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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 409: Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1{alpha}
In this study, we investigated the molecular mechanism underlying the docetaxel-induced degradation of HIF-1α and cell death in cancer cell under hypoxia. Pretreatment of docetaxel increased the polyubiquitination and proteasome mediated-degradation of HIF-1α and cell death in cancer cells under hypoxia. Under hypoxia, pharmacological inhibitors or siRNAs for PHD1 (prolyl hydroxylase 1) effectively prevented HIF-1α degradation and cancer cell death through inhibiting docetaxel-mediated activation of PHD1. In addition, siRNA-mediated knockdown of JNK2 blocked docetaxel-induced degradation of HIF-1α and cancer cell death...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oh, E.-T., Song, M.-J., Lee, H., Choi, Y.-J., Park, H. J. Tags: Tumor Biology Source Type: research
Abstract 245: Identification of novel immune checkpoints as potential therapeutic targets in pancreatic ductal adenocarcinoma (PDAC) using RNAi screening
CONCLUSION: We set up a robust and systematic method to identify novel immune checkpoints for pancreatic cancer. Further functional validation of our candidate genes will prove their use as therapeutic targets.Citation Format: Antonio Sorrentino, Tillmann Michels, Ayse Nur Menevse, Nisit Khandelwal, Marco Breinig, Isabel Poschke, Rienk Offringa, Michael Boutros, Philipp Beckhove. Identification of novel immune checkpoints as potential therapeutic targets in pancreatic ductal adenocarcinoma (PDAC) using RNAi screening. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Sorrentino, A., Michels, T., Menevse, A. N., Khandelwal, N., Breinig, M., Poschke, I., Offringa, R., Boutros, M., Beckhove, P. Tags: Immunology Source Type: research
Abstract LB-247: Querying the RAS genomic network with siRNAs and and flow cytometry: Automatic, multidimensional phenotyping of 135 cancer cell lines by Gaussian mixture fitting and expectation maximization
To discover novel therapeutic modalities and genomic predictors of response, large screen utilizing small molecules or sh/siRNA are performed on increasingly large collections of cancer cell lines. However these screens suffer from two main limitations: 1) the off-target effects of the probes 2) the coarse measurement of the cellular response that cannot distinguish between different outcomes such as proliferation block and apoptosis.Here we profile 50 lung cancer cell lines using highly specific combinations of siRNAs against effector nodes of KRAS, and measured several characteristics of phenotypic response by flow cytom...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Amzallag, A., Yuan, T. L., Bagni, R., Yi, M., Stephens, R., Ramawamy, S., McCormick, F., Benes, C. H. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 254: TiMi1 is a novel immune-checkpoint in solid tumors identified via a tumor-infiltrating lymphocyte (TIL)-based RNAi screening
In this study, we established and utilized a novel high throughput RNAi screening to identify new immune checkpoint molecules in melanoma using antigen-specific patient-derived tumor infiltrating lymphocytes (TILs) in conjunction with primary HLA-matched melanoma cells. Using this approach, we screened a siRNA library targeting more than 1200 surface receptors and kinases to explore novel targets for immunotherapy.Briefly, HLA-A2 and luciferase positive M579-A2-luc melanoma cells were reversely transfected with the siRNA library and then co-cultured with MART1- and gp100-specific TILs to validate the TIL-mediated tumor lys...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Michels, T., Hartl, C. A., Khandelwal, N., Breinig, M., Sorrentino, A., Mader, C., Umansky, L., Poschke, I., Offringa, R., Boutros, M., Eisenberg, G., Lotem, M., Beckhove, P. Tags: Immunology Source Type: research
Abstract 436: SDF1{alpha} / CXCR4 axis might be associated with growth-interaction between cancer-associated fibroblasts and gastric cancer cells in hypoxic tumor microenvironment
Conclusion: Hypoxic microenvironment switch the driver signaling from FGF7/FGFR2 to SDF-1/CXCR4 in diffuse type of gastric cancer. CXCR4/SDF1 axis might play an important role for the proliferation of gastric cancer in hypoxic tumor microenvironment.Citation Format: Haruhito Kinoshita, Masakazu Yashiro, Hiroaki Kasashima, Go Masuda, Tamami Morisaki, Tatsunari Fukuoka, Katsunobu Sakurai, Takahiro Toyokawa, Kenjiro Kimura, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. SDF1α / CXCR4 axis might be associated with growth-interaction between cancer-associated fibroblasts and gastric cancer cells ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kinoshita, H., Yashiro, M., Kasashima, H., Masuda, G., Morisaki, T., Fukuoka, T., Sakurai, K., Toyokawa, T., Kimura, K., Kubo, N., Tanaka, H., Muguruma, K., Ohira, M., Hirakawa, K. Tags: Tumor Biology Source Type: research
Abstract 475: Identification of SHANK2 as a tumor suppressor disrupted by recurrent somatic structural variation (SV) in neuroblastoma
Background. Neuroblastoma is a malignancy of the developing sympathetic nervous system which exacts significant morbidity and mortality in children. Large sequencing efforts have revealed a relative paucity of somatic point mutations in this and other childhood cancers. Structural variations (SVs) including translocations, inversions, deletions, duplications, and other complex events can occur in germline DNA or be acquired somatically in tumors. Recurrent somatic SVs affecting known genes are likely to be functional and may elucidate novel tumor suppressors or oncogenes.Methods. We are performing whole-genome sequencing (...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Conkrite, K., Ferraro, N., McDaniel, L., Oldridge, D. A., Attiyeh, E., Asgharzadeh, S., Diamond, M., Guidry Auvil, J., Davidsen, T., Smith, M., London, W. B., Seeger, R., Khan, J., Gerhard, D. S., Maris, J. M., Diskin, S. J. Tags: Tumor Biology Source Type: research
Abstract 287: Specific delivery of immunostimulatory RNA via nanoparticles blocks growth of primary and disseminated ovarian tumors
One important mechanism of immune evasion is the accumulation of tumor-infiltrating regulatory T cells creating an immunosuppressive microenvironment in situ. Many new therapies target immune checkpoint receptors, CTLA-4 and PD-1, on immunosuppressive T-cells to reverse tumor immune evasion. Small interfering RNAs (siRNAs) are double stranded, sequence-specific inhibitors of gene expression. The paradigm for using siRNA to block cancer is to target mRNA sequences of oncogenes. Several limitations have suppressed the use of siRNA in human cancer therapy, such as off-target effects and lack of tumor-specific delivery. Additi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Primiano, T., Chang, B.-i. Tags: Immunology Source Type: research
Abstract LB-290: Multiple distinct mechanisms disrupt let-7 miRNA biogenesis and function in neuroblastoma
The let-7 microRNA family are known tumor suppressors often deregulated in cancer, yet the underlying mechanisms of let-7 disruption remain poorly understood. Neuroblastoma, a neural crest derived tumor, is defined in part by poor prognosis associated with genetic amplification of MYCN, itself a let-7 target. The let-7 biogenesis inhibitor LIN28B has recently been implicated as a critical regulator of MYCN, but we have employed siRNA and CRISPR-mediated gene disruption to show that LIN28B is dispensable for both MYCN protein expression and growth of MYCN-amplified neuroblastoma cell lines despite robust de-repression of le...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Powers, J. T., Tsanov, K. M., Roles, F., Ebright, R., Seligson, M., de Soysa, Y., Cahan, P., Theissen, J., LaPier, G. S., Pearson, D. S., Berthold, F., Daley, G. Q. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-291: microRNA regulation of Nrf2: A link between autophagy and oxidative stress
Understanding the relationship between autophagy and excessive oxidative stress is crucial for determining the fate of cancer cells exposed to redox-active chemotherapeutic agents. Previous studies have shown that Mitoquinone (MitoQ), a redox active, mitochondrialy targeted ubiquinone derivative, can induce autophagy through the generation of excess reactive oxygen species and stimulate the antioxidant response involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in breast cancer cells. Nrf2 is a transcription factor that is up-regulated during oxidative stress and activates the antioxidant response element, which ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Pokrzywinski, K. L., Rao, V. A. Tags: Molecular and Cellular Biology 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 LB-299: Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells
Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (T-IC, also known as cancer stem cells). Here we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knockdown gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosph...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Gilboa-Geffen, A., Hamar, P., Wheeler, L. A., Trifonova, R., Petrocca, F., Wittrup, A., Lieberman, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 313: Examining the role of ABCA1 cholesterol transporter in ovarian cancer spheroids
Epithelial ovarian cancer (EOC) is a devastating disease which accounts for a large proportion of gynaecological cancer-related deaths. Poor survival is largely due to late diagnosis of the disease which typically presents with peritoneal dissemination. In order to achieve reduced tumor burden and improved survival, it is imperative to identify new prognostic markers and potential therapeutic targets. Recent work by our group identified high ATP- Binding Cassette A1 (ABCA1) transporter expression as being associated with poor outcome in EOC. ABCA1 has been widely studied as a cholesterol transporter, however there is littl...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Williams, R., Russell, A., Bongers, A., Sagnella, S., Fife, C., Jessup, W., DeFazio, A., Chenevix-Trench, G., Haber, M., Norris, M., Henderson, M. Tags: Tumor Biology Source Type: research
Abstract 325: Multiple myeloma in a physiologically relevant Me-HA -3D Hydrogel: Discovering new phenotypes of drug resistance
In this study we have shown that Hyaluronic acid (HA) based 3D hydrogel support human metastatic MM cancer cells survival and thus reveal new oncogenic mechanisms of drug resistant cancer stem cells.Experimental approaches: Bone marrow derived CD138 positive cells and BMSCs were isolated from MM patient samples (with IRB approval) using magnetically labeled CD138 MicroBeads (autoMACS Pro Starting Kit). Bone marrow stromal cells (BMSCs) were cultured as described by us earlier. Cell viability measurements and quantitative RT-PCR for c-myc and other related gene targets were performed using total RNA. Me-HA-3D hydrogels were...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Narayanan, B. A., Duan, B., Narayanan, N. K., Butcher, J. B., Mazumder, A. Tags: Tumor Biology Source Type: research
Abstract 336: CD73 induces actin polymerization to protect epithelial cell-cell adhesions: Loss of this physiological reflex in endometrial carcinoma
We previously reported that ecto-5′nucleotidase (CD73)-generated adenosine prevents hypoxia-mediated breakdown of the epithelial barrier in normal endometrium in vivo and that CD73 is down-regulated in advanced stage endometrial carcinomas (EC). Loss of CD73 occurred specifically in the carcinoma cells. CD73-generated adenosine is heightened in tissues overwhelmed by inflammation, ischemia, or hypoxia. We hypothesized that the loss of CD73 in EC supports tumor progression by negating the reflex of extracellular adenosine to protect epithelial cell integrity. CD73 was associated with epithelial differentiation in vitro in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Bowser, J. L., Blackburn, M. R., Dunner, K., Broaddus, R. R. Tags: Tumor Biology Source Type: research
Abstract 353: Vorinostat enhances anti-tumor effects of cisplatin in head and neck cancer cells by targeting cancer stem cells
Conclusions: Taken together, our results suggest that targeting of HDACs with Vorinostat could be an effective treatment strategy for the treatment of HNSCC patients that do not respond to currently used treatment regimens.Citation Format: Bhavna Kumar, Arti Yadav, Theodoros N. Teknos, Pawan Kumar. Vorinostat enhances anti-tumor effects of cisplatin in head and neck cancer cells by targeting cancer stem 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 353. doi:10...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kumar, B., Yadav, A., Teknos, T. N., Kumar, P. Tags: Tumor Biology Source Type: research
