tbuckley/cabot-search huggingface dataset:
Abstract 4753: Ablation of N1-S1 hepatocellular carcinoma in rat livers with nanosecond pulsed electric fields and induction of protective immunity.
Authors: Ru Chen, Nova Sain, Tye Harlow, Peter Shires, Gary Long, Ricahrd Heller, Stephen Beebe
Journal: Cancer Research (2013)

Abstract Nanosecond pulsed electric fields (nsPEFs) could be used to ablate local tumor masses through minimally invasive or open surgery delivery, but further pre-clinical studies are needed. NsPEFs not only induces permanent permeabilization of cells, but also impacts intracellular organelles and result in apoptosis and other forms of cell death in vitro and in vivo. Hepatocellular carcinoma (HCC) is the third most common cancer cause of mortality worldwide. A diagnosis of HCC carries a guarded prognosis, especially when metastasis is documented. Presently, reliable, curative treatments without recurrence for very early, early, and intermediate HCC stages are still in urgent need of attention. In these studies, we specifically test the efficacy of nsPEFs in an orthotopic HCC rat tumor model. Orthotropic insertion of stably transfected (mcherry and/or luciferase) N1-S1 cells in Sprague Dawley rat livers was used as a model for treating HCC. Cells were treated with pulses with 100 ns duration and electric field strengths of 50 kV/cm. Different pulse numbers were applied. Recent results suggest that treatments of 300 or 500 pulses were more effective when separated by a 6 minute interval than when applied as a continuous, uninterrupted single treatment. However over time and treatment of more than 20 animals, 1000 nanosecond pulses treatment consistently showed successful ablation by effectively inducing tumor cell death. A single treatment of 1000 nsPEFs successfully induces cell apoptosis by activating caspase-9, caspase-3, but not caspase-8 in some cells, indicating induction of intrinsic apoptosis mechanisms as well as caspase-independent cell death, like that observed in vitro with human Jurkat cells. More importantly, rats successfully treated with 1000 pulses showed protective responses to a second N1-S1 intra-hepatic challenge injection of N1-S1 cells, suggesting a host immune response, which is under exploration. As an ideal potential therapy for HCC, nsPEFs treatment did not show any damaging impact on liver blood flow. These studies demonstrate for the first time, successful intra-hepatic treatment of HCC with a potential induction of immunogenic cell death and a host immune response after nsPEF ablation. Citation Format: Ru Chen, Nova Sain, Tye Harlow, Peter Shires, Gary Long, Ricahrd Heller, Stephen Beebe. Ablation of N1-S1 hepatocellular carcinoma in rat livers with nanosecond pulsed electric fields and induction of protective immunity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4753. doi:10.1158/1538-7445.AM2013-4753
Abstract 1341: Mice expressing activated PI3K develop advanced colon cancer
Authors: Dustin A. Deming, Alyssa A. Leystra, Zahm D. Christopher, Mohammed Farhoud, Terrah J. Paul Olson, Jaime N. Hadac, Laura A. Nettekoven, Dawn M. Albrecht, Linda Clipson, Ruth Sullivan, Mary Kay Washington, Jose R. Torrealba, Jamey P. Weichert, Richard B. Halberg
Journal: Cancer Research (2012)

Abstract Background: Mutations in PIK3CA are a common feature of human cancers and multiple new PI3K inhibitors are in clinical development. These mutations are present in 20-30% of colorectal cancers in humans; however, the effects of such mutations on the intestinal mucosa have not been previously studied in animal models. Here we demonstrate that the expression of a dominant active form of the PI3K protein in the mouse intestine results not only in hyperplasia but also advanced neoplasia. Methods: Mice carrying a transgene in which the fatty acid binding protein promoter is fused to Cre recombinase (FC) were crossed to mice carrying a transgene encoding a chimeric protein with the iSH2 domain of the p85 subunit fused to the N-terminus of p110 (PIK3ca*). Progeny carrying both transgenes (FC PIK3ca*) express this constitutively active form of p110 in epithelial cells of the distal small bowel and colon. Results: Invasive mucinous adenocarcinomas develop in the proximal colon by only 50 days of age. These tumors are very aggressive, spreading into the mesentery and adjacent organs, and their histological characteristics are strikingly similar to those of invasive colon cancers in humans. Neoplastic cells exhibit a high rate of cell proliferation as seen by increased Ki67 immunohistochemical staining and phosphorylation of AKT, pS6, and p4E-BP1 by western blot demonstrating downstream signaling of PI3K. Interestingly, these cells did not exhibit perturbations in ERK and WNT signaling. Consistent with the lack of aberrant WNT signaling, no benign polypoid intermediaries were identified. Together, the results indicate that tumors in this model form via a non-canonical mechanism. A cohort of FC PIK3ca* mice were imaged by FDG dual hybrid PET/CT colonography and mice with similar sized tumors were divided into control and experimental arms. The experimental arm was treated with rapamycin (6mg/kg/day) for 14 days. Both groups were re-imaged 14 days later. The full results of the rapamycin treatment will be presented. Conclusion: This unique model of advanced colonic invasive adenocarcinomas has the potential to further our understanding of human disease and facilitate the development of therapeutics, especially inhibitors targeting downstream of PI3K. 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 1341. doi:1538-7445.AM2012-1341
Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation
Authors: Seth L. Masters, Vasiliki Lagou, Isabelle Jéru, Paul J. Baker, Lien Van Eyck, David A. Parry, Dylan Lawless, Dominic De Nardo, Josselyn E. Garcia-Perez, Laura F. Dagley, Caroline L. Holley, James Dooley, Fiona Moghaddas, Emanuela Pasciuto, Pierre-Yves Jeandel, Raf Sciot, Dena Lyras, Andrew I. Webb, Sandra E. Nicholson, Lien De Somer, Erika van Nieuwenhove, Julia Ruuth-Praz, Bruno Copin, Emmanuelle Cochet, Myrna Medlej-Hashim, Andre Megarbane, Kate Schroder, Sinisa Savic, An Goris, Serge Amselem, Carine Wouters, Adrian Liston
Journal: Science Translational Medicine (2016)

A mutation in pyrin that disrupts regulation leads to autoinflammatory disease.
Loss of Heterozygosity on Chromosome 11q13 in Microdissected Human Male Breast Carcinomas
Authors: J. Sanz-Ortega, R. Chuaqui, Z. Zhuang, M. E. Sobel, J. Sanz-Esponera, L. A. Liotta, M. R. Emmert-Buck, M. J. Merino
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Loss of Heterozygosity on Chromosome 11q13 in Microdissected Human Male Breast Carcinomas Get access Julian Sanz-Ortega, Julian Sanz-Ortega Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Rodrigo Chuaqui, Rodrigo Chuaqui Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhengping Zhuang, Zhengping Zhuang Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark E. Sobel, Mark E. Sobel Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Julian Sanz-Esponera, Julian Sanz-Esponera Hospital Universitario “San Carlos, ”Madrid, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Lance A. Liotta, Lance A. Liotta Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael R. Emmert-Buck, Michael R. Emmert-Buck Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria J. Merino Maria J. Merino * Department of Surgical Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer InstituteBethesda, MD Correspondence to : Maria J. Merino, M.D., National Institutes of Health, Bldg. 10, Rm. 2N212, Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 18, 20 September 1995, Pages 1408–1410, https://doi.org/10.1093/jnci/87.18.1408 Published: 20 September 1995 Article history Received: 06 February 1995 Revision received: 11 July 1995 Accepted: 18 July 1995 Published: 20 September 1995
AB0652 Relationship of periodontal disease with rheumatoid arthritis
Authors: S. Vahabi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis is the most prevalent chronic inflammatory muscle disease. It is correlated with periodontal disease due to similar factors that exist in their pathogenesis <h3>Objectives</h3> The present study assessed the relationship of periodontal disease with rheumatoid arthritis (RA). <h3>Methods</h3> In this case-control study, 30 RA patients along with similar number of matched controls were selected among patients referred to Imam Khomeini Hospital. Periodontal parameters including plaque index (PI), bleeding on probing (BOP), percentage of sites with CAL≥3mm, percentage of sites with PD≥4mm, clinical attachment loss (CAL) and probing depth (PD) were determined in cases and controls. ESR, number of painful and inflamed muscles and severity of disease were evaluated in RA patients. Periodontal parameters of cases and controls were statistically analyzed by Mann-Whitney U and Student t-tests while the relationship of periodontal parameters with RA findings were assessed by means of Spearman and Pearson's correlation coefficients with an alpha error level less than 0.05. <h3>Results</h3> PD (4.17mm vs. 3.6mm: p&lt;0.0001), CAL (4.89mm vs. 4.18mm; p&lt;0.002), percentage of sites with PD&gt;4mm (58.83% vs. 44.33%; p&lt;0.002), percentage of sites with CAL&gt;3mm (74.13% vs. 64.4%; p&lt;0.001), percentage of sites with bleeding on probing (9.67% vs. 6.87%; p&lt;0.0001) and PI index (85.73% vs. 80.63%; p&lt;0.0001) were significantly higher in RA patients than controls. In this group, direct and significant correlations were found between serologic findings, disease severity and number of painful and inflamed joints with periodontal factors. <h3>Conclusions</h3> Severity of periodontal disease increases in patients with rheumatoid arthritis. Thus, rheumatoid arthritis is a risk factor for periodontal disease. <h3>Disclosure of Interest</h3> None Declared
P1-11-11: Wait Times for Breast Cancer Care in Manitoba 2009–2010. Time To Face the Challenge.
Authors: T Carpenter-Kellett, M Nashed
Journal: Cancer Research (2011)

Abstract Background: Wait times for patients with breast cancer to receive oncological treatment vary significantly. In Manitoba, the radiation treatment wait times improved in the year 2005 compared to 2001. However, other parts of the patient's journey have lengthened and negated the reduction seen in radiation treatment wait times. Aims: To examine the overall time from disease suspicion to treatment of breast cancer patients from June 2009 to June 2010 and to compare to the previously published wait times. Methods: This population-based retrospective study looked at representative samples of women newly diagnosed with breast cancer. Patients were followed from the time of first presentation, either to their family physician or after a suspicious screening mammogram, to the time adjuvant treatment was started. Each patient's journey was subdivided into different chronological stages. The data was compared to the wait times reported in 2005. Results: 363 patients’ data was collected and analyzed. The median elapsed time in days for each phase of the journey was calculated. Total wait times from suspicion to diagnosis were also calculated. The wait times of most stages of the patients’ journey have worsened when compared to 2005. However, there was some improvement in the diagnostic part of the journey. Delays to surgery and pathology have contributed to lengthening of the total journey. There was also a systematic and repetitive administration delay at each transition. Screen-detected cases had a shorter journey than those who presented through a family physician. Conclusions: In spite of improvements achieved in the wait times at some stages of the journey, the total length of the patient journey has not been shortened. This represents not only individual team failures but also a built in complexity in the health system. In order to achieve a meaningful cut in wait times for breast cancer patients, the entire trajectory of care needs to be addressed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-11.
The value of Endoscopic ultrasonography in the assessment of ulcerative colitis
Authors: Guo Wen, Liu Si-de, Bai Lan, Cheng Tian-ming, Chen Cun-long, Zhi Fa-chao, Jiang Bo
Journal: Endoscopy (2011)

Objective: To evaluate the value of endoscopic ultrasonography (EUS) in the diagnosis of ulcerative colitis (UC).
AB0473 Work-related disability in takayasu’s arteritis: a british series
Authors: P. Mehta, J. Mason
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Takayasu’s arteritis (TA) is an inflammatory disorder which is most active during working years, thus affecting productivity. <h3>Objectives</h3> We aimed to survey the frequency and associated reasons of work-related disability amongst patients attending our tertiary referral TA centre and also how work may affect patients’ health with respect to their Takayasu’s arteritis. <h3>Methods</h3> Approval was obtained from the Research Ethics committee. A postal questionnaire survey was sent to 90 patients attending our TA clinic. Consent was implied, by return of questionnaires. <h3>Results</h3> 41 responses were received, 90% were female with a median age of 52 years. The median age at first symptoms was 34 years and at diagnosis of TA 38 years. 63% were White British. 12% had high-school education, 29% university degrees and 24% vocational qualifications. 29% were taking no medication, 59% steroids, 51% immunosuppressants and 2% TNF-blockers.10% considered themselves to have significant co-morbidities (all Crohn’s disease). 17% were homemakers, 27% retired (55% of these were medically retired), 49% employed and 7% unemployed. 81% of the 21 patients currently not working, had been working before TA was diagnosed. 71% of these patients stated they were not working because of TA. The most common reasons for this were claudication (47%) and neurological symptoms/deficit (27%). 43% patients felt their TA had improved after stopping work. Of the 49% working, 70% were full-time and 30% part-time. 85% had made changes to their work because of TA – reduced hours (35%) and changed job (50%). 41% felt their TA had improved after these changes. The mean number of sick days was 5days/year, with 2 days attributed to TA. The mean visual analogue scale assessments for the effect of TA on productivity at work was 7.9, the effect of TA on regular activities was 6.78 and the effect of work on TA was 5.92. <h3>Conclusions</h3> Work-related disability in TA is high and underappreciated. A large number of patients give up work or change their work practice because of TA. Claudication and neurological effects were the most common reasons given. The perceived effects of TA on productivity at work and the effects of work on patients’ health are considerable. <h3>Disclosure of Interest</h3> None Declared
Abstract 4875: Combining immunohistochemistry and proteomics for improved antibody validation in complex FFPE tissues
Authors: Claudia Schuster, Falk Hlubek, Katharina Malinowsky, Sibylle Liebmann, Daniela Berg, Claudia Wolff, Simone Reu, Jens Neumann, Claudius Faber, Heinz Hoefler, Thomas Kirchner, Karl-Friedrich Becker
Journal: Cancer Research (2011)

Abstract Personalized cancer treatment strategies depend on comprehensive and detailed characterization of individual human cancers. Translation of biomarker research into successful and tailored medical therapy at tumor and patient level require the identification and development of informative biomarkers that could be used to improve early diagnosis and prognosis. In clinical pathology, particularly IHC evaluation of biomarkers in tissue is considered as gold standard for diagnostic and therapeutic decisions, having a direct influence on patient management and therapeutic treatment. Although antibody-based approaches are established and successfully integrated into both clinical and research applications, for personalized treatment regimens new demands have been placed on the quality, reproducibility and accuracy of antibody-based assays. There is an ongoing debate on implementation and standardization of validation guidelines to provide for reliable and reproducible antibody-based tools in clinical management and basic research. To overcome variations of epitope specificity in immunohistochemistry, we introduce a novel approach combining extraction of immunoreactive proteins from FFPE tissue with Western Blot analysis and IHC using the same archival tissue of interest for antibody validation. This tandem application allows for specific characterization of the antigen, taking advantage of the main properties of both technologies: localization of the protein of interest in tissue sections stained by IHC and specification of the biochemical identity by molecular weight analysis in immunoblot experiments. We assessed a panel of antibodies used in both, academic research as well as routine diagnostics for their usability across various validation platforms. While a significant proportion of the antibodies tested showed reliable specificity in both assays, some proved to be unsuited for dual application in IHC and WB, failing in either assay. The results presented here, reflect the heterogeneity in antibody specificity and emphasize the advantage of combining a series of suitable methods to ensure reproducibility and specific epitope detection. Based on our results presented here, we propose an improved step by step strategy to validate antibody immunoreactivity and control for variability across protocols. 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 4875. doi:10.1158/1538-7445.AM2011-4875
Abstract LB-339: Claudin-7 increases chemosensitivity to cisplatin in human NCI-H522 lung cancer cells
Authors: John E. Hoggard, Zhe Lu, Qun Lu, Yan-Hua Chen
Journal: Cancer Research (2010)

Abstract Lung cancer is a leading cause of cancer death for both men and women worldwide. The 5-year survival rate for lung cancer is only 15%, and it accounts for approximately 1.4 million deaths every year. Recently, it has been reported that changes in expression level of claudin proteins, a family of tight junction integral membrane proteins, has been associated with several types of cancer tissues. Claudin proteins are vital components of the tight junction complex, playing a crucial role in maintaining cell polarity, adhesion, and paracellular permeability. Studies have illustrated that claudin-7 expression is lost in head, neck, invasive breast cancer, and certain types of lung cancer. The aim of this study is to investigate the role of claudin-7 in human lung adenocarcinoma cancer cells. We transfected claudin-7 cDNA tagged with myc into NCI-H522 cells, which have no detectable expression of claudin-7. H522 cells transfected with vector alone were used as a control. Claudin-7 expression in transfected cells was confirmed by western blot analysis and immunofluorescence microscopy probing for claudin-7 and myc tag. Flow cytometry analysis demonstrated that cells transfected with claudin-7 had a significantly higher percentage of cell apoptosis when compared to that of the vector transfected cells. Cell viability analyzed by MTT assays was significantly decreased, and cell apoptosis by Annexin V assays was significantly increased in claudin-7 transfected cells compared to that of vector transfected cells after cisplatin treatment. Cisplatin is an anti-cancer drug clinically used to treat tumors in several tissues including lung tumors. Furthermore, we found that claudin-7 transfected cells exhibited upregulation of caspase-3, -8, and -9. We propose that claudin-7 expression in H522 lung cancer cells increases chemosensitivity to cisplatin through increased activation of the caspase pathway. This work is supported by NIEHS. 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 LB-339.