tbuckley/cabot-search huggingface dataset:
Comparison of the demographics of patients enrolled (E) versus those not enrolled (NE) on therapeutic clinical trials at a comprehensive cancer center
Authors: S. Goodin, D. C. Vamos, M. P. Kane, J. Nishioka, S. Lisi, J. R. Neceskas, J. Aisner, E. H. Rubin, M. B. Todd, W. J. Shih
Journal: Journal of Clinical Oncology (2007)

17065 Background: In the U.S., representation of minorities and the elderly in clinical trials has been low yet few reports have evaluated this potential barrier to enrollment by comparing the demographics of patients E vs NE within an institution. Therefore, we compared these groups to determine if there were significant differences in demographics at our center. Methods: For all E patients, demographic data is collected in a clinical trial database. For evaluated NE patients, data was captured through a ‘non-protocol’ form. A univariate analysis was performed on the demographic data, including gender, age, race, and insurance status, for each year to determine if there were differences in patients E vs NE on a therapeutic clinical trial. Results: From June 2003 through December 2005, there were 912 E patients and data available on 474 NE patients. The results were consistent for each year from 2003 to 2005, and therefore combinable, with no statistical difference in any parameter for E patients versus NE patients during any year with the exception of gender (p=0.05; Chi-square). The distribution of patients E by gender is 52% (474/912) female vs 48% (438/912) male and NE is 69% (325/474) female vs 31% (149/474) male. The mean age of E patients was 55 vs 56 years for NE patients, with 32% vs 33% representing those &gt;65years, respectively. For the E patients, 84% were white, 7.2% black, 4.6% Asian, 4.2% unknown, and 0.4% Hawaiian/Pacific Islander (H/PI). For the NE patients, where race was not consistently available, 65% were white, 9.3% black, 3.2% Asian, 20.5% unknown, and 2.1% H/PI. In both groups, most patients had private insurance (E 60%, NE 54%), followed by Medicare (E 27.5%, NE 29%), Medicaid (E 4%, NE 9%), self pay (E 7.5%, NE 7.4%), and unknown (E 1.3%, NE 0.4%). Conclusions: When comparing E vs NE patients, gender was the only factor that differed significantly. Although this result suggests that males were more likely to be E in a clinical trial, this finding should be interpreted with caution, since this difference might relate to differences in trial availability. While lower enrollment rates for the elderly and minority patients have been identified nationally, enrolling this group of patients does not appear to be a barrier at our center. No significant financial relationships to disclose.
IB-09 * STING AGONIST INDUCES POTENT ANTI-GLIOMA IMMUNITY VIA INDUCTION OF TYPE-I IFN SIGNALS IN THE TUMOR MICROENVIRONMENT
Authors: T. Ohkuri, A. Ghosh, A. Kosaka, J. Zhu, M. Ikeura, M. David, S. Watkins, S. Sarkar, H. Okada
Journal: Neuro-Oncology (2014)

While type-I interferons (IFNs) play critical roles in antiviral and antitumor activity, it remains to be elucidated how type-I IFNs are produced in sterile conditions of the tumor microenvironment and directly impacts tumor-infiltrating immune cells. We report that both human and de novo mouse gliomas show increased expression of type-I IFN messages, and in mice, CD11b+ brain-infiltrating leukocytes (BILs) are the main source of type-I IFNs that is induced partially in a STING (stimulator of IFN genes)-dependent manner. Consequently, glioma-bearing StingGt/Gt mice showed shorter survival, and lower expression levels of Ifns compared with wild-type mice. Furthermore, BILs of StingGt/Gt mice show increased CD11b+ Gr-1+ immature myeloid suppressor and CD25+ Foxp3+ regulatory T (Treg) cells, while decreased IFN-g-producing CD8+ T cells. CD4+ and CD8+ T cells that received direct type-I IFN signals demonstrate lesser degrees of regulatory activity and increased levels of antitumor activity, respectively. Finally, intratumoral administration of a STING agonist (cyclic diguanylate monophosphate; c-di-GMP) improves the survival of glioma-bearing mice associated with enhanced type-I IFN signaling, Cxcl10 and Ccl5 and T cell migration into the brain. In a combination with subcutaneous OVA peptide-vaccination, c-di-GMP increased OVA-specific cytotoxicity of BILs and prolonged the survival. These data demonstrate significant contributions of STING to antitumor immunity via enhancement of the type-I IFN signaling in the tumor microenvironment, and imply a potential use of STING agonists for development of effective immunotherapy, such as the combination with antigen-specific vaccinations.
Sex, Trials, and Datatapes
Authors: R. S. Ungerleider, M. A. Friedman
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Sex, Trials, and Datatapes Get access Richard S. Ungerleider, Richard S. Ungerleider Cancer Therapy Evaluation Program, Division of Cancer Treatment. National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael A. Friedman Michael A. Friedman * Cancer Therapy Evaluation Program, Division of Cancer Treatment. National Cancer InstituteBethesda, Md. * Correspondence to: Michael A. Friedman, MD. Executive Plaza North, Room 742F, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 1, 2 January 1991, Pages 16–17, https://doi.org/10.1093/jnci/83.1.16 Published: 02 January 1991 Article history Received: 15 October 1990 Accepted: 16 October 1990 Published: 02 January 1991
Abstract 10476: Effect of High-dose Oral Multi-vitamins and Minerals in Patients Not Treated With Statins in the Trial to Assess Chelation Therapy
Authors: Gervasio A Lamas, Erminia Guarneri, Daniel B Mark, Robin Boineau, Ryan Bradley, Christine Goertz, Yves Rosenberg, Eldrin F Lewis, Jeanne Drisko, Lauren Lindblad, Kerry L Lee
Journal: Circulation (2015)

Introduction: Trials of conventional dose vitamin therapy have been largely negative for coronary prevention. TACT studied an ultra-high dose regimen of oral multivitamins and multiminerals (MVM) in post-MI patients. Patients off statins were a pre-specified subgroup. Methods: 1708 patients were randomized in a double-blind factorial trial, to EDTA-based chelation or placebo, and oral MVM or oral placebo. MVM consisted of a 28-component mixture (or placebo), taken as 3 caplets twice daily throughout the 5 year study participation. To our knowledge, the oral antioxidant doses are the highest tested in a clinical trial. The primary endpoint was total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The results of oral vitamins versus placebo were not significant [HR (95%CI) 0.89 (0.75,1.07), p=0.212]. However, the pre-specified subgroup of patients not taking statins demonstrated an interaction with MVM (p=0.012). Both unadjusted analyses and comparisons adjusted for baseline prognostic factors were performed. Results: There were 460 (27%) (MVM: 224, placebo: 236) TACT participants not taking statins at baseline. Common reasons were: patient refusal 32%, physician preference 28%, and other 23%. Median duration of MVM therapy was 31 months (IQR 13-59 months).76% of patients completed one full year on vitamins, while 48% completed all 5 years. MVM patients had a 38% reduction in the primary composite endpoint compared with placebo (HR = 0.62, 95% CI: 0.44-0.87, p=0.006, FIGURE). Adjusted analyses reduced the significance of the findings without materially changing the HR (HR = 0.67, 95% CI: 0.47, 0.96, p=0.03). In patients taking statins, there was no beneficial effect of MVM (p=0.774). Conclusion: The present analyses cannot exclude a beneficial effect of MVM treatment for post-MI patients not taking statins. This unexpected result deserves confirmatory testing since it could be quite useful in practice if correct.
Gastric penetration of epicardial pacemaker leads 8 years after cardiac surgery
Authors: T. Molnár, K. Farkas, A. Palkó, E. Eszlári, M. Bitay, E. Nagy, A. Pálinkás, F. Nagy, G. Bogáts, T. Wittmann
Journal: Endoscopy (2010)

Foreign bodies penetrating the gastric wall from the serosal side occur infrequently in endoscopic practice. A 79-year-old man with a 1-month history of weakness and black stool was referred to our department. He had undergone an aortic valve replacement and coronary artery bypass grafting in 2001. Laboratory findings showed anemia. Diagnostic gastroscopy revealed erosions on the anterior wall of the body of the stomach, in the middle of which two wires were detected penetrating into the gastric lumen ([Fig. 1]).
PTH-112 Infliximab Promotes Steroid free Remission in Patients with Chronic Active Ulcerative Colitis– a UK Single Centre Experience
Authors: T C Shepherd, K Greveson, E Cronin, G Erian, F Jaboli, E Despott, M Hamilton, C Murray
Journal: Gut (2013)

<h3>Introduction</h3> The role of infliximab (IFX) in the salvage treatment of acute severe ulcerative colitis (UC) is well established and both licenced and approved in the UK. Studies have demonstrated that IFX IS effective in the treatment of chronic steroid dependent/refractory UC <sup>(1)</sup> In the UK IFX is not routinely approved for the treatment of chronic steroid-dependent colitis. Our aim was to assess the long-term outcomes of patients treated with IFX for chronic active UC in a single UK IBD centre. <h3>Methods</h3> A retrospective single centre review was undertaken of patients with severe active UC who received IFX (5mg/kg) between May 2008 and April 2012. Clinical remission was defined as complete steroid withdrawal, normalisation of bowel frequency and absence of blood with defecation. Treatment with IFX was only continued if steroid free remission was maintained. <h3>Results</h3> 23 patients were included.10 (43%) of patients were treated with induction therapy only (0, 2 &amp; 6 wks) due to funding constraints. 6 (60%) of this group were not on thiopurines, having been either unresponsive or intolerant. 5 (50%) entered clinical remission-median follow up 18 months (IQR 15–25) &amp; 2 (20%) had colectomy. 13 (57%) were treated with induction and maintenance therapy. Of these 7 (85%) were already established on a thiopurine without clinical response. All 13 (100%) entered clinical remission as defined, median follow up 21 months (IQR 11–26). 1 patient required dose escalation to 10mg/kg. None of the patients in the maintenance group were admitted during this time. No significant side effects were reported in either group. <h3>Conclusion</h3> In our patients treated with IFX for chronic active UC, IFX maintenance therapy appears to have more sustained steroid free remission rates compared with induction therapy only. All patients treated this way avoided colectomy, hospital admission and had complete steroid free remission during follow-up. Experience of maintenance IFX therapy for UC in the UK is limited due to funding constraints but our data confirms the efficacy of this approach in carefully selected patients the response rate may be higher than in other published series. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Rutgeerts P, Sandborn WJ, Feagan BG,<i> et al.</i> Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005; 353:2462–2476.
FRI0214 Rituximab in rheumatoid arthritis – interim analysis of the non-interventional bridging study
Authors: A. Krause, P.-M. Aries, H.-M. Lorenz, U. Müller-Ladner, G. Neeck, H. Rusch, J. Wendler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The BRIDGING study collects clinical routine data on the efficacy and safety of rituximab (RTX) in patients suffering from severe active rheumatoid arthritis (RA). <h3>Methods</h3> BRIDGING is an ongoing German prospective, non-interventional study with a duration of observation of 6 months for each patient and – in case of re-therapy – for another 6 months. Data to be recorded are treatment data, relevant data on the course of RA such as activity scores, pain intensity and adverse events (AE). In total, the documentation of 1,600 patients is intended. <h3>Results</h3> As yet baseline data of 1327 patients are available. 72.5% of the patients are female, 40.2% smokers or ex-smokers. 57.2% had positive anti-CCP and 70.1% positive rheumatoid factors. The mean age was 60.1 years, the mean baseline DAS28 was 5.3. 68.9% received pre-treatment with DMARD+TNF, another 6.4% other medications in addition, 23.7% received only DMARDs and 0.8% only TNFi. In 757 of the 1327 patients with active RA (DAS28&gt;3.2 at baseline) a duration of observation of at least 24 weeks was documented. 635 of these patients were seropositive, 66 seronegative (56 no data). Non-smokers had a lower rate of positive anti-CCP (57.3%) than smokers (68.0%) and ex-smokers (65.2%). All 757 patients received the first RTX infusion, 693 patients also the second; the dosage was 1000 mg in 97.8% and 97.7% of patients, resp. The scores for pain intensity, HAQ and DAS 28 are shown in Table 1 for seropositive and seronegative patients. Mean improvement of DAS 28 after 24 weeks was 1.7. DAS 28 improvement was not dependent on pre-treatment and not affected by tuberculosis, solid tumors or lymphoma as concomitant diseases or by smoking. At week 24 the DAS28 was available in 384 patients: LDA (low disease activity) was reached in 29.7%, remission in 16.4%; moderate and good EULAR response was achieved in 47.7% and 26.8% of patients, resp. In total, 948 AEs were reported in 394 of the 1327 patients incl. 89 serious RTX adverse drug reactions (ADRs). Among these were 19 serious infectious ADRs, representing a rate of 4.2 per 100 patient years. There was no case of newly acquired tuberculosis. One patient died during the observational period. <h3>Conclusions</h3> Following RTX therapy, improvements of all activity parameters could be shown in extensively pre-treated patients suffering from severe RA. Safety results correspond with the known safety profile of RTX. The study confirms the benefit of RA patients from RTX therapy in daily clinical practice. <b>Disclosure of Interest</b>: A. Krause Consultant for: Roche, P.-M. Aries Consultant for: Roche, H.-M. Lorenz Consultant for: Roche, U. Müller-Ladner Consultant for: Roche, G. Neeck: None Declared, H. Rusch Employee of: Roche Pharma AG, J. Wendler Consultant for: Roche
Chronic Active and Lupoid Hepatitis Caused by a Laxative, Oxyphenisatin
Authors: Telfer B. Reynolds, Robert L. Peters, Suyenori Yamada
Journal: New England Journal of Medicine (1971)

Abstract In six patients with chronic constipation, chronic active liver disease developed after one to two years of daily ingestion of laxative preparations containing oxyphenisatin; in a seventh liver disease occurred after ingestion of laxatives of unknown composition. Clinical features were jaundice, fatigue, firm hepatomegaly and, occasionally, spider angiomas and splenomegaly. Laboratory abnormalities included an increase in transaminase activity of 10 to 40 times, decreased prothrombin, depressed serum albumin and raised globulin. Two patients had positive LE-cell tests, two others had antinuclear antibody and three had smooth-muscle antibody; none had hepatitis-associated antigen. Liver biopsies showed areas of collapse and fibrosis, with stromal lymphocytic infiltrate and focal areas of hepatocytolysis. All patients improved after changing laxatives. Challenge with oxyphenisatin in three patients caused abrupt rises in transaminase activity. A toxic etiology should be considered, therefore, in al...
Tips for a Physician in Getting the Right Job, Part XII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2014)

The type and caliber of the questions asked by a job hunter is one of the ways an interviewer will evaluate the candidate. Questions that show poor preparation should not be asked, such as failure to read what the employer sent to the job seeker or not doing elementary research on the practice, the organization, or the community. Asking about insignificant details also is not helpful. Not having any good questions to ask is a negative in an interview. This article discusses many possible important questions for the applicant to ask during an interview.
CLINICAL USEFULNESS OF 3D SPECKLE TRACKING STRAIN ACUTELY ONSET AFTER STEMI
Authors: Noriaki Iwahashi, Masaomi Gohbara, Kozo Okada, Nobuhiko Maejima, Mitsuaki Endo, Kengo Tsukahara, Yoshio Tahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura, None Yo
Journal: Journal of the American College of Cardiology (2013)
Abstract 2157: Is CDK6 the target of amplification at 7q21 in esophageal adenocarcinoma
Authors: Amin Ismail, Zhongren Zhou, Liana Toia, Marie Reveiller, Santhoshi Bandla, Arjun Pennathur, James Luketich, Tony Godfrey
Journal: Cancer Research (2010)

Abstract Introduction: The cyclin-dependent kinase 6 (CDK6) is a positive regulator of the cell cycle. It binds to D-type cyclins and phosphorylates the pRb tumor suppressor proteins allowing progression through the G1-phase of the cell cycle. Amplification of the 7q21 chromosomal region has been reported in esophageal adenocarcinoma (EAC) and it has been proposed that CDK6 is the key gene targeted by this event. However, overexpression of CDK6 in vitro suppresses proliferation of breast cancer cells and causes nuclear accumulation of pRb2 tumor suppressor protein. Thus, it remains unclear whether amplification and overexpression of CDK6 is truly driving the 7q21 amplicon in EAC. Methods: For DNA copy number analysis we analyzed genomic DNA from 83 EAC tumors using Affymetrix 6.0 SNP arrays. Protein expression was analyzed in tissue microarrays comprised of 116 independent EAC samples and pre-EAC lesions (15 high grade dysplasia (HGD), 18 low grade dysplasia (LGD), and 283 cases of columnar cell change (CCM)) using a monoclonal antibody against CDK6. CDK6 was overexpressed by stable transfection of OE19, OE33 and Flo1A esophageal cancer cells using CDK6 cDNA under the control of the pCMV promoter. Results: The microarray DNA copy number analysis showed amplification of the 7q21 region in at least 25% of cases. The minimal amplicon contained CDK6 along with 4 other genes. Immunohistochemistry showed both cytoplasmic and nuclear CDK6 staining in EAC (36, 31.3%), HGD (6, 40.0%), LGD (5, 27.7%), and the CCM (29, 10.2%). Overexpression of CDK6 in EAC cell lines caused either suppression of proliferation and anchorage independence (OE19 cells) or had no effect on proliferation (OE33 and Flo1A cells). The suppression of proliferation in OE19/CDK6 cells is dependent on the kinase activity of CDK6 as OE19 cells overexpressing a kinase-deficient form of CDK6 proliferate normally. As previously reported in breast cancer cells, pRb2 (p130) tumor suppressor protein is upregulated in OE19/CDK6 cells. The upregulation of pRb2, however, does not seem to account for the hypo-proliferative effect of OE19/CDK6 cells as it is also upregulated in normally proliferative cells that overexpress the kinase-negative form of CDK6. Conclusion: Although CDK6 is amplified and overexpressed in EAC and its preneoplastic lesions, it does not seem to account for the tumorigenic importance of the 7q21 amplicon. CDK6 overexpression in vitro does not show any mitogenic phenotype in EAC tumor cells. The presence of other genes within the minimal amplicon raises the possibility that one or more of them might drive such a potential. 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 2157.
Abstract 2097: ARHI (DiRAS3): A novel component in the formation of the autophagy initiation complex
Authors: Zhen Lu, Warren S. Liao, Maojie Yang, Fengqin Gao, Robert Bast
Journal: Cancer Research (2011)

Abstract The maternally imprinted Ras-related tumor suppressor gene Aplasia Ras homolog member I (ARHI; also known as DiRAS3) is downregulated in more than 60% of ovarian cancers. We reported that re-expression of ARHI in vitro at physiologic levels induces autophagy by blocking PI(3)K-Akt signaling and inhibiting mTOR activity, and participates directly in the autophagic vesicles, co-localizing with MAP-LC3-II in the vesicle membrane. Nucleation of autophagic vesicles is controlled by the activity and formation of multi-protein complexes that include Beclin-1 and several other positive and negative regulators. While binding of Beclin-1 to Vps34 and ATG14 forms proautophagic complexes to promote autophagy, binding of Bcl-2 to Beclin-1, however, disrupts the Beclin-1:Vps34 interaction and inhibits autophagy. The mechanisms that regulate the switch between different binding partners to Beclin-1, and therefore controls the level of autophagy is not clear. Here we report that ARHI physically interacts with endogenous Beclin-1 and Vps34 in ovarian cancer cells. Interaction with ARHI decreases the association between Beclin-1 and its negative regulator Bcl-2, by disrupting Beclin-1 homodimerization. An N-terminal deletion of ARHI that cannot induce autophagy fails to block Beclin-1 homodimerization and cannot disrupt Beclin-1:Bcl-2 interaction. Consistent with its role in promoting the formation of autophagy initiation complex, cells with knockdown of ARHI fail to respond to starvation-mediated dissociation of Beclin-1:Bcl-2 interaction and are unable to induce Beclin-1:Vps34 complex formation. Finally, ARHI knockdown decreases PI(3)KC3 activity and reduces starvation-mediated autophagy. Taken together, our results suggest that ARHI is a positive and necessary regulator of Beclin-1:Vps34 complex and that ARHI regulates starvation-mediated autophagy by promoting the formation of the autophagy initiation complexes. 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 2097. doi:10.1158/1538-7445.AM2011-2097
SP0013 The young adult with juvenile idiopathic arthritis - key clinical issues
Authors: H. Foster
Journal: Annals of the Rheumatic Diseases (2013)

Many children and young people with Juvenile Idiopathic Arthritis have ongoing problems with active disease or sequelae from previous disease or treatments. Many require continuity of care into adulthood and pose a number of clinical challenges within adult musculoskeletal services. This talk will cover key clinical issues that arise, present a review of the literature and provide guidance for management. Topics to be included are the role of biologic agents (and factors that influence the choice of agent), uveitis, osteoporosis, pregnancy, surgery and cardiovascular disease. The role of specialist services and the need for training is emphasised. <h3>Disclosure of Interest</h3> H. Foster Grant/Research support from: Pfizer, Genzyme, BioMarin