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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 B45: Silencing ss3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jenny G. Parvani, Maneesh D. Gujrati, Margaret A. Mack, William P. Schiemann, Zheng-Rong Lu Tags: Drug Delivery and Nanomedicine Source Type: research

Abstract C05: Pulmonary laminin 332 in tumor cell migration and breast cancer survival
Metastasis to the lung often leads to the demise of the patient, thus a greater understanding of the process might lead to strategies for better cancer control. Tumor cell metastatic ability is determined by both intrinsic properties of tumor cells and contributions from the microenvironment. The goal of this study was to determine the role of the extracellular matrix protein laminin 332 (LN332) in breast cancer progression. Because tumor cell motility is a requirement for metastasis, we hypothesize that lung tissue harbors substances that induce tumor cell migration. In order to better characterize the interaction of brea...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Carpenter, P. M., Sivadas, P., Ziogas, A., Anton-Culver, H. Tags: Tumor Microenvironment and Metastasis Source Type: research

Abstract B21: Exostosin 1 regulates cancer cell stemness in breast cancer cells
Cancer stem cells (CSCs), a group of cancer cells, are associated with resistance to radiation and chemotherapy and are implicated in recurrent of cancer. Exostosin 1 (EXT1) gene is widely reported as tumor suppressor and its indispensable role in elongation of heparan sulfate (HS) can speculate probable role as tumor promotor. In recent years, a number of tumors are reported to over express EXT1. Here, we investigated the role of EXT1 in the maintenance of cancer cell stemness. MCF7/ADR cells developed by exposing MCF7, breast cancer cells, to doxorubicin for several months in culture, showed high resistance to doxorubici...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Manandhar, S., Kim, C.-g., Oh, S. Y., Lee, S.-H., Seok, J., Jung, Y.-D., Lee, H.-E., Choi, Y.-S., Lee, Y. M. Tags: Therapeutic Targeting Tumor Microenvironment Source Type: research

Abstract PR07: Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1
Cancer cells spread from a primary tumor to secondary loci is responsible for more than 90% of cancer related mortality. Hematogenous metastasis is a complex process [1]. It includes a chain of events that can be summarized as follows: migration from primary tumor site and intravasation of the primary tumor cancer cells into the blood flow, dissemination through the circulation, extravasation in different organs, survival in the new microenvironment and colonization with generation of a new tumor.Recently our group presented a microfluidic 3D model reproducing the effects of the CXCL5-CXCR2 interaction between bone cells a...
Source: Cancer Research - May 25, 2016 Category: Cancer & Oncology Authors: Gilardi, M., Bersini, S., Kamm, R. D., Moretti, M., Vanoni, M. Tags: Circulating Evidence of Tumor Metastasis Source Type: research

Abstract B22: Loss of LncRNA XIST induces Epithelial to Mesenchymal Transition in Breast Cancer
Brain is one of the major sites of metastasis of breast cancer, and approximately 20% of patients with aggressive breast cancer eventually develop the metastatic disease in the brain. Long non-coding RNAs (lncRNA) have recently drawn much attention due to their wide functional variations and potential roles in tumor progression. By performing lncRNA array analysis comparing non-metastatic primary tumors with brain metastatic tumors from breast cancer patients, we identified that lncRNA XIST expression was significantly down-regulated in brain metastatic tumors. The result of Taqman PCR validated the results in tumor sample...
Source: Cancer Research - May 25, 2016 Category: Cancer & Oncology Authors: Liu, Y., Xing, F., Wu, K., Sharma, S., Watabe, K. Tags: Genetics and Evolution of Metastatic Tumors Source Type: research

Abstract C54: High caveolin-1 expression in a cohort of African American women with triple-negative breast cancer
In this study, gene expression profiling, using the Almac BC DSA Research Tool, was performed on archived FFPE samples, obtained from CA and AA women diagnosed with early stage (Node 0) TNBC. Unsupervised hierarchical clustering revealed a pattern of differential gene expression in the AA cohort compared to CA. Using the TNBC type: A Subtyping Tool for TNBC, we found a distinct distribution pattern of TNBC molecular subtypes in the AA cohort, which was very different than the CA cohort; Basal-like (14%), Immunomodulatory (43%) and Mesenchymal (43%). Gene expression analyses, comparing the AA and CA cohort (fold change >...
Source: Cancer Epidemiology Biomarkers and Prevention - April 14, 2016 Category: Cancer & Oncology Authors: Getz, J. E., Teoh, D. B., Nasser, S., Legendre, C. R., Tembe, W., Yellapantula, V., Ahearn, M. E., Gomez, C. R., Jorda, M., Wong, S. M., Pegram, M. D., Carpten, J. D., Baumbach-Reardon, L. L. Tags: Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B24: Regulation of DARC isoforms among ancestry groups and associations with aggressive breast cancer subtypes
Biological mechanisms that drive disparate incidences of aggressive breast cancer in women of African descent are still largely unknown. Despite the fact that White women are more often diagnosed with breast cancer, African-American women have more severe cases and more often die from their breast cancer. Certain clues surrounding the tumor behavior and aggressive nature of cancers in African Americans point to physiological contexts, perhaps even the immunological microenvironment of the cancer sites. We hypothesize that higher mortality rates, coupled with lower incidence of breast cancer in this population, compared to ...
Source: Cancer Epidemiology Biomarkers and Prevention - April 14, 2016 Category: Cancer & Oncology Authors: Vollum, K., Hutchins, R., Brown, A. M., Perez, C., Davis, M. B. Tags: Cancer Genetics/Gene Expression: Poster Presentations - Proffered Abstracts Source Type: research

Abstract IA06: Spatial systems biology of cancer
International efforts have now defined the genomic landscapes of most major human cancer types. The genomic landscape of breast cancer is particularly well described in several recent publications. The high level view of this disease suggests a remarkable level of inter- and intra-tumor heterogeneity, the presence of a few recurrent and many rare genomic aberrations and substantial genomic and epigenomic heterogeneity. The challenge now is to understand how these aberrations and tumor extrinsic influences from the microenvironment collaborate to deregulate aspects of cell differentiation, proliferation, apoptosis, DNA repa...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Gray, J. Tags: Genomics - Sporadic and Hereditary: Oral Presentations - Invited Abstracts Source Type: research

Abstract PR06: Modeling the tumor microenvironment to identify novel loss of function mutations in breast cancer progression
Recent next generation sequencing studies have comprehensively mapped the genetic landscape of breast cancer and revealed that only a small number of genes are recurrently mutated in more than 10% of unselected tumors (i.e. TP53, PIK3CA and GATA3), and that the vast majority of recurrent mutations occur at low frequencies. Although some have been shown to be drivers (i.e. confer a selective advantage), such as oncogenic ERBB2 mutations, there is a myriad of significantly altered lower frequency mutations whose functional impact is unknown.We utilized a functional genomics approach silencing the 200 most frequently mutated ...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Peck, B., Maguire, S., Morrison, E., Wai, P., Natrajan, R. Tags: Tumor Heterogeneity (Intratumor and Intertumoral): Oral Presentations - Proffered Abstracts Source Type: research

Abstract A35: WNT4 signaling mediates endocrine response and resistance in invasive lobular carcinoma cells
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer, affecting ~30,000 U.S. women annually. Over 90% of ILC are estrogen receptor (ER)-positive, however, endocrine therapy may have poorer efficacy in a subset of ILC patients compared to invasive ductal carcinoma (IDC) patients. Based on these observations, we assessed genome-wide ER-mediated gene expression and ER genomic binding in ILC cell lines MDA MB 134VI (MM134) and SUM44PE (44PE), to identify novel mediators of ER signaling and putative therapeutic targets specifically in ILC.Among ILC-specific estrogen-regulated genes, the most strongly indu...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Sikora, M. J., Bahreini, A., Alexander, C. M., Oesterreich, S. Tags: Luminal Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A58: Expression and function of endothelin converting enzyme 1 and endothelin receptors in breast cancer invasion
The endothelin axis, comprised of the active peptides endothelin 1-3 (ET1-3), the endothelin A receptor (ETAR) and endothelin B receptor (ETBR), and endothelin converting enzyme 1 (ECE1) has been studied in numerous cancers. In clinical samples of breast cancer, increased levels of ET1, ECE1, and the endothelin receptors have been reported, and several studies correlate expression of these proteins with poor prognosis. The endothelin pathway is known to induce mitogen activated protein kinase activation, leading to increased survival, proliferation, and migration, but the precise role of ECE1 and the endothelin receptors i...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Belles, M. E., Halaka, M., Do, J. M., Majmudar, P., Sidani, R., Stephen, H., Watson, M., Conway, R. E. Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A68: Penfluridol suppresses triple-negative breast cancer metastasis to brain by inhibiting integrin signaling
Breast cancer is the second leading cause of cancer related deaths in US. Breast tumor metastasis to brain is major cause of deaths. Brain metastasis of triple negative breast cancer cells (TNBC) is highly resistant to current therapies and is a cause of reduced survival rates in patients. In current study, we evaluated penfluridol, a first generation, highly potent antipsychotic drug against three different highly aggressive TNBC cell line. The IC50 of penfluridol was around 6 µM in 4T1, MDA-MB-231 and HCC-1806, breast cancer cells respectively. Our result showed that the expression of integrinβ4, integrin&alph...
Source: Molecular Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Ranjan, A., Gupta, P., Srivastava, S. K. Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research

Abstract PR01: Role of mitochondrial folate transporter in metabolism of tumor cells
The objective of the present study is to identify modulators of cellular metabolism among transportome genes which could potentially be exploited as targets in pancreatic ductal adenocarcinoma (PDAC). Indeed cancer cells have the ability to adapt in order to survive stressful environment where oxygen and nutrients are limited due to the poor vasculature and outgrowth of stromal component. Thus, disrupting mechanisms of metabolic adaptation could inhibit tumor proliferation or sensitize tumor cells to treatment. Ion channels and transporters provide the link between cancer cells, stroma and matrix. Additionally these protei...
Source: Molecular Cancer Research - January 15, 2016 Category: Cancer & Oncology Authors: Kovalenko, I., Schockel, L., Glasauer, A., Haegebarth, A., Christian, S. Tags: Therapeutic Targets From Cancer: Oral Presentations - Proffered Abstracts Source Type: research

Abstract PR03: P53 inhibits the expression of the pyrimidine catabolic gene Dihydropyrimidine dehydrogenase (DPYD)
Fluorouracil (5-FU) a widely used chemotherapeutic drug whose unpredictable pharmacokinetics is controlled by the pyrimidine catabolic gene dihydropyrimidine dehydrogenase (DPYD), that has recently also been shown to be a gatekeeper of the epithelial-to-mesenchymal transition (EMT) in breast cancer. Relatively little is known about the transcriptional control of DPYD and here we show for the first time an interaction between p53 and DPYD (involved in catabolism of pyrimidines as well as 5-FU) where p53 represses both the base-line expression of DPYD and that following 5-FU administration in vitro and in vivo. This mechanis...
Source: Molecular Cancer Research - January 15, 2016 Category: Cancer & Oncology Authors: Gokare, P. R., Finnberg, N., Dai, J., El-Deiry, W. Tags: Cancer Metabolic Pathways: Oral Presentations - Proffered Abstracts Source Type: research

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