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An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules
Conclusion Considering the heterogeneity and complexity of ovarian cancer, we demonstrated a new method to predict the prognosis of ovarian cancer based on the clustering information and gene co-expression network in each subtype of cancer patients. We divided the ovarian cancer data into three subtypes by clustering analysis and we found that the survival risks in these three subtypes were significantly different. We mined the important communities based on the co-expression networks in each subtype. There are 50, 73, and 92 communities in the first, second and third subtype, respectively. Next, we constructed a new ense...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Abstract A30: Characterizing the non-linear dependency of the CDK5-Rb axis in non-small cell lung cancer
In spite of recent therapeutics advances and early detection, lung cancer is still the leading cause of cancer-associated deaths worldwide. The five-year survival rates for its two major subtypes, small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are estimated to be 6% and 18%, respectively. This high mortality is due to its aggressive nature even when detected at an early stage. Besides its aggressive nature and tendency for early metastasis, another feature of lung cancer is the inactivation of the retinoblastoma protein (Rb) that is observed in both lung cancer subtypes. NSCLC exhibits Rb inactivation...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jaileene Perez-Morales, Mauricio Cabrera-Rios, Jonathan Gonzalez-Flores, Pedro Santiago-Cardona Tags: Systems Biology Source Type: research

LSC Abstract - Histone deacetylase 7 mediated metabolic remodeling: A new crosslink between pulmonary hypertension and cancer
Pulmonary arterial smooth muscle cells (PASMCs) from Pulmonary Hypertension (PH) patients and several PH animal models are characterized by suppressed mitochondria-dependent apoptosis and hyperpolarization. Similarly to lung cancer (LC) cells, PH-PASMCs have reduced glucose oxidation and increased cytoplasmic glycolysis. Protein acetylation and its enzymes such as histone deacetylases (HDACs) may play a role in the control of metabolism.We assessed the regulation of Class IIa HDACs (HDAC4, 5, 7 and 9) in human and experimental models of PH and lung cancer. By using primary culture of healthy (control-PASMCs), idiopathic de...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Gamen, E., Chelladurai, P., Grimminger, F., Savai, R., Seeger, W., Savai Pullamsetti, S. Tags: ERS Lung Science Conference 2016 Source Type: research

Abstract B05: WHSC1L1 and estrogen-independent activation of estrogen receptor-alpha (ER{alpha}) in 8p11 amplicon-bearing cell lines
The 8p11-p12 genomic region is amplified in 15% of breast cancers and 21% of lung squamous cell carcinomas (LSCC) and is associated with poorer prognosis. This genomic region harbors several oncogenes, three of which are epigenetic modifiers of chromatin (WHSC1L1, KAT6A, ASH2L). WHSC1L1 is a histone methyltransferase (HMT) that is expressed in 2 isoforms. The long isoform (WH-long) encompasses the entire coding region and is associated with dimethylation of lysine 36 on histone 3 (H3K36me2) to facilitate transcriptional elongation. The short isoform (WH-short) is produced by alternative splicing at exon 10, resulting in a ...
Source: Cancer Research - January 14, 2016 Category: Cancer & Oncology Authors: Mills, J. N., Irish, J., Turner-Ivey, B., Ethier, S. P. Tags: Cancer Genomics and Epigenomics Source Type: research

Abstract LB-C22: Acquired resistance to the cMET inhibitor savolitinib in lung cancer models through EGFR/mTOR/MYC deregulation and adoption of PIM signaling
Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments. Aberrant receptor tyrosine kinase (RTK) signaling is a well-documented driver of disease onset and progression in multiple cancer types, including non-small cell lung cancer (NSCLC), where the cMET RTK contributes to tumor progression, maintenance and resistance to targeted therapies. Here, we explore the therapeutic potential of the potent and selective cMET inhibitor savolitinib (volitinib, AZD6094, HMPL-504) in NSCLC and begin to elucidate mechanisms of acquired savolitinib resistance in preclini...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Henry, R. E., Barry, E. R., Ladd, B., Markovets, A., Beran, G. J., Ren, Y., Zhou, F., Castriotta, L., Adam, A., Qing, W., Su, W., Clark, E., D'Cruz, C. M., Schuller, A. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B119: Blocking metabolic stress response with genetic knockdown and selective ligands of sigma-1 receptor in cancer cells
In this study we examined whether Sig1R sustains proliferation, survival and tumorigenic properties of human cancer cells. Knockdown of Sig1R using small interfering RNA (siRNA) in human prostate and lung cancer cell lines had profound effect on proliferation, clonogenic capability and tumor-sphere formation, indicating reversal of the tumorigenic and stem-like phenotype in absence of Sig1R. Next, in the attempt to discover pharmacological agents that could phenocopy the effects of the genetic knockdown in cancer cells we tested a series of structurally diverse Sig1R ligands selected for high affinity and selectivity for t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Civenni, G., De Monte, C., Sereni, F., Allegrini, S., Bosotti, R., Laurini, E., Wunsch, B., Pricl, S., Carbone, G. M., Catapano, C. V. Tags: New Molecular Targets: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C145: Targeted radiosensitization of non-small cell lung cancer (NSCLC) through ADAM17 inhibition
Conclusions: These findings implicate that radiotherapy significantly activates ADAM17 in non–small cell lung cancer (NSCLC) cells, which results in shedding of multiple survival factors, growth factor pathway activation and contributes to treatment resistance. We provide a sound rationale for repositioning ADAM17 inhibitors as short-term adjuvants to improve the radiotherapy outcome of NSCLC.Citation Format: Ashish Sharma, Sabine Bender, Oliver Riesterer, Angela Broggini-Tenzer, Martin Pruschy. Targeted radiosensitization of non-small cell lung cancer (NSCLC) through ADAM17 inhibition. [abstract]. In: Proceedings of...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Sharma, A., Bender, S., Riesterer, O., Broggini-Tenzer, A., Pruschy, M. Tags: Radiotherapeutics: Poster Presentations - Proffered Abstracts Source Type: research

Abstract LB-B02: Acquisition of stem cell-like properties accompanying with Src family kinase/Focal adhesion kinase activation contributes to acquired resistance to afatinib in lung cancer cells
Conclusions] Together, our present study presents that increase of cancer stem like cells and SFK/FAK activation could be a mechanism responsible for acquired resistance to afatinib. We would further discuss the association of ALDH1 expression and SFK/FAK activation with afatinib resistance in lung cancer.Citation Format: Yuichi Murakami, Kahori Sonoda, Koichi Azuma, Kosuke Watari, Michihiko Kuwano, Mayumi Ono. Acquisition of stem cell-like properties accompanying with Src family kinase/Focal adhesion kinase activation contributes to acquired resistance to afatinib in lung cancer cells. [abstract]. In: Proceedings of the A...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Murakami, Y., Sonoda, K., Azuma, K., Watari, K., Kuwano, M., Ono, M. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract LB-A13: Cellular characterization of the selective inhibition of UBA5 by organometallic, adenosine-based inhibitors
Cells that undergo higher protein turnover, such as pancreatic secretory cells and cancerous cells, have the propensity to undergo endoplasmic reticulum (ER) stress. If left uncorrected, ER stress can result in the initiation of apoptosis. To avoid these fates, cells have developed support systems to counteract the apoptotic effects of ER stress, such as conjugation of certain stress-associated proteins with the ubiquitin-fold modifier 1 (UFM1) ubiquitin-like protein. Our research has recently focused on the discovery and in vitro validation of the first selective inhibitor of the UFM1 pathway, 5C-Z, which selectively targ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: da Silva, S. R., Geletu, M., Javed, F., Paiva, S.-L., Lewis, A. M., Li, H., Gunning, P. T. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A2-18: The challenges of using large-scale genomics data to identify novel drivers of lung cancer
Lung cancer is one of the major causes of cancer deaths worldwide and only 30% of patients survive the disease for at least one year after diagnosis. Patients are often too frail to receive systemic chemotherapy and there is an urgent need for less toxic, efficacious, targeted therapies. Despite recent efforts with large-scale genomics data we still lack knowledge about driver mutations for the majority of lung cancers.Increasingly, cancer researchers are using online cancer genomic databases to identify novel targets to investigate. A comparison of two prominent databases from different institutes (CCLE and COSMIC) reveal...
Source: Cancer Research - November 15, 2015 Category: Cancer & Oncology Authors: Hudson, A. M., Yates, T., Wirth, C., Li, Y., Trotter, W., Fawdar, S., Miller, C., Brognard, J. Tags: Genomics and Target Discovery Source Type: research

Abstract A36: Combined inhibition of PI3K isoforms and mTOR kinase is critical for cancer stem cell inhibition by VS-5584
We report here that VS-5584 is up to 30-fold more potent at inhibiting the proliferation and survival of CSCs than non-CSCs in breast cancer cell lines using multiple orthogonal CSC assays. Moreover, VS-5584 preferentially induced apoptosis in Aldefluor-positive CSCs relative to Aldefluor-negative non-CSCs as measured by Annexin V and Caspase 3/7 assays. In contrast, paclitaxel induced more apoptosis in non-CSCs than CSCs cells. VS-5584 also preferentially diminished CSCs in human breast and small cell lung cancer xenograft models in vivo, as evidenced by marked reduction of tumor-initiating capacity in an in vivo limiting...
Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Kolev, V. N., Wright, Q. G., Weaver, D. T., Padval, M. V., Pachter, J. A., Xu, Q. Tags: Preclinical and Clinical Studies in Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B47: Therapeutic KRAS silencing in lung and colon cancer models
This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional "undruggable" targets.Citation Format: Chad Pecot, Sherry Wu, Seth Bellister, Rajat Bhattacharya, Anshumaan Maharaj, Cristian Rodriguez-Aguayo, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Gabriel Lopez-Berestein, Lee M. Ellis, Anil Sood. Therapeutic KRAS silencing in lung and colon cancer models. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR;...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Pecot, C., Wu, S., Bellister, S., Bhattacharya, R., Maharaj, A., Rodriguez-Aguayo, C., Gonzalez-Villasana, V., Rupaimoole, R., Lopez-Berestein, G., Ellis, L. M., Sood, A. Tags: RAS Targeting: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A47: IL-4 receptor-targeted delivery of liposomal doxorubicin and siRNA to tumor
Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Using phage displayed-random peptide libraries, we have identified IL4RPep-1 (IL-4 receptor-binding peptide-1), CRKRLDRNC, that binds to IL-4 receptor (IL4R). IL4R is over-expressed on many types of cancer cells including lung cancer and breast cancer. Peptides have smaller size and in turn may exert better tissue penetration than bulky antibodies. IL4RPep-1 bound to H226 lung tumor cells that over-express IL4R, while little binding was observed in H460 lung tumor cells that expres...
Source: Cancer Research - January 12, 2015 Category: Cancer & Oncology Authors: Padmanaban, G., Vadevoo, S. M. P., Chi, L., Lee, B.-H. Tags: Translational and Therapeutic Potential of the Tumor Microenvironment Source Type: research

Abstract 21: Quantitative FRET technology for SUMOylation cascade and high-throughput screening assay for SUMOylation inhibitor in cancer drug discovery
The ubiquitin–proteasome system and ubiquitin-like protein pathways, such as SUMOylation, are critical in protein homeostasis and activities in vivo and are emerging as a new strategy to treat many acute and chronic human diseases, such as cancers. Although various kinase inhibitors have been developed as target-based therapy, solid tumors are still challenges in clinical therapy because various resistant are developed after kinase inhibitor treatments, and therapeutic agents with novel mechanisms are urgently needed. SUMO has been shown to modify various critical proteins, such as p53, MDM2, Estrogen receptor and androg...
Source: Cancer Research - December 12, 2014 Category: Cancer & Oncology Authors: Liao, J., Wiryawan, H., Li, Y., Song, Y., Liu, Y., You, J., Jiang, L., Malik, H. K., Saavedra, A. N., Qu, S. Tags: Poster Presentations Source Type: research