tbuckley/cabot-search huggingface dataset:
Abstract 3292: A genetically engineered mouse model for high grade serous “ovarian” carcinoma arising in the fallopian tube
Authors: Ruth Perets, Katherine W. Muto, Jonathan G. Bijron, Chin T. Kenneth, Barish B. Poole, Christopher P. Crum, Daniela M. Dinulescu, Ronny Drapkin
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the most lethal gynecologic malignancy because the vast majority of cases are detected in late stage, a finding that has thwarted attempts to understand the pathogenesis and cell-of-origin of this disease. The traditional view of epithelial ovarian pathogenesis asserts that all tumor subtypes share a common origin in the ovarian surface epithelium (OSE). There is robust data to support the OSE as the site of origin for many ovarian tumors, including low-grade carcinomas and borderline tumors. However, the pathogenesis of high-grade serous ovarian carcinoma, the most common type of ovarian cancer, continued to defy explanation by the OSE model. More recent studies suggested that the fallopian tube epithelium (FTE), rather than the OSE, may be the site-of-origin for a majority of pelvic serous carcinomas (PSC, defined as ovarian, peritoneal and tubal high grade serous carcinomas). We show here that the FTE can be site of origin for PSC by genetically engineering a mouse model that specifically targets the FT secretory cell with defined genetic alterations that are characteristic of human PSC. These mice develop tubal intraepithelial serous carcinomas, a precursor to PSC, that are morphologically and immunophenotypically similar to the lesions described in human patients. Furthermore, these intraepithelial lesions progress to widespread peritoneal disease that recapitulates the presentation of high-grade PSC in women. The tumors express common serous markers such as P53, αH2A.X, PAX8 and CA-125. Taken together our model is the first fully genetically engineered mouse model that truly recapitulates human serous carcinoma pathogenesis. Our model serves as proof-of-concept that the FTE can be site-of-origin to PSC. 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 3292. doi:1538-7445.AM2012-3292
Hunting for the Cause: How Far to Go
Authors: Stephen G. Pauker, Richard I. Kopelman
Journal: New England Journal of Medicine (1993)

A 71-year-old man consulted his doctor because he had had stiffness and swelling of his hands and feet, especially in the morning, for the previous six weeks.Swelling of the hands and feet suggests arthritis or an edematous state, perhaps due to a low serum albumin level and a decrease in oncotic pressure. Swelling that is more pronounced in the morning is consistent with generalized edema, such as would occur with the nephrotic syndrome, cirrhosis, or constrictive pericarditis.He had noticed an 8-lb (3.6 kg) weight gain and weakness of his legs, which he attributed to the . . .
Tc-99m Sestamibi SPECT Imaging of a Brain Metastasis in a Man With Lung Tumor and Increased Sexual Activity
Authors: MOHAMED-LAKDAR MIRA, NICULAIE POPA, ERIC HUYSMANS, ANDRÉ LENAERS, ANDRÉ SCHOUTENS
Journal: Clinical Nuclear Medicine (1996)

Whole body and SPECT Tc-99m sestamibi scintigraphy successfully identified and suggested the proliferative nature of a left frontal brain lesion and of a pulmonary tumor (low-grade adenocarcinoma) in a 74-year-old man with increased sexual activity, right-sided hemiparesis, and slight motor aphasia. Behavioral changes (hyper- or hyposexuality) have been mainly reported in patients with temporal or frontal brain lesions particularly with lesions located in the limbic region. A Tc 99m-MDP bone scan failed to show any evidence of bone involvement. Laboratory data were in normal range except for CEA (11.4 ng/100 mL; normal, < 6).
SAT0331 Identifying knee osteoarthritis phenotypes and comparing clinical outcomes - data from the must osteoarthritis cohort:
Authors: N. Østerås, P. Mowinckwl, M.A. Risberg, K.B. Hagen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It has been suggested that the heterogeneous population of persons with knee osteoarthritis (OA) consists of different phenotypes or subgroups, which may have important implications for clinical care and research. In a recent paper by Knoop et al. 2011 five distinct knee OA phenotypes were identified. <h3>Objectives</h3> To identify and compare different knee OA phenotypes in a Norwegian OA cohort according to the method suggested by Knoop et al. 2011. <h3>Methods</h3> Data from 106 persons in the "Musculoskeletal pain in Ullensaker STudy" (MUST), an ongoing population-based study of individuals with self-reported knee OA, was included. Phenotypes were identified by K-means cluster analysis based on four clustering variables: severity of radiographic knee OA, lower extremity muscle strength (the 30-second Chair Stand Test), body mass index (BMI), and "emotional problems" (a single COOP/WONCA item). The phenotypes were compared on clinical outcome variables: self-reported pain and function, and the Six-Minute Walk Test. <h3>Results</h3> The mean age (sd) was 65 (8.9) years, and there were 65% females (n=69). Mean BMI was 28.4 (4.5), and for 60% (n=64) the ACR criteria for knee OA were fulfilled. Five different phenotypes were identified in the cluster analysis (Table 1). Comparing the phenotypes on clinical outcome variables there was a gradient from the first, strong and little affected phenotype, to the fifth showing higher levels of pain and disability, and shorter walked distance. Contrary to the findings by Knoop et al, it was not the fifth phenotype that was characterised with "emotional problems". <h3>Conclusions</h3> The phenotype characteristics identified in the present study were similar to those described by Knoop et al. Thus, the present study gives empirical support to the hypothesis that tailoring the treatment of knee OA to phenotype, might optimize the clinical effect. <h3>References</h3> Knoop J et al. 2011 <h3>Disclosure of Interest</h3> None Declared
AB1009 Patients with rheumatic diseases are at risk of osteoporosis development
Authors: L. Myasoutova, S. Lapshina, A. Vasilyev
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Evaluation of changes in bone mineral density (BMD) in patients with rheumatic diseases. <h3>Methods</h3> A retrospective analysis of protocols of X-ray densitometry was performed in patients who were at the dispensary observation in the Rheumatologic Centre of Kazan City in the period from January 2010 to January 2011. The changes of BMD in two points were taken into account: the lumbar spine and proximal femur. T-score was evaluated in postmenopausal women and men older than 50 years. Z-test was evaluated in women before menopause and men younger than 50 years. 347 patients were included in analysis. 231 of them had rheumatoid arthritis (RA), 63 – ankylosing spondylitis (AS) and 53 had osteoarthritis (OA). <h3>Results</h3> 85 (24.5%) of 347 patients (74 women and 11 men) had osteoporosis and 143 (41.8%) patients (121 women and 21 men) had osteopenia according to the criteria of WHO. Distribution by rheumatic diseases was as follows. 55 (23.8%) of 231 patients with RA had osteoporosis and 89 (38.5%) – osteopenia. 13 (20.6%) of 63 patients with the AS had osteoporosis and 32 (50,8%) – osteopenia. Osteoporosis and osteopenia were revealed in 17 (32.1%) and 24 (45.3%) of 53 patients with OA, respectively. <h3>Conclusions</h3> Osteoporosis is often met in rheumatic diseases, especially in RA and AS. However, the prevalence of osteopenia is even higher and this situation requires the actions for prevention of osteoporosis and fractures. In addition, osteoporosis and osteopenia in OA were observed much more often than it was thought previously. <h3>Disclosure of Interest</h3> None Declared.
Soundings: Is omniscience enough?
Authors: Colin Douglas
Journal: BMJ (2006)

In the real world, some of us know a little about a lot, quite a few know a lot about a little, and there is a troubling minority that knows practically everything about hardly anything. That's in the real world. But when it comes to examining in the Practical Assessment of Clinical Examination Skills for the Membership of the Royal College of Physicians, we are all omniscient.

It takes a bit of getting used to. I have seen a gastroenterologist fiddling anxiously with an ophthalmoscope at quarter past eight in the morning and clearly wishing it made half as much sense of things as his trusty colonoscope; but by the coffee break he is a changed man: a calm authority on the widespread spiculated pattern of retinitis pigmentosa, chatting casually with candidates about Usher's syndrome, Refsum's, and Laurence-Moon-Biedl.

Clearly we get some assistance: from briefings provided by a registrar who has passed the exam sufficiently recently still to know this stuff; from the quick look round before the candidates arrive; from the better informed candidates as they come and go; and from each other as the day goes on. But the convention that we all have it all at our fingertips all of the time seems to me at best precarious, at worst hypocritical.

A year or so ago I spent a morning with an honest fellow-examiner: a most unusual, unsettling, but eventually liberating experience. She was a forthright Ulsterwoman from a specialty that does much good but sees very little of what we saw that day. She was refreshingly—no, shatteringly—explicit about what was going on. (“D'you mind me asking...? D'you actually know a lot about this kind of stuff, Colin? Because I don't.”)

Her frankness made an honest man of me. I said I knew a bit about, um, some of it, but had examined before and, er, usually more or less got by: honest confession, good for the soul.

We got by that day, and it was more fun than usual because it felt a lot less hypocritical. And of course among the exotica were the standard exam war horses: the multiple sclerosis, the kidney transplant, the Marfan's, the knobbly liver—the things the candidates know we know they know they have to know, and knowing this makes it easier for all concerned. That day we were omniscient enough.
1255 REGULATION OF PATATINE-LIKE PHOSPOLIPASE DOMAIN-CONTAINING PROTEIN-3 (PNPLA3) EXPRESSION BY FATTY ACIDS AND ALCOHOL IN VITRO AND IN VIVO
Authors: E. Patsenker, V. Schneider, H. Saegesser, S. Buch, J. Hampe, A. Stadlmayr, C. Datz, F. Stickel
Journal: Journal of Hepatology (2012)
Acute Cerebellar Ataxia
Authors: Robert M. McAllister, Klaus Hummeler, Lewis L. Coriell
Journal: New England Journal of Medicine (1959)

A CUTE cerebellar ataxia of childhood has been reviewed by several authors.1 2 3 Approximately 75 case reports have appeared in the literature; however, the syndrome is probably more common than this figure suggests. The disease is characterized by sudden onset in children one to twelve years of age, especially two to five, without apparent cause or in the course of an acute infectious disease. There is usually no fever, and cerebellar signs such as staggering gait, intention tremors, hypotonia, dysarthria, dysmetria and nystagmus are the major clinical manifestations. Signs of involvement of other areas of the central nervous system occur but . . .
657 THE EFFECT OF COFFEE CONSUMPTION ON THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN HEPATITIS B VIRUS ENDEMIC AREA
Authors: S.S. Lee, E.S. Jang, S.H. Lee, S.H. Hwang, S.Y. Ahn, J. Lee, Y.S. Park, J.H. Hwang, J.-W. Kim, N. Kim, D.H. Lee, H.Y. Kim, S.-H. Jeong
Journal: Journal of Hepatology (2013)
P5-05-05: Human Papiloma Virus Identification in Intraductal Papilloma and Breast Cancer Using Broad-Spectrum Primers.
Authors: FL Balci, O Bender, F Coskun, AP Duzgun, B Saylam, E Yuney, S Rota, I Fidan, S Feldman, A Soran
Journal: Cancer Research (2011)

Abstract Background There is limited data about Human Papiloma Virus (HPV) presence in intraductal papilloma, and there are some conflicted studies about the effects of HPVs on breast cancer. Most of these studies have methodological pitfalls as well. We conducted a retrospective paraffin block study to understand the presence of HPV in papilloma and cancer tissues with broad-spectrum primers. Methods: Twenty seven intraductal papilloma and 18 breast cancer patients’ paraffin blocks were obtained from the patients who underwent ductoscopy aided papillomectomy or mastectomy. In totally 87 histopathological samples, HPV-DNA were identified by real time PCR and broad-spectrum genotyping was performed by in situ hybridization. The cancer patients were evaluated according to the status of Estrojen Reseptor (ER), Progesteron Reseptor (PR) and ErbB-2 positivity. Results: The mean age±SD was 49±16 in papilloma and 52±14 in breast cancer patients. We found that 29.6% (8 of 27) of intraductal papillomas and 44.4% (8 of 18) of breast cancer paraffin blocks had HPV-DNA positivity by PCR in situ hybridization with broad spectrum primers. Fifty percent (4 of 8) of HPV-DNA positive papillomas had only type 11; in one, only type 6; in one, mixture of type 6,11; in one, mixture of type 11, 39; and in one, mixture of type 11, 39, 82 was detected. Breast cancer lesions had only type 11 of HPV-DNA positivity in 62.5% (5 of 8) of cases; in one, mixture of type11, 39; in one, mixture of type 11, 82; in one, mixture of type 6, 11, 39 was detected. In seven HPV-DNA positive cancer patients, ER/PR and/or ErbB-2 was positive, but it was only positive in one triple negative patient. Conclusion: HPVs may have a role in developing papilloma and breast cancer. Validation of HPVs role in the etiology of breast cancer/papilloma, require further studies to understand whether the HPVs are episomal or integrated during the tumorigenesis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-05.
Becker's Nevus
Authors: Muriel Sadlier, Grainne M O'Regan
Journal: New England Journal of Medicine (2015)

A healthy 15-year-old boy presented with an area of pigmentation on his chest; it had been present since childhood but had become darker and developed hair. Examination revealed a tan-colored patch with coarse dark hairs, spanning his upper chest and extending onto the right shoulder and back.
Echocardiography of Mitral Valve Prolapse
Authors: JUDY BURGESS, RALPH CLARK, KEITH COHN
Journal: Circulation (1974)

of the leaflet connection to each of the mitral leaflets.However, as observed at the operating table, there was prolapse of both leaflets rather than flail leaflets.We suggest that, despite chordae rupture, the echo- cardiographic picture is more compatible with mitral valve prolapse rather than with a flail posterior mitral valve leaflet.
Erratum: Corrigendum: Multiphoton imaging reveals a new leukocyte recruitment paradigm in the glomerulus
Authors: Sapna Devi, Anqi Li, Clare L V Westhorpe, Camden Y Lo, Latasha D Abeynaike, Sarah L Snelgrove, Pam Hall, Joshua D Ooi, Christopher G Sobey, A Richard Kitching, Michael J Hickey
Journal: Nature Medicine (2016)
Abstract 4049: MiR-187 is a marker of poor prognosis in estrogen receptor-positive breast cancer
Authors: Laoighse Mulrane, Stephen Madden, Donal J. Brennan, Sharon F. McGee, Karin Jirström, Laura van't Veer, Rene Bernards, Des Higgins, William M. Gallagher, Darran P. O'Connor
Journal: Cancer Research (2010)

Abstract Resistance to endocrine-directed therapy represents a significant problem in the management of breast cancer. Here we describe an integrated bioinformatics and translational pathology approach to identifying novel microRNAs (miRNA) controlling this phenomenon. Differential gene expression can, in part, be attributed to the activity of specific miRNAs. Given a database of miRNA binding site motifs and gene expression levels determined by transcriptomic profiling, correspondence analysis, between group analysis and co-inertia analysis can be combined to produce a ranked list of miRNAs associated with a specific gene signature and phenotype. We have applied this approach to examine gene expression data from 69 breast cancer patients treated with tamoxifen (1) and have identified miR-187 as the principle miRNA associated with poor response to anti-estrogen therapy. Expression of miR-187 was subsequently evaluated in a cohort of breast cancer patients (n=111), by locked nucleic acid in situ hybridisation (LNA-ISH) on tissue microarrays, and quantified by automated image analysis. LNA-ISH signal was validated by miR-187-specific Taqman PCR in a subset of tumours. High miR-187 expression was significantly associated with poor outcome in ER+ breast cancer patients (p = 0.05) and correlated with increased tumour size (p=0.009), higher grade (p=0.005) and PR negativity (p=0.014). Additionally, the prognostic significance of the miR-187 target genes OCA2 and HIPK3 was examined in an independent dataset comprising 155 breast cancer patients treated with adjuvant tamoxifen (2). Low mRNA expression of both OCA2 (p=0.0001) and HIPK3 (p=0.016) was found to be significantly associated with poor outcome. These data support the hypothesis that miR-187 and its targets play an important role in anti-estrogen resistance and may be useful as biomarkers to aid treatment options and as potential drug targets to restore tamoxifen sensitivity in resistant patients. 1. Kok M et al. Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 2009;113(2):275 2. Chanrion M et al., A gene expression signature that can predict the recurrence of tamoxifen-treated primary breast cancer. Clin Cancer Res 2008;14(6):1744-52. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4049.
Abstract 5095: Biochanin A, a natural isoflavone inhibits angiogenesis in glioma.
Authors: Aditi Jain, James C.K. Lai, Alok Bhushan
Journal: Cancer Research (2013)

Abstract Malignant gliomas like glioblastoma multiforme are the most lethal form of adult brain tumor. Patients with this disease survive for only 12-15 months after diagnosis. Angiogenesis, a process of formation of new blood vessels is a pathological hallmark of glioblastoma and plays an important role in tumor growth and survival. Although angiogenesis holds promise as a drug target, recent studies have highlighted that glioblastoma acquires aggressive invasive characteristics when treated with anti-angiogenic monotherapy. Therefore, there is an urgent demand for therapies which effectively target angiogenesis and limit invasion in glioblastoma. Previously, our laboratory has found that biochanin A, a dietary isoflavone inhibits invasion in human glioblastoma cells. In this study, we determined the effects of biochanin A on brain tumor angiogenesis using rat brain tumor cells (C6) and endothelial (bEnd.3) cells. Our cell survival data indicate a dose dependent decrease in cell survival of both C6 and bEnd.3 cells treated with biochanin A (5μM-70μM) for 72 hours. Biochanin A also inhibited ERK and AKT pathway in these cells. Zymography invasion assay demonstrated a decrease in enzymatic activity of MMP's in biochanin A treated C6 and bEnd.3 cells. Apart from these signaling molecules, angiogenesis is also driven by hypoxia through upregulation of hypoxia inducible factor (HIF-1α) which releases vascular endothelial growth factor (VEGF), a key player of angiogenesis. We found that biochanin A at 35 μM inhibited protein expressions of both HIF-1α and VEGF in C6 cells treated with cobalt chloride, a chemical inducer of hypoxia. Biochanin A was also effective in inhibiting angiogenesis in an ex vivo chick chorioallantoic membrane model. These findings indicate that we may use biochanin A as a dual targeted agent that inhibits two processes, invasion and angiogenesis at similar concentrations. Thus, our study will allow the formulation of new and improved therapies for glioblastoma and ultimately enhance patient survival. (This study was supported by NIH INBRE grant #P20R16454, University Research Committee grant and Mountain States Tumor and Medical Research Institute grant). Citation Format: Aditi Jain, James C.K. Lai, Alok Bhushan. Biochanin A, a natural isoflavone inhibits angiogenesis in glioma. [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 5095. doi:10.1158/1538-7445.AM2013-5095
Effect of the antimouse GITR mab plus chemotherapy on survival and tumor immunity.
Authors: J. Ponte, D. Doty, R. Christmas, P. Ponath, L. Vaickus, M. Rosenzweig
Journal: Journal of Clinical Oncology (2010)

e13147 Background: Glucocorticoid-induced tumor necrosis factor receptor (GITR) is an immune modulator found on many cell types, including T cells. Tolerx's antimouse (m) GITR Mab (2F8) is a potent adjuvant in a prime boost model. 2F8 enhanced humoral and cellular immunity after vaccination with H5N1 hemagglutinin. Unlike alum and incomplete Freund's adjuvant, the humoral response mediated by 2F8 was skewed to a Th1- type response. The response was durable, did not require Fc-FcR interactions, and was antigen specific. Methods: The efficacy of 2F8 with chemotherapy was evaluated in mice with established CT26 murine colon carcinomas. Results: Combination therapy—a single dose of a chemotherapeutic agent followed the next day by a single dose of 2F8—significantly reduced tumor burden and prolonged survival compared with chemotherapy alone. Cumulative data with two chemotherapeutic agents revealed > 60% complete remissions with combination therapy compared with < 10% with chemotherapy alone. In complete responders, combination therapy elicited specific and robust memory responses to IV or SC CT26 cells. CD8+ T cell depletion ablated efficacy, confirming the importance of T effector cells in anti-mGITR-mediated immunotherapy. CD4+ T cell depletion revealed that CD4+ T cells may not be important for initiating the anti-tumor immune response but are crucial for maintaining the response, which suggests that T helper cells may be an important target of anti-mGITR. Depletion of NK cells did not affect efficacy. Combination therapy enhanced CD8+ T cell number, reduced the number of T regulatory cells (Tregs), altering the Treg/Teff ratio. Lastly, combination therapy resulted in fewer splenic myeloid-derived suppressor cells than mice treated with an isotype control, 2F8 alone, or chemotherapy alone. Conclusions: Anti-mGITR appears to have multiple beneficial mechanisms of action that potentially augment antitumor immunity. These findings support the evaluation of our antihuman GITR Mab, TRX518, in clinical oncology indications. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tolerx Tolerx