tbuckley/cabot-search huggingface dataset:
Abstract C37: BMAL1 depletion represses growth of mesothelioma through induction of mitotic catastrophe
Authors: Momen H.K.A. Elshazley, Yoshinor Hasegawa, Mitsuo Sato, Tetsunari Hase, Kenya Yoshida, Shinya Toyokuni, Yoshitaka Seikido, Kohei Yokoi, Noriyasu Usami, Masashi Kondo
Journal: Cancer Research (2011)

Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising from the mesothelial cells lining the pleura. Asbestos exposure is considered the most important carcinogenic factor that has been mentioned in relation to MPM. Although the incidence of MPM continues to increase, it remains resistant to the currently available therapeutic modalities. Thus, identification of more efficient therapeutics based on its molecular abnormalities is highly recommended. Recently, a genome-wide expression analysis showed deregulation of the circadian rhythm pathway in MPM, including overexpression of BMAL1, a central player in the circadian clock machinery. In this study we explored the consequences of targeting BMAL1 in MPM. This was accomplished by genetic knockdown of BMAL1 with small interference RNA (siRNA) and short hairpin lentiviral expression system. The majority of MPM cell lines expressed higher levels of BMAL1 than the nontumorigenic mesothelial cell line (Met-5A). Immunohistochemical analysis revealed that BMAL1 is constitutively expressed in the cytoplasm with granular pattern in a subset of clinical MPM specimens. Long-term depletion of BMAL1 induced senescence and downregulation of IL-8 and BcL-2 in ACC-MESO-1-cells. Notably, RNAi-mediated knockdown of BMAL1 resulted in suppression of cell growth and induction of apoptosis in MPM cell lines with limited consequences in Met5A. Moreover, ACC-MESO-1 cells, which expressed the highest level of BMAL1, underwent drastic morphological changes including micronucleation, multiple nuclei, and increased cellular volume. Consistently, cell cycle profiling revealed substantial increase in apoptotic and polyploidy cells with concomitant decrease in Wee1, cyclin B, p21, and increase in cleaved caspase 3 and cyclin E proteins by Western blot analysis. Taken together, these results suggest that mitotic catastrophe could be the main cause of cells death in ACC-MESO-1 cells after BMAL1 knockdown. BMAL1 plays an important role in MPM and serves as an attractive therapeutic target for MPM with high therapeutic index. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C37.
New High-Priority Trials
Authors: J. A. Steele
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article New High-Priority Trials Get access Julie A. Steele Julie A. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 2, 16 January 1991, Page 88, https://doi.org/10.1093/jnci/83.2.88 Published: 16 January 1991
Abstract 438: The CFP nude mouse as a host for color-coded imaging of the tumor microenvironment
Authors: Atsushi Suetsugu, Mohamed K. Hassanein, Jose Reynoso, Shigetoyo Saji, Hisataka Moriwaki, Michael Bouvet, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract We have developed a color-coded model to study the tumor microenvironment using cancer cells expressing RFP or GFP implanted in nude mice expressing cyan fluorescent protein (CFP). When RFP or GFP HCT-116 were injected subcutaneously in CFP expressing nude mice, CFP expressing cancer-associated fibroblasts migrated to the tumor site. CFP-expressing tumor blood vessels were observed in the tumor. Other CFP host stromal cells were observed throughout the tumor mass. When RFP HCT-116 cells were transplanted in the spleen of CFP nude mice, they formed tumors in the liver. When RFP HCT-116 cancer cells were transplanted in the tail vein of CFP nude mice and they formed tumors in the lung. CFP-expressing host cells were observed in these tumors. When the RFP mouse mammary cancer cell line (RFP MMT) was injected subcutaneously in the CFP nude mouse, numerous CFP-expressing fibroblasts and CFP-expressing blood vessels was observed in the resulting tumor. A large inflammatory population of different CFP-expressing white blood cells surrounded the necrotic area of the tumor suggesting a relationship of these cells to tumor necrosis. GFP and RFP HCT-116 cancer cells were co-injected subcutaneously in CFP-nude mice and tumor growth was followed for 21 days. This three-color model enabled visualization of the tumor mass and its neovasculature in addition to a detailed visualization of other host reactions. GFP HCT-116 cancer cells were initially injected subcutaneously in RFP-nude mice and tumors formed within 14 days. At this point, the tumor mass which consisted of GFP cancer cells and RFP stroma derived from the RFP nude mouse, was harvested and transplanted to a CFP-nude mouse. CFP host cells invaded the growing transplanted tumor containing dual-color cancer cells and RFP stroma. Thus the CFP-nude mouse adds another color to the pallet to study the human tumor microenvironment allowing 4 types of cells to be simultaneously imaged in tumors. 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 438. doi:10.1158/1538-7445.AM2011-438
1083 RATHER THE ALLELIC VARIATION OF IL28B BUT NOT OF CYP27B1 OR HCV GENOTYPE PREDICT SPONTANEOUS ELIMINATION OF HCV-INFECTION
Authors: A. Amanzada, S. Schneider, A. Lindhorst, F. Moriconi, L. Reinhardt, P. Wietzke-Braun, S. Mihm, G. Ramadori
Journal: Journal of Hepatology (2012)
AB0882 To Determine the Factors Influencing the Lean Body Mass in Patients with Juvenile Idiopathic Arthritis
Authors: A. Hari, S. Rostom, R. Lahlou, D. Khnaba, R. Bahiri, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To determine the factors influencing the lean body mass in patients with juvenile idiopathic arthritis. <h3>Methods</h3> A cross sectional study in patients with juvenile idiopathic arthritis (JIA) according to the International League of Association of Rheumatology criteria was conducted. Sociodemographic parameters and clinical data related to the disease were collected. Lean body mass was measured by dual energy X-ray absorptiometry on Lunar Prodigy machine at the full body. Disease activity of the JIA was assessed by the number of painful joints (PJ), number of swollen joints (SJ), thevisual analogic scale (VAS) painassessed by patient (VASp) and physician (VASd), and biological parameters (ESR,CRP). The daily food intake was assessed by a questionnaire for 7 consecutive days. Two nutritionists analyzed the diet to identify its macronutrient and oligonutriments content. Food intake was analyzed by Bilnut Version 2.01 software 1991, which was validated. <h3>Results</h3> Thirty-three patients with JIA were included. The mean age was 10±4.35 years with a male predominance (54.5%). Twenty-four percent had a systemic form, 27% an oligoarticular and 48% a polyarticular form. The median disease duration was 2 years (1-4.5). The median duration of taking corticosteroids was 3 years (1-6).The median of lean mass, PJ, SJ, VASp, VAS d, ESR and CRP were respectively 20.5g (15.96-33.45), 3 (1-9), 1 (0-3), 20 (10-50) 35 (25-50.5) 20 (10.5-40).The median content of the feed proteins, lipids and carbohydrates was respectively1.7g (0-4.75), 0.8 g (0-11.65), and 11.1g (0-32.8).There was no correlation between lean mass and JIA disease activity parameters: PJ (r=0.06, p=0.7), SJ (r=0.25, p=0.23), VASp (r=0.16, p=0.46), VASd (r=0.02, p=0.9), ESR (r=0.13, p=0.54), CRP (r=0.10, p=0.64).There was no correlation between lean body mass and the cumulative duration and taking of corticosteroids with respectively (r =0.15, p=0.61) dose (r=0.28, p=0.33).There was no correlation between lean mass and content of feed on protein (r=0.17, p=0.41), fat (r=0.14, p=0.32), or carbohydrate (r=0.32, p=0.12). <h3>Conclusions</h3> This study suggests that there was no correlation between lean body mass, disease activity parameters, and taking corticosteroids in children with JIA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5267
The reporting quality of randomised controlled trials in ophthalmic surgery in 2011: A systematic review
Authors: Alexander Yao, Ankur Khajuria, Christian Camm, Eric Edison, Riaz Agha
Journal: International Journal of Surgery (2013)

Purpose Randomised controlled trials (RCTs) represent a gold standard for evaluating therapeutic interventions. However, poor reporting clarity can prevent readers from assessing potential bias that can arise from a lack of methodological rigour. The Consolidated Standards of Reporting Trials statement for non-pharmacological interventions 2008 (CONSORT NPT) was developed to aid reporting. RCTs in ophthalmic surgery pose particular challenges in study design and implementation. We aim to provide the first assessment of the compliance of RCTs in ophthalmic surgery to the CONSORT NPT statement. Method In August 2012, the Medline database was searched for RCTs in ophthalmic surgery reported between 1 January 2011 and 31 December 2011. Results were searched by two authors and relevant papers selected. Papers were scored against the 23-item CONSORT NPT checklist and compared against surrogate markers of paper quality. The CONSORT score was also compared between different RCT designs. Results In all, 186 papers were retrieved. Sixty-five RCTs, involving 5803 patients, met the inclusion criteria. The mean CONSORT score was 8.9 out of 23 (39%, range 3.0–14.7, SD 2.49). The least reported items related to the title and abstract (1.6%), reporting intervention adherence (3.1%), and interpretation of results (4.7%). No significant correlation was found between CONSORT score and journal impact factor (R1⁄4 0.14, P1⁄4 0.29), number of authors (R1⁄4 0.01, P1⁄4 0.93), or whether the RCT used pairedeye, one-eye, or two-eye designs in their randomisation (P1⁄4 0.97). Conclusions The reporting of RCTs in ophthalmic surgery is suboptimal. Further work is needed by trial groups, funding agencies, authors, and journals to improve reporting clarity. Eye advance online publication, 12 September 2014; doi:10.1038/eye.2014.206
Stomach Cancer after Partial Gastrectomy for Benign Ulcer Disease
Authors: Göran Lundegårdh, Hans-Olov Adami, Charles Helmick, Matthew Zack, Olav Meirik
Journal: New England Journal of Medicine (1988)

We followed for 25 to 33 years 6459 patients who had undergone partial gastrectomy for benign ulcer disease to determine the incidence of stomach cancer. The overall risk was no different from that among sex- and age-matched controls from the Swedish Cancer Registry (standardized incidence ratio = 0.96; 95 percent confidence limits, 0.78 and 1.16). However, when the patients were classified according to the duration of follow-up after operation, sex, surgical procedure, diagnosis at the time of operation, and age at operation, differences in risk were observed between the subgroups. After adjustment for potential confounding variables, the average adjusted risk increased 28 percent (adjusted standardized incidence ratio = 1.28; 95 percent confidence limits, 1.11 and 1.49) for each successive five-year interval after operation. The adjusted risk was greater among women than men (adjusted standardized incidence ratio = 1.96; 95 percent confidence limits, 1.18 and 3.24). Patients who had undergone a Billroth I anastomosis had a lower crude risk, both overall (standardized incidence ratio = 0.40; 95 percent confidence limits, 0.20 and 0.71) and after we controlled for other confounding variables (adjusted standardized incidence ratio = 0.27; 95 percent confidence limits, 0.12 and 0.62), than did those who had undergone a Billroth II procedure. The adjusted risk of stomach cancer was greater among patients operated on for gastric ulcer than among those operated on for duodenal ulcer (adjusted standardized incidence ratio = 2.21; 95 percent confidence limits, 1.45 and 3.35). Risk decreased with increased age at operation. Between successive strata of age at operation (<39, 40 to 49, 50 to 59, and ≥60 years of age), the adjusted risk decreased on the average by about half (adjusted standardized incidence ratio = 0.52; 95 percent confidence limits, 0.41 and 0.66). (N Engl J Med 1988; 319:195–200.)
445P Overall survival (OS) with afatinib (A) vs chemotherapy (CT) in patients (pts) with NSCLC harboring EGFR mutations (mut): Subgroup analyses by race in LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6)
Authors: Y.-L. Wu, L.V. Sequist, M. Schuler, N. Yamamoto, C. Zhou, C.-P. Hu, K. O'Byrne, V. Hirsh, T. Mok, V. Zazulina, J.C.-H. Yang
Journal: Annals of Oncology (2015)
Abstract 3983: Real-time imaging of human thyroid cancer progression in a fluorescent orthotopic nude mouse model
Authors: Hop S. Tran Cao, Sharmeela Kaushal, Cynthia S. Snyder, Weg M. Ongkeko, Robert M. Hoffman, Michael Bouvet
Journal: Cancer Research (2010)

Abstract We report here a novel orthotopic mouse model of human thyroid cancer that can be imaged non-invasively with the use of red fluorescent protein (RFP). Human thyroid cancer cell lines NPA (papillary) and KAK-1 (anaplastic) were stably transfected to express RFP or the green fluorescent protein (GFP). The cells were then injected into the thyroid glands of 8-week old athymic mice. The animals were noninvasively imaged weekly, and sacrificed when premorbid. Their tumor was subsequently resected en bloc with the respiratory system for further processing and analysis. H&amp;E staining was performed to confirm the pathological diagnosis. Both anaplastic and papillary thyroid cancer cell lines led to the robust development of orthotopic fluorescent tumors in nude mice. While RFP-expressing tumors were easily identified transcutaneously, autofluorescence of the skin prevented visualization of GFP-expressing tumors, making GFP a suboptimal model. Injection of 5 × 10^5 cells was as efficacious in allowing tumor development as 5 × 10^6 cells. Tumors were first visualized for both cell lines via whole-body noninvasive imaging as early as four weeks post-implantation and could be monitored over time. The time to premorbid conditions varied greatly between mice and seemed to be associated with the tumor growth pattern rather than tumor size. The earliest appearance of morbidity was five weeks post-implantation in an animal with cachexia due to local compression of the esophagus by the tumor. Other mice died at later stages from metastatic disease. The bright fluorescence of the tumors allowed identification of multiple micrometastases at necropsy in the lungs, lymph nodes, and the vascular system, lesions that were not visible under white light. In summary, we have developed a novel orthotopic fluorescent mouse model of thyroid cancer that should serve a valuable role in the understanding of this disease and in the evaluation of new therapeutics, allowing assessment of the tumor response over time. 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 3983.
Abstract 3343: Targeting thyroid cancer stem cells with PPARγ agonists
Authors: Dang L. Vu-Phan, Ron Koenig, Max Wicha
Journal: Cancer Research (2010)

Abstract Ligand activation of PPARγ is reported to inhibit proliferation and promote differentiation in many tissue types, including thyroid. Nonetheless, clinical trials treating thyroid cancer with the PPARγ agonist rosiglitazone yielded disappointing results when the measured outcomes were reacquisition of radioiodine uptake and overall survival. We report here evidence that PPARγ agonists preferentially target cancer stem cells and may still be useful for treatment of thyroid cancer in a different context, especially in combination with reagents that can target the remaining bulk of the tumor. We used for our studies FTC236 and FTC238, two related cell lines derived from follicular thyroid carcinoma metastases to lymph node and lungs. Both cell lines had robust PPARγ expression and harbored no known PPARγ fusion protein. Stem cell populations within the cell lines were measured using the Aldefluor (Aldf) assay for Aldehyde Dehydrogenase activity. Both cell lines have 5-10% Aldf+ cells. Populations which contained Aldf+ were the only ones capable of forming passageable sphere colonies in serum free suspension cultures and the only ones capable of forming tumors in NOD/SCID mice. Furthermore, FTC populations grown as spheres had six times more Aldf+ cells than those grown on plastic; therefore serum free suspension cultures was an effective way to enrich for FTC stem cells. FTC cells grown on plastic expressed PPARγ at five times the level seen in FTC spheres. We activated PPARγ signalling in FTC cells by addition of rosiglitazone or CAY10410, a chemical analogue of the natural PPARγ agonist 15-deoxy-Δ12,14-Prostaglandin-J2. At concentrations which exhibited less than 50% growth inhibitory effects, PPARγ agonists reduced the Aldf+ percentage of the treated population by 90%. Addition of PPARγ agonists into suspension cultures at the same concentrations reduced sphere formation by 80%. We identified the Aldefluor positive fraction as the tumorigenic and sphere-forming cancer stem cell population within our FTC cell lines. This population exhibited reduced PPARγ expression and was depleted upon treatment with PPARγ agonists. We hypothesize that downregulation of PPARγ signalling is required for maintenance of the stem cell phenotype and that induced activation of PPARγ is a possible strategy for targeting thyroid cancer stem cells. 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 3343.
Abstract 62: Detection and comparison of EGFR mutations in matched tumor tissue, cell block, pleural effusion and serum with PNA clamping and direct sequencing in NSCLC with malignant pleural effusion.
Authors: Chan Kwon Park, Chang Dong, Jin Woo Jin Woo, Kwan Hyoung Kim, Jick Hwan Ha, Chin Kook Rhee, Young Kyoon Kim, Sang Haak Lee, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim
Journal: Cancer Research (2013)

Abstract Background: Peptide nucleic acid (PNA)-mediated real-time PCR clamping was recently used to detect mutations because it has higher sensitivity than conventional direct sequencing. Pleural effusion and serum samples could be good sources of detecting the epidermal growth factor receptor (EGFR) mutational status of non-small cell lung cancer (NSCLC) patients. Methods: We studied 37 NSCLC patients with malignant pleural effusion. In each patient, EGFR mutational status was measured from the samples of tumor tissue, cell block, pleural effusion and serum using both PNA clamping and direct sequencing. The concordance between PNA clamping and direct sequencing, and the diagnostic performance of pleural effusion was investigated. Results: The detection rate of EGFR mutation in the pleural effusion and the serum was 27% and 2.8%, respectively by both PNA clamping and direct sequencing. The κ coefficient between the two methods were 0.68 (p-value = 0.0007), 0.91 (p-value &amp;lt; 0.0001), 0.75 (p-value &amp;lt; 0.0001) and -0.01 (p-value = 0.8639) in tissue, cell block, pleural effusion and serum, respectively. The diagnostic performance of pleural effusion compared with combined tumor tissue plus cell block showed sensitivity 89%, specificity 100%, positive predictive value 100% and negative predictive value 95% with PNA clamping, and sensitivity 67%, specificity 90%, positive predictive value 75% and negative predictive value 86% with directing sequencing. Interestingly, a patient who was confirmed EGFR mutation only with the PNA clamping showed significant response to EGFR TKI (tyrosine kinase inhibitor). Conclusion: Despite the limited role of serum samples, pleural effusion had a diagnostic performance comparable with tumor tissue and cell block to detect EGFR mutational status in NSCLC. Although the diagnostic performance of PNA clamping was similar to that of direct sequencing, additional benefit is expected considering the response to the EGFR TKI. Citation Format: Chan Kwon Park, Chang Dong, Jin Woo Jin Woo, Kwan Hyoung Kim, Jick Hwan Ha, Chin Kook Rhee, Young Kyoon Kim, Sang Haak Lee, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim. Detection and comparison of EGFR mutations in matched tumor tissue, cell block, pleural effusion and serum with PNA clamping and direct sequencing in NSCLC with malignant pleural effusion. [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 62. doi:10.1158/1538-7445.AM2013-62
Dementia and flu are blamed for increase in deaths in 2015 in England and Wales
Authors: Jacqui Wise
Journal: BMJ (2016)

The spike in deaths seen in 2015 in England and Wales was mainly due to an increase in dementia and Alzheimer’s related deaths and flu outbreaks among older people, an analysis by the Office for National Statistics (ONS) has concluded.1

Provisional figures showed 529 613 registered deaths in England and Wales in 2015, an increase of 28 189 (5.6%) on the previous year. Some 86% of the extra deaths occurred in people over 75, and 38% were in people over 90. This was the largest number of deaths in a single year since …
Gastroduodenal ulceration following liver radioembolization with yttrium-90
Authors: N. Veloso, C. Brandão, B. Gonçalves, L. Costa, N. Coimbra, M. Jacome, L. Moreira Dias
Journal: Endoscopy (2013)

Radioembolization or selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an effective locoregional treatment for unresectable primary and metastatic malignancies of the liver [1]. SIRT is a straightforward method of delivering microspheres containing 90Y (a high-energy β-emitting radioisotope) to the microvasculature of malignancies whilst sparing the normal liver parenchyma.
Detection of gastric MALT lymphoma spreading to the small bowel by enteroscopy
Authors: W. Dolak, M. Raderer, J. Maresch, L. Muellauer, A. Puespoek, A. Chott, M. Haefner
Journal: Endoscopy (2011)

Mucosa-associated lymphoid tissue (MALT) lymphoma is thought to be a multifocal disease with sometimes synchronous involvement of various mucosal structures. In this study we aimed to evaluate the potential involvement of the small bowel in patients suffering from gastric MALT lymphoma by analyzing the results of enteroscopy, a technique that allows easy and safe access to the small bowel with the potential for histological assessment of biopsy samples. We have retrospectively evaluated 347 enteroscopies and found nine patients with gastric MALT lymphoma who had undergone push enteroscopy with serial biopsies during staging. All patients tolerated enteroscopy without side effects, and no local complications occurred. In eight cases no evidence of duodenal or jejunal involvement was found macroscopically or by histological assessment of biopsies, while in one patient enteroscopy revealed jejunal MALT lymphoma infiltration with macroscopic accentuation of mucosal parts and consecutive histopathological verification more distal than 50 cm. This single-center retrospective analysis shows that enteroscopy can provide additional diagnostic information in patients with gastric MALT lymphoma, although the number of patients was small and only one out of nine patients showed hitherto undetected MALT lymphoma deposits. Further studies may quantify the additional diagnostic yield provided by this easy and safe endoscopic method.