tbuckley/cabot-search huggingface dataset:
Abstract 539: A preclinical model to evaluate the risk of increased dietary fat consumption and prostate cancer progression
Authors: Yasuyuki Kobayashi, Marco A. De Velasco, Yuji Hatanaka, Yutaka Yamamoto, Motoyoshi Tanaka, Nozawa Masahiro, Nobutaka Shimizu, Kazuhiro Yoshimura, Mitsuyama Kodama, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2012)

Abstract Prostate cancer (PCa) is a common disease in older men that is highly associated with various dietary factors including the increased consumption of fats, red and processed meats. Although results from large clinical studies have shown inconsistent findings with regards to obesity and prostate cancer-related mortality, increasing evidence has suggested a link between obesity and an increase in prostate cancer-specific mortality. To better understand the effects of increased dietary fat in prostate carcinogenesis, we developed a preclinical model using prostate-specific PTEN conditional knockout mice. This model is based on the conditional inactivation of PTEN in the prostate to alter PI3K/Akt/mTOR signaling, resulting in a stage-specific development and progression of cancer, with the ability to further develop castrate-refractory prostate cancer in a manner similar to humans. We previously showed that consumption of a high-fat diet (13.6% high fat plus N-nitroso-N-methylurea) for 75 weeks augmented prostate cancer progression in PTEN-mutant mice resulting increased metastases and decreased survival. To determine the molecular mechanisms involved in tumor promotion we randomized PTEN-mutant mice with non-castrate and castrate refractory prostate cancer to a high fat diet for 50 weeks. Chronic consumption of a high-fat diet results in increased tumor growth compared to controls. Mice fed a high fat diet showed increased levels of circulating adipokines and pro-inflammatory cytokines that include leptin, TIMP-1 IL-6, IL-10, IL-11 IGF-II, HGF and LIF. Mice fed the high fat diet also showed increased levels of tumor cell proliferation, transcriptional Stat-3 activation and neovascular angiogenesis. These findings provide evidence for the tumor promoting effects of a high fat diet and establish a preclinical model for the future development of novel chemopreventive strategies. 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 539. doi:1538-7445.AM2012-539
Abstract 4972: High-throughput functional profiling of dedifferentiated liposarcoma cell lines
Authors: Shantanu Banerji, Jordi Barretina, Aimee Crago, Abbie Frederick, Michael Okamoto, Barbara Weir, Glenn Cowley, David Root, Marc Ladanyi, Sam Singer, Matthew L. Meyerson
Journal: Cancer Research (2011)

Abstract We previously profiled several adult soft-tissue sarcoma subtypes using sequencing, copy number analysis, and gene expression arrays. This high-throughput genetic profiling revealed dozens of candidate genes deserving of further functional validation. To prioritize genes, we performed a pooled shRNA screen to identify essential genes in liposarcoma. Dedifferentiated liposarcoma (DDLS) served as a model for this approach as multiple robust cell lines are available. Five DDLS cell lines (DDLS8817, LPS141, FU-DDLS-1, RDD8107, and LP6) were infected with a pool of 54,020 lentiviral shRNAs targeting ∼11,000 genes (median 5 shRNAs per gene) and passaged for 16 doublings. DNA was extracted and hairpin sequences were PCR amplified and hybridized to a custom microarray that interrogates all shRNAs in the pool. shRNAs were ranked according to their differential abundance between early and late passages. Genes corresponding to the most significantly depleted shRNAs are presumed to affect cell proliferation and are candidate oncogenes. We compared the pattern of hairpin depletion in the DDLS cell lines to a panel of over 60 cell lines representing other common cancers screened with the same pooled shRNA library. The 5 DDLS cell lines clustered into 3 distinct groups. Only one gene appeared to be essential in all 3 groups: WWTR1 (TAZ1), a master-regulator of adipocyte differentiation. Twenty-eight genes appeared essential in at least two DDLS groups including MDM2 and ZBTB2, both reported to negatively regulate the tumor suppressor gene TP53. Low-throughput in vitro experiments have confirmed that WWTR1 knockdown using two shRNA clones inhibits LPS141 proliferation by 78 and 75% after 4 days as compared to scramble (p=0.004 and 0.06 respectively). Our complementary genome-scaled functional screen has confirmed a known oncogene in DDLS and revealed additional candidate genes that appear to have a role in proliferation. Further integration of existing datasets may nominate additional genes essential for liposarcoma pathogenesis. 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 4972. doi:10.1158/1538-7445.AM2011-4972
L'application endoscopique du macroclip OTSC pour les hémorragies digestives sévères chez les patients anticoagulés. Une étude rétrospective bi-centrique sur les 5 dernières années
Authors: E Wedi, A Sportes, J Hochberger
Journal: Endoscopy (2015)

Le clip OTSC (OVESCO, Allemagne) est un nouvel outil endoscopique récemment utilisé pour le traitement des hémorragies digestives, des fistules et lors de procédures expérimentales de type NOTES.
Abstract 3190: Heparanase modulates Shh and Wnt3a signaling in human medulloblastoma cells
Authors: Lon D. Ridgway, Michael E. Wetzel, Dario Marchetti
Journal: Cancer Research (2010)

Abstract The pathogenesis of medulloblastoma (MB), the most common and aggressive brain tumor in children, is poorly understood. MB tumors are characterized by a massive expansion of external granule layer cells of the cerebellum in response to Purkinje neurons secreted factors such as Sonic hedgehog (Shh) and Wnt3a. Understanding the modulation of Shh/Wnt signaling is critical to developing new treatments for medulloblastoma. Shh and Wnt3a are involved in the induction of MB cell proliferation, and bind heparan sulfate glycosaminoglycan chains (HS-GAG). HS-GAG are components of syndecans as cell-surface HS proteoglycans (HSPG), important co-receptors involved in the control of signaling by extracellular matrix - based ligands. We hypothesized that Shh/Wnt3a - induced MB cell signaling is mediated by syndecans, altering syndecan carboxy terminal (CT) - associated molecules and downstream targets. We also hypothesized that these events are regulated by heparanase (HPSE), the only functional mammalian endoglycosidase cleaving HS-GAG at intrachain site and widely implicated in cancer metastasis. We compared regulation of Shh/Wnt3a signaling by exogenous HPSE in human MB lines possessing increased invasive abilities (D721 &amp;gt; D556 &amp;gt; D283). We identified GEF-H1, a small GTPase inhibitor, as a new component of syndecan-4 - associated signaling complex. Secondly, we demonstrated that HPSE modulated the expression and localization of GEF-H1, β-catenin, and N-Myc in a Shh/Wnt3a - dependent manner, altering MB cell proliferation. Thirdly, we showed that corresponding, GEF-H1 - regulated, small GTPase (Rac/Rho) activities are stimulated differently among MB lines and promote cell invasiveness. Thus, the HSPG/HPSE axis is implicated in two critical MB cell signaling systems and biological outcomes - proliferation and invasion, and potentially relevant as novel target for treatment of invasive MB. 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 3190.
Abstract 3745: IL-10 polymorphisms, smoking, and Helicobacter pylori infection on the risk of noncardia gastric cancer in Koreans
Authors: Jeongseon Kim, Young Ae Cho, Aesun Shin, Soo-Jeong Cho, Chan Gyoo Kim, Jong Yeul Lee, Young-Woo Kim, Il-Ju Choi
Journal: Cancer Research (2011)

Abstract Background: Genetic variations of interleukin-10 (IL-10) and environmental factors are assumed to influence inflammation and gastric carcinogenesis. Therefore, we aimed to investigate the association between IL-10 polymorphisms, smoking, and Helicobacter pylori (H. pylori) infection on the noncardia gastric carcinogenesis in Koreans. Methods: We genotyped 3 promoter polymorphisms (−1082 A&amp;gt;G, -819T&amp;gt;C, -592A&amp;gt;C) on the IL-10 gene in 495 noncardia gastric cancer patients and 495 sex- and age-matched controls. Multiple logistic regression models were used to detect the effects of IL-10 genetic variants, smoking, and H. pylori infection on gastric cancer risk, stratified by histological type of gastric cancer. Results: The IL-10-819C allele and -592C allele are in complete linkage disequilibrium, and IL-10-819C/-592C carriers are associated with a higher risk of noncardia gastric cancer, particularly with a risk of intestinal type cancer (OR [95% CI] = 1.50 [1.08−2.08]), than those with the wild type homozygote genotypes. Compared to nonsmokers carrying the wild type homozygotes, current smokers carrying IL-10-1082G and -819C/-592C showed 4.91 (95% CI = 2.49−9.69) and 6.82 (95% CI = 2.94−15.84) times increased risk of intestinal type gastric cancer, respectively. In addition, smokers with H. pylori infection were in the highest risk of intestinal gastric cancer compared with non-smokers without H. pylori infection, and this association was particularly stronger among IL-10-1082G carriers than AA carriers (OR [95% CI] = 15.54 [5.52−43.72]). Conclusion: Inflammation-related genetic variants may interact with smoking and H. pylori infection on the risk of noncardia gastric cancer, particularly intestinal type. Therefore, high risk group may reduce the risk of gastric cancer by modifying their lifestyles. 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 3745. doi:10.1158/1538-7445.AM2011-3745
SPECT Myocardial Perfusion in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Soon-Ah Park, Kwang Ho Cho, Nam-Ho Kim, Chung-Yong Yang, Seong Hoon Park
Journal: Clinical Nuclear Medicine (2013)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary small vessel disease. Although the symptoms are exclusively neurological, arteriopathy is generalized. We performed cardiac evaluation using myocardial perfusion single photon emission computed tomography (SPECT), dual-source 128-channel multidetector computed tomography (MDCT) angiogram, echocardiogram, and electrocardiogram (ECG) in a 46-year-old woman with CADASIL. No abnormal findings were observed on MDCT angiogram, echocardiogram, or ECG. However, SPECT demonstrated reversible perfusion defects in the left anterior descending artery territory. We suggest that myocardial perfusion SPECT is a valuable tool to identify risk from cardiovascular accident in CADASIL patients.
Hepatic-Artery Ligation for Hepatic Hemangiomatosis
Authors: Alfred A. deLorimier, Ellen B. Simpson, Richard S. Baum, Erik Carlsson
Journal: New England Journal of Medicine (1967)

THE involuting hemangioma (capillary hemangioma or hemangioendothelioma) of childhood is a congenital vascular malformation, which progressively enlarges in early infancy, becomes stationary for a variable period and then spontaneously regresses. About 60 per cent of all cutaneous lesions are present at birth; the remainder become evident within two months after birth. Capillary hemangiomas attain their maximum growth in the first six months in half the cases and in six to twelve months in the rest. After a stationary period, involution occurs before six months of age in 16 per cent of the patients, between six to twelve months in 65 . . .
POST-SHOCK ELECTROMECHANICAL DISSOCIATION DURING DEFIBRILLATION THRESHOLD TESTING
Authors: Hiroyuki Ito, Nitish Badhwar, Mitsuharu Kawamura, Vasanth Vedantham, Zian Tseng, Byron Lee, Randall Lee, Gregory Marcus, Edward Gerstenfeld, Melvin Scheinman
Journal: Journal of the American College of Cardiology (2016)
Morphometric and clinico-pathologic predictors of high Gleason Scores in prostatic needle biopsies: An analysis in 181 cases of prostatic adenocarcinoma
Authors: Girish Venkataraman, Vijayalakshmi Ananthanarayanan, Saeedeh Masoom, Xiao Ke Huang, James Sinacore, Robert C. Flanigan, Eva M. Wojcik
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

692 

Gleason Score (GS) is a well known predictor of patient outcomes in prostate cancer. Therefore, identification of combinations of clinical and non-GS pathologic variables that will help predict high GS (GS≥7) will be useful in predicting survival outcomes in prostate cancer. We analyzed a total of 181 prostatic needle biopsies performed at Loyola University from a cohort of patients diagnosed with prostate cancer between the years 1998-2002. Clinical/demographic variables including age, PSA, PSAD, TRUS findings were abstracted from the medical records. Biopsy variables including the highest biopsy GS, percentage of carcinoma at the biopsy site with the highest GS (PCARBX) were extracted. The needle biopsies were also stained with the nuclear stain Feulgen and ploidy analysis was performed using the CAS-200 system (Becton Dickinson). In addition, separate analysis of nuclear morphometry for 28 Markovian and non-Markovian nuclear features was performed using the Nuclear Morphometry Suite (Bacus Labs). All data were analyzed using SPSS 12. Multivariate logistic regression (LR) was performed using the forward Wald conditional model to identify sets of variables that predicted high GS. PSA and PSAD were log-transformed for multivariate analysis. A total of 93 cases had low GS (GS≤6) and 88 had high GS (GS≥7). The median PSA in the GS≥7 group was significantly higher than the median PSA in the GS≤6 group (p=0.000; Mann Whitney's U test). The mean PCARBX was also significantly higher in the GS≥7 group (56.09 vs.34.07, p=0.000; t-test). There was significant association of aneuploidy with high GS (Chi-square=38.25; p=0.000). LR analysis utilizing the clinical, biopsy non-GS parameters and morphometric parameters identified 3 variables that correctly predicted 74.3% of the cases high GS (GS≥7): namely morphometric sum optical density (Odds Ratio {OR}: 1.76; 95%CI: 1.302, 2.379), morphometric Coefficient of Variation (OR: 9E+007; 95%CI: 22.46, 4E+014) and PCARBX (OR 1.03; 95%CI: 1.015, 1.045). A receiver operator characteristic (ROC) curve plotted with this final model had an area under the ROC curve of 0.816 (95% CI: 0.755-0.816). None of the clinical or biochemical indicators were significant in predicting high GS. In conclusion, the percentage of carcinoma at the biopsy site with the highest GS in combination with the morphometric sum optical density and coefficient of variation adequately discriminate high GS. This information may be useful when incorporated into nomograms for predicting prostatic biopsy outcomes.
Abstract 1934: Hyperthermia enhances the anti-tumor activity of adoptive transfer of naïve T cells
Authors: Tsuguhiro Matsumoto, Satoshi Kokura, Takeshi Ishikawa, Jun Funaki, Satoko Adachi, Tetsuya Okayama, Naoyuki Sakamoto, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Osamu Handa, Hideyuki Konishi, Naoki Wakabayashi, Nobuaki Yagi, Yuji Naito, Akiko Kato, Keisuke Tomita, Tatsuji Enoki, Toshikazu Yoshikawa
Journal: Cancer Research (2010)

Abstract Objective: Recently, in the case of the adoptive immunotherapy, less-differentiated T cell (naïve T cells) has been postulated to be more effective for tumor regression than late effector T cells. On the other hand, hyperthermia augments MHC class I antigen presentation via HSPs expression and attenuates the production of immunosuppressive cytokines such as IL-10 and TGF-beta from cancer tissue. There is increasing evidence that the use of hyperthermia is effective as an adjunct to cancer immunotherapy. Therefore, the purpose of this study was to evaluate the effects of hyperthermia on adoptive transfer of naïve T cells in a subcutaneous B16 melanoma model. Experimental design: Male C57BL/6 mice were injected s.c. with B16 murine melanoma cells. Splenocytes for adoptive transfer were isolated from tumor-bearing mice and primary stimulation was accomplished using plate-bound anti-CD3 monoclonal antibody. Cells were expanded in culture media containing IL-2, IL-7 and recombinant human fibronectin fragment (FN-CH296). Prior to adoptive transfer, CD62Lhigh and CD62Llow populations were sorted using a MACS CD62L-positive selection column. Subcutaneous B16 bearing mice were treated with hyperthermia on day 3 and day 4, and then mice were treated with two doses of CD62Lhigh or CD62Llow cells via a tail vein on day 6 and day 10. Tumor volume, body weight and the number of regulatory T cell (Treg) within spleen were examined on day 17. Results: The tumor volume significantly decreased in CD62Lhigh adoptive transfer therapy combined with hyperthermia compared to CD62Llow adoptive transfer therapy combined with hyperthermia or hyperthermia alone. The body weight and the number of Treg within spleen did not have the significant difference among these groups. Conclusion: These data suggest that hyperthermia enhances the anti-tumor effect of adoptive transfer therapy using naïve T cells, but not late effector T cells. Hyperthermia would have potential to activate and expand naïve T cell in vivo after adoptive transfer. These results may benefit further efforts on developing novel adoptive immunotherapies based on hyperthermia. 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 1934.
Daniel Carrión's Experiment
Authors: Myron G. Schultz
Journal: New England Journal of Medicine (1968)

IN the continuing debate that envelops the practice of human experimentation, many classic examples of physician self-experimentation are cited by modern authors to dramatize their opinions. Purkinje's dosing himself with sufficient digitalis to kill nine cats to induce teichopsia, the death of Obermeier from self-inoculated cholera (after he failed to give himself relapsing fever) and the deaths of Lazear and ultimately Carroll in the now famous yellow-fever experiments are but a few of the cases used to illustrate either the folly or the exalted beneficence of their perpetrators.In the present age of corporate medical endeavor, when studies involving human . . .
SAT0380 Silent Osteonecrosis of the Femoral Head Following High-Dose Corticosteroids in Patients
Authors: N. Kianmehr, A. Bidari, M. Mofidi, N. Bahar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoncrosis (ON) is reputed to be one of the most disabling complications following Corticosteroid(CS) medication. However, evidence regarding risk of asymptomatic prevalence among different diseases and the impact of variable steroid regimens are conflicting. <h3>Objectives</h3> We aimed to determine the prevalence of ON of femoral head in asymptomatic patients with systemic rheumatic diseases who received high-dose CS and also clarify its relationship with different dosages and regimens. <h3>Methods</h3> Fifty consecutive patients receiving high dose CS for rheumatic diseases who have no pelvic pain were included to this study. MRI of both hips was performed on all patients using a 1.5 Tesla to diagnose ON. <h3>Results</h3> Among 50 study subjects, 18 (36%) developed ON of the femoral head. The groups with and without ON were comparable in terms of sex, age and mean starting CS dose. There was no statistical difference in the type of CS regimen including daily dose, peak dose and cumulative dose between the ON and non ON groups. However, both the cumulative CS dose and the duration of time in which high dose CS (equivalent to 30mg prednisolone or more) was given were associated with the prevalence of silent ON <h3>Conclusions</h3> According to high prevalence of 0N in our selected patients with no other identifiable risk factor for ON, monitoring of high risk patients with periodic hip MRI would have diagnose necrosis in early stage. <h3>References</h3> Felson DT, Anderson JJ. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. (1987) Lancet. Apr 18;1(8538):902-6. Colwell CW Jr, Robinson CA, Stevenson DD, et al. Osteonecrosis of the femoral head in patients with inflammatory arthritis or asthma receiving corticosteroid therapy.(1996) Orthopedics. Nov;19(11):941-6. Kale N, Agaoglu J, Tanik O. Correlation of cumulative corticosteroid treatment with magnetic resonance imaging assessment of avascular femoral head necrosis in patients with multiple sclerosis. (2010) Neurol Int. November 26; 2(2): e17. <h3>Acknowledgements</h3> The authors would like to acknowledge Deputy of research in Tehran University of Medical Sciences <h3>Disclosure of Interest</h3> None Declared
P128 The challenges of hypertonic saline in non-CF bronchiectasis
Authors: T. M. Small, H. Groves, P. McAlinden, J. Davison, A. DeSoyza
Journal: Thorax (2010)

<h3>Background</h3> Non-Cystic Fibrosis (CF) bronchiectasis is an understudied clinical area. Many studies are extrapolated from CF despite prior evidence suggesting this is not wholly appropriate. Recent BTS guidelines have suggested a role for Hypertonic Saline (HS) after findings from Kellet et al (2008). In that study, a nebulised (7%) HS challenge test was done and subjects were to be excluded from ongoing HS therapy if they reported ‘chest tightness’, ‘wheeze’ or ‘difficulty in breathing’, or had a 10% reduction in spirometry following inhalation of HS. Notably none of 23 patients were excluded on these criterion. We hypothesised that a fall in FEV<sub>1</sub> greater than 10% would be more common in a non study population but of limited clinical significance. <h3>Methods</h3> We reviewed our 6% hypertonic saline challenge (baseline, post 2.5 mg Salbutamol and post 6% HS) data from consecutive patients commenced on this therapy due to mucus retention despite other interventions (eg, physiotherapy and/or mucolytic) Results: 33 patients were identified (20F, 13M) mean age 61.5±13 years, mean baseline FEV<sub>1</sub> was 1.37L±0.7 (range 0.4–2.65) mean FEV<sub>1</sub>% predicted 54%±25% (range 23–111%). One patient9s data were excluded due to inability to reproducibly perform spirometry. The mean change in FEV<sub>1</sub> from baseline was +4.3%±10.8 % (range −21 to −36) and fall from post Salbutamol was −0.64±11.6% (range −14 to +14%). Seven patients have stopped HS therapy either due to chest tightness or taste (20%). <h3>Conclusions</h3> This cohort is larger than that previously reported and includes a wider range of airflow obstruction severity. No exclusion criterion were applied to trying HS. The overall fall during an acute HS challenge in an unselected bronchiectasis population is small. Despite this many patients discontinue HS within 3 months of initiation.