tbuckley/cabot-search huggingface dataset:
Abstract 3966: 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1
Authors: Hye-Young Hong, Woo-Kwang Jeon, Sung-Ji Park, Hyung-Ju Jang, Ji-Yeon Choi, Byung-Chul Kim
Journal: Cancer Research (2010)

Abstract The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 ζ and 14-3-3 σ on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-β1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-β1-mediated growth inhibition displayed increased expression of 14-3-3 ζ and decreased expression of 14-3-3 σ compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 σ or 14-3-3 ζ, we showed that 14-3-3 σ is required for TGF-β1-mediated growth inhibition whereas 14-3-3 ζ negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 ζ increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-β1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 ζ phosphorylation sites in Smad3 markedly reduced the 14-3-3 ζ-mediated inhibition of TGF-β1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 ζ in the suppression of TGF-β1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 σ or 14-3-3 ζ contributes to TGF-β1 resistance in cancer cells. Following are results of a study on the “Human Resource Development Center for Economic Region Leading Industry” Project, supported by the Ministry of Education, Science &amp; Technology(MEST) and the National Research Foundation of Korea(NRF) 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 3966.
P5-08-06: Comparison of Mammographic Density between Ductal Carcinoma In Situ and Benign Breast Disease.
Authors: JW Lee, EJ Shin, OV Yi, JW Lee, HJ Shin
Journal: Cancer Research (2011)

Abstract Background: High breast density is an independent risk factor for breast cancer as well as benign breast diseases. However there are few studies about breast density of ductal carcinoma in situ (DCIS) and benign breast disease(BBD). In this study, we investigated patterns of breast density of DCIS and BBD, and comparatively analyzed breast densities of DCIS and BBD. Material and Methods From 2008 to 2009, 345 patients underwent surgery for DCIS at Asan Medical Center, and 295 patients for BBD at 2010. We retrospectively reviewed each groups and estimated cranio-caudal view of digital mammogram of unaffected breast by computer-assisted thresholding methods, using Cumulus 4, version 4.0. For BBD we included atypical ductal hyperplasia, fibroadenoma, papilloma(atypical/intraductal), phyllodes tumor(benign/borderline), and excluded unavailable mammogram(mostly, because of scanned films from outside hospitals and previously diagnosed breast cancer). Results Mean ages of each group were 46.51 year old in DCIS group and 41.43 year old in BBD group, and the mean percentage density(PD) were 44.89% and 45.27%, respectively. There was no significant difference between two groups in total population(p=0.79). We categorized into two groups according to the age, ≥50 and &amp;lt;50, for each DCIS and BBD group. Mean percentage density of below 50 year old was 52.92% in DCIS gruop and 49.58% in BBD group(p=0.031). Mean percentage density above 50 year old was 33.67% in DCIS group and 33.29% In BBD group(p=0.867). Conclusion The mean values and distribution patterns of PD were similar between BBD group and DCIS group. However, in the subgroup aged under 50, the DCIS group has significantly higher breast density than the BBD group. Although the causal association of breast density with breast cancer has been relatively well documented, this kind of cross-sectional study has an inherent limitation. The absolute difference between the DCIS group and the BBD group under age 50 (3.34% in table2) needs more investigation for its clinical implications. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-06.
Europe does well in science research league
Authors: J. Wise
Journal: BMJ (1997)

Small European countries such as Switzerland and Sweden produce some of the highest quality scientific research in the world, according to an analysis comparing the scientific strength of different countries.

The analysis, published in Science , found that the United States topped the league both in the share of papers published in science, engineering, and medicine and in the quality of the research (1997;275:793-6). The top seven countries in terms of the share of papers and share of citations were the world's seven largest economies—the so called G7 countries (see table). …
QUALITY OF CARE FOR ACUTE SEVERE COLITIS. MUCH DONE, MORE TO DO
Authors: D J Gibson, N Rafter, D Keegan, K Byrne, S Martin, P R O'Connell, D C Winter, J M Hyland, H E Mulcahy, G Cullen, G A Doherty
Journal: Gut (2013)

<h3>Introduction</h3> Optimal management of in-patients with Ulcerative Colitis (UC) is important, as it is associated with morbidity and mortality. The national IBD audit in the UK has defined quality standards for the care of acute colitis. <h3>Aims/Background</h3> To assess whether our management of patients with acute UC complies with suggested quality standards and identify areas for quality improvement. <h3>Method</h3> This was a retrospective review of all patients admitted with a principle discharge diagnosis of UC in a tertiary referral centre between January 2010-November 2011. Patients admitted electively either for endoscopy or UC related surgery were excluded. <h3>Results</h3> 91 patients were identified with a principal discharge diagnosis of UC; 39 patients were excluded (elective admission for surgery or endoscopy). 52 patients hospitalised with acute severe colitis were considered eligible for further study. M:F ratio=36:16. Median age was 47.0 (+/−17.68). Median length of stay was 8 days. 44 patients were admitted medically and 8 were admitted surgically. Stool sample for culture and sensitivity and C Difficile toxin was sent in 40 of 52 cases (76.9%). 40 patients (76.9%) underwent flexible sigmoidoscopy within 4 days of admission. 48 patients (92.3%) received steroids, of whom 72.9% were prescribed bone protection. VTE prophylaxis was prescribed in 46/52 (85.7%). 37/52 (53.8%) patients were assessed by a dietician during their admission. Medical teams were more likely to send stool samples (81% vs 50%) and prescribe bone protection for those on steroids (73% vs 38%), whereas rates of VTE prophylaxis prescription were comparable (89% vs 88%) between medical and surgical admissions. <h3>Conclusion</h3> This study highlights good practice in the care of patients with acute severe colitis but identifies areas for quality improvement. All patients should have a stool sample sent at admission and should receive VTE prophylaxis. The use of an intergrated care pathway for patients with acute severe colitis may assist in ensuring quality standards are optimized.
Traumatic Necrosis of Pretibial Muscles
Authors: Carl Pearson, Raymond D. Adams, D. Denny-Brown
Journal: New England Journal of Medicine (1948)

AN UNUSUAL case in which the pretibial muscles of both legs became acutely swollen, painful and paralyzed after a period of vigorous activity was recently observed on one of the medical wards of the Boston City Hospital. The clinical features were puzzling, and it was only after a biopsy had disclosed hemorrhage and necrosis that a clue to the nature of this disorder was obtained. Since we were unfamiliar with this condition and are unable to find verification of exactly similar cases in the medical literature, the following case is reported.Case ReportS. T., a 24-year-old man, who had . . .
Abstract 1345: Evidence for genetic mediation of lung cancer through hay fever.
Authors: Anthony D'Amelio, Chi H. Nguyen, Randa El-Zein, Margaret R. Spitz, Xifeng Wu, Carol J. Etzel
Journal: Cancer Research (2013)

Abstract Introduction: In the past decade, advances in genetics have led to the discovery of numerous lung cancer susceptibility variants. The majority of these variants have been found to influence lung cancer susceptibility via tobacco exposure or nicotine addiction; however, recently, researchers have observed lung cancer susceptibility variants that mediate through Chronic Obstructive Pulmonary Disease (COPD). Studies involving potential genetic factors related to other lung-related conditions, such as pneumonia and/or hay fever have been limited. The genetic variants related to underlying mechanism of hay fever on the development of lung cancer are interesting to pursue as hay fever has been showed to be protective against lung cancer. Methods: Cases included 1154 histological-confirmed Caucasian lung cases from MD Anderson Cancer Center in Houston, Texas, and controls included 1137 individuals recruited through the Kelsey-Seybold Clinics in Houston, Texas. These cases and controls were a subset of participants from a lung cancer case-control study conducted that has available Genome-wide association study (GWAS) data (317,498 SNPs). We first conducted an association analysis in PLINK to determine the association of each SNP with both lung cancer and hay fever and find SNPs that showed a joint significance for both hay fever and lung cancer in opposite directions (p-value &amp;lt; 0.05 for both). We then performed mediation analyses with the SNPs that showed significance for both hay fever and lung cancer. Finally, we inferred SNPs in regions that contained a collection of tag SNPs that mediate lung cancer risk through hay fever. Results: Two hundred and forty six SNPs were found to be statistically significant (p-value &amp;lt; 0.05) for both hay fever (protection) and lung cancer (risk), and 76 of these SNPs maintained their significance level after mediation analysis. SNP rs7159751 on chromosome 14 had the highest mediation effect of 19.83%. A collection of SNPs on the Neuregulin 3 gene (NRG3) that mediate lung cancer risk through hay fever was found on Chromosome 10 which has been shown to activate the JAK-STAT signal transduction pathway and stimulate lung epithelial cell proliferation. Conclusion: This is the first study to have investigated the mediation effects of hay fever on lung cancer risk. Our data supports the mediation role of certain SNPs in lung cancer through hay fever and points to specific transduction pathway. Future studies are needed to validate these results in external populations. Citation Format: Anthony D'Amelio, Chi H. Nguyen, Randa El-Zein, Margaret R. Spitz, Xifeng Wu, Carol J. Etzel. Evidence for genetic mediation of lung cancer through hay fever. [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 1345. doi:10.1158/1538-7445.AM2013-1345
Abstract 3260: Identification and synthesis of benzimidazole carboxamides as potent inhibitors of focal adhesion kinase (FAK)
Authors: Sharad K. Verma, Jack D. Leber, Louis V. LaFrance, Mei Li, Celine Duquenne, Guanglei Cui, William H. Miller
Journal: Cancer Research (2011)

Abstract Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates signals from integrins and growth factor receptors. FAK has been reported to play a role in the regulation of cell survival, growth, spreading, migration and invasion. Overexpression of FAK mRNA and/or protein has been documented in many human tumors, including cancers of the breast, colon, thyroid, and prostate. FAK is regulated and activated by phosphorylation on multiple tyrosine residues. More significantly, there is evidence that phosphorylated FAK is increased in malignant compared to normal tissues. Accordingly, compounds that inhibit FAK activity are expected to be useful for the treatment of cancer. Cross-screening of the GSK compound collection led to the identification of benzimidazole carboxamides having weak FAK inhibitory activity. As benzimidazole carboxamides are known kinase templates, a structure based hit-to-lead optimization campaign was executed. Team efforts culminated in the rapid identification of a series of substituted benzimidazole carboxamides having highly potent and selective inhibitory activity towards FAK (i.e. FAK IC50 &amp;lt; 10 nM). The structure-based optimization of this series including the synthesis, binding mode, and profile of lead compounds will be described. 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 3260. doi:10.1158/1538-7445.AM2011-3260
Back to Nature
Authors: Jocelyn James, Daniel R. Kaul, Zachary D. Goldberger, Sanjay Saint, Shawn J. Skerrett
Journal: New England Journal of Medicine (2015)

A 28-year-old man presented with severe bifrontal headache, nausea, anorexia, sweats, and temperatures as high as 40.3°C. He reported no confusion, photophobia, visual changes, neck stiffness, sensory loss, sore throat, cough, dyspnea, diarrhea, or abdominal pain.
Abstract 1967: Ligand-dependent TGFβ signalling potential
Authors: Sarah E. McLean, John Di Guglielmo
Journal: Cancer Research (2011)

Abstract Transforming growth factor beta (TGFβ) is a cytokine which regulates many normal biological processes such as organogenesis and cell cycle control. Its signaling pathway is under intense study as it is commonly dysregulated in pathophysiological conditions such as cancer and fibrosis. The TGFβ signalling cascade is initiated by the binding of ligand to cell-surface serine-threonine kinase receptors. Binding of ligand to the TGFβ receptors initiates phosphorylation of intracellular signalling proteins called Smads, which can then enter the nucleus and initiate specific transcriptional programs. There are three TGFβ ligands which can activate canonical Smad signalling: TGFβ1, TGFβ2 and TGFβ3. These ligands share significant sequence homology (70-80%) but have different spatial and temporal patterns of expression in development. Although TGFβ1 and TGFβ3 are highly expressed in the tumour microenvironment, the role of TGFβ3 has been largely over-looked and thought to be the same as TGFβ1. The objective of the present study is to evaluate the signalling capacity of TGFβ1 and TGFβ3 in non-small cell lung cancer cells. Using dose response studies, we show that TGFβ1 ligand induces Smad2 phosphorylation to a greater extent than TGFβ3. We also show that TGFβ3 induces a lower reduction in steady-state levels of E-cadherin, a protein involved in cell-cell adhesion, compared to TGFβ1. To evaluate the transcriptional programs of both ligands, we used microarray technology to assess gene transcription in non-small cell lung cancer cells treated with TGFβ1 or TGFβ3. Consistent with our signalling data, we found that TGFβ3 induces far fewer genes than TGFβ1. Future studies will evaluate the differential roles of TGFβ1 and TGFβ3 in cancer cell migration and epithelial-to-mesenchymal transition. 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 1967. doi:10.1158/1538-7445.AM2011-1967
P2-16-09: Nipple-Areolar Sparing Mastectomy: Utility of the Lateral Inframammary Incision in Immediate Implant-Based Reconstructions.
Authors: AA Guth, K Blechman, C Levovitz, K Small, D Axelrod, N Karp, M Choi
Journal: Cancer Research (2011)

Abstract Purpose: Nipple and/or areola-sparing mastectomy as a therapeutic or prophylactic procedure for breast cancer is rapidly gaining popularity as the literature continues to support it safety. The lateral inframammary fold (IMF) approach provides adequate exposure and eliminates visible scars on the anterior surface of the breast, making this incision cosmetically superior to radial or periareolar approaches. Methods: We reviewed 58 consecutive nipple and/or areola-sparing mastectomies performed through a lateral IMF incision with immediate implant-based reconstruction, with or without tissue expansion, between June 2008 and February 2011. Prior to incision, breasts were lightly tumesced with dilute anesthetic solution with epinephrine. Sharp dissection, rather than electrocautery, was used as much as possible to minimize thermal injury to the mastectomy flap. When indicated, acellular dermal matrix was placed as an inferolateral sling. Subsequent fat grafting to correct contour deformities was performed in select patients. Three-dimensional (3D) photographs assessed changes in volume, antero-posterior projection, and ptosis. Retroareolar/nipple tissue underwent routine intraoperative frozen section analysis in cancer cases. Results: Mean patient age was 44 years, and mean follow-up time was 14 months. Depending upon the judgment of the oncologic surgeon, 44 (76%) mastectomies were nipple/areola-sparing, and 14 (24%) were areola-sparing. Thirteen mastectomies (22%) were therapeutic, the remaining 45 mastectomies (78%) were prophylactic. Five of the nine sentinel lymph node biopsies (56%) were performed through the lateral IMF incision without the need for a counter-incision. Acellular dermal matrix was used in 44 (76%) breasts. Average permanent implant volume was 313 cc (range 170 to 750 cc), and average fat grafting volume was 90 cc (range 36 to 177 cc). Mastectomy flap necrosis, requiring operative debridement, occurred in three breasts (5%). One of these breasts required a salvage latissimus dorsi myocutaneous flap to complete the reconstruction. Of the 44 nipple/areola sparing mastectomies, three (7%) required operative debridement and reconstruction for partial nipple necrosis. No statistically significant differences existed between therapeutic and prophylactic mastectomies for developing partial skin or nipple necrosis (p = 0.65). Morphologic outcomes using 3D scan measurements showed reconstructed breasts were larger, more projected, and less ptotic (196 vs. 248 cc, 80 vs. 90 mm, 146 vs. 134 mm, p &amp;lt; 0.01 for each parameter). Conclusion: Excellent results can be achieved with immediate implant-based reconstruction of nipple and/or areola-sparing mastectomy through a lateral IMF incision. NAC survival is reliable, and complication rates are low. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-09.
Differentiation of Right-Upper-Lobe Pneumonia from Bronchogenic Carcinoma
Authors: William M. M. Kirby, Wayne S. Waddington, Byron F. Francis
Journal: New England Journal of Medicine (1957)

IT is well established that slowly resolving pneumonias may indicate the presence of underlying pulmonary neoplasms. Even when special studies such as sputum cytology and bronchoscopy are negative, thoracotomy is often performed in such cases because of the possibility that a tumor is present. Although these principles are unquestionably sound, the risks of thoracotomy are by no means negligible, especially in elderly patients with borderline pulmonary function. In such cases it is obviously desirable to avoid a major surgical procedure whenever possible.The present paper is concerned with 23 patients observed during the past six years in whom delayed resolution . . .
Unanswered Questions About Margin Recommendations for Primary Cutaneous Melanoma
Authors: Joyce Y. Wong, Vernon K. Sondak
Journal: Journal of the National Comprehensive Cancer Network (2012)

Radical wide excision with appropriate margins based on depth of tumor invasion has been the standard adopted in NCCN and national clinical practice guidelines in oncology based on randomized controlled trial data. When carefully scrutinized, however, questions remain unanswered about what constitute appropriate margins in many frequently encountered clinical situations. In addition to the single characteristic of tumor depth, factors such as primary tumor location, histologic classification, and even specific patient characteristics may all contribute to risk for local recurrence, and therefore should potentially be considered in margin recommendations. This article addresses current uncertainty surrounding optimal margin status in primary cutaneous melanoma.
Abstract 2414: The inhibitory effect of heat treatment against Epithelial-Mesenchymal Transition (EMT) in human colon adenocarcinoma cell line
Authors: Satoko Adachi, Satoshi Kokura, Takeshi Ishikawa, Naoyuki Sakamoto, Manabu Okajima, Tatsuzo Matsuyama, Tatsuzo Matsuyama, Reiko Tsuchiya, Yuji Nito, Toshikazu Yoshikawa
Journal: Cancer Research (2012)

Abstract Background and Aim: In order to improve the prognosis of patients with advanced cancer, novel interventions for metastatic disease are required. While anti-tumor effects of hyperthermia have been well studied and assessed, its effects on cancer metastasis is unknown. We reported that the production of transforming growth factor-β (TGF-β) by cancer cell lines was reduced by the heat treatment, furthermore the production of the intratumoral TGF-β was also reduced by whole body hyperthermia in mouse subcutaneous tumor model. Recently, the importance of Epithelial-Mesenchymal Transition (EMT) in the progression of many cancers is recognized and many studies have shown that transforming growth factor-β (TGF-β) can induce EMT. Therefore, it is expected that heat treatment could inhibit TGF-β-induced EMT. In this study, we investigated the inhibitory effect of the heat treatment on TGF-β-induced EMT in the human colon adenocarcinoma cells. Methods: To study the effects of heat treatment on EMT, human colon adenocarcinoma cell line, HT29 cell, was used and treated with heat (43 degrees Celsius) for 1 h followed by the stimulation of TGF-β (10ng/ml). HT29 cells were examined for morphological changes using the inverted phases-contrast microscope, and the localization of E-cadherin as the epithelial adhesion factor on the cell was analyzed with fluorescent immunostaining using confocal microscope. The EMT-related factors such as vimentin, fibronectin, ZEB-1, Snail were analyzed by RT-PCR. Furthermore, the activation of nuclear factor kappa B (NF-κB) was analyzed in the nuclear extracts using an ELISA method. Results: After treatment with TGF-β, HT29 cells changed their morphology from a typical epithelium to mesenchymal spindle-shaped, and this morphological change was attenuated by the heat treatment. The expression of E-cadherin, which is the component of epithelial adhesion, was down-regulated by TGF-β, and this effect was attenuated when HT29 cells were treated with heat before the stimulation with TGF-β. The up-regulation of EMT-related factors such as fibronectin and Snail induced by TGF-β was decreased by the heat treatment. Furthermore, TGF-β treatment caused an activation of NF-κB, and heat treatment significantly attenuated TGF-β-indueced NF-κB activation in HT29 cells. Conclusions: Our results suggest that the heat treatment could suppress TGF-β-induced EMT via the inhibition of NF-κB, supporting its potential as a treatment for cancer metastasis. 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 2414. doi:1538-7445.AM2012-2414