tbuckley/cabot-search huggingface dataset:
Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival
Authors: Jung S. Byun, Sandeep K. Singhal, Samson Park, Dae Ik Yi, Tingfen Yan, Ambar Caban, Alana Jones, Partha Mukhopadhyay, Sara M. Gil, Stephen M. Hewitt, Lisa Newman, Melissa B. Davis, Brittany D. Jenkins, Jorge L. Sepulveda, Adriana De Siervi, Anna María Nápoles, Nasreen A. Vohra, Kevin Gardner
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor–positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation. Experimental Design: Data and biospecimens from 262 AA and 293 EA patients diagnosed with breast cancer from 2001 to 2010 at a major medical center were analyzed by IHC for functional biomarkers of luminal differentiation, including estrogen receptor (ESR1) and its pioneer factors, FOXA1 and GATA3. Integrated comparison of protein levels with network-level gene expression analysis uncovered predictive correlations with race and survival. Results: Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race: ESR1 [EA HR = 0.47; 95% confidence interval (CI), 0.31–0.72 and AA HR = 0.77; 95% CI, 0.48–1.18]; FOXA1 (EA HR = 0.38; 95% CI, 0.23–0.63 and AA HR = 0.53; 95% CI, 0.31–0.88), and GATA3 (EA HR = 0.36; 95% CI, 0.23–0.56; AA HR = 0.57; CI, 0.56–1.4). In addition, we identify genes in the downstream regulons of these biomarkers highly correlated with race and survival. Conclusions: Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical outcome. Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival.
Deregulation and the Assault on Science and the Environment
Authors: Jonathan M. Samet, Thomas A. Burke
Journal: Annual Review of Public Health (2020)

The quality of the environment is a major determinant of the health and well-being of a population. The role of scientific evidence is central in the network of laws addressing environmental pollution in the United States and has been critical in addressing the myriad sources of environmental pollution and the burden of disease attributable to environmental factors. We address the shift away from reasoned action and science to a reliance on belief and document the efforts to separate regulation from science and to remove science-based regulations and policies intended to protect public health. We outline the general steps for moving from research to policy, show how each has been undermined, offer specific examples, and point to resources that document the enormity of the current efforts to set aside scientific evidence.
A Study of the Impact of the 21-Gene Breast Cancer Assay on the Use of Adjuvant Chemotherapy in Women With Breast Cancer in a Mexican Public Hospital
Authors: J.E. Bargallo-Rocha, F. Lara, R.J. Shaw Dulin, V. Perez-Sánchez, C. Villarreal-Garza, H. Maldonado-Martinez, A. Mohar-Betancourt, C. Yoshizawa, E. Burke, C. Chao
Journal: Annals of Oncology (2012)
Association of Cisplatin Induced Nephrotoxicity with Clinical Characteristics and Treatment Methods in Patients with Thoracic Malignancy
Authors: T. Yoshida, S. Niho, M. Toda, T. Ogawa, S. Matsumoto, S. Umemura, K. Yoh, K. Goto, H. Ohmatsu, Y. Ohe
Journal: Annals of Oncology (2012)
IiWRKY34 positively regulates yield, lignan biosynthesis and stress tolerance in Isatis indigotica
Authors: Ying Xiao, Jingxian Feng, Qing Li, Yangyun Zhou, Qitao Bu, Junhui Zhou, Hexin Tan, Yingbo Yang, Lei Zhang, Wansheng Chen
Journal: Acta Pharmaceutica Sinica B (2020)

Yield potential, pharmaceutical compounds production and stress tolerance capacity are 3 classes of traits that determine the quality of medicinal plants. The autotetraploid Isatis indigotica has greater yield, higher bioactive lignan accumulation and enhanced stress tolerance compared with its diploid progenitor. Here we show that the transcription factor IiWRKY34, with higher expression levels in tetraploid than in diploid I. indigotica, has large pleiotropic effects on an array of traits, including biomass growth rates, lignan biosynthesis, as well as salt and drought stress tolerance. Integrated analysis of transcriptome and metabolome profiling demonstrated that IiWRKY34 expression had far-reaching consequences on both primary and secondary metabolism, reprograming carbon flux towards phenylpropanoids, such as lignans and flavonoids. Transcript–metabolite correlation analysis was applied to construct the regulatory network of IiWRKY34 for lignan biosynthesis. One candidate target Ii4CL3, a key rate-limiting enzyme of lignan biosynthesis as indicated in our previous study, has been demonstrated to indeed be activated by IiWRKY34. Collectively, the results indicate that the differentially expressed IiWRKY34 has contributed significantly to the polyploidy vigor of I. indigotica, and manipulation of this gene will facilitate comprehensive improvements of I. indigotica herb.
A Small Hypoxia Signature Predicted pCR Response to Bevacizumab in the Neoadjuvant GeparQuinto Breast Cancer Trial
Authors: Thomas Karn, Tobias Meissner, Karsten E. Weber, Christine Solbach, Carsten Denkert, Knut Engels, Peter A. Fasching, Bruno V. Sinn, Iris Schrader, Jan Budczies, Frederik Marmé, Volkmar Müller, Uwe Holtrich, Bernd Gerber, Christian Schem, Brandon M. Young, Claus Hanusch, Elmar Stickeler, Jens Huober, Marion van Mackelenbergh, Brian Leyland-Jones, Tanja Fehm, Valentina Nekljudova, Michael Untch, Sibylle Loibl
Journal: Clinical Cancer Research (2020)

In breast cancer, bevacizumab increased pCR rate but not long-term survival and no predictive markers are available to identify patients with long-term benefit from the drug.We profiled 289 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) biopsies of HER2-negative patients from the GeparQuinto trial of neoadjuvant chemotherapy ± bevacizumab by exome-capture RNA-sequencing (RNA-seq). In a prospectively planned study, we tested molecular signatures for response prediction. IHC validation was performed using tissue microarrays.We found strong agreement of molecular and pathologic parameters as hormone receptors, grading, and lymphocyte infiltration in 221 high-quality samples. Response rates (49.3% pCR overall) were higher in basal-like (68.9%) and HER2-enriched (45.5%) than in luminal B (35.7%), luminal A (17.9%), and normal-like (20.0%) subtypes. T-cell (OR = 1.60; 95% confidence interval, 1.21-2.12; P = 0.001), proliferation (OR = 2.88; 95% CI, 2.00-4.15; P < 0.001), and hypoxia signatures (OR = 1.92; 95% CI, 1.41-2.60; P < 0.001) significantly predicted pCR in univariate analysis. In a prespecified multivariate logistic regression, a small hypoxia signature predicted pCR (OR = 2.40; 95% CI, 1.28-4.51; P = 0.006) with a significant interaction with bevacizumab treatment (P = 0.020). IHC validation using NDRG1 as marker revealed highly heterogenous expression within tissue leading to profound loss of sensitivity in TMA analysis, still a significant predictive value for pCR was detected (P = 0.025).Exome-capture RNA-seq characterizes small FFPE core biopsies by reliably detecting factors as for example ER status, grade, and tumor-infiltrating lymphocytes levels. Beside molecular subtypes and immune signatures, a small hypoxia signature predicted pCR to bevacizumab, which could be validated by IHC. The signature can have important applications for bevacizumab treatment in different cancer types and might also have a role for novel combination therapies of bevacizumab with immune checkpoint inhibition.
The role of tumor vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFR) polymorphisms in the prediction of clinical outcome for advanced renal cell carcinoma patients receiving first-line sunitinib.
Authors: Maristella Bianconi, Mario Scartozzi, Luca Faloppi, Riccardo Giampieri, Elena Maccaroni, Alessandro Bittoni, Michela Del Prete, Cristian Loretelli, Laura Belvederesi, Alessandro Conti, Luciano Burattini, Daniele Minardi, Rosa Rita Silva, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2012)

e15074 Background: metastatic renal cell carcinoma (mRCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic strongholds are TKIs directed against the VEGF family (sunitinib and sorafenib). The aim of our study is to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms, in determining the clinical outcome of mRCC patients receiving first-line sunitinib Methods: 41 histologic samples (biopsies and surgical specimens) of mRCC patients were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first line treatment. Results: VEGF A rs833061 C&gt;T polymorphism was statistically significant in PFS (17 months for C vs 4 months for T; P = 0,0029) and OS (35,93 months for C vs 11 months for T; P = 0,0267). VEGF A rs699947 A&gt;C was statistically significant for PFS (17 months for A vs 3,97 months for C; P = 0,0023) and OS (35,93 months for A vs 10,98 for C; P = 0,0272). VEGF A rs2010963 G&gt;C was significant in PFS (16,98 months for G vs 4,65 for G/C vs 2,73 for C; P = 0,0188). VEGR3 rs6877011 C&gt;G was significant in PFS (8,22 months for C vs 2,22 for C/G; P = 0,0361) and OS (35,93 months for C vs 12,08 for C/G; P = 0,0183). Conclusions: in our analysis patients with C polymorphism of rc833061, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line. These polymorphisms of the VEGF-A gene are probably connected with a better control of the neoangiogenesis process during TKIs therapy, maybe leading to vasculature normalization. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first line therapy. VEGFR-3 role is still matter of debate but seems to be involved in vessels sprouting and architecture.
Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
Authors: Katharina Schimmel, Mira Jung, Ariana Foinquinos, Gorka San José, Javier Beaumont, Katharina Bock, Lea Grote-Levi, Ke Xiao, Christian Bär, Angelika Pfanne, Annette Just, Karina Zimmer, Soeun Ngoy, Begoña López, Susana Ravassa, Sabine Samolovac, Heike Janssen-Peters, Janet Remke, Kristian Scherf, Seema Dangwal, Maria-Teresa Piccoli, Felix Kleemiss, Fabian Philipp Kreutzer, Franziska Kenneweg, Julia Leonardy, Lisa Hobuß, Laura Santer, Quoc-Tuan Do, Robert Geffers, Jan Hinrich Braesen, Jessica Schmitz, Christina Brandenberger, Dominik N. Müller, Nicola Wilck, Volkhard Kaever, Heike Bähre, Sandor Batkai, Jan Fiedler, Kevin M. Alexander, Bradley M. Wertheim, Sudeshna Fisch, Ronglih Liao, Javier Diez, Arantxa González, Thomas Thum
Journal: Circulation (2020)

Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis.Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II-mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing.High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds.We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction.
Hyperbaric Oxygenation and Ep (Cisplatin and Etoposide) Chemotherapy in Treatment of Patients with Advanced Non Small Cells Lung Cancer (NSCLC)
Authors: M.V. Kopp, I.A. Koroleva, S.V. Kozlov, L.V. Shaplygin, M.E. Popova, J.G. Kutyreva
Journal: Annals of Oncology (2012)
Dacomitinib (PF-00299804), An Irreversible Pan-Her Tyrosine Kinase Inhibitor (TKI), For First-Line Treatment of EGFR-Mutant or Her2-Mutant or -Amplified Lung Cancers
Authors: M. Kris, Z. Goldberg, P.A. Janne, D. Kim, R. Martins, T.S.K. Mok, J. O'Connell, S. Ou, I. Taylor, H. Zhang
Journal: Annals of Oncology (2012)
New primary care network contract won’t work, GPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2020)

A proposed new contract for general practices to participate in primary care networks contains unrealistic demands and will pile new layers of bureaucracy on overstretched practices, GPs have warned.

NHS England and NHS Improvement published draft service specifications for the primary care networks directed enhanced service (DES) in a consultation released on 23 December.1 Practices that sign up from April 2020 will be required to provide five national services over a phased period of a year.

The draft document stipulates that from September 2020 GPs will have to visit patients in care homes at least once a fortnight as part of an enhanced care service in residential homes. And from April 2020 primary care networks will be expected to …
Ghulam Jeelani Drabu
Authors: Khalid J Drabu, Tariq J Drabu, Yasmin J Drabu, Reefat K Drabu
Journal: BMJ (2020)

Ghulam Jeelani Drabu was born in Rajpora, Kashmir, on 21 August 1926, the fifth son of a well respected family of landowners who were fruit merchants. He was one of 13 siblings—eight brothers and five sisters. His father ensured that he received his basic education in the village school of Rajpora and his secondary education in the city of Srinagar. It was decided by his elder brother that he should study medicine, and before India’s partition he gained entrance into the prestigious King Edward Medical College in Lahore. He graduated in 1948 and bore witness to the partition of the Indian subcontinent; events that did not allow him to return home for 18 years. During the partition he worked in refugee camps and witnessed and felt deeply sad about the human suffering brought about by this political upheaval.

After graduating—as he had qualified in the newly formed Pakistan—Ghulam was …
Effect of Japanese Traditional Medicine, TJ-41, on Quality of Life for Patients with Non-Small Lung Cancer Receiving Outpatient Chemotherapy
Authors: Y. Ishiura, H. Yamamoto, Y. Terasaki, W. Fukushima, H. Hirosawa, F. Tanikawa, H. Hayase, K. Maruyama, C. Oabata, N. Hirokami, K. Kasahara
Journal: Annals of Oncology (2012)
A Randomized Phase II Study of Axitinib Plus Pemetrexed/Cisplatin (PEM/CIS) for Non-Small-Cell Lung Cancer (NSCLC)
Authors: A. Ono, N. Yamamoto, T. Takahashi, H. Murakami, T. Naito, K. Kaira, Y. Umeyama, C.P. Belani
Journal: Annals of Oncology (2012)
How Effective and Safe Is Factor XI Inhibition in Preventing Venous Thrombosis?
Authors: Kenneth A. Bauer
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Validation Study of a Prognostic Classification System in Patients with Metastatic Colorectal Cancer who Received Irinotecan-Based Second-Line Chemotherapy
Authors: Y. Naito, K. Shitara, K. Yamazaki, S. Yuki, H. Yasui, Y. Kawamoto, T. Takano, Y. Komatsu, K. Muro
Journal: Annals of Oncology (2012)
Advanced delivery strategies facilitating oral absorption of heparins
Authors: Guihua Fang, Bo Tang
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Heparins show great anticoagulant effect with few side effects, and are administered by subcutaneous or intravenous route in clinics. To improve patient compliance, oral administration is an alternative route. Nonetheless, oral administration of heparins still faces enormous challenges due to the multiple obstacles. This review briefly analyzes a series of barriers ranging from poorly physicochemical properties of heparins, to harsh biological barriers including gastrointestinal degradation and pre-systemic metabolism. Moreover, several approaches have been developed to overcome these obstacles, such as improving stability of heparins in the gastrointestinal tract, enhancing the intestinal epithelia permeability and facilitating lymphatic delivery of heparins. Overall, this review aims to provide insights concerning advanced delivery strategies facilitating oral absorption of heparins.
The characterisation of subjective cognitive decline
Authors: Frank Jessen, Rebecca E Amariglio, Rachel F Buckley, Wiesje M van der Flier, Ying Han, José Luis Molinuevo, Laura Rabin, Dorene M Rentz, Octavio Rodriguez-Gomez, Andrew J Saykin, Sietske A M Sikkes, Colette M Smart, Steffen Wolfsgruber, Michael Wagner
Journal: The Lancet Neurology (2020)
Phase I Clinical Trial of Cancer Vaccine Combined with Chemotherapy Targeting both Tumor Antigen and Immune Tolerance Against Advanced Solid Tumors
Authors: M. Murahashi, Y. Hijikata, Y. Tanaka, H. Inoue, T. Marumoto, Y. Nakanishi, K. Yoshida, T. Tsunoda, Y. Nakamura, K. Tani
Journal: Annals of Oncology (2012)
Disease Progression Clinically Judged without Confirmation by Image Diagnosis in a Randomized Phase III Trial of advanced Gastric Cancer (JCOG9912)
Authors: H. Kawai, N. Boku, Y. Yamada, N. Fuse, H. Yasui, A. Sawaki, W. Koizumi, J. Mizusawa, K. Nakamura, A. Takashima
Journal: Annals of Oncology (2012)
Efficacy of Gemcitabine as Second-Line Therapy after Failure of S-1 Therapy for Metastatic Pancreatic Carcinoma
Authors: M. Fukahori, S. Kondo, H. Ueno, S. Shimizu, S. Mitsunaga, M. Ikeda, T. Yamaguchi, Y. Sakamoto, C. Morizane, T. Okusaka
Journal: Annals of Oncology (2012)
Progressive Dyspnea in a Woman With Genital Skin Lesions
Authors: Hiroyuki Teruya, Mitsuru Mukaigawara, Kazuhito Hirata
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor
Authors: Xiaoqi Sun, Di Liu, Xiaoyu Xu, Yifeng Shen, Yanjuan Huang, Zishan Zeng, Meng Xia, Chunshun Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Hypoxia is a typical feature of solid tumors, which highly limits the application of the oxygen-dependent therapy. Also, the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor. Thereby, we designed a novel localized injectable hydrogel combining the photothermal therapy (PTT) and the thermodynamic therapy (TDT), which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy. In our study, gold nanorods (AuNRs) and 2,2′-Azobis[2-(2-imidazalin-2-yl)propane] dihydrochlaride (AIPH) were incorporated into the hydrogel networks, which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide (NIPAM) and hydrophilic glycidyl methacrylate modified hyaluronic acid (HA-GMA) to fabricate an injectable and near-infrared (NIR) responsive hydrogel. The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation, but also generate free radicals even in hypoxic condition. Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors, achieving the controlled drug release on demand. The designed hydrogel with a sufficient loading capacity, excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation. The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen. Therefore, this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.