tbuckley/cabot-search huggingface dataset:
Mutant KRAS and BRAF gene expression profiles in colorectal cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60-00 trial.
Authors: S. Tejpar, V. Popovici, M. Delorenzi, E. Budinska, H. Estrella, M. Mao, P. Yan, S. Weinrich, E. Van Cutsem, A. Roth
Journal: Journal of Clinical Oncology (2010)

3505 Background: KRAS and BRAF activating mutations (mut) are frequent in colorectal cancer (CRC). Both genes act in the ERK pathway, but they occur in different CRC subtypes and have different prognostic implications, suggesting they might entail disruptions in different signaling pathways. Methods: RNA extracted from 1378 formalin-fixed tissues was used for expression profiling on the Affymetrix-based ALMAC platform Colorectal Cancer DSA. KRAS G12S, G13V, G13C, G13D, G12R, G13A, G12V, G12D, G12G, G12C, G12A, G12G mut and BRAF V600 were assessed. BRAF mut vs KRAS mut and BRAF or KRAS mut versus double wildtype (wt) were compared. Statistical analysis of differential expression was performed with standard methods in R. Classifiers were constructed using AdaBoost and DLDA algorithms and performance estimated by cross-validation. Results: KRAS mut were found in 37%, BRAF mut in 8%. Outcome correlations were reported (Roth A,JCO 2010). To date, 244 hybridized samples were analyzed (25 BRAF mut, 91 KRAS mut), additional samples are ongoing. (a) Gene expression downstream of KRAS and BRAF mut is highly different (common 6 genes, different 166). Supervised classification using 42 genes achieved an AUC of 0.98 (95% CI: 0.97-0.99) in separating KRAS from BRAF mut. (b) BRAF mut induce highly consistent gene expression changes (in 725 genes, < 1% FDR) in comparison to wt, allowing trained classifiers to discriminate BRAF mut from wt with an AUC of 0.94 (95% CI:0.92-0.96), using 30 selected genes. The differential gene expression downstream of BRAF indicates unique activation of key developmental pathways, including Wnt, TGF-β and MAPK. (c) KRAS mut tumors are heterogeneous in their gene expression signatures.The AUC of trained classifier (KRAS mut vs. wt) was 0.73 (95% CI:0.69-0.76), using 148 selected genes, indicating that the signatures explain a large part of the variance, but there is additional heterogeneity within the KRAS mut and wt subgroups. Conclusions: KRAS and BRAF mutations induce very different downstream gene activation in CRC. The strikingly uniform and novel BRAF mut downstream gene signature, might lead to novel therapeutic avenues for these aggressive tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
The effect of sex and age on the comorbidity burden of OSA: an observational analysis from a large nationwide US health claims database
Authors: Babak Mokhlesi, Sandra A. Ham, David Gozal
Journal: European Respiratory Journal (2016)

Obstructive sleep apnoea (OSA) is a highly prevalent condition but studies exploring the burden of OSA-associated comorbidities have been limited by small sample sizes with underrepresentation of women. We queried the Truven Health MarketScan Research Databases 2003–2012, which is a collection of health insurance claims for working adults and retirees with employer-sponsored health insurance. Adults with a diagnostic code for OSA with at least 12 months of follow-up from the index date of OSA diagnosis were compared to a matched random sample. Comorbidities were assessed using International Classification of Diseases, Ninth Edition, codes. A logistic regression model was constructed to test the independent association between OSA and comorbidities. Our cohort included 1 704 905 patients with OSA and 1 704 417 matched controls. All comorbidities were significantly more prevalent in OSA patients. Type 2 diabetes and ischaemic heart disease were more prevalent in men but hypertension and depression were more prevalent in women with OSA. In contrast, the sex differences in the prevalence of congestive heart failure, arrhythmias and stroke were less pronounced. The prevalence of comorbidities increased with age but the effect of age varied based on the specific comorbidity. The divergence between OSA and controls was more pronounced after the sixth decade of life for most cardiovascular diseases ( i.e. heart failure, ischaemic heart disease, stroke and arrhythmias), while depression exhibited an opposite trend. In a fully adjusted model, the odds of all comorbidities were significantly increased in OSA patients. In a large, nationally representative sample of working and retired people, OSA is strongly associated with significant comorbidities in both men and women with unique sex differences emerging.
CLINICAL AUDIT ON THE DIAGNOSTIC YIELD OF BRUSHING CYTOLOGY IN BILIARY AND PANCREATIC MALIGNANCY DETECTED ON ERCP AND EUS
Authors: S Anwar, H Mushtaq, N Ullah, S McKiernan
Journal: Gut (2013)

<h3>Introduction</h3> Patients with suspected pancreatobiliary malignancy on radiological imaging are often referred for endoscopic investigations with a view to obtain a definitive histological diagnosis. <h3>Aims/Background</h3> To evaluate the diagnostic yield of brush cytology in biliary and pancreatic malignancy detected on ERCP and EUS. <h3>Method</h3> We collected data from 01/01/2012 to 31/12/2012. 56 patients in total had brushings done at ERCP. Most common indications for ERCP were malignancy(68%) CBD stones (23%) pancreatitis(7%) and cholangitis (2%).Out of these 56 patients 38 had EUS and 30 patients had FNA. <h3>Results</h3> 56 patients had ERCP brushings done, 30 were suspected of malignancy by radiology. Definite diagnosis of malignancy was in 23 patients, 6 had inflammatory stricture and one patient had PSC, of the remaining 26 patients 15 had CBD stones, five had chronic pancreatitis, three had cholangitis and three had stent insertion due to indeterminate stricture. The sensitivity of biliary brushings were 74% and specificity of 93%, 26% had false negative results and all these patients had positive FNA. 38 patients had EUS done eight had inflammatory changes and 30 patients had FNA done. FNA was positive in 18 patients so the sensitivity was 78% and specificity was 100%. Five patients had false negative FNA (Positive ampullary biopsies) four had chronic pancreatitis, two had cholangitis and one had PSC. <h3>Conclusion</h3> Brush cytology, in conjunction with EUS-FNA and radiological investigations, is a useful technique in the assessment of patients with suspected pancreatobiliary neoplasia.(1234)
Air embolism after percutaneous transhepatic biliary drainage and subsequent endoscopic retrograde cholangiopancreatography (ERCP)
Authors: G. Maccarone, T. Shakoor, B. Ellis
Journal: Endoscopy (2011)

A 45-year-old man presented with a 5-day history of obstructive jaundice. The patient underwent an initial attempt at endoscopic retrograde cholangiopancreatography (ERCP), however the common bile duct was inaccessible. He then underwent percutaneous biliary drainage. A guide wire was left positioned in the duodenum, and the patient was transferred from radiology to the endoscopy unit for ERCP. An endoscope was passed and the previously placed guide wire was visualized at the ampulla. A cholangiogram showed multiple filling defects in the common duct. At this point there was clear access to the duct endoscopically and the percutaneous guide wire was removed. There was some initial bleeding from the percutaneous site, but pressure was applied for hemostasis. A basket was used to attempt to clear the common bile duct, but at this point fresh clot came from the papilla. A stent was placed and the procedure was terminated. The patient then became profoundly bradycardic and cardiopulmonary resuscitation (CPR) was initiated. He required cardioversion for ventricular tachycardia and a transesophageal echocardiogram was carried out. This showed clear evidence of pulmonary outflow obstruction as well as a patent foramen ovale (PFO), with air being shunted from the right to the left. However, the patient's vital signs stabilized without any further intervention. On brain magnetic resonance imaging (MRI) the patient was found to have multiple areas of acute infarction in the frontal, parietal, and occipital lobes, consistent with an embolic event. He initially had a moderate functional deficit but has eventually regained near complete recovery.
Abstract 3084: Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription by suppressing vitamin D receptor gene expression in mouse colon epithelial cells
Authors: Marsha DeSmet, James C. Fleet
Journal: Cancer Research (2012)

Abstract The active metabolite of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D), binds to the vitamin D receptor (VDR) and stimulates anti-cancer transcriptional events in many cell lines including colon cancer cells. However, we found that tumors which form in the distal colon of mice with an APC allele deletion had significantly lower VDR mRNA levels compared to RNA isolated from the distal colon of wild-type mice (-92%, p≤0.05). These data suggest that colon carcinogenesis may impair 1,25(OH)2D-regulated chemoprevention in colon epithelial cells. APC inactivation and KRAS activation are early events in the development of distal colon that may suppress VDR gene expression. Compared to immortalized colonic epithelial cells derived from the “Immorto” mouse (YAMC), cells from a cross between APCmin and “Immorto” mice (IMCE), and YAMC cells overexpressing the v-Ha-RAS gene (YAMC-RAS) have significantly lower VDR mRNA (-80%; p≤0.05) expression. Previous research shows that constitutively active (ca) RAS signaling suppresses 1,25(OH)2D action in many cell lines so we conducted additional studies on the impact of this mutation. YAMC-RAS cells had a significant reduction in 1,25(OH)2D-induced CYP24 mRNA expression (-40%; p≤0.05). Consistent with lower VDR mRNA levels, YAMC-RAS cells also had lower VDR protein levels than YAMC cells and the suppression of 1,25(OH)2D-induced CYP24 expression in YAMC-RAS was overcome with VDR over-expression. The mechanism for RAS-mediated suppression of VDR mRNA levels was further explored. First we hypothesized that caRAS signaling expression reduced VDR mRNA stability, however, YAMC and YAMC-RAS cells treated with 4 µg/ml of the transcription inhibitor actinomycin D for up to 12 h had no significant difference in the VDR mRNA half-life (about 8 h). Next we examined whether caRAS signaling reduced accessibility within chromosomal regions in the VDR gene previously identified as necessary for VDR gene expression. Using a DNAse I hypersensitivity assay we found that in YAMC-RAS cells there was a significant reduction (p≤0.05) in chromosome accessibility on the proximal promoter (-23%, 300 bp upstream of exon 1), an enhancer region located 6 kb upstream of the transcriptional start site (-56%), and an enhancer region located in exon 2 (-100%) compared to the YAMC cells. These data show that caRAS signaling suppresses 1,25(OH)2D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription. Supported by NIDDK Award DK54111and AICR Award 09A098 to JCF Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3084. doi:1538-7445.AM2012-3084
PMO-225 Use of infliximab for acute severe ulcerative colitis in a district general hospital
Authors: A Alisa, S Musa, S Zar, A Mahmood
Journal: Gut (2012)

<h3>Introduction</h3> The prevalence of Ulcerative colitis (UC) in the UK is 243/100 000 and carries a high lifetime risk of surgery (20%–30%). Acute severe UC (ASUC) is potentially a life threatening condition. Traditionally urgent medical treatment includes intravenous steroids followed by IV Ciclosporin in non-responders. In 2010, NICE recommended the use of Infliximab in ASUC in patients in whom ciclosporin is contraindicated or clinically inappropriate. Randomised control trials suggest colectomy is required in 30% of Infliximab recipients at 3 months and 50% at 3 years.<sup>1 2</sup> This retrospective study reports our experience at a busy district general hospital in South West London. <h3>Methods</h3> The Biologic database at St. Helier9s Hospital was interrogated to identify all cases of ASUC that gained funding for. Infliximab data collection was from January 2009 to June 2011. All patients had a UC disease activity index score (UCDAI)&gt;10. Disease site was classified by the Montreal classification. Follow-up ranged from 6 to 36 months post treatment. <h3>Results</h3> 20 patients had funding approved. 17/20 (85%) patients received Infliximab, 3/20 (15%) clinically settled pre-administration. There were 9 (53%) males and 8 (47%) females, median age 47 (range 19–57). 9 (53%) patients had left sided disease and 8/17 (47%) had extensive colitis. Median UCDAI was 11 (range 10–13). The median disease duration 4 years (range 0–15 years). During the acute presentation (pre-Infliximab), 11/17 (65%) patients received steroids, 11/17 (65%) were already on azathioprine, 15/17 (88%) 5-ASA, 3/17 (18%) 6-MP and 1/17 (6%) Tacrolimus. Following steroid therapy 4/17 (24%) had received Ciclosporin. Urgent colectomy was required in 2/17 (12%) patients. A further 6/17 (35%) underwent elective colectomy post induction, median 5 months (range 2–12 months). Complications were experienced in 3/17 (18%) and included 1 lichen planus, 1 Raynauds, 1 arthralgia. There was no mortality reported. <h3>Conclusion</h3> Following Infliximab therapy urgent colectomy was avoided in the majority (82%) of patients. Our elective colectomy rate was not to dissimilar to those reported by main randomised control trials. Infliximab was well tolerated and provided rescue therapy prior to latent elective surgery. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Jarnerot G</b>, <i>et al. Gastroenterology</i> 2005;<b>128</b>:1805–11. 2. <b>Gustavsson A</b>, <i>et al. Aliment Pharmacol Ther</i> 2010;<b>32</b>:984–9.
Apocrine carcinoma of the breast: clinical presentations, multimodality imaging findings and pathologic correlation.
Authors: O Woo, A Kim, K Cho, B Seo, E Kang
Journal: Cancer Research (2009)

Abstract Abstract #4029 Background : &amp;#x2028; Apocrine carcinoma (AC) of the breast is a rare malignant tumor and is lack of standardized criteria for the diagnosis. Thus clinicopathological features and radiologic findings have not been determined. We retrospectively analyzed the clinical presentation and the multimodality imaging findings of mammography, ultrasography and MRI and correlated with pathologic results.&amp;#x2028; Materials and Methods : &amp;#x2028; We retrospectively examined data on 850 patients who had been surgically treated for primary breast carcinoma between 2003 and 2008. Among them, there were 10 cases with the diagnosis of apocrine carcinoma.&amp;#x2028; Ten patients underwent mammography and ultrasonography and six patients underwent MR imaging. Eight patients underwent pre-operative US-guided core needle biopsy. We analyzed the radiologic findings and pathologic results.&amp;#x2028; Results : &amp;#x2028; The present study showed that the frequency of apocrine carcinoma was 1.2%. Almost all patients were symptomatic and painless lump was the most common complaint. Patient ranged in age from 38 to 62 year (mean, 50.5 years). The mean lesion size was 1.9cm (range, 1.1-3.5cm).&amp;#x2028; Common imaging features were as follows: mass or focal asymmetry without microcalcifications (n=7), mass with microcalcifications (n=3) on mammography; a mass with an round to irregular shape (n=9), indistinct-margin(n=8) on ultrasonography. On six dynamic contrast-enhanced MRI, enhancing masses in 3, mass with spotty nodular enhancement adjacent to the tumor in 3, which showed rapid enhancement and delayed washout pattern in five cases and plateau enhancement pattern in one case. Specifically, 3 patients had unilateral multifocal cancer. Two patients showed ipsilateral axillary lymphadenopathy.&amp;#x2028; Pathologic examination revealed AC (n=3), AC with apocrine carcinoma in situ (n=3), apocrine carcinoma in situ (n=1) and, AC with intraductal component and EIC positivity (n=3). Mass with spotty nodular enhancement on MRI was correlated with intraductal component and EIC positivity.&amp;#x2028; Conclusion : &amp;#x2028; The radiologic findings of apocrine carcinoma of the breast are not specific. Occasionally, apocrine carcinoma shows mass with spotty nodular enhancement adjacent to the tumor on MRI and this finding is correlated with intraductal component and EIC positivity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4029.
BURDEN OF ARRHYTHMIAS IN PATIENTS WITH ALCOHOLIC CARDIOMYOPATHY: FINDINGS FROM THE NATIONWIDE INPATIENT SAMPLE 2003-2011
Authors: Prakash Harikrishnan, Tanush Gupta, Dhaval Kolte, Chandrasekar Palaniswamy, Sahil Khera, Wilbert Aronow, Marjan Mujib, Kathir Subramanian, Diwakar Jain, Sachin Sule, Gregg Fonarow, Ali Ahmed, Howard Cooper, Jason Jacobson, Sei Iwai, Julio Panza
Journal: Journal of the American College of Cardiology (2015)
People lack awareness of link between alcohol and cancer, survey finds
Authors: Anne Gulland
Journal: BMJ (2016)

Most people do not link the consumption of alcohol with an increased risk of cancer, a report by Cancer Research UK has found.1

In a survey of 2100 adults in England, just 13% of respondents identified cancer when asked, “Which, if any health conditions, do you think can result from drinking too much alcohol?”

The survey also highlighted a lack of understanding of the link between drinking alcohol and the risk of developing certain types …
Beneficial Six-Year Outcome of Smoking Cessation in Older Men and Women with Coronary Artery Disease
Authors: Bonnie Hermanson, Gilbert S. Omenn, Richard A. Kronmal, Bernard J. Gersh
Journal: New England Journal of Medicine (1988)

We investigated the effects of cigarette smoking and cessation of smoking in a cohort of 1893 men and women from the Coronary Artery Surgery Study (CASS) registry who were 55 years of age or older and had angiographically documented coronary artery disease. The six-year mortality rate was greater among continuing smokers (n = 1086) than among those who quit smoking during the year before enrollment in the study and abstained throughout the study (n = 807) (relative risk, 1.7 [95 percent confidence limits, 1.4, 2.0]). Continuing smokers were also at higher risk of either myocardial infarction or death (1.5 [1.2, 1.7]). There was no diminution of the beneficial effect with increasing age. The relative risks of death were 1.7 (1.4, 2.1) and 1.6 (1.1,2.3) for the groups 55 to 64 years old and 65 or older, respectively, and 1.6 (1.4,1.9) for comparable subgroups among CASS subjects 35 to 54 years of age. When subjects were arrayed according to risk quartile, the benefits of smoking cessation were greatest in those at moderate risk. We conclude that smoking cessation lessens the risk of death or myocardial infarction in older as well as younger persons with coronary artery disease. (N Engl J Med 1988; 319:1365–9.)
Endoscopic ultrasonography-guided antegrade diathermic dilation for the treatment of complete obstruction of a pancreaticogastrostomy
Authors: Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
Journal: Endoscopy (2014)

Endoscopic ultrasonography (EUS)-guided rendezvous is a new and challenging technique. We present a case in which we successfully used a diathermic dilator to treat a complete pancreaticogastrostomy obstruction.
Abstract 5427: Andrographolide is a novel inhibitor of interleukin-6 and suppresses prostate tumor growth
Authors: Jae Yeon Chun, Ramakumar Tummala, Nagalakshmi Nadiminty, Wei Lou, Chengfei Liu, Joy Yang, Christopher P. Evans, Allen C. Gao
Journal: Cancer Research (2011)

Abstract INTRODUCTION AND OBJECTIVES: Elevated interleukin-6 (IL-6), a major mediator of the inflammatory response, has been implicated in androgen receptor (AR) activation, cellular growth and differentiation, plays important roles in the development and progression of prostate cancer, and is a potential target in cancer therapy. METHODS: In an attempt to identify potential inhibitors of IL-6, DU145 human prostate cancer cells that express IL-6 autocrine loop were treated with compounds from the Natural compound library (TimTec LLC, Newark, DE) for 24 hours. The Natural compound Library consisted of 440 natural compounds with minimal purity of 95%. The media were collected and used for measurement of IL-6 protein by ELISA. Compounds that decreased the levels of IL-6 protein by 50% were selected for further characterization. RESULTS: We found that andrographolide, a diterpenoid lactone isolated from a traditional Chinese and Indian medicinal plant Andrographis paniculata, could inhibit IL-6 expression and suppress IL-6-mediated signals. Andrographolide inhibits IL-6 expression at both mRNA and protein levels in a dose-dependent manner. Andrographolide suppresses both IL-6 autocrine- and paracrine-loop induced cell signaling including Stat3 and Erk phosphorylation. Furthermore, andrographolide inhibits cell viability and induces apoptotic cell death in both androgen-stimulated and castration-resistant human prostate cancer cells without causing significant toxicity to normal immortalized prostate epithelial cells. Moreover, treatment of andrographolide in mice bearing castration-resistant DU145 human prostate tumors that express constitutive IL-6 autocrine loop significantly suppresses tumor growth. CONCLUSIONS: Taken together, these results demonstrate that andrographolide could be developed as a therapeutic agent to treat both androgen-stimulated and castration-resistant prostate cancer possibly by suppressing IL-6 expression and IL-6-induced signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5427. doi:10.1158/1538-7445.AM2011-5427
Case 30-1996
Authors: David N. Caplan, David N. Louis
Journal: New England Journal of Medicine (1996)

Presentation of CaseAn 81-year-old, right-handed man was admitted to the hospital because of progressive disorientation and repeated falls.The patient had been well until six weeks earlier, when he was believed to have been in an unwitnessed automobile accident, with swelling of the forehead. There were scratches on his car, but he could not recall details of the accident. He began to fall frequently and had episodes of slurred speech. He became unable to dress himself, prepare his own meals, or care for a grandchild. He became lost while crossing the street to visit his children's home and often . . .