Journal of biological response modifiers最新文献

Interferon protects normal human granulocyte/macrophage colony-forming cells from Ara-C cytotoxicity. 干扰素保护正常人粒细胞/巨噬细胞集落形成细胞免受Ara-C细胞毒性。

Journal of biological response modifiers Pub Date : 1990-12-01

C M Richman, C A Slapak, B Toh

引用次数: 0

A phase I study of high-dose interleukin-2 in combination with interferon-alpha 2b. 高剂量白介素-2联合干扰素- α 2b的I期研究。

Journal of biological response modifiers Pub Date : 1990-12-01

M Sznol, J W Mier, J Sparano, E R Gaynor, G R Weiss, K A Margolin, M H Bar, M J Hawkins, M B Atkins, J P Dutcher

{"title":"A phase I study of high-dose interleukin-2 in combination with interferon-alpha 2b.","authors":"M Sznol, J W Mier, J Sparano, E R Gaynor, G R Weiss, K A Margolin, M H Bar, M J Hawkins, M B Atkins, J P Dutcher","doi":"","DOIUrl":"","url":null,"abstract":"Our group and others have conducted phase II trials of high-dose interleukin-2 (IL-2) or IL-2 with the adoptive transfer of in vitro activated lymphocytes in patients with advanced malignancies. Although durable complete and partial responses were seen in patients with renal cell carcinoma and metastatic melanoma, overall response rates were low and toxicity was substantial. In preclinical models, the combination of IL-2 and interferon-alpha has synergistic antitumor activity. Based on these data, and our prior experience with high-dose IL-2 (Cetus), we conducted a trial to determine the maximum tolerated dose of IL-2 (0.4, 0.8, and 1.2 mg/m2) administered together with a fixed dose of interferon-alpha 2b (3 x 10(6) u/m2) intravenously every 8 h on days 1-5 and 15-19. Patients were monitored in the intensive care unit and given pressor support for hypotension as needed. Twenty-four patients were entered (6, 10, and 8 at each IL-2 dose, respectively; 14 renal cell carcinoma, 7 melanoma, 2 colon, and 1 hepatoma). The median age was 56 years, the male to female ratio was 19:5, and performance status was 0 or 1 (Eastern Cooperative Oncology Group) in all patients. Toxicity was similar at all dose levels, but the onset was earlier in the treatment course as the dose of IL-2 was escalated in successive cohorts; therefore, more doses were withheld at the higher dose levels. The major toxicities resulting in the interruption or stopping of treatment were hypotension requiring pressors, dyspnea, and neurotoxicity. Grade 1 or 2 fever, nausea and vomiting, fatigue, and cutaneous reactions were common at all dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 6","pages":"529-37"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice. 粒细胞集落刺激因子对抗癌药物致小鼠造血损伤的影响。

Journal of biological response modifiers Pub Date : 1990-12-01

Y Mizushima, T Morikage, T Kuwahara, S Yano

{"title":"Effects of granulocyte colony-stimulating factor on hematopoietic injury induced by anticancer drugs in mice.","authors":"Y Mizushima, T Morikage, T Kuwahara, S Yano","doi":"","DOIUrl":"","url":null,"abstract":"The in vivo effects of the subcutaneous administration of the granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced hematopoietic injury were evaluated in BALB/c mice. Mice treated with chemotherapeutic drugs were injected once a day for up to 12 days with 2 micrograms of recombinant human G-CSF, and following this, bone marrow cellularity, spleen weight, and peripheral blood cell counts were measured 24 h after cessation of the G-CSF treatment. Treatment of normal mice had minimal effect on the elevation of the white blood cell (WBC) count or on the hosts' resistance to K. pneumoniae infection. Spleen weight was significantly higher in normal mice treated with G-CSF, and the platelet counts were slightly lower. In mice treated with cyclophosphamide (150 mg/kg), G-CSF treatment caused an elevation of WBC and an enhancement of antibacterial resistance. Variable amounts of an accelerated recovery of neutrophils by G-CSF treatment was also observed in nimustine hydrochloride (50 mg/kg)-, mitomycin c (MMC) (8 mg/kg)-, or vindesine sulfate (VDS) (4 mg/kg)-treated mice. A significant decrease in PLT counts was observed in MMC- or VDS-treated hosts given G-CSF. These results indicate that administration of G-CSF may facilitate hematopoietic recovery in chemotherapy-treated cancer patients and that it may help them to increase their resistance to life-threatening infection. Conversely, treatment with G-CSF and chemotherapeutic drugs may cause a more severe thrombocytopenia than is observed with only chemotherapy treatment.","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 6","pages":"576-83"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12870689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Receptors for human plasminogen on the biological response modifier OK-432. 人纤溶酶原在生物反应修饰剂OK-432上的受体。

Journal of biological response modifiers Pub Date : 1990-12-01

M Ullberg, W Tewodros, G Kronvall

引用次数: 0

Priming effect of orally administered muramyl dipeptide on induction of endogenous tumor necrosis factor. 口服muramyl二肽诱导内源性肿瘤坏死因子的启动效应。

Journal of biological response modifiers Pub Date : 1990-12-01

T Okutomi, H Inagawa, T Nishizawa, H Oshima, G Soma, D Mizuno

引用次数: 0

Phase II evaluation of recombinant gamma-interferon in patients with advanced pancreatic carcinoma: a Southwest Oncology Group study. 重组γ -干扰素在晚期胰腺癌患者中的II期评估:一项西南肿瘤组的研究。

Journal of biological response modifiers Pub Date : 1990-12-01

D D Von Hoff, T R Fleming, J S Macdonald, P J Goodman, J Van Damme, T D Brown, T O'Rourke, L G Feun, M D Keppen

引用次数: 0

Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon-alpha 2a: clinical effects. 持续输注重组白细胞介素-2和间歇重组干扰素- 2a的临床效果。

Journal of biological response modifiers Pub Date : 1990-12-01

R M Bukowski, S Murthy, J Sergi, G T Budd, S McKeever, S V Medendorp, R Tubbs, V Gibson, J Finke

引用次数: 0

Immunotherapy with lymphokine-activated natural killer cells and recombinant interleukin-2: a feasibility trial in metastatic renal cell carcinoma. 淋巴因子活化的自然杀伤细胞和重组白细胞介素-2的免疫治疗:转移性肾细胞癌的可行性试验。

Journal of biological response modifiers Pub Date : 1990-12-01

T Hercend, F Farace, D Baume, F Charpentier, J P Droz, F Triebel, B Escudier

{"title":"Immunotherapy with lymphokine-activated natural killer cells and recombinant interleukin-2: a feasibility trial in metastatic renal cell carcinoma.","authors":"T Hercend, F Farace, D Baume, F Charpentier, J P Droz, F Triebel, B Escudier","doi":"","DOIUrl":"","url":null,"abstract":"Clinical immunotherapy trials have been performed recently where ex vivo interleukin-2 (IL-2)-activated peripheral blood mononuclear cells (i.e., the \"LAK\" cells) have been transfused in addition to IL-2 infusions. In such protocols, patients have received highly heterogeneous cell suspensions and the nature of the effector cells that may have contributed to tumor regression has remained unclear. In certain animal models, it has appeared that natural killer lymphocytes were the effector cell type responsible for tumor regression. To test whether NK cells could eventually be relevant for the treatment of human tumors, we have performed a feasibility trial where purified lymphokine-activated natural killer (LANAK) cells have been prepared and transfused to a limited series of renal cell carcinoma patients receiving IL-2 (continuous infusions at 3 x 10(6) U/m2/day). Natural killer lymphocytes (1-2 x 10(6] were purified from peripheral blood mononuclear cells and expanded during 4-5 weeks in the presence of IL-2 on microtiter plates containing feeder layers cells. In vitro, the resulting LANAK cell suspensions were 100 times (range of 2 to 10(3] more efficient against Daudi target cells than their autologous LAK counterparts. Twelve patients were included; 9 received the two planned courses of treatment with LANAK cells and IL-2. Overall toxicity was relatively moderate. Besides occasional chills, there were no apparent secondary effects due to cell infusions. The mean number of LANAK cells transfused per patients was 45.1 x 10(9), ranging from 7 to 125 x 10(9). The biodistribution of LANAK cells was similar to that reported previously for LAK cells with no preferential localization to tumor sites. We conclude from this study that using well-defined populations of effector lymphocytes is a feasible cellular therapy approach that may lead to improved understanding and efficacy of the novel immunotherapy methods.","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 6","pages":"546-55"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recombinant alpha-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo. 重组干扰素增强体内抗黑色素瘤单克隆抗体的肿瘤靶向性。

Journal of biological response modifiers Pub Date : 1990-12-01

J L Murray, A A Zukiwski, K Mujoo, M G Rosenblum

{"title":"Recombinant alpha-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo.","authors":"J L Murray, A A Zukiwski, K Mujoo, M G Rosenblum","doi":"","DOIUrl":"","url":null,"abstract":"To determine whether recombinant human alpha-interferon (rIFN alpha A) could enhance tumor uptake of an antimelanoma monoclonal antibody (Mab) 96.5 in vivo, groups of nude mice bearing P97 antigen-positive human melanoma subcutaneous xenografts were given i.m. injections of normal saline or rIFN alpha A daily for 10 days. On day 7, mice received either 5 micrograms of 111In-labeled Mab 96.5 or irrelevant 111In-labeled subclass-matched or non-subclass-matched control Mabs. Animals were killed 72 h later and the percent injected dose per gram (%ID/g) in tumor and normal organs was determined. There was a significant (p less than 0.001) increase in 96.5 in tumors of IFN-treated mice compared to saline-treated mice and mice receiving irrelevant Mabs. There was also a significantly increased uptake of 96.5 in blood, heart, lung, kidney, and muscle of IFN-treated vs. control mice (p less than 0.05). This finding was most likely due to increased antigen shedding since significant differences in %ID/g were not observed between IFN-treated and control mice bearing antigen-negative tumors. Furthermore, P97 content in tumor and tissues of IFN-treated mice bearing melanoma xenografts was significantly higher than in mice without tumors. In summary, IFN enhanced targeting of 96.5 via an antigen-specific mechanism. These data confirm and extend previous studies in other tumor systems, and suggest that clinical trials of Mabs plus IFN might be useful in overcoming poor Mab localization that occurs as a result of antigenic heterogeneity in humans.","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 6","pages":"556-63"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A phase II trial of recombinant tumor necrosis factor in patients with metastatic colorectal adenocarcinoma: a Southwest Oncology Group study. 重组肿瘤坏死因子在转移性结直肠癌患者中的II期试验:一项西南肿瘤组的研究。

Journal of biological response modifiers Pub Date : 1990-12-01

R P Whitehead, T Fleming, J S Macdonald, P J Goodman, J Neefe, T J Braun, L J Swinnen, E M Hersh

{"title":"A phase II trial of recombinant tumor necrosis factor in patients with metastatic colorectal adenocarcinoma: a Southwest Oncology Group study.","authors":"R P Whitehead, T Fleming, J S Macdonald, P J Goodman, J Neefe, T J Braun, L J Swinnen, E M Hersh","doi":"","DOIUrl":"","url":null,"abstract":"Tumor necrosis factor (TNF) induces hemorrhagic necrosis in the Meth A mouse tumor model and has shown cytostatic and cytotoxic antitumor effects against a wide range of human tumors both in vitro and as human tumor xenografts in nude mice. Because of in vitro activity against colorectal tumors and antitumor responses in colon cancer patients in phase I trials, this phase II study was undertaken. Patients were treated with TNF administered daily for 5 days/week every other week at a dose of 150 micrograms/m2/day as a 30-min i.v. infusion. One cycle consisted of 4 weeks of treatment over an 8-week period. Twenty-five patients have been entered into this study with three patients ineligible. The 22 eligible patients ranged in age from 38-73 years and had initial performance status of 0 in 10 patients, 1 in 10 patients, and 2 in 2 patients. No complete or partial responses were seen. Two patients had stable disease (no response) and 18 patients progressed. Two patients had no evaluation and were assumed to have had no response. The response rate is therefore 0%, with a 95% exact confidence interval of 0% to 15%. There was one grade 4 toxicity consisting of nausea and vomiting. Most common grade 3 toxicities were chills and fever in four patients, nausea and vomiting in three patients, and anemia and elevated liver enzymes in two patients. Headache, myalgia/arthralgia, and elevated serum triglycerides were frequently seen. Mildly elevated levels of fibrin split products were seen after TNF treatment in 5/13 evaluable patients and one ineligible patient.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"9 6","pages":"588-91"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0