tbuckley/cabot-search huggingface dataset:
DNA structural polymorphism in the proximal promoter of the vascular endothelial growth factor gene
Authors: Kexiao Guo, Vijay Gokhale, Laurence Hurley, Daekyu Sun
Journal: Cancer Research (2008)

3189  Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. A polyguanine/polycytosine (polyG/polyC) tract in the proximal promoter of the VEGF gene is essential for its promoter activity. Because this polyG/polyC tract is very dynamic in nature, it is able to unwind into single-stranded DNA and adopt non-B-DNA conformations, which potentially play a role in VEGF transcriptional regulation. In this study, we characterized the secondary structures that are formed in the guanine-rich (G-rich) and cytosine-rich (C-rich) strands of this tract using various biochemical and biophysical techniques. It was revealed that, in the presence of 100 mM KCl, the G-rich strand is able to adopt two parallel G-quadruplex loop isomers containing three G-tetrads with three double-chain-reversal loops of either 1:4:1 or 1:2:3. Our CD melting experiment and polymerase stop assay suggested that the G-quadruplex containing 1:4:1 double-chain-reversal loops is the more thermodynamically stable conformation that the G-rich strand readily adopts. This provides strong evidence that the sequences and sizes of the loops are critical for the formation and stability of G-quadruplexes. Our molecular model showed that the guanines at the 5’-end and the 3’-end of the G-quadruplex provide a stable capping structure. The complementary C-rich strand is able to form an intramolecular i-motif structure at slightly acidic pH, which involves six C-C+ base pairs and three loops of 2:3:2. One guanine and cytosine in one of the loops stabilize the i-motif by stacking interactions. Taken together, our results demonstrate that the G-quadruplex and i-motif structures are able to form in the G-rich and C-rich strands respectively of the polyG/polyC tract in the VEGF proximal promoter under conditions that favor the transition of B-DNA to non-B-DNA conformations. These unique secondary structures may be novel targets for anti-angiogenesis therapy in cancer.
In pursuit of a flawless aphrodite: paving the way to scarless oncoplastic breast surgery
Authors: Liling Zhu, Shunrong Li, Luyuan Tan, Xiaolan Zhang, Jiannan Wu, Fengxi Su, Kai Chen, Erwei Song
Journal: Cancer Communications (2019)

Breast cancer is the most commonly diagnosed malignancy in women worldwide [1, 2] and in the twentieth century, mastectomy was the primary surgical treatment for breast cancer patients. Advances in breast-conserving surgery (BCS) propelled a change in treatment rational from “maximum tolerable” to “minimum effective” therapy. Oncoplastic breast surgery aims to restore the shape of the breast and has been widely adopted since the past decade. Although the cosmetic outcome has been significantly improved, the scar remaining on the surgeried breast skin is still a major pitfall that urges urgent consideration. In this editorial, we review a series of techniques that can be incorporated in oncoplastic breast surgery to minimize scarring, signifying the beginning of an era for scarless oncoplastic surgery.
Extended Mutational Profiling By MSK-IMPACTTM Identifies Mutations Predicting Thromboembolic Risk in Patients with Solid Tumor Malignancy
Authors: Andrew Dunbar, Kelly Bolton, Sean M. Devlin, Francisco Sanchez-Vega, Jianjiong Gao, Jodi V. Mones, Jonathan M. Wills, Daniel Kelly, Mirko Farina, Sirish Kishore, Krishna Juluru, Neil Iyengar, David M. Hyman, Ahmet Zehir, Wungki Park, Alok A Khorana, Gerald A. Soff, Simon Mantha
Journal: Blood (2019)
Human Stem Cells Armed with Bispecific Antibodies Home to Injury-Specific Molecules in Myocardial Infarcts in Nude Rats.
Authors: Lawrence G. Lum, Pamela A. Davol, Richard E. Sievers, Ryan C. Grabert, Qizhi Fang, Jonathan M. Gall, Michael S. Yee, James W. Larrick, Randall J. Lee
Journal: Blood (2004)
Signaling Profiles of T Cells during Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Sydney X. Lu, Vanessa M. Hubbard, Melanie Y. Chow, Theo D. Kim, David Y. Suh, Adam Kochman, Johannes Zakrzewski, Javier Cabrera-Perez, Onder Alpdogan, Marcel M.R.M. van den Brink
Journal: Blood (2005)
A Temporizing Solution to “Artemisinin Resistance”
Authors: Xin-Hui S Chan, Nicholas J White, Tran T Hien
Journal: New England Journal of Medicine (2019)

The authors reply: We do not advocate oral monotherapy with artemisinins.Instead, we en-courage the appropriate use of ACTs and fully support global efforts to eliminate malaria.Recent data show that regionally applied treatment and control measures have been highly effective in the Greater Mekong Subregion. 1 Therapy with dihydroartemisinin-piperaquine fails because of resistance to piperaquine 2 and also perhaps because dihydroartemisinin is more prone to decomposition than artesunate. 3 More recent studies of pyronaridine-artesunate, including a study from Vietnam, confirm that cure rates are higher than 95% and reassure us that effective treatments are available. 4 Thus, artemisinins remain the only available drug class that can manage and eliminate P. falciparum if ACTs are appropriately adjusted, as we elaborated in our Perspective article.Furthermore, our global community should acknowledge a shared future in which no country is neglected.Urgent actions to control malaria should be focused on areas where the highest disease burdens are present, such as in Africa, where, for example, Nigeria bears 25% of the world's malaria burden. 5
The Biological and Clinical Implications of the Alternative Splicing Landscape of 1,258 Myeloid Neoplasm Cases
Authors: Courtney E Hershberger, Devlin C Moyer, Wencke Walter, Stephan Hutter, Claudia Haferlach, Torsten Haferlach, Jaroslaw P. Maciejewski, Richard A Padgett
Journal: Blood (2019)
Analysis of β Globin Mutations in the Indian Population: Presence of Rare and Novel Mutations and Region Wise Heterogeneity.
Authors: Eunice S. Edison, Ramachandran V. Shaji, G.D. Sankari, Auro Viswabandhya, Anu Moses, Biju George, Vikram Mathews, Alok Srivastava, Mammen Chandy
Journal: Blood (2007)
Neurofibromas of Rat Ears Produced by Prolonged Feeding of Crude Ergot
Authors: Arthur A. Nelson, O. Garth Fitzhugh, Herman J. Morris, Herbert O. Calvery
Journal: Cancer Research (1942)

*   Read in part at the Forty-first Annual Meeting of the American Association of Pathologists and Bacteriologists, New York City, April 11, 1941.
Severe Lipoatrophy in a Patient With Type 2 Diabetes in Response to Human Insulin Analogs Glargine and Degludec: Possible Involvement of CD4 T Cell–Mediated Tissue Remodeling
Authors: Tamara Turk Wensveen, Dora Fučkar Čupić, Dubravka Jurišić Eržen, Bojan Polić, Felix M. Wensveen
Journal: Diabetes Care (2019)

Lipoatrophy in response to insulin therapy is a rare condition resulting in a loss of subcutaneous adipose tissue at the site of injection. Since the introduction of humanized insulins, insulin-induced lipoatrophy (IIL) is almost exclusively associated with T1D. IIL was suggested to be an aspect of autoimmunity (1,2), but its underlying pathophysiology is poorly understood. …
Splicing Regulator p54nrb/Non–POU Domain–Containing Octamer‐Binding Protein Enhances Carcinogenesis Through Oncogenic Isoform Switch of MYC Box–Dependent Interacting Protein 1 in Hepatocellular Carcinoma
Authors: Zhixiang Hu, Liangqing Dong, Shengli Li, Zhe Li, Yejun Qiao, Yuchen Li, Jie Ding, Zhiao Chen, Yangjun Wu, Zhen Wang, Shenglin Huang, Qiang Gao, Yingjun Zhao, Xianghuo He
Journal: Hepatology (2019)

Background and Aims Alternative splicing (AS) is a key step that increases the diversity and complexity of the cancer transcriptome. Recent evidence has highlighted that AS has an increasingly crucial role in cancer. Nonetheless, the mechanisms underlying AS and its dysregulation in hepatocellular carcinoma (HCC) remain elusive. Here, we report that the expression of RNA‐binding protein p54 nrb /non‐POU domain‐containing octamer‐binding protein (NONO) is frequently increased in patients with HCC and is associated with poor outcomes. Approach and Results Knockdown of NONO significantly abolished liver cancer cell proliferation, migration, and tumor formation. RNA‐sequencing revealed that NONO regulates MYC box–dependent interacting protein 1 (or bridging integrator 1 [BIN1]; also known as amphiphysin 2 3P9) exon 12a splicing. In the normal liver, BIN1 generates a short isoform (BIN1‐S) that acts as a tumor suppressor by inhibiting the binding of c‐Myc to target gene promoters. In HCC, NONO is highly up‐regulated and produces a long isoform (BIN1‐L, which contains exon 12a) instead of BIN1‐S. High levels of BIN1‐L promote carcinogenesis by binding with the protein polo‐like kinase 1 to enhance its stability through the prevention of ubiquitin/proteasome‐dependent cullin 3 degradation. Further analysis revealed that NONO promotes BIN1 exon 12a inclusion through interaction with DExH‐box helicase 9 (DHX9) and splicing factor proline and glutamine–rich (SFPQ). Notably, frequent coexpression of DHX9–NONO–SFPQ is observed in patients with HCC. Conclusions Taken together, our findings identify the DHX9–NONO–SFPQ complex as a key regulator manipulating the oncogenic splicing switch of BIN1 and as a candidate therapeutic target in liver cancer.
Assessing factors for predictive response to ADC targets in clinical tissue for companion diagnostic development.
Authors: Steven James Potts, Joseph Krueger, Holger Lange, David Eberhard, George David Young
Journal: Journal of Clinical Oncology (2013)

e22187 Background: One premise of antibody-drug conjugates (ADC) is that the bound mAb-antigen complex on the cell surface will internalize and be metabolized by lysosomal proteases to release the free drug. Thus, the efficacy of an ADC is dependent not only on the presence of cell surface antigens, but also intact delivery of the conjugated drug. In most cases, the biological mechanisms behind these processes have not been elucidated. Furthermore, the extracellular stability of the ADC may be affected by the activity of the target proteases in the tumor microenvironment outside of the lysozome. These concepts are especially important for CDx approaches, which would ideally account not only for the degree of cell surface expression of the target, but also receptor internalization and potential effects of tumor microenvironment. Although in vitro approaches exist to measure these attributes, there are no clinically amenable approaches to measure these critical parameters. Methods: Flagship Biosciences has invented several proprietary approaches for measuring critical properties of the therapeutic target on the cell surface or inside the cell, as well as properties of the TME which could be used to predict efficacy to an ADC using FFPE biopsies. These image analysis approaches have been designed specifically in context of ADC CDx programs to: 1) Accurately define cell surface target expression independent of cytoplasmic expression; 2) Assess critical factors in the TME which may affect delivery of the drug to the intracellular target; and 3) Multiplex these evaluations for an integrative answer to be derived from a typical clinical biopsy. Results: The measurement of cytoplasm/membrane localization was evaluated on several hundred tissue sections, and the methodology was found to be highly reproducible, with coefficients of variation lower than that observed by manual pathologist accessment. Conclusions: Our approach discretely measures endpoints of cell surface biomarker prevalence, biomarker membrane/cytoplasmic ratio, heterogeneity, stromal contribution, inflammatory environment, and other important cell-by-cell outputs from a single FFPE slide in the context of typical drug discovery.
Efficacy of nifekalant hydrochloride for the prevention of ventricular tachyarrhythmia : the QT interval should be prolonged but not so much
Authors: J Ohashi, Satoshi Yasuda, Kazuhiro Satomi, Takashi Kurita, Shiro Kamakura, Hiroshi Nonogi, Shunichi Miyazaki
Journal: Circulation (2004)
Sustained Polyclonal Hematopoietic Repopulation after Successful SCID-X1 Gene Therapy by Means of a Non Random Integrating Pseudotyped Gammaretrovector.
Authors: Kerstin Schwarzwaelder, Manfred Schmidt, Steven Howe, Claudia Prinz, Manuela Wissler, Sonja Schmidt, Annette Deichmann, Hanno Glimm, Bobby Gaspar, Adrian Trasher, Christof von Kalle
Journal: Blood (2004)
LSD1/KDM1A inhibitors in clinical trials: advances and prospects
Authors: Yuan Fang, Guochao Liao, Bin Yu
Journal: Journal of Hematology & Oncology (2019)

Histone demethylase LSD1 plays key roles during carcinogenesis, targeting LSD1 is becoming an emerging option for the treatment of cancers. Numerous LSD1 inhibitors have been reported to date, some of them such as TCP, ORY-1001, GSK-2879552, IMG-7289, INCB059872, CC-90011, and ORY-2001 currently undergo clinical assessment for cancer therapy, particularly for small lung cancer cells (SCLC) and acute myeloid leukemia (AML). This review is to provide a comprehensive overview of LSD1 inhibitors in clinical trials including molecular mechanistic studies, clinical efficacy, adverse drug reactions, and PD/PK studies and offer prospects in this field.
Mental health issues and psychological factors in athletes: detection, management, effect on performance and prevention: American Medical Society for Sports Medicine Position Statement—Executive Summary
Authors: Cindy Chang, Margot Putukian, Giselle Aerni, Alex Diamond, Gene Hong, Yvette Ingram, Claudia L Reardon, Andrew Wolanin
Journal: British Journal of Sports Medicine (2019)

The American Medical Society for Sports Medicine convened a panel of experts to provide an evidence-based, best practices document to assist sports medicine physicians and other members of the athletic care network with the detection, treatment and prevention of mental health issues in competitive athletes. This statement discusses how members of the sports medicine team, including team physicians, athletic trainers and mental health providers, work together in providing comprehensive psychological care to athletes. It specifically addresses psychological factors in athletes including personality issues and the psychological response to injury and illness. The statement also examines the athletic culture and environmental factors that commonly impact mental health, including sexuality and gender issues, hazing, bullying, sexual misconduct and transition from sport. Specific mental health disorders in athletes, such as eating disorders/disordered eating, depression and suicide, anxiety and stress, overtraining, sleep disorders and attention-deficit/hyperactivity disorder, are reviewed with a focus on detection, management, the effect on performance and prevention. This document uses the Strength of Recommendation Taxonomy to grade level of evidence.
Assessing Whether Infertile Men Have a Higher Risk of Prostate Cancer
Authors: Rita Rubin
Journal: JAMA (2019)

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
Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy
Authors: Zuan-Fu Lim, Patrick C. Ma
Journal: Journal of Hematology & Oncology (2019)

The biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance. Tumor cells employ different mechanisms to resist the targeting agent. Most commonly in EGFR-mutant non-small cell lung cancer, secondary resistance mutations on the target kinase domain emerge to diminish the binding affinity of first- and second-generation inhibitors. Other alternative resistance mechanisms include activating complementary bypass pathways and phenotypic transformation. Sequential monotherapies promise to temporarily address the problem of acquired drug resistance, but evidently are limited by the tumor cells' ability to adapt and evolve new resistance mechanisms to persist in the drug environment. Recent studies have nominated a model of drug resistance and tumor progression under targeted therapy as a result of a small subpopulation of cells being able to endure the drug (minimal residual disease cells) and eventually develop further mutations that allow them to regrow and become the dominant population in the therapy-resistant tumor. This subpopulation of cells appears to have developed through a subclonal event, resulting in driver mutations different from the driver mutation that is tumor-initiating in the most common ancestor. As such, an understanding of intratumoral heterogeneity-the driving force behind minimal residual disease-is vital for the identification of resistance drivers that results from branching evolution. Currently available methods allow for a more comprehensive and holistic analysis of tumor heterogeneity in that issues associated with spatial and temporal heterogeneity can now be properly addressed. This review provides some background regarding intratumoral heterogeneity and how it leads to incomplete molecular response to targeted therapies, and proposes the use of single-cell methods, sequential liquid biopsy, and multiregion sequencing to discover the link between intratumoral heterogeneity and early adaptive drug resistance. In summary, minimal residual disease as a result of intratumoral heterogeneity is the earliest form of acquired drug resistance. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers of minimal residual disease and contribute to preemptive combinatorial targeting of both drivers of the tumor and its minimal residual disease cells.
Longitudinal Tracking of Acute Myeloid Leukemia Stem Cells in Xenografts and Patients By microRNA Reporters and Single Cell RNA Sequencing
Authors: Matteo Maria Naldini, Gabriele Casirati, Matteo Barcella, Stefano Beretta, Ivan Merelli, Carolina Caserta, Giacomo Desantis, Francesca Pavesi, Fabio Ciceri, Bernhard Gentner
Journal: Blood (2019)
Phase II Trial of Combination of the Histone Deacetylase Inhibitor ITF2357 and Meclorethamine Demonstrates Clinical Activity and Safety in Heavily Pretreated Patients with Relapsed/Refractory Hodgkin Lymphoma (HL)
Authors: Carmelo Carlo-Stella, Anna Guidetti, Simonetta Viviani, Valeria Bonfante, Pinuccia Valagussa, Alfonso Marchianò, Flavio Crippa, Stefania Zambelli, Cinzia Fasola, Paolo Corradini, Corrado Tarella, Massimo Di Nicola, Alessandro M. Gianni
Journal: Blood (2008)
Myeloid cell–targeted miR-146a mimic inhibits NF-κB–driven inflammation and leukemia progression in vivo
Authors: Yu-Lin Su, Xiuli Wang, Mati Mann, Tomasz P. Adamus, Dongfang Wang, Dayson F. Moreira, Zhuoran Zhang, Ching Ouyang, Xin He, Bin Zhang, Piotr M. Swiderski, Stephen J. Forman, David Baltimore, Ling Li, Guido Marcucci, Mark P. Boldin, Marcin Kortylewski
Journal: Blood (2019)
Non-Inferiority of Anagrelide Compared to Hydroxyurea in Newly Diagnosed Patients with Essential Thrombocythemia: The ANAHYDRET-Study.
Authors: Heinz Gisslinger, Robert Kralovics, Mirjana Gotic, Jercy Holowiecki, Miroslav Penka, Rudolf Widmann, Petro Petrides
Journal: Blood (2007)
Comparative Analysis of Methods for Assessment of Circulating Endothelial Progenitor Cells Indicated Heterogeneity of Subpopulations at Various Stages of Differentiation.
Authors: Varda R. Deutsch, Haim Shmilovich, Anastasia Abashidze, Hylton Miller, Gad Keren, Elizabeth Naparstek, Jacob George
Journal: Blood (2004)
Improved Outcome for Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) with Poor Risk Cytogenetics – Result from An Analysis on 172 Patients Receiving FLAMSA-RIC Conditioning for Allogeneic Stem Cell Transplantatioin (SCT).
Authors: Tim Pfeiffer, Michael Schleuning, Matthias Eder, Marta Krejci, Karin Kolbe, Christof Scheid, Renate Arnold, Armin Gerbitz, Donald Bunjes, Ernst Holler, Gesine Bug, Maximillian Christopeit, Hildegard Greinix, Matthias Stelljes, Wolfgang A. Bethge, Daniel V Oruzio, Elke Dammann, Margret Rothmayer, Ralf Meyer, Jiri Mayer, Rainer Schwerdtfeger, Arnold Ganser, Hans-Jochem Kolb, Christoph Schmid
Journal: Blood (2008)
Lyposomal Doxorubicin (Caelyx), Cyclophosphamide - Rituximab (DC-R) Plus GM-CSF as a Salvage Therapy in B-Diffuse Large Cell Lymphoma (B-DLCL) after Autologous Stem Cell Transplantation (ASCT) Failure.
Authors: Attilio Olivieri, Mauro Montanari, Debora Capelli, Ilaria Scortechini, Guido Gini, Silvia Trappolini, Pietro Leoni
Journal: Blood (2005)
Autoreactive CD8+ T cell exhaustion distinguishes subjects with slow type 1 diabetes progression
Authors: Alice E. Wiedeman, Virginia S. Muir, Mario G. Rosasco, Hannah A. DeBerg, Scott Presnell, Bertrand Haas, Matthew J. Dufort, Cate Speake, Carla J. Greenbaum, Elisavet Serti, Gerald T. Nepom, Gabriele Blahnik, Anna M. Kus, Eddie A. James, Peter S. Linsley, S. Alice Long
Journal: Journal of Clinical Investigation (2019)

Although most patients with type 1 diabetes (T1D) retain some functional insulin-producing islet β cells at the time of diagnosis, the rate of further β cell loss varies across individuals. It is not clear what drives this differential progression rate. CD8+ T cells have been implicated in the autoimmune destruction of β cells. Here, we addressed whether the phenotype and function of autoreactive CD8+ T cells influence disease progression. We identified islet-specific CD8+ T cells using high-content, single-cell mass cytometry in combination with peptide-loaded MHC tetramer staining. We applied a new analytical method, DISCOV-R, to characterize these rare subsets. Autoreactive T cells were phenotypically heterogeneous, and their phenotype differed by rate of disease progression. Activated islet-specific CD8+ memory T cells were prevalent in subjects with T1D who experienced rapid loss of C-peptide; in contrast, slow disease progression was associated with an exhaustion-like profile, with expression of multiple inhibitory receptors, limited cytokine production, and reduced proliferative capacity. This relationship between properties of autoreactive CD8+ T cells and the rate of T1D disease progression after onset make these phenotypes attractive putative biomarkers of disease trajectory and treatment response and reveal potential targets for therapeutic intervention.
中国的独生子女政策与家庭理想子女数、子女性别偏好和出生性别比：国家计划生育和生殖健康调查结果
Authors: 屈坚定, Hesketh, Therese
Journal: BMJ (2006)

目的分析中国独生子女政策对人口生育率、理想子女数和出生性别比的影响。资料2001年国家计划生育委员会在中国大陆31个省、自治区、直辖市进行了计划生育／生殖健康抽样调查。实际调查访问15～49岁育龄妇女39585人，调查有效率为98．3％。结果在39585名妇女中，共有73202次怀孕，活产56830个婴儿。35岁以上妇女（n=17078）的生育率是1．94，其中，城市地区1．43，农村2．11；35岁以下妇女（n=11543）的生育率是1．73，城乡分别是1．25和1．79。出生性别比从1980至1989年的1．11上升到1996至2001年的1．23，平均为1．15。小型家庭的妇女大多是年龄较轻，受教育程度较高的城市妇女。35％的妇女喜欢一个孩子，57％的喜欢两个，多数妇女的理想子女数为1～2个孩子。结论实行人口控制政策后，出生率已经下降，大多数妇女的理想子女数也减少，但是，人口出生性别比却出现了不平衡。
Current Smoking Is Associated With Lower Concentrations of High-Sensitivity Cardiac Troponin T in Patients With Stable Coronary Artery Disease
Authors: Julia B. Skranes, Brian L. Claggett, Peder L. Myhre, Magnus N. Lyngbakken, Scott D. Solomon, Marc S. Sabatine, Marc A. Pfeffer, Torbjørn Omland
Journal: Circulation (2019)