tbuckley/cabot-search huggingface dataset:
Abstract 1571: Decrypting the transcriptome profile of Pak4 using next generation sequencing
Authors: Chetan Rane, Misaal Patel, Li Cai, Audrey Minden
Journal: Cancer Research (2017)

Abstract The PAK4 (p-21 Activated Kinase 4) protein kinase has long been associated with cancer because of its key roles in regulating cell proliferation, cell cycle progression and cell morphology. The PAK4 gene is amplified in different types of cancers, including breast cancer. PAK4 overexpression is associated with oncogenic transformation in several breast cancer cell lines, while PAK4 inhibition has been shown to significantly reduce their tumorigenic potential. However, there is limited information available on PAK4’s mechanism of action in promoting tumorigenesis. To gain an insight into PAK4 downstream signaling pathways, we performed Next Generation Sequencing (NGS) on RNA samples collected from non-transformed immortalized mouse mammary epithelial cells (WT iMMECs) and iMMECs overexpressing PAK4. Research from our lab has shown that unlike WT iMMECs, iMMECs overexpressing PAK4 formed tumors when injected into mammary fat pads of mice, suggesting a central role for PAK4 in tumor formation. Previous studies to delineate PAK4 signaling pathways have mostly focused on substrates phosphorylated by PAK4. This study, however, takes into account genes which may act downstream of PAK4 and play an important role in mediating long term PAK4 function. RNA-seq analysis offers the ability to discover new genes and splice variants and measure transcript expression. mRNA was isolated in triplicates from WT iMMECs and iMMECs overexpressing PAK4; mRNA from each condition was then sequenced using Illumina NextSeq platform. The RNA-seq data generated was analyzed using Top Hat and Cufflinks software, which created a list of genes whose expression was significantly different in these two cell types, and previously unknown to be regulated by PAK4 (26 genes were up regulated and 51 genes were down regulated by more than a log2 fold change of 3). A qPCR analysis of 8 of these genes validated the sequencing data. Among the different genes we identified, we chose to focus on ParvB, which is consistently down regulated by almost seven fold in the iMMECs overexpressing PAK4. Previous studies have suggested a tumor suppressor role for ParvB in regulating breast tumorigenicity. We hypothesize that PAK4 mediates mammary tumor formation through ParvB downregulation. Additional studies investigating the role of ParvB in the PAK4 signaling pathway are under investigation. Future studies will also involve studying the other genes we found to be regulated by PAK4 overexpression and determining their role in tumorigenesis. Citation Format: Chetan Rane, Misaal Patel, Li Cai, Audrey Minden. Decrypting the transcriptome profile of Pak4 using next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1571. doi:10.1158/1538-7445.AM2017-1571
Abstract 2521: Inhibition of metabolic reprogramming by zerumbone alters the tumorigenic potential of hepatocellular cancer
Authors: Nissar A. Wani, Bo Zhang, Kun-yu Teng, Juan Barajas, Kalpana Ghoshal, Rafael Brüschweiler, Samson T. Jacob
Journal: Cancer Research (2017)

Abstract Incidence of hepatocellular carcinoma (HCC) that represents ~90% of all cases of primary liver cancer is on the rise worldwide. Sorafenib, the only approved targeted therapy, prolongs median survival only by ∼3 months. Thus, new therapeutic strategies are urgently needed. In this study, we investigated therapeutic potential of zerumbone, a sesquiterpene from an edible ginger, against HCC. Zerumbone inhibited proliferation and clonogenic survival of HCC cells by blocking glycolysis and pentose phosphate pathway, arresting cells at G2/M phase of cell cycle and inducing apoptosis. To uncover the underlying molecular mechanisms of its action on HCC cells, we employed several unbiased approaches. First, phosphokinase array showed significant inhibition PI3K/AKT/mTOR and STAT3 signaling in zerumbone-treated HCC cells. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) of the microarray data revealed that zerumbone-deregulated genes showed positive correlation with PI3/AKT/mTOR and STAT3 pathways and those involved in metabolism, apoptosis and cell cycle. Notably, the alteration in expression of genes regulated by PI3/AKT/mTOR or STAT3 pathways and downregulated by zerumbone in HCCs is associated with poor patient survival. These results implicate that treatment with this dietary sesquiterpene might lead to a better outcome in HCC patients. Indeed, zerumbone treatment significantly inhibited growth and lung metastasis of orthotopic HCC xenografts in NSG mice. These findings reveal novel therapeutic strategies targeting cancer metabolism. Collectively, these observations underscore the therapeutic potential of zerumbone in HCC. Citation Format: Nissar A. Wani, Bo Zhang, Kun-yu Teng, Juan Barajas, Kalpana Ghoshal, Rafael Brüschweiler, Samson T. Jacob. Inhibition of metabolic reprogramming by zerumbone alters the tumorigenic potential of hepatocellular cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2521. doi:10.1158/1538-7445.AM2017-2521
Abstract 5014: Drug discovery for NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model
Authors: Dong Hyuk Ki, Shuning He, A. Thomas Look
Journal: Cancer Research (2017)

Abstract Children and young adults with type 1 neurofibromatosis (NF1) are at risk to develop plexiform neurofibromas, which can undergo malignant transformation to malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are among the most frequently occurring sarcomas in children and young adults and are especially problematic in NF1 patients. Currently, complete surgical excision is the only curative therapy for NF1-associated MPNST, but these tumors are often not completely resectable. Therefore, it is very important to identify promising drugs that can be rapidly moved into clinical trials to improve the therapy of patients with MPNSTs. We have developed a faithful zebrafish model of NF1-associated MPNST by using genome engineering to develop zebrafish lines harboring loss-of-function mutations of the duplicated nf1a and nf1b genes and p53. Our nf1 and p53 deficient zebrafish models develop MPNSTs that are very similar to human NF1-associated MPNST, and thus are ideal for experiments to test the efficacy of FDA-approved small molecule drugs in vivo. To test the FDA-approved drugs for activity against MPNST tumor cells, about 100 Sox10:mCherry expressed MPNST primary tumor cells were transplanted into dechorionized 2 day-post-fertilization (dpf) larval fish using a micro-injector. MPNST-implanted embryos were exposed to individual test compounds added to the fish water at a range of concentrations and to the vehicle control. After 4-days of treatment, quantitative assessment of the remaining mCherry-labeled tumor cell numbers were measured using the ImageJ software for each treated embryo. Currently, trametinib and sunitinib caused marked antitumor effects indicated by reduced numbers of mCherry-labeled nf1-deficient MPNST cells compared to the DMSO control in this study. We are now applying this embryonic implantation assay to identify combinations of FDA-approved drugs that have a high degree of efficacy against MPNST and can be rapidly “repurposed” to improve the treatment of this disease. Citation Format: Dong Hyuk Ki, Shuning He, A. Thomas Look. Drug discovery for NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5014. doi:10.1158/1538-7445.AM2017-5014
Lack of Prognostic Significance of the Conventional and Novel Prognostic Markers in Trisomy 12 Chronic Lymphocytic Leukemia (CLL)
Authors: Valter Gattei, Riccardo Bomben, Michele Dal Bo, Antonella Zucchetto, Francesca Rossi, Massimo Degan, Federico Pozzo, Tamara Bittolo, Vanessa Bravin, Tiziana D'Agaro, Claudia Perini, Annalisa Chiarenza, Kari G. Chaffee, Giovanni D'Arena, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Davide Rossi, Giovanni Del Poeta, Gianluca Gaidano, Tait D. Shanafelt, Pietro Bulian
Journal: Blood (2016)
Abstract 2538: MiR-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3
Authors: Ming Yang
Journal: Cancer Research (2017)

Abstract Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promote cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues. To further elucidate regulatory mechanisms of miR-638 in autophagy, we performed a computational nomination of its target genes through intersecting the results of multiple prediction algorithms. DACT3, a key regulator of Wnt/β-catenin signaling, was predicted to be regulated by miR-638 by all programs and confirmed by experimental results. Depletion of DACT3 phenocopied effects of miR-638 overexpression, demonstrating its importance in autophagy. These results elucidate that the miR-638-DACT3 axis might be an important molecular pathway in controlling and autophagy and tumorigenesis. Our data in clinical tissue samples highlight miR-638 and DACT3 with histological marker for cancer detection and potentially therapeutic implications. Citation Format: Ming Yang. MiR-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2538. doi:10.1158/1538-7445.AM2017-2538
Abstract 4427: An integrated analysis package of miRNA and mRNA expression dataAn integrated analysis package of miRNA and mRNA expression data
Authors: Ti-Tai Wang
Journal: Cancer Research (2017)

Abstract MicroRNAs(miRNAs) are small and non-coding RNAs that can regulate gene expression by binding on the 3’UTR of target mRNAs and inhibiting mRNAs to translate protein, or even promoting mRNAs degradation. In various complex disease and pathological conditions, we can identify dysregulated which are the causative factors. Therefore, it is an essential approach to explore the interactions between miRNA and gene in certain diseases, such as cancers. However, challenge arises when we are trying to validate the interactions by doing bench experiments. The numbers of miRNA-gene interactions are too large to be validated. Currently, most prediction algorithms only provide its own result and low consistency rates across independent methods have been reported. Therefore, it is necessary to develop a systematic method to perform a comprehensive analysis by using the expression profiles from genes and miRNAs concurrently. To address these issues, we developed an R package named as anamiR. AnamiR is able to perform an integrated analysis of mRNA and miRNA with the phenotype information. The analysis procedures are briefly summarized as the follows. Initially, differential expression analysis would be applied to the raw data. Subsequently, the anamiR package can identify significant pairs of miRNAs and genes if their Pearson correlation coefficients are lower than the pre-defined threshold. Next, the significant pairs were compared to the embedded database in anamiR, which included two validated and several predicting miRNA-gene databases. Lastly, functional analysis is also available in this package to characterize the biological functions and signaling pathways of dysregulated miRNAs and genes. A breast cancer dataset was analyzed by using anamiR, which identified nine miRNA-gene interactions for deeper studying. Among these interactions, there are two miRNAs and nine genes included. miR-497-5p and miR-204-5p which both were mentioned in breast cancer frequently, are found by anamiR. The anamiR package is freely available at Bioconductor. Citation Format: Ti-Tai Wang. An integrated analysis package of miRNA and mRNA expression dataAn integrated analysis package of miRNA and mRNA expression data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4427. doi:10.1158/1538-7445.AM2017-4427
Abstract LB-174: Patient navigation in Appalachia: results from a survey of current practices
Authors: Mark B. Dignan, Sharon Dwyer, Carol White, Elizabeth A. Rohan, Dana White, Georgina Castro, Reda Wilson, Mary Boyd, Eric Stockton
Journal: Cancer Research (2017)

Abstract Purpose: The Appalachian region of the US includes 420 counties in 13 states that begin with New York, follow the Appalachian Mountains and extend to Mississippi. The region has a heterogeneous population that shares distinct cultural characteristics, high rates of unemployment, low income, and high rates of chronic disease, including cancer. Patient navigators (PN) provide one-on-one guidance and assistance through the health care continuum from prevention to end-of-life and address barriers and enhance access to healthcare through the use of individual navigators who are sensitive to the needs, interests and values of the community. Although there are numerous PN training programs available, there are no known programs that are designed for the Appalachian population. As a first step in developing such a program, we designed and conducted a survey of PN training needs in Appalachia. Methods: With guidance from formative research involving a variety of stakeholders, we identified key individuals, professional groups, health care systems, and public health agencies serving the Appalachian region. We developed a 26-item survey to collect information on current patient navigation programs, sources of current training, and training needs. After pretesting, the survey was distributed online. Data were collected from June, 2015 through May, 2016. Results: A total of 152 responses were received. The responses were from community based organizations (29.3%), academic medical centers (15.5%), hospitals (35.8%), and community cancer centers (19.5%). PN was currently provided by individuals from a variety of professional backgrounds, chiefly nursing (32.8%) and social work (8.4%), and 15.3% were community navigators. Only 63.8% of respondents reported having received formal PN training. About half (47.3%) indicated that they were interested in attending PN training and suggested specific content and format. Conclusions: Survey respondents identified a need for PN training that focuses on Appalachia. These results supported the development of an Appalachia Patient Navigation Training Program, currently underway. Note: This abstract was not presented at the meeting. Citation Format: Mark B. Dignan, Sharon Dwyer, Carol White, Elizabeth A. Rohan, Dana White, Georgina Castro, Reda Wilson, Mary Boyd, Eric Stockton. Patient navigation in Appalachia: results from a survey of current practices [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-174. doi:10.1158/1538-7445.AM2017-LB-174
Abstract 5387: Droplet digital PCR for sensitive quantification of DNA methylation in non-invasive material: Development of a robust control
Authors: Heidi D. Pharo, Kim Andresen, Marine Jeanmougin, Guro E. Lind
Journal: Cancer Research (2017)

Abstract Background: Droplet digital PCR (ddPCR) is a highly sensitive method for quantification of nucleic acids, with great potential for detection of biomarkers present in low quantities. As for DNA methylation analyses using ddPCR, there is no consensus on whether or not a control should be included. The aim of the present study was to; 1) demonstrate that use of a control is essential in such analyses, and 2) develop a robust control with better performance than the existing alternatives. Results and methods: A 4-gene control panel was developed in our lab, and its performance compared to the existing alternatives ACTB and C-LESS-C1. This was done through analyzing the methylation level of four target genes in DNA from 34 colon cancer cell lines. All ddPCRs were performed using the QX200™ PCR platform (BioRad). Details will be presented. Conclusions: In summary, use of a control is essential for robust and consistent ddPCR based DNA methylation, and can prevent erroneous interpretation of technical artifacts. Citation Format: Heidi D. Pharo, Kim Andresen, Marine Jeanmougin, Guro E. Lind. Droplet digital PCR for sensitive quantification of DNA methylation in non-invasive material: Development of a robust control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5387. doi:10.1158/1538-7445.AM2017-5387
Abstract LB-245: Immunohistochemical study of MAGI-2 expression in lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon
Authors: Zhiming Liao
Journal: Cancer Research (2017)

Abstract Introduction MAGI-2 (Membrane Associated Guanylate Kinases Inverted 2) is a scaffolding protein that interacts with PTEN in shutting off the Pi3K/AKT pathway. MAGI-2 suppresses AKT by enhancing PTEN function and its protein stability. In this study, we examined the protein expression of MAGI-2 in normal tissues and various solid tumors by immunohistochemistry (IHC). Methodology An IHC study of MAGI-2 was performed on normal tissue and tumor tissues from prostate (34 cases), ovary (95 cases), urinary bladder (92 cases), pancreas (88 cases), liver (2 cases), colon (2 cases), and lymphoma (185 cases). MAGI-2 staining intensity was semi-quantitatively scored using a 0-3 scale. Percent positive rate of MAGI-2 was calculated for carcinomas from prostate, urinary bladder, ovary, pancreas, liver, colon, and lymphoma. Results In normal tissues, MAGI-2 was detectable by IHC mostly in follicle area of the tonsil or lymph node and in the cuboidal or columnar epithelium of several organs (skin, urinary bladder, breast, fallopian tube, small intestine, colon, prostate, adrenal gland, and thyroid). The protein expression of MAGI-2 was higher in tumor cells than in their adjacent normal tissues from prostate, urinary bladder, ovary, pancreas, lymph node, liver, and colon. The positive rate of MAGI-2 was 100% for invasive prostate adenocarcinoma (34/34 cases), 82% for ovarian adenocarcinoma (78/95 cases), 76 % for urinary bladder carcinoma (70/92 cases), 62 % of pancreatic adenocarcinoma (55/88 cases), 83 % for diffuse large B-cell lymphoma ( 135/163 cases), 80 % for follicular B-cell lymphoma (8/10 cases), 67% for non-Hodgkin B-cell lymphoma (6/9 cases), 0% for small lymphocytic B-cell lymphoma (0/3 cases), 100% for colon adenocarcinoma (2/2 cases), and 100% for hepatocellular carcinoma (2/2 cases). Conclusions MAGI-2 is overexpressed in most lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon, but it is not detectable in small lymphocytic B-cell lymphoma by IHC for this study. Citation Format: Zhiming Liao. Immunohistochemical study of MAGI-2 expression in lymphomas and carcinomas from prostate, urinary bladder, ovary, pancreas, liver, and colon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2017-LB-245
Head and Neck Carcinoma Immunotherapy: Facts and Hopes
Authors: Theresa L. Whiteside
Journal: Clinical Cancer Research (2017)

Abstract Cancer of the head and neck (HNC) is a heterogeneous disease of the upper aerodigestive tract, encompassing distinct histologic types, different anatomic sites, and human papillomavirus (HPV)–positive as well as HPV-negative cancers. Advanced/recurrent HNCs have poor prognosis with low survival rates. Tumor-mediated inhibition of antitumor immune responses and a high mutational burden are common features of HNCs. Both are responsible for the successful escape of these tumors from the host immune system. HNCs evolve numerous mechanisms of evasion from immune destruction. These mechanisms are linked to genetic aberrations, so that HNCs with a high mutational load are also highly immunosuppressive. The tumor microenvironment of these cancers is populated by immune cells that are dysfunctional, inhibitory cytokines, and exosomes carrying suppressive ligands. Dysfunctional immune cells in patients with recurrent/metastatic HNC can be made effective by the delivery of immunotherapies in combination with conventional treatments. With many promising immune-based strategies available, the future of immune therapies in HNC is encouraging, especially as methods for genetic profiling and mapping the immune landscape of the tumor are being integrated into a personalized approach. Efficiency of immune therapies is expected to rapidly improve with the possibility for patients' selection based on personal immunogenomic profiles. Noninvasive biomarkers of response to therapy will be emerging as a better understanding of the various molecular signals co-opted by the tumors is gained. The emerging role of immunotherapy as a potentially beneficial addition to standard treatments for recurrent/metastatic HNC offers hope to the patients for whom no other therapeutic options exist. Clin Cancer Res; 24(1); 6–13. ©2017 AACR.
Corrigendum to “Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems for targeted drug delivery in pancreatic cancer” [J. Control. Release 239 (2016) 39–48]
Authors: Barbara Grünwald, Jennifer Vandooren, Erica Locatelli, Pierre Fiten, Ghislain Opdenakker, Paul Proost, Achim Krüger, Jean Paul Lellouche, Liron Limor Israel, Louis Shenkman, Mauro Comes Franchini
Journal: Journal of Controlled Release (2017)
Targeting MicroRNAs in Prostate Cancer Radiotherapy
Authors: Jie Ni, Joseph Bucci, Lei Chang, David Malouf, Peter Graham, Yong Li
Journal: Theranostics (2017)

Radiotherapy is one of the most important treatment options for localized early-stage or advanced-stage prostate cancer (CaP).Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy.There is great interest in investigating mechanisms of radioresistance and developing novel treatment strategies to overcome radioresistance.MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level, participating in numerous physiological and pathological processes including cancer invasion, progression, metastasis and therapeutic resistance.Emerging evidence indicates that miRNAs play a critical role in the modulation of key cellular pathways that mediate response to radiation, influencing the radiosensitivity of the cancer cells through interplaying with other biological processes such as cell cycle checkpoints, apoptosis, autophagy, epithelial-mesenchymal transition and cancer stem cells.Here, we summarize several important miRNAs in CaP radiation response and then discuss the regulation of the major signalling pathways and biological processes by miRNAs in CaP radiotherapy.Finally, we emphasize on microRNAs as potential predictive biomarkers and/or therapeutic targets to improve CaP radiosensitivity.