tbuckley/cabot-search huggingface dataset:
Abstract 2498: Tumorspheres cultured from circulating epithelial tumor cells (CETCs) overexpress stem cell markers in patients with solid cancers
Authors: Katharina Pachmann, Monika Pizon, Dorothea Schott, Ulrich Pachmann
Journal: Cancer Research (2016)

Abstract Background: Solid malignancies continuously shed tumor cells which may enter the circulation, spread to other tissues and initiate metastases, but it is assumed that only a small subpopulation among CETCs is capable of metastasis formation, the subpopulation of CETCs capable of forming tumorspheres in vitro and carrying stem cells properties. The aim of this study was to characterize the pattern of expression of the tumorspheres as compared to CETCs. Methods: Blood samples were obtained from patients diagnosed with solid tumors. CETCs were enumerated with the maintrac method and subsequently cultivated in epithelial stem cell-selective medium. Immunofluorescence and qRT-PCR were performed to examine the metastatic ability of tumorspheres in vitro. Results: Analysis of surface markers in non-adherent tumorspheres forming from CETCs under stem cell- selective conditions after a period of 14 days showed typical phenotype for cancer stem cells depending on type of cancer. Furthermore, spheres had high enzymatic activity for ALDH 1. Array qRT-PCR analysis revealed that putative stem cell markers, such as Oct4, Sox2, Nanog, EpCAM, ALDH1 and CD133 are overexpressed in relation to house-keeping genes RPL13a and GAPDH in tumor spheres in contrast to the significantly lower expression level of these stem cell markers in individually isolated CETCs. High expression level of pluripotency genes in tumorspheres was associated with aggressive tumor behaviour in terms of tumor progression and type of cancer. Conclusion: Here we show that stem cell markers are overexpressed in tumorspheres as compared to CETCs. Obviously only a small population of CETCs can be grown into spheres which possess stem cell properties and most probably are responsible for recurrence and treatment failure. Precise characterization of CETCs and tumorspheres on the single cell and sphere level will contribute to a better understanding of metastasis formation and lead to development of cancer stem cell based cancer therapy. Citation Format: Katharina Pachmann, Monika Pizon, Dorothea Schott, Ulrich Pachmann. Tumorspheres cultured from circulating epithelial tumor cells (CETCs) overexpress stem cell markers in patients with solid cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2498.
Locking doors in mental health hospitals does not reduce suicide or absconding, shows study
Authors: Susan Mayor
Journal: BMJ (2016)

Mental health hospitals with locked door policies have no lower rates of suicide, attempted suicide, or patients leaving without staff authorisation than hospitals with open doors, a large observational study has shown.1 Results found that treatment on open wards was associated with lower risk of suicide attempts and patients absconding.

Inpatient psychiatric wards in the UK are increasingly keeping their doors locked with the aim of preventing suicide and patients absconding with possible risk of self harm or harm to others, but there is little evidence for this.

Researchers analysed data from 21 German psychiatric inpatient hospitals for the 15 years between 1998 and 2012 to investigate …
Smaller employers are less likely to provide occupational health support
Authors: Paul J Nicholson, David P Fox
Journal: BMJ (2016)

Feary and colleagues’ definition of occupational asthma (OA)1 differs from the UK consensus definition: “asthma which is induced by exposure in the working environment to airborne dusts, vapours or fumes, in workers with or without pre-existing asthma.”2

OA can be sensitiser induced (about 90% of cases), characterised by latency between first exposure …
Abstract 4770: The regulation of pre-ribosomal RNA synthesis by LKB1
Authors: Rui Jin, Faken Liu, Xiuju Liu, Henry Huang, Scott C. Wilkinson, Diansheng Zhong, Fadlo R. Khuri, Haian Fu, Adam I. Marcus, Yulong He, Wei Zhou
Journal: Cancer Research (2016)

Abstract LKB1 is commonly thought of as a tumor suppressor gene, because its hereditary mutation is responsible for a cancer syndrome, and somatic inactivation of LKB1 is found in non-small cell lung cancer, melanoma, and cervical cancers. Unlike other tumor suppressors whose main function is to either suppress cell proliferation or promote cell death, one of the functions of LKB1 is to suppress cell proliferation in order to promote cell survival under energetic stress conditions. We recently discovered that LKB1 promotes pre-ribosomal RNA synthesis under uridine down-regulated condition. The mechanistic basis of this finding is that LKB1 activates TIF-IA-mediated pre-riobosomal RNA synthesis, partly through the control of its cellular localization. Immuno-coprecipitation study revealed that the interaction between TIF-IA and nuclear transportation machinery may be regulated by LKB1. Our finding also has important clinical implication because the suppression of de novo UTP synthesis preferentially promotes apoptosis in LKB1-inactivated cells. This unique, pro-survival function of LKB1 led us to exploit the vulnerability of LKB1-null cells in their defect in sensing intracellular UTP depletion. Such targeted agents represent a novel treatment strategy because they only induce cell killing when LKB1 is absent. Citation Format: Rui Jin, Faken Liu, Xiuju Liu, Henry Huang, Scott C. Wilkinson, Diansheng Zhong, Fadlo R. Khuri, Haian Fu, Adam I. Marcus, Yulong He, Wei Zhou. The regulation of pre-ribosomal RNA synthesis by LKB1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4770.
Ventricular Septal Rupture After a Nonpenetrating Chest Trauma
Authors: Franck Thuny, Alexis Jacquier, Alberto Riberi, Jean-François Avierinos, Sébastien Renard, Frédéric Collart, Xavier Luanika, Jean-Michel Bartoli, Dominique Métras, Gilbert Habib
Journal: Circulation (2005)
Abstract 4563: Role of ezrin in PKA dependent colorectal cancer cell fate
Authors: Premila Leiphrakpam, Michael G. Brattain
Journal: Cancer Research (2016)

Abstract Introduction: Metastasis is the main cause of cancer related death in CRC. However, the molecular basis of CRC metastasis is poorly understood. Ezrin is a known cAMP dependent AKAP. We have found ezrin hyperphosphorylation at T567 is critical for CRC cell survival. In this study we evaluated the dependency of PKA activation with ezrin phosphorylation at T567 on its downstream cell survival mechanisms. Methods: Small molecule ezrin kinase inhibitor NSC668394 was used to test the effect of inhibition of ezrinT567 phosphorylation on PKA activation and its downstream cell survival signaling. A genetic knockdown approach was utilized to further confirm the result. In another approach, growth factor mediated activation of ezrin T567 phosphorylation was performed and ezrin/PKA signaling was then analyzed for its downstream cell survival effects. To further confirm the findings ezrin phospho-mimetic (T567D) and phospho-deficient (T567A) mutants were generated through site directed mutation approaches. Results: We demonstrated that dephosphorylation of ezrin at T567 activates PKA in a cAMP independent manner and leads to CRC cell death through inhibition of XIAP and survivin. Moreover, the stable knockdown of ezrin showed similar result. Interestingly, ligand mediated ezrin hyperphosphorylation at T567 has the opposite effect in which there is cAMP dependent PKA activation leading to CRC survival through upregulation of XIAP and survivin. This was further confirmed with ezrin T567 phospho-mimetic and phospho-deficient mutants which demonstrate PKA activation by cAMP dependent and independent mechanisms respectively leading to different CRC cell fates. Therefore, ezrin signaling demonstrated two opposing pathways in which both requires activation of PKA and yet result in different CRC cell fates by regulating XIAP and survivin expression. Conclusions: Two different ezrin signaling dependent pathways were identified which are dependent on the same enzymatic activity but with opposite effects on CRC cell fates. Therefore, ezrin might be a novel target that could be utilized for the development of new therapeutic strategies and further understanding the mechanism of ezrin/cAMP-PKA activation and its role in CRC cell survival could have potential impact for treatment of distant metastasis in CRC. Citation Format: Premila Leiphrakpam, Michael G. Brattain. Role of ezrin in PKA dependent colorectal cancer cell fate. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4563.
Abstract 3181: Expression changes of the chromatin modifier PBRM1 in human renal cell carcinomas in relation to histopathological features
Authors: Hans Krause, Anica Högner, Burkhard Jandrig, Ergin Kilic, Carsten Kempkensteffen
Journal: Cancer Research (2016)

Abstract Recent next-generation sequencing studies of clear cell renal cell carcinoma (ccRCC) have identified point mutations in chromatin-modifying genes, among them PBRM1 which is now the second most frequently mutated gene in RCCs (in up to 41% ccRCCs cases) and belongs to the m1 TCGA (The Cancer Genome Atlas) subset. The occasional presence of PBRM1 mutations in the absence of VHL mutations indicates, that PBRM1 might be another driver tumor suppressor gene in ccRCCs. We were interested in examining PBRM1 expression at mRNA and protein levels and correlated these findings to histopathological features of RCC patients. Relative gene expression (RGE) data were obtained by Q-PCR from matched tumor and adjacent normal fresh frozen ccRCC tissues from 57 patients who underwent radical nephrectomy at our clinic. Papillary (pRCC) as well as chromophobic cases (chRCC) were added to analyze the expression of splice variants of PBRM1. Comparative Western blot analyses as well as semi-quantitative immuno-histochemical staining (IHC) for PBRM1 and VHL were performed on all ccRCC cases. In 78.9% of cases (45/57) PBRM1 mRNA was downregulated at least 1.5-fold, 7% (4/57) showed PBRM1 upregulation, and 14% (8/57) displayed no obvious expression changes between tumor and corresponding tumor tissue. Interestingly, 21 of 45 ccRCCs tumor tissues expressed splice variant 4 more abundantly when compared to normal tissue, whereas the normal tissue preferentially expressed splice variant 1 that includes an additional exon. Remarkably, this differential expression picture is completely reversed in pRCC and chRCC cases. The majority of 57 ccRCCs displayed weak nuclear PBRM1 staining (52.6%), whereas 31.6% showed moderate and 15.8% strong staining. However, we were not able to demonstrate a significant correlation of IHC expression levels, neither to tumor staging nor to Fuhrman grading. The observed high frequency of decreased expression of the chromatin-remodeling gene PBRM1 on mRNA (78.9%) and protein levels (52.6%), respectively, as wells as a high mutation rate (about 15% in our data set) indicate a substantial role of PBRM1 in the tumorigenesis of ccRCCs. Preferences in the expression of different PBRM1 splice variants warrant further investigation with regard to renal cell carcinoma development. Citation Format: Hans Krause, Anica Högner, Burkhard Jandrig, Ergin Kilic, Carsten Kempkensteffen. Expression changes of the chromatin modifier PBRM1 in human renal cell carcinomas in relation to histopathological features. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3181.
BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice
Authors: Mohamed-Amine Hamouda, Arnaud Jacquel, Guillaume Robert, Alexandre Puissant, Valentine Richez, Romeo Cassel, Nina Fenouille, Sandrine Roulland, Jerome Gilleron, Emmanuel Griessinger, Alix Dubois, Beatrice Bailly-Maitre, Diogo Goncalves, Aude Mallavialle, Pascal Colosetti, Sandrine Marchetti, Martine Amiot, Patricia Gomez-Bougie, Nathalie Rochet, Marcel Deckert, Herve Avet-Loiseau, Paul Hofman, Jean-Michel Karsenti, Pierre-Yves Jeandel, Claudine Blin-Wakkach, Bertrand Nadel, Thomas Cluzeau, Kenneth C. Anderson, Jean-Gabriel Fuzibet, Patrick Auberger, Frederic Luciano
Journal: The Journal of Experimental Medicine (2016)

Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions. In addition, the tumors are serially transplantable in irradiated wild-type mice, underlying the tumoral origin of the disease. Eµ-bcl-b plasmocytes show increased expression of a panel of genes known to be dysregulated in human MM pathogenesis. Treatment of Eµ-bcl-b mice with drugs currently used to treat patients such as melphalan and VELCADE efficiently kills malignant plasmocytes in vivo. Finally, we find that Bcl-B is overexpressed in plasmocytes from MM patients but neither in MGUS patients nor in healthy individuals, suggesting that Bcl-B may drive MM. These findings suggest that Bcl-B could be an important factor in MM disease and pinpoint Eµ-bcl-b mice as a pertinent model to validate new therapies in MM.
TP53 Mutations Are Present In 15.7% Of ALL, Are Especially Frequent In ALL With MYC-Rearrangement and In ALL With Low Hypodiploid Chromosome Status and Are Associated With Poor Prognosis
Authors: Claudia Haferlach, Sandra Weissmann, Sabrina Kuznia, Susanne Schnittger, Wolfgang Kern, Alexander Kohlmann, Torsten Haferlach
Journal: Blood (2013)
FOLIE A DEUX (?)
Authors: C. Mercier
Journal: BMJ (1906)

IT is not very unusual for husband and wife mutually to charge each other with insanity, and cases have occurred to me in which it was some little time before I could decide which was indeed the true patient.In the ease I am about to describe, the difficulty was so unusually g:, reat thlat, of two practitioners who had examined the couple before me, and at whose instance I was consulted, one was prepared to certify the husband, while the oteer was equally convinced that the wife was insane.Teey were Colonial people, who had come to London partly for sight-seeing and partly for self-improvement.For a short time they stayed at a well-known hotel, at whlich they hiad stayed before.They left this, and went to anothier large hotel close by.After some days they quitted this hotel, leaving some hundreds of pounds worth of jewellery behind them, and went into veryrespectable lodgings.The same night the lady rushed up to the land- lady declaring that the husband was out of his mind, and was trying to murder her.The landlady went down, found the husband quite tranquil, and persuaded the wife to return.Next day tee couple quitted this lodging for another, leaving all their clothes and belongings behind them.After two nights in the n-ew lodginig they trans- ferred themselves to hotel No. 2, and thle next day they both arrived at breakfast time at the house of some ladies, strangers to them, but friends of other members of their family.These ladies live a quiet life in a suburban town, and were so much embarrassed by the sudden irrup- tion into their peaceful circle of this conniubial thunder- storm, that they sent for assistance to their friend and medical adviser, Dr. C. On his appearancee, the wife, in much excitement, declared that her husband was insane, violent, and dangerous, and imploredhimn to be calm and restrain himself.The husband, much agitated, thoughl the calmer of the two, did not protest against the charge, and, after an agitating and stormy scene, the whirlwind tore itself out of the house and
Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating
Authors: Tom Holvoet, Marie Joossens, Jun Wang, Jerina Boelens, Bruno Verhasselt, Debby Laukens, Hans van Vlierberghe, Pieter Hindryckx, Martine De Vos, Danny De Looze, Jeroen Raes
Journal: Gut (2016)

We read with interest the work by Halmos et al 1 in which they describe the effects of dietary FODMAP (Fermentable Oligo-, Di- and Mono- saccharides And Polyols) restriction in patients with IBS on the intestinal microbiota. They showed that low FODMAP intake was associated with reduced total bacterial and lower relative abundance of butyrate-producing Clostridium cluster XIVa, changes that are generally considered unfavourable.2 Therefore, they discourage long-term dietary FODMAP restriction, a suggestion also supported by the recent work of McIntosh and colleagues who noticed unfavourable changes in both microbiota and metabolome of patients with IBS who were on a low FODMAP diet.3 Although low FODMAP intake reduces GI symptoms in almost 75% of patients with IBS, the effects of this diet on the intestinal microbiota might be disadvantageous in the long run.

Combining these observations with the important role for the intestinal microbiota in IBS pathogenesis,4 we report here faecal microbiota transplantation (FMT) as an alternative to FODMAP restriction in patients with IBS. We applied FMT in 12 refractory IBS patients (Rome III criteria) with intermittent diarrhoea and severe bloating, …
Maladies transmissibles à Rome lors du Jubilé 2000
Authors: P Giorgi Rossi, M. Sangalli, A. Faustini, F Forastiere, C. A. Perucci
Journal: Eurosurveillance (2003)

En 2000, l'annee du Jubile, 26 millions de personnes ont visite Rome. En 1997, un systeme perfectionne de surveillance des maladies infectieuses avait ete mis en place, specialement pour les toxi-infections alimentaires collectives (TIAC), les meningites et les legionelloses. Ce reseau d'alerte rapide relie les services de sante publique aux principales sources de diagnostic et a la surveillance basee sur les laboratoires. Une surveillance internationale a ete mise en place pour la legionellose associee au voyage. Des mesures de controle specifiques ont ete adoptees pour les TIAC. L'incidence globale de ces maladies n'a pas augmente, et aucun pathogene atypique n'a ete isole dans les toxi-infections alimentaires, ni dans les meningites en 2000, compare a 1998-99. Les cas de maladie du legionnaire et de TIAC touchant des touristes etrangers ont augmente (10/4 et 7/2 observes/prevus respectivement). Trois des six TIAC concernant des pelerins ont eu lieu dans des hotelleries religieuses. Alors qu'un accroissement des cas de legionellose et de toxi-infections alimentaires chez les touristes a ete identifie par le systeme de surveillance, l'annee du Jubile n'a pas eu d'influence sur l'epidemiologie des maladies infectieuses parmi la population residant dans le Latium.
Rituximab and 2-Chlorodeoxyadenosine in Hairy Cell Leukemia as First Line Treatment: A Faster Way to Remission. Report of Five Cases.
Authors: Giuliana Farina, Giulio Giordano, Stefano Papini, Bruno Zappacosta, Arnaldo Carbone, Massimiliano Guerriero, Sergio Storti
Journal: Blood (2007)
Intracranial Hemorrhage (ICH) In Patients (Pts) Presenting with Myeloid Leukemia to a Tertiary Care Center
Authors: Farshid Dayyani, Sarah Schellhorn Mougalian, Kiran Naqvi, Farhad Ravandi, Jorge Cortes, Elias Jabbour, Stefan Faderl, William G. Wierda, Deborah A. Thomas, Susan O'Brien, Sherry A. Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2010)
Abstract 1768: Racial/ethnic differences in endometrioid endometrial cancer survival among cases identified through the National Cancer Database
Authors: Anna B. Beckmeyer-Borowko, Caryn E. Peterson, Katherine C. Brewer, Mary O. Otoo, Faith G. Davis, Kent F. Hoskins, Charlotte E. Joslin
Journal: Cancer Research (2016)

Abstract OBJECTIVES: Past research suggests that at the local level, Non-Hispanic whites (NHW) have better survival when diagnosed with endometrioid endometrial cancer (EEC) than non-Hispanic blacks (NHB), Hispanics, and American Indians; however, little is known about survival differences at a national level and among other minorities. This study examined whether racial and ethnic differences in 5-year survival are present in U.S. women (NHW, NHB, Hispanics, non-Hispanic Asians (NHA), non-Hispanic Pacific Islanders/Hawaiians (NHPI), non-Hispanic American Indians/Aleutians or Eskimos (NHAI/AN) and non-Hispanics Others (NHO). METHODS: EEC cases from the National Cancer Database were analyzed to evaluate racial/ethnic differences in 5-year survival among women diagnosed with EEC between 1998 and 2007. Chi-Square test was used to examine whether differences in demographic, clinical, institutional, and treatment variables varied by race/ethnicity. Multivariable Cox proportional hazard regression models were fit to estimate the adjusted hazard ratio (HR) and 95% confidence interval (95% CI) between race/ethnicity and survival. RESULTS: A total of 178,310 women were diagnosed with EEC between 1998 and 2007. Of these; 74.8% were NHW, 8.3% were NHB, 13.9% were Hispanic, 1.8% were NHA, 0.2% were NHPI, 0.2% were NHAI/AN and 0.8% were NHO. Adjusting for covariates, NHB (HR = 1.29; 95%CI 1.24-1.34) and NHPI (HR = 1.59; 95%CI 1.50-1.67) had poorer survival than NHW. Yet results show that NHA (HR = 0.83; 95%CI 0.74-0.92) and NHO (HR = 0.81; 95%CI 0.69-0.94) had a better survival when compared to NHW. No survival differences were detected between Hispanics, NHAI/AN and NHW. CONCLUSIONS: Results identify racial/ethnic differences in 5-year survival among women diagnosed with EEC cancer in the U.S. between 1998 and 2007. NHA and NHO had a better and NHB and NHPI had a poorer survival when compared to NHW. Citation Format: Anna B. Beckmeyer-Borowko, Caryn E. Peterson, Katherine C. Brewer, Mary O. Otoo, Faith G. Davis, Kent F. Hoskins, Charlotte E. Joslin. Racial/ethnic differences in endometrioid endometrial cancer survival among cases identified through the National Cancer Database. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1768.