Biomedical subjects

Kensei Yamaguchi

Publications and source records attributed to Kensei Yamaguchi.

10 recordsLinked to original sources

PubMed2007

[Chemotherapy in advanced gastric cancer--to ensure timely and appropriate switch to subsequent treatment options].

Since irinotecan, S-1, docetaxel, and paclitaxel were approved, therapeutic options for chemotherapy in the treatment of gastric cancer have increased. It is suggested that the efficient use of the primary drugs prolongs life in the treatment of progressive colorectal cancer. Also, physicians have discussed ways to take full advantage of the drugs in the treatment of gastric cancer. In first-line treatment in other countries, combination therapy usually includes the administration of two drugs, while in Japan, where therapies based on S-1 have been developed, the most appropriate strategy must be determined after reporting the results of phase III trials in 2007. In the clinic, treatment must be selected on the basis of solid evidence in consideration of the organ dysfunction associated with progressive gastric cancer. The timing of any changes in the treatment should be considered because the cancer easily metastasizes to the peritoneum. Throughout the world, various regimens have been developed that replace cisplatin with oxaliplatin or mainly use oral fluoropyrimidine. Molecular target drugs, now being evaluated in phase II trials, will also be used in the treatment of gastric cancer in the near future. Novel therapies will be developed in Asia and Japan where the incidence of gastric cancer is high.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Characterization of a novel oncogenic K-ras mutation in colon cancer.

Activating mutations of RAS are frequently observed in subsets of human cancers, indicating that RAS activation is involved in tumorigenesis. Here, we identified and characterized a novel G to T transversion mutation of the K-ras gene at the third position of codon 19 (TTG) which substituted phenylalanine for leucine in 3 primary colon carcinomas. Biological and biochemical activity was examined using transformed NIH3T3 cells expressing mutant or wild-type K-ras. Transformants harboring the K-ras mutation at codon 19 showed proliferative capacity under serum-starved conditions, less contact inhibition, anchorage-independent growth, tumorigenicity in nude mice and elevation of active Ras-GTP levels. These results indicated that this novel mutation possesses high oncogenic activity.

Amino Acid Sequence↗

PubMed2006

Immunohistochemical and mutational analysis of c-kit in gastrointestinal neuroendocrine cell carcinoma.

BACKGROUND: Gastrointestinal neuroendocrine cell carcinoma (NEC) is a highly aggressive tumor with poor prognosis, for which an effective therapy is highly desirable. Recently, use of a c-kit inhibitor achieved excellent results against gastrointestinal stromal tumor (GIST) that showed c-kit overexpression and mutation in most cases. According to recent studies, 17-44% of pulmonary NEC also expressed c-kit and the antitumor effect of c-kit inhibitor was demonstrated in vitro against small cell carcinoma of the lung. As gastrointestinal NECs are clinicopathologically similar to pulmonary NECs, we investigated c-kit expression and mutation in gastrointestinal NEC. METHODS: Surgically resected gastrointestinal NEC was examined for c-kit expression by immunohistochemistry and RT-PCR. Mutation of the c-kit gene was also investigated by means of single-strand conformation polymorphisms (SSCP). RESULTS: Twenty-six percent (6 out of 23 patients) of gastrointestinal NEC expressed c-kit protein. c-kit protein expression was demonstrated in 1 out of 4 colorectal, 1 out of 2 duodenal, 4 out of 16 gastric and no esophageal (sample size of 1) NECs. The results of immunohistochemistry for c-kit were consistent with the RT-PCR. No c-kit gene mutation was found in gastrointestinal NEC. CONCLUSION: The frequency of c-kit expression in gastrointestinal NEC was similar to that previously reported for pulmonary NEC. These findings suggest that c-kit inhibitor may be effective against some gastrointestinal NECs.

Aged↗

PubMed2006

A phase II Study of the global dose and schedule of capecitabine in Japanese patients with metastatic colorectal cancer.

BACKGROUND: Although the standard 3-week capecitabine regimen (1250 mg/m(2) twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m(2) twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC). METHODS: Previously untreated patients with MCRC received oral capecitabine 1250 mg/m(2) twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis. RESULTS: Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23-48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2-6.7 months). The median overall survival was 20.2 months (95% CI, 16.6-27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients. CONCLUSIONS: The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.

Administration, Oral↗

PubMed2006

Carcinogenic role of tumor necrosis factor-alpha inducing protein of Helicobacter pylori in human stomach.

Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-alpha is an endogenous tumor promoter, we identified the TNFalpha inducing protein (Tipalpha) gene family, and confirmed Tipalpha and HP-MP1 as new carcinogenic proteins of H. pylori.Tipalpha protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tipalpha gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-kappaB activation, and discusses the carcinogenic role of Tipalpha in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tipalpha is also discussed.

Amino Acid Sequence↗

PubMed2006

Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer.

BACKGROUND: Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. METHODS: Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP. RESULTS: In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18 mg/m2, with CDDP 3 mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16 mg/m2 with CDDP, 3 mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). CONCLUSION: The RD was determined to be TXL 14 mg/m2, with CDDP 3 mg/m2.

Aged↗

PubMed2006

[Capecitabine].

Capecitabine, an oral fluoropyrimidine carbamate, is adopted worldwide. As the treatment for metastatic colorectal cancer, capecitabine showed at least comparable efficacy with a favorable safety profile to bolus 5-FU/LV. In a large phase III trial (Xeloda Adjuvant Chemotherapy Trial: X-ACT), as the adjuvant treatment of patients with resected stage III colon cancer, capecitabine showed at least comparable disease-free survival, overall survival, and relapse-free survival with a favorable safety profile to bolus 5-FU/LV. Additionally, capecitabine-based combination regimens with oxaliplatin or irinotecan are now under evaluation. In phase II studies, capecitabine has shown the promising results in combination therapy. In Japan, capecitabine has been evaluated since 1994. In a recent phase II study, which evaluated the global dose as first-line treatment for metastatic colorectal cancer, the response rate was 35% (95% CI 23.1-48.4). The median time to disease progression was 169 days and the median overall survival was 617 days. Hand-foot syndrome (HFS), a characteristic adverse event of capecitabine, was observed in 73.3% of the patients, but the grade 3/4 was observed in 13.3% of the patients and only one patient discontinued the treatment due to HFS. An immediate approval of capecitabine in Japan is expected.

Antimetabolites, Antineoplastic↗

PubMed2004

The clinical features of rectal cancers with high-frequency microsatellite instability (MSI-H) in Japanese males.

Colorectal cancers with high-frequency microsatellite instability (MSI-H) are known to display striking differences in their clinical and pathological features compared to microsatellite stable (MSS) cancers. Previous studies revealed that MSI-H cancers are more likely to occur in women, irrespective of the higher incidence of colorectal cancer in men. In this study we investigated the gender-specific clinico-pathological features of MSI positive colorectal cancer in Japanese individuals. A series of 478 colorectal carcinomas were collected in an unbiased manner and analyzed for microsatellite instability status. Seven percent, 6% and 87% of tumors showed MSI-H, low-frequency microsatellite instability (MSI-L) and MSS, respectively. A comparison of gender indicated a statistical significance in terms of the distribution of the subsite and age of onset of MSI-H colorectal cancer. In general, MSI-H cancers prone to develop in the proximal colon however, we found that about 36% of MSI-H cancers in men developed in the rectum. These rectal cancers were more likely to have a mucinous component and multiple colorectal cancers including critical lesion. These findings should be useful to find MSI positive rectum cancer.

Age of Onset↗

PubMed2004

[A clinical study using octreotide in relieving gastrointestinal symptoms due to bowel obstruction in a terminally ill cancer patient].

Terminally ill cancer patients with complicated bowel obstructions often have poor quality of life (QOL) due to gastrointestinal symptoms such as nausea and vomiting. Many of these patients are inoperable because of poor general conditions, and half of these patients can't be managed by conventional antiemetics. There are many reports indicating octreotide is effective for these patients. In the present study, 13 patients (5 patients without a nasogastric tube and 8 patients with) were administered octreotide at 300 microg/day by 24 hours continuous subcutaneous infusion. Among the effectively evaluable 10 cases, 6 cases (60.0%) were assessed as effective according to the efficacy criteria based on the JCOG toxicity scale. In the 6 cases who had nasogastric tubes, the nasogastric aspirates decreased from 890 ml (550-1,950) to 480 ml (180-1,790). Vomiting was successfully controlled after the removals of nasogastric tubes in 4 out of 6 cases (66.7%), regarding safety, 2 out of 13 cases (15.4%) showed an excess of liver enzymes but no clinically suspected adverse effect was observed. Octreotide is effective and well tolerated in terminally ill cancer patients with malignant bowel obstruction.

Adult↗

PubMed2002

Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer.

BACKGROUND: To increase the options for agents for gastric cancer chemotherapy, we performed a phase II clinical trial on the use of a 3-h infusion of paclitaxel to confirm its efficacy and the feasibility of its use in patients with advanced gastric cancer. METHODS: Thirty-two (32) patients with measurable metastatic gastric cancer were enrolled in this study. Seventeen patients (53%) had received prior chemotherapy for metastatic disease, 4 patients (13%) had adjuvant chemotherapy alone, and 11 patients (34%) were chemotherapy-naive. Paclitaxel was intravenously infused for 3 h, at a dose of 210 mg/m(2), once every 3 weeks. To prevent hypersensitivity reactions, standard premedication was administered to all patients. RESULTS: Nine (28%; 9/32 ) objective partial responses (PRs) were observed (95% confidence interval [CI], 14%-47%), and the remaining 23 patients showed stable (12 patients; 37.5%) and progressive disease (11 patients; 34.4%). The median time to response was 20 days (range, 14-38 days). The median response duration was 87 days (range, 50-103 days). The median survival of all patients was 234 days (range, 13-646+ days). The major adverse reactions were myelosuppression (grade 3/4 leukopenia and neutropenia were observed in 59% and 88% of the patients, respectively), alopecia, and peripheral neuropathy. Peripheral neuropathy was observed in 19 patients, however, most of the patients recovered after the completion of treatment. CONCLUSION: A 3-h infusion of paclitaxel is an effective therapy for advanced gastric cancer and is clinically well tolerated by the patients.

Adenocarcinoma↗