tbuckley/cabot-search huggingface dataset:
SGN-LIV1A, an antibody-drug conjugate (ADC), in patients with LIV-1–positive breast cancer.
Authors: Ana Kostic, Martha Anderson, Steven Duniho, Jamie Miyamoto, Albina Nesterova, Django Sussman
Journal: Journal of Clinical Oncology (2014)

TPS1143 Background: First identified as an estrogen-inducible gene in a breast cancer cell line, LIV-1 is a multispan transmembrane protein of the solute-carrier family 39 with putative zinc transporter and metalloproteinase activity. As a downstream target of STAT3, it promotes the epithelial-to-mesenchymal transition that is important in the malignant progression to metastasis. LIV-1 is expressed in a number of cancers with the highest prevalence and level of expression in breast, prostate, and melanoma. Additionally, LIV-1 has been linked with malignant progression to metastasis and associated with lymph node involvement in breast cancer. Normal tissue expression is predominantly limited to hormonally regulated tissues, including breast and prostate. SGN-LIV1A is an ADC composed of a humanized anti-LIV-1 monoclonal antibody conjugated to the microtubule-disrupting agent MMAE via a protease-cleavable linker. In vitro, SGN-LIV1A shows target-specific internalization and cytotoxic activity against LIV-1-positive neoplastic cell lines. Significant dose-dependent tumor regression was demonstrated in mouse xenograft models. Methods: The primary objective of this phase 1, open label, multicenter study is to evaluate the safety and tolerability, and to identify the maximum tolerated dose of SGN-LIV1A using a 3+3 dose-escalation study design. Pharmacokinetics, immunogenicity, and antitumor activity will also be evaluated. Eligible patients are adult females who have hormone receptor-positive /HER2-negative or triple-negative metastatic breast cancer. Tumor tissue obtained at baseline must be positive for expression of LIV-1 per central assessment. Patients must have received at least 2 prior cytotoxic regimens in the metastatic setting and have measurable disease per RECIST v1.1. Pre-existing neuropathy ≥ Grade 2 is not permitted. SGN-LIV1A will be administered IV every 3 weeks at protocol-defined doses starting at 0.5 mg/kg. Patients who achieve an objective response or stable disease will be eligible to continue treatment until disease progression. Enrollment for this US-based trial began in late 2013. Clinical trial information: NCT01969643.
Obesity in ireland is fuelling incidence rates of oesophageal adenocarcinoma
Authors: A Ryan, S Rowley, JV Reynolds
Journal: Endoscopy (2005)

Background: Obesity may be responsible for the rising incidence of oesophageal adenocarcinoma(ACA). Between 1994–2004 the incidence of obesity in Ireland increased by 67% and National Cancer Registry reported a 38% increase in ACA cases.
Idelalisib Rapidly Improves Platelets Function in Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Gianluigi Reda, Ramona Cassin, Andrea Artoni, Anna Lecchi, Bruno Fattizzo, Silvia La Marca, Paolo Bucciarelli, Flora Peyvandi, Agostino Cortelezzi
Journal: Blood (2016)
Abstract 18117: Increased Vascularization In Shoulder Regions Of Carotid Plaques Taken From Patients With Diabetes Mellitus
Authors: Goran M Bergstrom, Sofia Stromberg, Josefin Kjelldahl, Bjorn Fagerberg, Fredrik J Olson
Journal: Circulation (2010)

Introduction: Increased vascularization is considered an important contributing factor for plaque vulnerability. Patients with diabetes suffer from microvascular proliferative disease resulting in ...
CHIP-ping Away at Atherosclerosis
Authors: John F. Keaney
Journal: New England Journal of Medicine (2017)

Efforts at prevention of cardiovascular disease hinge on the concept of risk factors that, when treated, attenuate the incidence of the disease. Since the concept of cardiovascular risk factors was first proposed in the Framingham Heart Study,1 many distinct risk algorithms have been developed to target preventive measures in patients who should benefit the most. Among the many risk factors used in these algorithms, age typically emerges as the strongest predictor of cardiovascular risk. Several explanations have been offered for how age contributes to cardiovascular disease. Aging is associated with the acquisition and exposure duration of other established risk factors . . .
Increased symptom reporting in middle school athletes based on history of previous concussions
Authors: Rosemarie Scolaro Moser, Philip Schatz
Journal: British Journal of Sports Medicine (2017)

Objective Given findings of increased symptomatology in high school, college, and professional athletes with history of multiple concussions, we sought to identify incidence of symptom reporting at baseline, in middle-school youth athletes on the basis of concussion history. Design Pre-test only. Participants A multi-centre sample of 2,600 middle-school athletes, ages 10–14, who completed baseline evaluations, were assigned to groups on the basis of concussion history: None (N=1210), One (N=1191), Two or more (N=199). Intervention The Post-Concussion Symptom Scale (PCSS) was administered during athletes’ pre-season baseline evaluations. Cross-sectional analyses (ANOVAs) were used to examine symptoms reported at the time of baseline testing by concussion history group Main results Otherwise healthy middle school athletes with a concussion history were statistically (p&lt;0.001) more likely to report symptoms of headache, light sensitivity, irritability, drowsiness, difficulty falling asleep, and sleeping less than usual, than middle school athletes with no history of concussion. Analysis of symptom clusters revealed increased endorsement of symptoms in physical and sleep clusters on the basis of concussion history (p&lt;0.001), but not in cognitive or emotional clusters. Conclusions Developmentally, younger athletes may be less insightful in identifying their cognitive or emotional symptoms. Younger athletes who sustain multiple concussions may experience residual symptoms, which may be precursors to future concussion-related difficulties. These results raise poignant implications for: 1) symptom reporting in younger athletes, thus affecting research and clinical assessment, and 2) the possible impact of early concussion residuals on future functioning of college and professional athletes. Competing interests Dr. Schatz serves on the ImPACT Scientific Advisory Board.
Abstract P043: The COP9 Signalosome Regulates Autophagy
Authors: Huabo Su, Faqian Li, Mark J Ranek, Ning Wei, Xuejun (XJ) Wang
Journal: Circulation Research (2011)

By indiscriminately degrading portions of cytoplasm for self-supply of nutrients, non-selective autophagy helps the cell to survive starvation. Selective autophagy, however, removes defective/surplus organelles and protein aggregates, thereby playing an important role in quality control in the cell. A utophagy is involved in the pathophysiology of a variety of disease, including common forms of heart disease. Mechanisms regulating autophagy, especially selective autophagy, remain poorly understood. The COP9 signalosome (CSN) is an evolutionarily conserved protein complex consisting of 8 subunits (CSN1 through CSN8). CSN was purported to regulate ubiquitin-proteasome system (UPS) mediated proteolysis. We recently reported UPS malfunction and the accumulation of ubiquitin positive aggregates in the cardiomyocytes of mice with perinatal cardiomyocyte-restricted Csn8 knockout (CR-Csn8KO), which displayed massive cardiomyocyte necrosis, congestive heart failure, and premature death. Here we report that Csn8/CSN is required for the removal of autophagosomes in cardiomyocytes, an exciting discovery that has not been reported in any types of cells. CR-Csn8KO mouse hearts show marked increases in LC3-II, indicative of increased autophagosomes. The increase in LC-II is accompanied by a significant increase in p62 protein levels, which is evident as early as 1 week of age, long before the accumulation of a surrogate UPS substrate becomes discernible. The increase in autophagosomes is confirmed by probing with a transgenic GFP-LC3 and by electron microscopy. Autophagic flux assessments reveal that the removal of autophagosomes in cardiomyocytes is impaired by Csn8 deficiency and the defective fusion between autophagosomes and lysosomes may be responsible. Rab7 transcript and protein levels in the heart are significantly decreased by Csn8 deficiency. Confocal microscopy reveals a striking reciprocal relationship between increases in GFP-LC3 puncta and the decreased Rab7 expression. Rab7 knockdown impairs the removal of autophagosomes in cultured cardiomyocytes. Hence, Csn8/CSN is a central regulator in not only the UPS but also autophagy. Csn8/CSN supports autophagosome-lysosome fusion likely by stimulating Rab7 expression.
Features of p53 expression in residual tumors in Russian women after neoadjuvant chemotherapy of breast cancer stage T1-3N0-1.
Authors: Irina Vladimirovna Kolyadina, Irina Poddubnaya, Olga Pavlikova, Dmitrii Komov, Yulia Andreeva, Georgii Frank, Yana V Vishnevskaya
Journal: Journal of Clinical Oncology (2017)

e12121 Background: Residual tumor is an important prognostic factor after neoadjuvant therapy, however, p53 expression in the residual breast tumors poorly understood. Methods: In our study included 164 Russian women (24-76, median age - 47) with breast cancer stage T1-3N0-1 treated in RCRC from 2004 to 2016. Biological subtype of primary tumor was luminal A (8,1%), luminal B HER2-negative (43,6%), luminal HER2+ (15,4%), triple negative (22,8%) and non-luminal HER2+ (10,1%). After neoadjuvant chemotherapy by anthracycline ± taxanes (in HER2+ cancer ± trastuzumab) patients had radical surgery. We analyzed pathological response after neoadjuvant therapy and features of p53 expression in residual tumors. Results: The rate of pCR was 23% for all women, and was a very various for biological type (luminal A – 0%, HER2- luminal B - 11%, HER2+ luminal - 38%, triple negative – 35% and HER2+ non-luminal - 50%), p=0,003. In 15% cases pathological response was a very similar to pCR, in 62% - was low. In analyze of 38 residual tumors we found p53 low expression (&lt;10% stained cells) in 66% cases and high (&gt;10% stained cells) - in 34%. We did not find any correlation between p53 rate in residual tumors and stage, Ki67 and PR-status (p&gt;0,05). But p53 expression strongly correlated with age, tumor grade and biological type (p&lt;0,05). So, high rate of p53 was found more often in women &lt;45 years (50%) vs women 45-59 years (15,4%) and patients 60 years older (20%), p=0,04. All G1-tumors was p53-negative, p53 high expression was seen in 29% of G2 tumors and 80% - G3, p=0,04. The high rate of p53 residual tumor was seen in luminal A subtype in 0%, HER2- luminal B – 30%, HER2+ luminal – 75%, triple negative -50%, HER2+ non-luminal - 100%, p=0,01. Conclusions: High expression of p53 in the residual tumors after neoadjuvant chemotherapy is associated with younger age and unfavorable biological characteristics that may be a very important for the further prognosis in breast cancer.
Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin–N-cadherin pathway after spinal cord injury
Authors: Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Journal: Nature Medicine (2017)
Faut-il faire une coloscopie de dépistage avant sigmoidectomie pour sigmodite?
Authors: S Nahon, F Agret, P Lahmek, B Lesgourgues, T Tuszynski, T Rahme, N Delas
Journal: Endoscopy (2005)

But La realisation d'une coloscopie de dépistage d'un cancer colorectal avant sigmoidectomie pour sigmodite est frCquente. Cependant, si cette attitude peut être justifiée par l'âge souvent avancé des patients, elle n'est pas pour autant basée sur une médecine factuelle.
The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study
Authors: Tanya S. Glaser, Lauren E. Doss, Grace Shih, Divya Nigam, Robert D. Sperduto, Frederick L. Ferris, Elvira Agrón, Traci E. Clemons, Emily Y. Chew
Journal: Ophthalmology (2015)
Knowledge and understanding of genetic test results in men undergoing multigene testing for inherited prostate cancer.
Authors: Veda N. Giri, Sarah Hegarty, Elias Obeid, Colette Hyatt, Carolyn Y Fang, Amy Leader
Journal: Journal of Clinical Oncology (2017)

1516 Background: Genetic counseling (GC) for prostate cancer (PCA) risk is an emerging field, with limited insights regarding needs of males considering genetic testing (GT). Genetic Evaluation of Men is a prospective multigene testing study to identify inherited mutations linked to PCA, with testing following GC. We surveyed men pre-GT and post-GT on knowledge of cancer risk and genetics (KCRG) and understanding of personal GT results to identify GC needs. Methods: Eligibility for males affected or high-risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Demographic, clinical, and FH data were obtained from participants and medical records. Pre-GT survey included questions on KCRG (15 items) and health literacy/numeracy (6 items). Post-GT survey additionally included understanding of GT results (9 items). Personal and FH were categorized into three hereditary cancer syndromes (HCS) linked to PCA. Factors associated with baseline KCRG were assessed by univariable models followed by multivariable linear regression. McNemar’s test was used to assess concordance of understanding GT results vs. actual results. Results: Among 109 men (mean age 63 years, 81% White, 59% PCA diagnosis) who completed pre- and post-surveys, factors associated with higher pre-test KCRG included meeting HCS criteria (p = 0.006) and higher numeracy (p = 0.025). On multivariable analysis, HCS remained significantly predictive of higher KCRG (p = 0.040). However, of 101 men who responded definitively regarding understanding of personal GT results, 13 responded incorrectly on mutation status indicating significant disagreement with actual results (McNemar’s p &lt; 0.001). Of these 13 men, 12 had &gt; = 1 variant of uncertain significance (VUS). Additionally, 6 men were unsure whether they carried a mutation when their GT results found VUS but no mutations. Conclusions: This is the first report of knowledge and understanding of genetics and cancer risk in the context of multigene testing for PCA. While personal/FH of HCS was associated with higher KCRG, understanding of personal GT results was lacking, and warrants tailored GC strategies for multigene testing for inherited PCA.
Eribulin improved overall survival in patients with HER-2 negative metastatic breast cancer: Comparison to bevacizumab plus paclitaxel.
Authors: Mitsuhiko Iwamoto, Nodoka Umezaki, Juuna Matsuda, Kanako Kawaguchi, Risa Terasawa, Nayuko Sato, Hiroya Fujioka, Kosei Kimura, Satoru Tanaka, Kazuhisa Uchiyama
Journal: Journal of Clinical Oncology (2016)

e12035 Background: Eribulin mesylate demonstrated to significant improvement in overall survival (OS) in patients with heavily pretreated, locally recurrent or metastatic breast cancer when compared to treatment of physician's choice. On the other hand, Bevacizumab improved progression fee survival (PHS), but did not do OS. Thus, OS does not necessarily accord with PHS, and there was few clinical study that assess OS as primary endpoint. Methods: HER-2 negative metastatic breast cancer (MBC) patients who underwent chemotherapy of eribulin monotherapy or bevacizumab plus paclitaxel for first to fourth line chemotherapy in our department from November 1, 2011 to September 30, 2015 were reviewed. Kaplan-Meier method was utilized to estimate median OS and log-rank test was used to compare OS. The primary efficacy measure assessed OS, which was calculated as the time from the diagnosis of MBC until death from any case. Results: A total of 56 patients with MBC were assessed in this study (eribulin (E):29cases, bevacizumab+paclitaxel (B):22cases, both eribulin and bevacizumab plus paclitaxel:5cases). Biology studies revealed as follows; luminal (E:75.9%, B:72.7%), triple-negative (E:24.1%, B:27.3%) The median OS in E group was 47.4 months compared to 21.2 months in B group. OS was significantly prolonged in E group compared to B group (p= 0.027). However, PFS in B group (8.3 months) was not significantly better than that in E group (4.9 months) (p= 0.09). Additionaly, clinical benefit rates (CBR) between B group (72.2%) and E group (58.4%) were not significant (p= 0.08). Conclusions: The present study was retrospective and non-randomized study. In addition, subjective bias may have had impact on the results. However, eribulin significantly improved OS of HER-2 negative MBC patients comparing to that of the patients who underwent bevacizumab plus paclitaxel. A larger prospective study to confirm these findings is needed.
Incorporation of NCCN guideline information in NGS-based cancer testing panel design.
Authors: John Leamon
Journal: Journal of Clinical Oncology (2017)

e13099 Background: NGS has revolutionized medical genomics. However, challenges remain in data analysis and interpretation due to the sheer volume of sequencing data produced. As such, optimized panel design is essential to effectively reduce data analysis burden while ensuring inclusion of critical variants. Ideally a panel should target biomarkers of clinical actionability, such as inclusion an active clinical trial or in the NCCN guideline. As information constantly evolves it is difficult if not impossible for any individual laboratory to capture and reflect real-time view in their panel design. Here we present an objective process for biomarker panel design utilizing a comprehensive database to identify key variants with clinical actionability. Methods: QIAGEN has built a bioinformatics database that comprehensively captures relevant scientific and clinical literature, curated through automated and manual processes. This database covers critical information including the NCCN guideline used by laboratories to interpret their sequencing results. We used this database to design an NGS biomarker panel focused on hotspot mutations clinically associated with clear clinical evidence in breast, lung, colon, breast/ovarian, melanoma cancers. Coverage of key variants is then compared with alternative commercial panels. Results: Comparative analysis indicated the QIAGEN panel covered substantially more relevant variants than either of the other ones. Over 100 variants are unique to the QIAGEN Panel. One such example is a point mutation in ERBB2 (S301F) which occurs in Non-Small Cell Lung Cancer (NSCLC) and is referenced in the NCCN guideline. Such finding would be missed if a sample harboring this mutation is tested with alternative panels. Conclusions: This study supports the value of utilizing comprehensive mutational databases in gene panel design. Specifically, the QIAGEN gene panel designed using this approach compared favorably against alternative commercial panels, employing fewer amplicons to provide superior coverage of variants with known actionability. These results demonstrate that optimal panel design permits improves the effectiveness and efficiency of NGS biomarker testing.
Abstract 262: Deletion Of E2f1 Promotes Bone marrow Progenitor Cell Differentiation And Ischemic Cardiac Repair
Authors: Shiyue Xu
Journal: Circulation Research (2014)

Background: We have previously shown that knockout of E2F1 in mice enhances angiogenesis following induction of hind limb ischemia. Recent studies suggest that suppression of E2F1 enhances oxidative phosphorylation in a variety of cell types. Since an increase in oxidative phosphorylation in stem/progenitor cells is often associated with cell differentiation, we hypothesize that E2F1-deficiency may promote bone marrow (BM) progenitor cell differentiation thereby impact on ischemic cardiac repair. Methods and Results: We cultured bone marrow (BM) Lin- progenitor cells under hypoxic and normxic conditions for 24 h, then measured the expression of metabolism associated genes and evaluated cell proliferation and differentiation. We also performed adoptive BM transplantation to reconstitute BM of WT mice with E2F1-/- or WT BM, followed by surgical induction of myocardial infarction (MI), to compare the role of BM E2F1 in the cardiac repair in vivo. Notably, we found that the expression levels of pyruvate dehydrogenase kinase (PDK)-4 and PDK2, two critical inhibitors of mitochondrial oxidative phosphorylation, in the E2F1-/- BM Lin- progenitor cells is markedly lower than those in WT cells (P&lt;0.01, n=4). After culture in the EPC differentiation medium for 7 days, the expression levels of EPC markers, CD31 and KDR , were significantly higher in E2F1-/- cells than in WT control cells (P&lt;0.05, n=3). Although there was no significant difference in the proliferating rate between WT and E2F1-/- BM Lin- progenitor cells cultured in normoxia, when cultured under hypoxic condition the proliferating rate of E2F1-/- cells were markedly greater than that of WT cells (P&lt;0.05, n=3). Consistently, the infarcted size in mice transplanted with E2F1-/-eGFPTg BM was significantly smaller than in mice transplanted with WTeGFPTg BM (P&lt;0.01, n=5). Conclusions: Genetic deletion of E2F1 in the BM progenitor cells enhances oxidative metabolism that may result in enhanced differentiation towards endothelial lineage and increased proliferation in the ischemic/hypoxic tissue environment. Therefore, inhibition of E2F1 in BM progenitor cells may improve the recovery from cardiac ischemic injury.
Reviews and Meta-analyses of Psychotherapy Efficacy for Borderline Personality Disorder—Reply
Authors: Ioana Alina Cristea, Corrado Barbui, Pim Cuijpers
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