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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 109 records · Page 6Linked to original sources
PubMed1997

Lymph node metastasis and relation to tumor growth potential and local immune response in advanced gastric cancer.

To evaluate the relation between the degree of lymph node metastasis and the growth potential of tumour cells and the local immune function in gastric cancer, we analyzed data on 444 patients with advanced serosally invasive gastric cancer who underwent curative gastrectomy. Tumour growth potential was evaluated based on the value proliferating cell nuclear antigen (PCNA) in the primary tumour, and dendritic cell infiltration into the tumour was determined as an indicator of local immune function. The values of PCNA labeling in the primary tumour increased and the infiltration of dendritic cells into the tumour decreased in relation to the extent of lymph node metastasis. High growth potential and low immune function were seen in cases with n3 lymph node metastasis. There was a reverse relation between the PCNA labeling index and dendritic cell infiltration. A variety of forms of recurrence was noted in patients with lymph node metastasis while the prognosis was less favorable, in relation to the degree of lymph node metastasis. Thus, the potential for nodal spread appears to be associated with the growth potential of tumour cells and with the local immune status of the tumour.

Cell Count↗
PubMed1997

Reversal of in vivo drug resistance by the transforming growth factor-beta inhibitor decorin.

Transforming growth factor-beta (TGF-beta) has been implicated in the in vivo resistance of the EMT-6/CTX and EMT-6/ CDDP murine mammary tumors. Both of these tumors have a higher number of intratumoral vessels than the EMT-6/ parent tumor. Animals bearing the resistant tumors have higher plasma levels of TGF-beta than animals bearing the parent tumors; however, upon treatment with cytotoxic therapies there is a greater rise in plasma TGF-beta levels in animals bearing the parent tumor than in animals bearing the resistant tumors. In situ hybridization for TGF-beta mRNA and immunohistochemical staining for TGF-beta protein showed that the resistant tumor levels of this growth factor are higher than those of the parent tumor prior to treatment; however, after cytotoxic therapy the increase in TGF-beta is greater in the parent tumor than in the resistant tumors. Treatment of tumor-bearing animals with the naturally occurring TGF-beta inhibitor decorin did not alter the sensitivity of the parent tumor to cyclophosphamide or to CDDP as determined by tumor cell survival assay. However, administration of decorin increased the sensitivity of the EMT-6/CTX tumor to cyclophosphamide and of the EMT-6/CDDP tumor to CDDP so that the drug resistance of these tumors was nearly ablated. A similar pattern was observed in the drug response of the bone marrow granulocyte-macrophage colony-stimulating factor of animals bearing each of the 3 tumors.

Animals↗
PubMed1997

Dynamics of tumor oxygenation, CD31 staining and transforming growth factor-beta levels after treatment with radiation or cyclophosphamide in the rat 13762 mammary carcinoma.

PURPOSE: Tumors are dynamic tissues that undergo marked molecular, biochemical, and physiologic changes in response to cytotoxic anticancer therapies. Understanding the changes in tumor oxygenation and transforming growth factor-beta expression may allow improved treatment regimens to be developed. METHODS AND MATERIALS: The effects of a single dose of radiation therapy (20 Gy) or a single dose of chemotherapy (cyclophosphamide, 250 mg/kg) on several molecular and physiologic parameters of the rat 13762 mammary carcinoma growing subcutaneously in female Fischer 344 rats were explored. RESULTS: Treatment of the tumor-bearing animals with 20 Gy of radiation killed about two logs (99%) of the 13762 tumor cells, and treatment with cyclophosphamide (250 mg/kg) killed about 1.5 logs (95%) of the 13762 tumor cells. Hypoxia, as determined by a pO2 electrode, initially decreased in the tumors of treated animals until 6 h. posttreatment and then increased, so that 24 h. after administration of the radiation therapy or the chemotherapy the number of intratumoral vessels as determined by CD31 staining increased until about 24 h after cytotoxic therapy. Transforming growth factor-beta1, measured by radioimmunoassay, peaked in the serum between 6 h and 18 h and again between 72 h and 96 h after radiation therapy and peaked in the tumor at 24 h and again at 72 h after radiation therapy. The first serum peak after cyclophosphamide was 3 h after drug injection, with second peaks at 36 h and 48 h after drug administration. In the tumor, transforming growth factor-beta1 peaked between 6 h and 8 h after drug administration and again 36 h and 72 h after drug. Apoptosis was maximal 6 h after 20 Gy and 24 h after cyclophosphamide. Vascular endothelial growth factor was also increased in tumors after cytotoxic therapy. CONCLUSIONS: These changes in the tumor physiologic status are sufficient to protect the tumor from a second cytotoxic insult administered days afterwards and to result in a restructuring of the tissue.

Animals↗
PubMed1997

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗
PubMed1997

Improved surgical results after combining preoperative hyperthermia with chemotherapy and radiotherapy for patients with carcinoma of the rectum.

PURPOSE: The aim of this study is to evaluate long-term results of preoperative hyperthermia combined with chemotherapy and irradiation (HCR therapy) in patients with carcinoma of the rectum. METHODS: Postoperative prognoses were compared among 36 patients with carcinoma of the rectum, who were given preoperative HCR therapy followed by surgery, and 52 patients undergoing surgery alone without any preoperative therapy. RESULTS: There were significant differences in the prognosis between patients given preoperative HCR therapy plus surgery and those having surgery alone, and five-year survival rates were 91.3 and 64 percent, respectively. Particularly, for patients with tumors invading beyond the muscularis propria and/or with positive lymph node metastasis, a significantly longer survival was obtained with HCR plus surgery than in surgery alone (86.5 vs. 50.9 percent and 92.9 vs. 51.7 percent, respectively). However, no significant differences were observed in the postoperative prognosis for cases with no lymph node metastasis and/or with tumors limited to the muscularis propria between these two groups. CONCLUSIONS: These data clearly demonstrated the effectiveness of preoperative HCR therapy for improving long-term results of patients with carcinoma of the rectum, especially those demonstrating an advanced stage of disease.

Aged↗
PubMed1997

Tumor size as a simple prognostic indicator for gastric carcinoma.

BACKGROUND: Tumor size can be measured easily before or during operation with no special tools, but its prognostic use in patients with gastric carcinoma is still unclear. METHODS: Clinicopathologic data of 479 patients who underwent curative operation for gastric carcinoma were studies. The relationship between tumor size and survival of patients was investigated. RESULTS: The patients were divided into three groups: 182 with tumors measuring < 4 cm (group I), 252 with tumors of 4-10 cm (group II), and 45 with tumors of > or = 10 cm (group III). The 10-year survival rates for group I, II, and III patients were 92%, 66% and 33%, respectively (p < 0.01), and the three groups were significantly different with regard to depth of invasion (p < 0.01), number and level of lymph node metastasis (p < 0.01), and stage of disease (p < 0.01). Multivariate analysis indicated that tumor size independently influenced the survival of patients. CONCLUSIONS: Tumor size clinically serves as a simple predictor of tumor progression and survival of patients in gastric carcinoma.

Adenocarcinoma↗
PubMed1997

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.

Adult↗
PubMed1997

The effects of an intrathecal NMDA antagonist (AP5) on the behavioral changes induced by colorectal inflammation with turpentine in rats.

Visceral pain, especially that associated with inflammation of visceral organs, is poorly understood and difficult to treat clinically. The purpose of this study was to investigate the effects of intrathecal 2-amino-5-phosphonovaleric acid (AP5, a competitive NMDA antagonist) upon a visceromotor response to distension of colonic tissue inflamed by exposure to turpentine. All experiments were conducted under pentobarbital anesthesia. Animals were prepared with a laminectomy from T12 to L1 to facilitate intrathecal drug administration. Colonic distension thresholds for a visceromotor response were determined in the presence and absence of AP5. Animals were divided into two groups. The NS group received 50 microl of saline intrathecally and the AP5 group 10 mM of AP5 in 50 microl saline. After baseline measurements, intrathecal drugs were administered. Five minutes later, the effects of intrathecal drugs were measured, then 1 ml of 25% turpentine was administered anorectally. Subsequent measurements were made every 5 minutes for the next 90 minutes. Visceromotor thresholds to colorectal distension (CRD) were significantly decreased 50 min after turpentine administration in the NS group. There was no threshold change in the AP5 group. This study suggests that the administration of the competitive NMDA receptor antagonist AP5 in this model blocks the effect of turpentine sensitization on visceromotor response to CRD. The absence of AP5 effects in animals not sensitized by turpentine suggests that NMDA systems may be involved in the sensitization.

2-Amino-5-phosphonovalerate↗
PubMed1997

Surgical treatment and outcome for node-negative gastric cancer.

BACKGROUND: The clinicopathologic characteristics and prognosis for patients with node-negative gastric cancer have heretofore remained to be determined. METHODS: We analyzed data on 730 of our patients with node-negative gastric cancer who underwent curative gastric resection in the Department of Surgery II, Kyushu University Hospital, between 1965 and 1990, with reference to prognostic factors. The presence of lymph node metastasis was determined by means of routine hematoxylin-eosin staining of excised tissues. RESULTS: The 5-year survival rate was 91.7% and the 10-year rate was 88.5%; thus the prognosis was good for patients with node-negative gastric cancer. When the prognosis was analyzed by stratification of each clinicopathologic factor, the survival time was shorter for older patients when the size of the tumor was larger, when the tumor involved the entire stomach, and when-tissues revealed infiltrative growth, serosal invasion, and lymphatic invasion. Extensive lymph node dissection was performed for 86.6% of the patients, and for these patients the prognosis was better, with a statistical difference. In a multivariate analysis, tumor size, serosal invasion, and extensive lymph node dissection proved to be independent prognostic factors for patients with node-negative gastric cancer. CONCLUSIONS: Prophylactic lymph node dissection for patients with gastric cancer will prolong the survival time.

Adult↗
PubMed1997

Potentiation of the cytotoxicity of carboquone by flavone acetic acid combined with hyperthermia.

Flavone acetic acid (FAA) has shown the effectiveness of vasoactive drugs in the selective reduction of tumor blood flow. A FAA-mediated decrease in tumor blood flow may produce sufficient hypoxic conditions within the tumor. Carboquone (CQ), a naturally occurring prototype bioreductive alkylating agent like mitomycin C (MMC), has been shown to be selectively more cytotoxic toward hypoxic tumor cells. We have reported enhancement of the combined antitumor effects of MMC plus FAA and hyperthermia (HT). In this study, we examined the combined effects of FAA, CQ and HT. In vitro, although HT (43 degrees C, 60 min) reduced the colonogenicity to 0.58 in CQ (0.01 microg/ml) alone, the combined cytotoxicity of CQ and HT was not enhanced with exposure to FAA at a concentration of 100 microg/ml. In vivo, the tumor growth time, calculated as the time required to reach twice the initial tumor volume, for CQ (2 mg/kg) alone, FAA (150 mg/kg) alone, CQ+FAA, CQ+HT (43 degrees C, 15 min), FAA+HT and FAA+CQ+HT was 6.1, 5.1, 7.1, 8.0, 7.6 and 13.4 days, respectively. A significant enhancement of antitumor effects by trimodality therapy with CQ, FAA and HT was observed, when compared to the treatment with CQ and FAA (p < 0.05). The possible mechanisms of an increased antitumor response achieved with the combination of CQ, FAA and HT may be explained in the following way: the FAA-mediated decrease in tumor blood flow produced sufficient hypoxic conditions within the tumor, and these resulted in a significant increase of the antitumor effects of CQ and HT.

Animals↗
PubMed1997

DNA typing of HLA class I (HLA-A) and class II genes (HLA-DR, -DQ and -DP) in Japanese patients with gastric cancer.

Gastric cancer is multifactorial disease and several reports have described genetic factors involved in pathogenesis of gastric cancer. Recently, it was reported that HLA class II gene DQB1*0301 was strongly associated with gastric cancer in Caucasian population (20). We performed DNA typing of HLA class I (HLA-A) and HLA class II genes (HLA-DR, DQ and DP) to elucidate the HLA alleles or HLA haplotypes associated with gastric cancer in Japanese population using polymerase chain reaction-sequence-specific oligonucleotide probe analysis in 88 unrelated patients with gastric cancer and 525 unrelated healthy controls. We observed slight difference in frequencies of some HLA alleles and haplotypes between gastric cancer patients and controls; however, after Bonferroni correction, statistical significance was not confirmed. It is possible that environmental factors such as diet cover the contribution of genetic factors to the disease in Japanese population, which has a higher frequency of gastric cancer than do Caucasian populations, most likely due to more exposure to environmental risk factors.

Adult↗
PubMed1997

Morbidity after D2 and D3 gastrectomy for node-positive gastric carcinoma.

BACKGROUND: Several studies show various rates of morbidity and mortality after radical operation for gastric carcinoma. Whether or not extended lymph node dissection should be done is still controversial. STUDY DESIGN: The medical records of 214 patients with node-positive gastric carcinoma who underwent radical gastrectomy and extended lymph node dissection (D2, D3) from 1975 to 1990 were analyzed with reference to the type and cause of postoperative complications. RESULTS: The overall morbidity rate was 36 percent and was significantly different between patients with distal gastrectomy (19 percent) and total gastrectomy (53 percent) (p < .01). Morbidity after distal gastrectomy correlated with blood loss (593 g compared with 438 g; p < .05) and transfusion (43 percent compared with 21 percent; p < .05), whereas morbidity after total gastrectomy was closely linked to splenectomy (64 percent compared with 40 percent; p < .05) and duration of the operation (227 minutes compared with 204 minutes; p < .05). The morbidity rate was not different, however, between D2 dissection (33 percent) and D3 dissection (40 percent) groups. CONCLUSIONS: Radical gastrectomy and extended lymph node dissection can be performed with an acceptable morbidity, but total gastrectomy with splenectomy was associated with high morbidity in patients with node-positive gastric carcinoma.

Adenocarcinoma↗
PubMed1997

Surgical results of perforated gastric carcinoma: an analysis of 155 Japanese patients.

OBJECTIVES: Free perforation of gastric carcinoma accounts for less than 1% incidence of acute abdominal crisis in Japan, and this problem occurs much less frequently in Western countries. To clarify the characteristics of patients with perforated gastric carcinoma (PGC) and to investigate a treatment of choice, we reviewed the data of Japanese patients with PGC. METHODS: A total of 155 cases of PGC reported in the Japanese literature from 1985 to 1994, including one patient of our own experience, were studied. The clinicopathologic features, including tumor stage and patient survival, were analyzed. RESULTS: There were 27 stage I tumors (19%), 16 stage II tumors (12%), 42 stage III tumors (30%), and 55 stage IV tumors (39%). Emergency gastrectomy was done in 128 patients (83%), with the mortality and 5-yr survival rate was 7 and 40%, respectively. The survival of patients was influenced by the gross type of tumor, serosal invasion, lymph node metastasis, stage of the disease, and operative curability. The 5-yr survival rate of stage I and II patients was 76% and that of curatively treated patients was 74%. CONCLUSIONS: Recent Japanese results of emergency gastrectomy for PGC are satisfactory. Long-term survival is expected in curatively treated patients with stage I and II tumors.

Abdomen, Acute↗
PubMed1997

Prognostic factors of node-negative gastric carcinoma: univariate and multivariate analyses.

BACKGROUND: The presence or absence of lymph node metastasis closely correlates with survival of patients with gastric carcinoma. Although prognostic significance of the number and level of lymph node metastasis has been clarified, clinicopathologic features and prognostic indicators of node-negative gastric carcinoma have not yet been studied. STUDY DESIGN: The records of 435 patients who underwent curative D2 or D3 gastrectomy for gastric carcinoma between 1977 and 1987 were analyzed retrospectively. Clinicopathologic data of 252 patients having no lymph node metastasis were compared with those of 183 patients with lymph node metastasis. Prognostic factors were investigated by univariate and multivariate analyses. RESULTS: Compared with node-positive cases, node-negative cases were characterized by frequent location in the lower two thirds of the stomach (85 percent), tumor size less than 4 cm (54 percent), grossly superficial type (69 percent), and tumor invasion not beyond the muscularis propria (77 percent). The 10-year-survival rate for patients with node-negative tumors was 93.4 percent. Multivariate analysis demonstrated that depth of wall invasion and age of patient were independent prognostic factors. CONCLUSIONS: Node-negative gastric carcinoma is associated with a favorable outcome because of small progression of the disease. The depth of wall invasion and patient age were the most important prognostic factors.

Female↗
PubMed1997

Scientific basis for the combination of tegafur with uracil.

Fujii et al reported that Uracil potentiated the antitumor activity of fluorouracil (5-FU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur). This effect was due to inhibition of the degradation of 5-FU, yet the phosphorylation of 5-FU was unaffected. The molar ratio of tegafur and uracil was 1:4, a combination that has since been widely prescribed in Japan for the treatment of cancer patients. We present here our experimental and clinical results when investigating the antineoplastic effects of this combination of drugs--known as UFT--and provide evidence that UFT is an effective treatment for patients with cancer.

Chemotherapy, Adjuvant↗
PubMed1996

Expression of multidrug-resistance-associated protein (MRP) and chemosensitivity in human gastric cancer.

Evidence has accumulated that, in addition to the MDR1 gene-coded P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP) also mediates the multidrug resistance (MDR) of various human tumors. In the case of gastric cancer, there is little or no involvement of P-glycoprotein, and the mechanisms of MDR remain to be understood. To search for a possible relationship between expression of MRP and sensitivity to anti-cancer agents in gastric cancer, 4 gastric cancer cell lines, 43 human gastric carcinomas and 17 adjacent normal gastric tissue samples were analyzed. Expression of MRP mRNA was evaluated using reverse transcription PCR (RT-PCR) and Southern hybridization. Sensitivity of the test samples to the anti-cancer drugs cisplatin (CDDP), doxorubicin (DXR) and etoposide (VP-16) was examined using the MTT¿3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl [2H]-tetrazolium bromide¿ assay. Immunohistochemical staining with the use of the MRP antibody (MRPr1) was done to confirm the findings regarding the expression of mRNA levels. The MRP expression evaluated with RT-PCR and Southern hybridization as well as with immunohistochemical staining revealed that 23 of 43 gastric-cancer tissues (53.5%), 15 of 17 normal gastric tissues (88%) and 3 of 4 gastric-cancer cell lines (75%) were positive. The MTT assay showed that DXR was significantly more sensitive (p < 0.01) in gastric carcinoma tissues lacking MRP expression than in those with positive expression. The same tendency was seen with the other agents used. Of the cell lines, one which showed no MRP expression also had a higher sensitivity to CDDP, DXR and VP-16 than the other positive cases. These results show that MRP expression is involved in MDR of human gastric cancer and is inversely related to the chemosensitivity of tumor cells against some anticancer drugs.

ATP-Binding Cassette Transporters↗
PubMed1996

Interaction of interleukin-11 with cytotoxic therapies in vitro against CEM cells and in vivo against EMT-6 murine mammary carcinoma.

Interleukin-11(rhIL-11) is a cytokine that has been shown to enhance the recovery of bone marrow and intestinal crypt cells after cytotoxic insult with radiation or anticancer drugs. The current study examined the effects of rhIL-11 on the response of CEM human lymphoblastic leukemia cells and on the EMT-6 murine mammary carcinoma in vivo to cytotoxic anticancer therapies. Exposure of CEM cells to rhIL-11 for 24 hr did not alter the cytotoxicity of melphalan or radiation, increased the cytotoxicity of CDDP (100 muM) and 4-hydroperoxycyclophosphamide (50 betaM) and decreased the cytotoxicity of 5-fluorouracil and ara-C toward the cells. Treatment of mice bearing the EMT-6 tumor with rhIL-11 twice daily for 4 days prior to and the day of cytotoxic therapy resulted in no significant change in the tumor cell killing or bone marrow CFU-GM killing by melphalan, cyclophosphamide, thiotepa, CDDP, radiation, 5-fluorouracil or ara-C. Administration of rhIL-11 twice per day on days 7-18 to EMT-6 tumor bearing animals receiving high dose chemotherapy (melphalan, thiotepa or cyclophosphamide) as a single dose on day 7 followed by mobilized peripheral blood cells on day 8 and rhG-CSF on days 8-20, tended to prolong the tumor growth delay produced by the drugs. This rhIL-11 treatment also resulted in a more rapid recovery of white blood cells and granulocytes in the animals. Furthermore, animals treated with rhIL-11 had improved survival rates compared with animals receiving all other normal tissue support without rhIL-11.

Animals↗