tbuckley/cabot-search huggingface dataset:
Studies in Carcinogenesis. XVII. Local Effect of Repeated Application of 3,4-Benzpyrene and of Human Smegma to the Vagina and Cervix of Mice
Authors: M. Fishman, M. J. Shear, Harry F. Friedman, Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1942)

Studies in Carcinogenesis. XVII. Local Effect of Repeated Application of 3,4-Benzpyrene and of Human Smegma to the Vagina and Cervix of Mice Get access M. Fishman, M. Fishman assistant in medicine Tumor Clinic, Beth Israel Hospital, Boston Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Shear, M. J. Shear principal biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Harry F. Friedman, Harry F. Friedman director of Tumor Clinic Beth Israel Hospital, Boston Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold L. Stewart Harold L. Stewart senior pathologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 4, February 1942, Pages 361–367, https://doi.org/10.1093/jnci/2.4.361 Published: 01 February 1942
SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling
Authors: Victor S Cortez, Tyler K Ulland, Luisa Cervantes-Barragan, Jennifer K Bando, Michelle L Robinette, Qianli Wang, Andrew J White, Susan Gilfillan, Marina Cella, Marco Colonna
Journal: Nature Immunology (2017)
Diagnosis, management, and causes of meningitis in the Gaza Strip: an analysis of guidelines, field assessment, and microbiological study
Authors: Bjørn G Iversen, Siri L Feruglio, Susanne Dudman, Abdelnasser Soboh, Majdi Dher, Nedal Ismael Ghuneim, Khaled Abu Ali, Mahmoud Daher, Dominique A Caugant, Kirsti Vainio, Rand Salman
Journal: The Lancet (2017)
Abstract 483: Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African Americans and Caucasians
Authors: Marisa Shiina, Yutaka Hashimoto, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Shahryari Varahram, Priyanka Kulkarni, Prita Dasgupta, Mitsuho Sumida, Guoren Deng, Rajvir Dahiya
Journal: Cancer Research (2017)

Abstract African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal tissues. We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3’ untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in African-American cells (MDA-PCa-2b) compared to the Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans. Citation Format: Marisa Shiina, Yutaka Hashimoto, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Shahryari Varahram, Priyanka Kulkarni, Prita Dasgupta, Mitsuho Sumida, Guoren Deng, Rajvir Dahiya. Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African Americans and Caucasians [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 483. doi:10.1158/1538-7445.AM2017-483
Abstract 2323: The inhibitory role of Kaempferol-3-<i>O-</i>rutinoside induced AMPK activation on the growth of human breast cancer cell lines
Authors: Chea Ha Kim
Journal: Cancer Research (2017)

Abstract Solidago virga-aurea, herbaceous perennial plant of the family Asteraceae, has astringent, diuretic, and antiseptic assets. In our current study, we found that kaempferol-3- O -rutinoside (KR) from Solidago virga-aurea extract prompted cellular apoptosis in breast cancer cells. The present study was conducted to investigate its effects on MCF-7 cells with respect to the induction of inhibitory effect on cell viability against MDA-MB-231 and MCF-7 breast cancer cell lines. In addition, apoptotic protein, especially Bim, was also increased in KR treated MDA-MB-231 and MCF-7 cell line. However, an anti-apoptotic protein, Bcl-xL, was not changed by KR. To find out positive regulator of Bim expression, FOXO (forkhead-box transcription factor, group O) 3a and AMPK (5' AMP-activated protein kinase) protein expressions were examined in KR treated cells. Immunoblot analysis showed dramatically increased expressions of FOXO3a and AMPK in KR treated MDA-MB-231 and MCF-7 cells. In addition, cell cycle analysis indicated that G0/G1 arrest was intensely increased in KR treated MDA-MB-231 and MCF-7 cells. Moreover, phospho-AMPK (pT172) and phospho-FOXO3a (S472) expression were also increased in KR treated MDA-MB-231 and MCF-7 cells. Our results suggest that KR induces apoptosis by AMPK-FOXO3a mediated Bim expression. The mechanisms of KR mediated AMPK and FOXO3a regulation is not fully elucidated yet, but further studies about these molecular mechanisms between two proteins will give some ideas for cancer therapies for certain breast cancer patients. Citation Format: Chea Ha Kim. The inhibitory role of Kaempferol-3-O-rutinoside induced AMPK activation on the growth of human breast cancer cell lines [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 2323. doi:10.1158/1538-7445.AM2017-2323
Abstract 403: CRISPR/Cas9 genome-wide sgRNA libraries for loss-of-function and gain-of-function genetic screens
Authors: Donato Tedesco, Paul Diehl, Mikhail Makhanov, Sylvain Baron, Alex Chenchik
Journal: Cancer Research (2017)

Abstract Genome-wide loss-of-function screening is a fundamental method to identify genes responsible for driving biological processes. Complex pooled lentiviral-based libraries expressing large numbers of genetic disruptors, such as shRNAs (RNAi) or sgRNAs (CRISPR), make large-scale cell screening practical. While RNAi-based approaches have proven to be an effective strategy for these screens, recent work has showed CRISPR-based technologies offer not only an effective alternative, but distinct advantage. We will present unpublished data from genetic screens in human cancer cell lines using CRISPR-Knockout (KO), CRISPRi and CRISPRa technologies, as well as RNAi. Although loss-of-function shRNA and sgRNA pooled library screens are similar in concept, the gene loss of function is achieved by different mechanisms (mRNA degradation with RNAi, full gene disruption with CRISPR-KO, transcriptional inhibition with CRISPRi), so some divergences are expected and indeed observed when comparing results obtained using one method versus the other. Furthermore, contrary to RNAi, CRISPR technology can be modified to activate gene expression (CRISPRa), thus enabling the use of genome-wide gain-of-function screening in gene function studies. Citation Format: Donato Tedesco, Paul Diehl, Mikhail Makhanov, Sylvain Baron, Alex Chenchik. CRISPR/Cas9 genome-wide sgRNA libraries for loss-of-function and gain-of-function genetic screens [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 403. doi:10.1158/1538-7445.AM2017-403
Abstract 2955: Gr1-MDSCs and Tregs modulate the prostate cancer progression
Authors: Sanjay Kumar, James Stokes, Udai Singh, Karyn Scissum Gunn, Upender Manne, Selvarangan Ponnazhagan, Manoj K. Mishra
Journal: Cancer Research (2017)

Abstract Myeloid-derived suppressor cells (MDSCs) and Regulatory T cells (Tregs) are the major components of immunosuppressive network that play a critical role in tumor immune evasion. The mechanisms by which tumors induce expansion of suppressive cells and the crosstalk between Gr1-MDSCs (Gr1+, CD11b+, F4/80+) and Tregs relative to TGF-β secretion remain incompletely defined. Prior studies have suggested that MDSCs may contribute to Treg recruitment in cancer. Herein, the goal of this investigation is to examine the role of TGF-β mediated generation of Tregs and Gr1-MDSCs during prostate cancer progression and clearance. To achieve this goal, matrigel system was used along with transgenic adenocarcinoma of mouse prostate (TRAMP-C1, C2 and C3 cell) in C57BL/6 mice. Interestingly, TRAMP-C3 cells are characterized as non-tumorigenic; however, TRAMP-C1 and TRAMP-C2 cells do form tumor. Mice were administered with serial log concentration of TRAMP (C1, C2 and C3) cells along with the matrigel. After three weeks, matrigels along with or without tumor were excised from tumor bearing mice, single cell suspensions was prepared and cells were flow analyzed for GR1-MDSCs and Tregs. Additionally, the TGF-β level was also estimated (colorimetric) in culture supernatant in context to MDSCs and Treg expansion. Our initial findings suggest that the expression of Gr1-MDSCs (Gr1+, CD11b+, F4/80+) and Foxp3+ Tregs increased in TRAMP-C1 and C2 as compared to TRAMP-C3 bearing C57BL/6 mice. These findings indicate that the modulation of Gr1-MDSCs and Tregs could help in tumor suppression. Citation Format: Sanjay Kumar, James Stokes, Udai Singh, Karyn Scissum Gunn, Upender Manne, Selvarangan Ponnazhagan, Manoj K. Mishra. Gr1-MDSCs and Tregs modulate the prostate cancer progression [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 2955. doi:10.1158/1538-7445.AM2017-2955
Abstract 920: ICAM-1(CD54) is involved in the osteogenic differentiation of mesenchymal stem cells and affects the progression of osteosarcoma cells
Authors: Yidan Zhang, Sajida Piperdi, Nikolas Zaphiros, Pratistha Koirala, Tingting Ren, Michael Roth, Jonathan Gill, Bang Hoang, David Geller, Rui Yang, Wendong Zhang, Xiuquan Du, Jinghang Zhang, Richard Gorlick
Journal: Cancer Research (2017)

Abstract Purpose: The aim of this study is to validate the relationship between the expression of ICAM-1(CD54), a cell surface glycoprotein, and osteogenic differentiation of mesenchymal stem cells (MSCs) and the role of ICAM-1 in the progression of osteosarcoma (OS) cells. Experimental Design: To compare the gene expression profiles between MSCs and MSCs after osteogenic induction, a microarray analysis was first performed. The differences in expression of specific genes including ICAM-1 were confirmed using western blot and flow cytometry. MSCs were sorted into two groups of cells by CD105+CD44+CD54+ and CD105+C44+CD54- and properties of these cells were compared. Expression of ICAM-1 among tumor cell lines and xenograft OS cells were tested at the protein level. ICAM-1 was stably, constitutively overexpressed in multiple cell types. Differences in osteogenic differentiation potential between normal cell lines and transformed cell lines were studied using alizarin red S staining. Motility, proliferation and invasion as well as the metastatic potential of the transformed and normal cells were evaluated. Results: The initial microarray analysis revealed that ICAM-1 expression was significantly increased in MSCs after osteogenic induction for 15 days (p=0.042). Consistent results were achieved in western blot and flow cytometry analysis. Further microarray analysis between CD105+CD44+CD54+ and CD105+C44+CD54- groups determined that NF-kB signaling pathway was differentially activated. As for OS cells, ICAM-1 is not expressed at high level among OS tumor cell lines and is inconsistently expressed in xenograft OS cells. Enhanced osteogenic differentiation potential was observed in ICAM-1 overexpressing cells. Although there were no major difference in in vitro motility, proliferation or invasion tests, substantially less lung nodules occurred with transformation as compared to the normal control. Conclusions: ICAM-1 is involved in the osteogenic differentiation of mesenchymal stem cells and its down regulation may be involved in the progression of osteosarcoma cells. Citation Format: Yidan Zhang, Sajida Piperdi, Nikolas Zaphiros, Pratistha Koirala, Tingting Ren, Michael Roth, Jonathan Gill, Bang Hoang, David Geller, Rui Yang, Wendong Zhang, Xiuquan Du, Jinghang Zhang, Richard Gorlick. ICAM-1(CD54) is involved in the osteogenic differentiation of mesenchymal stem cells and affects the progression of osteosarcoma cells [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 920. doi:10.1158/1538-7445.AM2017-920
Abstract 2601: COSMIC-3D: exploring cancer mutations in three dimensions for drug design and discovery
Authors: Harry C. Jubb, Harpreet Saini, Marcel Verdonk, Simon Forbes
Journal: Cancer Research (2017)

Abstract Explosions in the availability of cancer genomic data and protein structure data give us the potential to explore cancer molecular biology at an unprecedented scale, and in atomic detail. We present COSMIC-3D, which combines COSMIC, the most comprehensive cancer mutation database available (http://cancer.sanger.ac.uk), with the wealth of publicly available 3D protein structure data, to create a resource with which the protein-structural nature of cancer can be probed. COSMIC-3D will help us understand which cancer mutations drive the progression of cancers, by identifying which are in functional sites that have an effect on driving cell growth and proliferation, and where they are clustered in protein structures across the proteome, for specific cancer types. Through understanding the effects of cancer mutations on known and predicted drug binding sites, we aim to predict potential new drug targets in cancers, and improve the specificity and efficacy of new or existing drugs, by using protein structure with cancer mutation data to guide mutation-specific drug design. COSMIC-3D is available as a web interface at http://cancer.sanger.ac.uk/cosmic3d, and enables interactive exploration of the cancer mutome in a 3D peptide environment, showing all forms of exonic point mutation. Individual mutant locations can be highlighted as molecular surfaces, while recurrence across nonsynonymous substitutions is visualized as 3D heat-maps. Cancer mutations can also be visualised in combination with precalculated small-molecule “druggable” binding sites, providing a powerful visual approach for development of hypotheses across structural, functional, and drug-resistance impacts of cancer variants. COSMIC-3D shows, for example, the steric occlusion of the binding site of ATP-competitive small-molecule inhibitors in the EGFR kinase domain by the mutation of L858 to arginine; these kinds of insights can be applied to novel cancer targets for any protein-structural mutation of interest. The human cancer structural proteome comprising COSMIC-3D extends to nearly 8,500 human genes; 1/3rd of genes in COSMIC. Over 30,000 human protein structures are available across these genes, to which over 345,000 cancer mutations are mapped. From structure based druggability prediction, over 6,500 proteins in COSMIC are predicted to have small-molecule druggable binding sites, making COSMIC-3D a powerful and exciting resource for the exploration and guidance of drug design and discovery in oncology. Citation Format: Harry C. Jubb, Harpreet Saini, Marcel Verdonk, Simon Forbes. COSMIC-3D: exploring cancer mutations in three dimensions for drug design and discovery [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 2601. doi:10.1158/1538-7445.AM2017-2601
Abstract 3429: Oncogenic function of miR-23b-3p in hepatocellular carcinoma
Authors: Hiroshi Tanabe, Masamichi Hayashi, Hiroyuki Sugimoto, Keisuke Kurimoto, Sho Hirabayashi, Mitsuro Kanda, Hideki Takami, Yokiko Niwa, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Masahiko Koike, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Cancer Research (2017)

Abstract Background: miR-23b has been identified as various cancer-related biomarkers. Interestingly, it works as an oncogenic miRNA in lymphoma, renal cancer and glioma, while it works as a tumor suppressor miRNA in pancreatic cancer, bladder cancer and prostate cancer (Donadeli M et al, Cancer Lett, 2014). We have previously reported miR-23b-3p as a oncomiR in NSCLCs (Begum S, Hayashi M et al, Sci Rep, 2015). To find the correlation to other carcinogenesis, we focused on miR-23b function in hepatocellular carcinoma (HCC). Methods: miR-23b-3p expression was examined in 9 HCC cell lines (SK-Hep1, HuH2, HLE, PLC/PRF/5, HuH1, HuH7, HLF, Hep3B, HepG2). The downstream of miR-23b-3p overexpression was examined by Cancer Pathway Finder (Qiagen). Results were applied to 125 clinical HCC samples (2002-2011 surgically resected). Results: Transfection experiments were performed for HepG2 (miR-23b-3p highly expressed) by siRNA and for SK-Hep1 (lowly expressed) by miRNA mimic. Cancer cell proliferation was activated by miR-23b-3p overexpression, and diminished by its inhibition. In order to find the associated genes, miR-23b-3p overexpressed SK-Hep1 cells were compared with parental SK-Hep1 cells by global gene expression analysis. ANGP1, ERCC5 and G6PD genes were upregulated, while KDR, WEE1, OCLN genes were downregulated. We also detected additional two genes (AUH and MICU3) by TargetScan Release 5.2. Clinical HCC samples were divided into miR-23b-3p upregulated 48 cases (38%) and downregulated 77 cases (62%). Upregulated cases were correlated with aged patients (P=0.015), capsule invasion positive (P=0.039) and serosal invasion positive (P=0.049). Also, they showed significantly poor recurrence free survival (HR=1.64, P=0.037, 95%CI:1.03-2.59) and overall survival (HR=3.10, P=0.001, 95%:1.57-6.29) in multivariable analysis. Conclusion: miR-23b-3p increased the HCC cell proliferation, and indicated the invasive type of HCCs. It functions as a oncogenic biomarker in HCCs and might be a therapeutic target. Citation Format: Hiroshi Tanabe, Masamichi Hayashi, Hiroyuki Sugimoto, Keisuke Kurimoto, Sho Hirabayashi, Mitsuro Kanda, Hideki Takami, Yokiko Niwa, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Masahiko Koike, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera. Oncogenic function of miR-23b-3p in hepatocellular carcinoma [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 3429. doi:10.1158/1538-7445.AM2017-3429
Abstract 1125A: β-hydroxybutyrate inhibits histone deacetylase activity and radiosensitizes malignant glioma cells
Authors: Eric C. Woolf, Alex P. Rossi, Helena B. Silva-Nichols, Kara D. Gardner, Nelofer Syed, Adrienne C. Scheck
Journal: Cancer Research (2017)

Abstract Several preclinical studies support the use of the therapeutic ketogenic diet (KD) and/or caloric restriction (CR) as an adjuvant to cancer therapy. This data not only suggests that this approach alters multiple hallmarks of cancer growth, but that it may also enhance other therapeutic modalities. We have demonstrated that the unrestricted KD greatly increases survival in a mouse model of malignant glioma when administered in combination with radiation, yet the underlying mechanisms are not fully elucidated. Mounting evidence suggests that the abnormal epigenetic landscape in tumors may, among other things, impact radiosensitivity. Specifically, many cancers exhibit increased histone deacetylase (HDAC) activity which contributes to the epigenetic milieu found in tumors and alters DNA damage repair. It was recently demonstrated that the ketone body β-hydroxybutyrate (BHB) inhibits HDAC activity in normal mouse tissue. As the use of HDAC inhibitors as anti-cancer agents has generated great interest, we examined the effect of BHB on HDAC activity and radiosensitivity in the context of malignant glioma. We found that BHB radiosensitizes mouse glioma, human glioma and human glioma stem-like cells in vitro. We also demonstrate that BHB inhibits HDAC activity in a dose dependent manner and alters key components of DNA damage repair. Taken together this data opens up another avenue for understanding the mechanisms underlying the KD and its impact on radiation therapy, ultimately helping us better understand how to implement it for clinical use in oncology. Citation Format: Eric C. Woolf, Alex P. Rossi, Helena B. Silva-Nichols, Kara D. Gardner, Nelofer Syed, Adrienne C. Scheck. β-hydroxybutyrate inhibits histone deacetylase activity and radiosensitizes malignant glioma cells [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 1125A. doi:10.1158/1538-7445.AM2017-1125A
Abstract 3821: Biochemical parameters of breast cancer patients in Nigeria
Authors: Sandra A. Udegbe, Atinuke G. Oyinbo, Andiyenema N. Akaiso, Kingsley E. Nwaonumah, Emeka Eze Iweala
Journal: Cancer Research (2017)

Abstract Studies have revealed the importance of differential biochemical parameters of cancer patients in the development of critical biomarkers for accurate diagnosis and treatment. There is a dearth of information on the biochemical characteristics of breast cancer patients in Nigeria which may vary from other climes. The discovery of new biomarkers will provide a deeper understanding of the disease and wider scope of diagnosis and hence improvement in management of breast cancer. In this line of investigation, we examined some biochemical parameters including Alanine transaminase (ALT), Alkaline phosphatase (ALP), Low density lipoprotein (LDL), High density lipoprotein (HDL) and triglycerides (TRIG) in the plasma of 53 breast cancer patients and 14 controls. The data obtained indicates that there were no significant differences in the ALP, LDL and TRIG while ALT and HDL were significantly difference. This indicates the possible implication of ALT and HDL in breast cancer disease in Nigeria and their potential to be further developed into biomarkers for diagnosis. Citation Format: Sandra A. Udegbe, Atinuke G. Oyinbo, Andiyenema N. Akaiso, Kingsley E. Nwaonumah, Emeka Eze Iweala. Biochemical parameters of breast cancer patients in Nigeria [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 3821. doi:10.1158/1538-7445.AM2017-3821