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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 2958: Discovering therapeutic epigenetic targets using whole genome siRNA screening
Conclusions: A whole genome siRNA screen in combination with the DNMT inhibitor decitabine identified many new target genes that might be epigenetic regulators and potential targets for drug development.Citation Format: Yasuyuki Okamoto, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Jean-Pierre J. Issa. Discovering therapeutic epigenetic targets using whole genome siRNA screening. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2958. doi:10.1158/1538-7445.AM2015-2958
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Okamoto, Y., Chung, W., Garriga, J., Jelinek, J., Issa, J.-P. J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3012: The Snm1B/Apollo DNA nuclease functions in resolution of replication stress and maintenance of genome stability
A critical aspect of normal cellular processes is the maintenance of genomic stability. Defects in cellular responses to DNA damage can lead to an accumulation of unrepaired or misrepaired lesions and ultimately, increased genome instability. Genomic DNA is constantly damaged through exposure to exogenous agents as well as during endogenous processes, including DNA replication. Progression of the replication fork can be impaired by structural or physical blocks leading to fork stalling. If stalled forks are not properly restarted or repaired, they can collapse, leading to chromosomal damage including breaks, deletions, and...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Das, I., Mason, J., Sekiguchi, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3024: Lack of CK1{delta} increases DNA damage and genomic instability due to defects in DNA repair and mitotic checkpoints
Casein kinase 1 delta (CK1δ) is a conserved serine/threonine protein kinase that regulates diverse cellular processes including vesicle trafficking and circadian rhythm. We previously reported that CK1δ is a mediator of Wnt-3a-dependent neurite outgrowth (Greer and Rubin, JCB, 2011) and ciliogenesis (Greer et al. MBoC, 2014). Mice that lack Csnk1d exhibit a perinatal lethal phenotype and typically weigh 30-50% less than their wild type littermates, however, the exact causes of death and small size are unknown. We hypothesized that the absence of CK1δ contributes to cellular stresses that adversely affect cell survival. ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Greer, Y. E., Gao, B., Yang, Y., Lipkowitz, S., Rubin, J. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3027: Investigating the function of NONO, a novel double strand break repair factor, and exploring its potential role as a biomarker for melanoma
We investigated the in vivo function of NONO, a protein that has been shown to promote a distinct sub-pathway of nonhomologous end joining (NHEJ) repair in vitro and in cultured cells. We used a gene trap strategy to create a null mutant for Nono, the mouse homolog of the human NONO gene. We investigated hematopoietic stem cells (HSCs), which are known to be sensitive to deficiencies in other DNA repair proteins. Nono-deficient mice showed reduced bone marrow and spleen cellularity. HSCs from Nono-deficient mice showed severe impairment in competitive repopulation assays in primary and secondary recipients. HSCs from Nono-...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Li, S., Shu, F., Khan, M. K., Pollack, B. P., Li, Z., McLemore, M., Dynan, W. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3045: Novel altered mitochondrial genes in prostate cancer progression
Conclusions: We have identified mitochondria genes that are differentially expressed in PCa cells lines and prostatectomy tissues with different malignancy phenotypes. These findings are currently being validated using disease stratified TMAs. Further studies are focusing on uncovering the mechanisms responsible for progression and metastasis of PCa that are modulated by mitochondria associated genes. These could assist in the development of novel diagnostic and therapeutic strategies for the disease.Citation Format: Tanya C. Burch, J S. Rhim, Julius O. Nyalwidhe. Novel altered mitochondrial genes in prostate cancer progre...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Burch, T. C., Rhim, J. S., Nyalwidhe, J. O. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2804: The thiazolidinedione pioglitazone enhances the cancer preventive activity of the rexinoid LG100268 in Her2/neu induced breast cancer
Two major unresolved issues for breast cancer prevention are the lack of effective preventive agents for estrogen receptor (ER)-negative disease and the potential toxicity of long-term pharmacologic treatment. The ability of retinoid X receptor (RXR)-selective retinoids (rexinoids) to inhibit breast cancer formation independently of ER-status was previously demonstrated in various preclinical models. The goal of our study was to identify ideal druggable targets for the synergistic amplification of the cancer preventive effect of synthetic rexinoids and test the efficacy of a low-dose combination treatment in vivo. We ident...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Uray, I. P., Rodenberg, J. M., Zhang, Y., Hill, J. L., Brown, P. H. Tags: Prevention Research Source Type: research
Abstract 3047: Mitochondrial DNA copy variation and TFAM expression in astrocytoma
Mitochondrial dysfunction plays a role in determining the phenotype through bioenergetic depletion and increased production of ROS in several diseases, including cancer. We have previously demonstrated a relevant reduction of mitochondrial DNA (mtDNA) copy number in astrocytoma of different grades of malignancy, predominantly in grade IV-glioblastoma (GBM). We observed a stepwise increase of TFAM in parallel to the increase of malignancy, and TFAM expression was higher in GBM patients with overall survival longer than 24 months than less than 12 months. TFAM is codified in the nucleus and transported into mitochondria, whe...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Marie, S. K., Silva, R., Lerario, A., Uno, M., Oba-Shinjo, S. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3071: MicroRNA-486 (miR-486) promotes invasion by targeting RECK in nasopharyngeal carcinoma cells
Nasopharyngeal carcinoma (NPC) is a common cancer in Taiwanese and people living in the southeastern region of China. In order to investigate NPC pathogenesis, our laboratory has previously established NPC-TW01 cell line, which was derived from a Taiwanese NPC patient. We also established a NPC-TW01N1 cell line, which was derived from the NPC xenograft in SCID mouse. Both NPC-TW01 and NPC-TW01N1 cell lines have an identical DNA profile (STR). NPC-TW01N1 cell line has higher malignant potency than NPC-TW01 line. For example, the proliferation and invasion capabilities of NPC-TW01N1 line were higher than that of NPC-TW01 lin...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lin, C.-T., Wu, C.-D. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3072: miR-551b amplification regulates STAT3 expression and resistance to anoikis of ovarian cancer cells
In conclusion, our results propose that the STAT3 expression induced by miR551b is the key mechanism regulates survival and metastasis of HGSOC cells.Citation Format: Pradeep Chaluvally Raghavan, Sunila Pradeep, Yiling Lu, Anil Sood, Gordon Mills. miR-551b amplification regulates STAT3 expression and resistance to anoikis of ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3072. doi:10.1158/1538-7445.AM2015-3072
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chaluvally Raghavan, P., Pradeep, S., Lu, Y., Sood, A., Mills, G. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3088: Inhibition of CDK5 in colorectal cancer
Conclusions: CRC is the second leading cause of cancer related deaths mainly due to the metastatic disease. There are currently no effective pharmacologic treatments for CRC metastases. We have shown that CDK5 is upregulated and overexpressed in metastatic tumors when compared to primary colon tumors. Inhibition of CDK5 either by knockdown or through the use of small molecule inhibitors decreased downstream phosphorylation of specific targets and reduced expression of anti-apoptotic mediators. Together, these data suggest that CDK5 might play a role in metastatic CRC and we’ve identified a potential inhibitor, 20-223 whi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Robb, C. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2844: RNA interference kinome-wide screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition ER-positive breast cancer
Background: Small molecule inhibitors that target the CDK4/6/cyclinD1 pathway are in clinical development. Clinical trials combining the CDK4/6 inhibitor pallbociclib and the aromatase inhibitor letrozole have demonstrated significantly improved clinical outcomes in patients with ER-positive breast cancer. This combination is likely to be approved for the treatment of patients with this breast cancer subtype. However, as for other targeted therapies, development of resistance to CDK4/6 inhibitors in a significant fraction of patients is anticipated. Therefore, there is a need to develop potent therapeutic strategies to cir...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Jansen, V. M., Bhola, N. E., Bauer, J. A., Arteaga, C. L. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3108: MicroRNA-200B inhibits arsenic-transformed cell migration by targeting protein kinase C{alpha} signaling pathway
Arsenic is one of the most common environmental pollutants and long term exposure to arsenic is associated with increased risk of multiple types of cancer including lung cancer. Despite extensive studies, the mechanism of arsenic carcinogenicity has not been elucidated. MicroRNAs (miRNAs) are a large class of small non-coding RNAs and have been shown to play important roles in many fundamental processes of cancer. MiRNA-200b (miR-200b) is a member of miR-200 family, which contains 5 members. The miR-200 family has been shown to inhibit tumor cell migration; however, the underlying mechanisms are not clearly defined. We rec...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, Z., Humphries, B., Yang, C. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3109: A functional microRNA screening approach that identifies microRNAs affecting melanoma cell invasion
Melanoma is a fast progressing tumor which tends to metastasize at small size and at early time point. miRNA profiling has been performed for a variety of cancer types, however, the results obtained differ substantially among published studies. Therefore, it is of major interest to unravel miRNA networks involved in melanoma progression as, for example, in tumor cell invasion. In order to follow this aim, we established a functional screening approach based on a high-throughput invasion assay using a human miRNA mimics library consisting of 988 miRNAs (miRBase Version 13.0). Applying this strategy, we could identify miRNAs...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Weber, C. E. M., Luo, C., Hotz–Wagenblatt, A., Osen, W., Holland–Letz, T., Eichmuller, S. B. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3147: Generation of exhaustion-resistant memory CD8 T-cells by simultaneous downmodulation of mTORC1 and PD-1 in activated CD8 T-cells
CD8 memory T cells play a crucial role in controlling chronic infections and certain malignancies. It is possible to expand the population redirecting early-activated T-cells toward memory differentiation by altering intracellular signaling of mTORC1 pathway. Indeed, treatment with mTORC1 inhibitor rapamycin increased formation of memory cells as published previously; however, animals treated with the drug exhibited signs of immune suppression and rapamycin-generated CD8 memory T-cells failed to protect animals against melanoma challenge. We introduced highly efficient RNAi-based method to downmodulate mTORC1 signaling spe...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Berezhnoy, A., Levay, A., Rajagopalan, A., Puplampu-Dove, Y., Gilboa, E. Tags: Immunology Source Type: research
Abstract 2904: Induction of autophagy reveals a cytoprotective mechanism by which DNA polymerase gamma (pol-{gamma}) prevents UVB-induced skin cancer
In this study, we identified tyrosine 964, which is near the active site of polγ, as the target of nitration-induced inactivation by the use of LC/MS/MS mass spectroscopy coupled to immunoprecipitation, Western blotting and a 3` to 5` exonuclease activity assay. Treatment of mouse skin epithelial cells with UVB radiation validated the presence of polγ nitration and reduction of its enzymatic activity in vivo. To determine the effect of UVB in autophagic responses, mouse skin epithelial (JB6) cells were transfected with GFP-labeled LC-3 cDNA and exposed to UVB radiation, or wild-type C57BL/6 mice were exposed to UVB radia...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dhar, S. K., Bakthavachalu, V., Izumi, T., Chen, J., Zhu, H., St. Clair, D. K. Tags: Molecular and Cellular Biology Source Type: research
