tbuckley/cabot-search huggingface dataset:
Cetuximab with chemotherapy (CT) as first-line treatment for metastatic colorectal cancer (mCRC): Analysis of the CRYSTAL and OPUS studies according to <i>KRAS</i> and <i>BRAF</i> mutation status.
Authors: C. Bokemeyer, C. Kohne, P. Rougier, C. Stroh, M. Schlichting, E. Van Cutsem
Journal: Journal of Clinical Oncology (2010)

3506 Background: The CRYSTAL and OPUS studies showed that adding cetuximab to CT in the first-line treatment of mCRC significantly improved treatment outcome compared with CT alone, in patients (pts) with KRAS wild-type (wt) tumors. This pooled analysis of the CRYSTAL and OPUS pt populations evaluated overall survival (OS), progression-free survival (PFS), and best overall response (OR) using updated data. Methods: The analysis was performed on individual pt data from both studies for all efficacy endpoints according to KRAS/BRAF mutation status. KRAS and BRAF mutation status was determined by quantitative PCR. Treatment arms were compared according to mutation status using log rank and Cochran-Mantel-Haenszel tests. Results: The data with respect to KRAS wt and BRAF tumor mutation status are presented in the Table. Conclusions: This analysis confirms that the addition of cetuximab to CT first line in pts with KRAS wt tumors achieves a statistically significant improvement in OR rate, PFS, and OS compared with CT alone. The best outcome was observed in pts with KRAS wt/BRAF wt tumors (90% of KRAS wt pts). BRAF mutation status does not appear to be a strong predictive biomarker for the addition of cetuximab to CT but the sample size may be too small to be reliable. KRAS wt (n=845) KRAS wt/BRAF wt (n=730) KRAS wt/BRAF mt (n=70) CT (n=447) Cetuximab + CT (n=398 ) CT (n=381) Cetuximab + CT (n=349) CT (n=38) Cetuximab + CT (n=32 ) Median OS months (95% CI) 19.5 (17.8–21.1) 23.5 (20.7–25.7) 21.1 (19.5–23.6) 24.8 (22.1–27.0) 9.9 (5.7–13.6) 14.1 (8.8–18.5) Hazard ratio (95% CI) p (heterogeneity p value) 0.81 (0.69–0.94) 0.0062 (0.6996) 0.84 (0.71–1.00) 0.0479 (0.6980) 0.62 (0.36–1.06) 0.0764 (0.0478) Median PFS months (95% CI) 7.6 (7.4–8.4) 9.6 (8.9–11.3) 7.7 (7.4–9.0) 10.9 (9.2–11.9) 3.7 (2.1–7.9) 7.1(3.7–9.1) Hazard ratio (95% CI) p (heterogeneity p value) 0.66 (0.54–0.80)<0.00010.3332 0.64 (0.52–0.79)<0.00010.3362 0.67 (0.34–1.29)0.23010.3778 OR rate, % 38.5 57.3 40.9 60.7 13.2 21.9 Odds ratio (95% CI) p (heterogeneity p value) 2.16 (1.64–2.86) <0.00010.5568 2.27 (1.68–3.07) <0.0010.5891 1.60 (0.45–5.67) 0.4606 0.1727 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA, Merck Serono Merck Serono, Pfizer Merck Serono, Pfizer Merck Serono, Pfizer
Attention deficit hyperactivity disorder in adults
Authors: Amanda E Olagunju, Faraz Ghoddusi
Journal: American Journal of Psychiatry (1994)

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder involving functionally disruptive inattentive and/or hyperactive/impulsive behaviors, such as being easily distracted, regularly failing to follow through on tasks, being restless, or often interrupting others. ADHD diagnosed in childhood often persists into adulthood, with 14.6% of U.S. adults meeting the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria for ADHD. When evaluating for adult ADHD, other mental disorders should be included in the differential diagnosis due to the substantial overlap of symptoms and ADHD concurrence with anxiety/stress, mood, personality, impulse control, and substance use disorders. An ADHD diagnosis requires a comprehensive clinical history and evaluation, patient symptom and function assessment (e.g., Adult ADHD Self-Report Scale, Conners Adult ADHD Rating Scales), and gathering of collateral information. Clinical guidelines recommend a subset of amphetamine and methylphenidate stimulants as first-line pharmacotherapy, which may be more effective when combined with psychotherapy. For adults unable to take stimulants or with concurrent anxiety/depression, options include atomoxetine, viloxazine, and bupropion. To monitor for patient misuse or diversion of stimulants, physicians should consider employing controlled substance agreements and prescription drug monitoring programs.
Abstract P1-14-21: Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: Development of a specific predictor
Authors: C Jankowski, S Guiu, M Cortet, D Hudry, L Arnould, C Charon-Barra, I Desmoulins, R Rouzier, P Fumoleau, B Coudert, F Reyal, C Coutant
Journal: Cancer Research (2016)

Abstract Purpose: The aim of this study was to assess the M.D Anderson Cancer Center / Gustave Roussy Institute (MDACC/IGR) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of HER2 tumors treated with preoperative chemotherapy with trastuzumab. Then, we combine clinical and pathological variable associated with pCR into a new nomogram specific of HER2 tumors treated by preoperative chemotherapy with trastuzumab. Methods: Data from 270 patients treated with preoperative chemotherapy with trastuzumab at Curie Institute and at Georges Francois Leclerc Cancer Center were used to assess MDACC/IGR nomogram and then to develop a nomogram for pCR based on multivariate logistic regression. Model performance was quantified with respect to calibration and discrimination. Results: The IGR/MDACC was not accurate to predicting pCR in HER2 tumors treated by preoperative chemotherapy with trastuzumab with poor discrimination (AUC=0,54, IC [0,51-0,58]) and poor calibration (p=0,01). After uni and multivariate analysis, the new pCR nomogram was based on T stage (TNM), hormonal receptor status, and ki67(%). The model had a good discrimination 0,74 (IC95% : [0,70-0,79]) and a good calibration (p=0,93). Conclusion: To our knowledge, this is the first nomogram to predict pCR in HER2 tumors treated by preoperative chemotherapy with trastuzumab. To ensure exportability, the model need to be evaluate with a external validation set. Citation Format: Jankowski C, Guiu S, Cortet M, Hudry D, Arnould L, Charon-Barra C, Desmoulins I, Rouzier R, Fumoleau P, Coudert B, Reyal F, Coutant C. Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: Development of a specific predictor. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-21.
Abstract B12: Rapamycin-induced miR-21 promotes the survival of mTORC1 hyperactivated cells in tuberous sclerosis complex models
Authors: Hilaire C. Lam, Harilaos Filippakis, Katherine A. Cottrill, Alicia Llorente Lope, Damir Khabibullin, Carmen Priolo, Barbara Ogorek, Stephen Y. Chan, Ana Pereira, Elizabeth P. Henske
Journal: Cancer Research (2016)

Abstract Background: Tuberous sclerosis complex (TSC) is a multisystem, hamartomatous disease associated with tumors of the brain, skin and kidney, as well as progressive cystic lung destruction characteristic of lymphangioleiomyomatosis (LAM). TSC is caused by mutations in TSC1 or TSC2, resulting in hyperactive mechanistic Target of Rapamycin (mTOR) 1 signaling. Rapamycin and related rapalogs inhibit mTORC1 activity and stabilize tumors in TSC patients, but tumor progression proceeds at pretreatment rates following cessation of therapy. MicroRNA repress target gene expression and are commonly dysregulated in cancers. In previously published work, we identified a group of rapamycin responsive miRNA, rapa-miRs. Surprisingly the most upregulated rapa-miRs, miR-21 in particular, are known pro-survival oncogenic miRNA (oncomiRs). We hypothesize that inhibiting miR-21 and downstream targets may lead to more complete and durable responses to mTORC1 inhibitors. Methods: We utilized qRT-PCR to determine the kinetics of miR-21 induction with rapamycin in various cell types and in mouse xenografts. Mimics and inhibitors were used to determine the functional consequences of miR-21 in TSC2-null cells. Expression profiling was used to identify miRNA target genes. Bioinformatics and network analysis approaches were implemented to identify biological relationships between the miR-21 targets. Results: Our initial screens identified miR-29b, -21, -24, -221, -106a and -199a as candidate rapa-miRs. Rapamycin induced miR-21 greater than 1.5 fold in diverse cell lines and in mouse xenografts. We have identified pro-cell death targets, PPIF, TP53BP2 and PDCD4, which are negatively regulated by miR-21 upon rapamycin treatment. Network analysis using the Consolidated Interactome (CI) revealed that rapa-miRs inhibit multiple key pro-apoptotic targets. These data suggest that rapa-miRs regulate proteins critical for cell fate determination and survival in response to rapamycin treatment. Conclusions: Rapamycin induces pro-survival oncomiR, miR-21, which may be a valuable target for therapeutic intervention in TSC. Citation Format: Hilaire C. Lam, Harilaos Filippakis, Katherine A. Cottrill, Alicia Llorente Lope, Damir Khabibullin, Carmen Priolo, Barbara Ogorek, Stephen Y. Chan, Ana Pereira, Elizabeth P. Henske. Rapamycin-induced miR-21 promotes the survival of mTORC1 hyperactivated cells in tuberous sclerosis complex models. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B12.
Acute Lymphoblastic Leukemia
Authors: Janet M. Torpy
Journal: JAMA (2009)

Acute Lymphoblastic LeukemiaA cute lymphoblastic leukemia (ALL) is the most common cancer in children and represents about one-quarter of all cancers among persons younger than 15 years.Acute lymphoblastic leukemia is a cancer of the blood and bone marrow (spongy tissue in the center of bone).In ALL, too many bone marrow stem cells develop into a type of white blood cell called lymphocytes.These abnormal lymphocytes are not able to fight infection very well.Also, as the number of these lymphocytes increases, there is less room for healthy white blood cells, red blood cells, and platelets.This may lead to infection, fatigue, and easy bleeding.The January 28, 2009, issue of JAMA includes an article about genetic variations associated with treatment response in childhood ALL.This Patient Page is based on one previously published in the March 21, 2007, issue of JAMA.
The Lumleian Lectures on Some Points in the Natural History of Primitive Dry Pleurisies
Authors: A. Clark
Journal: BMJ (1885)

A CAREFUL study of the cases related with more or less comipleteness in my first lecture, leads naturally and necessarily to the secoind stage of this inquiry.A full understanding of the clinical demands a solution of the pathological problem.They are inseparably con- nected, and find their common origin in dynamic disturbances, which, although sometimes intangible, invisible, and incalculable, constitute the ultimate nature or essence of disease.What, then, is the nature of the visible pathological changes originatinlg, underlying, maintain- ing, and continuing the symptoms and signs characteristic of the course and issues of the cases set forth as the grounds of this inquiry?But, before describing those changes as I have observed them in the course of my examinations, I must clear the way to the better under- standing of them by some remarks on the minute anatomy of the lung, and on the structural characters of a blood-clot formed in freshly drawn blood.Setting aside the earlier, and in sundry ways almirable, accounts of the minute anatomy of the lung given by Addison, Rainey, Rind- fleisch, Schultze, Charot, Sappey, Lefort, and Waters, and confining our examination to the accounts more recently published by such ob- servers as Schafer and Klein, we shall learn from them the views received and adopted at the present time.Here is what Schafer savs (Quain's Anatomy, vol.ii, page 514)."After a certain stage of sub- division, each bronchial tube reduced to a small size is termed a lobular or respiratory bronchial tube, and its walls become beset with small hemispherical saccules termed air-cells or alveoli.They occur at first only here and there, and confined to one side of the tube only, but at length almost cover it, so that the tube in a great measure loses its cylindrical character.At length it ends in an enlarged completely sacculated passage termed the alveolar passage, from which are given off blind ramifications, somewhat enlarged towards their extremities, and everywhere closely beset with the air-cells.These enlarged terminations are named infundibula."In oider to give as exact an expression as possible of these views, he illustrates them by a diagram given at page 516 of the work already cited.From Klein's Atkas and from his more recelit masterly little Handbook of Histology, I extract the following account, which, on the whole, is the simplest, clearest,
Determinants of Central Nervous System (Cns) Metastases in a Cohort of 620 Early Breast Cancer Patients After 11 Years Follow Up: Role of Disseminated Tumor Cell (Dtc) in Bone Marrow (Bm) Detected at Primary Diagnosis
Authors: D. Loirat, F.C. Bidard, L. Chaltiel, F. Berger, V. Diéras, Y. De Rycke, S. Alran, Y. Kirova, P.H. Cottu, A. Vincent-Salomon, X. Sastre-Garau, J. Pierga
Journal: Annals of Oncology (2014)
Abstract 4143: Discrete clones cooperate to promote tumor progression through a non-cell-autonomous mechanism in intestinal cancers
Authors: Alyssa A. Leystra, Amanda M. Wisinger, Christopher D. Zahm, Kristina A. Matkowskyj, Chelsie K. Sievers, Alex Schwartz, Dawn M. Albrecht, Linda Clipson, Dustin A. Deming, Michael A. Newton, Richard B. Halberg
Journal: Cancer Research (2015)

Abstract Background: The process of tumor evolution has often been described as a single initiated cell propagating a tumor with subclones of that cell acquiring distinct molecular changes and competing for dominance within the tumor. However, colon tumors are now known to often be derived from multiple initiated progenitor cells. Distinct initiated clones might cooperate or alternatively compete during tumorigenesis, progression, and therapy. Methods: Mice carrying the Min allele of Apc and expressing an oncogenic form of PI3K in a subset of colonic epithelial cells develop multiple adenomas and adenocarcinomas in the colon. We utilized cell lineage tracing to follow the progeny of individual progenitor cells through tumor establishment, progression, and treatment with GDC 0941, a PI3K inhibitor. Results: Nearly half (44%; 30/68) of the tumors were derived from at least two progenitor clones, one of which expressed the oncogenic form of PI3K and one of which did not. The presence of both types of clones correlated to an increased frequency of either clone becoming invasive (p = 0.0002). Additionally, the presence of both clones appeared to protect susceptible clones from targeted therapy. Conclusions: Taken together, these data indicate that genetically distinct tumor progenitors can establish a single lesion, and moreover cooperation amongst diverse clonal populations provides a fitness advantage during tumor progression and therapy. Citation Format: Alyssa A. Leystra, Amanda M. Wisinger, Christopher D. Zahm, Kristina A. Matkowskyj, Chelsie K. Sievers, Alex Schwartz, Dawn M. Albrecht, Linda Clipson, Dustin A. Deming, Michael A. Newton, Richard B. Halberg. Discrete clones cooperate to promote tumor progression through a non-cell-autonomous mechanism in intestinal cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4143. doi:10.1158/1538-7445.AM2015-4143
Size and targeting to PECAM vs ICAM control endothelial delivery, internalization and protective effect of multimolecular SOD conjugates
Authors: Vladimir V. Shuvaev, Silvia Muro, Evguenia Arguiri, Makan Khoshnejad, Samira Tliba, Melpo Christofidou-Solomidou, Vladimir R. Muzykantov
Journal: Journal of Controlled Release (2016)
Effectiveness of after-school interventions at increasing moderate-to-vigorous physical activity levels in 5- to 18-year olds: a systematic review and meta-analysis
Authors: Ruth Mears, Russell Jago
Journal: British Journal of Sports Medicine (2016)

Physical activity in children improves cardiovascular, mental, metabolic and skeletal health. Many children fail to meet the national recommendation of at least 60 min per day of moderate-to-vigorous physical activity (MVPA). After-school programmes provide an opportunity to engage children in physical activity. This systematic review and meta-analysis examine the effectiveness of after-school interventions at increasing MVPA levels in children and adolescents.Systematic review and meta-analyses.A literature search was conducted using MEDLINE, EMBASE and PsychINFO databases from January 1950 to April 2015.Inclusion criteria-Population: participants aged 5-18 years.an after-school programme in a school-based setting as the main component of an intervention to increase physical activity levels.individual-level measure of time spent in MVPA.quasi-experimental, pilot, non-randomised or randomised trials.conference abstracts, unpublished articles, dissertations and non-English language papers.1387 records were identified through database searching. After removal of duplicates, there were 748 records. 15 articles met the inclusion criteria for the systematic review. 6 studies were eligible for meta-analysis and the pooled intervention effect at end point follow-up was 4.84 min/day of MVPA (95% CI -0.94 to 10.61). The effectiveness of after-school interventions varied considerably and comparisons between studies limited by different methodological study designs. Subgroup analyses within a small minority of studies revealed significant benefits in overweight/obese children and boys. There was a lack of convincing evidence that interventions based on theories of behaviour change were more effective than those with no underlying theory.After-school physical activity interventions to date have had mixed effectiveness on increasing MVPA levels. More robust evaluations of extracurricular physical activity interventions are required, particularly studies that use objective assessment of physical activity.
Abstract P4-14-13: Pertuzumab (P) use in first-line HER2-positive metastatic breast cancer (mBC) in US community oncology practices: Treatment patterns and outcomes
Authors: N Robert, H-P Goertz, L Asmar, W-Y Tseng, X Jiao, C Portera, B Yoo, D Patt, V Antao
Journal: Cancer Research (2016)

Abstract Background: Pertuzumab was FDA-approved in 6/2012 for use in first-line in combination with trastuzumab (H) and docetaxel for patients (pts) with HER2-positive mBC. This retrospective study investigated the clinical characteristics, treatment patterns, safety, and outcomes for pts with HER2-positive mBC who received a P-containing regimen in first-line in US community oncology practices. Methods: This study utilized iKnowMed electronic health records, Claims Data Warehouse, and Social Security Death Index. Pts with HER2-positive mBC, who received a P-containing regimen between 6/2012 and 6/2014 and were followed through 12/2014, had ≥2 visits within the McKesson Specialty Health/US Oncology Network, and were not on clinical trials during the study period, were eligible. Results: Of the 322 pts who received a P-containing regimen in the first-line setting, 25% were ≥65 years of age, 63% were post-menopausal, 61% had hormone receptor-positive mBC, 84% had a performance status of 0 or 1, and 76% had a Charlson Comorbidities Index of 0. Twenty-one percent of pts had 1 site of metastasis noted, 32% had 2 sites, and 47% had 3 or more sites. Pts with de novo mBC made up 40% of this cohort. Of the pts with recurrent mBC, over 60% received H in the early-stage BC setting. In the first-line mBC setting, 93% of the 322 pts received H+P+taxane, and 7% received H+P with other chemotherapy agent(s). Common adverse events reported included: fatigue (49%), diarrhea (44%), nausea (33%), peripheral neuropathy (33%), neutropenia (24%), and rash (22%). Further analyses including outcomes of these 322 pts will be presented. Conclusions: First-line P was given in combination with H and chemotherapy agent(s) (93% taxane). No new safety signals were observed. More details on the clinical characteristics, specific treatment patterns, and safety will be presented, along with the progression-free survival of these pts receiving first-line P-containing therapy in a real-world setting. Citation Format: Robert N, Goertz H-P, Asmar L, Tseng W-Y, Jiao X, Portera C, Yoo B, Patt D, Antao V. Pertuzumab (P) use in first-line HER2-positive metastatic breast cancer (mBC) in US community oncology practices: Treatment patterns and outcomes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-13.
Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles
Authors: Christopher G. England, Hyung-Jun Im, Liangzhu Feng, Feng Chen, Stephen A. Graves, Reinier Hernandez, Hakan Orbay, Cheng Xu, Steve Y. Cho, Robert J. Nickles, Zhuang Liu, Dong Soo Lee, Weibo Cai
Journal: Biomaterials (2016)
Abstract P2-08-26: Tumor-associated macrophages and platelet-derived growth factor C as a prognostic marker for breast cancer patients
Authors: T-K Yoo, K-M Lee, H Jung, YR Na, SH Seok, W Han
Journal: Cancer Research (2016)

Abstract Introduction: Tumor related inflammation plays an important role in breast cancer progression, tumor-associated macrophages (TAMs) being a crucial part of this microenvironment. Platelet-derived growth factor-C (PDGF-C) is abundant in the breast cancer microenvironment having an anti-apoptotic effect on macrophages. Previous reports suggest that tumor cell derived PDGF-C promotes TAM survival, enhancing tumor progression. In this study we analyzed the prognostic value of PDGF-C density associated with TAM infiltration in human breast cancer. Materials and Methods: TAM and PDGF-C density was evaluated by immunohistochemistry of CD163+, CD68+ and PDGF-C myeloid cells in tumor stroma. Tissue microarrays from 140 invasive breast cancer cases were used. Survival analysis to evaluate the impact of TAM and PDGF-C density on disease free survival (DFS) was done using Kaplan-Meier and Cox regression analysis. Results: Infiltration of CD163+ and CD68+ macrophages into tumor stroma had a tendency, but not significant, for reduced DFS (p=0.204, p=0.314 respectively). Whereas PDGF-C strong density was significantly associated with worse DFS (p=0.024). This inverse correlation with DFS was demonstrated stronger when PDGF-C density was combined with CD163+ and CD68+ macrophage infiltration (p=0.008, p=0.018, respectively). But, CD163+ or CD68+ infiltration with strong PDGF-C density did not demonstrate as an independent prognostic factor when adjusting for tumor size, lymph node metastasis, hormone receptor and histologic grade. This result is probably due to small number of patients having both TAM infiltration and strong PDGF-C density. Conclusion: Our results show that PDGF-C infiltration adversely affects DFS and also enhances the inverse correlation between tumor-associated macrophages and DFS. To support these results, a study with larger numbers is on progress. Citation Format: Yoo T-K, Lee K-M, Jung H, Na YR, Seok SH, Han W. Tumor-associated macrophages and platelet-derived growth factor C as a prognostic marker for breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-26.