tbuckley/cabot-search huggingface dataset:
The Greater Genomic Landscape: The Heterogeneous Evolution of Cancer
Authors: Luay M. Almassalha, Greta M. Bauer, John E. Chandler, Scott Gladstein, Igal Szleifer, Hemant K. Roy, Vadim Backman
Journal: Cancer Research (2016)

Results have historically shown a broad plasticity in the origin of tumors and their functions, with significant heterogeneity observed in both morphologies and functional capabilities. Largely unknown, however, are the mechanisms by which these variations occur and how these events influence tumor formation and behavior. Contemporary views on the origin of tumors focus mainly on the role of particular sets of driver transformations, mutational or epigenetic, with the occurrence of the observed heterogeneity as an accidental byproduct of oncogenesis. As such, we present a hypothesis that tumors form due to heterogeneous adaptive selection in response to environmental stress through intrinsic genomic sampling mechanisms. Specifically, we propose that eukaryotic cells intrinsically explore their available genomic information, the greater genomic landscape (GGL), in response to stress under normal conditions, long before the formation of a cancerous lesion. Finally, considering the influence of chromatin heterogeneity on the GGL, we propose a new class of compounds, chromatin-protective therapies (CPT), which target the physical variations in chromatin topology. In this approach, CPTs reduce the overall information space available to limit the formation of tumors or the development of drug-resistant phenotypes. Cancer Res; 76(19); 5605-9. ©2016 AACR.
Impact of an outright ban on the availability of commercial tanning services in Victoria, Australia
Authors: C. Sinclair, N. Cleaves, K. Dunstone, J. Makin, S. Zouzounis
Journal: British Journal of Dermatology (2016)

Australian states have introduced an outright ban on commercial artificial tanning sunbeds. This was based on evidence from systematic reviews affirming a strong association between tanning bed use and increased risk of melanoma. The implementation of the ban provides an opportunity to assess the effectiveness of the legislation in preventing access to artificial UV radiation. Compliance with the ban has been enforced and monitored by government departments. We additionally monitored online tanning bed advertisements before and after the ban, showing a decline over time in the number of sunbeds advertised for sale on gumtree.com.au and ebay.com.au, from a peak of 115 advertisements in May 2014 to 50 or fewer per month from February 2015. There was also an increase in advertised price, with the percentage of sunbeds offered in Victoria on gumtree.com.au at higher than $2 000 increasing from around 25% between January and June 2014 to 65% in the quarter following the introduction of the ban. Advertisements on gumtree.com.au from individuals wishing to access a sunbed in a private home in Victoria increased from only isolated instances in the months immediately prior to the ban, to between 25 and 77 advertisements per month in the quarter following the ban. In summary, the introduction of an outright ban of commercial sunbeds has achieved a dramatic reduction in the availability of harmful artificial UV radiation sources in Australia. Long-term benefits to the health of the population and a reduction in costs to the health system are expected to result.
Using a prospective comprehensive database to define features that impact the outcome of patients with glioblastoma multiforme.
Authors: K. M. Field, M. Rosenthal, S. Kosmider, P. Gibbs, K. Drummond
Journal: Journal of Clinical Oncology (2010)

2092 Background: Glioblastoma multiforme (GBM) is the most common malignant adult brain tumor. To date, potential discrepancies in outcomes related to sociodemographic parameters or comorbidities have not been well explored. Methods: Data on patients (pts) with GBM were accessed from a prospectively collected dataset over 7 years (2002-2009) at a single institution. Both univariable and multivariable Cox regression analyses were performed to establish the relationship between demographic variables and survival. Results: In total, 246 pts were evaluated; the median age was 63.1 years. The majority of pts were male (59%), from a major city (70%), born in Australia (57%) and not requiring an interpreter (91%). All levels of the Index of Relative Socioeconomic Advantage/Disadvantage (IRSAD) scale (a zip code based measure) were equally represented. 8.1% (n=20) were enrolled on to a clinical trial. In univariable analysis, median survival was significantly increased for pts under 70 years (9.3m vs. 4.9m, p<0.0001), those with a better ECOG performance status (9.3 m for ECOG 0-2 vs. 3.9 m for ECOG 3-4, p=0.005), those with IRSAD score 8-10 (more advantaged) vs. 1-4 (more disadvantaged) (9.2 m vs. 6.9 m, p=0.02); and those participating in a clinical trial (16.2 m vs. 7.3 m, p=0.0076). Gender, country of birth, residence (urban vs. regional), requirement for an interpreter, and diabetes or smoking status did not significantly impact survival. Results of multivariable analysis are shown (Table 1). Conclusions: This study is the first to examine the impact of demographics and comorbidities on GBM diagnosis and outcome. Our data show that age, ECOG PS, and enrollment on a clinical trial are all significantly associated with improved outcomes. The trend for a survival advantage for those in a higher IRSAD group, while not statistically significant in multivariable analysis, may warrant further exploration. Variable Hazard ratio + 95% CI P value Age <70 Referent >70 1.76 (1.16–2.65) 0.007 ECOG PS 0–2 Referent 3–4 1.60 (1.06–2.42) 0.025 Clinical trial Yes Referent No 0.55 (0.30–1.00) 0.05 IRSAD score 1–4 0.81 (0.51–1.29) 0.38 7–10 Referent Gender Male Referent Female 1.33 (0.92–1.91) 0.13 No significant financial relationships to disclose.
GENETIC DELETION OF INTESTINAL ALKALINE PHOSPHATASE ACTIVATES RESIDENT HEPATIC CELLS AND LEADS TO AN INFLUX OF IMMUNE CELLS WITHIN THE LIVER
Authors: Klaas Poelstra, Detlef Schuppan, Yury Popov, Jose L. Millan, Madhu S. Malo, Richard A. Hodin
Journal: Hepatology (2009)
Hidden in Plain Sight: Lung Impairment in Ischemic Heart Disease
Authors: Surya P. Bhatt
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

the recent FLAME (EFfect of Indacaterol Glycopyrronium vs Fluticasone Salmeterol on COPD Exacerbations) dual bronchodilator study careful documentation of exacerbation histories in the previous year was employed with electronic monitoring during the trial and expected exacerbation rates were achieved (12).The COPD management landscape is currently changing, and we now know that in higher risk patients (FEV 1 , 50% predicted and with a history of prior exacerbations), a dual bronchodilator (indacaterol/glycopyrronium) is more effective than a LABA/ICS in reducing exacerbations, with the study performed in patients with COPD where only 20% had two or more exacerbations in the previous year (12).Thus, studies are now required in a similar COPD patient group when roflumilast is added to dual bronchodilators and compared with standard therapy.However, these studies will need enhanced exacerbation detection and monitoring to achieve true exacerbation rates.Meanwhile, the results from the RE 2 SPOND trial suggest that the addition of oral roflumilast is especially effective in a group of "super exacerbators" who are at risk of very frequent exacerbations and hospital admission and these patients should be specifically targeted for additional antiinflammatory therapy on top of standard COPD therapy.We now need to further understand mechanisms of this important "super exacerbator" COPD patient group.
Radiation Therapy Modalities for Prostate Cancer
Authors: Nancy P. Mendenhall, Steven Schild, Jerry Slater
Journal: JAMA (2012)

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
Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia (ALL) at Diagnosis and/or at First Relapse: Results from the GET-LALA Group.
Authors: Oumedaly Reman, Arnaud Pigneux, Francoise Huguet, Norbert Vey, Andre Delannoy, Nathalie Fegueux, Stephane de Botton, Aspasia Stamatoullas, Olivier Tournilhac, Agnes Buzyn, Christiane Charrin, Claude Boucheix, Jean Gabert, Veronique Lheritier, Jean-Paul Vernant, Denis Fiere, Herve Dombret, Xavier Thomas
Journal: Blood (2007)
Phase II study of anlotinib for treatment of advanced soft tissues sarcomas.
Authors: Yihebali Chi, Yongkun Sun, Jianqiang Cai, Yang Yao, Xiaonan Hong, Zhiwei Fang, Ping Sun, Guowen Wang, Qiong Wu, Guofan Qu, Shusen Wang, Jianmin Song, Jianchun Yu, Yongkui Lu, Xia Zhu, Xiaohui Niu, Zhiyong He
Journal: Journal of Clinical Oncology (2016)

11005 Background: No standard therapies are available in China for Soft tissues sarcomas (STS)patients who failed to chemotherapies. Anlotinib is a multi-target RTK inhibitor, with VEGFR1/2/3, FGFR1/2/3, PDGFRα/β, c-Kit, Ret ect. Recommended dose in phase I is 12 mg daily, 2 weeks on/1 week off. This single-arm, multi-center phase II study (NCT01878448) to assess efficacy and safety of Anlotinib for treatment of STS patients who failed to conventional therapies. Methods: Pathological types of advanced STS mainly include malignant fibrous histiocytoma (MFH), liposarcoma, leiomyosarcoma, synovial sarcoma (SS) and other sarcomas, but excluding RMS, chondrosarcoma, GIST etc. Patients with measurable indicators (RECIST1.1) were treated with Anlotinib. Efficacy was assessed every 6 weeks. The primary endpoint was disease PFR at week 12 (PFR12w ). Results: From April 2013, we recruited 166 patients in 15 centers in China, including 100 males and 66 females, average age is 44 (15-70). Pathological types included SS (n=47), leiomyosarcoma (n=26), fibrosarcoma (n=18), MFH (n=19), alveolar soft part sarcoma (ASPS, n=13), liposarcoma (n=13), others (n=30). As of May 2015, 154 patients were assessable for efficacy: PFR12w was 57.23%, mPFS was 5.63 months.22 patients achieved PR over time (19 pts confirmed, and ORR was 11.45%. See below table. 166 patients were assessable for safety. Common grade III/IV AEs include: hypertension(n=8), pneumothorax(n=5), thyroid hypofunction(n=2), proteinuria(n=1), hand-foot-skin reaction(n=1), diarrhea(n=1), triglyceride increase (n=2), hyperglycemia (n=1). 24 patients (14.5%) had dose adjustment during treatment, reducing to 10 mg daily, 2 weeks on/1 week off. Conclusions: Anlotinib is effective to many pathological types of soft tissue sarcoma, particularly to ASPS and SS. Overall PFR12w reached 57.23%. Meanwhile, Anlotinib is well tolerated, while pneumothorax needs to be noticed. A randomized, controlled clinical trial is ongoing. Yihebali Chi and Sun Yongkun contributed equally to this work. Clinical trial information: NCT01878448. Case (n) RR% PFR12w % Overall 166 11.45 57.23 SS 47 12.77 63.83 leiomyosarcoma 26 7.69 69.23 fibrosarcoma 18 11.11 61.11 MFH 19 5.26 47.37 liposarcoma 13 7.69 53.83 ASPS 13 46.15 76.92 others 30 3.33 33.33
Lenalidomide and Dexamethasone Alone Is Equivalent To Lenalidomide and Dexamethasone With Autologous Stem Cell Transplant In Newly Diagnosed Multiple Myeloma: Interim Study Results Of a Randomized Trial
Authors: Jordan M. Schecter, Kristen Kipps, Amy O'Sullivan, Kent A. Griffith, Daniel Normolle, Markus Mapara, Robert Redner, Suzanne Lentzsch
Journal: Blood (2013)
CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling
Authors: Denis Lane, Isabelle Matte, Claude Laplante, Perrine Garde-Granger, Alex Carignan, Paul Bessette, Claudine Rancourt, Alain Piché
Journal: Molecular Cancer (2016)

Ovarian cancer (OC) ascites consist in a proinflammatory tumor environment that is characterized by the presence of various cytokines, chemokines and growth factors. The presence of these inflammatory-related factors in ascites is associated with a more aggressive tumor phenotype. CCL18 is a member of CCL chemokines and its expression has been associated with poor prognosis in some cancers. However, its role in OC progression has not been established. Therefore, the aim of the current study was to elucidate the role of ascites CCL18 in OC progression.ELISA and tissue microarrays were used to assess CCL18 in ascites and phospho-Pyk2 expression in cancer tissues respectively. Cell migration was assessed using Boyden chambers. CCL18 and ascites signaling was examined in ovarian cancer cells utilizing siRNA and exogenous gene expression.Here, we show that CCL18 levels are markedly increased in advanced serous OC ascites relative to peritoneal effusions from women with benign conditions. Ascites and CCL18 dose-dependently enhanced the migration of OC cell lines CaOV3 and OVCAR3. CCL18 levels in ascites positively correlated with the ability of ascites to promote cell migration. CCL18 blocking antibodies significantly attenuated ascites-induced cell migration. Ascites and CCL18 stimulated the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) in CaOV3 and OVCAR3 cells. Most importantly, the expression of phosphorylated Pyk2 in serous OC tumors was associated with shorter progression-free survival. Furthermore, enforced expression of Pyk2 promoted tumor cell migration while siRNA-mediated downregulation of Pyk2 attenuated cell migration. Downregulation of Pyk2 markedly inhibited ascites and CCL18-induced cell migration.Taken together, our findings establish an important role for CCL18, as a component of ascites, in the migration of tumor cells and identify Pyk2 as prognostic factor and a critical downstream signaling pathway for ascites-induced OC cell migration.
Muscle‐Monitoring Textiles: Cutaneous Recording and Stimulation of Muscles Using Organic Electronic Textiles (Adv. Healthcare Mater. 16/2016)
Authors: Maria Papaiordanidou, Seiichi Takamatsu, Shahab Rezaei‐Mazinani, Thomas Lonjaret, Alain Martin, Esma Ismailova
Journal: Advanced Healthcare Materials (2016)

Electronic textiles is an emerging field providing novel and non-intrusive solutions for healthcare. On page 2001, Esma Ismailova and co-workers evaluate the potential of conducting polymercoated textiles in monitoring and stimulating muscle activity. Such textile electrodes are able to assess high quality muscular monitoring and to perform transcutaneous electrical stimulations.
Validation of tumoral matrix-metalloproteinase-9 (MMP-9) mRNA expression as a molecular prognostic factor for metastatic gastroesophageal cancer.
Authors: A. Atmaca, K. Steinmetz, C. Pauligk, R. M. Wirtz, N. Homann, R. Hofheinz, C. Petry, H. Altmannsberger, E. Jaeger, S. Al-Batran
Journal: Journal of Clinical Oncology (2010)

4017 Background: This study aimed at establishing MMP-9 mRNA expression as molecular prognostic factor for metastatic gastroesophageal cancer. Methods: Tumor samples from 3 prospective studies of the AIO were used for trainig and validation. MMP-9 mRNA was isolated from paraffin embedded tissues using a nanotechnology method. The expression was assessed by qRT-PCR. Results: The training cohort included 131 pts, who were derived from a randomized phase III trial. At the cut-off with the highest predictive value, 25 pts had high and 106 pts low MMP-9 expression. Median OS was 3.57 vs. 10.5 months (log rank p = 0.00000065) in pts with high vs. low MMP-9 expression, respectively. 1- and 2-yr survival rates were 9% vs. 44% and 0 vs. 21%, respectively. This prognostic impact remained significant when data were analyzed in the multivariate setting or were categorized according to the quartile or median distributions of MMP-9 expression. The validation cohort comprised 92 pts, who were derived from the phase II studies FLOT and FLOT65+. We used the pre-specified best cut-off. Again, high MMP-9 expression significantly predicted survival, with median OS being 5.9 vs. 11.9 months (log rank p = 0.025) in pts with high vs. low MMP-9 expression, respectively. 1- and 2-yr survival rates in the validation cohort were 27 vs. 50% and 0 vs. 26% for high and low MMP-9 expression, respectively. Conclusions: Tumoral MMP-9 mRNA expression is the first validated molecular prognostic factor in pts with metastatic gastroesophageal cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Siemens Healthcare Diagnostics
Anti-Tumour Effect of Zoledronate in Cells from B Chronic Lymphoytic Leukemia and Low-Grade Lymphoma Patients.
Authors: Deborah Vidal Vasconcellos, Karina Lani Silva, Eric Delfraro de Paula Castro, Arthur Coelho Moellman, Maria do Socorro Pombo-de-Oliveira, Raquel Ciuvalschi Maia
Journal: Blood (2004)
US Surgeon General writes to all US doctors about opioids
Authors: Owen Dyer
Journal: BMJ (2016)

The Surgeon General of the United States, Vivek Murthy, has written to 2.3 million prescribing healthcare professionals—the first time the government’s chief physician has sought their support to solve a public health crisis—urging them to help tackle America’s problem with opioids.

He wrote, “Everywhere I travel, I see communities devastated by opioid overdoses. I meet families too ashamed to seek treatment for addiction. And I will never forget my own patient whose opioid use disorder began with a course of morphine after a routine procedure.”

Murthy’s letter asked doctors to take a pledge on a website and to follow a set of enclosed prescribing guidelines. He noted that opioid prescriptions had quadrupled since 1999—enough to give every adult in the US their own bottle of pills—but overall reported pain had not declined. …
Surveillance Systems to Track and Evaluate Obesity Prevention Efforts
Authors: Deanna M. Hoelscher, Nalini Ranjit, Adriana Pérez
Journal: Annual Review of Public Health (2017)

To address the obesity epidemic, the public health community must develop surveillance systems that capture data at levels through which obesity prevention efforts are conducted. Current systems assess body mass index (BMI), diet, and physical activity behaviors at the individual level, but environmental and policy-related data are often lacking. The goal of this review is to describe US surveillance systems that evaluate obesity prevention efforts within the context of international trends in obesity monitoring, to identify potential data gaps, and to present recommendations to improve the evaluation of population-level initiatives. Our recommendations include adding environmental and policy measures to surveillance efforts with a focus on addressing underserved populations, harmonizing existing surveillance systems, including more sensitive measures of obesity outcomes, and developing a knowledgeable workforce. In addition, the widespread use of electronic health records and new technologies that allow self-quantification of behaviors offers opportunities for innovative surveillance methods.
A Large Verrucous Plaque on the Calf
Authors: Adam S. Aldahan, Alyx C. Rosen, Shasa Hu
Journal: JAMA Dermatology (2016)

A man in his 20s presented with a large, verrucous plaque on his right calf; the lesion initially appeared as a small, bluish plaque at a young age and had gradually increased in size with subsequent development of wart-like features. What is your diagnosis?
Comparative Analysis of Bispecific Antibody and Streptavidin-Targeted Radioimmunotherapy for B-cell Cancers
Authors: Damian J. Green, Shani L. Frayo, Yukang Lin, Donald K. Hamlin, Darrell R. Fisher, Sofia H.L. Frost, Aimee L. Kenoyer, Mark D. Hylarides, Ajay K. Gopal, Theodore A. Gooley, Johnnie J. Orozco, Brian G. Till, Shyril O'Steen, Kelly D. Orcutt, D. Scott Wilbur, K. Dane Wittrup, Oliver W. Press
Journal: Cancer Research (2016)

Streptavidin (SA)-biotin pretargeted radioimmunotherapy (PRIT) that targets CD20 in non-Hodgkin lymphoma (NHL) exhibits remarkable efficacy in model systems, but SA immunogenicity and interference by endogenous biotin may complicate clinical translation of this approach. In this study, we engineered a bispecific fusion protein (FP) that evades the limitations imposed by this system. Briefly, one arm of the FP was an anti-human CD20 antibody (2H7), with the other arm of the FP an anti-chelated radiometal trap for a radiolabeled ligand (yttrium[Y]-DOTA) captured by a very high-affinity anti-Y-DOTA scFv antibody (C825). Head-to-head biodistribution experiments comparing SA-biotin and bispecific FP (2H7-Fc-C825) PRIT in murine subjects bearing human lymphoma xenografts demonstrated nearly identical tumor targeting by each modality at 24 hours. However, residual radioactivity in the blood and normal organs was consistently higher following administration of 1F5-SA compared with 2H7-Fc-C825. Consequently, tumor-to-normal tissue ratios of distribution were superior for 2H7-Fc-C825 (P < 0.0001). Therapy studies in subjects bearing either Ramos or Granta subcutaneous lymphomas demonstrated that 2H7-Fc-C825 PRIT is highly effective and significantly less myelosuppressive than 1F5-SA (P < 0.0001). All animals receiving optimal doses of 2H7-Fc-C825 followed by 90Y-DOTA were cured by 150 days, whereas the growth of tumors in control animals progressed rapidly with complete morbidity by 25 days. In addition to demonstrating reduced risk of immunogenicity and an absence of endogenous biotin interference, our findings offer a preclinical proof of concept for the preferred use of bispecific PRIT in future clinical trials, due to a slightly superior biodistribution profile, less myelosuppression, and superior efficacy. Cancer Res; 76(22); 6669-79. ©2016 AACR.