tbuckley/cabot-search huggingface dataset:
An Optimized Risk Stratification Model in Acute Promyelocytic Leukemia Identifies Patients with an Exceptionally Good Prognosis Regarding the Incidence of Relapse
Authors: Anna Hecht, Daniel Nowak, Verena Nowak, Benjamin Hanfstein, Thomas Büchner, Karsten Spiekermann, Christel Weiss, Wolf-Karsten Hofmann, Eva Lengfelder, Florian Nolte
Journal: Blood (2014)
Abstract P4-11-01: A genetic model of mammary gland fibrosis and cancer risk
Authors: J Wu, D Crowe
Journal: Cancer Research (2017)

Abstract Ductal cells of the mammary gland arise from mammary stem cells (MSC) and consist of estrogen receptor a negative (ER-) luminal cells and a small ER+ luminal population. Luminal cells are maintained by the proliferation of ER- luminal progenitor (LP) cells, which are expanded in basal subtype breast cancer. Human breast LP cells exhibit telomere DNA damage, which is associated with mammographic density and increased cancer risk. Short telomeres resulting from the DNA damage response correlate with aggressive breast cancer phenotypes. Telomeric repeat factor 2 (TRF2) binds to telomeres and protects them from the DNA damage response. TRF2 expression is reduced in most human breast cancers but the phenotypic advantages of this genetic alteration are unknown. To determine the effects of telomere DNA damage on mammary gland function and tumor phenotype, we deleted TRF2 expression in mammary gland epithelium. Mammary glands lacking TRF2 expression exhibited increased telomere DNA damage response, histopathological and functional degeneration, and prominent ductal fibrosis. MSC from TRF2 deficient glands were unable to completely regenerate mammary glands following transplantation to cleared fat pads. TRF2 deficient mammary tumors also demonstrated telomere DNA damage response but exhibited rapid onset and increased proliferation. Tumor derived LP cells underwent expansion but exhibited high telomere DNA response and failed to form tumors following transplantation. In contrast, the severely depleted MSC population was highly tumorigenic and maintained telomeres via the ALT mechanism. Telomere DNA damage response in mammary tumors resulted in p53 dependent ER+ cellular differentiation and sensitivity to anti-estrogen therapy. Our results provide a new in vivo model for exploring mechanisms of mammographic density, stem cell differentiation, cancer risk, and therapeutic sensitivity. Citation Format: Wu J, Crowe D. A genetic model of mammary gland fibrosis and cancer risk [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-11-01.
Long-Term Outcomes In Survivors of Childhood Cancer Treated with Hematopoietic Cell Transplantation (HCT) Versus Conventional Therapy: a Report From the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS)
Authors: Saro Armenian, Can-Lan Sun, Toana Kawashima, Mukta Arora, Wendy Leisenring, Charles A. Sklar, K. Scott Baker, Liton Francisco, Jennifer Berano Teh, George Mills, F. Lennie Wong, Joseph Rosenthal, Lisa Diller, Melissa M. Hudson, Kevin C. Oeffinger, Leslie L. Robison, Smita Bhatia
Journal: Blood (2010)
Abstract A16: Smad4 pathways modulate induction of the chemokine Ccl20 and repress inflammation-induced carcinogenesis in mouse colon
Authors: Anna L. Means, Tanner J. Freeman, Connie J. Weaver, Chanjuan Shi, Mary K. Washington, Bronson C. Wessinger, Tasia Brown, David K. Flaherty, Kevin P. Weller, Robert J. Coffey, Keith T. Wilson, Robert D. Beauchamp
Journal: Cancer Research (2017)

Abstract Inflammation regulates many aspects of gut homeostasis but is also a key component of colon cancer progression. While TGFβ signaling is known to regulate inflammatory responses within immune cells, we have uncovered a novel regulatory pathway in which TGFβ and BMP signaling suppress responses to inflammatory stimuli within the colonic epithelium. Using mice with conditional deletion of Smad4 in intestinal epithelium, we found that CCL20 expression was increased with Smad4 loss. Similarly, in murine immortalized colonocytes and human colon cancer cell lines, blocking TGFβ and/or BMP receptors increased CCL20 expression. CCL20 is upregulated in response to inflammatory signals such as TNF and IL-1β. CCL20 is also upregulated in colon cancer but the mechanism is not understood. We found that pre-treatment of colonocytes or colon cancer cells with TGFβ1 and BMP2 completely suppressed TNF- or IL-1β-induced CCL20 expression at the level of gene transcription. By chromatin immunoprecipitation, we found that TGFβ1/BMP2 treatment impaired binding of NFκB and phospho-STAT3 to the CCL20 promoter. To understand the significance of this regulation in chronic inflammation, we subjected Smad4 deleted and control mice to three rounds of dextran sodium sulfate (DSS)-mediated damage to the distal colon. We found that loss of Smad4 in mouse colonic epithelium was sufficient to induce tumorigenesis following damage-induced inflammation. Following DSS-mediated damage, Smad4-null epithelium developed invasive colorectal adenocarcinoma within two months of DSS treatment while Smad4+ control mice never develop tumors following DSS exposure. The Smad4 null tumors were histologically similar to those of human colitis-associated colon cancers. Prior to tumor formation, we saw an increase in CD8+ cells in Smad4-deleted colons, suggesting that tumor progression involves bidirectional crosstalk between the epithelium and immune cells and that this crosstalk is regulated in part by Smad4-mediated signaling within the epithelium. SMAD4, TGFβ receptors, or BMP receptors are often mutated in colon cancer. This loss of TGFβ and/or BMP signaling likely facilitates epithelial-immune cell crosstalk in colitis-associated colon cancers. Citation Format: Anna L. Means, Tanner J. Freeman, Connie J. Weaver, Chanjuan Shi, Mary K. Washington, Bronson C. Wessinger, Tasia Brown, David K. Flaherty, Kevin P. Weller, Robert J. Coffey, Keith T. Wilson, Robert D. Beauchamp. Smad4 pathways modulate induction of the chemokine Ccl20 and repress inflammation-induced carcinogenesis in mouse colon. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A16.
GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors
Authors: Shu-Ling Chiu, Graham Hugh Diering, Bing Ye, Kogo Takamiya, Chih-Ming Chen, Yuwu Jiang, Tejasvi Niranjan, Charles E. Schwartz, Tao Wang, Richard L. Huganir
Journal: Neuron (2017)
Clinical pharmacokinetic (PK)/pharmacodynamic (PD) model for Debio 1143, a novel antagonist of IAPs in cancer treatment.
Authors: Elisabeth Rouits, Per Olsson Gisleskog, Bruno Gavillet, Annick Menetrey, Mel Sorensen, Claudio Zanna, Gregoire Vuagniaux, Valerie Nicolas-Metral
Journal: Journal of Clinical Oncology (2014)

2585 Background: Inhibitors of apoptosis proteins (IAPs) modulate multiple processes, including caspase activation and NF-kB signaling. Expression and/or overexpression of IAPs have been reported for a variety of tumor types and are correlated with tumor growth and resistance to apoptosis induced by standard chemo and radiation therapies. The small molecule Debio 1143 is an orally-active IAP antagonist able to promote apoptosis in tumor cells. Methods: In a first-in-human Phase I study in patients with advanced cancer, Debio 1143 was given orally once daily on days 1-5 every 2 or 3 weeks. Ten dose levels ranging from 5 mg to 900 mg were explored. Blood samples were taken on days 1-5 for PK (Debio 1143) and PD assessments (IAPs levels, blood markers of apoptosis and inflammation) with rich sampling at day 1 and day 5. A population PK model was built within NONMEM 7.2. Further to a graphical PK vs PD check, population PK/PD models were explored. Results: The PK of Debio 1143 was well described by a two-compartment model with two absorption pathways. Debio 1143 bioavailability appeared to decrease after repeated administrations, suggesting a possible time-dependent PK. Graphically, markers of target engagement (cIAP1 PBMCs levels) and apoptosis (caspase-3 generated cytokeratine-18 fragments plasma levels [CK18-M30]) showed changes with Debio 1143 PK. cIAP1 levels could be fitted using an indirect response model where the elimination of cIAP1 was stimulated by Debio 1143. The CK18-M30 data was best fitted by a model with a delayed effect, onsetting after the first day. Simulations of d14q21 treatment predicted a clear decrease in cIAP1, with small differences between 100 mg and 200 mg dosing. A CK18-M30 increase ranging from 20 to 200% is predicted at day 14 after 200 mg qd. Conclusions: Debio 1143PK is compatible with oral administration q5d21. A clear relationship between PK and markers of target engagement or apoptosis was evidenced over the dose range explored. Findings from the q14d21 simulations indicate a promising PK/PD relationship for such schedule. Results from ongoing studies including PK/safety and PK/efficacy exploration will also feed the model to support Debio 1143 treatment optimization.
High-Sensitivity C-Reactive Protein (hs-CRP) and Pentraxin 3 (PTX3) Are Increased in Essential Thrombocythemia and Polycythemia Vera.
Authors: Tiziano Barbui, Alessandra Carobbio, Barbara Bottazzi, Pio Zilio, Anna Salvi, Ivan Cuccovillo, Silvia Salmoiraghi, Guido Finazzi, Alberto Mantovani, Alessandro Rambaldi
Journal: Blood (2009)
Prognosis of Patients with AML Carrying 11Q23/MLL Reciprocal Translocations : A Retrospective Study of 191 Cases from the French AML-Intergroup
Authors: Anne Banos, Antoine Jaquet, Anne Auvrignon, Nicole Dastugue, Christine Terré, Isabelle Luquet, Sylvie Castaigne, Marina lafage Pochitaloff, Thierry Leblanc, Pierre Fenaux, Francoise Huguet, Francis Witz, Didier Blaise, Josy M. Reiffers, Jean Luc Harousseau, Gerard Socie, Bruno Lioure, Christian Bastard, Herve Dombret, Arnaud Pigneux
Journal: Blood (2008)
Synergism of co-delivered nanosized antioxidants displayed enhanced anticancer efficacy in human colon cancer cell lines
Authors: Lipika Ray, Manish Kumar Pal, Ratan Singh Ray
Journal: Bioactive Materials (2017)

Combination of chemopreventive and/or therapeutic agents is the imminent smart approach to cope up with cancer because it may act on multiple targets through different pathways. In the present study, we have synthesized multiple chemopreventive and/or therapeutic agents (Curcumin, Quercetin and Aspirin) loaded nanoparticles by simple cation-anion interaction among the amine groups of chitosan (CS) and phosphate groups of sodium hexametaphosphate (SHMP). These nanosized bioactive materials (CS-SHMP-CQA-NPs) were well characterized and found most effective in colon cancer cell line (HCT-116) compared to other cancer cell lines. Triplex chemopreventive and/or therapeutic agents-loaded NPs were synergistically inducing apoptosis in HCT-116 cells compared to two-chemopreventive agents-loaded NPs as evident by an increase in sub-G1 cells (percent), and chromatin condensation along with the decrease in mitochondrial membrane potential (MMP). Interestingly, Chou-Talalay analysis revealed that CS-SHMP-CQA-NPs showed strong synergistic effect in its all doses. Thus, our study demonstrates that nanoparticles based bioactive materials significantly inhibit the growth of HCT-116 cells and thus could be a promising approach for colon cancer chemoprevention.
Increasing the Use of Lithium and Clozapine in US Suicide Prevention
Authors: Tarun Bastiampillai, Steven S. Sharfstein, Stephen Allison
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
Bortezomib in Multiple Myeloma: Treatment and Retreatment. A Single Center Experience.
Authors: Antonios G. Bilalis, Konstantinos Papadimitriou, Anastasia Pouli, Konstantinos Papanastasiou, Seraphem Tsakanikas, Panagiota Stefanitsi, Anastasia Sioni, Georgios Koropoulis, Marina Stamatelou
Journal: Blood (2007)
Abstract P4-12-14: Folate receptor alpha (FOLR1) expression in triple-negative breast cancer (TNBC)
Authors: X Cui, PJ McIntire, PS Ginter, L Irshaid, Z Chen, SJ Shin
Journal: Cancer Research (2017)

Abstract Background Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein expression is enriched in triple-negative breast cancer (TNBC). Newly developed anti-FOLR1 therapy could potentially be used for patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value. Design Immunohistochemistry was performed for FOLR1 (26B3.F2, Biocare, RTU) on tissue microarray (TMA) slides consisting of 62 primary TNBC. Membranous staining in ≥5% of cells was deemed positive in a given case. Statistical analyses correlating FOLR1 protein expression with clinicopathologic parameters and clinical outcome [disease-free survival (DSF) and overall survival (OS) (range: 16 to 196 months, mean: 111 months)] were performed. Results 62 cases of primary TNBC from 61 patients were studied. All patients were female and the mean age was 55 years (range 30 to 91 years). Histologically, almost all tumors were invasive ductal carcinoma (94%; 58/62) and grade 3 (89%; 55/62). Most were pT1 tumors (71%; 44/62) or pT2 (27%; 17/62). For the majority of patients, the nodal status was N0 (61%; 38/62) or N1 (24%; 15/62) and the stage was 1 (53%; 33/62) or 2 (32%; 20/62). Most cases were negative for FOLR1 (84%; 52/62). FOLR1 expression did not correlate with any clinicopathologic parameters, DFS or OS (P&amp;gt;0.05). Conclusion Similar to other studies, we found no correlation with FOLR1 expression and common clinicopathologic parameters and clinical outcome in TNBC. While FOLR1 expression has been previously reported to confer poor prognosis in breast cancer (all types), our findings suggest that in TNBC specifically, FOLR1 expression is not prognostically significant. Citation Format: Cui X, McIntire PJ, Ginter PS, Irshaid L, Chen Z, Shin SJ. Folate receptor alpha (FOLR1) expression in triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-14.
Characterization of Leukemias with ETV6-ABL1 Fusion
Authors: Marketa Zaliova, Anthony V. Moorman, Giovanni Cazzaniga, Martin Stanulla, Richard C. Harvey, Kathryn G. Roberts, Sue L. Heatley, Mignon L. Loh, Marina Konopleva, I-Ming Chen, Olga Zimmermannova, Claire Schwab, Owen Smith, Marie-Joelle Mozziconacci, Christian Chabannon, Myungshin Kim, J.H. Frederik Falkenburg, Alice Norton, Karen Marshall, Oskar A. Haas, Julia Starkova, Jan Stuchly, Stephen P. Hunger, Deborah White, Charles G. Mullighan, Cheryl L Willman, Jan Stary, Jan Trka, Jan Zuna
Journal: Blood (2015)
Abstract P1-03-06: Improvement in risk predictive value of Nottingham prognostic index by determining GP88 tumor tissue expression for estrogen receptor positive breast cancer patients
Authors: G Serrero, DM Hawkins, PA Bejarano, O Ioffe, KR Tkaczuk, RE Elliott, JF Head, J Phillips, AK Godwin, J Weaver, D Hicks, B Yue
Journal: Cancer Research (2017)

Abstract Background: The Nottingham Prognostic Index (NPI), which includes nodal status, tumor size and histological grade was established to provide predictive value information on post-surgery survival for primary breast cancer patients. Attempts to improve NPI's performance have included addition of other biomarker expression and morphological features such as vascular invasion. In the present study, we investigated whether expression of the autocrine growth and survival factor GP88 (progranulin), known to be overexpressed in breast cancer, whereas it is negative in normal mammary tissue, would improve NPI's predictive value. Methods: We examined the tumor tissue GP88 expression by immunohistochemistry (IHC) in formalin fixed paraffin embedded tissue sections from 508 cases of estrogen receptor positive (ER+) invasive ductal carcinoma (IDC) with known clinical outcomes (disease-free and overall survivals) and with known NPI. GP88 IHC tumor tissue expression was determined using an anti-GP88 antibody (clone 6B3) developed in our laboratory. GP88 expression was scored (0, 1+, 2+, 3+) by two board certified pathologists and classified into two IHC score groups of GP88 &amp;lt; 3+ (0, 1+, 2+) and GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) and overall survival (OS) outcomes was then examined by Kaplan Meier analysis, Cox proportional Hazard (CPH) ratio and Pearson's C2 test. Results: Kaplan-Meier survival graphs categorized by NPI scores (&amp;lt; 3.4, 3.4-5.4, and &amp;gt;5.4) and by GP88 expression (&amp;lt; 3+ and 3+) showed that for each NPI subgroup, patients with GP88 IHC score of 3+ had a worse disease-free survival (DFS) and overall survival (OS) than patients within the same NPI subgroup with tumors that had GP88 IHC score &amp;lt; 3+. When adjusted for NPI, high GP88 score was highly significantly associated with recurrence with a hazard ratio of 3.30 (95% CI 2.12 to 5.14). Conclusions: The data suggest that measuring GP88 tumor tissue expression by IHC at time of diagnosis for breast cancer patients with primary ER+ IDC could provide recurrence prediction and survival information complementary to that provided by the determination of NPI alone and thus may be useful for risk management of patients diagnosed with breast cancer. Citation Format: Serrero G, Hawkins DM, Bejarano PA, Ioffe O, Tkaczuk KR, Elliott RE, Head JF, Phillips J, Godwin AK, Weaver J, Hicks D, Yue B. Improvement in risk predictive value of Nottingham prognostic index by determining GP88 tumor tissue expression for estrogen receptor positive breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-06.
Clinical characteristics of patients from the worldwide registry on peripartum cardiomyopathy (<scp>PPCM</scp>)
Authors: Karen Sliwa, Alexandre Mebazaa, Denise Hilfiker‐Kleiner, Mark C. Petrie, Aldo P. Maggioni, Cecile Laroche, Vera Regitz‐Zagrosek, Maria Schaufelberger, Luigi Tavazzi, Peter van der Meer, Jolien W. Roos‐Hesselink, Petar Seferovic, Karin van Spandonck‐Zwarts, Amam Mbakwem, Michael Böhm, Frederic Mouquet, Burkert Pieske, Roger Hall, Piotre Ponikowski, Johann Bauersachs
Journal: European Journal of Heart Failure (2017)
Emergency care and resuscitation plans
Authors: David Pitcher, Zoe Fritz, Madeleine Wang, Juliet A Spiller
Journal: BMJ (2017)

When a person's heart or breathing stops and the cause is reversible, immediate cardiopulmonary resuscitation (CPR) offers a chance of life.However, when a person is dying-for example, from organ failure, frailty, or advanced cancer-and his or her heart stops as a final part of a dying process, CPR will not prevent death and may do harm."Do not attempt CPR" (DNACPR) decisions were first documented in the 1970s, to try to protect people from receiving CPR that they did not want, that would not work, or would not give them overall benefit.2][3][4] Despite national guidance in the UK (see "Further educational resources" box), misunderstandings, poor communication, and inconsistent DNACPR documentation persist. 4Exploring and achieving a shared understanding among patient, family, and healthcare team of realistic and individualised care preferences may sometimes be done badly or not even attempted.Here we draw on evidence (box 1), collated for a broader project, to outline how clinicians might plan with their patients.We offer suggestions on how clinicians and their patients might better think ahead, consider, discuss and record patient-centred recommendations, not only about CPR but also other elements of emergency care and treatment.In a linked article Fritz et al explain why a change in practice and culture, timing and context of these conversations is needed.
Elevated axonal membrane permeability and its correlation with motor deficits in an animal model of multiple sclerosis
Authors: Gary Leung, Melissa Tully, Jonathan Tang, Shengxi Wu, Riyi Shi
Journal: Translational Neurodegeneration (2017)

It is increasingly clear that in addition to myelin disruption, axonal degeneration may also represent a key pathology in multiple sclerosis (MS). Hence, elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology, but also elucidate additional therapeutic targets. The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice. Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud's adjuvant emulsion, followed by two intraperitoneal injections of pertussis toxin. Behavioral assessment was performed using a 5-point scale. Horseradish Peroxidase Exclusion test was used to quantify the disruption of axonal membrane. Polyethylene glycol was prepared as a 30% (w/v) solution in phosphate buffered saline and injected intraperitoneally. We have found evidence of axonal membrane disruption in EAE mice when symptoms peak and to a lesser degree, in the pre-symptomatic stage of EAE mice. Furthermore, polyethylene glycol (PEG), a known membrane fusogen, significantly reduces axonal membrane disruption in EAE mice. Such PEG-mediated membrane repair was accompanied by significant amelioration of behavioral deficits, including a delay in the emergence of motor deficits, a delay of the emergence of peak symptom, and a reduction in the severity of peak symptom. The current study is the first indication that axonal membrane disruption may be an important part of the pathology in EAE mice and may underlies behavioral deficits. Our study also presents the initial observation that PEG may be a therapeutic agent that can repair axolemma, arrest axonal degeneration and reduce motor deficits in EAE mice.