tbuckley/cabot-search huggingface dataset:
Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.
Authors: Aimaz Afrough, Heather Lin, Angelica M. Gutierrez-Barrera, Jennifer Keating Litton, Vicente Valero, Banu Arun
Journal: Journal of Clinical Oncology (2013)

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.
Defining the Cell Type through Which the Asthma-Associated Intercellular Junction Protein Alpha-T-Catenin Drives Asthma Phenotypes in Mice
Authors: Sergio E. Chiarella, Francisco J. Gonzalez-Gonzalez, Alexandra C. McQuattie-Pimentel, Benjamin D. Singer, G.R. Scott Budinger, Robert P. Schleimer, Cara J. Gottardi
Journal: Journal of Allergy and Clinical Immunology (2017)
MPTH-35. CLINICOPATHOLOGICAL STUDY OF LONG SURVIVORS OF GLIOBLASTOMA (GBM) – MULTI-INSTITUTIONAL RETROSPECTIVE SURVEY
Authors: Takamitsu Fujimaki, Mariko Kawashima, Kenji Wakiya, Naoya Hashimoto, Toshiki Yoshimine, Toshihiro Kumabe, Motoo Nagane, Hikaru Sasaki, Tetsuya Ueba, Jyun-ichi Adachi, Ryo Nishikawa, Kouji Yamazaki, Hideo Takeshima, Kaori Sakurada, Takamasa Kayama, Atsushi Sasaki
Journal: Neuro-Oncology (2016)

Only a small subsets of patients with glioblastoma (GBM) survives more than 5 years. To analyze clinico-pathological features of “long survivor” will leads to better management of GBM. With the retrospective survey of records in 9 institutes, 22 patients were identified who survived 5 year or longer after initial surgery. Clinical course, neuroimages and unstained slides from FFPE specimen were obtained. Among 22 cases registered, diagnosis of GBM was confirmed in16 patients with central pathological review, Six patients were diagnosed as non-GBM (anaplastic astrocytoma 1, anaplastic oligodendroglioma 1, anaplastic ependymoma 1, pilocytic astrocytoma 1, PNET 1) and excluded from further analysis. There were 7 men and 9 women with the age range of 14 - 77 (median 44.5 year old). KPS before surgery were 60 - 100 (median 80), The extent of surgery were total in 10, subtotal in 4 and partial removal in 2. All patients received concomitant radiation chemotherapy (60-64Gy, median 64). The chemotherapeutic regiments were nitrosourea based in 8 and temozolomide in 8. The patients were followed for 65 to 214 months (median 96 months). With histopathological analysis including immunohistochemistry, 2 patients were diagnosed to have IDH-1mutation. Another 2 patients had giant cell features. Lymphocyte infiltration was observed strongly in 3 patients and moderately in 6 patients. Range of MIb-1 index was diverse; 4 – 41% (Mean 15.6, Median 13.5). In conclusion long survivors of GBM were younger in age, in good KPS and received extensive surgical resection. Histological examination showed favorable features and immunological reaction might play some role in certain patients.
Novel Population Pharmacokinetic Modeling of Arabinosyl Cytosine Triphosphate: Insights On Potential Preferential Formation of Ara-CTP Directly From Elacytarabine As Well As From Ara-C
Authors: Corinne Seng Yue, Varsha V. Gandhi, Susan O'Brien, Farhad Ravandi, Tove Flem Jacobsen, Hubert Dirven, Steinar Hagen, Petter-Arnt Hals, Murray Ducharme
Journal: Blood (2012)
Targeting MTHFD2 in Acute Myeloid Leukemia
Authors: Yana Pikman, Alexandre Puissant, Gabriela Alexe, Andrew Furman, Stacey Frumm, Linda Ross, Liying Chen, Nina Fenouille, Christopher F. Bassil, Caroline A Lewis, Richard M. Stone, Daniel J. DeAngelo, Ilene Galinsky, Andrew L Kung, Matthew Vader Heiden, Michael T. Hemann, Versha Banerji, Kimberly Stegmaier
Journal: Blood (2015)
Intentional Weight Loss and Endometrial Cancer Risk
Authors: Juhua Luo, Rowan T. Chlebowski, Michael Hendryx, Thomas Rohan, Jean Wactawski-Wende, Cynthia A. Thomson, Ashley S. Felix, Chu Chen, Wendy Barrington, Mace Coday, Marcia Stefanick, Erin LeBlanc, Karen L. Margolis
Journal: Journal of Clinical Oncology (2017)

Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women’s Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.
Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers
Authors: Alexis B. Cortot, Zoulika Kherrouche, Clotilde Descarpentries, Marie Wislez, Simon Baldacci, Alessandro Furlan, David Tulasne
Journal: JNCI Journal of the National Cancer Institute (2016)

Inhibitors of the receptor tyrosine kinase (RTK) MET have been ineffective at treating cancer, possibly because of lack of knowledge that would allow selection of tumors likely to respond to this treatment. In contrast, specific epidermal growth factor receptor (EGFR) inhibitors have been used successfully against lung tumors displaying activating mutations in the kinase domain of EGFR. Recent publications describe a set of mutations causing MET exon 14 skipping, and importantly, several case reports describe objective responses to MET-targeting tyrosine kinase inhibitors in patients with such mutations. These observations suggest a novel therapeutic strategy for fighting cancer, especially in the lung. Exon 14 encodes the MET juxtamembrane domain targeted by mechanisms that negatively regulate receptor stability and activity. In this review, we describe the molecular mechanisms leading first to exon 14 skipping and then to activation of the MET receptor and how this process differs from that triggered by classical RTK-activating mutations in the kinase domain. We detail the clinical characteristics of patients carrying these mutations and the sensitivity of their tumors to MET inhibitors. Lastly, we discuss future challenges related to MET mutations in cancers, including patient screening and anticipating resistance to MET inhibitors.
Sustained Effect and Clinical Outcomes in Chronic Spontaneous Urticaria in Patients Receiving Omalizumab for Several Years
Authors: Roselle Catherine Yu Madamba, Marta Ferrer, Olga Vega Matute, Ruben Martinez, Gabriel Gastaminza, Maria Jose Goikoetxea, Carmen D'Amelio, Amalia Bernad
Journal: Journal of Allergy and Clinical Immunology (2017)
Incidence and Characteristics of Secondary Myelodysplastic Syndrome Developing During Lenalidomide-Based Regimens In Relapsed and/or Refractory Multiple Myeloma Patients
Authors: Donna E. Reece, Esther Masih-Khan, Rashmi S. Goswami, Sharon Fung, David Barth, Christine Chen, Vishal Kukreti, Haowei (Linda) Sun, Saima Dean, Suzanne Trudel
Journal: Blood (2010)
Crossover from one aromatase inhibitor (AI) to another in the Exemestane and Letrozole Pharmacogenetics (ELPh) trial.
Authors: Kunal C. Kadakia, Kelley M Kidwell, Nicholas J. Seewald, Claire Frances Snyder, David A. Flockhart, Janet S Carpenter, Julie L. Otte, Daniel F. Hayes, Anna Maria Storniolo, Vered Stearns, Norah Lynn Henry
Journal: Journal of Clinical Oncology (2016)

158 Background: Tolerance of AI therapy can be poor due to treatment-emergent toxicities and can lead to early discontinuation (non-persistence). Patients often switch from one AI to another when toxicities develop; however, limited prospective data exist on patients who switch AI. Here we describe the effect of switching from E to L or L to E on tolerance of and persistence with therapy. Methods: Postmenopausal women initiating AI therapy were enrolled on the ELPh trial and randomized to E or L. Those that stopped their AI for self-reported intolerance were offered crossover to alternate AI after a 2-6 week washout. Kaplan-Meier estimates of proportions on AI after 1, 3, and 6 months were assessed during 1 st and 2 nd AI. Associations between time on 2 nd AI and clinicopathologic factors were analyzed using univariable Cox proportional hazards model. To evaluate effect of crossover on patient-reported outcomes, multiple questionnaires, including a pain visual analog scale (VAS), were assessed serially. Results: 83 women, mean age 60 years, 45% prior chemotherapy, and 31% with prior tamoxifen use, participated in the crossover protocol. 71% reported improvement in symptoms a mean 4.72 weeks after discontinuing 1 st AI therapy. Median time on 1 st AI was 6.8 months (95% CI 5.8-9 months), and on 2 nd AI was 11.5 months (6.9-24.2). The probability of persistence at 1, 3, and 6 months for the 1 st AI was 94%, 76%, and 55% and for the 2 nd AI was 89%, 73%, and 62%, respectively. There was no significant association between duration on 2 nd AI and 1 st AI (L vs. E), duration on 1 st AI, age, body mass index, or prior therapies. The change in pain VAS from baseline to 1 or 3 months was not significantly different during treatment with the 1 st or 2 nd AI. Conclusions: Although all AI medications have similar mechanisms of activity, nearly two-thirds of patients who are intolerant of one AI are able to maintain therapy for at least 6 months following switch to 2 nd AI. Switching is a reasonable approach for women who cannot tolerate 1 st AI that may improve persistence with therapy. The mechanisms for intrapatient variation in tolerance warrant further study. Clinical trial information: NCT00228956.
OS1.8 IRE1-mediated immunomodulation in glioblastoma
Authors: S. Lhomond, T. Avril, N. Dejeans, R. Pineau, H. Loiseau, M. Maurel, A. Samali, O. Pluquet, A. Chatziioannou, E. Chevet
Journal: Neuro-Oncology (2016)

response to TMZ involving different classes of RNAs, both coding and noncoding.RESULTS: We developed a pipeline to build the "RNA interactome" and revealed lncRNAs involved in regulatory circuits of GBM response to TMZ.We next inferred putative biological functions for key lncRNAs by in silico gene co-expression analysis.Interestingly, lncRNAs were mapped to processes linked to drug sensitivity, cell cycle regulation and/or developmental pathways.By exploring public datasets of The Cancer Genome Atlas (TCGA) in which part of the identified lncRNAs were annotated, we identified several TMZ-regulated lncRNAs that are correlated with patient survival.CONCLUSION: Altogether, this integrative analysis of small RNA-seq and RNA-seq data provides new RNA-based predictors of chemoresistance, as well as potential targets to counteract TMZ resistance in GBM.
MErCuRIC1: A phase 1a study of MEK1/2 inhibitor PD-0325901 with cMET inhibitor crizotinib in patients with advanced solid tumours
Authors: R. Wilson, M.R. Middleton, J. Houlden, S. Van Schaeybroeck, C.D. Rolfo, E. Elez, J. Taieb, T. André, A. Bardelli, P. Laurent-Puig, J. Tabernero, M. Peeters, T. Maughan, C. Roberts, S. Love, M. Lawler, M. Salto-Tellez, M. Grayson, V. Popovici, F. Di Nicolantonio
Journal: Annals of Oncology (2016)
The effectiveness of behavioural and cognitive behavioural therapies for insomnia on depressive and fatigue symptoms: A systematic review and network meta-analysis
Authors: Andrea Ballesio, Maria Raisa Jessica V. Aquino, Bernd Feige, Anna F. Johann, Simon D. Kyle, Kai Spiegelhalder, Caterina Lombardo, Gerta Rücker, Dieter Riemann, Chiara Baglioni
Journal: Sleep Medicine Reviews (2017)
Allogeneic and Syngeneic Hematopoietic Cell Transplants in Patients with AL-Amyloidosis: A Report from the European Group for Blood and Marrow Transplantation (EBMT).
Authors: Stefan O. Schoenland, Michel Baccarani, Andrew Campbell, Enric Carreras, Catherine Cordonnier, Leanthe Grommisch, Veronique Leblond, Timothy J. Littlewood, Leo F. Verdonck, L. Wood, Pierre Zachee, Axel R. Zander, Hartmut Goldschmidt, Dietger Niederwieser, Goesta Gahrton
Journal: Blood (2004)
Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC).
Authors: Lajos Pusztai, Roman Yelensky, Bailiang Wang, Rony Avritscher, William Fraser Symmans, Doron Lipson, Gary A. Palmer, Stacy L. Moulder, Philip Stephens, Yun Wu, Maureen T. Cronin
Journal: Journal of Clinical Oncology (2012)

10559 Background: The aim of this study was to assess the frequency of genomic alterations in breast cancer potentially treatable with approved targeted agents or investigational drugs in clinical trials. NGS was performed in a CLIA setting (Foundation Medicine). Methods: DNA was extracted from needle biopsies of 33 pre-therapy primary and 17 MBCs (mean age 52 yrs; 58% ER+, 20% HER2+, 30% triple negative) obtained prospectively for biomarker discovery and preserved in RNAlater. Patients with MBC received an average of 7 drugs (range 5-17) including adjuvant therapy before biopsy for this research; 13 biopsies were from soft tissues, 3 from liver and 1 from bone. Sequencing was targeted to 3230 exons in 182 cancer-related genes and 37 introns in 14 genes often rearranged in cancer. Average median depth was &gt;1200x. Results: All biopsies yielded sufficient DNA. NGS revealed a total of 117 known driver mutations across 36 genes (per-tumor average=2.5, range 1-6), including 37 base substitutions (32%), 28 indels (24%), 42 amplifications (36%) and 10 homozygous deletions (9%). NGS identified HER2 gene amplification in 6/7 cases scored HER2+ by FISH. The average number of functionally important alterations was surprisingly similar, 2.3 in primaries vs 2.8 in heavily treated MBCs (p=0.32). Remarkably, 25/33 (76%) of primary and 14/17 (82%) of MBCs had at least 1 genomic alteration targetable with an FDA approved drug or novel agent in clinical trials. These included: ERBB2 alterations (n=9), PIK3CA mutations (n=8), NF1 mutations (n=4, candidate for PI3K/MEK inhibitors), AKT1-3 mutations (n=5, PI3K inhibitors), BRCA1/2, (n=6, PARP inhibitors), and CCND2 (n=3)/CDKN2A (n=3) mutations (CDK inhibitors). Numerous other alterations with less apparent therapeutic implications were also observed. Conclusions: Comprehensive NGS profiling in breast cancer needle biopsies showed high frequency of genomic alterations linked to a clinical treatment option or clinical trials of targeted therapies. These results demonstrate it is feasible to use NGS to guide targeted therapy. Prospective testing of the diagnostic/predictive value of this patient selection approach is currently under way.
Advancing the Health of Lesbian, Gay, and Bisexual Adults
Authors: Susan D. Cochran, Ilan H. Meyer, Vickie M. Mays
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Case-Control Study Using Array-Based Genotyping Produced a Panel of Genes Associated with Risk to Acute Myelogenous Leukemia (AML).
Authors: Il-Kwon Lee, Hee Nam Kim, Yeo-Kyeoung Kim, Kyeong-Soo Park, Deok-Hwan Yang, Je-Jung Lee, Myung Geun Shin, Chan Choi, Hoon Kook, Tae Ju Hwang, Moo Rim Park, Deog Yeon Jo, Jong Ho Won, Hyeoung-Joon Kim
Journal: Blood (2007)
An Atypical Severe Combined Immunodeficiency (SCID) Case Diagnosis Complicated by Alternative Care in the Era of Newborn Screening (NBS) for SCID
Authors: Taylor Alberdi, Johana B. Castro-Wagner, Bhumika Patel, Sonia Joychan, David Lindsey, Frederico R. Laham, Krisztian Csomos, Boglarka Ujhazi, Carla M. Duff, Jessica Trotter, Jack J. Bleesing, Attila Kumanovics, Yenhui Chang, Jamie H. Hale, Panida Sriaroon, Greg Hale, Benjamin R. Oshrine, Luigi Notarangelo, Roshini S. Abraham, Anne Marie Comeau, Aleksandra Petrovic, Jennifer W. Leiding, Jolan E. Walter
Journal: Journal of Allergy and Clinical Immunology (2017)
Relationships Among Depression and Levels of Cytokines and Testosterone in Patients with Chronic Abacterial Prostatitis
Authors: G.N. Drannik, I.I. Gorpynchenko, K.R. Nurimanov, T.V. Poroshina, V.S. Savchenko, Lawrence M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2017)
Abstract 59: Role of Follistatin 315 in Regulating Cardiac Hypertrophy in Physiology and Pathophysiology
Authors: Zhaobin Xu, Alisa D Blazek, Eric Beck, Jenna Alloush, Jackie Li, Alan Schneyer, Sudha Agarwal, Timothy Hewett, Noah Weisleder
Journal: Circulation Research (2015)

Heart failure is characterized by initial compensatory changes, including the myocyte hypertrophy, chamber dilation, and matrix remodeling, that proceed until progressive dysfunction produces end stage heart failure and mortality. Recently, the roles of secreted factors in the heart that could regulate pathological hypertrophy, including follistatin (FST) and related molecules, have been examined by various investigators. FST is a molecule that blocks secretion of follicle-stimulating hormone from the pituitary and regulates members of the transforming growth factor beta (TGF-β) family including myostatin. Here we tested the effects of a particular FST isoform, FST288, on heart function in mice. The gene encoding FST produces three isoforms that differ in biological activities and cell surface binding capabilities. The FST315 isoform contains all six exons, and proteolytic cleavage of the FST315 C-terminal tail results in production of FST303. The lack of exon 6, which codes for the acidic C-terminal tail of the putative full-length protein, results in FST288. The missing acidic C-terminal tail region found in soluble FST315 allows FST288 to bind cell surface heparin-sulfated proteoglycans, accounting for the differential actions of these FST isoforms. Since mice that are null for the FST gene die embryonically, we used genetically modified mice that express only the FST288 isoform to test the role of FST315 in adult heart. Examination of these animals suggests that the loss of FST315 expression has limited effects on the heart at the resting state. When these mice are subjected to pressure overload through transverse aortic constriction (TAC) surgery they appear to be resistant to the compensatory cardiac hypertrophy present in wild type mice by 4 weeks post surgery. Both cardiac structure (examined by histology) and function (as measured by echocardiography and pressure/volume loops) following TAC are improved in the genetically modified mice when compared to wild type mice. This response is likely due to modification of the myostatin signaling pathway, one of the major targets of FST315. Overall, our data illustrates that FST315 is an important contributor to the progression of pressure overload induced cardiac hypertrophy.
The Evolution of Burn Therapy—Then and Now
Authors: Valencia Long
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal