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Tetsuro Kubota

Publications and source records attributed to Tetsuro Kubota.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Recent studies of sentinel lymph node. Multicenter prospective clinical trials of SN biopsy for gastric cancer].

The sentinel node (SN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. Recently, the validity of the SN concept in gastric cancer has been demonstrated by a number of single institutional studies, and prospective multi-center trials are presently ongoing. The Gastric Cancer Surgical Study Group of the Japan Clinical Oncology Group (JCOG) organized a multi-center prospective study of SN mapping by the dye-guided method using subserosal injection of indocyanine green. If the JCOG study reveals favorable results, in terms of false-negative rates, the dye-guided method will be utilized as a routine practice for open surgery in a wide range of institutions. If not, we will need to consider introduction of radioguided method or add further technical improvements, even for open surgery. A study group in the Japan Society of Sentinel Node Navigation Surgery is also conducting a multi-center prospective trial of SN mapping by a dual tracer method with blue dye and radio-active colloid. Even if the SNNS study demonstrates acceptable detection rates and low false-negative rates, we need to conduct a feasibility study of laparoscopic SN mapping for gastric cancer as the next step. The results of these clinical trials should provide useful perspectives on the future direction of SN navigation surgery for gastric cancer.

Clinical Trials as Topic↗
PubMed2005

TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis.

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.

Administration, Oral↗
PubMed2005

[Preoperative combination chemotherapy with TS-1 is effective in a case gastric cancer with peritoneal dissemination].

We report a case of peritoneal cancer dissemination with Type 4 gastric cancer, successfully treated with combination chemotherapy with TS-1. The patient was a 59-year-old female, who complained of abdominal distension with pain, weight loss, and poor appetite. She was diagnosed as unresectable Type 4 gastric cancer, T3N2MOHOP1CY1M0, Stage IV with massive ascites (cytology: Class V). After 2 courses of combined chemotherapy with TS-1 and cisplatin (CDDP), primary tumor reduction was confirmed and no cancer cells were detected from a pathological investigation with biopsied specimens by endoscopy. As additional therapy for remained ascites, intraperitoneal administration of paclitaxel and docetaxel was performed, resulting in a remarkable decrease of ascites with cytological disappearance of cancer cells. The patients underwent total gastrectomy with lymph node dissection, pathological diagnosis of primary site and lymph nodes showed grade 2 effect, and no cancer cells were detected in ascites and peritoneum, microscopically. While she died of peritoneal recurrence after the surgery, the case suggested the clinical advantage of controlling the advanced cancer-bearing state by combination chemotherapy with TS-1, instead of surgery.

Adenocarcinoma↗
PubMed2005

[Influence and provision for comprehensive insurance system--digestive surgery].

The diagnostic procedure combination (DPC) was introduced in 82 institutions from April 2003. DPC is similar to the diagnosis-related group and prospective payment system, which is widely used in the USA. The payment of DPC is calculated by multiplying the cost/day in each DPC, hospital stay in days, and index of each hospital, which is determined by several variables including the mean hospital stay in the previous year. After the introduction of DPC, clinical and diagnostic examinations, and cancer chemotherapy were shifted from the inpatient to outpatient setting in our institution, as well as in most of the other institutions reported by the Ministry of Health, Labor and Welfare. Because of the examinations in the outpatient clinic, the preoperative hospital stay was shortened. To validate the safety and effectiveness of cancer chemotherapy in the outpatient clinic, a central system was established in our institution by unifying the protocols and limiting the maximum administered doses by computer. After introduction of DPC, the average hospital stay was shortened in most institutions including ours. In spite of the satisfaction of the patients surveyed, the benefits of DPC should be confirmed based on the final outcome in terms of clinical therapeutic results.

Diagnosis-Related Groups↗
PubMed2004

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Esophageal Neoplasms↗
PubMed2004

Surgery for advanced gastric cancer after coronary artery bypass grafting using the right gastroepiploic artery: report of a case.

Ischemic heart disorders are often treated by coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). We report the case of a 57-year-old man with a history of CABG using the RGEA, who underwent D2 radical total gastrectomy followed by Roux-en-Y anastomosis, with successful dissection of the #6 lymph nodes, while preserving the RGEA. The patient had a 9-month history of gastric cancer, during which time the Maruyama Vaccine (Specific Substance Maruyama, or SSM) was given as alternative therapy. This case report serves to demonstrate that radical gastrectomy can be safely performed after CABG using the RGEA, and that gastric cancer will progress in spite of SSM therapy.

Adenocarcinoma↗
PubMed2004

Diagnosis and treatment of a gastric hamartomatous inverted polyp: report of a case.

Gastric hamartomatous polyps are rare and difficult to diagnose. We report the case of a 43-year-old woman admitted to our hospital after an upper gastrointestinal series revealed a submucosal tumor. Upper gastrointestinal endoscopy showed a submucosal tumor (SMT), which was eroded with a depression on its surface, in the upper corpus. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. A laparoscopic wedge resection of the stomach allowed us to perform complete resection of the tumor, which measured 2.8 cm in diameter. The pathological diagnosis was a gastric hamartomatous inverted polyp. The postoperative course was uneventful. Only 27 cases of gastric hamartomatous polyps have been reported in Japan. Hamartomatous inverted polyps without a stalk are classified as the "SMT type" because the tumor is inverted into the submucosal layer, whereas polyps with a stalk are classified as the "polyp type." All of the polyps in past reports were resected endoscopically; however, laparoscopic wedge resection may be indicated for SMT-type hamartomatous inverted polyps larger than 2.0 cm in diameter.

Adult↗
PubMed2004

Clinical and pathological disappearance of peritoneal dissemination in a patient with advanced gastric cancer receiving chemotherapy with S-1 and low-dose cisplatin.

A 54-year-old woman with severe abdominal distention suffered from massive ascites. Cytological examination revealed adenocarcinoma cells, leading to a diagnosis of peritonitis carcinomatosa. Gastrointestinal fiberscopy (GIF) resulted in a histological diagnosis of type 4 advanced gastric cancer with signet-ring cell carcinoma. The clinical diagnosis was confirmed to be cT3(SE)cN1cM0cH0cP1, cStage IV gastric cancer, type 4, according to the Japanese classification of gastric carcinoma. The patient was treated with S-1 and low-dose cisplatin (CDDP) in order to alleviate the critical state of the disease. After the third cycle of the regimen, the clinical response of P1 was classified as a partial response (PR) according to the World Health Organization (WHO) criteria. The patient's appetite loss and abdominal discomfort were markedly alleviated. The patient experienced grade 2 leukocytopenia throughout the regimen. Surgery was performed. Ascites and peritoneal disseminated lesions were not observed, and cytological examination of the peritoneal washes was negative. Total gastrectomy with D1 lymph node dissection was performed, and the surgical diagnosis was sT3(SE)sN0sM0sH0sP0; sStage II. Microscopically, viable cancer cells were found to be scattered throughout the subserosal-serosal layers in the resected stomach. All of the samples from lesions that were potentially cancers involving peritoneal dissemination were diagnosed as fibrous scar tissues without any viable cancer cells. The patient is alive without recurrence at 10 months after surgery and 14 months after the initial chemotherapy. Thus, systemic chemotherapy with S-1/low-dose CDDP achieved desirable control of peritoneal disseminated cells, as assessed microscopically, suggesting that the regimen may be an effective strategy for the treatment of advanced gastric cancer with peritonitis carcinomatosa.

Ascites↗
PubMed2004

Differences between scirrhous and non-scirrhous human gastric carcinomas from the aspect of proMMP-2 activation regulated by TIMP-3.

Gastric carcinomas can be classified into scirrhous carcinomas (SC), i.e. 'linitis plastica' or Borrmann 4 gastric cancer, and non-scirrhous carcinomas (NSC). SC are characterized by diffuse invasive growth patterns with marked fibrosis, frequent peritoneal dissemination and lymph-node metastases and poor prognosis, while NSC show medullary growth patterns and common hematogenous metastases. To study the differences in local expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between SC and NSC, we examined the expression of MMPs and TIMPs in human gastric carcinoma tissues by several methods including sandwich-enzyme immunoassay systems, gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR, immunoblotting, immunohistochemistry and in situ zymography. Of the seven MMPs and two TIMPs tested, only proMMP-2 levels were remarkably higher in SC than in NSC (P < 0.01), and proMMP-2 activation ratio was significantly lower in SC than in NSC (P < 0.05). TIMP-3 mRNA levels were remarkably about 2-fold higher in SC than in NSC tissues (P < 0.01). TIMP-3 production in SC was confirmed by immunoblotting and TIMP-3 was immunolocalized to stromal fibroblasts in SC. TIMP-3 mRNA levels inversely correlated with proMMP-2 activation ratios, although the expression levels of MT1-MMP and MT2-MMP were not different in SC and NSC. By in situ zymography, gelatinolytic activity appeared to be weaker in SC than in NSC. All these data suggest that proMMP-2 activation is down-regulated by TIMP-3 expressed in scirrhous gastric carcinomas. Our findings may explain the differences in clinical behaviors of SC and NSC.

Adenocarcinoma, Scirrhous↗
PubMed2004

A randomized phase II clinical trial of tailored CPT-11 + S-1 vs S-1 in patients with advanced or recurrent gastric carcinoma as the first line chemotherapy.

A randomized phase II clinical trial has been designed and started in the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) to select the better regimen between tailored CPT-11 + S-1 and the standard S-1 treatment for advanced or recurrent gastric cancer as the first line chemotherapy. Selection of the better treatment for general clinical practice in this clinical trial will lead to a more precise assignment of a promising regimen for a future phase III randomized trial, placing continuous 5-FU infusion as the reference arm. In this trial, subsidiary pharmacokinetic analysis for the tailored dose arm is also proposed. In order to continue chemotherapy for a long time and to obtain longer survival, our study design for the tailored therapy could be exploited, especially in the field of general clinical practice.

Antimetabolites, Antineoplastic↗
PubMed2004

Docetaxel enhances the cytotoxicity of cisplatin to gastric cancer cells by modification of intracellular platinum metabolism.

We have examined the combined anticancer effects of docetaxel (DOC) and cisplatin (CDDP) in vitro using the gastric cancer cell lines MKN-45, MKN-74, and TMK-1. Treatment of the cell lines with 30 microg/ml of DOC for 24 h followed by incubation with 3 or 10 microg/ml of CDDP for 24 h showed a clear synergistic effect. Sequence dependency of the agents was observed in these cell lines: DOC followed by CDDP (DC) showed a stronger antitumor effect than CDDP followed by DOC (CD) in all cell lines. To clarify the mechanism of action of the DC combination, total intracellular platinum (Pt) levels were evaluated after treatment with CDDP alone or combined with DC. For the MKN-45 and -74 cell lines, cells treated with DOC (10 microg/ml for 12 h) and then CDDP showed significantly increased intracellular Pt accumulation compared to cells treated with CDDP alone. We also investigated alterations in intracellular glutathione (GSH) concentration in response to DOC and CDDP. MKN-45 and -74 cells pretreated with DOC (10 microg/ml for 12 h) showed significantly increased intracellular GSH levels compared to cells administered CDDP only. To explain these findings, messenger RNA (mRNA) levels for multidrug resistance-associated protein-1 (MRP-1), the ATP-dependent pump for Pt-GSH complexes, were quantified in CDDP-treated MKN-45 cells with and without DOC pretreatment. While CDDP administration increased MRP-1 mRNA expression in MKN-45 cells, MRP-1 was not up-regulated after CDDP administration in DOC pretreated MKN-45 cells. Our results suggested that the enhanced CDDP toxicity due to DOC pretreatment may be related to the accumulation of intracellular Pt-GSH complexes, because DOC appears to suppress the MRP-1 up-regulation induced by CDDP exposure in gastric cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

[Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer].

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).

Adult↗
PubMed2004

Inhibition of DNA methyltransferase by antisense oligodeoxynucleotide modifies cell characteristics in gastric cancer cell lines.

DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors, relating to cell differentiation or carcinogenesis. In the present study, we designed an antisense oligodeoxynucleotide of DNMT1 (AS/MT: 5'-CGGTAC GCGCCGGCATCT-3') and demonstrated successful inhibition of DNMT1 expression by AS/MT at the protein level, using gastric cancer cell lines in vitro. E-cadherin protein expression was increased, and both cyclin D1 and PCNA were decreased by AS/MT treatment. AS/MT also induced suppression of cell growth as determined by BrDU uptake incorporation, in a dose-dependent manner, suggesting specificity of AS/MT. Simultaneously, morphological alterations were observed in both TMK-1 and MKN-45 cells after 24 h incubation with 2 micro M of AS/MT. The cells changed shape from their original forms to dispersed, fibroblast-like cells with neurite-like processes, accompanied by an increased adhesive potential of the cells. An in vivo model of peritoneal dissemination using the nude mouse system showed an increased malignant potential of AS/MT treated TMK-1 cells as demonstrated by a greater number of peritoneal tumor nodules in the AS/MT as compared to the NS/MT treated group, 34.8+/-4.3 vs. 22.4+/-3.0 nodules, respectively (p=0.0039). The total wet tumor weight in the AS/MT group (350+/-47.4 g) was significantly greater than that in the NS/MT group (248+/-41.5 g) (p=0.0065). In conclusion, the inhibition of DNA methylation by DNMT1 by an antisense oligodeoxynucleotide influences cell morphology and adhesion, as well as cell growth in gastric cancer cells in vitro. Moreover, these alterations in the characteristics of cancer cells resulted in an increased ability to attach onto the peritoneum in the nude mouse system in vivo, suggesting that strict clinical guidelines will be necessary to utilize such a DNA methylation inhibitor, since it does not always mean a therapeutic antitumor strategy.

Adenocarcinoma↗
PubMed2004

[Cancer chemotherapy in DPC].

After the introduction of DPC in 2003, cancer chemotherapy treatment was moved to our outpatient clinic. We have initiated an outpatient cancer chemotherapy center, and the chemotherapy regimens were developed for various kinds of cancer: 1 for esophageal, 7 for gastric, 9 for colon, 38 breast and 10 for hepato-biliary-pancreatic cancer. Since cancer chemotherapy on an outpatient basis is a world-wide trend, we should maintain the quality of cancer chemotherapy for inpatients in our outpatient center.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

[A randomized phase II clinical trial of tailored CPT-11 + TS-1 vs TS-1 in patients with advanced or recurrent gastric carcinoma as the first-line chemotherapy (JFMC31-0301)].

The Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) has designed and initiated a randomized Phase II clinical trial planned as a first-line of chemotherapy for advanced or recurrent gastric cancer. The trial focuses on two groups and selecting the better of two regimens. The first group was given tailored CPT-11, adjusting individual optimal dosage using toxicity-based grading as an index in combination with TS-1, and the second group was given standard TS-1 treatment. The aim of this tailored dosage regimen for each individual patient is to continue chemotherapy as long as possible, and eventually, to prolong survival. In this trial, subsidiary pharmacokinetics analysis for the tailored arm is also proposed. We would like to introduce the significance and theory of tailored dosage chemotherapy in this paper.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Lewis type 1 antigen synthase (beta3Gal-T5) is transcriptionally regulated by homeoproteins.

The type 1 carbohydrate chain, Galbeta1-3GlcNAc, is synthesized by UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T). Among six beta3Gal-Ts cloned to date, beta3Gal-T5 is an essential enzyme for the synthesis of type 1 chain in epithelium of digestive tracts or pancreatic tissue. It forms the type 1 structure on glycoproteins produced from such tissues. In the present study, we found that the transcriptional regulation of the beta3Gal-T5 gene is controlled by homeoproteins, i.e. members of caudal-related homeobox protein (Cdx) and hepatocyte nuclear factor (HNF) families. We found an important region (-151 to -121 from the transcription initiation site), named the beta3Gal-T5 control element (GCE), for the promoter activity. GCE contained the consensus sequences for members of the Cdx and HNF families. Mutations introduced into this sequence abolished the transcriptional activity. Four factors, Cdx1, Cdx2, HNF1alpha, and HNF1beta, could bind to GCE and transcriptionally activate the beta3Gal-T5 gene. Transcriptional regulation of the beta3Gal-T5 gene was consistent with that of members of the Cdx and HNF1 families in two in vivo systems. 1) During in vitro differentiation of Caco-2 cells, transcriptional up-regulation of beta3Gal-T5 was observed in correlation with the increase in transcripts for Cdx2 and HNF1alpha. 2) Both transcript and protein levels of beta3Gal-T5 were determined to be significantly reduced in colon cancer. This down-regulation was correlated with the decrease of Cdx1 and HNF1beta expression in cancer tissue. This is the first finding that a glycosyltransferase gene is transcriptionally regulated under the control of homeoproteins in a tissue-specific manner. beta3Gal-T5, controlled by the intestinal homeoproteins, may play an important role in the specific function of intestinal cells by modifying the carbohydrate structure of glycoproteins.

Amino Acid Motifs↗