UFT was administered orally until the appearance of disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were entered into this study. Of 21 patients evaluable for response, no patient achieved an objective tumor response; one showed no change, and the remaining 20 showed progressive disease. The median survival time for all patients was 4.2 (range: 0.9-9.0) months. The most common toxicities were nausea/vomiting and anorexia. Five patients (23%) had to discontinue UFT treatment because of gastrointestinal toxicity. CONCLUSION: This schedule of UFT did not demonstrate a significant anti-tumor activity against metastatic pancreatic cancer.

Adenocarcinoma↗

PubMed2002

Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma.

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.

Adult↗

PubMed2001

Phase I and pharmacokinetic study of 5-fluorouracil administered by 5-day continuous infusion in patients with hepatocellular carcinoma.

PURPOSE: In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated. METHODS: Patients with hepatocellular carcinoma no longer amenable to established forms of treatment were eligible for the study. The starting dose of 5-fluorouracil was 300 mg/m(2) per day and doses were escalated in 50 mg/m(2) per day increments in successive cohorts of three new patients if tolerated. Pharmacokinetic studies were performed at the time of the first course of therapy. RESULTS: Enrolled in the study were 20 patients. The maximum tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity was stomatitis. Other toxicities were mild and well tolerated. Age, gender and associated liver cirrhosis were significant factors influencing 5-fluorouracil clearance. With regard to biochemical parameters, serum alanine aminotransferase and cholesterol levels were correlated with 5-fluorouracil clearance. CONCLUSIONS: The maximum tolerated dose for 5-day continuous infusion of 5-fluorouracil in hepatocellular carcinoma patients was 500 mg/m(2) per day. The recommended dose for phase II studies using this schedule is 450 mg/m(2) per day. Furthermore, the pharmacokinetic data obtained in this study may be useful in determining chemotherapy dosage adjustments for reduction of toxicity.

Adult↗

PubMedDate not supplied

Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients with metastatic melanoma.

The immunogenicity of dendritic cell (DC)-based vaccines has been shown in patients with advanced cancer, but it has not yet been established whether the elicited cancer-specific immunity is durable and whether it can be maintained by boosting vaccinations. The authors showed earlier, in 18 HLA-A*0201 metastatic melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34-DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T-lymphocyte (CTL) activity against melanoma cell lines. The authors show here that the melanoma peptide-specific CD8+ T-cell immunity is short-lived, but it could be reactivated in 7 of 11 patients who received four boosting vaccinations with peptide-loaded CD34-DCs. Expansion of recall memory CD8+ T cells was confirmed by tetramer binding and CTL activity against melanoma peptide-pulsed T2 cells. In two patients boosted over 15 months, induced melanoma peptide-specific recall memory CD8+ T cells lasted at least 6 months. Thus, boosting vaccination with peptide-loaded CD34-DCs can expand long-lived tumor peptide-specific immunity.

Antigens, CD34↗

PubMedDate not supplied

Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.

Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-gamma in direct ELISPOT. Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-alpha-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.

Adult↗

PubMedDate not supplied

Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.

Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naive CD8 T cells in vitro, thereby providing an option to overcome human leukocyte antigen restriction inherent to loading DC vaccines with peptides. We have vaccinated 20 patients with stage IV melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand. A total of 8 vaccines were administered at monthly intervals. The first patient was accrued December 2002 and the last November 2003. Fourteen patients were alive at 12 months, 9 patients were alive at 24 months, and 8 patients are alive as of January 2006. The estimated median overall survival is 22.5 months with a range of 2 to 35.5 months. Vaccinations were safe and tolerable. They induced, in 2 patients who failed previous therapy, durable objective clinical responses, 1 complete regression (CR) and 1 partial regression (PR) lasting 18 and 23 months, respectively. Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen. Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma.

Adult↗

PubMedDate not supplied

Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy.

BACKGROUND/AIMS: Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy have not been fully examined. This study investigated prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy. METHODOLOGY: Sixty-five consecutive chemo-naive patients with advanced biliary tract cancer, who received chemotherapy, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 180 days, 21%, and 5%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0, 1, serum C-reactive protein level of < or = 1.0mg/dL, serum albumin level of > or = 3.5g/dL, serum lactate dehydrogenase level of < or = 500 U/L, and being female were independent favorable prognostic factors. A prognostic index based on the coefficients of these prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 246, 152, and 33 days, respectively. CONCLUSIONS: The results may be helpful for predicting life expectancy, determining treatment strategies, and designing future clinical trials in patients with advanced biliary tract cancer.

Adult↗

PubMedDate not supplied

Evaluation of acute intestinal toxicity in relation to the volume of irradiated small bowel in patients treated with concurrent weekly gemcitabine and radiotherapy for locally advanced pancreatic cancer.

BACKGROUND: Treatment of concurrent gemcitabine and radiotherapy for pancreatic cancer was reported to have a higher rate of severe acute intestinal toxicity. This study evaluated the acute intestinal toxicity in relation to the volume of irradiated small bowel and other factors using dosimetric analyses in pancreatic cancer patients treated with gemcitabine-based chemoradiotherapy. MATERIALS AND METHODS: The patient population was derived from a phase II trial of concurrent weekly gemcitabine and radiotherapy for locally advanced pancreatic cancer. Gemcitabine was administered weekly at a dose of 250 mg/m2. The total dose was 50.4 Gy in 28 fractions using a four-field conformal technique. A dose-volume histogram was generated for the small bowel, colon and planning target volume (PTV) and dosimetric parameters were recorded. Correlations between the acute intestinal toxicity and the volume of irradiated small bowel and other factors were evaluated. RESULTS: Forty-two patients enrolled between July 2001 and July 2002 were analyzed. Grade 3+ acute intestinal toxicities were observed in twenty-four (62%) patients. There was no correlation between the acute intestinal toxicity and the volume of irradiated small bowel. However, the total volume of PTV was shown to be significantly correlated with the development of Grade 3+ acute intestinal toxicity (p = 0.021). CONCLUSION: The volume of irradiated small bowel did not directly influence the acute intestinal toxicity, but only the volume of PTV significantly correlated with severe acute intestinal toxicity.

Adult↗