tbuckley/cabot-search huggingface dataset:
Abstract 3111: Synthetic lethality in head and neck cancer
Authors: Shayanne A. Lajud, Taku Yamashita, Ziying Han, Jun Zheng, Anas Mouchli, Orysia Bezpalko, Bert W. O'Malley, Daqing Li
Journal: Cancer Research (2012)

Abstract Current treatment for advanced stage head and neck squamous cell carcinoma (HNSCC) typically include both radiation and chemotherapy, which is associated with significant morbidity. Our main objective was to explore a novel adjuvant molecular therapy approach to minimize the chemoradiation-induced side effects and toxicities, while maintaining therapeutic anti-tumor effects in HNSCC through the mechanism of synthetic lethality that has been already exploited to a limited extent in clinical trials for breast cancer. It has been demonstrated that synthetic lethality is based on the roles of Poly(ADP-ribose)polymerase-1 (PARP-1) in DNA single-stranded break (SSB) repair, and BRCA-1 and -2 in double-stranded break (DSB) repair. By simply inhibiting PARP-1 in tumor cells carrying a mutation in the Brca genes, one would expect complete tumor regression. The MRN complex (Mre11, Rad50, and Nbs-1) is well recognized as a key sensor of DSBs and acts by recruiting and activating DNA damage response proteins. These concepts led us to investigate the concept of introducing a mutation to the MRN complex, in combination with PARP-1 inhibition, thereby creating “dual hits” that would result in synthetic lethality within tumors expressing wild-type Brca genes such as HNSCC. Human HNSCC tumor cell lines and a mouse model with human HNSCC were used in the study. Wild-type MRN and PARP expressions were detected in these tumor cells. In vitro and in vivo studies were performed to evaluate synthetic lethality effects after combining PARP-1 inhibition with adenovirus-mediated Nbs-1 (Ad-Nbs-1) gene transfer treatment, which we had previously shown to impair MRN expression. Telomere length was measured to investigate the potential mechanism of synthetic lethality. Our study demonstrates that significant synthetic lethality was found with combined PARP-1 inhibition and Ad-Nbs-1 treatment in both in vitro and in vivo experiments; it also suggests that the telomere maintenance may play an important role in synthetic lethality. In conclusion, we propose an important novel mechanism responsible for the synthetic lethality of PARP-1 inhibitors and MRN disruption based on their roles on telomere maintenance. Our findings emphasize the potential benefits of our therapeutic approach and deserve further investigation to help obviate the toxicities associated with existing treatment regimens for HNSCC patients. 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 3111. doi:1538-7445.AM2012-3111
Acute Benign Pericarditis
Authors: Morton G. Brown
Journal: New England Journal of Medicine (1951)

PERICARDITIS not associated with tuberculosis, rheumatic fever or other expected causes was the subject of a study by Barnes and Burchell1 in 1942. Certain features of this disorder, such as the rapid changes in heart size,2 the difficulty in differential diagnosis from acute coronary occlusion,3 the specificity of the electrocardiographic pattern,4 and the lack of complications,5 , 6 have been commented on in subsequent reports. Few data concerning the subsequent courses of these patients have been recorded.During the past four years 13 patients with acute pericarditis have been studied at this hospital. Case reports concerning 7 of these patients illustrating the . . .
Abstract 5066: Genome sequence and epigenome map of bladder cancer development from occult field effects
Authors: Bogdan A. Czerniak, Tadeusz Majewski, Jolanta Bondaruk, Shizhen Zhang, Sangkyou Lee, Keith Baggerly, Colin Dinney, H. Barton Grossman, Xifeng Wu, Jean-Pierre Issa, Wei Zhang, Richard Gibbs, Steven E. Scherer
Journal: Cancer Research (2012)

Abstract We are pursuing a unique strategy to identify early events in bladder cancer development by the genome-wide analysis of somatic changes in tissues from resected bladders and characterized pathologically as urothelial carcinoma. We then extend this analysis into precursor intraurothelial lesions and normal tissue. Here we report on the construction of a high resolution whole-organ histologic and genetic map of bladder cancer development that tracks its progression from in situ precursor conditions to invasive clinically aggressive cancer using total genome and exome sequencing and complemented with HumanOmni 2.5-8 v1 SNP-based Illumina genotyping, combined with CpG island methylation and cDNA microarray platforms derived from 12 whole-organ cystectomy specimens with invasive urothelial carcinoma. This approach provided a high resolution integrated map of structural genome, epigenome, and transcriptome alterations that parallel the development of bladder cancer from early field effects to invasive disease. By analyzing genome-wide patterns of structural genomic, epigenomic, and transcriptome changes, we found three major waves of alterations associated with growth advantage of successive clones reflecting a stepwise conversion of normal urothelial cells into cancer cells. This approach is significant for the identification of specific chromosomal regions as well as epigenetically and transcriptionally modified gene ontologies involved in early clonal expansion of intraurothelial neoplasia and their clonal evolution to carcinoma in situ progressing to invasive cancer. These studies suggest involvement of specific gene networks in early clonal expansion of intraurothelial neoplasia antecedent to microscopically recognizable precursor lesions such as dysplasia and carcinoma in situ. This map represents a prerequisite for specific studies on the mechanisms of incipient phases of bladder cancer development and should have a significant impact on the understanding of human carcinogenesis. 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 5066. doi:1538-7445.AM2012-5066
Digoxin Therapy and Mortality after Myocardial Infarction
Authors: J.E. Muller, Z.G. Turi, P.H. Stone, R.E. Rude, D.S. Raabe, A.S. Jaffe, H.K. Gold, N. Gustafson, W.K. Poole, E. Passamani, T.W. Smith, E. Braunwald
Journal: New England Journal of Medicine (1986)

Recent studies have led to controversy about whether long-term digoxin therapy after confirmed or suspected myocardial infarction increases mortality. We analyzed the mortality experience in 903 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS). As in previous studies, the decision to treat or not to treat with digoxin was made by the patient's personal physician on the basis of the usual clinical indications. Cumulative mortality was 28 percent for the 281 digoxin-treated patients as compared with 11 percent for the 622 patients who did not receive digoxin (P less than 0.001; follow-up interval, six days to 36 months; mean, 25.1 months). However, patients treated with digoxin had more base-line characteristics predictive of mortality than did their counterparts. Adjustment for these differences with two separate applications of the Cox method yielded P values of 0.14 and 0.34 for tests of difference in mortality, providing no evidence for a significant excess mortality associated with digoxin. Thus, the findings in the MILIS population do not support the assertion that digoxin therapy is excessively hazardous after infarction, but the existence of an undetected harmful effect can only be excluded with a randomized study. Until the results of such a study are available, we recommend careful consideration of whether any treatment of ventricular dysfunction is actually needed, consideration of alternatives to digoxin therapy, and restriction of digoxin use to the subgroup of patients (with severe chronic congestive failure and a dilated left ventricle) previously shown to have a beneficial clinical response.
Abstract 1537: Role of S100PBP in pancreatic adenocarcinoma
Authors: Kate E. Lines, Namaa Audi, Claude Chelala, Nilu Wijesuriya, Hemant Kocher, Helen Hurst, Tatjana Crnogorac-Jurcevic
Journal: Cancer Research (2011)

Abstract We have recently discovered a 37kDa novel S100P-binding protein, S100PBP which exhibits no homology to any currently known protein. We have therefore explored its expression in a wide range of normal and cancer tissues, and performed several in vitro functional assays to define its putative roles. In order to determine S100PBP localization in human samples immunohistochemistry was performed on a multi-organ tissue array (Pantomics) and on an in-house made pancreatic tissue array including normal pancreas, primary cancer and metastatic lesions. To determine S100PBP functions cells with both silenced and stably over-expressing S100PBP were established. Affymetrix gene expression arrays and a battery of functional assays including adhesion, migration and invasion were performed using these cells. We show that S100PBP is ubiquitously expressed in different normal and tumor specimens in a cell and tissue type dependent manor. In normal pancreas S100PBP is widely expressed in both exocrine and endocrine compartments while in pancreatic adenocarcinoma it is present in early precursor lesions, PanINs, and retained in some cancer cells, but with significantly lower intensity. We further show that in pancreatic cancer cells S100PBP binds, in addition to S100P, several other S100 proteins, namely S100A2, S100A4 and S100A6 in a calcium-dependant fashion. Over-expression of S100PBP also causes changes in the expression levels of S100P and S100A9, which were both down-regulated, while the levels of the S100A4 transcript increased. Furthermore, manipulation of S100PBP expression leads to phenotypic changes affecting the adhesive, migratory and invasive capacity of pancreatic cancer cells, which varied depending on the cellular context and constellation of presence of different S100 proteins. Both over-expression and silencing of S100PBP also induced an increase/decrease in Cathepsin Z levels, respectively. This protease appears to be critically important for inducing the observed changes in cellular adhesion. In summary, S100PBP is ubiquitously expressed and modulates the function of several S100 proteins, as well as Cathepsin Z, and appears to play an important role in the adhesive, migratory and invasive capabilities of pancreatic cancer cells. 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 1537. doi:10.1158/1538-7445.AM2011-1537
Can genetics explain the higher risk of worsening knee pain in offspring of people with total knee replacement for severe primary knee osteoarthritis?
Authors: Ting Zou, Li Yang, Ashley M Lee, Xia Tan, Elizabeth Wong, Harrison X Bai
Journal: Annals of the Rheumatic Diseases (2016)

those with severe knee osteoarthritis (OA) had an increased risk of worsening knee pain over 8 years when compared with controls who had no family
Abstract 4151: High definition circulating tumor cells in patients with non-small cell lung cancer
Authors: Marco Wendel, Lyudmila Bazhenova, Jorge Nieva, Kelly Bethel, Dena Marrinucci, Edward H. Cho, Craig Yoshioka, Madelyn Luttgen, Loressa Uson, Thomas Metzner, Anand Kolatkar, Melissa Torrey, Peter Kuhn
Journal: Cancer Research (2011)

Abstract Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast, and colorectal cancer. However, there is little knowledge about CTC incidence rates and morphologic heterogeneity in non-small cell lung cancer (NSCLC) and their correlation to disease progression and usability for clinical staging. Here, we present a fluid phase biopsy approach that identifies CTCs without surface receptor-based enrichment, and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. The HD-CTC assay will be used to monitor HD-CTC counts and morphology in early stage, locally advanced, and metastatic NSCLC patient over time. 150 newly diagnosed NSCLC patients are being enrolled for this project. At the time of diagnosis 50 of the patients will have early stage cancers (stage I-II); 50 patients will have locally advanced (stage III) cancers, and 50 will be patients presenting with metastatic (stage IV) disease. Blood samples from each patient will be obtained at the time of diagnosis and 6 months later. We present here an interim data set that shows an incidence rate of 78% at baseline with a median CTC count of 19.5/ml of blood (range 0-441.6). Our preliminary data demonstrates that, despite stringent morphologic inclusion criteria for the definition of HD-CTCs, our HD-CTC assay shows high sensitivity in the detection of lung cancer CTCs. 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 4151. doi:10.1158/1538-7445.AM2011-4151
PTU-294 Responsibility deal: has the uk billion unit alcohol reduction pledge really been achieved? implications for future policy
Authors: C Record
Journal: Gut (2015)

<h3>Introduction</h3> A reduction in the overall strength of alcohol products with stable alcohol volumes has the potential to considerably reduce alcohol harm. In 2011 a consortium of alcohol producers and retailers pledged to remove 1 billion units from the market by reducing product strength and on Dec 19<sup>th</sup>2014 the Health Improvement Analytical Team of the Department of Health reported<sup>1</sup>that 1,346 million units were removed from the market between 2011 and 2013. If true, this is a substantial improvement and will be welcomed by those concerned with alcohol harm reduction. <h3>Method</h3> UK HMRC alcohol clearance (consumption) data<sup>2</sup>over the past 10 years was analysed. <h3>Results</h3> The reduction in the number of units between 2011 and 2013 has mainly been achieved by reductions in the average strength of beer, which has reduced from between 4.53 and 4.40% in the years 2004 to 2011 to 4.14% in 2013. This accounted for 1.2 billion of the 1.3 billion total reduction. Since there were only minor reductions in the strength of wine and cider while spirit strength increased the evidence suggests that the reduction in beer strength is most likely to have been due to the simultaneous introduction of a 25% tax supplement on high strength and a 50% tax rebate on low strength beers rather than through the operation of the pledge. <h3>Conclusion</h3> The UK Government should encourage and support the removal of alcohol units from the market by relating duty on all alcohol products more closely to their strength. In particular they should reduce the strength of beer attracting the high strength tax supplement from &gt;7.5% to &gt;5%, apply the high strength supplement to cider &gt;5% and to wine &gt;10%, and apply the tax rebate to cider &lt;2.8%. Alcohol harm currently costs the nation 21 billion pounds per year. A 2.5% reduction in alcohol consumption (1.25 billion units) would lead to a total cost reduction for health, crime and workplace absences of 5.1 billion pounds over 10 years.<sup>3</sup>Thus for a meaningful reduction in alcohol harm there needs to be a much greater unit reduction than currently pledged. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Responsibility Deal: Monitoring the number of units of alcohol sold. Second interim report, 2013 data:- https://www.gov.uk/government/statistics/units-of-alcohol-sold https://www.uktradeinfo.com/Statistics/Tax%20and%20Duty%20Bulletins/Alcohol1014.xls <i>Making the case for a minimum unit price in England and Wales,</i>Alcohol Health Alliance Briefing Paper 2014
CD27 Agonism Plus PD-1 Blockade Recapitulates CD4+ T-cell Help in Therapeutic Anticancer Vaccination
Authors: Tomasz Ahrends, Nikolina Bąbała, Yanling Xiao, Hideo Yagita, Hans van Eenennaam, Jannie Borst
Journal: Cancer Research (2016)

While showing promise, vaccination strategies to treat cancer require further optimization. Likely barriers to efficacy involve cancer-associated immunosuppression and peripheral tolerance, which limit the generation of effective vaccine-specific cytotoxic T lymphocytes (CTL). Because CD4(+) T cells improve CTL responsiveness, next-generation vaccines include helper epitopes. Here, we demonstrate in mice how CD4(+) T-cell help optimizes the CTL response to a clinically relevant DNA vaccine engineered to combat human papillomavirus-expressing tumors. Inclusion of tumor-unrelated helper epitopes greatly increased CTL priming, effector, and memory T-cell programming. CD4(+) T-cell help optimized the CTL response in all these aspects via CD27/CD70 costimulation. Notably, administration of an agonistic CD27 antibody could largely replace helper epitopes in promoting primary and memory CTL responses, acting directly on CD8(+) T cells. CD27 agonism improved efficacy of the vaccine without helper epitopes, more so than combined PD-1 and CTLA-4 blockade. Combining CD27 agonism with CTLA-4 blockade improved vaccine-induced CTL priming and tumor infiltration, but only combination with PD-1 blockade was effective at eradicating tumors, thereby fully recapitulating the effect of CD4(+) T-cell help on vaccine efficacy. PD-1 blockade alone did not affect CTL priming or tumor infiltration, so these results implied that it cooperated with CD4(+) T-cell help by alleviating immune suppression against CTL in the tumor. Helper epitope inclusion or CD27 agonism did not stimulate regulatory T cells, and vaccine efficacy was also improved by CD27 agonism in the presence of CD4(+) T-cell help. Our findings provide a preclinical rationale to apply CD27 agonist antibodies, either alone or combined with PD-1 blockade, to improve the therapeutic efficacy of cancer vaccines and immunotherapy generally. Cancer Res; 76(10); 2921-31. ©2016 AACR.
Kidney Patients Poll Experts, Fight for Approval of Interleukin-2
Authors: Jill Waalen
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Kidney Patients Poll Experts, Fight for Approval of Interleukin-2 Get access Jill Waalen Jill Waalen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 324–325, https://doi.org/10.1093/jnci/83.5.324 Published: 06 March 1991
A straw man's neogenome
Authors: Oscar Vilarroya
Journal: Behavioral and Brain Sciences (2012)

Abstract The neogenome has indeed changed how to understand the relationship between genotype and phenotype. However, this does not imply a paradigm shift, but simply a normal development of a young science. Charney creates a straw man out of the myth of an immutable genetics, and conveys the wrong idea that heritability studies and gene association studies are no longer valid.
Abstract 477: CD49fhi/CD90lo from primary human osteosarcoma cells are enriched for tumor initiating property
Authors: Patrice Penfornis, David Z. Cai, Michael R. Harris, Spandana Induru, Mark Meyer, Radhika R. Pochampally
Journal: Cancer Research (2011)

Abstract Osteosarcoma (OS) is one of the most prolific forms of cancer among adolescents, resulting in a severe decrease in life expectancy unless detected early. Though several previous studies have suggested various tumor-initiating properties of osteosarcoma, major limitations for understanding have been observed due the OS's restrictive ability to expand in in vivo models. In this study, we are reporting the use of primary osteosarcoma cells for characterizing the tumor initiating property. Human OS samples were collected during biopsies or surgeries, expanded in vitro, phenotyped for multiple cell-surface markers by Fluorescence Activated Cell Sorting (FACS) analysis and then injected subcutaneously into nu/nu mice. We observed that cells showing an expression of the CD49fhi/CD90lo cell surface marker produced a more aggressive tumor. In vitro treatment of this cell population with amiloride, a potassium-sparing diuretic, decreased the cells ability to express the CD49f protein. In vivo, amiloride treatment also dramatically decreased tumor growth when injected into nu/nu mice when compared to controls, indicating that CD49fhi/CD90lo is an important marker in tumor initiation. The transfection of CD49fhi cells with a shCD49f lentiviral construct showed a 20% decrease in their overall ability to migrate in a trans-well assay, and experienced a two-fold decrease in their capability to form colonies (CFU assay). Subcutaneous injections of the transfected cells expressing shRNA for CD49f reduced tumor growth by 30% compared to controls. In conclusion, our data suggests that the CD49fhi/CD90lo cell population is linked to a more aggressive osteosarcoma tumor growth and that this cell surface marker could be a potential candidate for the characterization of TICs in osteosarcoma. 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 477. doi:10.1158/1538-7445.AM2011-477
Use of alcohol to reduce stress
Authors: A. M. Thornett, R. Thornett
Journal: BMJ (2014)

The association between parental influence during childhood and the consumption of alcohol by children in adult life noted by Gornall is an important reason for introducing minimal pricing for alcohol.1 Reducing consumption through price increases has the potential to break such familial cultural norms of behaviour and reduce the detrimental health and economic effects of alcohol. However, we should not ignore other reasons why people drink.

My surgery is located in an affluent suburb of Birmingham. Superficially, alcohol does …