Robert O Dillman, Andreea A Nanci, Scott T Williams, Richard B Kim, Russell L Hafer, Colleen L Coleman, Peter C Wang, Christopher M Duma, Peter V Chen, Senthamil R Selvan, Andrew N Cornforth, Carol DePriest
{"title":"Durable complete response of refractory, progressing metastatic melanoma after treatment with a patient-specific vaccine.","authors":"Robert O Dillman, Andreea A Nanci, Scott T Williams, Richard B Kim, Russell L Hafer, Colleen L Coleman, Peter C Wang, Christopher M Duma, Peter V Chen, Senthamil R Selvan, Andrew N Cornforth, Carol DePriest","doi":"10.1089/cbr.2010.0819","DOIUrl":"https://doi.org/10.1089/cbr.2010.0819","url":null,"abstract":"<p><p>A patient with metastatic melanoma who experienced a durable complete response after treatment with a patient-specific vaccine has been described in this article. This 59-year-old woman presented with cervical spine metastases and, within the year, had experienced local disease progression and, despite various therapies, metastases to the axilla, rectum, gall bladder, and multiple soft-tissue sites. She had previously received radiation therapy, combination chemotherapy, interleukin-2 plus interferon biotherapy, and gamma knife radiosurgery, and undergone multiple surgical resections. At the time vaccine therapy was initiated, she had multiple, new, measurable, soft-tissue metastases that were increasing in size. She was treated with a vaccine consisting of autologous dendritic cells incubated with irradiated tumor cells from an autologous tumor cell line and suspended in granulocyte-macrophage colony stimulating factor (GM-CSF), with subcutaneous injections once a week for 3 weeks and monthly for 5 months. There was evidence of disease regression by the completion of therapy. A few months later a complete response was documented by radiologic scans, and subsequently reconfirmed at 6-month intervals. She remains in complete remission >2.5 years after starting the vaccine, and >2 years after completing the vaccine, and survives >4 years after her initial presentation with bone, bowel, and lymph node metastases. This is the first time she has been in a complete remission since her initial diagnosis. Patient-specific vaccines can sometimes induce durable complete regression of progressing soft-tissue melanoma metastases.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"553-7"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40076412","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}
Vikas Srivastava, Deepa Sinha, Anjani K Tiwari, Himanshu Sharma, Raj Bala Sharma, Vinay K Singh, Anil K Mishra
{"title":"Quantitative structure-activity relationship analysis of 4(3H)-quinazolone derivatives as tyrosine kinase inhibitors by multiple linear regression.","authors":"Vikas Srivastava, Deepa Sinha, Anjani K Tiwari, Himanshu Sharma, Raj Bala Sharma, Vinay K Singh, Anil K Mishra","doi":"10.1089/cbr.2010.0791","DOIUrl":"https://doi.org/10.1089/cbr.2010.0791","url":null,"abstract":"<p><p>Computational chemistry is playing an increasingly important role in drug design and discovery, structural biology, and quantitative structure-activity relationship studies. A series of 4(3H)-quinozolone derivatives were screened for two-dimensional quantitative structure-activity relationship studies and subsequently their absorption, distribution, metabolism, and excretion (ADME) properties with the use of soft modeling techniques after selecting suitable descriptors for molecular structure. Multiple linear regression analysis was performed for this study. The final quantitative structure-property relationship mathematical models were found as follows: Equation [Y= log (1MIC)] [symbol: see the text] pMIC= 1. 0:2165κ(1) - 2.082χ(3) - 0.3235μT - 0.2185μx - 100.6qN - 35.42. 2. 0:2185κ(1) - 2.1575χ(3) - 0.3622μT - 0.2142μx - 100.4qN - 31.25. 3. 0:0015ω - 2.0822χ(3) - 0.1252μT - 0.2180μx - 112.9qN - 36.05. 4. 2:108χ(3) - 0.0035ET - 0.2033μx - 3.489qesp - 92.60qN - 33.20. 5. 0:2140κ(1) - 2.186χ(3) - 0.0036Oxxx - 0.0016Oxyy - 78.02qN - 31.52.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"559-62"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40082181","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}
Jian Fan, Jia-Qian Zhou, Guang-Rong Yu, Dong-Dong Lu
{"title":"Glucose transporter protein 1-targeted RNA interference inhibits growth and invasion of the osteosarcoma cell line MG63 in vitro.","authors":"Jian Fan, Jia-Qian Zhou, Guang-Rong Yu, Dong-Dong Lu","doi":"10.1089/cbr.2010.0784","DOIUrl":"https://doi.org/10.1089/cbr.2010.0784","url":null,"abstract":"<p><p>Malignant cells show increased glucose uptake, which is thought to be mediated by glucose transporters. Glucose transporter protein 1 (Glut-1) is critical for growth, proliferation, and migration of tumor cells and Glut-1 overexpression is associated with poor overall survival in osteosarcoma patients. The present study was designed to determine the role of Glut-1 in the growth and invasion of the osteosarcoma cell line MG63, using RNA interference technology in vitro. shRNA-expressing lentiviral vectors targeting the Glut-1 gene were constructed, which were stably expressed in MG63 cells. The level of Glut-1 mRNA was investigated using real-time reverse transcription-polymerase chain reaction, and the protein expression of Glut-1 mRNA was observed using western blotting. MG63 cellular glucose uptake, proliferation, and migration were detected by methyl thiazole tetrazolium assay and flow cytometry. A Glut-1-specific shRNA-expressing lentiviral vector was obtained, which could efficiently inhibit the mRNA and protein expression of Glut-1 to ∼82%-85% in MG63 cells. Downregulation of Glut-1 inhibited the cellular glucose uptake, growth, and invasion of MG63 cells in vitro. These results indicate that RNA interference targeting of Glut-1 could be an effective strategy for the treatment of osteoscarcoma patients.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"521-7"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40080257","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}
Jeffry A Siegel, Michael G Stabin, Robert M Sharkey
{"title":"Renal dosimetry in peptide radionuclide receptor therapy.","authors":"Jeffry A Siegel, Michael G Stabin, Robert M Sharkey","doi":"10.1089/cbr.2010.0805","DOIUrl":"https://doi.org/10.1089/cbr.2010.0805","url":null,"abstract":"<p><p>Abstract This study evaluates the predictive value of absorbed dose, biological effective dose, and time-dose-fractionation factors for use in patients receiving peptide radionuclide receptor therapy treatments by reanalyzing data in two different patient populations that have been reported in the literature. The analysis suggested that the alternative time-dose-fractionation model is as good and, in some cases, may be better in predicting kidney toxicity in these two patient populations than biological effective dose. This study suggests that future investigations proceed with more critical evaluation of different dosimetric quantities that may be more clinically useful in providing optimal patient treatment prescriptions for peptide radionuclide receptor therapy, rather than rely solely on a single methodology derived from experience with external-beam therapy.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"581-8"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40076502","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":"Preparation of 177Lu-labeled oxine in lipiodol as a possible agent for therapy of hepatocellular carcinoma: a preliminary animal study.","authors":"Suresh Subramanian, Tapas Das, Sudipta Chakraborty, Haladhar Dev Sarma, Sharmila Banerjee, Grace Samuel, Meera Venkatesh","doi":"10.1089/cbr.2010.0792","DOIUrl":"https://doi.org/10.1089/cbr.2010.0792","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer with high morbidity. (131)I-lipiodol is used clinically and has been found to be effective for the treatment of HCC. However, this preparation has its limitations, including compromised yield and stability of exchange labeling and unnecessary dose burden from gamma emissions. In the present study, (177)Lu-oxine in lipiodol was considered as a possible alternative for radioiodinated lipiodol. Oxine or 8-hydroxyquinoline was labeled with (177)Lu obtained by neutron irradiation of natural lutetium. Under optimized conditions, the radiolabeled complex was obtained with yields >98% and adequate in vitro stability. (177)Lu-oxine dispersed in lipiodol showed appreciable uptake into rat liver cells (normal and HCC-induced) in vitro. (177)Lu-oxine-lipiodol showed initial localization in the liver, but subsequent leakage of radioactivity with deposition in the skeletal tissue was seen. The studies suggest that (177)Lu-oxine dispersed in lipiodol might not be suitable for treatment of HCC.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"539-43"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40076503","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}
Magali Van Steenkiste, Ruth Oltenfreiter, Francis Frankenne, Liesbet Vervoort, Erik Maquoi, Agnes Noel, Jean-Michel Foidart, Christophe Van De Wiele, Filip De Vos
{"title":"Membrane type 1 matrix metalloproteinase detection in tumors, using the iodinated endogenous [123I]-tissue inhibitor 2 of metalloproteinases as imaging agent.","authors":"Magali Van Steenkiste, Ruth Oltenfreiter, Francis Frankenne, Liesbet Vervoort, Erik Maquoi, Agnes Noel, Jean-Michel Foidart, Christophe Van De Wiele, Filip De Vos","doi":"10.1089/cbr.2010.0789","DOIUrl":"https://doi.org/10.1089/cbr.2010.0789","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) are principal participants in tumor development. In addition to serve as a useful biochemical marker, MMP expression may also provide a target for the diagnostic in vivo imaging of tumors, using a radiolabeled inhibitor. This study investigates the use of membrane type 1 (MT1)-MMP as target for in vivo tumor diagnosis. Specific binding of the endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2) to MT1-MMP has been previously described. In this study, biodistribution and imaging experiments were performed on MT1-MMP-overexpressing (S.1.5) and control (C.IV.3) tumor-inoculated mice using [(123)I]-recombinant human TIMP-2 (rhTIMP-2) as radioligand and [(123)I]-rhTIMP-1 as control. The expression profile was controlled in vitro and on tumor extracts. rhTIMP-2 as well as rhTIMP-1 were labeled using the Iodogen method and characterized. Biodistribution of [(123)I]-rhTIMP-2 showed a tumor uptake of 2.87% ± 1.58% ID/g at 3 hours postinjection in S.1.5. Tumor values of [(123)I]-rhTIMP-1 and [(123)I]-rhTIMP-2 evaluated in S.1.5 and C.IV.3, respectively, were significantly lower. Planar imaging revealed significant uptake of [(123)I]-rhTIMP-2 in S.1.5 compared with contralateral background areas. This could not be observed in C.IV.3 and with [(123)I]-rhTIMP-1 in S.1.5. All tumors were well established (200-800 mg). These results suggest that rhTIMP-2 holds potential for development of radiotracers for in vivo imaging in overexpressing MT1-MMP but not in similar tumors that do not express this protease.</p>","PeriodicalId":518937,"journal":{"name":"Cancer biotherapy & radiopharmaceuticals","volume":" ","pages":"511-20"},"PeriodicalIF":3.4,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.2010.0789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40080256","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}