tbuckley/cabot-search huggingface dataset:
Preclinical assessment of docetaxel-based chemotherapy on a panel of human non small cell lung cancer (NSCLC) xenografts. A study of the laboratory of preclinical investigation of the Curie Institute.
Authors: Fariba Nemati, Jean-Gabriel Judde, Gonzague de Pinieux, Patricia de Cremoux, Alain Chapelier, Alain Livartowski, Marie-France Poupon, Didier Decaudin
Journal: Cancer Research (2008)

1203  Anticipate the efficacy of new therapeutic modalities by experimental assays should be critically useful for the clinics. This can be done in vivo by using human cancers grafted into immunodeficient mice. Treatment of advanced NSCLC is still today particularly inefficient and all efforts must be done to improve it. The aim of this study was therefore to validate a panel of xenografts for testing in vivo the efficacy of new compounds or new combination of drugs. Seven human xenografts have been obtained from 6 NSCLC patients, in whom three adenocarcinoma and 3 epidermoid cancers. Five xenografts were originated from metastatic lesions and 2 from primary lung lesions. Two xenografts came from the same patient but from initial primary (ML5) and secondary adrenal metastatic sites (IC14). In all cases, histological diagnosis of the xenografts reproduced that of the original patient’s tumor. In vivo treatments were intraperitoneally administered on mice bearing 100-400 mm3 NSCLC xenografts, namely docetaxel (D)(20 mg/kg every three weeks), cisplatin (C)(1 mg/kg/d every 3 weeks), vinorelbine (V)(1.25 mg/kg/d a week), and gemcitabine (G)(80 mg/kg/d a week). Docetaxel given as single agent chemotherapy induced a significant response in 5 of the 7 NSCLC xenografts (71%) with an optimal tumor growth inhibition ranged between 44% (ML5) and 88% (IC14). Surprisingly, ML5 tumor was less sensitive to docetaxel than IC14 xenograft. Docetaxel combinations were tested on the sensitive IC8 and on the more resistant IC1 tumors. Docetaxel combinations were tested on the sensitive IC8 and on the resistant IC1 tumors. On both tumors, no difference of tumor growth inhibition was observed between docetaxel treatment and docetaxel combined with any other drug (cisplatin, vinorelbine, or gemcitabine). Relative expression of genes putatively involved in drug response has also been studied in all xenografts of the panel and data will be presented further. In conclusion, we show that our series of NSCLC xenografts directly obtained from patients showed significant response to docetaxel and that docetaxel-combined chemotherapies did not improve it. By reproducing the clinical outcome of NSCLC disease, this series of NSCLC xenografts therefore constitutes a useful model for preclinical assays.
Abstract 12635: Nationwide Long-term Follow-up of Pulmonary Atresia With Ventricular Septal Defect
Authors: Anu Kaskinen, Juha-Matti Happonen, Ilkka P Mattila, Olli M Pitkänen
Journal: Circulation (2015)

Introduction: The naturally poor survival of pulmonary atresia with ventricular septal defect (PA+VSD) has improved due to evolved perioperative and surgical treatment. Studies including PA+VSD patients, both with and without major aortopulmonary collateral arteries (MAPCAs), with extensive follow-up are scarce. This nationwide study aimed to investigate survival and surgical treatment in PA+VSD patients with and without MAPCAs. Methods: Study comprised 109 PA+VSD patients born in Finland between 1970 and 2007. We reviewed retrospectively medical records and operative reports through December 2011, as well as first available angiograms and preoperative angiograms prior to repair attempt. Results: The median follow-up time for the total study population, including also patients who died during the follow-up, was 11.4 years (IQR 0.8 - 21.1). The incidence of PA+VSD, which could be determined reliably from 1995 to 2007, was 6.1 per 100 000 live births. Although the patients with (n = 43) or without MAPCAs (n = 66) showed no difference in survival (p = 0.74), the patients without MAPCAs had better probability to achieve repair (64% vs. 28%, p &lt; 0.0001). The bigger size of true central pulmonary arteries assessed by McGoon index at first angiogram [HR 0.66 (CI95% 0.49 - 0.88) per 0.5 McGoon index units, p = 0.006] and achievement of repair [HR 0.07 (CI95% 0.03 - 0.17), p &lt; 0.0001] improved the overall survival. After successful repair survival was 93% at 1 year and 91% from 2 years on. Palliated patients, instead, had survival at 1, 5, 10, and 20 years of age of 55%, 42%, 34%, and 20% respectively. However, patients with right ventricle - pulmonary artery connection and septal fenestration had better survival than rest of the palliated patients (p = 0.001). Palliation with a systemic-pulmonary artery shunt increased McGoon index by 41% (p &lt; 0.0001). Conclusions: The patients with MAPCAs had higher risk to remain palliated than patients without, although their survival was similar. Survival of PA+VSD was influenced by the initial size of true central pulmonary arteries and whether repair was achieved. Although palliative procedures may not improve the final outcome of PA+VSD, palliative surgery may have a role in its treatment.
Guiding policy to reduce the burden of COPD: the role of epidemiological research
Authors: Guy B Marks
Journal: Thorax (2018)

In  Thorax , Bhatt and colleagues’ interesting cross-sectional analysis of data from the COPDGene study cohort demonstrates, somewhat unsurprisingly, that the compound (multiplicative) measure of cumulative exposure to tobacco smoking, ‘pack-years’, is a suboptimal index of exposure with respect to effects on indices of airflow obstruction, spirometric lung volume and emphysema.1 This is unsurprising because there is no biological basis for assuming that the effects should be manifest by a simple multiplicative relationship between duration of smoking and estimated average number of cigarettes smoked per day. Compound measures are convenient, but usually not robust, measures for epidemiological investigation. This study confirms that it is almost always more appropriate (and powerful) to analyse the individual components of the exposure separately and to model the interaction between them.

Perhaps more surprising is the near absence of any effect of the estimated …
Where sports medicine and physical activity for health intersect – occasion for opportunity or improbable idealism?
Authors: Jane S Thornton
Journal: British Journal of Sports Medicine (2018)

While sport and exercise medicine can often feel like two separate disciplines, it is at the intersection of these solitudes where the most novel and innovative research is pushing our field. Where they meet, opportunities for patients and further research become widely apparent.

In this Canadian Academy of Sport and Exercise Medicine (CASEM)-led issue, we highlight 7 key articles that begin to bridge this gap between general exercise recommendations and sport-specific interventions.

First is a systematic review on exercise prescription for overhead athletes with shoulder pathology. Alexis Wright and colleagues demonstrate that this field is dominated by expert opinion, with limited scientific evidence for any one specific exercise, underlining the fact that this field is ripe for further well-designed studies. ( see page 241 ) And remember BJSM has a systematic review competition – keep BJSM in mind for top quality systematic reviews!

Further …
Abstract 19223: Left Ventricular Strain Rate Can Predict Rehospitalizations With Congestive Heart Failure After Transcatheter Aortic Valve Replacement
Authors: Makoto Amaki, Atushi Okada, Yusuke Shimahara, Hideaki Kanzaki, Yasuhiro Hamatani, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Tomoyuki Fujita, Junjiro Kobayashi, Yasuda Satoshi, Toshihisa Anzai
Journal: Circulation (2016)

Background: Transcatheter aortic valve replacement (TAVR) has become important treatment of choice for severe aortic stenosis in patients with high surgical risks. However, previous report demonstr...
OBSTETRICS AND GYNÆCOLOGY.
Journal: JAMA (1884)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract O.06: Epidemiology of Kawasaki Disease in Canada (2004-2011)
Authors: Brian W McCrindle, Sunita O’Shea, Brendan Lew, Sameer Masood, Dirk Bock, Lillian S Lai, Rejane F Dillenburg, Bailey Bernknopf, Nita Chahal, Rae S Yeung, Cedric Manlhiot
Journal: Circulation (2015)

Introduction: We have previously documented in consecutive triennial systematic surveillances a rise in the incidence of KD in Ontario, Canada between 1995 and 2004 followed by a stabilization at 24-26 cases per 100,000 children &lt;5 year old per year between 2004 and 2009. Previous studies have been limited to the province of Ontario; we sought to determine the incidence of KD across Canada and by province. Methods: We queried the Canadian hospital discharge database (Canadian Institute for Health Information) for hospital admissions associated with a discharge diagnosis of KD (either primary or secondary) between 2004 and 2011. Multiple admissions for a given patient were not counted as separate incident cases unless &gt;2 months from the original admission and associated with IVIG treatment. Denominators were derived from population data from the 2001, 2006 and 2011 Censuses. Results: The annual incidence of KD during the study period was 21.9, 6.8 and 1.1 cases per 100,000 children &lt;5 years, 5-9 years and 10-14 years old, respectively (4,340 cases total). Stratification by region showed the lowest incidence to be in Saskatchewan (11.8/100,000 children &lt;5 year old), followed by Manitoba (17.3), Alberta (17.7), Quebec (18.1), British Columbia (20.6), Atlantic Provinces (22.5) and finally Ontario (27.5, similar to that noted on previous systematic surveillances). The incidence remained stable over the study period, confirming the plateau reached in the previous systematic Ontario surveillance between 2004-2009. An increased incidence was noted for children &lt;5 years old, male gender and winter months. There was a moderate correlation between proportion of the provincial population of Asian descent and KD incidence (r=0.58). Coronary artery aneurysms affected 5.8% of patients, and 1.9% experienced major cardiac complications or had cardiac interventions. Conclusions: The previous increase in the incidence of KD has plateaued, indicating that the true annual incidence fluctuates between 20-22 and 24-27 cases per 100,000 children &lt;5 years for Canada as a whole, and 24-27 cases for the province of Ontario. Differences in annual incidence observed between provinces remain to be explained, but may reflect racial, genetic or environmental factors.
Differential Regulation of T Cells By PI3K Delta Inhibitors in a CLL Murine Model
Authors: Kamira Maharaj, John J. Powers, Alex Achille, Mibel Pabon-Saldana, Renee Fonseca, Susan Deng, Hari P Miskin, Dave Maryanski, Eva Sahakian, Javier Pinilla-Ibarz
Journal: Blood (2017)
Separation of blood and lymphatic vascular networks is regulated by the hematopoietic signaling proteins SLP-76 and Syk.
Authors: F Abtahian, A Guerriero, M M Lu, Z Rong, A Mocsai, E E Myers, H Bin, D Jackson, V A Ferrari, V Tybulewicz, C A Lowell, J J Lepore, G A Koretzky, M L Kahn
Journal: Blood (2002)
BACE1 elevation engendered by GGA3 deletion increases β-amyloid pathology in association with APP elevation and decreased CHL1 processing in 5XFAD mice
Authors: WonHee Kim, Liang Ma, Selene Lomoio, Rachel Willen, Sylvia Lombardo, Jinghui Dong, Philip G. Haydon, Giuseppina Tesco
Journal: Molecular Neurodegeneration (2018)

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the production of amyloid beta (Aβ), the toxic peptide that accumulates in the brains of Alzheimer's disease (AD) patients. Our previous studies have shown that the clathrin adaptor Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) plays a key role in the trafficking of BACE1 to lysosomes, where it is normally degraded. GGA3 depletion results in BACE1 stabilization both in vitro and in vivo. Moreover, levels of GGA3 are reduced and inversely related to BACE1 levels in post-mortem brains of AD patients. In order to assess the effect of GGA3 deletion on AD-like phenotypes, we crossed GGA3 −/− mice with 5XFAD mice. BACE1-mediated processing of APP and the cell adhesion molecule L1 like protein (CHL1) was measured as well as levels of Aβ42 and amyloid burden. In 5XFAD mice, we found that hippocampal and cortical levels of GGA3 decreased while BACE1 levels increased with age, similar to what is observed in human AD brains. GGA3 deletion prevented age-dependent elevation of BACE1 in GGA3KO;5XFAD mice. We also found that GGA3 deletion resulted in increased hippocampal levels of Aβ42 and amyloid burden in 5XFAD mice at 12 months of age. While levels of BACE1 did not change with age and gender in GGAKO;5XFAD mice, amyloid precursor protein (APP) levels increased with age and were higher in female mice. Moreover, elevation of APP was associated with a decreased BACE1-mediated processing of CHL1 not only in 12 months old 5XFAD mice but also in human brains from subjects affected by Down syndrome, most likely due to substrate competition. This study demonstrates that GGA3 depletion is a leading candidate mechanism underlying elevation of BACE1 in AD. Furthermore, our findings suggest that BACE1 inhibition could exacerbate mechanism-based side effects in conditions associated with APP elevation (e.g. Down syndrome) owing to impairment of BACE1-mediated processing of CHL1. Therefore, therapeutic approaches aimed to restore GGA3 function and to prevent the down stream effects of its depletion (e.g. BACE1 elevation) represent an attractive alternative to BACE inhibition for the prevention/treatment of AD.
Satisfaction with care and likelihood to recommend ratings attributed to dermatology trainees
Authors: Laura E. McDermott, Margaretta Midura, Vassiliki Papagermanos, Joslyn Kirby, Karolyn A. Wanat, Leah T. Belazarian, Cory Dunnick, Jessica S. Mounessa, Stephanie A. Savory, Nidhi Avashia-Khemka, Andrew Strunk, Amit Garg
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 22: Identification of the Nature of Cardiac Resident c-kit <sup>+</sup> Cells
Authors: Chen-Leng Cai, Nishat Sultana, Lu Zhang, Jianyun Yan, Jiqiu Chen, Weibin Cai, Shegufta Razzaque, Dongtak Jeong, Wei Sheng, Lei Bu, Mingjiang Xu, Guo-Ying Huang, Roger Hajjar, Bin Zhou, Anne Moon
Journal: Circulation Research (2016)

Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. For more than a decade, c-kit, a receptor tyrosine kinase expressed in certain types of hematopoietic stem cells, has been recognized as a marker of resident CSCs in mammals. It was shown that c-kit + cells are multipotent, with differentiation potential to become cardiomyocytes, endothelial, and smooth muscle cells in vitro and after cardiac injury. Here, we provide new insights into the nature of cardiac resident c-kit + cells. By targeting the c-kit locus with several reporter genes in mice, we unexpectedly found that c-kit + cells rarely co-localizes with cardiac progenitor marker Nkx2.5 or myocardial marker cTnT. Instead, c-kit labels an endocardial population from embryonic stage to adulthood. After acute cardiac injury, the c-kit + cells still retain their endothelial identity and do not become cardiomyocytes. Our study supports the notion that cardiac c-kit + cells are in fact endothelial cells and not CSCs. This finding suggests an urgent need to re-evaluate the mechanisms by which c-kit + cells contribute to heart repair or regeneration given their endothelial identity.
Uniform spatial distribution of the cellular response to cisplatin and docetaxel in HNSCC
Authors: Iris-Susanne Horn, Christof Granzow, Werner Rittgen, Gunnar Wichmann, Andreas Dietz
Journal: Cancer Research (2008)

LB-182    Background:  Using biopsy material to predict the efficacy of non-surgical treatment for solid tumors leaves most of the tumor untested. Results may be dubious unless they are shown to be representative of the entire tumor.  Methodology:  After obtaining informed consent, 3 fragments were each excised from different areas of freshly resected head and neck squamous cell carcinomas (HNSCC) of 14 untreated patients. The specimens were weighed and studied by means of a colony formation assay starting with mincing followed by collagenase digestion for 16 hours. Digests were distributed to extracellular matrix-coated wells of microtiter plates containing graded concentrations of cisplatin or docetaxel which covered the range from 0.5 x to 32 x the tolerated plasma levels (TPL; cisplatin: 6.67 µM, docetaxel: 0.55 µM). Controls received solvent only. Internal standards: KB cells were exposed to fittingly graded concentrations made of the media and drug solutions from the colony formation test. After incubation for 72 hr, formed colonies were methanol-fixed and Giemsa stained, and KB cells were evaluated numerically. Numbers of epithelial cell colonies per well were determined by microscopy. Tests with average ≥ 2 such colonies per control well were included. Cut-off concentrations sufficient to suppress colony formation, and IC 50  values in both tumor tests and KB cell experiments were determined.  Results:  Twelve of the colony formation tests met inclusion criteria. Internal KB cell standards conformed to predetermined rated values. Sample wet weight averaged 146 ± 59 mg (range: 65 to 668 mg). Cisplatin: Throughout, hormesis was absent, and cut-off was reached. Inhibitory zones averaged 8.7 ± 3.8 µM (range: 4.2 to 16.3 µM). Cut-off concentrations were identical in 3 samples of 7 tumors, and in 2 of the samples of the remaining 5 tumors, with the 3 rd  sample deviating by ± 1 gradient step. IC 50  values (n = 9) averaged 6.7 ± 3.1 µM (range: 3.9 to 16.6 µM). Intratumoral variability of IC 50  values missed statistical significance (p  rd  sample deviating by + 1 gradient step. IC 50  values averaged 1.7 ± 0.7 µM (range: 0.8 to 2.9 µM). Intratumoral variability of IC 50  values missed statistical significance (p  Conclusions:   The microheterogeneity was quantitated of the hormetic and/or inhibitory effects of cisplatin and docetaxel ex vivo. The inhibitory effects observed in separately processed samples taken from different areas of individual tumors were nearly identical. This suggests that the chemoresponse in a single biopsy sample represents that of the entire tumor.
Abstract 11916: Circulating Concentrations of Orexin A Predict Left Ventricular Myocardial Remodeling
Authors: Nasrien E Ibrahim, Dustin J Rabideau, Hanna K Gaggin, Arianna M Belcher, Michael J Conrad, Petr Jarolim, James L Januzzi
Journal: Circulation (2016)

Introduction: Left ventricular reverse remodeling (LVRR) may occur with guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF); LVRR is associated with better outcome in this setting. Molecular factors predictive of LVRR are not well understood. Background: Recent data suggest the minor allele for rs7767652 (upstream to the hypocretin/orexin receptor-2 [ HCRTR2 ] gene) is inversely associated with likelihood for LVRR after GDMT. Infusion of orexin A (the HCRTR2 receptor ligand) was protective against LV remodeling. Hypothesis: Concentrations of circulating orexin A predict LV remodeling in HFrEF (left ventricular ejection fraction [LVEF] &lt;40%) patients treated with GDMT. Methods: We measured concentrations of orexin A in 113 HFrEF patients at baseline and at 10 months. Patients underwent echocardiography at the same time points. Measures of LV remodeling included LV end-diastolic and end-systolic volume index (LVEDVi, LVESVi) and LVEF. Results: As a function of the median baseline orexin A concentration of 1.04 ng/mL, there was no difference between groups in baseline characteristics, and no difference in concentrations of other prognostic biomarkers. Subjects with baseline orexin A ≥ 1.04 ng/mL had significantly greater reduction in LVEDVi and LVESVi and a trend towards greater improvement in LVEF at 10 months. Significantly fewer subjects with a baseline Orexin A concentration ≥ 1.04 ng/mL had increase in LVEDVi or LVESVi at study completion ( Table ). In binomial regression adjusted for age, gender, and baseline LV volumes, subjects with a baseline orexin A ≥ 1.04 ng/mL were less likely to have increase in LVEDVi (relative risk [RR] 0.51; 95% confidence interval [CI]: 0.30-0.84, P = 0.007) or LVESVi (RR 0.49; 95% CI: 0.28-0.85, P = 0.01). Follow up orexin concentrations did not add to baseline values for predicting LVRR. Conclusions: Orexin A is a unique prognostic biomarker for myocardial remodeling in chronic HFrEF.