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Treated Tumors (treated + tumor)
Selected AbstractsIn vitro and in vivo tumor growth inhibition by a p16-mimicking peptide in p16INK4A -defective, pRb-positive human melanoma cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005Douglas M. Noonan The cell cycle regulatory pathway responsible for the control of the late-G1 checkpoint is found recurrently altered in human malignant melanoma, often due to lack of functional p16 or pRb (pRb-1) proteins. Here we examined the ability of p16-derived peptides to mimic p16 function in two exemplary human melanoma cell lines: the p16-defective, pRb-positive A375M cells and p16-positive, pRb-defective A2058 cells. The synthetic p16-mimicking peptides strongly induced apoptosis in p16,, pRb+ A375M cells in vitro, while they had significantly less activity on p16+, pRb, A2058 cells. The most active p16-mimicking peptide, p16-AP9, also potently inhibited in vivo growth of the A375M melanoma. Treated tumors showed a threefold smaller volume (P,<,0.025) and a significant reduction of the mitotic index and of PCNA expression. Growth of A2058 cells in vivo was not affected by treatment with the p16-mimicking peptide. Our results demonstrate that p16-mimicking peptides can induce apoptosis in vitro and that can inhibit tumor growth in vivo in p16-defective, pRb-expressing human melanoma cells, suggesting that p16-mimicking peptides can represent a promising tool for targeted therapy in selected cancer phenotypes. © 2004 Wiley-Liss, Inc. [source] Intra-tumoral Salmonella typhimurium induces a systemic anti-tumor immune response that is directed by low-dose radiation to treat distal diseaseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Francesca Avogadri Abstract Salmonella typhimurium is a facultative anaerobic bacterium able to multiply preferentially in tumors and inhibit their growth. The mechanisms through which Salmonella exerts its anti-cancer properties are not fully understood. We recently showed that intra-tumoral Salmonella injection results not only in the regression of even bulky tumor masses, but also impacts on the growth of distant untreated lesions. Here we describe how Salmonella exerts its systemic anti-cancer effects and means to potentiate them. The outburst of an early inflammatory reaction in the treated tumor promotes the development of an immunostimulatory cytokine environment both locally and in the draining lymph node. Within the next 10,days, an efficient cross-presentation of endogenous tumor antigens by dendritic cells at the tumor-draining lymph node leads to the priming of effective anti-tumor CD8+ T cell responses. This potentially broadly reactive T cell repertoire can be directed to other pre-established melanomas by low-dose radiotherapy enhancing the Salmonella anti-cancer effect. We demonstrate that Salmonella -based therapy coupled to low-dose radiotherapy dampens tumor immune escape mechanisms at different levels and allows controlling systemic disease in a CD8+ T cell-dependent manner. [source] Effect of Perilesional Injections of PEG-Interleukin-2 on Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 11 2000Baruch Kaplan MD Background: Multiple modalities are available for the treatment of basal cell carcinoma (BCC). The most commonly used modalities include simple excision, Mohs micrographic surgery, curettage and electrodessication, cryosurgery, and irradiation therapy. Interleukin-2 (IL-2) is a cytokine produced chiefly by activated T lymphocytes and has effects on various components of the immune system. Until now the primary clinical use of IL-2 has been in advanced stages of metastatic melanoma and renal cell carcinoma. Systemic administration of IL-2 is known to cause significant toxicity. Objective: The objective of this study was to evaluate the therapeutic efficacy and safety of perilesional PEG-IL-2 injections in patients with BCC in an open label, uncontrolled pilot study. Methods: Patients with histologically confirmed primary BCC over 18 years of age were included in the study. Lesions were treated by injecting a total volume of 0.5 cc of IL-2 in a radial fashion in the subcutaneous tissue. Injection dosages ranged from 3000 to 1,200,000 IU in one to four weekly dosages. A total of 12 tumors were treated in eight patients. Results: Overall response rates were as follows: complete response in 8 of 12 treated tumors (66.6% cure rate), partial response in 3 of 12 injected tumors (25% partial response rate), stable disease with no improvement in 1 treatment site (8.4%). Side effects included local pain, swelling, and erythema, and in one patient flulike symptoms. There were no significant changes of blood tests as compared to baseline levels. Conclusions: The therapeutic response induced by perilesional PEG-IL-2 injections was found to be an encouraging, safe, and well-tolerated treatment of BCC. Further studies including a larger patient population and long-term follow-up are necessary in order to substantiate these findings. [source] Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft modelINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Maria Virginia C.L. Appleyard Abstract We sought to determine whether seliciclib (CYC202, R-roscovitine) could increase the antitumor effects of doxorubicin, with no increase in toxicity, in an MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice bearing established MCF7 xenografts. Post-treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real-time PCR. Seliciclib significantly enhanced the antitumor effect of doxorubicin without additional murine toxicity. MIB1 (ki67) immunohistochemistry demonstrated reduced proliferation with treatment. The levels of p21 and p27 increased after treatment with doxorubicin or seliciclib alone or in combination, compared to untreated controls. However, no changes in p53 protein (DO1, CM1), survivin or p53 phosphorylation (SER15) were observed in treated tumors compared with controls. In conclusion, the CDK inhibitor seliciclib (R-roscovitine) enhances the antitumor effect of doxorubicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis. © 2008 Wiley-Liss, Inc. [source] EGFR tyrosine kinase inhibition radiosensitizes and induces apoptosis in malignant glioma and childhood ependymoma xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Birgit Geoerger Abstract Malignant gliomas and childhood ependymomas have a high rate of treatment failure. Epidermal growth factor receptor (EGFR) activation has been implicated in the tumorigenesis and radioresistance of many cancers, including brain tumors. Therefore, combining EGFR targeting with irradiation is a potentially attractive therapeutic option. We evaluated the tyrosine kinase inhibitor gefitinib for its antitumor activity and potential to radio-sensitize in vivo in two xenograft models: an EGFR amplified glioma and an EGFR expressing ependymoma, both derived from primary tumors. When administered at 100 mg/kg for 5 consecutive days, gefitinib-induced partial tumor regression in all treated EGFR amplified IGRG88 glioma xenografts. The addition of 1 Gy of irradiation prior to gefitinib administration resulted in 5 complete and 4 partial regressions for the 9 treated tumors as well as a significant tumor growth delay of 33 days for the combined treatment compared to 19 days for each therapy alone, suggesting additive antitumor activity. Tumor regression was associated with inhibition of AKT and MAPK pathways by gefitinib. In contrast, the ependymoma IGREP83 was sensitive to irradiation, but remained resistant to gefitinib. Combined treatment was associated with inhibition of radiation-induced MAPK phosphorylation and significant induction of apoptotic cell death though radiation-induced AKT phosphorylation was maintained. Depending on the scheduling of both therapies, a trend towards superior antitumor activity was observed with combined treatment. Thus, EGFR targeting through tyrosine kinase inhibition appears to be a promising new approach in the treatment of EGFR-driven glioma, particularly in combination with radiation therapy. © 2008 Wiley-Liss, Inc. [source] Diffusion-weighted MRI for monitoring tumor response to photodynamic therapyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Hesheng Wang MS Abstract Purpose: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor response to photodynamic therapy (PDT). Materials and Methods: Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4 Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect. Results: Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was 0.511 ± 0.119 × 10,3 mm2/s pre-PDT and 0.754 ± 0.181 × 10,3 mm2/s 24 h after the PDT. There is no significant difference in ADC values pre-PDT and 24 h after PDT in the control tumors (P = 0.20). Conclusion: The change of tumor ADC values measured by DW-MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4-PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409,417. © 2010 Wiley-Liss, Inc. [source] Gene Therapy for Head and Neck Cancer ,THE LARYNGOSCOPE, Issue 5 2000Lyon L. Gleich MD Abstract Objectives/Hypothesis New treatment methods are needed for head and neck cancer to improve survival without increasing morbidity. Gene therapy is a potential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology and treatment strategies. Given the current technological vector limitations in transmitting the therapeutic genes, treatments that require the fewest number of cells to be altered by the new gene are optimal. Therefore an immune-based gene therapy strategy was selected in which the tumors were transfected with the gene for an alloantigen, human leukocyte antigen (HLA),B7, a class I major histocompatibility complex (MHC). This would restore an antigen presentation mechanism in the tumor to induce an antitumor response. This gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design Prospective trial. Methods Twenty patients with advanced head and neck cancer who had failed conventional therapy and did not e-press HLA-B7 were treated with gene therapy using a lipid vector by direct intratumoral injection. The gene therapy product contained the HLA-B7 gene and the ,2-microglobulin gene, which permits complete e-pression of the class I MHC at the cell surface. Patients were assessed for any adverse effects, for changes in tumor size, for time to disease progression, and for survival. Biopsy specimens were assessed for pathological response, HLA-B7 e-pression, apoptosis, cellular proliferation, CD-8 cells, granzyme, and p53 status. Results There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a partial response and two patients had stable disease. Two of the tumors completely responded clinically, but tumor was still seen on pathological examination. The time to disease progression in the responding patients was 20 to 80 weeks. The median survival in patients who completed gene therapy was 54 weeks, compared with 21 weeks in patients whose tumors progressed after the first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA-B7 was demonstrated in the treated tumors, and increased apoptosis was seen in the responding tumors. Conclusion Significant advances have been made in the field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in the treatment of cancer and can induce tumor responses in head and neck tumors. Alloantigen gene therapy has significant potential as an adjunctive treatment of head and neck cancer. [source] | ||||||||||