tbuckley/cabot-search huggingface dataset:
Traditions, Values, and Humanitarian Action
Authors: J. F. Fennelly
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 5283: Association between body mass index and prostate cancer among African American men
Authors: Margaret S. Pichardo, Cheryl J. Smith, Wei Tang, Tiffany Dorsey, Stefan Ambs
Journal: Cancer Research (2017)

Abstract Prostate cancer (PCa) is a leading cause of cancer death in US men. Yet, the etiology of prostate cancer remains poorly understood, with only older age, African ancestry, family history of the disease, and multiple germline genetic variations being established disease risk factors. Prostate cancer occurs more often in African-American (AA) men and Caribbean men of African descent than in men of other race/ethnicities. While it has been previously suggested that obesity (measured using body mass index [BMI, kg/m2]) may worsen disease-related outcomes among prostate cancer patients, the relationship of obesity and prostate cancer risk, using race as a predictor, has not been fully explored. Using multivariable logistic regression, we estimated the risk of total PCa for 976 cases and 1,032 age-matched controls, with equal proportions of European-American (EA) and AA men. Among men in the NCI Maryland Prostate Cancer Case-Control Study, BMI was inversely associated with disease outcomes in AA men, but not among EA men. Consistent with previous literature, BMI in EA men was shown to be positively associated with overall prostate cancer risk. Our findings suggest an obesity paradox, where obesity may protect against incidence of PCa among AA men. Studies are needed to elucidate the underlying mechanisms responsible for the differential effects of obesity in AA and EA men with prostate cancer. Citation Format: Margaret S. Pichardo, Cheryl J. Smith, Wei Tang, Tiffany Dorsey, Stefan Ambs. Association between body mass index and prostate cancer among African American men [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 5283. doi:10.1158/1538-7445.AM2017-5283
Abstract 1334: Mesenchymal cell sub-populations selectively modulate paracrine hedgehog signaling in triple negative breast cancer
Authors: Karla P. Ramos, Maribella Domenech
Journal: Cancer Research (2017)

Abstract Recent studies correlate Hedgehog (Hh) signaling with reduced survival rates in triple negative breast cancer (TNBC) patients. Activation of hedgehog signaling in the adjacent mesenchyme has been shown to promote tumor growth and it is a poor prognosis factor for TNBC. We developed a novel tumor-mesenchymal in vitro model of hedgehog signaling in TNBC to evaluate the role of mesenchymal cell sub-populations in the proliferative potential and stem cell markers of breast cancer cells using a custom designed multiwell array. As a source of mesenchymal cell sub-populations we evaluated myofibroblasts, mesenchymal stem cells derived from bone marrow or adipose tissue and tumor cells that undergo epithelial-mesenchymal transition (EMT). Tumor cells were culture with 1 or 2 mesenchymal cell sub-populations in adjacent compartments +/- SHH ligand for 72-96hrs. Active Hh signaling was confirmed by up-regulation of main Hh target genes (e.g. Gli1, Patch1). Paracrine Hh signaling only in bone marrow-derived mesenchymal stem cell and EMT significantly increased proliferation (10-15%) of TNBC and normal breast cancer cell lines. Addition of adipose-derived mesenchymal stem cells or pharmacological Hh inhibitors (Cyclopamine and Gant61) partially abolished tumor growth indicating that other non-canonical signals are involve in paracrine Hh-driven tumors. Cancer stem cell markers were selectively modulated in co-cultures. Our results suggest that paracrine Hh signaling-driven by bone marrow and EMT mesenchymal are potential therapeutic targets to treating TNBC. Citation Format: Karla P. Ramos, Maribella Domenech. Mesenchymal cell sub-populations selectively modulate paracrine hedgehog signaling in triple negative breast 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 1334. doi:10.1158/1538-7445.AM2017-1334
Abstract 3176: Inhibition of HER2/β-catenin signaling by penfluridol overcomes resistance to paclitaxel in breast cancer
Authors: Nehal Gupta, Parul Gupta, Sanjay Srivastava
Journal: Cancer Research (2017)

Abstract Paclitaxel is a first line treatment option for patients with metastatic breast cancer. However, inherited or acquired resistance is a limiting factor for therapy with paclitaxel. The mechanism of paclitaxel resistance remains obscured and hinders the development of therapeutic strategies. HER2 is an oncogene overexpressed in about 30% of breast cancer patients and plays role in drug resistance leading to poor prognosis. To identify more clinically relevant mechanism of paclitaxel resistance, we developed resistance to paclitaxel in MCF-7 and 4T1 breast cancer cell lines. The continuous exposure to paclitaxel for several months resulted in &amp;gt;1000 fold resistance in MCF-7 cells and &amp;gt;100 fold resistance in 4T1 cells. Western blot analysis showed enhanced expression of HER2, β-catenin and downstream molecules such as TCF/LEF, c-Myc, Cyclin D in these resistant cells. We have recently demonstrated that penfluridol, an anti-psychotic drug, suppresses the growth of triple negative metastatic breast cancer cells (Ranjan and Srivastava, Cancer Res 2016; 76(4): 877-890), giving us the rationale to evaluate whether penfluridol inhibits HER2 and β-catenin signaling. Our current results showed that penfluridol treatment not only suppressed HER2 but also inhibited β-catenin expression. We also observed down regulation of LEF-1/TCF, Cyclin D1 and c-Myc expression with penfluridol treatment in paclitaxel sensitive as well as resistant cells resulting in reduced survival of cells. Our results further showed that penfluridol treatment synergistically enhanced the growth suppressive effects of paclitaxel in MCF-7 and 4T1 paclitaxel resistant cells. Treatment of paclitaxel resistant 4T1 cells with 1.5μM of penfluridol in combination with 50nM of paclitaxel resulted in 65% of cell growth suppression whereas either treatment alone was not cytotoxic at all. We also observed an enhanced down regulation of proteins involved in paclitaxel resistance such as HER2, β-catenin, c-Myc and Cyclin D1 as well as increase in apoptotic markers such as Cl-PARP and Cl-Caspase3 when paclitaxel treatment was combined with penfluridol in resistant cells. Taken together, our results provided a novel insight into the mechanism of resistance to paclitaxel and also opened new avenues for application of penfluridol in cancer therapeutics. Further detailed mechanistic and in vivo studies are in progress. (Supported in part by RO1 grant CA129038, awarded by National Cancer Institute, NIH). Citation Format: Nehal Gupta, Parul Gupta, Sanjay Srivastava. Inhibition of HER2/β-catenin signaling by penfluridol overcomes resistance to paclitaxel in breast 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 3176. doi:10.1158/1538-7445.AM2017-3176
Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?
Authors: Kenneth F Baker, John D Isaacs
Journal: Annals of the Rheumatic Diseases (2017)

The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.
Abstract 3977: Neutrophils fertilize the pre-metastatic omental niche in ovarian cancer
Authors: WonJae LEE, Honami Naora
Journal: Cancer Research (2017)

Abstract More than 60% of ovarian cancer patients present with peritoneal carcinomatosis that almost always involves the omentum, a fat pad that suspends from the stomach. However, the mechanisms that promote the tropism of ovarian cancer cells for the omentum are poorly understood. Because the omentum is the major peritoneal conduit and reservoir for immune cells, we hypothesized that immune cells control the propensity of ovarian cancer cells to implant on the omentum. In this study, we evaluated changes in immune cell populations in the omentum and in other visceral fat pads in the peritoneal cavity in mouse xenograft models of ovarian cancer. Intriguingly, the proportion of neutrophils was observed to dramatically increase in the omentum prior to tumor cell implantation at this site. On the other hand, the proportion of neutrophils did not substantially increase in other visceral fat pads. Furthermore, the proportion of macrophages did not significantly increase in any of the fat tissues prior to tumor cell implantation. Collectively, these findings raise the possibility that early recruitment of neutrophils to the pre-metastatic omental niche promotes a microenvironment that is conducive to ovarian cancer cell implantation at this site. Citation Format: WonJae LEE, Honami Naora. Neutrophils fertilize the pre-metastatic omental niche in ovarian 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 3977. doi:10.1158/1538-7445.AM2017-3977
Abstract 2611: A crowdsourcing-based clinical trial information curation and searching system
Authors: Pengfei Yu, Qingxuan Song, Yang Han, Guanghui Hu
Journal: Cancer Research (2017)

Abstract Targeted cancer therapies based on actionable mutations identified are the future of cancer treatment. Besides those approved by the Food and Drug Administration (FDA) for different types of cancers, many other target therapy drugs are in development under different phases of clinical trials. Access to information about these clinical trials is important to health care professionals and patients. Public clinical trials database (www.clinicaltrials.gov) provides a very comprehensive resource for clinicians and researches to search for relevant clinical trials based on different kinds of searching criteria. However, due to the complexity of wording and phasing upon submission, some of the searching results returned by native search engine did not perfectly match the search criteria. Many undesired results are presented with false positives and false negatives when users are searching for clinical trials targeting specific actionable mutations. To tackle this problem, we developed a crowd-sourcing based clinical trial curation and searching system on top of the information extracted from public database. We divide the information extracted from clinicaltrials.gov into three different levels: standard, easy-to-clean and unstructured. With the crowdsourcing approach, our online system can harness the brainpower of biological scientists to translate the most unstructured information such as cancer types, gene mutations into standard format that is easy to be queried. In the searching phase, we combine the aspects of actionable mutation, cancer type, location, and clinical trial phase to select the best matches between patient conditions and clinical trials in our curated database. With the same searching criteria, our system can provide more relevant clinical trials compared with those provided by clinicaltrials.gov. The curation system is currently open to reviewers with eligibility check. And the search engine is publicly available at: https://agis.admerahealth.com/AGIS/ClinTrials/. Citation Format: Pengfei Yu, Qingxuan Song, Yang Han, Guanghui Hu. A crowdsourcing-based clinical trial information curation and searching system [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 2611. doi:10.1158/1538-7445.AM2017-2611
Obstetrics and Gynaecology
Journal: JAMA (1922)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical Notes, Suggestions, and New Instruments
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 5008: The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation
Authors: Gino B. Ferraro, David P. Kodack, Vasileios Askoxylakis, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Alexander Z. Cao, Rakesh R. Ramjiawan, Divya Bezwada, Bhushankumar Patel, Youngchul Song, Carlotta Costa, Kamila Naxerova, Christina Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G. Duda, Ryan C. Miller, Marni B. Siegel, Carey K. Anders, Melinda Sanders, Valeria M. Estrada, Robert Schlegel, Carlos L. Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A. Engelman, Rakesh K. Jain
Journal: Cancer Research (2017)

Abstract Brain metastases represent a devastating progression of luminal breast cancer. While targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade PI3K inhibition despite efficient drug delivery. In comparison to extracranial disease, there is increased HER3 expression and phosphorylation in the brain lesions. HER3 blockade overcomes the resistance of both HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, leading to striking tumor growth delay and significant improvement of mouse survival. Collectively, these data provide a mechanistic basis underlying therapeutic resistance in the brain microenvironment and identify rapidly translatable treatment strategiesfor HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases. Citation Format: Gino B. Ferraro, David P. Kodack, Vasileios Askoxylakis, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Alexander Z. Cao, Rakesh R. Ramjiawan, Divya Bezwada, Bhushankumar Patel, Youngchul Song, Carlotta Costa, Kamila Naxerova, Christina Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G. Duda, Ryan C. Miller, Marni B. Siegel, Carey K. Anders, Melinda Sanders, Valeria M. Estrada, Robert Schlegel, Carlos L. Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A. Engelman, Rakesh K. Jain. The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation [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 5008. doi:10.1158/1538-7445.AM2017-5008
Abstract 3196: Genetic and pharmacologic approaches to overcome epithelial to mesenchymal mediated chemoresistance in breast cancer
Authors: Michael J. Crowley, Nasser Altorki, Vivek Mittal, Dingcheng Gao
Journal: Cancer Research (2017)

Abstract Development of resistance to conventional chemotherapy remains a major barrier to effective treatment of breast cancer. We and others have recently demonstrated in breast and pancreatic cancer models that epithelial-mesenchymal transition (EMT) may not be a critical mediator of cancer metastasis, however, it contributes to cancer drug resistance (Fischer et al. Nature 2015; Zeng et al Nature 2015). Importantly, blocking EMT through miR-200 family abrogated chemoresistance, indicating potentials for clinical translation. Using our novel EMT lineage tracing system, we have performed both genetic (CRISPR/Cas9 mediated genome-wide targeted mutagenesis) and pharmacological (high-throughput small molecule libraries) screens, to identify potential candidates to overcome EMT-mediated chemoresistance in breast cancer metastasis. The identified molecules provide not only novel mechanistic insights but also attractive anti-metastatic strategies for breast cancer treatment and the design of future clinical trials. Citation Format: Michael J. Crowley, Nasser Altorki, Vivek Mittal, Dingcheng Gao. Genetic and pharmacologic approaches to overcome epithelial to mesenchymal mediated chemoresistance in breast 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 3196. doi:10.1158/1538-7445.AM2017-3196