tbuckley/cabot-search huggingface dataset:
Abstract IA26: Finding mechanisms of cancer drug resistance through functional genetic screens
Authors: Rene Bernards
Journal: Cancer Research (2011)

Abstract Unresponsiveness to therapy remains a significant problem in the treatment of cancer, also with the new classes of cancer drugs. In my laboratory, we use functional genetic approaches to identify biomarkers that can predict responsiveness to targeted cancer therapeutics; drugs that specifically inhibit molecules or pathways that are often activated in cancer. Nevertheless, it remains poorly explained why a significant number of tumors do not respond to these therapies. We aim to elucidate the molecular pathways that contribute to unresponsiveness to targeted cancer therapeutics using a functional genetic approach. This will yield biomarkers that may be useful to predict how individual patients will respond to these drugs. Furthermore, this work may allow the development of drugs that act in synergy with the established drug to prevent or overcome drug resistance. To identify biomarkers that control tumor cell responsiveness to cancer therapeutics, we use multiple complementary approaches. First, we use genome wide loss-of-function genetic screens (with shRNA interference libraries) in cancer cells that are sensitive to the drug-of-interest to search for genes whose down-regulation confers resistance to the drug-of-interest (resistance screens). In addition, we use single well siRNA screens with a low dose of the drug to screen for genes whose inhibition enhances the toxicity of the cancer drug (sensitizer screens). As a third approach, we use gain of function genetic screens in which we search for genes whose over-expression modulates drug responsiveness. Once we have identified candidate drug response biomarkers in relevant cell line models, we ask if the expression of these genes is correlated with clinical response to the drug-of-interest. For this, we use tumor samples of cancer patients treated with the drug in question and whose response to therapy is documented. In a fourth and distinct approach we perform high throughput sequencing of the “kinome” (some 600 genes) or whole exome of tumor samples to identify connections between cancer genotype and drug responses. Examples of these four approaches to identify mechanisms of resistance to different cancer drugs will be presented. 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 IA26.
Endoscopic creation of an omental patch with an over-the-scope clip system after endoscopic excavation and resection of a large gastrointestinal stromal tumor of the stomach
Authors: Klaus Mönkemüller, Shabnam Sarker, K. Baig
Journal: Endoscopy (2014)

A 75-year-old woman with a history of complex aortic aneurysm repair, rheumatoid arthritis, hypertension, atherosclerosis, and atrial fibrillation was found to have a 35-mm gastrointestinal stromal tumor (GIST) of the gastric fundus ([Fig. 1 a]). Endoscopic ultrasound revealed the GIST to be originating from the muscularis propria.
Abstract 1634: Targeting L1 cell adhesion molecule using lentivirus-mediated short hairpin RNA interference reverses aggressiveness of oral squamous cell carcinoma
Authors: Wu I-Hui, Shiao-Chen Hung, Shui-Sang Hsue, Chia-Hui Liao, Hsien-Chi Wang, Pei-Hsin Chuang, Shian-Ying Sung, Chia-Ling Hsieh
Journal: Cancer Research (2011)

Abstract Oral cancer consistently ranks as one of the ten most frequently diagnosed cancers in the world. Despite multidisciplinary treatment with surgery, chemotherapy, and radiation, more than 50% of patients with oral squamous cell carcinoma (OSCC) receiving therapy will eventually develop recurrent and metastatic disease, which carries a particularly poor prognosis. Characterization of the specific molecular alternations associated with OSCC cell growth, invasion, and metastasis can advance our understanding of the molecular mechanisms underlying cancer induction and progression as well provide a basis for the development of new and effective therapeutic treatments for cancer patients. The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in OSCC has not been investigated. In the present study, we demonstrated overexpression of L1CAM in OSCC cells, but not in normal keratinocytes, using both clinical specimens and cell lines. This overexpression demonstrated a strong correlation with less differentiation and a higher invasion potential of cancer cells, supporting the significance of L1CAM in human OSCC tumor progression. Targeting L1CAM gene expression in SCC4 cells overexpressing L1CAM using a lentivirusmediated small hairpin RNA (shRNA) led to a significant reduction in cell proliferation in vitro via retardation of cell cycle at the G1 phase. In addition, shRNA knockdown of L1CAM strongly attenuated the migration and invasion of SCC4 cells, and this was also observed to parallel increased E-cadherin levels and decreased levels vimentin, fibronectin, and Snail-family transcription factors, indicating that L1CAM expression was related to the epithelial-mesenchymal transition. Furthermore, while mice receiving orthotopically placed control SCC4 cells died within 40 days due to invasive tumor growth and regional lymph node metastasis, prolonged animal survival and complete suppression of tumor progression was observed in mice implanted with L1CAM-deficent SCC4 cells, further substantiating the fundamental importance of L1CAM in OSCC pathophysiology. Our findings suggested that L1CAM is a critical mediator of tumor progression in OSCC, and targeting L1CAM using lentivirus-mediated shRNA may be a useful molecular pharmaceutical approach for the treatment of advanced OSCC. 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 1634. doi:10.1158/1538-7445.AM2011-1634
Abstract 3047: 2-Methoxyestradiol inhibits proliferation and induces apoptosis through modulation of miR-7/FLIP signaling in prostate cancer cells
Authors: Saikartik Kumar, Rita Ghosh, Addanki P. Kumar
Journal: Cancer Research (2010)

Abstract Prostate cancer is the second most common cause of death related to cancer in Western societies. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of 17-β estradiol inhibits tumor cell proliferation in various cancer cells, including in the prostate. Previous studies from our laboratory showed that 2-ME2 (i) inhibits proliferation of both androgen responsive and independent cells through induction of apoptosis involving G2/M check point block; (ii) prevents the development of prostate tumors in transgenic adenocarcinoma of mouse prostate (TRAMP) model. Although various molecular targets have been proposed, the mechanism of action behind its antiproliferative activity is still uncertain. Here we investigated the hypothesis that 2-ME2 may induce apoptosis in prostate cancer cells through modulation of microRNA (miRNAs). MicroRNAs are small non-coding RNAs that down regulate gene expression during cellular processes including proliferation and apoptosis. These studies led to the identification of miR-7 and −10 as predominantly up-regulated in response to 2-ME2 treatment in prostate cancer cell lines. Knock-down of miR-7 and −10 using mercury LNA probes showed resistance to 2-ME2-induced proliferation of prostate cancer cells. Additional studies to assess the effect of miR-7 knock-down to regulate apoptosis gene expression identified FLIP (FLICE -inhibitory protein) as one of the downstream targets of miR-7. We have shown that high grade prostate tumors express FLIP at higher levels compared to low grade and inhibition of prostate tumor development by 2-ME2 in preclinical animal model is associated with down regulation of FLIP. In addition overexpression of FLIP has been shown to contribute to resistance to apoptosis. We interpret our findings to suggest that up regulation of miR-7 following treatment with 2-ME2 inhibits FLIP leading to reduced proliferation and induction of apoptosis. Therefore our results may provide a molecular basis for the ability of 2-ME2 to suppress proliferation and to induce apoptosis in prostate cancer cells through modulation of miR-7 mediated inhibition of antiapoptotic genes including FLIP. Supported by ACS RSG-04-169 and NIH CA 135451 (APK). 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 3047.
ASSOCIATION OF NONINVASIVELY MEASURED LEFT VENTRICULAR MECHANICS WITH IN-VITRO MUSCLE PERFORMANCE: A PROSPECTIVE STUDY OF HYPERTROPHIC CARDIOMYOPATHY PATIENTS UNDERGOING SURGICAL MYECTOMY
Authors: Ashwat Singh Dhillon, Wendy Sweet, Zoran Popovic, Nicholas Smedira, Bruce Lytle, Randall Starling, Harry Lever, Christine Moravec, Milind Desai
Journal: Journal of the American College of Cardiology (2012)
Gold Therapy in Rheumatoid Arthritis
Authors: James S. Browning, Raymond M. Rice, W. Vernon Lee, Leslie M. Baker
Journal: New England Journal of Medicine (1947)

TREATMENT of rheumatoid arthritis with gold compounds, initiated in Europe twenty years ago, has gradually grown in favor in American medicine during the past ten years. Recently, Fraser1 condensed the literature on chrysotherapy in this disease and noted that most observers report a favorable response in 70 to 80 per cent of patients. Short, Beckman and Bauer2 found more than forty publications on gold therapy in the English literature up to 1946, almost all of which were favorable toward this type of treatment. Since these recent summaries are available, a review of the literature on this subject is not attempted . . .
Case 73-1962
Authors: William F. McNeely, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A seventy-six-year-old woman entered the hospital because of dyspnea.About four years previously the patient began to experience mild exertional dyspnea, without chest pain or cough. Three months before entry the dyspnea increased in severity, and mild orthopnea developed. On physical examination at that time the heart was slightly enlarged, and a Grade 2 precordial systolic murmur, loudest at the apex, with no transmission, was audible. The neck veins were not distended; fine, moist rales were heard at both lung bases, and ++ pitting edema of the ankles was observed. The blood pressure was 230 . . .
Abstract 583: Ghrelingene expression avoiding the D-ribose caused HepG2 cell death.
Authors: Jia Huei Shiu, Chin Hao Huang, Tai Lin Lee, Shih Chieh Lee, Shu Ying Liu, Meng Feng Tsai
Journal: Cancer Research (2013)

Abstract Liver cancer patients could suffer from high saccharide environment due to the malfunction of liver. To mimic this high saccharide environment, HepG2 cells were culture with 30 mM D-riboses. We found that this high concentration of saccharide cause cell death. Cinnamon was report to reduce glucose in model rats. We hypothesized that the administration of cinnamon extracts may benefit liver cancer patients whose metabolism is defected. To test the hypothesis, three different chemical subtypes of cinnamon extracts were added into the culture medium. The adding of all three cinnamon extracts protected HepG2 cells from D-ribose administration and increased around 20% of surviving cells. These protections were even better than the addition of aminoguanidine hemisulfate salt, a chemical used in the treatment of diabetes. The expressions of ghrelin gene and two ghrelin-related genes was monitored by RT-PCR. Ghrelin gene expression was up-regulated in cinnamon treated cells. Also, the ghrelin modify gene, MBOAT4, and ghrelin process enzyme, furin, gene were all detected in HepG2 cells and cinnnamon treated cells. These results demonstrated that if ghrelin expressed in HepG2 cell and maybe liver as well, it can be processed properly. Both ghrelin transcript variants 1 and 3 recombinant plasmid were transfected into HepG2 cells and both transcript variants protected HepG2 cells from the addition of D-ribose without the administration of cinnamon extracts. We conclude that the cinnamon avoids HepG2 cell damage from D-ribose induced oxidative stress by inducing ghrelin gene expression, and through the ghrelin signaling increases cell surviving. Since ghrelin level is abnormally regulated in patients with hepatocellular carcinoma and post-hepatitic liver cirrhosis, the understanding of how ghrelin been regulated in liver may benefit liver disease patients. Citation Format: Jia Huei Shiu, Chin Hao Huang, Tai Lin Lee, Shih Chieh Lee, Shu Ying Liu, Meng Feng Tsai. Ghrelingene expression avoiding the D-ribose caused HepG2 cell death. [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 583. doi:10.1158/1538-7445.AM2013-583
NONINVASIVE ESTIMATION OF PULMONARY CAPILLARY WEDGE PRESSURE: A STUDY USING LEFT ATRIAL VOLUME, FUNCTION AND DEFORMATION PROPERTY ASSESSED BY SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Yoshie Fujii, Yoshiaki Kawase, Nozomi Nomura, Keiko Ogawa, Ryuhei Tanaka, Hidemaro Sato, Hiroki Kondo, Jun Kikuchi, Tatsuya Saigusa, Takayoshi Kato, Taiji Miyake, Tomohiro Tsunekawa, Munenori Okubo, Kunihiko Tsuchiya, Shinji Tomita, Hitoshi Matsuo, Masanori Kawasaki, Shinya Minatoguchi
Journal: Journal of the American College of Cardiology (2015)
Determinants of Lung Function, COPD, and Asthma
Authors: Dana B. Hancock, Stephanie J. London
Journal: New England Journal of Medicine (2011)

Drs. Cicardi and Banerji Reply: On behalf of all the authors, we thank Giavina-Bianchi et al. for their consideration of our studies of new agents for hereditary angioedema, particularly in regard to concern surrounding the use of placebo rather than an established therapy as a comparison drug.Head-to-head comparative studies would certainly be of great interest.However, when our studies were performed, neither icatibant nor ecallantide was approved, and the efficacy of the C1 inhibitor concentrate Berinert P had not been fully established in properly designed controlled studies.Although it is a potentially weaker therapy, tranexamic acid (the active drug that was compared with icatibant in the For Angioedema Subcutaneous Treatment-2 trial) was an approved therapy that was accepted by the scientific community for the treatment of acute attacks of hereditary angioedema. 1 Since our studies were performed in accordance with both the Declaration of Helsinki 2 and expert consensus, 3 we consider them ethically acceptable.
Gastrointestinal Bleeding Detected on a Routine Tc-99m MDP Bone Scan
Authors: LUVENIA W. BENDER, MICHAEL S. ZINSMEISTER
Journal: Clinical Nuclear Medicine (1999)

A 59-year-old woman with a history of renal cell carcinoma and end-stage renal disease who was receiving peritoneal dialysis returned to the hospital 24 hours after discharge with bright red blood per rectum. A bone scan was requested to evaluate metastatic disease. A Tc-99m MDP whole-body bone scintigram showed uptake in the region of the transverse, descending, and sigmoid colon 2 days before a positive result of Tc-99m-labeled RBC bleeding scan was obtained.
SAT0102 Interpretation of Patient Reported Outcomes Measurement Information System (PROMIS®) by Rheumatologists
Authors: V. Nagaraja, D.A. Fox, S. Francis, P. Khanna, T. Laing, R.M. Marks, S.U. Monrad, V. Ognenovski, K. Phillips, O. Singer, D. Khanna
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS<sup>®</sup>) roadmap initiative is a cooperative research program designed to develop, evaluate, and standardize item banks to measure patient-reported outcomes (PROs) across different medical conditions as well as the US population (www.nihpromis.org). It has comprehensive items banks that assess physical, mental, and social well-being. <h3>Objectives</h3> To assess the interpretation of PROMIS report by rheumatologists at a University Hospital. <h3>Methods</h3> Four focus group discussions consisting of eleven rheumatologists were held at UM Health System. The panelists were first presented with an overview of PROMIS process followed by a series of patient reports With a focus on the evaluating which report was feasible to use in day-to-day practice and clinically meaningful, the following questions were asked by: (i) What do you think of this report? (ii) Do you understand what this report is communicating? (iii) Is there anything you would change about this report to make this better? <h3>Results</h3> All the rheumatologists agreed on the following suggestions: (i) Representation of the item scores as thermal graphs or `heat map" was easier to interpret (ii) Provide average scores for the U.S. population and rheumatology patients, (iii) Provide both average and percentile scores, and (iv) Provide pictorial depiction of most bothersome symptom and urgency for referral. Based on these discussions, we modified the PROMIS heat map (Fig. 1) to include: (i) average scores for rheumatologic disorders (bold square), (ii), an open diamond to indicate the individual scores of the patients, and (iii) thickness of the diamond indicates the severity of these symptoms in the patient with an urgency for intervention (thicker equates to greater urgency). <h3>Conclusions</h3> This presents the first step to assess feasibility of incorporating PRO in rheumatology practice. The PROMIS report card when integrated with the electronic medical record can contribute towards meaningful use. It may improve patient satisfaction and physician-patient relationship. Our long-term goal is to integrate PROMIS into a busy academic practice and assess its effectiveness. <h3>Disclosure of Interest</h3> V. Nagaraja Employee of: Salary support from the United States Department of Veterans Affairs., D. Fox: None declared, S. Francis: None declared, P. Khanna: None declared, T. Laing: None declared, R. Marks: None declared, S. Monrad: None declared, V. Ognenovski: None declared, K. Phillips: None declared, O. Singer: None declared, D. Khanna Grant/research support: NIH/NIAMS K24 AR063120-02 <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2626
Case 45-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case A forty-six-year-old housewife entered the hospital because of pain in the right knee. At the age of four years the patient first experienced pain in the right knee on weight bearing. Thereafter, she fell frequently and limped. Six months later physical examination showed a severe flexion deformity of the knee, and an x-ray film demonstrated a marked increase in the density of the soft tissues about the joint, a distended joint capsule and considerable atrophy of the bones of the joint. A cast and splint traction afforded some improvement. Two years later she was sent to a . . .
Abstract 888: Reduced folate carrier gene polymorphism (RFC 80G&amp;gt;A): Associations with clinical outcome in NMYC amplified neuroblastoma patients
Authors: Diana T. Lau, Jayne Murray, Murray Norris, Glenn M. Marshall, Michelle Haber, Lesley J. Ashton
Journal: Cancer Research (2010)

Abstract Background Folate plays an important role in cell function, division and differentiation. Gene polymorphisms in the folate pathway have been shown to influence folate uptake and metabolism. The aims of our study were to examine how specific gene variants in the folate pathway influence the clinical outcome of childhood neuroblastoma and to measure the correlation between specific genotypes and levels of gene expression. Methods Common single nucleotide polymorphisms (SNPs) in the folate pathway were examined in DNA from 174 children diagnosed with neuroblastoma between 1985 and 2000. Cox proportion hazard analysis was used to investigate the association between the presence or absence of specific gene polymorphisms and the risk of relapse or death in the 5 year follow up period, while adjusting for known prognostic cofactors. Relative quantification of reduced folate carrier (RFC) mRNA expression was performed in a subset of 43 neuroblastoma tissues by real-time quantitative PCR. Results No significant difference in EFS was observed between individuals with different folate genotypes (P&amp;gt;0.05). However, in multivariate analysis children homozygous for the RFC 80A gene variant were significantly less likely to relapse or die compared to those with RFC 80G allele after adjusting for prognostic factors such as NMYC status, stage and age at diagnosis (HR=0.46; 95% CI=0.24-0.90, P=0.024). Moreover, in those patients with NMYC amplification, the cumulative 5 year EFS was 0% in those homozygous for RFC 80GG; 9% in those heterozygous for RFC 80GA; and 50% in those homozygous for RFC 80AA (Log-rank test, P=0.005). However, no apparent association was observed for any of the additional gene polymorphisms examined (P&amp;gt;0.05) even after adjusting for NMYC status, age, or tumour stage at diagnosis. Quantitative mRNA analysis in a subset of 43 patients showed that expression of RFC was three times higher in those with RFC 80GG genotype compared to those with other genotypes, although this was not statistically significant (P=0.587). Conclusions Our results show that the RFC 80A variant allele confers superior survival in patients with NMYC amplification. These findings suggest that the RFC G80A polymorphism may play an important role in modifying folate transport in rapidly dividing neuroblastoma cells regulated by NMYC proto-oncogene. 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 888.