Cancer biotherapy最新文献

{"title":"The integration of high-dose chemotherapy and biotherapy: initial 5-year experience with autologous bone marrow transplantation in a comprehensive community cancer center.","authors":"R O Dillman,&nbsp;N M Barth,&nbsp;K Mahdavi,&nbsp;L A VanderMolen,&nbsp;S K Nayak,&nbsp;A O'Connor","doi":"10.1089/cbr.1995.10.25","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.25","url":null,"abstract":"<p><p>Perhaps the best example of the integration of chemotherapy and biotherapy is autologous stem cell rescue following high dose chemotherapy. This analysis was undertaken to determine the outcome for patients treated in an autologous bone marrow transplant program, which was initiated in January 1989, and to illustrate the impact which biological response modifiers have had on the toxicity, survival, and costs associated with this aggressive treatment approach. Patients with metastatic cancer and good performance status were treated according to disease-specific treatment protocols. Peripheral blood stem cells [PBSC] came into use in 1990, hematopoietic colony stimulating factors [CSFs] in 1991. Outcome was monitored prospectively from the inception of the program. Five years after the program's inception, 75 patients had undergone 96 intensive chemotherapy treatments followed by autologous PBSC rescue. This included 35 patients with breast cancer, 15 with lymphoma or Hodgkin's Disease, five ovary, four melanoma, three sarcoma, three lung cancer, three leukemia, three testicular, two myeloma, one non-lung small cell carcinoma, and one medulloblastoma. Twenty-one patients underwent back-to-back cycles of intensive therapy and rescue; 14 of whom had breast cancer. Twelve patients were treated in 1989, 14 in 1990, 18 in 1991, 14 in 1992, and 17 in 1993. While four of the first 12 patients died within 60 days of reinfusion of cells in 1989, no patients have died within this time frame as a direct result of therapy during the subsequent four years. No patients have been lost to follow-up. Median survival was only eight months in 1989, but has not been reached for subsequent years. For all patients, median failure-free survival (FFS) is 17.2 months; 1-year FFS is 57%, 2-year 36%, and 3-year 29%. Median overall survival (OS) is 30.4 months; 1-year OS 66%, 2-year 52%, and 3-year 42%. From 1990-1993, for patients with metastatic breast cancer (21), and recurrent lymphoma (15), FFS and OS are comparable to the best results published from academic teaching hospitals. Twenty-one patients have survived over two years, 18 of whom continue in remission. Patients were hospitalized for an average of 31 days in 1989, 28.9 in 1990, 24.5 in 1991, and only 13.0-14.0 days in 1992-1993. Two patients were treated entirely as outpatients. Average hospital charges for the 96 treatments have been $120,000 with a range of $15,000 to $461,000, and currently average around $100,000.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 1","pages":"25-36"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18783198","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}

{"title":"Interferon-alpha/5-fluorouracil: a novel outpatient chemo/immunotherapy for progressive metastatic renal cell carcinoma.","authors":"E Lopez Hanninen,&nbsp;H Poliwoda,&nbsp;J Atzpodien","doi":"10.1089/cbr.1995.10.21","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.21","url":null,"abstract":"<p><p>In metastatic renal cell carcinoma, most conventional antineoplastic drugs have yielded no or little efficacy. To evaluate the tolerance and therapeutic efficacy of second line chemo/immunotherapies, we treated patients with advanced metastatic renal cell carcinoma upon progression after previous antineoplastic therapy employing an outpatient combination of subcutaneous (SC) recombinant interferon-alpha (rIFN-alpha) and intravenous (IV) 5-fluorouracil(5-FU). Thirty-three patients with metastatic renal cell carcinoma received SC doses thrice weekly of rIFN-alpha at 10 million U/m2 over 8 consecutive weeks. Additionally, patients received IV 5-FU at 750 mg/m2 in weeks 1-3 and 5-7; treatment cycles were repeated until disease progression. Of 33 patients, one achieved a complete remission (response duration, 24 months) and two patients presented with partial remissions (median response duration, 7 months) of pulmonary metastases upon rIFN-alpha/5-FU after failing SC recombinant interleukin-2 (rIL-2) and rIFN-alpha. The present chemo/immunotherapy regimen was overall well tolerated with low to moderate systemic toxicity and predominantly constitutional symptoms i.e., fever, chills, and malaise. In summary, the second line outpatient chemo/immunotherapy regimen of SC rIFN-alpha/IV 5-FU demonstrated a limited albeit significant efficacy in pretreated patients with progressive metastatic renal cell cancer.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 1","pages":"21-4"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18783197","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}

{"title":"In vitro cell-mediated immune responses induced by a polyvalent allogeneic melanoma vaccine.","authors":"A Adler,&nbsp;R Oraz,&nbsp;J C Bystryn","doi":"10.1089/cbr.1995.10.211","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.211","url":null,"abstract":"<p><p>Peripheral mononuclear cells (PMNC) from 18 melanoma were monitored for vaccine-related changes in their immune responses by measuring functional activity and phenotypic expression of PMNC prior to- and following 4-6 vaccinations. Assays included: cytolytic responses directed against melanoma cell lines included in the vaccine (M20, M14, HM54 and SKMel28), control melanoma (SKMel23) and non-melanoma (SKCo1, K562 and Daudi) cell lines. Direct lytic responses were significantly enhanced following vaccine treatment, mainly against M20 cell line and was further augmented following In Vitro Stimulation (IVS) by Mit-C-treated M20 or M14 cells. No evidence was found of augmentation of NK or LAK activity by vaccine treatment. Significantly enhanced proliferative responses to of vaccine-treated patients' PMNC to melanoma cell lines were also observed. The human melanoma cell lines used for vaccine preparation (M14, M20 and SKMel28) are high expressors of HLA class I, while high expression of HLA-DR only on M20 cells. Cell surface markers' study indicate a shift in CD4/CD8 ratio from 1.1 to 2.1 and increase in CD25 and HLA-DR positive cells. In M20-stimulated cultures of post-vaccine patients' PMNC the predominant phenotype was CD3+/CD4+. In conclusion, we have demonstrated that treatment with polyvalent allogeneic melanoma vaccine significantly augments T-cell mediated CD3+/CD4+), anti-melanoma lytic and proliferative responses, non-MHC-restricted.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"211-24"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530211","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}

{"title":"Selenium (Se) cytotoxicity in drug sensitive and drug resistant murine tumour.","authors":"J Shallom,&nbsp;A Juvekar,&nbsp;M Chitnis","doi":"10.1089/cbr.1995.10.243","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.243","url":null,"abstract":"<p><p>Selenium is known to inhibit growth rate of neoplastic cells. We have investigated the role of selenium (Se) in resensitization of the adriamycin (ADR) resistant murine P388/ADR cells to the action of ADR. The experiments were performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se was observed to be dose dependent i.e. Se at a concentration of 5 x 10(-8)M resulted in potentiation of DNA biosynthesis whereas 5 x 10(-6)M and 5 x 10(-5)M Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR there was a further increase in inhibition of DNA biosynthesis. In P388/ADR cells, Se at 5 x 10(-6)M and 5 x 10(-8)M concentration resulted in inhibition of DNA biosynthesis, which increased further when combined with ADR indicating resensitization of these cells to the action of ADR. The inhibition was observed to be partially irreversible. These results were further confirmed in the in vivo and in vitro bioassays where the Se and Se+ ADR treatments resulted in increased lifespan of tumor bearing mice.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"243-8"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530214","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}

{"title":"Interleukin-15 and the growth of tumor derived activated T-cells.","authors":"W M Lewko,&nbsp;T L Smith,&nbsp;D J Bowman,&nbsp;R W Good,&nbsp;R K Oldham","doi":"10.1089/cbr.1995.10.13","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.13","url":null,"abstract":"<p><p>Interleukin-15 was tested to determine whether this recently discovered cytokine was capable of stimulating the growth of tumor derived activated T cells in culture (TDAC, also referred to as tumor infiltrating lymphocytes). When established cultures of IL-2 induced, IL-2 dependent TDAC were tested, IL-15 stimulated growth in a dose dependent manner, alone or in the presence of IL-2. One established TDAC was cultured with IL-15 alone for 18 passages over a 10 week period. Comparing IL-2 and IL-15 treated cultures, growth rate with IL-15 was slower. IL-15 doubled the secreted interferon alpha and granulocyte-macrophage colony stimulating factor. IL-15 and IL-2 were compared in primary TDAC cultures. IL-15 induced TDAC outgrowth in 3 of 6 cultures. IL-2 induced outgrowth in all 6. Tumor cells were eliminated as TDAC grew out in both IL-2 and IL-15 treated cultures. These results suggested that IL-15 like IL-2, is capable of stimulating the growth of TDAC with antitumor activity, but with certain distinct effects which may be of interest therapeutically.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 1","pages":"13-20"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18780819","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}

{"title":"Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.","authors":"Y Kobayashi,&nbsp;K Kariya,&nbsp;K Saigenji,&nbsp;K Nakamura","doi":"10.1089/cbr.1994.9.63","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.63","url":null,"abstract":"<p><p>The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based on SOD activity in tumor tissue.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 1","pages":"63-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811600","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}

{"title":"Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.","authors":"B H Lau,&nbsp;H C Ruckle,&nbsp;T Botolazzo,&nbsp;P D Lui","doi":"10.1089/cbr.1994.9.153","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.153","url":null,"abstract":"<p><p>Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"153-61"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812769","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}

{"title":"Leukocyte-induced angiogenesis and subcutaneous growth of B16 melanoma.","authors":"M Gutman,&nbsp;R K Singh,&nbsp;S Yoon,&nbsp;K Xie,&nbsp;C D Bucana,&nbsp;I J Fidler","doi":"10.1089/cbr.1994.9.163","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.163","url":null,"abstract":"<p><p>We investigated the mechanism(s) by which systemic administration of doxorubicin (DXR) produced growth retardation of B16 melanomas in the subcutis of syngeneic mice. DXR or saline was injected intravenously (i.v.) into C57BL/6 mice, and B16-BL6 cells were implanted subcutaneously (s.c.) on day 3, 7, or 21 after DXR treatment. In the DXR-pretreated mice, the tumors grew at a slower rate than in control (saline-treated) mice. The experiments were repeated with a B16 variant resistant to DXR with similar results. Tumor growth retardation correlated with extent of myelosuppression monitored by counting bone marrow cells, circulating leukocytes and peritoneal macrophages. In DXR-pretreated mice reconstituted with 1 x 10(7) viable syngeneic spleen cells, the s.c. tumors grew at a rate similar to that in control mice. DXR treatment and spleen cell reconstitution experiments were repeated in BALB/c athymic nude mice. The results were very similar. The growth of s.c. tumors was directly correlated with the degree of peritumoral vascularity. These data indicate that in addition to its well-documented direct antitumor effects, DXR may produce retardation of tumor growth by producing myelosuppression and, hence, inhibition of host cell-induced tumor angiogenesis.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 2","pages":"163-70"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18535969","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}

{"title":"Enhancement of anti-cancer activity of cisdiaminedichloroplatinum by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) in vitro.","authors":"Y Kobayashi,&nbsp;K Kariya,&nbsp;K Saigenji,&nbsp;K Nakamura","doi":"10.1089/cbr.1994.9.351","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.351","url":null,"abstract":"<p><p>The protein-bound polysaccharide of Coriolus versicolor QUEL (PS_K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the effects of PS-K on cancer cell lines following administration of the anti-cancer drug cisdiaminedichloroplatinum (cisplatin). Cell proliferation of each cell line was inhibited markedly by cisplatin from 0.5 to 5 micrograms/0.5 ml per well. Fifty percent of the inhibitory concentration (IC50) was 0.33 micrograms/0.5 ml per well in NRK-49F and human ovarian cancer cells, and 1.5 micrograms/0.5 ml per well in H4-II-E. PS-K 50 micrograms/0.5 ml per well prevented cytotoxicity due to cisplatin toward NRK-49F, but enhanced the cytotoxicity on H4-II-E and human ovarian cancer cells. Increase in lipid peroxide and decrease in SOD activity were observed following an IC50 dose of cisplatin. With PS-K 50 micrograms/0.5 ml per well, all the above were augmented in H4-II-E and ovarian cancer cells, but diminished in NRK-49F cell line. PS-K may have effect on cancer patients through its combining with cisplatin.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"351-8"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18721021","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}

{"title":"Antitumor effect of exogenous/endogenous TNF (EET) therapy with cyclophosphamide on C6 glioma in rat.","authors":"S Ohshiro,&nbsp;H Inagawa,&nbsp;G Soma,&nbsp;T Fukushima,&nbsp;M Tomonaga","doi":"10.1089/cbr.1994.9.359","DOIUrl":"https://doi.org/10.1089/cbr.1994.9.359","url":null,"abstract":"<p><p>We earlier reported that endogenous TNF could be induced in mice as well as in patients by successive administration of exogenous TNF as a primer and OK-432 as a trigger, and we termed this exogenous/endogenous TNF (EET) therapy. We studied the effect of EET therapy with cyclophosphamide (CY) on tumor-transplanted rats. In order to induce endogenous TNF, 5 x 10(5) U/kg of recombinant human TNF-S(AM2) (rTNF; 5.6x10(6) U/mg protein) was injected intravenously (iv) as a primer followed by injection of 25 KE/kg of OK-432 as a trigger. TNF activity induced in serum was about 500 U/ml. Only 1 U/g of TNF was detected in the brain. To evaluate the antitumor effect, C6 glioma cells (1.6 x 10(4) cell/5 microliters) was transplanted into the brain. On day 7 of the transplantation, the rats were administered iv with CY (75 mg/kg), treated with EET therapy 7 days thereafter, and survival days were checked. No clear difference in survival days was observed between the rats treated with the EET and the control group. Three rats out of 6 treated with CY survived for more than 40 days, and all the rats treated with the combination of CY and EET continued to survive. The histological examination on day 44 revealed necrotic changes at the tumor lesions in all of the surviving rats, and the animals were evaluated as completely cured. These results suggest that applied treatment based on the EET therapy will be also effective against malignant brain tumors.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"9 4","pages":"359-67"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1994.9.359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18721022","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}