Biomedical subjects

H Yamaue

Publications and source records attributed to H Yamaue.

At least 37 records · Page 2Linked to original sources

PubMed1999

Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model.

We transduced the interleukin-2 (IL-2) gene into murine fibroblasts BALBCL7 or murine colon cancer CT26 using a retroviral vector. BALBCL7 transduced with IL-2 gene secreted 748 pg/ml of IL-2, whereas IL-2 gene-modified CT26 secreted 1,167 pg/ml of IL-2 (48 h incubation, 1x10(6)/ml). Then, we inoculated gene-modified BALBCL7 and/or CT26 cells into BALB/c female mice, and observed the tumor growth. The tumor growth was inhibited in mice inoculated with parental CT26 plus IL-2 gene-modified BALBCL7, compared with that in mice given parental CT26 alone (P<0.01). Moreover, we investigated the cytotoxic activity of spleen cells derived from mice treated with gene-modified cells, and performed phenotypic analysis of the effector cells. The killer cells derived from mice inoculated with IL-2 gene-modified BALBCL7 plus parental CT26 showed higher cytotoxic activity than those from mice inoculated with CT26 alone. The cytotoxic activity was almost completely blocked by anti-CD8 antibody (Ab), and partially blocked by anti-asialo GM1 Ab. Next, we inoculated CT26 tumor tissue into murine cecum orthotopically, and treated the animals with gene-modified BALBCL7 plus parental CT26. The tumor size in the cecum was significantly decreased, compared with parental CT26 alone (P<0.01).

Animals↗

PubMed1999

Tumor specific CTL therapy for advanced cancer and development for cancer vaccine.

BACKGROUND/AIMS: Advanced gastrointestinal (GI) cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of tumor specific cytotoxic T Lymphocyte (CTL) therapy as multidisciplinary treatment for patients with advanced cancer. METHODOLOGY: The enrolled advanced cancer patients had distant metastases derived from gastric cancer, colon cancer and bilio-pancreatic cancer. The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by various kinds of the activated killer cells. RESULTS: There was no severe toxicity, except fever and mild myelo-suppression. Six patients had complete response, and 18 patients had partial response out of 38 enrolled patients. The performance status was improved in responders (p<0.01); however, it was not changed in non-responders. Furthermore, the ratio of discharge of the responders was higher than that of non-responders. CONCLUSIONS: It was clarified that tumor-specific CTL therapy as multidisciplinary treatment is clinically valuable, especially in terms of quality of life. For developing the new strategy against cancer, CEA specific cancer vaccine trials have just started.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Intraoperative radiation therapy for a patient with bulky disease of mesenteric non-Hodgkin's lymphoma.

A long survival is rarely observed in patients demonstrating recurrent malignant lymphoma with bulky disease because of the appearance of chemoresistant tumor cells after extensive chemotherapy, and moreover the presence of bulky disease has also been consistently associated with a poorer response rate and a shortened survival, due to the fact that tumor size is the most significant factor for the treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old woman presenting with the chief complaint of abdominal fullness, who underwent intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence, based on the findings of regular abdominal computed tomographic scans, 60 months after initial chemotherapy and 28 months after IORT.

Female↗

PubMed1998

Successful immunochemotherapy for patients with malignant mesothelioma: report of two cases.

Malignant mesothelioma is a clinically aggressive tumor and has a poor prognosis; therefore, the selection of therapeutic strategies is important to improve the prognosis. Two patients with intraperitoneal malignant mesothelioma received combination therapy as follows: (1) case-oriented chemotherapy according to the results of a chemosensitivity test, and (2) adoptive immunotherapy using cytotoxic T lymphocytes (CTL). The chemosensitivity test was assessed by an MTT colorimetric assay. CTL was generated by a mixed culture with autologous tumor cells, and activated by immobilized anti-CD3 monoclonal antibody and interleukin-2. The MTT assay indicated that cisplatin and adriamycin were sensitive drugs in both patients, and they thus received the case-oriented chemotherapy according to the MTT assay. The activated CTL exhibited a high cytotoxicity against autologous malignant mesothelioma cells, and were transferred intraperitoneally. The patients were controllable for ascites, and the tumor masses gradually vanished (partial response). Chemoimmunotherapy is thus considered to be an effective treatment for intraperitoneal malignant mesothelioma, especially to improve the quality of life.

Adult↗

PubMed1998

Clinical effect of immunochemotherapy for a patient with advanced gallbladder cancer: report of a case.

A 56-year-old woman was admitted presenting with a sensation of abdominal fullness. She was diagnosed to have advanced gallbladder cancer with carcinomatous peritonitis, as well as lymph node and liver metastases. We obtained highly purified tumor cells and tumor-infiltrating lymphocytes (TIL) from extirpated cervical lymph nodes and peritoneal effusion, and the chemosensitivity of these cells was tested with an MTT assay. Intensive chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was then performed according to the results of the MTT assay. Thereafter, cytotoxic T-lymphocytes (CTL) were induced in mixed cultures of autologous tumor cells and peripheral blood lymphocytes, and adoptive immunotherapy was performed with TIL and CTL. The malignant ascites and metastatic lesions disappeared after the intraperitoneal administration of CDDP and the transfer of TIL and CTL, and subsequently the patient's quality of life improved. This patient could return to work; however, liver metastasis was later observed, and she died 14 months after the initial diagnosis. Combination therapy with anticancer drugs and activated killer cells was thus found to be effective in a patient with advanced gallbladder cancer.

Adenocarcinoma↗

PubMed1997

Duodenal obstruction by gallstone: case report of Bouveret's syndrome.

Bouveret's syndrome involves gastric outlet obstruction by gallstone. Herein we describe an unusual case of duodenal bulb obstruction by gallstone. An 80-year-old woman was hospitalized with a fifteen-day history of vomiting. Computed tomography (CT) showed pneumobilia and a round calcified mass in the second portion of the duodenum. Upper gastrointestinal tract series demonstrated the same sized oval radiolucency between the bulbus and the second portion of the duodenum. Endoscopic examination revealed a round black mass in the second portion of the duodenum, totally occupying the lumen. Endoscopic removal and destruction of the gallstone was attempted using a dye-laser, but the stone was too hard to crush. Eventually surgical enterolithotomy was successfully performed without cholecystectomy or closure of the fistula. Improved preoperative systemic management and prompt examination allowed earlier surgical intervention and reduced the morbidity. Surgical approach whether fistula closure should be performed remains controversial.

Aged↗

PubMed1997

Enhancement of tumor cell susceptibility to tumor-infiltrating lymphocytes by cisplatin.

Some means of enhancing the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TIL) are required in adoptive immunotherapy. This study was designed to investigate whether or not tumor cell lysis by TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. Autologous tumor cells and established cancer cell lines, including KATO-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the production of TNF alpha from TIL were analyzed. Tumor cells treated with 2 micrograms/ml cisplatin for 12 h in vitro were more susceptible to bulk-cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor cells showed a higher binding ratio to TIL than did non-treated tumor cells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of tumor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhancement of cytotoxic activity by TIL in cisplatin-treated tumor cells was caused by a higher binding ratio to TIL and higher susceptibility to the TNF produced by TIL.

Antigens, Neoplasm↗

PubMed1996

Synergistic effects of tamoxifen and cepharanthine for circumventing the multidrug resistance.

We examined the synergistic effects of tamoxifen (TAM) and cepharanthine (CEP) for doxorubicin (DOX) sensitivity using MTT assay. The augmentation of DOX sensitivity by TAM and CEP was significantly correlated with the P-glycoprotein expression. The cytotoxic effect of DOX with TAM and CEP was significantly higher than that of DOX alone, or DOX with TAM, and this synergistic effect was dominant in cell lines with high expression of P-glycoprotein. It was also examined that the intracellular concentration of DOX was increased in combined exposure of TAM and CEP, compared with the exposure of TAM, because TAM and CEP promoted the influx and inhibited the efflux of DOX. Thus, TAM and CEP might be able to circumvent DOX-resistance for treatment in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Tamoxifen circumvents the multidrug resistance in fresh human gastrointestinal cancer cells.

The resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. Tamoxifen (TAM) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we clarified the augmentation of DOX sensitivity by TAM using MTT assay in highly purified fresh human tumor cells obtained from 85 cancer patients. Moreover, the correlation between DOX sensitivity and P-glycoprotein expression was assessed by flow cytometry. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by TAM in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of TAM on cytotoxicity and P-glycoprotein expression. The concentration of DOX in tumor cells was increased in combined exposure of TAM with DOX, compared with the exposure of DOX alone. Thus, TAM might be able to circumvent DOX-resistance for treatment in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Nodular lymphoid hyperplasia of the terminal ileum: report of a case and the findings of an immunological analysis.

The immunological and immunohistochemical characteristics of a patient with nodular lymphoid hyperplasia (NLH) of the terminal ileum were investigated pre- and post-operatively. The patient presented with diarrhea, lower abdominal pain, and weight loss, and an abdominal X-ray following barium enema revealed multiple small nodules in the terminal ileum which were subsequently confirmed to be NLH by histological examination. Preoperatively, although the serum immunoglobulin levels were normal, the T-cell responses in the peripheral blood, including the phytohemagglutinin (PHA)-blastogenesis and the T4/T8 ratio, were impaired. However, following an ileocecal resection, the PHA-blastogenesis became augmented and the T4/T8 ratio recovered to within the normal range. The immunohistochemical findings revealed a more marked accumulation of T cells in the interstitium around the hyperplastic follicles than in the interstitium of the normal intestine.

CD4-CD8 Ratio↗

PubMed1996

Clinical evaluation of chemosensitivity testing for patients with colorectal cancer using MTT assay.

PURPOSE: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. The chemosensitivity test should be performed to individualize the chemotherapy for patients with colorectal cancer, which is less sensitive for anticancer drugs. The present study was designed to determine the chemosensitivity in fresh human colorectal cancer, using highly purified tumor cells, and the correlation of this sensitivity with clinical response. METHODS: We determined the chemosensitivity for cisplatin, mitomycin C, adriamycin, and 5-fluorouracil in vitro in 93 fresh human colorectal cancers using the MTT assay and performed chemotherapy according to results of the MTT assay. RESULTS: Inhibition rate of tumor cells for cisplatin was higher than those for other drugs. Fifteen patients who have evaluable lesions received chemotherapy according to results of the MTT assay. Clinical responses were obtained in 5 of 15 patients, and the inhibition rate for cisplatin was higher in responders than in nonresponders. CONCLUSIONS: It is suggested that the chemotherapy according to results of the MTT assay is effective in patients with colorectal cancer.

Adult↗

PubMed1996

Reconstruction with bilateral gluteus maximus myocutaneous rotation flap after wide local excision for perianal extramammary Paget's disease. Report of two cases.

PURPOSE: Extramammary Paget's disease is a rare dermatosis. Wide local excision is recommended in patients with perianal extramammary Paget's disease. After wide local excision, it is necessary to do reconstruction, with preservation of bowel function. We present here two cases of perianal Paget's disease, in which the patients were treated by reconstruction with bilateral gluteus maximus myocutaneous rotation flap after wide local excision. PATIENTS AND METHODS: A 55-year-old woman and 58-year-old man were admitted with anal pain and bleeding. Histologic examination of the perianal lesion revealed the presence of typical Paget's cells, and no underlying carcinoma and no distant metastasis was detected in either patient. Wide local excision, including the rectal mucosa, was performed, with reference to intraoperative frozen sections. Surgical defect was overlapped with bilateral gluteus maximus myocutaneous rotation flap, and the anus was reconstructed. RESULTS: Postoperative bowel function and quality of life were well preserved, and flaps healed satisfactorily. Patients have had no recurrence and have been able to return to work. CONCLUSION: Bilateral gluteus maximus rotation flap may be useful after wide local excision of perianal extramammary Paget's disease without underlying invasive carcinoma.

Anal Canal↗

PubMed1996

Clonal and functional analysis for the augmentation of tumour-infiltrating lymphocytes by interleukin 4.

In the adoptive immunotherapy for cancer, the amounts of induced effector cells play a major role in improving therapeutic efficacy. We have already demonstrated that interleukin 4 (IL-4) augments proliferation of tumour-infiltrating lymphocytes (TILs) without altering the cytotoxic activity against autologous tumour cells. The present study is designed to investigate how IL-4 augments TILs by using established TIL clones in terms of IL-2/IL-2 receptor system. CD4+, CD8+ and CD4+ CD8+ (double positive) TIL clones were established from cancer patients. At clonal level, IL-4 augmented the proliferation of IL-2-activated TIL clones irrespective of phenotypes. In order to clarify the mechanism of IL-4 at clonal level, the blocking assay by anti-IL-2 receptor alpha and beta chain and binding assay of IL-2 on the cell surface and the measurement of the internalisation of IL-2 in the cell were performed. It was clarified that IL-4 up-regulated the IL-2 receptor and then augmented the action of IL-2 molecule on the cell surface stimulated by IL-4. Furthermore, binding IL-2 internalised rapidly into the cells. Thus, it is suggested that signal transduction is augmented and proliferation of TILs is enhanced by IL-4 via the action of IL-2/IL-2 receptor system.

DNA↗

PubMed1996

Fibronectin promotes the proliferation of cytotoxic T lymphocytes generated from cancer patients.

We studied whether fibronectin (FN) enhances the activity of autologous tumour-reactive cytotoxic T lymphocytes (CTLs) generated from cancer patients. The proliferation of CTLs stimulated by immobilised anti-CD3 monoclonal antibody and interleukin 2 (IL-2) was enhanced three or four times by immobilised FN. whereas soluble FN did not alter the DNA synthesis of CTLs. Moreover, the cytotoxic activity of CTLs was augmented by FN stimulation against autologous tumour cells [4 h 51Cr release assay: FN(+) 16.7 +/- 4.7% vs FN (-) 11.8 +/- 3.1%; 16 h 51Cr release assay: FN(+) 24.8 +/- 4.7% vs FN (-) 16.5 +/- 5.7%, P<0.05]. The major cell surface phenotype of CTLs with FN was CD3+, CD4+ and CD25+ in 6 weeks' culture. Cytotoxicity against autologous tumour cells was inhibited by anti-HLA class I monoclonal antibody (MAb). The autologous tumour-killing activity of CTLs was suppressed by the elimination of CD4+ cells. Moreover, the cytokine production of CTLs was augmented by FN stimulation. Especially, the production of IL-2, interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly augmented by FN stimulation (P<0.05). Thus, CTLs generated by FN might have both killer and helper functions, since they could lyse autologous tumour cells and secrete various cytokines, including IL-2.

Adult↗

PubMed1996

Hepatic actinomycosis infiltrating the diaphragm and right lung.

Hepatic actinomycosis is a rare infectious disease caused by an anaerobic gram-positive bacterium of the genus Actinomyces. Herein, we describe an unusual case of hepatic actinomycosis involving the diaphragm and right lung. A 41-yr-old man was admitted to Wakayama Medical School Hospital presenting with right back pain and cough. Computed tomography and magnetic resonance image revealed a 5 x 10 cm tumor in the anterior superior segment of the liver, which extended to the diaphragm and right lung. Angiography demonstrated a hypervascular tumor and the enlarged right inferior phrenic artery feeding around the tumor. The patient underwent a hepatectomy with partial resections of the diaphragm and the right middle pulmonary lobe. Microscopically, the specimen showed sulfur granules and was positive for Gram stain and Grocott stain and negative for Ziehl-Neelsen stain. These findings were consistent with actinomycosis of the liver. His postoperative course was uneventful and no recurrence was observed 1 yr postoperatively. Although there are at least 36 well-documented cases until 1993, no other report has been found infiltrating the diaphragm and lung.

Actinomycosis↗

PubMed1995

Clinical significance of quantitative analysis of carcinoembryonic antigen assessed by flow cytometry in fresh human gastric cancer cells.

The expression of carcinoembryonic antigen(CEA) on tumor cells freshly excised from 51 patients with gastric cancer was studied using flow cytometry. The expression of CEA by flow cytometry was more quantitative than that by immunohistochemical staining. There was no relationship between the fluorescence intensity assessed by flow cytometry and serum CEA levels, except for patients with a high titer of serum CEA. The patients with high grade CEA expression on tumor cells by flow cytometry had poor prognoses, compared to patients with low CEA expression in undifferentiated gastric cancer. Thus, it is suggested that the quantitative CEA expression on tumor cells by flow cytometry could be a useful prognostic marker in postoperative gastric cancer patients.

Adenocarcinoma↗

PubMed1995

Generation of CD4+ cytotoxic T lymphocytes stimulated by immobilized anti-CD3 monoclonal antibody and interleukin-2 in cancer patients.

The proliferation of autologous tumor-reactive cytotoxic T lymphocytes (CTL), induced by autologous mixed lymphocyte tumor-cell culture, was remarkably enhanced by activation with immobilized anti-CD3 monoclonal antibody (MAb) and interleukin-2 (IL-2), as compared with IL-2 alone. The activated CTL exhibited high cytotoxicity against autologous tumor cells. Cytotoxicity against autologous tumor cells was inhibited by anti-HLA-DR MAb. In negative selection with immunomagnetic beads, cytotoxicity against autologous tumor cells was inhibited by the elimination of CD4+ cells. The major cell-surface antigens of the activated CTL were CD3+, CD4+, CD25+, CD45RO+ and CD45RA-, suggesting helper T cells, and the activated CTL produced IL-2. It is concluded that the CTL activated by immobilized anti-CD3 MAb and IL-2 were CD4 cells that had both killer and helper functions. Our findings indicate that adoptive immunotherapy using these activated CTL would be effective in cancer patients.

Antibodies, Monoclonal↗

PubMed1995

[Effects of chemotherapy on the basis of the results of MTT assay for patients with gastrointestinal cancer].

The chemosensitivity test should be performed to individualize the chemotherapy for patients with gastrointestinal cancer, which is one of the tumors most refractory to treatment by anticancer drugs. The present study was designed to determine the chemosensitivity in fresh human gastrointestinal cancer, using highly purified tumor cells, and the correlation of this sensitivity with clinical response. The clinical responses were obtained in 15 of the 25 patients, and 5 of the 15 patients with gastric cancer and colorectal cancer, respectively. The inhibition rates for anticancer drugs in responders were higher than in nonresponders. Thus, it is suggested that the chemotherapy according to the results of the MTT assay is effective in patients with gastrointestinal cancer.

Antineoplastic Agents↗