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Abstract 5472: Selinexor, a selective inhibitor of nuclear export (SINE), acts through NF-{kappa}B deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death
Conclusion: Inhibition of NF-κB transcriptional activity through forced nuclear retention of IκB appears to be an important mechanism in the selective tumor cell cytotoxicity of selinexor and related SINE compounds. Furthermore, the combination of selinexor and proteasome inhibitors, which are also known to act at least in part through inhibition of NF-κB, leads to synergistic activity in vitro and in vivo, suggesting that such combinations may provide clinically more effective than the single agents. A Phase 1 trial to study the safety and efficacy of selinexor in combination with carfilzomib in multiple myeloma is ong...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Landesman, Y., Kashyap, T., Crochiere, M., Klebanov, B., Friedlander, S., Senapedis, W., Carlson, R., Kauffman, M., Shacham, S. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 294: A novel cancer therapeutic strategy: inducing cytotoxic functions in tumor-associated macrophages
Macrophages are recognized as an important component of the tumor microenvironment. Previous studies have shown that they promote tumor growth and participate in the initiation and progression of metastatic spread. Methods are being developed to eliminate macrophages from the tumor, thereby inhibiting their negative effects. However, we believe that the best approach would be to transform the tumor-helping macrophages into tumor-killing macrophages that would both eliminate tumor cells directly and re-invigorate other immune cells around them to better fight the tumor. Our data indicates that we have found a way to induce ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Barham, W., Tikhomirov, O., Ortega, R., Saskowski, J., Thompson, C. S., Wilson, A., Blackwell, T., Mirafzali, Z., Khabele, D., Giorgio, T., Yull, F. E. Tags: Immunology Source Type: research

Abstract 2603: Specific growth suppression of wild-type p53 tumor cells by DNA-modified siRNA sequences targeting MDM2
Conclusions: Our 2 newly selected dsRDC-modified siRNAs had high knockdown activity and less nonspecific cytotoxicity. Thus, they represent potent therapeutic agents against cancers carrying wt p53 with MDM2 overexpression. Citation Format: Mitsuaki Hirose, Kenji Yamato, Rie Saito, Takunori Ueno, Sachiko Hirai, Hideo Suzuki, Shinji Endo, Ichinosuke Hyodo. Specific growth suppression of wild-type p53 tumor cells by DNA-modified siRNA sequences targeting MDM2. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer R...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hirose, M., Yamato, K., Saito, R., Ueno, T., Hirai, S., Suzuki, H., Endo, S., Hyodo, I. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 342: Telomerase-dependent oncolytic adenovirus sensitizes human osteosarcoma cells to chemotherapy through Mcl-1 downregulation
In this study, we investigated the chemosensitizing effect of OBP-301 in human osteosarcoma cells and the molecular mechanism in the OBP-301-mediated enhancement of cell death. We used four human osteosarcoma cell lines, HOS, MNNG/HOS, 143B and SaOS-2. OBP-301 is an attenuated adenovirus, in which the hTERT promoter drives the expression of E1 gene, and causes tumor-selective lysis in a variety of human malignant tumor cells with telomerase activity. OBP-301 infection enhanced the cytotoxic effect of chemotherapeutic agents, cisplatin and doxorubicin, that are commonly used for the treatment of osteosarcomas. The calculati...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Osaki, S., Omori, T., Tazawa, H., Hasei, J., Yamakawa, Y., Sasaki, T., Kunisada, T., Urata, Y., Ozaki, T., Fujiwara, T. Tags: Molecular and Cellular Biology Source Type: research

Abstract 2953: Rev-erb{alpha} modulates Myc-driven cancer cell growth and altered metabolism
Circadian rhythms are regulated by feedback loops comprising a network of factors that regulate Clock-associated genes. Chronotherapy seeks to take advantage of altered circadian rhythms in some cancers to better time administration of treatments to increase efficacy and reduce toxicity. While many cancers have perturbed expression of core circadian rhythm genes, the molecular basis underlying these perturbations and their functional implications in oncogenesis are still poorly understood, and so it is impossible to predict which cancers have altered circadian rhythms and would best benefit from chronotherapy. We have obse...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Altman, B. J., Hsieh, A., Gouw, A. M., Stine, Z. E., Venkataraman, A., Bellovin, D. I., Diskin, S. J., Lu, W., Zhang, S., Felsher, D. W., Maris, J. M., Lazar, M. A., Rabinowitz, J. D., Hogenesch, J. B., Dang, C. V. Tags: Molecular and Cellular Biology Source Type: research