tbuckley/cabot-search huggingface dataset:
Trop-2 is a novel PKC-dependent growth-stimulator trans-membrane molecule and a metastasis marker in human cancer
Authors: Saverio Alberti, Giovanna Vacca, Marco Trerotola, Emanuela Guerra, Cosmo Rossi, Rossana La Sorda, Rossano Lattanzio, Mauro Piantelli
Journal: Cancer Research (2006)

2483   Trop-2 is a 323 amino acid-long monomeric trans-membrane molecule involved in cell-cell adhesion, that transduces a calcium signal upon cross-linking (Ripani et al. Int. J. Cancer 76: 671,1998; Fornaro et al. Int. J. Cancer 62: 610, 1995). Global gene expression analysis of human cancers by SAGE and DNA arrays demonstrates that the TROP2 mRNA is overexpressed by cancers of the lung, stomach, colon, pancreas, kidney, liver and ovary. A large scale analysis of the expression of the Trop-2 protein was conducted in over 1500 cases human breast, colon, lung and ovary tumors and demonstrated that Trop-2 is overexpressed by a large fraction (42-85%) of the tumors analysed. These findings indicated a strong selective pressure for Trop-2 expression in cancer cells. Thus, we investigated a role of Trop-2 in transformed cell growth. Trop-2 expression significantly increased the growth rate of both fibroblastic / sarcomatous and epithelioid / cancerous cells at different stages of tumor progression both in man and in mouse (L, MTE, Igrov-1, KM12SM, 293) in vitro and in vivo. A deletion of the cytoplasmic region of Trop-2 abolished the Trop-2-dependent growth stimulation effect. Trop-2 is phosphorylated by PKC in Ser303 (Basu et al. Int. J. Cancer 62: 472, 1995). Mutagenesis of the Trop-2 cytoplasmic PKC phosphorylation site abolished the growth stimulatory role of Trop-2, showing dependence of PKC signaling. Yeast two hybrid, proteomic and phosphoproteomic analysis identified CREB and a novel homeodomain molecule as Trop-2 targets, starting unraveling the Trop-2 signaling pathway. Molecular modeling and N-terminal sequencing of the thyroglobulin domain of Trop-2 demonstrated a single proteolytic cleavage site between Arg87 and Thr88. Mutagenesis of the cleavage site abolished growth stimulation, indicating this as an activatory switch for Trop-2. Thus, Trop-2 is a novel, widespread, growth-stimulatory cell-surface molecule in human cancer. Strikingly, comparative gene expression profiling of metastatic cells indicated that TROP2 was the only gene up-regulated across different models and species. Consistently, most human colon, breast and ovary tumor metastases were verified to overexpress the Trop-2 protein, identifying Trop-2 as a unique marker of metastasis. Taken together, our findings identify Trop-2 as a novel key player in human tumor growth and as a unique marker of metastatic cancer. These results also candidate Trop-2 for novel diagnostic and therapeutic procedures.
Antiarrhythmic Effect of Reverse Ventricular Remodeling Induced by Cardiac Resynchronization Therapy
Authors: Luigi Di Biase, Maurizio Gasparini, Maurizio Lunati, Massimo Santini, Maurizio Landolina, Giuseppe Boriani, Antonio Curnis, Mario Bocchiardo, Antonio Vincenti, Alessandra Denaro, Sergio Valsecchi, Andrea Natale, Luigi Padeletti
Journal: Journal of the American College of Cardiology (2008)
Use of a geographic information system to map cases of measles in real-time during an outbreak in Dublin, Ireland, 2011
Authors: G Fitzpatrick, M Ward, O Ennis, H Johnson, S Cotter, M J Carr, B O’Riordan, A Waters, J Hassan, J Connell, W Hall, A Clarke, H Murphy, M Fitzgerald
Journal: Eurosurveillance (2012)

In 2011, there was a large measles outbreak in Dublin. Nationally 285 cases were notified to the end of December 2011, and 250 (88%) were located in the Dublin region. After the first case was notified in week 6, numbers gradually increased, with 25 notified in June and a peak of 53 cases in August. Following public health intervention including a measles-mumps-rubella (MMR) vaccination campaign, no cases were reported in the Dublin region in December 2011. Most cases (82%) were children aged between 6 months and 14 years, and 46 cases (18%) were under 12 months-old. This is the first outbreak in Dublin to utilise a geographic information system for plotting measles cases on a digital map in real time. This approach, in combination with the analysis of case notifications, assisted the department of public health in demonstrating the extent of the outbreak. The digital mapping documented the evolution of two distinct clusters of 87 (35%) cases. These measles cases were infected with genotype D4-Manchester recently associated with large outbreaks across Europe. The two clusters occurred in socio-economically disadvantaged areas and were attributable to inadequate measles vaccination coverage due in part to the interruption of a school-based MMR2 vaccination programme.
Dietary lutein inhibits DSS-induced colitis and associated colorectal carcinoma development in mice
Authors: Chun Liu, Roderick Bronson, Donald Smith, Robert Russell, Xiang-Dong Wang
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3815 

Background: Ulcerative colitis, characterized by chronic, relapsing, and remitting inflammation, is an established risk factor for colon cancer. High intake of dietary lutein has been consistently associated with a reduced risk for colon cancer in epidemiologic studies. However, it is unknown whether dietary lutein supplementation protects against colon carcinogenesis through the inhibition of colonic inflammation. Using an established dextran sulfate sodium (DSS)-induced colitis and associated colonic carcinoma mouse model, we evaluated the effects of dietary lutein supplementation at various doses on the DSS-induced inflammation, ulceration, hyperplasia, dysplasia, and cancers in the colon and rectum.    Methods: One hundred fifty female 8-week old Swiss-Webster mice (FER-Taconic) were assigned to one of ten groups (n = 15 in each group) for 18 weeks as follows: 1) 0.002% of lutein in the diet plus DSS; 2) 0.01% of lutein plus DSS; 3) 0.02% of lutein plus DSS; 4) 0.1% of lutein plus DSS; 5) DSS only; 6) 0.002% of lutein; 7) 0.01% of lutein; 8) 0.02% of lutein; 9) 0.1% of lutein; and 10) control without treatment. At week 4, the mice in groups 1-5 were provided with DSS for 4 cycles (1 cycle = 1 week 3% of DSS in drinking water followed by 2-week water) to initiate colitis and colorectal carcinoma.    Results: Dietary lutein supplementation increased plasma and colonic lutein concentrations in mice in a dose-dependent fashion. Plasma and colonic lutein concentrations in the groups that were provided with both dietary lutein and DSS were slightly lower than the corresponding groups that were supplemented with dietary lutein only. All four doses of dietary lutein (0.002%, 0.01%, 0.02%, and 0.1%) were found to reduce significantly the DSS-induced hemocult, loose stool, and severe colorectal hyperplasia. Dietary lutein at all four doses also decreased the DSS-induced severe colorectal inflammation and dysplasia, but only the doses of 0.002% and 0.01% were significant. In addition, all four doses of dietary lutein nonsignficantly lowered the DSS-induced colorectal cancer. Dietary lutein had no effect on the DSS-induced colorectal ulceration, except for the 0.1% of lutein group, which had significantly reduced numbers of ulceration as compared with the DSS only group. There were no detectable colorectal ulceration, inflammation, hyperplasia, dysplasia, and cancers in the groups administrated with dietary lutein only and the control (groups 6-10).    Conclusions: These data suggest that dietary lutein may provide a beneficial effect against the DSS-induced colorectal inflammation and associated cancer development in mice.
Reply to Wentao Liu, Xiaokun Zhao, Zhaohui Zhong's Letter to the Editor re: Marcus G. Cumberbatch, Matteo Rota, James W.F. Catto, Carlo La Vecchia. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. Eur Urol 2016;70:458–66
Authors: Marcus G. Cumberbatch, Matteo Rota, James W.F. Catto, Carlo La Vecchia
Journal: European Urology (2015)
Abstract 17717: Association of Depression with Soluble Urokinase- Type Plasminogen Activator Receptor and Other Markers of Inflammation and Immunity
Authors: Pankaj Manocha, Danny J Eapen, Riyaz S Patel, Hatem A Kassem, Ravi A Nanjundappa, Salman Sher, Nima Ghasemzadeh, Hamid S Syed, Ayman Samman Tahhan, Muhammad Hammadah, Amit J Shah, Pratik Pimple, Naureen Farook, Sarah S Kabani, Adil Niaz, Rostam Zafari, Tomasz Pielak, Christian W Thorball, Youssef O Garcia-Bengochea, Saket. Kumar, Heval M Kelli, Malik Obideen, Laurence Sperling, Emir Veledar, Ngoc-Anh Le, Charles L Raison, Arshed A Quyyumi, Viola Vaccarino
Journal: Circulation (2012)

Background: Depression, coronary artery disease (CAD), and inflammation may share pathophysiological links. Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker of inflammat...
Abstract 1109:In vivoloss of function screening reveals carbonic anhydrase IX (CAIX) as a key modulator of tumor initiating potential in primary pancreatic tumors
Authors: Nabendu Pore, Sanjoo Jalla, Brandon Higgs, Roger Liu, David A. Tice, Robert Hollingsworrth, Emil Michelotti, Claudio Sorio, Aldo Scarpa
Journal: Cancer Research (2015)

Abstract Re-programming of energy metabolism is one of the emerging hallmarks of cancer. Upregulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient derived pancreatic xenograft model. Lenti-viruses expressing shRNAs targeting twelve different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including CAIX, MCT4, and xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation since shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient derived pancreatic tumor model. Citation Format: Nabendu Pore, Sanjoo Jalla, Brandon Higgs, Roger Liu, David A. Tice, Robert Hollingsworrth, Emil Michelotti, Claudio Sorio, Aldo Scarpa. In vivo loss of function screening reveals carbonic anhydrase IX (CAIX) as a key modulator of tumor initiating potential in primary pancreatic tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1109. doi:10.1158/1538-7445.AM2015-1109
Haploidentical Transplantation For Patients With Advanced Hematologic Malignancies With Melphalan-Based Conditioning – Interim Results From a Phase II Clinical Trial
Authors: Sai Ravi Pingali, Milton Denai, Antonio Di Stasi, Partow Kebriaei, Uday R Popat, Amin Alousi, Paolo Anderlini, Simrit Parmar, Chitra M. Hosing, Borje S. Andersson, Qaiser Bashir, Sairah Ahmed, Betul Oran, Elizabeth J Shpall, Issa Khouri, Marina Konopleva, Gheath Alatrash, Richard E Champlin, Stefan O. Ciurea
Journal: Blood (2013)
P0281 : Decellularised human liver as a natural scaffold for 3D-disease modelling
Authors: G. Mazza, W. Al-Akkad, A. Telese, L. Longato, A. Hall, L. Urbani, B. Fuller, B. Davidson, M. Malago’, K. Moore, P. De Coppi, K. Rombouts, M. Pinzani
Journal: Journal of Hepatology (2015)
Autoantibody biomarker profiling for mucinous ovarian cancers
Authors: Liangdan Tang, Junzheng Yang, Allison Vitonis, Brian Liu, Daniel Cramer, Ross Berkowitz, Shu Ng
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4450 

Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Studies have suggested that patients with mucinous histologic subtypes of tumors respond poorly to standard platinum-taxane chemotherapy. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important biochemical pathways in disease. In order to study if there are specific antibody biomarkers in the plasma samples of mucinous ovarian cancer patients, we have initiated a screen by employing a reverse capture autoantibody microarray platform that uses native host antigens derived from mucinous ovarian tissues as baits for the capture of differentially labeled patient and control autoantibodies. By clustering analysis of the microarray data we have identified significant autoantibody biomarkers whose titers were elevated in the plasma samples of mucinous cancer patients. Interestingly, many of the antigens recognized by these autoantibody biomarkers are involved in the signaling pathways that regulate cytoskeleton remodeling, cell migration, growth and survival, suggesting that these antigens might be overexpressed in mucinous ovarian tumors and react with plasma autoantibodies. Further studies are required to evaluate functional significance and the clinical utility of these autoantibody biomarkers in mucinous ovarian cancer.
Abstract 18973: Left Ventricular Function Improvement After Recent MI in Patients Using a Wearable Cardioverter Defibrillator
Authors: Chingping Wan, Steven J Szymkiewicz
Journal: Circulation (2014)

Introduction: The wearable cardioverter defibrillator (WCD) has been used to protect AMI patients with reduced LVEF (≤35%) until ICD evaluation is recommended. The rate of EF improvement (e.g. EF&gt;35%) over the initial 8-12 weeks after AMI has not been reported. METHODS: The manufacturer-maintained registry was searched for AMI patients who received a WCD shock for VT/VF between 05/2008 and 02/2013. The treated group was matched (1: ~4) with event-free WCD patients by ICD-9 code (410.*), gender, age and prescription date. Chart notes were reviewed for clinical characteristics. Follow-up was assessed through the registry and Social Security Death Master File. RESULTS: There were 992 (age=63±12, female=20.2%) AMI patients included in the final analysis, 206 treated by WCD and 786 event-free patients. Median follow-up was 334 days. Mean length of WCD use was 67±506 (median=38) days. Subgroup clinical characteristics are presented in Table 1. In the event-free group, 289 (38.9%) patients showed EF improvement to &gt;35%. Nine (4.5%) in the treated group continued wearing the WCD until EF recovery, while 125 (60.7%) received ICD. Absence of recorded heart failure and/or diabetes were associated with LVEF recovery (p&lt;.0001). CONCLUSION: In our study, almost 40% of AMI patients with initial EF ≤35% had EF improvement in two months. The EF recovery group had lower rates of heart failure and diabetes. WCD allows time for left ventricular function recovery in low EF post MI patients, optimizing ICD implantation decisions.
Book: Textbook of Clinical Medicine for Asia
Authors: C. F Gilks
Journal: BMJ (1999)

Eds J Y Sung, P K T Li, J E Sanderson, J Woo Chinese University Press, $60, pp 848 ISBN 962 201 773 8 ——————— Rating:![Graphic][1]</img> This book reminds me just how advantaged we Western Europeans are in medical education. As students, we can read textbooks of medicine that are predicated on diseases common and relevant in our environment, with epidemiology, clinical features, and treatment based on information gathered from industrialised societies. Such advantages are even greater for those that have English as their first language because most medical literature uses this … [1]: /embed/inline-graphic-1.gif
Abstract 2992: Percutaneous Coronary Intervention With Drug Eluting Stents Versus Left Internal Mammary Artery Grafting For Patients With Isolated Lesion In The Proximal Segment Of Left Anterior Desceding Coronary Artery, Suffering From Chronic Stable Angina.
Authors: Sophia Vaina, Konstantinos Toutouzas, Chrysoula Patsa, Eleftherios Tsiamis, Elli Stefanadi, Ioannis Chlorogiannis, Anastasios Spanos, Dimitrios Illiopoulos, Mathaios Panagiotou, Manolis Vavouranakis, Eustratios Pattakos, Christodoulos Stefanadis
Journal: Circulation (2007)

Introduction: Coronary artery bypass grafting (CABG) with left internal mammary artery (LIMA) and percutaneous transluminal coronary angioplasty (PCI) with drug eluting stent (DES) implantation are both effective to treat ischemic heart disease. In the current study we evaluated the long term results of the two methods in patients (pts) with isolated proximal left anterior descending artery lesion (pLAD), suffering from chronic stable angina (CSA). Methods: We included 280 pts, 170 with DES implantation and 110 with LIMA grafting. Primary end points were the occurrence of major adverse cardiac events (MACE), defined as: Death, myocardial infarction and target vessel revascularization (TVR). Secondary end-points included the length of hospitalization, in-hospital complications and the recurrence of chest pain. Pts were followed-up clinically. Results: Mean follow-up period was two years (midrange, one to three years). MACE was 5.29% in the DES group and 2.72% in the surgical group (p=0.37). TVR was 3.52% after PCI and 0% after CABG (p=0.08). The event-free survival curve was similar between the two groups (Figure ). More in-hospital complications were observed in the surgical group compared with the PCI group (16.36% vs. 1.17%, respectively, p=0.01). Recurrent angina was 4.11% in the DES group and 6.36% in CABG group (p = 0.41). Conclusions : In the current study the two procedures had similar long-term results, even though the surgical approach was associated with increased in-hospital complications and longer hospitalization. Therefore, both revascularization modalities can be used to treat pLAD lesions in pts with CSA.
Methyl jasmonate, a plant stress hormone, inhibited proliferation and induced cell death in human prostate cancer cells in culture
Authors: Daniel E. Ezekwudo, Abiodun Elegbede
Journal: Cancer Research (2004)

2990  The jasmonates, consisting of cis-jasmone (CJ), methyl jasmonate (MJ), and jasmonic acid (JA) are a family of plant stress hormones. In plants, these compounds activate cellular responses to diverse conditions, including cell death, to protect plants that come under biotic stress such as insect attack or wounding. Human prostate cancer is a hormone-dependent cancer. We studied the effects of the jasmonates on the proliferation of human prostate adenocarcinoma cell lines (PC-3, HTB-81) and the human fibroblast cell line (HFL-1) using the mitochondrial dehydrogenase activity (MTT) and the colony formation (CFA) assays. The mechanism of inhibition of proliferation by these agents was studied using flow cytometry and western blotting techniques. Cytotoxicity assays showed that the jasmonates inhibited proliferation of the cells in both dose- and kinetic-dependent fashions. The relative efficacy, as measured by the concentration of agent that inhibited proliferation by 50% (IC50) was MJ>>CJ>JA. Flow cytometric and other analyses confirmed that the inhibition of proliferation by these agents was as a result of induction of cell death via apoptosis. Our results indicate a potential application of the jasmonates in the treatment of human prostate cancer. [The work was supported in part by grants from ACS #IRG-103719 and UNLV 2002-2003 Planning Initiative Award (to JAE)].
Abstract 21641: Blocking Endothelial-Monocyte-Activating-Polypeptide-II Improves Remodeling After Chronic Myocardial Infarction by Promoting Angiogenesis
Authors: Misun Park, Pallavi Solanki, Chull Hong, Shumin Gao, Luke F Fritzky, Stephen F Vatner, Margaret A Schwarz, Dorothy E Vatner
Journal: Circulation (2010)

Endothelial-monocyte-activating-polypeptide-II (EMAP-II) is a pro-inflammatory cytokine with anti-angiogenic properties. We examined whether blocking the effects of EMAP-II with a functional blocking antibody of EMAP-II (EMAP-II AB) affected myocardial remodeling and angiogenesis following chronic myocardial infarction (MI). C57BL/6J mice received either a control vehicle (IgG) or EMAP-II AB via i.p. injection after MI. At 4 weeks after MI, LV function, assessed by LV ejection fraction (EF), was reduced in the vehicle group (35±2%, n=7) compared with sham operated controls (72±1%, n=4). Blocking EMAP-II preserved LV EF (53±4%, n=10) compared with vehicle group, p<0.05. The interstitial collagen (%) was examined by Picric Acid Sirius Red staining. Blocking EMAP-II reduced the amount of interstitial fibrosis (4.8±0.5%) compared to the vehicle group (7.6±0.7%). Since % survival was greater in EMAP-II AB treated group (57%) than in the vehicle group (36%), it is likely that the above data underestimated the b...
Abstract 3857: The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS
Authors: Batchimeg Norjmaa, Takayuki Saitoh, Tetsuhiro Kasamatsu, Yusuke Minato, Noriaki Sunaga, Hirokazu Murakami
Journal: Cancer Research (2015)

Abstract Background: X-ray repair cross-complementing group 1 (XRCC1) is involved an important role in base excision repair (BER) system of DNA repair. Polymorphism in DNA repair genes may be modified of DNA repair capacity. However, it is unclear that the polymorphisms of XRCC1alter the clinical features of MDS patients. Our study was performed to evaluate the effect of the XRCC1Arg194Trp and the XRCC1Arg399Gln with the susceptibility and clinical features of MDS. Methods: We genotyped the polymorphisms by using polymerase chain reaction -restriction fragment-length polymorphism (PCR-RFLP) analysis in 119 patients with MDS [median 67.9 years, range 17.1-86.5 years; male/female 81/38; RCUD (n = 40), RARS (n = 6), RCMD (n = 21), MDS-U (n = 13), RAEB-1(n = 14), RAEB-2 (n = 12), others (n = 13)] and 202-health controls. Results: In the allele and genotype frequencies of the XRCC1Arg194Trp and the XRCC1Arg399Gln were not statistically significant difference in patients and the controls. However, Arg/Arg genotypes of XRCC1 194 and the XRCC1 399 were significantly associated with lower Hb. In addition, XRCC1 399 non Arg/Arg genotype was significantly associated with previous history of radiotherapy and multiple cancers. Furthermore, XRCC1Arg194Trp non Arg/Arg genotype and XRCC1Arg399Gln Arg/Arg genotype were significantly associated with poor prognosis of MDS patients. Conclusion: We found that the polymorphisms of XRCC1 may be affected the clinical features and the prognosis of MDS. Citation Format: Batchimeg Norjmaa, Takayuki Saitoh, Tetsuhiro Kasamatsu, Yusuke Minato, Noriaki Sunaga, Hirokazu Murakami. The polymorphisms of XRCC1 Arg194Trp and the XRCC1Arg399Gln affect the clinical features and the prognosis of MDS. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3857. doi:10.1158/1538-7445.AM2015-3857