tbuckley/cabot-search huggingface dataset:
Endoscopic ultrasound (EUS) aspect of duodenal bulb invasion by multifocal malignant pancreatic intraductal papillary mucinous neoplasm (IPMN)
Authors: L. Barresi, I. Tarantino, G. Curcio, A. Granata, R. Liotta, R. Gentile, M. Traina
Journal: Endoscopy (2011)

An 83-year-old woman came to our institute with abdominal pain, tomographic evidence of multiple pancreatic cystic lesions, and abnormal thickening of the pyloroduodenal region. Magnetic resonance imaging showed multiple cysts in the pancreatic body, isthmus, head, and uncinate process, some with clear communication with the pancreatic duct ([Fig. 1]), and a parietal thickening of the duodenum with contrast enhancement, in very close proximity to a cystic lesion in the pancreatic isthmus ([Fig. 2 a]). Endoscopic ultrasound (EUS) showed a multiloculated, septated cystic lesion in the pancreatic isthmus, with a hypoechoic pericystic lesion invading the duodenal bulb ([Fig. 2 b]). Gastroscopy confirmed a villous lesion in the duodenal bulb, involving the inferoposterior wall ([Fig. 2 c]). EUS showed that the intraduodenal lesion was heterogeneous with a solid-cystic aspect ([Fig. 2 d]). Biopsy of the duodenal lesion confirmed duodenal wall invasion by a malignant intraductal papillary mucinous neoplasm (IPMN) ([Fig. 2 e, f]).
Abstract 3264: AZD8186: a potent selective inhibitor of PI3Kβ targeting PTEN-deficient tumours dependent on dysregulated PI3Kβ signalling.
Authors: Urs Hancox, Sabina Cosulich, Hannah Dry, Lynsey Hanson, Clare Crafter, Bernard Barlaam, Martina Fitzek, Lara Ward, Marie Cumberbatch, Steve Powell, Rebecca Ellston, Mandy Lawson, Steve Wedge, Liz Harrington, Stephen Green, Simon T. Barry
Journal: Cancer Research (2013)

Abstract AZD8186 is a novel potent small molecule that targets the lipid kinase PI3Kβ with selectivity vs PI3Kα. AZD8186 reduces pAKT-S473 in the PTEN deficient MDA-MB-468 cell line with an IC50 &amp;lt;5nM, while in the PI3Kα-dependent PIK3CA mutant line BT474 it is 200 fold less potent. AZD8186 also demonstrates cellular activity versus PI3Kβ, inhibiting IgM-dependent pAKT-S473 with an IC50 of 15nM. In cell line panels, sensitivity to AZD8186 is associated in part with loss of PTEN function suggesting that targeting tumours that have lost normal levels of PTEN function through deletion, mutation or down regulation might enrich for sensitivity to AZD8186. Deficiencies in PTEN are described in a number of tumour types such as prostate, squamous lung, breast, renal and glioblastoma. AZD8186 has single anti-tumour activity in pre-clinical models representing each of these settings, which is associated with dynamic regulation of a number of key pathway biomarkers. Clinically, agents such as AZD8186 are likely to be used in combination. The use of AZD8186 in conjunction with either androgen therapy or docetaxol has been explored in cell lines and pre-clinical disease models. Combining AZD8186 with MDV-3100 resulted in synergistic inhibition of LNCAP prostate tumour cell growth, demonstrating the potential to combine with androgen therapy. Moreover in HCC70 (breast) and PC3 (prostate) tumour xenografts AZD8186 shows increased benefit in combination with docetaxel, demonstrating the ability to combine with cytotoxic chemotherapy. Exploration of dose and schedule revealed that efficacy can be maintained in combination with docetaxol at a lower dose of AZD8186 than required for monotherapy activity. Moreover efficacy was maintained when the frequency of AZD8186 dosing was reduced using a shorter intermittent schedule. Understanding how AZD8186 combines with standards of care for PTEN null disease segments provides important insight into how agents targeting PI3Kβ-dependent tumours may be used most effectively in the clinic. [Current affiliation for S. Cosulich is Novartis, Basel, Switzerland.] Citation Format: Urs Hancox, Sabina Cosulich, Hannah Dry, Lynsey Hanson, Clare Crafter, Bernard Barlaam, Martina Fitzek, Lara Ward, Marie Cumberbatch, Steve Powell, Rebecca Ellston, Mandy Lawson, Steve Wedge, Liz Harrington, Stephen Green, Simon T. Barry. AZD8186: a potent selective inhibitor of PI3Kβ targeting PTEN-deficient tumours dependent on dysregulated PI3Kβ signalling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3264. doi:10.1158/1538-7445.AM2013-3264
Sequential downgrading of dysplasia in ulcerative colitis using carbon dioxide-based cryotherapy
Authors: J. Lewis, S. Itzkowitz, H. Zhu, S. Ward, S. Anandasabapathy
Journal: Endoscopy (2012)

An 80-year old Caucasian woman with a 35-year history of left-sided ulcerative colitis (UC) underwent surveillance colonoscopy in January 2009. A random biopsy of the rectum revealed chronic colitis with low-grade dysplasia. A repeat colonoscopy in May 2009 revealed a polypoid area 3 cm from the anal verge with histological examination revealing low and high grade dysplasia. The patient declined colectomy and an attempt was made at local surgical excision. Biopsies revealed both low and high grade dysplasia with positive margins. The patient again refused colectomy. Two attempts were made to ablate visible dysplasia with argon plasma coagulation, but follow-up colonoscopies demonstrated recurrence including lesions at the dentate line. A novel approach utilizing carbon dioxide (CO2)-based cryotherapy (GI Supply, Camp Hill, Pennsylvania, USA) was initiated. Five treatment sessions were carried out at 8-week intervals with ablation of all dysplastic areas. At each session eight, 15-second pulses were applied. The patient reported no bleeding, diarrhea, or discomfort with the treatments. Histopathological examination revealed progressive downgrading and eventual ablation of all dysplastic mucosa ([Fig. 1 a -- c]).
Mutagen Sensitivity as a Risk Factor for Second Malignant Tumors Following Malignancies of the Upper Aerodigestive Tract
Authors: M. R. Spitz, A. Hoque, Z. Trizna, S. P. Schantz, C. I. Amos, T. M. King, M. L. Bondy, W. K. Hong, T. C. Hsu
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Mutagen Sensitivity as a Risk Factor for Second Malignant Tumors Following Malignancies of the Upper Aerodigestive Tract Get access Margaret R. Spitz, Margaret R. Spitz Department of Epidemiology, The University of Texas M. D. Anderson Cancer CenterHouston Correspondence to: Margaret R. Spitz, M.D., M.P.H., Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ashraful Hoque, Ashraful Hoque Department of Epidemiology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Zoltán Trizna, Zoltán Trizna Departments of Head and Neck Surgery and Head and Neck Thoracic Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Stimson P. Schantz, Stimson P. Schantz Department of Otolaryngology, Memorial Sloan-Kettering Cancer CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher I. Amos, Christopher I. Amos Department of Epidemiology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Terri M. King, Terri M. King Department of Epidemiology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Melissa L. Bondy, Melissa L. Bondy Department of Epidemiology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Waun K. Hong, Waun K. Hong Department of Head and Neck Thoracic Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar T. C. Hsu T. C. Hsu Department of Cell Biology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 22, 16 November 1994, Pages 1681–1684, https://doi.org/10.1093/jnci/86.22.1681 Published: 16 November 1994 Article history Received: 04 March 1994 Revision received: 18 August 1994 Accepted: 25 August 1994 Published: 16 November 1994
A CRISPR Way to Block PERVs — Engineering Organs for Transplantation
Authors: Daniel R. Salomon
Journal: New England Journal of Medicine (2016)

A challenge to xenotransplantation is the transmission of infectious agents, including endogenous retroviruses. A study of porcine endogenous retroviruses, and the use of a new tool (CRISPR-Cas9) to inactivate them, represents a step toward addressing this challenge.
DEVELOPMENT AND VALIDATION OF PROGNOSTIC MODELS FOR MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH AND HOSPITALISED BLEEDING IN STABLE MYOCARDIAL INFARCTION SURVIVORS
Authors: Laura Pasea, Sheng-Chia Chung, Mar Pujades Rodriguez, Em Jennings, Cathy Emmas, Mogens Westergaard, Saga Johansson, Harry Hemingway
Journal: Journal of the American College of Cardiology (2015)
Abstract 1304: Specific MUC1 isoforms function to regulate gene expression and tumor growth in pancreatic cancer
Authors: Paul M. Grandgenett, Stephanie K. Bunt, Ashley M. Mohr, Prakash Radhakrishnan, Tomofumi Hamada, Michael A. Hollingsworth
Journal: Cancer Research (2012)

Abstract Cancer cells, especially adenocarcinomas, express aberrant forms of mucins, as compared to their normal cell counterparts. These aberrant forms arise as a consequence of transformation-related alterations in expression of mucin mRNAs including alternative splice forms, and deregulation of enzymes that post-translationally modify mucin core proteins. Previous work has established that MUC1 is overexpressed and differentially glycosylated in adenocarcinomas and that this overexpression is associated with aggressive forms of pancreatic cancer. Most studies have focused on the full-length MUC1 isoform that contains the VNTR and all seven exons, but alternative splicing of MUC1 yields a minimum of 30 isoforms, of which several have been linked to malignancy in ovarian, cervical, and breast cancer. We evaluated expression of MUC1 alternate splice forms in a series of isogenic clonal pancreatic cancer cell lines that exhibit different properties of morphological differentiation, tumor growth and metastasis. The results revealed significant variation in splice variant expression between these isogenic cell lines and has implicated an association between isoform expression and metastatic potential. The knockdown of specific splice variants and MUC1 isoform families in S2-007 pancreatic cancer cells suggested that individual isoforms show differential capacity for regulating expression of target genes and miRNAs, which in turn led to differences in tumor growth rate and metastatic potential. Specifically, the stable knockdown of all members of the MUC1 X-family significantly altered expression of miRNAs 193b and 320 and reduced tumor growth in a pancreatic cancer animal model. MUC1 X-family also affected expression levels of several genes associated with Gemcitabine resistance and both pro and anti-inflammatory pathways that are predicted to influence disease progression and tumor associated immunosuppression. 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 1304. doi:1538-7445.AM2012-1304
Plasma Lipids and Lipoproteins in Vegetarians and Controls
Authors: Frank M. Sacks, William P. Castelli, Allen Donner, Edward H. Kass
Journal: New England Journal of Medicine (1975)

The possible effect of diet on plasma lipids was investigated in a group of vegetarians. Seventy-three men and 43 women who had adhered to a vegetarian diet for an average of three years were studied in the fasting state and compared with a randomly selected group of controls matched for age and sex. Mean cholesterol levels in milligrams per deciliter for vegetarians and controls, respectively, were 126 and 184; low-density lipoprotein, 73 and 118; very-low-density lipoprotein, 11.8 and 17.2; high-density lipoproteins, 42 and 49; and mean triglyceride levels 59 and 86. Mean weight and subscapular skinfold thicknesses were 58 kg and 6 mm for vegetarians and 73 kg and 17 mm for controls. Similar differences in lipid levels were found between subgroups of 42 vegetarians and controls with identical mean weights. Multiple regression analyses showed that consumption of dairy foods and eggs, but not body weight, was associated with the lipoprotein and cholesterol findings.
Abstract LB-377: Regulation of expression of choline kinase by a conserved HIF1 binding hypoxia-responsive element
Authors: Aditya Bansal, Robert A. Harris, Timothy R. DeGrado
Journal: Cancer Research (2010)

Abstract Hypoxic microenvironment and overexpression of choline kinase alpha (ChKa) have been associated with tumor malignancy, but the regulation of ChKa expression in hypoxic conditions is poorly understood. In this study, the effects of chronic hypoxia on choline metabolism and ChKa expression were examined in prostate cancer cell line, PC-3. Chronic hypoxia (1% O2, 24h) decreased proliferation rate and intracellular levels of phosphocholine, while intracellular levels of free choline were increased. Choline tracer uptake and washout studies confirmed the decreased rate of choline phosphorylation in hypoxic cells. Overexpression of HIF1a or DMOG exposure in normoxic PC-3 cells decreased both choline uptake and choline kinase activity. RT-PCR analysis showed decreased transcription of ChKa gene in hypoxic PC-3 correlating with decreased enzymatic activity of choline kinase in hypoxic cell extracts. Alignment of nucleotide sequence of the putative promoter region of ChKa from rat, mouse, chimpanzee and human revealed a highly conserved hypoxia responsive element upstream to transcription start site of ChKa. Electrophoretic mobility shift competition/supershift assay and chromatin immunoprecipitation-quantitative PCR assay confirmed binding of native HIF-1α protein to the conserved HRE. To understand the transcription control of ChKa under hypoxia, a putative promoter of ChKa was isolated from PC-3 genomic DNA and cloned into a luciferase (Luc) based reporter vector system. In PC-3, hypoxia decreased the expression of Luc under the control of the ChKa promoter. Mutation of the conserved HRE and subsequent Luc reporter assays demonstrated that this HRE is involved in hypoxia/HIF1α mediated regulation of ChKa. The results suggest that the decreased choline phosphorylation in PC-3 cells in response to hypoxia is mediated in part by the newly-identified conserved HIF1α binding HRE. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-377.
Changes in Bronchial Epithelium in Relation to Cigarette Smoking and in Relation to Lung Cancer
Authors: Oscar Auerbach, A. P. Stout, E. Cuyler Hammond, Lawrence Garfinkel
Journal: New England Journal of Medicine (1961)

IN 1957 two of us (O.A. and A.P.S.), with several collaborators, presented a report of progress on a study of the relative frequency of carcinoma in situ, squamous metaplasia, stratification and basal-cell hyperplasia in the lungs of nonsmokers and light and heavy smokers of cigarettes.1 The study was carried out on the lungs of 117 male patients dying with and without lung cancer by means of step sections of the entire tracheobronchial tree, totaling 208 sections per case. This was done in conformity with a rigidly observed plan, the details of which are fully described in the preceding publication. . . .
Incidental Detection of Pulmonary Infection During the Evaluation of Protein-Losing Enteropathy With In-111 Transferrin
Authors: SEIGO KINUYA, TAKAHARU MASUNAGA, RYOYU TAKEDA, TAKATOSHI MICHIGISHI, NORIHISA TONAMI
Journal: Clinical Nuclear Medicine (1997)

In-111 transferrin imaging was performed in a 71-year-old woman for the evaluation of protein-losing enteropathy. Although the result was negative for protein losing, the tracer accumulated in the lung suggesting an active pulmonary lesion. Pseudomonas infection was confirmed by bacteriological examination of the sputum.
Abstract P2-09-16: Effect of Continuous Statistically Standardized qPCR and IHC ER and PR on Disease-Free Survival in NCIC CTG MA.12
Authors: J-AW Chapman, T Nielsen, MJ Ellis, P Bernard, S Chia, K Gelmon, KI Pritchard, A Le Maitre, L Shepherd, V. Bramwell
Journal: Cancer Research (2010)

Abstract Background: Inter-laboratory comparability of ER and PR assay results has been problematic for decades. Statistical standardization has been proposed as an adjunct following good laboratory quality control. We demonstrate this process for ER and PR centrally assessed by qPCR and IHC. Methods: NCIC CTG MA.12 is a placebo-controlled trial of tamoxifen therapy following adjuvant chemotherapy in premenopausal women with early breast cancer. 672 women were accrued, 505 of whom had locally determined ER and/or PR positive tumours. ER was centrally assessed by qPCR and IHC for respectively 385 and 392 patients, and by PR, for 389 and 376. The effects on DFS of continuous 1) log2 (qPCR) and 2) ln (IHC % positive stain) in statistically standardized units were investigated for all women with all lab results, and in the subgroup with IHC ER+ and/or PR+ tumours. DFS is defined as the time from randomization to recurrence or death. Multivariate examinations were with adjusted Cox regression, with adjustment by stratification factors nodal status and chemotherapy type; ER and PR had forced inclusion in models, while trial therapy and baseline patient characteristics were added in step-wise mode (p&amp;lt;=0.05). Unvariate tests were with adjusted log-rank statistic and Kaplan-Meier plots for ER and PR (ER and PR 0; standardized cut-points for ER and PR with positive stain of &amp;lt;= 1.0; &amp;gt; 1.0, &amp;lt;= 0.0; &amp;gt; 0.0, &amp;lt;= 1.0; &amp;gt;1.0). Results: Median follow-up for the MA.12 trial was 9.7 years. Univariately, qPCR ER was not associated with DFS (p=0.19), while both qPCR PR (p=0.09) and IHC ER (p=0.08) had weak evidence of association, and IHC PR had p=0.04. Multivariately, patients randomized to tamoxifen had significantly better DFS (p=0.002-0.005) in all patients assessed and in those with ER and/or PR &amp;gt; 0; ER and PR by qPCR and IHC were not associated multivariately with DFS (P&amp;gt;0.05). ER and PR were not associated with DFS (P&amp;gt;0.05) for those who received tamoxifen, while qPCR ER and/or PR, and IHC ER were inconsistently associated with DFS for those on the placebo arm. Conclusions: In this subgroup of centrally assessed MA.12 patients, trial therapy was significantly associated with DFS. Similar non-significant multivariate results were obtained multivariately with statistically standardized, continuous qPCR and IHC ER and PR. We plan to further investigate adjunctive statistical standardization in larger NCIC CTG trials. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-16.
ENDOTHELIUM DEPENDENT AND INDEPENDENT VASODILATOR RESPONSES AFTER HEART TRANSPLANTATION: GEOGRAPHIC DISTRIBUTION AND ASSOCIATION WITH PROGRESSION OF CARDIAC ALLOGRAFT VASCULOPATHY
Authors: Kozo Okada, Takumi Kimura, Kojiro Miki, Paul Yock, Alan Yeung, Peter Fitzgerald, Helen Luikart, Kiran Khush, Yasuhiro Honda, William Fearon
Journal: Journal of the American College of Cardiology (2016)
Case 34-1998
Authors: David E. Gossman, Noah Liel-Cohen, Edi Brogi
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 71-year-old woman was admitted to the hospital because of fever, dyspnea, and hypotension.Her history included an inferior myocardial infarction 19 years earlier; hypertension; renal insufficiency ascribed to chronic pyelonephritis, with a creatinine level ranging from 1.8 to 2.2 mg per deciliter (159.1 to 194.5 μmol per liter); a left nephrectomy; and chronic paranoid schizophrenia. There was a mass in the right middle lobe and a calcified right hilar lymph node, both of which had remained unchanged on periodic radiographic assessment for seven years.Twelve weeks before the current admission, the patient was admitted to the . . .
Oral surgeon at centre of recent controversy had previously been reprimanded by GMC
Authors: C. Dyer
Journal: BMJ (2014)

A consultant maxillofacial surgeon who has been suspended by his employers since February 2013 pending a review of 88 cases was severely reprimanded by the General Medical Council 14 years ago over a case in which a patient died, it has emerged.

Roger Bainton, who holds medical and dental qualifications, was also suspended for a year by the General Dental Council over the same incident and lost his job as a surgeon at Aberdeen Royal Infirmary.

He went on to take up a post as a consultant oral and maxillofacial surgeon with the University Hospital of North Staffordshire NHS …
SAT0532 Increased Rates of Spontaneous Abortions, but not Stillbirths in Rheumatoid Arthritis
Authors: M. Wallenius, K. Å. Salvesen, A. K. Daltveit, J. F. Skomsvoll
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> New treatment options may influence pregnancy outcomes in patients with rheumatoid arthritis (RA), but very few studies after year 2000 have examined rates of spontaneous abortions and stillbirths in rheumatoid arthritis (RA)<sup>1,2</sup>. <h3>Objectives</h3> To examine currently relative risks of spontaneous abortions and stillbirths in RA patients versus references. <h3>Methods</h3> Data from the Medical Birth Registry of Norway (MBRN) in the period 1.12.1998 to 31.12.2009 were used to assess relative risks of previous spontaneous abortions (before week 12 of gestation, between weeks 12-22 of gestation) and stillbirths from week 22 of gestation among women diagnosed with RA compared with references. The diagnosis of RA was based on registration of diagnoses in MBRN according to the International Classification of Diseases (ICD)-10. Data on previous spontaneous abortions before gestational week 12 were voluntary self- reported data to MBRN, whereas data on previous spontaneous abortions after week 12 of gestation and stillbirths was obtained by linkage of all the women's births in the MBRN. For the self-reported data 90 % of patients and references had responded. Poisson regression analyses with adjustment for maternal age at time of last delivery, was applied to estimate relative risks of spontaneous abortions and stillbirths in patients versus references. <h3>Results</h3> <h3>Conclusions</h3> The risk for spontaneous abortion, both early and late, was significantly higher among patients than references, which is in contrast to most previous studies. The risk of stillbirths did not differ significantly between the groups. <h3>References</h3> Reed SD, Vollan TA, Svec MA. Pregnancy outcomes in women with rheumatoid arthritis in Washington State. Matern Child Health J 2006;10:361-6 Nørgaard M, Larsson H, Pedersen L et al. Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study. J Intern Med 2010;268:329-37 <h3>Acknowledgements</h3> The Medical Birth Registry of Norway (data delivery) The Liaison Committee between the Central Norway Regional Health Authority and NTNU (financial support) <h3>Disclosure of Interest</h3> None Declared