Cancer biotherapy最新文献

{"title":"The tyrosine residue at position 97 in the VH CDR3 region of a mouse/human chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the TAG72 antigen.","authors":"J Xiang,&nbsp;E Liu,&nbsp;L T Delbaere,&nbsp;Z Chen,&nbsp;X Luo,&nbsp;Y Qi,&nbsp;C Rathgeber","doi":"10.1089/cbr.1993.8.253","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.253","url":null,"abstract":"<p><p>One amino acid, tyrosine at position 96 and 97 in the VH CDR3 region of a mouse/human chimeric anti-TAG72 antibody cB72.3m4 was substituted by the phenylalanine residue and by a number of amino acids from different amino acid groups by the site-directed mutagenesis technique. The expression vector mpSV2neo-EP1-Vm11-16C1 containing mutant VH region fragments (Vm11-16) as well as the immunoglobulin enhances (E), promoter (P1) and the human genomic C1 region fragments, were transfected into a heavy-chain-loss mutant cell line B72.3Mut(K), respectively. Mutant chimeric cB72.3m11-16 antibodies were purified from the transfectant supernates and compared based upon their binding affinity for the TAG72 antigen relative to that of the original cB72.3m4 antibody. The data showed that a single amino acid substitution of tyrosine by phenylalanine and a number of amino acids including serine, asparagine, histidine and arginine at position 97 in the VH CDR3 region all resulted in approximate 18-fold lower binding affinity, whereas the substitution of tyrosine by phenylalanine at position 96 in the VH CDR3 region did not affect the binding affinity of the cB72.3m4 antibody. This suggests that the tyrosine residue at position 97 in the VH CDR3 region is in a contact position in the B72.3/TAG72 antibody/antigen interaction, and that the terminal hydroxyl group of the position 97 tyrosine side-chain contributes hydrogen bonding to the TAG72 antigen, whereas the position 96 tyrosine side-chain does not.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 3","pages":"253-62"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803804","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":"Sensitization of P388 murine leukemia cells to epirubicin cytotoxicity by reserpine.","authors":"A Viladkar,&nbsp;M Chitnis","doi":"10.1089/cbr.1993.8.77","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.77","url":null,"abstract":"<p><p>Reserpine, the crystalline active substance isolated from the Rauvolfia plant, produces a characteristic vasodepressor effect in hypertensive patients. Apart from its antihypertensive property, reserpine also possesses transquillising and vasodepressor action, hence it is employed as supportive therapy in the treatment of cardiac disorders. Doxorubicin is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin is a derivative of doxorubicin having more favourable therapeutic index than doxorubicin and possessing less hematologic and cardiac toxicity at comparable doses. The data presented in this paper show the effect of reserpine as a chemosensitizer, when used in combination with epirubicin on P388 murine leukemia cells sensitive (P388/S) and resistant to doxorubicin (P388/DOX) cells. Inhibition of 3H-TdR incorporation into DNA was used as an index of the cytotoxic effects of drug when used alone or in combination. The combination of reserpine (1 microM) and epirubicin (1.7, 8.6 and 17.2 microM) indicated a significant enhancement in the DNA biosynthesis inhibition in P388/S and P388/DOX cell lines. The most prominent feature of the multidrug-resistant cell is the reduced accumulation of the drug intracellularly. P388/DOX cells showed less accumulation of epirubicin in the cell as compared to that of the parental cell line. Further studies demonstrated that reserpine significantly enhanced the intracellular accumulation of epirubicin in both the cell lines. The nature of DNA damage caused by the combination of reserpine and epirubicin was irreversible when studied in P388/DOX cell line. The combination of reserpine (5mg/kg) and epirubicin (1mg/kg) significantly potentiated the antitumor activity of epirubicin in P388/DOX tumor bearing mice. These studies suggest that reserpine can be used as an adjuvant in the cancer chemotherapy to potentiate the antiproliferative activity of anticancer drugs.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"77-85"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.77","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18811594","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":"Sensitivity to bleomycin and arabinoside cytosine in lymphocytes of patients affected by neuroblastoma and in those of their parents.","authors":"P Vernole,&nbsp;B Tedeschi,&nbsp;D Caporossi,&nbsp;B Nicoletti","doi":"10.1089/cbr.1993.8.87","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.87","url":null,"abstract":"<p><p>Chromosomal instability has been described in patients affected by various tumors. We previously reported a high sensitivity to fragile sites induction by aphidicolin in lymphocytes from patients affected by neuroblastoma and in those from their parents. In the search for the most suitable clastogenic agent to enhance the possible differences between healthy controls and patients affected by tumors, we have now tested two other drugs: bleomycin, a radiomimetic agent already used in vitro on chromosomes of patients affected by other tumors and arabinoside cytosine, an inhibitor of DNA polymerases alfa and beta. We observed a high sensitivity to bleomycin both in patients and in their parents, but to arabinoside cytosine only in NB patients. Moreover, the two drugs induced more fragile sites in 1p in patients and in their parents than in healthy controls. This phenomenon, which we already observed after treatment with aphidicolin, might be related to the frequent deletions and loss of heterozigosity in 1p in neuroblastoma cells.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.87","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18535965","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":"Protective effects of crocetin on the bladder toxicity induced by cyclophosphamide.","authors":"S C Nair,&nbsp;K R Panikkar,&nbsp;R K Parthod","doi":"10.1089/cbr.1993.8.339","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.339","url":null,"abstract":"<p><p>Cyclophosphamide (CX) has been widely used as an anticancer agent, however obtaining a maximum therapeutic potential for CX has remained a challenge, for generating undesired toxic side effects to the bladder. Crocetin, a natural carotenoid has been employed in the present studies to ameliorate the bladder toxicity of CX. Interestingly, crocetin at a dose of 50 mg/kg modulated the release of chloroacteldehyde, a urotoxic metabolite of CX in the urine of mice given combined treatment. Crocetin at the same dose significantly elevated Glutathione-S-Transferase enzyme activity both in the bladder and the liver of mice treated with CX. The exact mechanism of the protective effect of crocetin is not known, presumable it may act as an antioxidant, trapping and scavenging free radicals during the detoxification process. In Sarcoma-180 tumor bearing mice, crocetin has the ability to protect against CX induced bladder toxicity without altering its antitumor activity. Our studies are important to identify antioxidant rescue agents to overcome dose-limiting toxicity of CX.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 4","pages":"339-43"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18805277","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":"Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A lipid).","authors":"W Fujimaki,&nbsp;K Itoh,&nbsp;T An,&nbsp;J B Gano,&nbsp;M I Ross,&nbsp;P F Mansfield,&nbsp;C M Balch,&nbsp;L B Augustus,&nbsp;D D Karkevitch,&nbsp;D Johnston","doi":"10.1089/cbr.1993.8.307","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.307","url":null,"abstract":"<p><p>We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 4","pages":"307-18"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18803810","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":"Clinical and pharmacological study of intrahepatic artery infusion of thiotepa.","authors":"L G Feun,&nbsp;G Blyden,&nbsp;J Yrizarry,&nbsp;M Dorvil,&nbsp;S Waldman,&nbsp;P Benedetto,&nbsp;E Donnelly,&nbsp;J Curtas,&nbsp;M George,&nbsp;N Savaraj","doi":"10.1089/cbr.1993.8.43","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.43","url":null,"abstract":"<p><p>Twenty patients with primary or metastatic liver cancer were treated on a clinical and pharmacological study with intrahepatic artery infusion of Thiotepa. Toxicity was tolerable and included nausea and fatigue. Uncommon side effects were myelosuppression, abdominal pain and anemia. One patient with gallbladder cancer had a partial response for 11 (+) months. Recommended dose of Thiotepa for future Phase II clinical trials is 1.0 mg/kg. Pharmacokinetics of intrahepatic Thiotepa revealed an extraction ratio similar to that reported for cisplatin. The data suggest increased hepatic clearance for Thiotepa either by binding or metabolism.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"43-8"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812888","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":"Hormone receptor assays and their value in breast cancer therapy.","authors":"E V Gaffney,&nbsp;A T Sharmanov,&nbsp;W E Moody,&nbsp;D P Halpin,&nbsp;W S Blakemore,&nbsp;C B Elliott","doi":"10.1089/cbr.1993.8.17","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.17","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812884","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":"A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma.","authors":"P A Palmer,&nbsp;J Atzpodien,&nbsp;T Philip,&nbsp;S Negrier,&nbsp;H Kirchner,&nbsp;H Von der Maase,&nbsp;P Geertsen,&nbsp;P Evers,&nbsp;E Loriaux,&nbsp;R Oskam","doi":"10.1089/cbr.1993.8.123","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.123","url":null,"abstract":"<p><strong>Purpose: </strong>To compare 2 treatment modalities with recombinant Interleukin-2 (rIL-2) for patients with advanced Renal Cell carcinoma (RCC): continuous intravenous infusion (CIV) alone versus subcutaneous (s/c) rIL-2 + Interferon-alpha (IFN-alpha).</p><p><strong>Patients and methods: </strong>Data have been collected on 425 patients with RCC, treated CIV rIL-2 alone, (225 patients), or rIL-2 by the s/c route (200 patients). Patients receiving s/c rIL-2 also received s/c IFN-alpha both drugs being administered on an outpatient basis. Patients receiving CIV rIL-2 were treated as inpatients. Patient eligibility criteria were similar on all studies, and included patients with progressive, advanced disease, but with an ambulatory performance status.</p><p><strong>Results: </strong>The overall response rate for the CIV schedules was not significantly different from the s/c regimens: 15% (95% confidence limits (CL) 10-20%) vs 20% (95%CL 14-26%) with 4% CR in both approaches. Durable responses were seen in both CIV and s/c schedules and there was no evidence of a significant difference in survival in multivariate analysis. There was however an important shift in the toxicity profile. The s/c regimens do not induce a clinically detectable capillary leak syndrome, which is the dose limiting toxicity for CIV regimens.</p><p><strong>Conclusion: </strong>Although the introduction of CIV regimens of rIL-2 was a major step forward compared to high-dose bolus, because most patients could be treated in a normal oncology ward, the s/c schedule of rIL-2 + IFN-alpha offers the possibility of outpatient (home) therapy, with no evidence of a reduction in efficacy.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 2","pages":"123-36"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18805274","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":"Unique pancreatic carcinoma cDNA found via subtracted libraries with limited normal tissue and tumor from the same patient.","authors":"M M Kowalczuk,&nbsp;J E Lafuze,&nbsp;R J Goulet,&nbsp;J Goldman","doi":"10.1089/cbr.1993.8.57","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.57","url":null,"abstract":"<p><p>We have approached the problem of isolating clones unique to specific malignancies such as T-cell acute lymphoblastic leukemia (ALL) and pancreatic adenocarcinoma by using subtractive hybridization techniques. Our initial studies involved using normal donor tissue (i.e., normal blood donors for ALL and cadaver renal transplant donors for normal pancreatic tissue) and cultured malignant cell lines. It occurred to us that normal pancreatic tissue from the same patient source as that of the malignant tissue might subtract out normal sequences more readily and enrich clones unique to pancreatic adenocarcinoma because of patient/donor identity. Using such a method meant that the amounts of tissue for overcoming this obstacle. We constructed independent UNI-ZAP-XR cDNA libraries (normal and malignant) and used them to amplify either the normal or malignant cDNA prior to subtractive hybridization. We then obtained rescued single stranded cDNA from the malignant ZAP library. The RNA which was not hybridized was isolated. The process was repeated and a double subtraction was effected. The residual non-hybridized RNA was used as a template for first and second strand synthesis. After the EcoRI adaptors were ligated to the double stranded cDNA it was cloned into Lambda ZAP II arms to form a double subtracted malignant cDNA library. A subtracted probe was prepared from the double subtracted cDNA library. Single stranded cDNA was rescued, double stranded plasmid was made, the plasmid DNA was digested with EcoRI, the digested DNA was run on a 1% SeaPlaque gel, and the insert cDNA was recovered using Ultra-Free MC and Ultra-Free Probind filters. The subtracted malignant cDNA library was probed with the subtracted probe and with normal cDNA (obtained from the normal ZAP library) and those plaques which were positive per the subtracted probe and negative per the normal cDNA were isolated; their cDNA inserts are being further characterized.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 1","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.57","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812890","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":"Enhanced activity against syngeneic murine tumors by intrasplenic injection of recombinant interleukin-2 (IL-2) and interleukin-1 (IL-1).","authors":"I Nakajima,&nbsp;M Ozaki,&nbsp;H Jinnai,&nbsp;Y Shilayama,&nbsp;T Hirohata,&nbsp;K Okuno,&nbsp;M Yasutomi","doi":"10.1089/cbr.1993.8.319","DOIUrl":"https://doi.org/10.1089/cbr.1993.8.319","url":null,"abstract":"<p><p>The antitumor activity of Interleukin-1 (IL-1), was assessed against the murine adenocarcinoma colon 26 tumor model in combination with Interleukin-2 (IL-2). Colon 26 tumor cells were inoculated on the back of syngeneic BALB/c mice. Fourteen days after inoculation, when the tumor nodule reached approximately 10 mm in diameter, tumor nodules were resected and Hank's solution, IL-2, IL-1, or IL-2 plus IL-1 were injected directly into the mouse spleen. One week after treatment, potent natural killer (NK) and enhanced lymphokine activated killer (LAK) cell activities were seen in the splenocytes treated by the combination of IL-2 plus IL-1. Furthermore the combination treatment by IL-2 plus IL-1 resulted in a significantly prolonged survival. Phenotypic analysis showed an increased number of percent positive cells expressing asialo GM 1 and IL-2 receptor after treatment with IL-2 plus IL-1. A possible role of IL-1 in augmentation of IL-2 dependent antitumor activity in vivo is discussed.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"8 4","pages":"319-26"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1993.8.319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18805275","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}