tbuckley/cabot-search huggingface dataset:
Abstract IA26: Role of ARID1A in SWI/SNF chromatin remodeling and ovarian cancer.
Authors: Ronald L. Chandler, Jesse Raab, Terry Magnuson
Journal: Clinical Cancer Research (2016)

Abstract ARID1A has emerged as the most frequently mutated chromatin remodeling protein in cancer and as a major tumor suppressor in endometriosis-associated cancers arising from the coelomic epithelium of the female reproductive tract. We have developed and characterized Arid1a conditional (floxed) and hypomorphic (valine-to-glycine substitution or V1068G) mutant mouse alleles. Mutant ARID1AV1068G is stably expressed and capable of assembling into a SWI/SNF complex with core catalytic properties, but nucleosome binding and promoter occupancy by ARID1A-containing SWI/SNF complexes (BAF-A) are reduced. Lowly penetrant hyperplastic outgrowths are observed within the oviducts of aged, hypomorphic Arid1aV1068G/+ females, but no tumors have been detected. Conversely, conditional inactivation of ARID1A in the ovarian surface epithelium (OSE) via intrabursal Adenovirus-CRE injection is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, mouse ovarian tumor cells carrying the ARID1A-PIK3CA mutational pattern are genomically stable, chemoresistant and dependent on cell autonomous Interleukin 6 (IL-6) signaling pathway for continued growth and survival. We have further shown that concurrent ARID1A loss and PIK3CA activation leads to an epithelial-to-mesenchymal transformation phenotype in isolated OSE cells. Our data highlight potential gene dose-dependent differences in ARID1A tumor suppressor activity in coelomic epithelial cell derivatives and suggest that many key features of ovarian tumorigenesis are conferred by the ARID1A-PIK3CA mutational pattern. Hence, our efforts to parse the tumor suppressor roles of ARID1A-containing SWI/SNF complexes in endometriosis-associated gynecologic cancers should extend to the Müllerian-derived ductal epithelium and include activating phosphoinositide 3-kinase mutations. Citation Format: Ronald L. Chandler, Jesse Raab, Terry Magnuson. Role of ARID1A in SWI/SNF chromatin remodeling and ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA26.
Renal and Renoprival Vascular Disease in the Rat
Authors: J CHURG
Journal: JAMA (1963)

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 IA03: From the clinic to the lab: Investigating immune responses to immune checkpoint therapies
Authors: Padmanee Sharma
Journal: Cancer Research (2016)

Abstract Immune checkpoint therapies, including anti-CTLA-4, anti-PD-1 and anti-PD-L1, have led to significant clinical responses in cancer patients. To investigate immunologic changes and mechanistic pathways that are elicited by these therapies, we conducted pre-surgical clinical trials, which permit access to sufficient tumor tissues for laboratory studies. The first pre-surgical trial was conducted with anti-CTLA-4 (ipilimumab) in a cohort of patients with localized bladder cancer. This trial provided access to sufficient tumor-infiltrating lymphocytes to conduct phenotypic and functional studies on these cells, which indicated the ICOS/ICOSL pathway as relevant for anti-tumor immune responses in the setting of anti-CTLA-4 therapy. In addition, since standard agents that enable tumor cell death may allow for priming of a T cell immune response that can be augmented by combination with CTLA-4 blockade, we conducted a pre-surgical clinical trial with androgen deprivation (hormonal) therapy ADT+ anti-CTLA-4 (ipilimumab), in the setting of patients with regional, high-risk prostate cancer. These pre-surgical clinical trials, and other tissue-based clinical trials, led to the identification of biomarkers and additional targets. These data, which are being used to design future immunotherapy trials, will be discussed in greater details. Citation Format: Padmanee Sharma. From the clinic to the lab: Investigating immune responses to immune checkpoint therapies. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA03.
Abstract A46: Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer
Authors: Birdal Bilir, Jeongseok Edward Lee, Nitya V. Sharma, Bato Lazarevic, Aud Svindland, Omer Kucuk, Carlos S. Moreno
Journal: Cancer Research (2016)

Abstract Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death among men in the United States, with an estimated 220,800 new cases and 27,540 deaths in 2015. Epidemiological studies have shown that dietary compounds have significant effects on prostate carcinogenesis. Among dietary agents, genistein, the major isoflavone in soybean, is of particular interest because high consumption of soy products has been associated with a low incidence of prostate cancer, suggesting a preventive role of genistein in prostate cancer. In spite of numerous studies to understand the effects of genistein on prostate cancer, the mechanisms of action have not been fully elucidated. Here, we investigated the differences in methylation and gene expression levels of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy (Lazarevic B, et al. Nutr Cancer 2011). This study was a randomized, placebo-controlled, double-blind clinical trial on forty-seven Norwegian patients who received 30 mg genistein or placebo capsules daily for 3-6 weeks before prostatectomy. Whole genome methylation and expression profiling identified significantly differentially methylated sites and expressed sites between placebo and genistein groups. Differentially regulated genes were involved in developmental processes, stem cell markers, proliferation, and transcriptional regulation. These findings highlight the effects of genistein on global changes in DNA methylation and gene expression in prostate cancer, and provide additional insight into the multiple molecular pathways involved in prostate tumorigenesis. Citation Format: Birdal Bilir, Jeongseok Edward Lee, Nitya V. Sharma, Bato Lazarevic, Aud Svindland, Omer Kucuk, Carlos S. Moreno. Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A46.
Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expandable Metallic Stents: Results of a Multicenter Study
Authors: T.  Nassif, F.  Prat, B.  Meduri, J.  Fritsch, A.  D.  Choury, J.  L.  Dumont, J.  Auroux, B.  Desaint, B.  Boboc, P.  Ponsot, J.  P.  Cervoni
Journal: Endoscopy (2003)

Background and Study Aims: Gastric outlet obstruction is a late event in the natural history of biliopancreatic tumours. Metallic self-expanding stents inserted under endoscopic and fluoroscopic guidance can be used for palliation. The aim of this study was to evaluate the feasibility, efficacy, and complications of endoscopic duodenal stenting in patients with malignant gastric outlet obstruction. Patients and Methods: Between August 1998 and November 2001, 63 patients (31 women, 32 men; mean age 73 ± 12) presenting with clinical symptoms of duodenal obstruction underwent endoscopic stenting with large metallic prostheses. Complications and clinical outcome were assessed both retrospectively and prospectively. Results: Of the patients, 58 needed one duodenal stent and two overlapping stents were required in five patients. Stenting was immediately successful in 60/63 patients (95 %). At the time of the duodenal procedure, 25 previously inserted biliary stents were still patent; biliary stenting was attempted during the same procedure in 18 patients; and 20 patients had no biliary stricture. There was no procedure-related mortality. There were complications in 30 % of patients: 13 stent obstructions, 4 stent migrations and 2 duodenal perforations (treated surgically). For 44 patients (70 %) there were no minor or major digestive problem during their remaining lifetime. An exclusively peroral diet was possible in 58 patients (92 %), but was considered satisfactory (solid or soft) in 46/63 patients (73 %). Of the patients, 53 (84 %) died between 1 and 64 weeks after the duodenal stenting (median survival 7 weeks). Conclusions: Endoscopic stenting for the palliation of malignant gastric outlet obstruction is feasible and well-tolerated in most patients. Most dysfunctions can be managed endoscopically.
Multidirectional instability of the glenohumeral joint: an unstable classification resulting in uncertain evidence-based practice
Authors: Kajsa Johansson
Journal: British Journal of Sports Medicine (2016)

The aim of this editorial is to discuss the pros and cons of some of the current classification systems of shoulder instability, with special emphasis on instability in more than one direction, and to summarise the basis for future clinical reasoning and research.

The term ‘multidirectional instability’ (MDI) is commonly used in adolescents and young adults, who can sometimes voluntarily subluxate their glenohumeral joints. They report pain, instability and shoulder disability, and present with symptomatic abnormal movement of the joint in two or more directions; the abnormal movement may predominate in one direction. The joint laxity may be congenital (in which case, it is often bilateral), or may due to the microtrauma of highly repetitive end-range movements, for example, in overhead athletes.

Classifying patients with shoulder instability is a challenge. Rockwood1 described four types of instability and patients with MDI fit into type 3, voluntary subluxation with no history of trauma, or type 4, atraumatic involuntary subluxation. Later, Kessel and Bayley …
Viruses and bacteria in Th2‐biased allergic airway disease
Authors: F. Lan, N. Zhang, E. Gevaert, L. Zhang, C. Bachert
Journal: Allergy (2016)

Abstract Allergic airway diseases are typically characterized by a type 2‐biased inflammation. Multiple distinct viruses and bacteria have been detected in the airways. Recently, it has been confirmed that the microbiome of allergic individuals differs from that of healthy subjects, showing a close relationship with the type 2 response in allergic airway disease. In this review, we summarize the recent findings on the prevalence of viruses and bacteria in type 2‐biased airway diseases and on the mechanisms employed by viruses and bacteria in propagating type 2 responses. The understanding of the microbial composition and postinfectious immune programming is critical for the reconstruction of the normal microflora and immune status in allergic airway diseases.
The Management of Crohn's Disease
Authors: T Fukushima, M Kawamoto, S Tsuchiya
Journal: Gut (1976)

Our therapeutic management to Crohn's disease was analyzed retrospectively. Among 17 cases with Crohn's disease, 14 (82%) were operated. Operative indications were due to obstruction (7), perforation (2), fistula (2), stenosis (2) and intractability (1). Postoperative recurrence was developed in 8 out of 14 (57%) and 4 were reoperated. Most of recurrent lesions were around the previous anastomosis. Operation per se does not cure the Crohn's disease but operation should be indicated when complicated obstruction, fistula and perforation. Nutritional treatment has been also performed 8 times. Crohn's disease activity index (CDAI) was decreased in all but one. In individual item of CDAI, frequency of bowel movement, abdominal pain and general status were improved but items such as anal lesion, fistula and fever were not improved. CDAI values were turned to remission value in all of cases with complicated stenotic lesions, but it remained in active stage in all cases with complicated fistula, obstruction and abscess. Nutritional treatment seemed less effective in cases complicated fistula, obstruction and abscess.
Extraordinary
Authors: Sunita Puri
Journal: JAMA (2014)

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
Gastrin
Authors: John H. Walsh, Morton I. Grossman
Journal: New England Journal of Medicine (1975)

Chemistry and PhysiologyHistoricalWHEN Bayliss and Starling1 discovered secretin in 1902, they quickly saw that they had uncovered not just a new substance but a new concept with broad biologic implications. They regarded secretin as a prototype of an entire system of "chemical messengers" that share with the nervous system the task of co-ordinating the activities of the whole body. Both systems provide mechanisms whereby stimuli received at one part of the body can control the activity of a distant part. In their first paper on secretin, Bayliss and Starling1 suggested gastric secretion as an . . .
Methadone is responsible for over half of accidental drug poisoning deaths in toddlers
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Methadone causes more toddlers’ deaths by unintentional poisoning in England and Wales than any other prescription drug, research published in the Archives of Disease in Childhood shows.1

To find out which prescribed drugs are most frequently implicated in cases of unintentional fatal poisoning in young children, UK researchers analysed national data on childhood poisonings and on hospital treatment or admissions to intensive care for unintentional poisoning from 2001 to 2013. During this period 28 children aged under 4 died in England and Wales as a result of unintentional poisoning with a prescribed drug, and methadone was implicated in 57% of these cases.

From 2002 to 2012 some 201 …
Plain radiography of the skull after investigation for raised calcium
Authors: David C Howlett, Joseph Dalby Sinnott
Journal: BMJ (2016)

A 63 year old man was being investigated for raised serum calcium and alkaline phosphatase. Plain radiography of the head was performed after a bone scan showed increased uptake in the patient’s skull. What does the radiograph show (fig 1)?



Fig 1 

The radiographic findings are consistent with a diagnosis of Paget’s disease of the bone.

### Discussion

The lateral skull radiograph shows marked calvarial thickening, with …
An outbreak of legionnaires’ disease in a municipality in northern Portugal
Authors: A M Correia, G Gonçalves, J Reis, J M Cruz, J A Castro e Freitas
Journal: Eurosurveillance (2001)

Eleven cases of legionnaires' disease, all patients living in the same municipality, were admitted to a district hospital in northern Portugal. Preliminary investigations suggested an association with the events of the annual festivities in that municipality. Legionella pneumophila was not isolated from any of the suspected sources, but evidence from a case control study suggested that an aerosol produced by a decorative fountain in the main square during the night of a rock concert was the likely vehicle of infection. The prevalence of smoking was higher among cases than controls.
Abstract P2-09-18: Exploration of the diagnostic utility of next generation sequencing with TruSight cancer panel for BRCA negative hereditary breast and ovarian cancer patients
Authors: D Dacheva, R Dodova, A Mitkova, K Kamenarova, R Tzveova, I Popov, A Vlahova, M Taushanova – Hadjieva, S Valev, T Dikov, K Timcheva, S Christova, V Mitev, R Kaneva
Journal: Cancer Research (2016)

Abstract Background. Breast cancer is the most commonly diagnosed malignancy and the most frequent cause of death in women due to cancer. About 5% to 10% of breast cancers are thought to be hereditary. Pathogenic mutations in BRCA1/2 genes across Hereditary Breast and Ovarian Cancer (HBOC) patients estimates are at around 15-20%. Other less common genes have also been associated with an increased risk of developing breast cancer, such as mutations in the TP53, PTEN, RAD51C, CDH1, ATM, CHEK2 or PALB2 tumor suppression genes. NGS based sequencing panels allow fast and simultaneous screening of large number of high- and low-penetrance susceptibility genes in these patients. Methods. In the current study we included a group of 31 Bulgarian female breast cancer patients, selected following the strict BCLC and NCCN criteria for hereditary cancer. All of them were prescreened by direct sequencing and MLPA analysis, and tested negative for pathogenic mutations in BRCA1 and BRCA2 genes. Next generation target resequencing using a panel of 94 cancer related genes (Illumina TruSight cancer panel) was performed to explore the hereditary component beyond BRCA1/2 genes in these patients. All detected mutations and variants of unknown clinical significance (VUSs) were confirmed by Sanger sequencing method. Results. Pathogenic and likely pathogenic mutations were found in 14 out of 31 BRCA1/2 negative patients: 1 new frameshift mutation in ATM gene; 6 new likely pathogenic missense mutations in PTCH1, RAD51C, MET, MUTYH, ATM and CHEK2; 7 previously reported pathogenic missense variants in WRN, ERCC4, PALB2, PRF1, RET, SDHB and AIP genes. In addition 27 VUSs (one new splice donor variant in ALK gene and 26 missense variants) were found. Conclusions. The use of next generation target resequencing with TruSight Cancer panel lead to identification of clinically relevant pathogenic variants in 45% of the investigated patients. This could be the preferred diagnostic method in HBOC patients, carefully selected according the strict BCLC and NCCN criteria. Citation Format: Dacheva D, Dodova R, Mitkova A, Kamenarova K, Tzveova R, Popov I, Vlahova A, Taushanova – Hadjieva M, Valev S, Dikov T, Timcheva K, Christova S, Mitev V, Kaneva R. Exploration of the diagnostic utility of next generation sequencing with TruSight cancer panel for BRCA negative hereditary breast and ovarian 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 P2-09-18.
International reliability of a diagnostic intake procedure for panic disorder
Authors: J B Williams, R L Spitzer, M Gibbon
Journal: American Journal of Psychiatry (1992)

Test-retest diagnostic reliability interviews using the Upjohn version of the Structured Clinical Interview for DSM-III (SCID) were conducted with 72 patients at 13 international sites of the Cross-National Collaborative Panic Study. Agreement on the diagnosis of panic disorder was very good. For the subtypes (uncomplicated, with limited phobic avoidance, and agoraphobia), agreement was fair to good.
A 4-6-year follow-up of 50 patients with primary dependence on sedative and hypnotic drugs
Authors: C Allgulander, S Borg, B Vikander
Journal: American Journal of Psychiatry (1984)

The authors studied 50 of 55 patients originally hospitalized for primary sedative-hypnotic dependence 4-6 years after hospital discharge. Forty-two (84%) of the patients had resumed using sedative-hypnotics, 26 (52%) were abusing drugs at follow-up, and 21 (42%) had been readmitted for drug abuse. Three patients experienced delirious states and six experienced epileptic seizures associated with withdrawal. Physical signs of alcoholism had developed in 11 (22%); four (8%) had committed suicide. Social deterioration was noted in 24 patients. CAT scan results did not deviate from those found in a matched control sample.
Effects of the Tyrosine Kinase Inhibitor AG957 and an Anti-Fas Receptor Antibody on CD34+ Chronic Myelogenous Leukemia Progenitor Cells
Authors: Carmelo Carlo-Stella, Ester Regazzi, Gabriella Sammarelli, Simona Colla, Daniela Garau, Aviv Gazit, Barbara Savoldo, Daniela Cilloni, Antonio Tabilio, Alexander Levitzki, Vittorio Rizzoli
Journal: Blood (1999)
p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells
Authors: Atsushi Umemura, Feng He, Koji Taniguchi, Hayato Nakagawa, Shinichiro Yamachika, Joan Font-Burgada, Zhenyu Zhong, Shankar Subramaniam, Sindhu Raghunandan, Angeles Duran, Juan F. Linares, Miguel Reina-Campos, Shiori Umemura, Mark A. Valasek, Ekihiro Seki, Kanji Yamaguchi, Kazuhiko Koike, Yoshito Itoh, Maria T. Diaz-Meco, Jorge Moscat, Michael Karin
Journal: Cancer Cell (2016)
Firearm Access and Risk of Suicide
Authors: Charles G. Kels
Journal: JAMA (2016)

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