Biomedical subjects

H Yamaue

Publications and source records attributed to H Yamaue.

At least 55 records · Page 3Linked to original sources

PubMed1994

Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3'-truncated interleukin-2 gene.

Tumor-infiltrating lymphocytes (TILs), T lymphocytes associated with solid tumors that can be grown with interleukin (IL)-2 in vitro, preferentially accumulate at tumor sites after adoptive transfer. Therefore, TILs can be considered for use as cellular vehicles in gene therapy. We transduced melanoma TILs with the IL-2 gene and clarified functional characteristics of the TIL transductants. TILs transduced with 3'-end-truncated IL-2 gene (480 bp) produced high amounts of IL-2 detected in supernatants when compared to TILs transduced with the native IL-2 gene containing 3'-end adenine-thymidine (AT)-rich sequences (650 bp). The level of IL-2 in supernatants was higher with the addition of anti-Tac antibody (Ab) to block the consumption of IL-2 by the TILs. These TILs could proliferate autonomously in the absence of exogenous IL-2, and the proliferation of TILs could be completely blocked by anti-IL-2 Ab or anti-IL-2 receptor Ab. Thus TILs transduced with IL-2 gene can proliferate through the autocrine loop. However, the expression of IL-2 from TILs transduced with the IL-2 gene was downregulated after 2 to 3 weeks of G418 selection. Our study indicates the feasibility of transduction and expression of a truncated 480-bp IL-2 gene into TILs and the possibility of employing adoptive immunotherapy protocols using TILs modified with this IL-2 gene.

Base Sequence↗

PubMed1993

Expression of carcinoembryonic antigen in fresh human gastric cancer cells assessed by flow cytometry.

The expression of carcinoembryonic antigen (CEA) by tumor cells from freshly excised human gastric cancers was investigated using flow cytometry (FCM). Highly purified fresh human cancer cells were obtained from solid tumors in 20 patients and from malignant ascites in 6 patients. Thirteen of the 26 tumors were positive for CEA by FCM. CEA expression was more common in well-differentiated tumors than in poorly differentiated tumors. CEA expression was investigated by both FCM and immunohistochemistry in 9 patients, and the two methods agreed in 8 of them. However, quantitative evaluation of CEA expression could only be performed by FCM and not by immunohistochemical staining. FCM could analyze the expression of CEA not only on the cell membrane but also in the cytoplasm, by using gastric cancer cells with or without Triton X-100 treatment. Thus, this study showed that CEA expression can be determined and evaluated quantitatively by FCM.

Aged↗

PubMed1993

An autoreactive T cell clone generated in the autologous mixed lymphocyte reaction in a patient with gastric carcinoma.

Autoreactive T cell clones were established from a patient with early gastric carcinoma and a healthy control in order to investigate the mechanism of suppression of autologous mixed lymphocyte reaction (AMLR) and its significance in immune surveillance against tumor. Clone 3F6 from the gastric carcinoma patient responded to only autologous non-T cells with less reactivity than 4 clones from the control subject. The proliferative response of clone 3F6 to interleukin-2 and immobilized anti-CD3 antibody was also suppressed when compared with the control clones. Autoreactive T cells were able to kill tumor cells and autologous PHA-blasts. The cytotoxic activity of clone 3F6 was also markedly suppressed when compared with the control clones. This data suggests that autoreactive T cells may be impaired in cancer patients and that this immunological disorder might cause the defective immune surveillance against tumors.

Autoimmunity↗

PubMed1992

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients.

The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR-killer cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumor-killing activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.

Adult↗

PubMed1992

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged↗

PubMed1992

In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan.

The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent.

Antigens, Surface↗

PubMed1992

The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumor-infiltrating lymphocytes from patients with malignant tumor.

In adoptive immunotherapy, the number of effector cells is one of the major factors relating to the therapeutic efficacy. We demonstrated that tumor-infiltrating lymphocytes (TILs) were stimulated to proliferate by incubation with interleukin 2 (IL-2) plus interleukin 4 (IL-4). TILs cultured with IL-2 plus IL-4 increased 3.1-fold more than TILs cultured with IL-2 alone. However, IL-4 did not alter the cytotoxic activity of TILs against autologous tumor cells and established tumor cell lines. It is suggested that IL-2 receptor is related to the mechanism of the proliferation of activated TILs cultured by combination with IL-2 and IL-4. Thus, the combination of IL-2 and IL-4 may increase the efficacy of adoptive immunotherapy using activated TILs.

Cytotoxicity, Immunologic↗

PubMed1992

Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432.

We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

Antigens, Neoplasm↗

PubMed1992

In vitro augmentation of the cytotoxic activity of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes by famotidine in cancer patients.

We investigated the in vitro effects of famotidine on the cytotoxic activity of peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs). The cytotoxic activity of PBMC was augmented by famotidine at a concentration of 10 ng/ml, which is equivalent to the serum level achieved by the intravenous administration of a dose of 20 mg. This response to famotidine was seen only in cancer patients. Both the cytotoxic activity and DNA synthesis of activated TILs were increased by the combination of interleukin-2 and 1 microgram/ml of famotidine. Augmentation of cytotoxic activity by famotidine occurred independently of any decrease in the population of suppressor T-cells. Thus, famotidine may have the potential to be used in adoptive immunotherapy with TILs for cancer patients.

Antigens, CD↗

PubMed1992

Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay.

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).

Adult↗

PubMed1991

Augmentation of cytotoxic activity by combination with interleukin 2 and interferon gamma.

The synergy of cytotoxic activity by interleukin 2 (IL-2) and interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the stronger cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the killer cell function, the cells were stimulated with IFN-gamma after washing of IL-2 or stimulated by IFN-gamma at various timing and duration without washing of IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to cytotoxic activity. The similar augmentation of cytotoxic activity was observed by the addition of IFN-gamma at any incubation periods with IL-2, compared with stimulation with IL-2 or IFN-gamma alone. The phenotypes of the killer cells by stimulation with IL-2, IFN-gamma alone or IL-2 plus IFN-gamma were mainly CD2+, CD16+, indicating the activated natural killer cells.

Cytotoxicity, Immunologic↗

PubMed1991

[Nasobiliary drainage for spontaneous bile peritonitis due to cholangiocarcinoma].

We report a case of cholangiocarcinoma presented with bile peritonitis, in which endoscopic nasobiliary drainage (ENBD) as well as pleural and abdominal drainages improved the general condition leading to a radical operation. The case was a 79-year-old woman with the chief complaints of fever and right hypochondralgia due to pleural effusion and infected ascites contaminated with bile including E. coli. However gall-stones were not recognized in any biliary trees. US-guided drainage was performed into the pleural and abdominal cavities because of poor condition. After continuous drainages, peritonitis was improved, but hematoemesis and tarry stool appeared. Emergent endoscopy revealed a multiple gastric ulcer, and the bleeding was stopped by an injection of ethanol. ERCP findings revealed a cholangiocarcinoma in superior and middle portion of the bile duct obstructed nearly completely. After improvement in general condition by ENBD, cholecystectomy, resection of extrahepatic bile duct and subtotal gastrectomy were performed followed the reconstruction with Roux-en-Y method. Postoperative course was uneventful and the patient was discharged at the postoperative 35th day. Thus, the appropriate and opportune multiple biliary drainages can save a patient with cholangiocarcinoma in poor condition and lead to tolerate the operation even if he or she is suffering from severe bile peritonitis.

Adenoma, Bile Duct↗

PubMed1991

Endoscopic microwave coagulation therapy for villous adenoma of the duodenum--a case report.

The effects of endoscopic microwave coagulation therapy on duodenal adenoma in a 58-year-old man are reported. The patient had a 35-mm sessile tubulo-villous adenoma in the duodenal bulb. Endoscopic polypectomy followed by microwave coagulation therapy for duodenal adenoma was performed to avoid a major surgical procedure which would disturb the physiological functions of the gastrointestinal tract. After partial polypectomy which included the core of the adenoma, the entire remaining adenoma was destroyed after three microwave therapy sessions. During a follow-up period of 14 months, neither endoscopic nor histologic evidence of recurrence has been noted. Endoscopic microwave coagulation therapy is considered to be useful in the treatment of large sessile duodenal villous adenoma, provided that repeated endoscopic follow-up surveillance is also performed.

Adenoma↗

PubMed1991

Chemosensitivity testing with highly purified fresh human tumour cells with the MTT colorimetric assay.

A major problem associated with the succinate dehydrogenase inhibition (SDI) test using tetrazolium dye (MTT) as a cancer chemosensitivity testing is the contamination of non-malignant cells in the tumour tissues. Highly purified fresh human tumour cells from 44 solid tumours and 24 malignant ascites were used for the MTT assay. The purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients. The OD570 obtained from tumour cells alone was higher than that from non-malignant cells. The chemosensitivity of tumour cells was distinct from that of non-malignant cells. Moreover, the chemosensitivity of highly purified tumour cells was also distinct from that of non-purified cells just separated from tumour tissues. 31 of the 68 patients had evaluable lesions, and received cancer chemotherapy according to the results of MTT assay using highly purified tumour cells. A clinical response was obtained in 10 of the 31 patients (response rate = 32.3%, 5 complete responses, 5 partial responses).

Adolescent↗

PubMed1991

Cisplatin treatment renders tumor cells more susceptible to attack by lymphokine-activated killer cells.

We investigated whether tumor cell lysis by lymphokine-activated killer (LAK) cells was enhanced by treatment of the tumor cells with cisplatin (CDDP) in vitro. Tumor cells were treated with CDDP in vitro, and the cytotoxic activity for LAK cells was measured by 4-h 51Cr-release assay. The alterations of succinate dehydrogenase (SD) activity, and DNA,RNA synthesis of tumor cells were analysed. The susceptibility of CDDP-treated (2 micrograms/ml, 2h) Daudi and KATO-III cells to lysis by short term-cultured LAK cells was enhanced, as was the susceptibility of CDDP-treated (2 micrograms/ml, 12h) autologous tumor and Daudi cells to lysis by long term-cultured LAK cells. SD activity and DNA synthesis in tumor cells were impaired by 12-h treatment with 2 micrograms/ml of CDDP, whereas those were not altered by 2-h treatment with 2 micrograms/ml of CDDP. The enhancement of the susceptibility of CDDP-treated tumor cells to long term-cultured LAK cells was thus elucidated; it was shown to be due to alterations of the tumor cells with regard to their SD activity and DNA synthesis. It is suggested that the combined therapy with CDDP and LAK cells offers hope for increasing the response rate and the long-term survival of cancer patients.

Cisplatin↗

PubMed1990

[Combination of adoptive immunotherapy and chemotherapy against advanced cancer with peritoneal dissemination].

In a case of advanced gastric cancer with bilateral Krukenberg's tumors and peritonitis carcinomatosa, total gastrectomy, splenectomy and bilateral oophorectomy was performed. Since progressive peritoneal dissemination was recognized, 150 mg of CDDP and 10 mg of MMC which were proved to be effective by chemosensitivity test of anticancer drugs were administered intraperitoneally. After one month, ascites increased. So LAK cells and TIL were transferred intraperitoneally 6 times. With this treatment ascitic collection remarkably decreased, the performance status improved and serum level of IAP and CA125 normalized. Thus, it is clarified that the combination of adoptive immunotherapy and chemotherapy possesses therapeutic efficacy against advanced gastric cancer with peritonitis carcinomatosa.

Adenocarcinoma, Mucinous↗

PubMed1990

Clinical evaluation of chemotherapy under angiotensin II-induced hypertension in patients with advanced cancer.

The clinical efficacy and indications for Angiotensin II (AT II)-induced hypertension chemotherapy were evaluated as a drug delivery system in 101 patients with advanced carcinoma. The sites of primary tumor studied included stomach (44), pancreas (18), colon (16), esophagus (6), bile duct (4), liver (3), breast (7) and 3 other single organs. Seventy four cases had distant metastases (lymph node (25), liver (29), peritoneum (16), and lung (4)). Additionally, the protocol was used 12 cases as postoperative adjuvant chemotherapy and 15 cases following exploratory laparotomy. The blood pressure was elevated to a level 1.5 times base-line. The regimens used consisted of MMC + ADR (55), FAM (38) and CDDP (8). The dosages administered were MMC 7 mg/m2, ADR 14 mg/m2 and 5-FU 350 mg/m2. The cancer chemotherapy protocol with AT II was repeated for an average of 2.6 cycles with a 2-3 week interval. The drug concentration in tumor tissues was increased 1.7 fold by AT II treatment. The response rate was 15.8% (CR 7 and PR 9), and in those patients with lymph node, liver and peritoneal metastases was 48.0, 6.9 and 6.3%, respectively. The serum levels of tumor markers decreased in 9 patients. Subjective symptoms, such as hoarseness, edema and pain, were improved. The mean survival in patients with distant metastasis who responded was 343 days, and in nonresponders was only 168 days (p less than 0.05). The side effects of this therapy were slight, typically being grade 1 and 2. Thus, the chemotherapeutic agents studied in conjunction with AT II were effective in patients with lymph node metastasis. Additionally, this regimen could be performed safely with minimal side effects.

Aged↗

PubMed1990

[Augmentation of cytotoxic activity by combination with interleukin 2 and interferon gamma].

The synergy of cytotoxic activity by Interleukin 2 (IL-2) and Interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the maximum cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the synergy of killer cell function, IFN-gamma was stimulated after washing-out IL-2 or stimulated at various timing and duration without washing-out IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to killer activity. The similar augmentation of killer activity was observed by the addition of IFN-gamma at any incubation period with IL-2, compared with that of stimulations IL-2 and IFN-gamma stimulation. The phenotypes of the killer cells by stimulation of IL-2, IFN-gamma alone or IL-2 and IFN-gamma were mainly CD2+, CD16+, namely, the phenotype of activated natural killer cells.

Cytotoxicity, Immunologic↗