tbuckley/cabot-search huggingface dataset:
Abstract LB-17: WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ
Authors: Siew Wee Chan, Chun Jye Lim, Caixia Huang, Yaan Fun Chong, Kieran Harvey, Wanjin Hong
Journal: Cancer Research (2010)

Abstract The transcriptional co-activators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. YAP and TAZ both possess WW domains which are important protein-protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY. The WW domains of YAP play complex regulatory roles as exemplified by two recent reports showing that they can positively or negatively influence YAP activity in a cell and context-specific fashion. In this study, we show that the WW domain of TAZ is important for it to transform both MCF10A and NIH3T3 cells and to activate transcription of ITGB2 but not CTGF, as introducing point mutations into the WW domain of TAZ (WWm) abolished its transforming and transcription-promoting ability. Using a proteomic approach we discovered potential regulatory proteins that interact with TAZ WW domain and identified Wbp2. The interaction of Wbp2 with TAZ is dependent on the WW domain of TAZ and the PPXY-containing C-terminal region of Wbp2. Knockdown of endogenous Wbp2 suppresses, whereas overexpression of Wbp2 enhances, TAZ-driven transformation. Forced interaction of WWm with Wbp2 by direct C-terminal fusion of full-length Wbp2 or its TAZ-interacting C-terminal domain restored the transforming and transcription-promoting ability of TAZ. These results suggest that the WW domain-mediated interaction with Wbp2 promotes the transforming ability of TAZ. 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-17.
Abstract 2927: Gefitinib, an EGFR inhibitor, prevents progression of PanINs to pancreatic carcinoma in a preclinical conditional <i>LSL-K-rasG12D</i> transgenic mice model
Authors: Altaf Mohammed, Naveena B. Janakiram, Li Qian, Venkateshwar Madka, Misty Ely, Stan Lightfoot, Vernon E. Steele, Chinthalapally V. Rao
Journal: Cancer Research (2010)

Abstract Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy is a devastating disease with dismal prognosis (5-year survival rate of less than 5%), and is the fourth leading cause of cancer deaths in the USA. Developing novel strategies to prevent or delay the progression of pancreatic cancer is currently of intense interest. We studied chemopreventive efficacy of gefitinib, an EGFR inhibitor on pancreatic intraepithelial neoplasms (PanINs) and adenocarcinoma in conditional LSL-K-RasG12D transgenic mice. LSL-K-RasG12D and P48Cre mice were bred and offspring of activated K-rasG12D were generated. Six-week old male KrasG12D (20/group) and wild-type (12/group) mice were fed (AIN-76A) diets containing 0, 100, and 200 ppm gefitinib for 35 weeks. At the time of sacrifice, pancreas were collected, weighed, and were evaluated histopathologically for PanINs and PDAC. To understand the molecular mechanisms, expression levels of PCNA, p38, cyclin D1, C2GNT, RhoA, β catenin, pERK, EGFR and Cav1, were determined in pancreatic tissues by IHC, immuno-fluorescence, immunoblotting and/or RT-PCR. Results suggest that mice fed with 100 and 200 ppm gefitinib had significantly reduced (p&amp;lt;0.0001) ductal adenocarcinomas incidence than control diet fed mice. Importantly, significant reduction of pancreatic ducts with carcinoma (&amp;gt;94%, p&amp;lt; 0.0001) and suppression of PanIN 3 (∼34%) was observed in mice fed diet with gefitinib. We did find statistically significant dose dependent inhibition of PanIN 1 &amp; 2 lesions between control and gefitinib fed groups. Also, mice fed gefitinib showed reduced pancreatic tumor weights (∼50%) compared to control diet fed mice. Furthermore, treated mice showed &amp;gt;75% of pancreas free from carcinoma. Also, pancreas of mice fed gefitinib diets showed significantly reduced expressions of PCNA, p38, EGFR, RhoA, C2GNT, β-catenin, pERK, caveolin-1, and a significant increase in cyclin B1 (p&amp;lt;0.005) levels compared to pancreas of control diet fed mice. In summary, our results suggest that gefitinib prevents the progression of pancreatic cancer precursor lesions in PanIN 1, 2 and 3 stages from further progressing to adenocarcinoma in a preclinical model. These data highlight the promise of chemoprevention in pancreatic cancer and administration of EGFR inhibitors represents an important strategy to prevent pancreatic cancer in high-risk patients. 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 2927.
354 PREVALENCE OF AND RISK FACTORS FOR COMBINED cART ASSOCIATED DRUG-INDUCED LIVER INJURY IN HIV/HBV COINFECTED, HIV/HCV COINFECTED, AND HIV MONOINFECTED PATIENTS
Authors: M. Mandorfer, B.A. Payer, T. Reiberger, N. Pfisterer, M.C. Aichelburg, A. Rieger, M. Trauner, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2013)
Abstract 5002: Posttranslational modification of E2F1 during melanoma progression
Authors: Peng Meng, Rita Ghosh
Journal: Cancer Research (2011)

Abstract Melanoma, the malignant tumor of melanocytes, accounts for approximately 78% of skin cancer related deaths. No current treatment significantly enhances disease-free survival once distant metastases have established. To facilitate the development of effective treatment strategies, it is imperative that we obtain a better understanding of the biology of melanoma cells as they progress through the various stages of disease. Previous studies have shown that E2F1, a transcription factor, is over-expressed in melanoma cells. Interaction between E2Fs and tumor suppressor, Rb is essential for regulation of cell cycle progression. E2F1 is known to be involved in other important biological processes, including DNA damage, DNA repair, differentiation, development, autophagy and apoptosis. However, the mechanism through which E2F1 is elevated in melanoma remains unknown. In normal cells in late S phase, E2F1 is recognized by the E3 ligase p45 SKP2, undergoes ubiquitination and is finally degraded in 26S proteasome. Since multiple post-translational modifications have been reported to affect the stability and functions of E2F1, we have hypothesized that during melanoma progression E2F1 fails to undergo degradation and this failure is due to post-translational modification of E2F1. In this study we have used melanoma cells of increasing disease progression. Our results show that primary melanoma cells have high level of E2F1 message and protein. We also found that E2F1 protein levels are not tightly regulated during cell cycle progression. Levels of E2F1 remain constantly high during cell cycle progression in the less metastatic melanoma cells. Consistent with these results, phosphorylation of E2F1 at Serine 337 is almost unchanged during cell cycle progression in the less metastatic melanoma cells. These results taken together suggest that this post-translational modification site may play an important role in stabilization of E2F1 in the primary melanoma cells that represent the radial and vertical growth phases of melanoma. Since modifications usually induce conformational changes, which may affect any following modifications, it is necessary to study the crosstalk among different modifications like acetylation and phosphorylation. The modifications towards the same direction may generate a specific array of modifications that can induce markedly stronger functional effects compared with those produced by the sum of single modifications. Therefore, it is intriguing to detect the coordination of different modifications and determine if there is such a modification array that regulates the stabilization and degradation of E2F1 resulting in the elevated E2F1 levels in melanoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5002. doi:10.1158/1538-7445.AM2011-5002
The Use of Hepatocyte Extraction Fraction To Evaluate Neonatal Cholestasis
Authors: VASUNDHARA TOLIA, SAM R. KOTTAMASU, DURDANA TABASSUM, PIPPA SIMPSON
Journal: Clinical Nuclear Medicine (1999)

Hepatobiliary scintigraphy is used routinely to evaluate infants with neonatal cholestasis. Hepatobiliary scintigraphy determines biliary patency by detecting radioactivity in the bowel on imaging, in duodenal and gastric aspirates, or all of these. During hepatobiliary scintigraphy, the hepatocyte extraction fraction (HEF) is calculated by deconvolution analysis. Normal values of HEF are more than 90%. It is believed that HEF may predict hepatic dysfunction, because, during hepatobiliary scintigraphy, the radiopharmaceutical used in this test is extracted by the hepatocytes from the blood stream. Therefore, a low value of HEF is seen with more severe hepatocellular disease. The goal of this study was to determine whether HEF has any correlation with synthetic liver function, whether HEF can differentiate obstructive from nonobstructive lesions that cause neonatal cholestasis, and whether HEF can predict the outcome of the different causes of neonatal cholestasis.A retrospective analysis of 68 hepatobiliary scintigraphy results was done in patients with neonatal cholestasis for a period covering 6 years.The HEF was available in 67 of these 68 patients, with a median value of 25% (range, 3.3% to 100%). The results of synthetic liver function tests (i.e., albumin and prothrombin time) were normal in all infants with neonatal cholestasis. No significant correlation was detected between HEF and the serum levels of total and direct bilirubin, albumin, alkaline phosphatase, and prothrombin time by exploratory data analysis (R = 0.08; small, P > 0.2). The HEF values in different causes of neonatal cholestasis were compared: extrahepatic biliary atresia, neonatal hepatitis, and a miscellaneous category consisting of alpha1-antitrypsin deficiency, ischemic hepatitis, paucity of bile ducts, and others. The outcomes of these diseases were assessed as resolution, continuing disease, transplantation, or death, but no predictive correlation was found with HEF.A single determination of HEF is of no value in assessing synthetic liver function (as assessed by albumin and prothrombin time), specific diagnoses, and outcomes in patients with neonatal cholestasis. Therefore, a low isolated value of HEF should not be considered suggestive of poor prognosis and outcome in these patients.
Role of Axillary Ultrasound in Defining Surgical Management of Breast Cancer Patients with Nodal Disease.
Authors: A. Syed, M. Garbos, A. Patel, H. Bradpiece, J. Stephanie
Journal: Cancer Research (2009)

Abstract Background:With the introduction of Sentinel Lymph Node Biopsy, breast cancer patients with nodal disease have to undergo second surgical axillary procedure. The aim of our study was to correlate the accuracy of ultrasound in redefining surgery in breast cancer patients.Methods:The records of all breast cancer patients who underwent Axillary Lymph Node Dissection (ALND) from January 2008 to December 2008 were reviewed. Of these, patients who had pre operative axillary ultrasound and/or fine needle aspiration cytology were included. All ultrasound were performed by the radiologist with special interest in breast imaging at our breast centre. Comparison of the ultrasound and FNA findings with ALND findings was performed.Results:Seventy Five patients had axillary ultrasound during this period. Twenty five patients (32.3%) had abnormal ultrasound findings. Of these, 22 patients had positive surgical staging and three patients had negative surgical staging. Ten of the abnormal axilla had FNAC done. Of these, seven patients had metastatic cells and all of these patients have finally proven to have positive axillary lymph nodes. Of the fifty patients (67.7%) with normal axilla, 34 patients had negative surgical staging and 16 had positive staging The sensitivity of ultrasound axilla was 57.89%, and specificity was 96%. The positive predictive value was 88% and the negative predictive value was 78.57%Discussion:Ultrasound examination of axilla is a safe and fast method of assessing the lymph nodal status in the preoperative staging of axilla. The results of our study are mostly in agreement with previous published studies. This will reduce the number of patients having to undergo a second axillary procedure, hence saving resources both financially and operating time. It will reduce the number of hospital admissions for the patient; improve cost effectiveness and the patient pathway. We therefore recommend routine axillary ultrasound with FNAC of suspicious/pathological nodes to avoid sentinel node procedure i.e., proceed directly to axillary clearance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1033.
TCT-236 The Diastolic Wave-Free Period Is The Most Suitable Period In The Cardiac Cycle For The Assessment Of A Coronary Stenosis: Implications For The Accurate Calculation Of The Instantaneous Wave-Free Ratio (iFR)
Authors: Sayan Sen, Ricardo Petraco, Sukhjinder Nijjer, Nicolas Foin, Christopher Broyd, Rodney Foale, Iqbal Malik, Ghada Mikhail, Darrel Francis, Alun Hughes, Jamil Mayet, Carlo Di Mario, Javier Escaned, Justin Davies
Journal: Journal of the American College of Cardiology (2012)
Unexpected Primary Osseous Lymphoma as the Cause of Lactic Acidosis in a Patient Suffering From Pancreatitis
Authors: Li Huo, Yaping Luo, Taiping Zhang, Zhaohui Zhu, Fang Li, Yupei Zhao
Journal: Clinical Nuclear Medicine (2010)

A 45-year-old man was admitted due to acute pancreatitis. A severe lactic acidosis was found. Following active therapy, the signs and symptoms from pancreatitis was improved, but acidosis was exacerbated. FDG PET/CT images were acquired to investigate the etiology of lactic acidosis and/or other unknown pathology. The images showed widespread abnormal FDG activity in the bone marrows throughout the body, suggestive of hematologic malignancy, which was confirmed as primary osseous non-Hodgkin lymphoma following a histopathological examination of the bone marrow. Chemotherapy against lymphoma was initiated and status of the lactic acidosis was rapidly corrected.
Aortic-Valve Homograft in the Treatment of Aortic Insufficiency
Authors: A. J. Kerwin, S. C. Lenkei, D. R. Wilson
Journal: New England Journal of Medicine (1962)

THE surgical relief of both congenital and acquired valvular obstruction has been one of the major advances in the recent history of cardiac surgery. Because of the technical difficulties involved the repair of incompetent valves has made much slower progress. In this situation a blind procedure is obviously unsatisfactory. The surgeon therefore requires direct visualization of the valve and sufficient time to evaluate the nature of the problem. An open procedure necessarily involves the maintenance of circulation by a heart-lung machine, with its attendant difficulties and increased morbidity rate. Notwithstanding good anesthetic and operative technics the surgeon may encounter such . . .
Reply to Grimminger &amp; Hölscher
Authors: J. Leyden, G. Harewood, D. McNamara
Journal: Endoscopy (2012)

We would like to thank Grimminger & Hölscher for their comments. It is true that the indications for colonoscopy were not reviewed in our study; however we would contend that that the surgical and gastroenterology patient cohorts were not notably dissimilar. In Ireland a significant proportion of gastrointestinal endoscopies are performed by surgeons; in some institutions all such procedures are done by surgeons. In 2006 – 2007, 40 % of colonoscopies at our institution were performed by the surgical service. Our endoscopy service is structured in such a way that much of the outpatient cohort is shared non-selectively between surgeons and gastroenterologists. Furthermore, patients with a prior history of surgery are not followed up exclusively by the surgical service, and the surgical clinics incorporate screening and surveillance colonoscopies.
Childhood Obesity and a Diabetes Epidemic
Authors: Albert P. Rocchini
Journal: New England Journal of Medicine (2002)

Childhood obesity has reached epidemic proportions; worldwide, approximately 22 million children under five years of age are overweight.1 During the past three decades, the number of overweight children in the Unites States has more than doubled. In 1983, 18.6 percent of preschool children in the United States were defined as overweight, and 8.5 percent were defined as obese; by 2000, 22.0 percent of preschool children were overweight and 10.0 percent were obese.1 Data from the National Longitudinal Survey of Youth indicate that the prevalence of overweight has increased by 21.5 percent among non-Hispanic black children, 21.8 percent among Hispanic children, . . .
Is capsule endoscopy a useful modality for the emergency triage of upper gastrointestinal hemorrhage?
Authors: Long Xu, Meifang Huang, Bing Xia
Journal: Endoscopy (2014)

We recently read the article by Gralnek et al. [1]. The authors conducted a proof-of-concept study, which we found quite interesting. However, we believe that two issues presented in the study warrant further review.
Alteration in the Natural History of Neurosyphilis by Concurrent Infection with the Human Immunodeficiency Virus
Authors: Donald R. Johns, Maureen Tierney, Donna Felsenstein
Journal: New England Journal of Medicine (1987)

Within the past 18 months, we have seen four cases of neurosyphilis at our institution (two of meningovascular syphilis, one of acute syphilitic meningitis, and one of asymptomatic neurosyphilis) in young homosexual men with serologic evidence of exposure to human immunodeficiency virus (HIV). Two of the four patients had neurosyphilis despite previous adequate therapy for early syphilis with benzathine penicillin. Meningovascular syphilis developed in one patient within four months after a primary infection, in a manner consistent with an accelerated course of syphilitic infection. These findings suggest the possibility that HIV infection may alter the natural course of syphilis because of the profound defects in cell-mediated immunity it causes. The possible potentiating effects of HIV on Treponema pallidum infection suggest the need for lumbar puncture in the evaluation of HIV-seropositive patients with syphilis, as well as modifications of the currently recommended treatment regimens for primary, secondary, and latent syphilis and neurosyphilis in this patient population. Neurosyphilis should probably be added to the growing list of infectious complications of the acquired immunodeficiency syndrome (AIDS) and may be the first such complication to appear.
Abstract PL01-01: Effective translation of cancer discoveries to cancer treatment
Authors: William N. Hait
Journal: Cancer Research (2011)

Abstract The objective of this presentation is to analyze the current status of translational research to understand the reasons for success, the barriers to further progress, and the insights that will continue to accelerate the enterprise. I will postulate that the most impactful drugs were developed because of specific observations about a type of malignancy rather than by studying targets in isolation. This will be tested by reviewing major scientific breakthroughs throughout the modern era of cancer treatment and will focus on the importance of biomarkers and companion diagnostic tests. Examples of how the merging of a deep understanding of a particular tumor type with modern cancer biology and cancer genomics will be presented. I will begin by attempting to define translation as the application of discoveries to the practice of medicine, a process that begins with a clinical observation that leads to a discovery, whose significance to a specific medical problem is recognized and acted upon. Each step in the process requires critical skill sets that span basic biology, pathology, pharmacology, clinical, and regulatory science. The challenges confronting those who participate have been carefully described and a variety of approaches to break down barriers are being continuously tested and upgraded. Although the success rate for drug development in oncology is lower than hoped, the number of new medical and biological entities moving into the clinic and on track for approval is immense, outpaces any other therapeutic area, and offers enormous hope to patients, physicians, and investigators alike. 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 PL01-01. doi:10.1158/1538-7445.AM2011-PL01-01
Abstract 1064: The combined activation of MET signaling and PKCα is sufficient to induce tumors in mouse skin.
Authors: Christophe Cataisson, Fan Liu, Lisa N. Wright, Anne Zhuang, Glenn Merlino, Stuart H. Yuspa
Journal: Cancer Research (2013)

Abstract Aberrant activation of MET signaling has been identified in multiple cancers but its relation to cancer-associated inflammation has not been explored. To address this issue in the context of skin carcinogenesis, a double transgenic mouse model (MT1-HGF/ K5-PKCα or DT) was generated. K5-PKCα mice that overexpress PKCα in basal keratinocytes develop a strong neutrophilic cutaneous inflammatory response upon topical TPA (12-tetradecanoylphorbol-13-acetate) application. These mice were crossed with MT1-HGF mice that overexpress HGF under a metallothionein promoter to create MT1-HGF/ K5-PKCα double transgenic (DT) mice and their respective controls. We observed that DT animals were very sensitive to squamous carcinogenesis. Using a low promoting dose of TPA that primarily activates PKCα in K5-PKCα or DT mice yielded an average of 6 tumors per mouse in the DT group; single transgenic K5-PKCα or MT-HGF mice developed an average of 1 tumor while WT developed none at this TPA dose. We hypothesize that in DT mice, keratinocyte-derived HGF synergizes with PKCα to drive tumor promotion and increase tumor growth. Primary keratinocytes derived from MT1-HGF or DT mice display a phenotype reminiscent of EGFR activated cells: increased expression of pro-inflammatory factors, upregulation of Keratin 8 (K8) and downregulation of K1 and K10 mRNAs. Indeed western blot analysis shows that EGFR is transactivated in MT1-HGF and DT keratinocytes and cell proliferation is elevated as well but not in K5-PKCα or WT keratinocytes. The release of CXCL1,a hallmark of RAS transformation, is augmented in RAS-keratinocyte cell culture supernatants with MT1-HGF and DT keratinocytes producing the most in the absence of RAS-transduction. Blockade of EGFR or IL-1 activity can mitigate the HGF-induced RAS-phenotype. K5-PKCα and DT mice exhibit the same acute inflammatory response and regenerative epidermal hyperplasia following low dose TPA treatment. When promoted for 10 weeks with TPA, 100% of DT mice but none of the single transgenic controls developed squamous papillomas in the absence of DMBA-mediated initiation. Our data suggest that the synergistic activity of Met and PKCα can substitute for the lack of RAS mutation during skin carcinogenesis. It remains to be determined if that mechanism could provide an alternate route to transformation in human skin tumors lacking RAS mutations. Citation Format: Christophe Cataisson, Fan Liu, Lisa N. Wright, Anne Zhuang, Glenn Merlino, Stuart H. Yuspa. The combined activation of MET signaling and PKCα is sufficient to induce tumors in mouse skin. [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 1064. doi:10.1158/1538-7445.AM2013-1064