tbuckley/cabot-search huggingface dataset:
Abstract 1486: Cxcr4/Sdf-1 expression in Her2/Neu breast cancer biopsies and its relation to adjuvant treatment
Authors: Natalia C. Ayala, Melina N. Lorenzini Campos, Mariana M. Gomez Pescie, Angel E. Alsina, Jorge R. Zimerman, Maria C. Zimmermann
Journal: Cancer Research (2018)

Abstract Background: Chemokines have a fundamental role in inflammation and in cancer progression. Chemokine receptor 4 (CXCR4) is a transmembrane receptor that belongs to the CXC chemokine receptor family and is the only known receptor for the Stromal Cell derived Factor-1(SDF-1). Many retrospective studies have documented that the expression of various chemokine receptors, particularly CXCR4, was associated with a poor prognosis in patients with breast cancer. In the present study, we proposed an SDF-1/CXCR4 induced expression in HER2/neu positive breast cancer biopsies. We, additionally, study its relation to patient's treatment, prior and post adjuvant therapy. Methods: Immunohistochemical staining of her2/neu and ki64 were analyzed in mammary tumor biopsies. Reduction mammoplasty of normal patients were also studied as normal controls. Stained hematoxilyn and eosin slides where previously revised to confirm histological diagnostic and tumoral classification based on established criteria. Additional information considering biological markers such as estrogen receptor (ER), progesterone receptor (PR) expression were also observed in histopathological reports. Quantitative PCR was performed by amplifying a conserved region of the CXCR-4 and SDF-1 genes, and their correlation to Her2/neu expression and adjuvant therapy were analyzed. Statistical analysis was assess using appropriate parametric and nonparametric tests. Results: Her2/neu breast tumor specimens expressed SDF-1 at varying levels and differed upon tumor classification. Expression of the receptor correlates mainly with the tumor type and degree. Quantitative PCR showed low constitutive CXCR4 expression in normal breast tissue that increased in breast tumor tissue, particularly in those expressing her2/neu. Variations upon treatment correspond to those of tumor progression to malignancies and recurrence. Conclusions: We established a correlation between the expression of SDF-1/CXCR4 and the tumoral characteristics prior and post adjuvant treatment. A more careful examination of experimental/clinical data may help to explain the mechanism(s) involving the SDF-1/CXCR4 signaling axis in the breast cancer pathophysiology. Citation Format: Natalia C. Ayala, Melina N. Lorenzini Campos, Mariana M. Gomez Pescie, Angel E. Alsina, Jorge R. Zimerman, Maria C. Zimmermann. Cxcr4/Sdf-1 expression in Her2/Neu breast cancer biopsies and its relation to adjuvant treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1486.
Abstract 5453: Novel pan-PI3K inhibitor WX008 demonstrates significant antitumor efficacy in three xenograft tumor models
Authors: Tao Yu, Lingwei Kong, Yong Wang, Peipei Jiang, Zhe min Rong, Chang jun Wang, Jing jie Huang, Dan Yao, Yu xin Qin, Cheng de Wu, Shu hui Chen, Xin Tian, Fei Liu, Ping Dong, Zhi Lin Chen
Journal: Cancer Research (2018)

Abstract Background: PI3K/Akt signaling pathway plays a key role in a series of cellular functions related to cell growth, proliferation, survival and differentiation. Dysregulation of the PI3K pathway is implicated in many human cancers. Thus we intended to discover novel pan-PI3K inhibitors to treat various solid tumors, such as colorectal cancer, gastric carcinoma, lung carcinoma and breast cancer, etc. Methods: We explored SAR based on a PI3K/mTOR dual inhibitor series to selectively improve the PI3K activity over that of mTOR. PI3Kα/mTOR enzymatic activity assays, MCF-7 cellular (p-AktS473) activity assay and mouse in vivo pharmacokinetic analyses were used to direct compound optimization. Compounds with superior in vitro activity and in vivo pharmacokinetic properties were then tested for in vivo antitumor efficacy in patient derived xenograft (PDX) tumor models. Results: WX008 was identified as a potent PI3K inhibitor with PI3Kα/mTOR IC50 of 0.07 nM/233 nM (selectivity 3328×) and superior MCF-7 cellular (p-AktS473) activity (IC50 of 5.91 nM). For its excellent pharmacokinetic properties WX008 was evaluated for in vivo antitumor efficacy. As results, WX008 displayed equivalent efficacy at much lower dose than BKM-120 in several PDX tumor models (Table 1). Table 1 In vivo efficacy of BKM-120 and WX008 Cmpd_IDBKM-120WX008CO-04-0032 PDX72% TGI @30 mpk86% TGI @8 mpkST-02-0013 PDX50% TGI @8 mpk 77% TGI @15 mpk53% TGI @4 mpk 90% TGI @8 mpkLU-01-0010 PDX74% TGI @30 mpk74% TGI @8 mpk Conclusions: WX008 is a novel potent pan-PI3K inhibitor with high selectivity over mTOR and inhibits tumor growth in several PDX tumor models. Citation Format: Tao Yu, Lingwei Kong, Yong Wang, Peipei Jiang, Zhe min Rong, Chang jun Wang, Jing jie Huang, Dan Yao, Yu xin Qin, Cheng de Wu, Shu hui Chen, Xin Tian, Fei Liu, Ping Dong, Zhi Lin Chen. Novel pan-PI3K inhibitor WX008 demonstrates significant antitumor efficacy in three xenograft tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5453.
Young Investigator Abstract Session - Vascular258Pro-atherogenic miR-103 inhibits endothelial proliferation by targeting lncWDR59259Circulating long-non coding RNA LIPCAR and left ventricular diastolic function in patients with uncomplicated type 2 diabetes mellitus260Circulating thrombospondin-1 inhibits coronary blood flow reserve in aging hearts through a CD-47-dependent decrease in NO in coronary arterioles261Endothelial cell adenosine deaminase acting on RNA-1 is critically involved in …
Authors: L Natarelli, D De Gonzalo Calvo, AJ Leblanc, FF Lunella, S Saxton, P Hartmann, Y Wei, C Geissler, G Csaba, R Zimmer, A Schober, F Schottmer, C Bang, R Toro, RW Van Der Meer, LJ Rijzewijk, JWA Smit, HJ Lamb, V Llorente-Cortes, T Thum, CD Nevitt, G Mckenzie, K Christian, J Austin, S Hencke, A Gatsiou, P Grote, C Amrhein, A Doddaballapur, T Braun, A Zeiher, S Dimmeler, K Stellos, SB Withers, J Ohanian, AM Heagerty
Journal: Cardiovascular Research (2016)
Virtual Care as a Specialty—Reply
Authors: Michael Nochomovitz, Rahul Sharma
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Bioinspired Mineral–Organic Bioresorbable Bone Adhesive
Authors: Alina Kirillova, Cambre Kelly, Natalia von Windheim, Ken Gall
Journal: Advanced Healthcare Materials (2018)

Abstract Bioresorbable bone adhesives have potential to revolutionize the clinical treatment of the human skeletal system, ranging from the fixation and osteointegration of permanent implants to the direct healing and fusion of bones without permanent fixation hardware. Despite an unmet need, there are currently no bone adhesives in clinical use that provide a strong enough bond to wet bone while possessing good osteointegration and bioresorbability. Inspired by the sandcastle worm that creates a protective tubular shell around its body using a proteinaceous adhesive, a novel bone adhesive is introduced, based on tetracalcium phosphate and phosphoserine, that cures in minutes in an aqueous environment and provides high bone‐to‐bone adhesive strength. The new material is measured to be 10 times more adhesive than bioresorbable calcium phosphate cement and 7.5 times more adhesive than non‐resorbable poly(methyl methacrylate) bone cement, both of which are standard of care in the clinic today. The bone adhesive also demonstrates chemical adhesion to titanium approximately twice that of its adhesion to bone, unlocking the potential for adherence to metallic implants during surrounding bony incorporation. Finally, the bone adhesive is shown to demonstrate osteointegration and bioresorbability over a 52‐week period in a critically sized distal femur defect in rabbits.
Diagnosis, treatment, and control of scabies: can we do better?
Authors: Daniel Engelman, Andrew C Steer
Journal: The Lancet Infectious Diseases (2018)

In 2017, the Department of Control of Neglected Tropical Diseases of WHO recommended that scabies be added to the neglected tropical disease portfolio and called for action to improve control efforts. Scabies affects around 200 million people at any one time, 1 Karimkhani C Colombara DV Drucker AM et al. The global burden of scabies: a cross-sectional analysis from the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017; 17: 1247-1254 Summary Full Text Full Text PDF PubMed Scopus (130) Google Scholar causes an intensely itchy rash, and leads to bacterial infection and autoimmune disease. 2 Engelman D Kiang K Chosidow O et al. Toward the global control of human scabies: introducing the International Alliance for the Control of Scabies. PLoS Negl Trop Dis. 2013; 7: e2167 Crossref PubMed Scopus (123) Google Scholar Although the greatest burden is in disadvantaged populations in resource-limited and tropical settings, scabies also causes a substantial health-care burden via institutional outbreaks in high-income and temperate settings. Scabies outbreaks in ten care homes for elderly people: a prospective study of clinical features, epidemiology, and treatment outcomesClinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia. Full-Text PDF Open Access
Abstract LB-024: The effects of chromatin structure on variation in fragment size of cell free DNA
Authors: Hui Xia, Xingya Li, Hua Bao, Xiangyuan Ma, Xue Wu, Yang W. Shao, Feixiang Wu, Shucai Zhang
Journal: Cancer Research (2018)

Abstract Liquid biopsy using cell-free DNA (cfDNA) has established its clinical utilities in multiple clinical cohorts. However, the exact mechanism by which cell-free DNA (cfDNA) is generated remains undetermined. The fragment size of cfDNA sheds important insights on elucidating the process. Previous studies qualitatively concluded that tumor-derived cfDNA is shorter than cfDNA from healthy cells, but the exact size distribution of tumor-derived cfDNA remains unclear. To better understand the mechanism of cfDNA generation and directly study cfDNA of tumor origins, we analyzed the deep targeted sequencing results of cfDNA from 605 patients with various cancer types, and developed a method that separates tumor cfDNA through identification of somatic variant alleles-containing fragments. We show that tumor-derived cfDNA has an increased proportion of fragments less than 150bp compared to healthy controls, while the most common size is still 166 bp. It has been speculated that differences in nucleosome wrapping may contribute to differing fragment lengths of cfDNA.To better understand the relationship between the magnitude of chromatin packaging and cfDNA length, we quantitatively analyzed the size distribution of cfDNA collected from 5 cancer patients in genomic regions with the varying degree of chromatin openness. We discovered that the fragment size of cfDNA was closely associated with chromatin inaccessibility and chromosome condensation as measured by transcriptional start sites, DNase I hypersensitivity, histone modifications, and Giemsa banding, or as implied by chromosomal sub-nuclear localization. The shortening occurs at both 5' and 3' ends of cfDNA fragments without bias. Taken together, these results collectively established a positive correlation between cfDNA fragment size and chromatin inaccessibility. Citation Format: Hui Xia, Xingya Li, Hua Bao, Xiangyuan Ma, Xue Wu, Yang W. Shao, Feixiang Wu, Shucai Zhang. The effects of chromatin structure on variation in fragment size of cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-024.
Abstract 3152: RhoA-myosinII axis protects circulating tumor cells from fluid shear stress-induced damage
Authors: Devon L. Moose, Ben L. Krog, Gretchen Burke, Lei Zhao, Lillian Rhodes, Michael D. Henry
Journal: Cancer Research (2018)

Abstract Circulating tumor cells (CTCs) are exposed to hemodynamic forces, which have long been thought to be mechanically destructive to CTCs. However, recent studies show that cancer cell lines from diverse histologies exhibit resistance to brief (millisecond) pulses of high-level (750-6400 dyn/cm2) fluid shear stress (FSS), whereas nontransformed epithelial cells are sensitive to this mechanical insult (PMID: 23226552, 26447202). Moreover, exposure of cancer cells to FSS results in cortical stiffening (PMID: 25908902). Herein, we elucidate the mechanism of FSS resistance in cancer cells, and extend these findings to experimental models of CTCs. We show that although some cancer cell lines exhibit elevated levels of membrane repair relative to nontransformed counterparts, intrinsic resistance to plasma membrane damage is a more consistent feature distinguishing cancer cells. FSS resistance is detectable in cancer cells acutely isolated from primary mouse TP53/PTEN mutant prostate tumors, not just a feature of cultured cancer cell lines. Our findings indicate that cancer cells respond to FSS by activation of RhoA-myosinII contractility, which protects them from nanometer-scale damage to the plasma membrane. Moreover, we present evidence that the RhoA myosinII axis protects CTCs from mechanical damage in animal models. Treatment of PC-3 cancer cells with a nontoxic dose of the myosin II inhibitor blebbistatin (20μM; 3h) reduced the number of intact cells arrested in the lung microvasculature immediately following tail vein injection. Additionally, treatment of mice bearing orthotopically implanted, metastatic PC-3 derived prostate tumors with blebbistatin (2.5mg/kg; 3h) acutely reduced steady-state CTC levels by approximately 10-fold. Taken together, our data indicate that viable CTCs actively resist destruction by hemodynamic forces and are likely to be more mechanically robust than is commonly thought. Citation Format: Devon L. Moose, Ben L. Krog, Gretchen Burke, Lei Zhao, Lillian Rhodes, Michael D. Henry. RhoA-myosinII axis protects circulating tumor cells from fluid shear stress-induced damage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3152.
Malnutrition and Mortality in Frail and Non-Frail Older Adults Undergoing Aortic Valve Replacement
Authors: Michael Goldfarb, Sandra Lauck, John G. Webb, Anita W. Asgar, Louis P. Perrault, Nicolo Piazza, Giuseppe Martucci, Kevin Lachapelle, Nicolas Noiseux, Dae H. Kim, Jeffrey J. Popma, Thierry Lefèvre, Marino Labinaz, Andre Lamy, Mark D. Peterson, Rakesh C. Arora, José A. Morais, Jean-Francois Morin, Lawrence G. Rudski, Jonathan Afilalo
Journal: Circulation (2018)

Background: Older adults undergoing aortic valve replacement (AVR) are at risk for malnutrition. The association between preprocedural nutritional status and midterm mortality has yet to be determined. Methods: The FRAILTY-AVR (Frailty in Aortic Valve Replacement) prospective multicenter cohort study was conducted between 2012 and 2017 in 14 centers in 3 countries. Patients ≥70 years of age who underwent transcatheter or surgical AVR were eligible. The Mini Nutritional Assessment-Short Form was assessed by trained observers preprocedure, with scores ≤7 of 14 considered malnourished and 8 to 11 of 14 considered at risk for malnutrition. The Short Performance Physical Battery was simultaneously assessed to measure physical frailty, with scores ≤5 of 12 considered severely frail and 6 to 8 of 12 considered mildly frail. The primary outcome was 1-year all-cause mortality, and the secondary outcome was 30-day composite mortality or major morbidity. Multivariable regression models were used to adjust for potential confounders. Results: There were 1158 patients (727 transcatheter AVR and 431 surgical AVR), with 41.5% females, a mean age of 81.3 years, a mean body mass index of 27.5 kg/m 2 , and a mean Society of Thoracic Surgeons-Predicted Risk of Mortality of 5.1%. Overall, 8.7% of patients were classified as malnourished and 32.8% were at risk for malnutrition. Mini Nutritional Assessment-Short Form scores were modestly correlated with Short Performance Physical Battery scores (Spearman R =0.31, P &lt;0.001). There were 126 deaths in the transcatheter AVR group (19.1 per 100 patient-years) and 30 deaths in the surgical AVR group (7.5 per 100 patient-years). Malnourished patients had a nearly 3-fold higher crude risk of 1-year mortality compared with those with normal nutritional status (28% versus 10%, P &lt;0.001). After adjustment for frailty, Society of Thoracic Surgeons-Predicted Risk of Mortality, and procedure type, preprocedural nutritional status was a significant predictor of 1-year mortality (odds ratio, 1.08 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.01–1.16) and of the 30-day composite safety end point (odds ratio, 1.06 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.001–1.12). Conclusions: Preprocedural nutritional status is associated with mortality in older adults undergoing AVR. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable patients.
Earnings of Employed and Self-employed US Health Care Professionals, 2001 to 2015
Authors: Kamyar Nasseh, Marko Vujicic
Journal: JAMA Network Open (2018)

Over the last 15 years, the health care practitioner landscape has changed significantly. Fewer practitioners are self-employed and more are employed by for-profit or nonprofit organizations. These shifts can have an impact on annual labor earnings.To examine trends in self-employment and employment and to assess the gap in annual labor earnings between self-employed and employed US health care professionals from 2001 to 2015.Survey study in which data on employment type (self-employed, employed by private sector, or employed by government) and annual labor earnings for 50 states and the District of Columbia were extracted from the 2001 to 2015 American Community Survey. The analyses were restricted to 175 714 self-identified dentists, physicians, pharmacists, optometrists, podiatrists, chiropractors, and physical therapists aged 30 years and older who worked at least 40 weeks per year and 20 hours per week. Controlling for age, sex, race/ethnicity, year, and state of residence, median regression models were used to measure the gap in annual labor earnings between self-employed and employed health care professionals.Annual labor earnings, defined as the sum of self-employment and wages or salary income.Our sample of 175 714 respondents included 99 077 physicians, 20 008 dentists, 26 143 pharmacists, 4238 optometrists, 6076 chiropractors, 1164 podiatrists, and 19 008 physical therapists. The weighted percentage of self-employed physicians decreased from 35.2% (95% CI, 34.4%-36.1%; 6807 of 18 726 physicians) in 2001 through 2005 to 24.7% (95% CI, 24.2%-25.2%; 10 974 of 41 205 physicians) in 2011 through 2015. The percentage of self-employed dentists decreased from 73.0% (95% CI, 71.2%-74.8%; 3117 of 4153 dentists) in 2001 through 2005 to 65.1% (95% CI, 63.7%-66.4%; 5260 of 7820 dentists) in 2011 through 2015. Among physicians, the regression-adjusted earnings gap reversed from $19 679 (95% CI, $14 431-$24 927; P < .001) during 2001 through 2005 to -$10 623 (95% CI, -$14 547 to -$6699; P < .001) during 2011 through 2015. Among dentists, the regression-adjusted earnings gap narrowed from $30 448 (95% CI, $23 040-$37 855; P < .001) during 2001 through 2005 to $21 291 (95% CI, $15 723-$26 859; P < .001) during 2011 through 2015. From 2001 to 2015 the earnings gap also reversed among pharmacists, optometrists, and podiatrists. The regression-adjusted earnings gap narrowed among chiropractors and physical therapists.Since 2001, the percentage of health care professionals who are self-employed declined, and the gap in earnings between self-employed and employed health care professionals narrowed.