tbuckley/cabot-search huggingface dataset:
Tissue-array analysis of molecular markers of cell signaling and apoptosis in fibrolamellar hepatocellular carcinomas (FL-HCC)
Authors: Ghassan El Maalouf, Sandrine Faivre, Christophe Le Tourneau, Alexandre Cortes, Chantal Dreyer, Jacques Belghiti, Francoise Degos, Eric Raymond, Valerie paradis
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4494 

Purpose: FL-HCC is a rare variant of HCC occurring in young patients without prior history of hepatic dysfunction. FL-HCC remains an orphan disease that displays resistance to cytotoxic chemotherapy. This study aimed to characterize molecular markers that may help understanding mechanisms of drug-resistance and to identify targets for novel therapies. Methods: Paraffin-embedded tumor tissues from 16 consecutive patients who underwent surgical resections of FL-HCC in our institution were collected, centrally reviewed, and further confirmed by immunohistochemistry (IHC) showing CK7 and CK19 expression in 100% and 60%, respectively. Levels of expression of EGFR, phospho-AKT(p-AKT), PTEN, p53 and bcl-2 were examined in those specimens using a semi-quantitative scoring system from 0 to 3 (0: no positivity, 1: positivity in   30% of tumor cells). Survival was analyzed using Kaplan-Meier analysis. Results: Expressions of EGFR and p-AKT were found in 94% and 69% of patients, respectively (Table 1). In contrast, PTEN was not expressed in any tumor specimens suggesting that PTEN loss of function and EGFR signaling may be involved in AKT-activation and may drive tumor growth. Bcl-2 and p53 are key proteins that may control cellular apoptosis. Interestingly, none of the specimens expressed bcl-2 and few specimens (3 patients - 18%) expressed p53 suggesting functional apoptosis. With median follow-up of 32 months, the median overall survival was 148 months. Although not statistically significant, there was a trend toward a better survival in patients with high phospho-AKT expression and low EGFR expression in tumors. Conclusions: Our study demonstrates that both activation of EGFR/AKT signaling pathway and functional apoptosis characterizes FL-HCC and may be involved in the pathogenesis of this tumor. Therefore, EGFR- and mTOR-inhibitors may be further evaluated as candidate drugs in FL-HCC.



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Sexual health services in England lack clear accountability and proper oversight, says report
Authors: Caroline White
Journal: BMJ (2015)

The changes to healthcare made under the previous health secretary, Andrew Lansley, have left sexual health and HIV services in England without any clear lines of accountability or proper oversight of the quality and outcomes they deliver, concludes a report by a cross party group of peers and MPs.1

The All Party Parliamentary Group on Sexual and Reproductive Health launched an inquiry last August, prompted by concerns that the new arrangements were fragmenting commissioning and service provision and creating “silos” in previously integrated areas of public health.

The reorganisation made local government accountable for the bulk of sexual health services, as part of its new public health remit, with the remainder split between primary care and NHS England (box).

But the report, which drew on written and spoken evidence to the inquiry from a wide range of people and organisations working in sexual and reproductive health, found that although the restructuring had created new national bodies, such as NHS England and Public Health England, lines …
TRPM4 in cardiac electrical activity
Authors: Romain Guinamard, Patrice Bouvagnet, Thomas Hof, Hui Liu, Christophe Simard, Laurent Sallé
Journal: Cardiovascular Research (2015)

TRPM4 forms a non-selective cation channel activated by internal Ca2+. Its functional expression was demonstrated in cardiomyocytes of several mammalian species including humans, but the channel is also present in many other tissues. The recent characterization of the TRPM4 inhibitor 9-phenanthrol, and the availability of transgenic mice have helped to clarify the role of TRPM4 in cardiac electrical activity, including diastolic depolarization from the sino-atrial node cells in mouse, rat, and rabbit, as well as action potential duration in mouse cardiomyocytes. In rat and mouse, pharmacological inhibition of TRPM4 prevents cardiac ischaemia–reperfusion injuries and decreases the occurrence of arrhythmias. Several studies have identified TRPM4 mutations in patients with inherited cardiac diseases including conduction blocks and Brugada syndrome. This review identifies TRPM4 as a significant actor in cardiac electrophysiology.
Unusual Locations for Lymphomas
Authors: Görgün Akpek, Esen K. Akpek, Shiyong Li, Richard W. Green, Terrence P. O’Brien, Michael J. Borowitz
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.11.2964 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11387371 Unusual Locations for Lymphomas Case 3. Successive Occurrence of Peripheral T-Cell Lymphoma With Bilateral Conjuctival Involvement in a Patient With Low-Grade B-Cell Lymphoma Görgün AkpekxGörgün AkpekSearch for articles by this author , Esen K. AkpekxEsen K. AkpekSearch for articles by this author , Shiyong LixShiyong LiSearch for articles by this author , Richard W. GreenxRichard W. GreenSearch for articles by this author , Terrence P. O’BrienxTerrence P. O’BrienSearch for articles by this author , Michael J. BorowitzxMichael J. BorowitzSearch for articles by this author Show More The John Hopkins University School of Medicine, Baltimore, MD, Copyright © 2001 American Society of Clinical Oncology https://doi.org/10.1200/JCO.2001.19.11.2964 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Cost-effectiveness of Confirmatory Testing Before Treatment of Onychomycosis
Authors: Anar Mikailov, Jeffrey Cohen, Cara Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2015)

Onychomycosis is the most common disease of the nail in adults. International guidelines urge health care professionals to perform confirmatory diagnostic testing before initiating systemic therapy. This approach was determined to be cost-effective in studies from the late 1990s but has not been evaluated more recently. The effect of testing on the costs of efinaconazole, 10%, topical solution treatment is unknown.To evaluate the cost and potential harm associated with 3 approaches to onychomycosis evaluation before treatment with oral terbinafine or efinaconazole, 10%.A decision analysis that compared the costs of 3 onychomycosis management algorithms based on recently published data of test statistics, disease prevalence, and relevant costs: (1) empirical therapy without confirmatory testing, (2) pretreatment confirmatory testing with potassium hydroxide (KOH) stain followed by periodic acid-Schiff (PAS) evaluation if KOH testing is negative, and (3) pretreatment testing with PAS. There was no direct patient evaluation. Selection of included studies was based on outcome variables and the quality of study design. The study was conducted from April 1, 2014, to September 1, 2015.Primary outcomes included direct cost of onychomycosis testing and therapy and cost to avoid harm when treating patients with oral terbinafine.At a disease prevalence of 75%, per-patient cost savings of empirical terbinafine therapy without confirmatory testing was $47 compared with the KOH screening model and $135 compared with PAS testing. The cost of testing necessary to prevent a single case of clinically relevant liver toxic effects related to terbinafine at a prevalence of 75% was between $18.2 million and $43.7 million for KOH screening and between $37.6 million and $90.2 million for PAS testing. At a prevalence of 75%, KOH screening and PAS testing before treatment with efinaconazole, 10%, saved $272 and $406 per patient per nail, respectively.These results show that empirical treatment with terbinafine for patients with suspected onychomycosis is more cost-effective than confirmatory testing across all prevalence of disease, with minimal effect on patient safety. In contrast, confirmatory testing before treatment with efinaconazole, 10%, is associated with reduced costs. Blanket recommendations for confirmatory testing before systemic therapy should be reconsidered and replaced with recommendations tailored to specific therapies.
O007 : All oral HCV therapy is safe and effective in patients with decompensated cirrhosis: Interim report from the HCV-target real world experience
Authors: R. Reddy, J.K. Lim, A. Kuo, A.M. Di Bisceglie, H.E. Vargas, J.S. Galati, G. Morelli, G.T. Everson, P.Y. Kwo, R.S. Brown, M.S. Sulkowski, T.G. Stewart, L. Akuskevich, M. Vainorius, J.A. Peter, D.R. Nelson, M.W. Fried, M.P. Manns
Journal: Journal of Hepatology (2015)
Cannulation of the Internal Thoracic Artery with a Central Venous Catheter
Authors: Robert J. Lentz, Kim L. Sandler, Alison N. Miller
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Figure 2. Digital subtraction angiography as contrast dye is injected into the central venous catheter confirms cannulation of the internal thoracic artery (at the solid arrow) several centimeters distal to its origin from the subclavian artery (dashed arrow). A 68-year-old man with Crohn’s disease and receiving adalimumab transferred to our institution for respiratory failure and shock complicating an influenza-like illness. He was intubated, and a right internal jugular central venous catheter (CVC) was placed under ultrasound guidance by house staff after three vessel cannulation attempts. Predilation, the position of the wire was misinterpreted as being within the internal jugular on the basis of ultrasound. The post-procedure chest radiograph appeared deceptively normal (Figure 1). Routine transduction for central venous pressure, however, revealed an arterial waveform. Contrast injection demonstrated the CVC to be within the internal thoracic artery (Figure 2). Computed tomography further delineated the path of the catheter (Figures 3 and 4), but the exact track from neck to internal thoracic artery remained unclear (Video 1). The patient died of progressive respiratory failure before planned surgical catheter removal. Antemortem cultures eventually grew Histoplasma capsulatum.
A randomized phase III study of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLD) in progressive/recurrent ovarian cancer (OC)
Authors: G. Ferrandina, D. Lorusso, S. Pignata, E. Breda, A. Savarese, M. Nardi, L. Scaltriti, M. Ludovisi, G. Scambia
Journal: Journal of Clinical Oncology (2007)

LBA5506 Background: This multi-center Phase III study was designed to compare the efficacy and safety of PLD vs GEM in ovarian cancer (OC) patients relapsing within 12 months from platinum/paclitaxel treatment. Methods: Recurrent OC patients failing only one line of platinum/paclitaxel regimen with a platinum-free interval (PFI) ≤12 months, and with measurable or evaluable disease were eligible. Patients were randomized to receive PLD 40 mg/m 2 d1 over 1 hr q 4 wk versus GEM 1,000 mg/m 2 d1,8,15 over 30 min q 4 wk. The primary endpoint was time to progression (TTP), with overall survival (OS), overall response rate (ORR), safety/toxicity, and quality of life (QoL) as secondary endpoints. A total of 147 patients was calculated to be required (alpha=0.05, beta=0.80) in order to detect an increase in median TTP from 12 to 19 weeks in control (PLD) versus experimental (GEM) arm. Results: As of December 2006, 147 patients were enrolled; 74 and 73 patients were randomized to PLD versus GEM, respectively: overall, median age was 65 yrs (range 28–80); 69 (46.9%) patients had a PFI &lt; 6 months, while 78 (53.1%) had a PFI between 6–12 months. response evaluation was possible in 129 cases: in PLD arm, the ORR was 15.9%, compared to an ORR=28.3% in GEM arm, p value=0.13). With a median follow up of 9 months, there was no difference in TTP between PLD and GEM arms (median TTP=16 versus 20 weeks, respectively; p value=0.44). Median OS was 56 weeks in PLD patients versus 50 weeks in GEM arm (p value=0.17). Total number of cycles was 301 in PLD arm, and 275 in GEM arm. Grade 3–4 leukopenia was documented in 8.7% of patients allocated to PLD versus 22.0% of patients administered GEM (p value=0.03); no difference in the distribution of severe anemia and thrombocytopenia was observed. There was no difference in non hematological toxicity. A total of 121 patients were considered for QoL data analysis: a trend to a better global QoL score was documented in PLD arm. (p value=0.015) Conclusions: PLD and GEM show similar activity in OC recurring within 12 months from primary treatment. No significant financial relationships to disclose.
Comparison of Radiation Doses and Best-Practice Use for Myocardial Perfusion Imaging in US and Non-US Laboratories
Authors: Mathew Mercuri, Thomas N. B. Pascual, John J. Mahmarian, Leslee J. Shaw, Madan M. Rehani, Diana Paez, Andrew J. Einstein
Journal: JAMA Internal Medicine (2015)

Mathew Mercuri, PhD; Thomas N. B. Pascual, MD; John J. Mahmarian, MD; Leslee J. Shaw, PhD; Maurizio Dondi, MD; Diana Paez, MD; Andrew J. Einstein, MD, PhD; for the INCAPS Investigators Group
The chemokines CXCL9 and CXCL13 as prognostic markers for metastasis and survival in rectal cancer patients after neoadjuvant chemoradiation.
Authors: Thilo Sprenger, Carl Ludwig Behnes, Lena-Christin Conradi, Anne Kauffels, Hendrik A. Wolff, Michael Ghadimi, Torsten Liersch, Ralph M Wirtz
Journal: Journal of Clinical Oncology (2015)

627 Background: Distant metastasis is a challenging problem in multimodal treatment of rectal cancer. Valid prognostic markers for the occurrence of metachronous metastasis could help to stratify patients who qualify for adjuvant chemotherapy and intensified follow-up procedures after preoperative chemoradiotherapy (CRT). Methods: We analysed 9 different genes known to prominently figure in crucial pathways of the tumor cell metabolism. mRNA was isolated and quantified from surgical specimens of 77 rectal cancer patients undergoing neoadjuvant CRT. The panel contains genes with relevant function in apoptosis (Birc5, XIAP, SMAC) and epithelial-mesenchymal transitions (SNAI2) as well as the cancer stem-cell marker CD133, the transcription factor ESR1 and the lymphocyte-chemokines CXCL9 and 13. The expression levels in post-CRT rectal cancers were correlated with the development of distant metastasis and with disease-free (DFS) and cancer-specific overall survival (CSS). Results: Intratumoral mRNA expression of the T-cell chemokine CXCL9 (p&lt;0.001) and the B-cell chemokine CXCL13 (p&lt;0.01) was inversely correlated with the occurrence of distant metastasis. Patients with isolated high CXCL9 (p&lt;0.0001) and CXCL13 levels (p&lt;0.01) had a significantly prolonged DFS. Patients with simultaneous expression of CXCL9 and 13 had an excellent DFS compared to patients without expression of any of the chemokines (p&lt;0.0001). Additionally, CXCL9 expression was correlated with an improved CSS (p&lt;0.05). There was no significant correlation between expression levels of the other genes tested and metastasis or survival. Conclusions: The post-CRT expression of the lymphocyte-chemokines CXCL9 and 13 is associated with reduced rates of distant metastases and improved survival in rectal cancers after CRT. Further investigations are needed to prospectively validate these results and characterize the underlying cellular and molecular mechanisms.
Co-expression networks identify distinct immune infiltrates in hepatocellular carcinoma
Authors: Derek Y Chiang, Alan Huang
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The vast majority of hepatocellular carcinoma (HCC) arise in the context of chronic inflammation, especially with hepatitis B or hepatitis C viral infection. Several studies have identified prognostic immune biomarkers in HCC tumors and peritumoral regions. Recently, a Phase 1
Single-center experience of male breast cancer: Molecular pathology and potential treatment implications.
Authors: S. J. Asghar, M. Doyle, F. MacSweeney, P. M. Calvert, B. M. Cantwell
Journal: Journal of Clinical Oncology (2010)

e21118 Background: Male breast cancer (MBC) is an uncommon disease. In contrast to female breast cancer, information regarding molecular pathology and treatment is limited. The aim of this study was to examine the molecular pathology and receptor biology in Irish men with breast cancer. Methods: Ten patients with MBC were identified from 1997-2008 from a single Irish hospital and the expression of the molecular markers were determined by immunochemistry. We examined the expression of oestrogen receptors (ER), progesterone receptors (PgR), HER-2/neu (EGFR 2), EGFR 1 and p53 mutation. Results: The majority of patients (8/10) were of ductal histologic type and similarly the majority were high grade (grade III - 7/10). All 10 patients had positivity of ER in tumours and in 9 of these 10, PgR was positive. No patients had (EGFR 2) HER-2 over-expression by immunochemistry or gene amplification. All 10 patients had negative staining for EGFR 1. Greater than 30% of tumour cells showed positive staining for p53, and thus by our criteria 6/10 patients were positive for p53 expression. Conclusions: Oestrogen receptor positivity was present in all our patients and this in keeping with the international literature which shows significantly higher ER positivity in male by comparison with female breast cancer. Both high levels of ER positivity and grade III tumours occurred in Irish MBC, in contrast to female patients where there is an inverse relationship between these pathological features. Since its first use in MBC tamoxifen remains the most potent endocrine therapy for male breast cancer. New molecular targeting agents (eg., histone deacetylase [HDAC]) inhibitors could have particular benefits in enhancing tamoxifen efficiency in MBC in view of the high levels of ER expression. Also dose escalation of tamoxifen supported by recent pharmacogenetics studies may be relevant to this group of patients. In view of > 50% of patients showing abnormal p53 assessments, alternative therapeutic strategies for this subgroup, such as proteasomal inhibitors could be explored. No significant financial relationships to disclose.
Differences in the quality of life of patients with chronic obstructive pulmonary disease living in different countries
Authors: Juliana Maria De S Pinto, Maria Tereza A.P. Morano, Ana María M. Nogueras, Jacinto R. González, Amanda S. Araújo, José Ignacio C. Arenillas
Journal: European Respiratory Journal (2011)

Aim: To evaluate the differences in the quality of life (QoL) of patients with Chronic Obstructive Pulmonary Disease (COPD) living in different countries.

Methods: A cross-sectional and comparative study with 80 COPD outpatients of the Respiratory Service of public hospitals of Salamanca (Spain) and Fortaleza (Brazil) from September to December 2010. The sampling was selected by pairs depending on the severity (Global Initiative for Chronic Lung Disease criteria). Socio-demographic and spirometric data (American Thoracic Society criteria) were collected. The QoL was evaluated by the Saint George Respiratory Questionnaire (SGRQ) and the World Health Quality of Life-Bref (WHOQOL-BREF). Descriptive analysis, the t-student test and the chi-square test were applied (SPSS).

Results: The severity was 7.5% of mild, 30% of moderate, 47.5% of severe and 15% of very severe COPD. The mean age of Brazilian patients was 66.6 years (SD 8.0years) and the Spanish one was 69.1 years (SD 8.9years). There were significant differences in gender, civil state, monthly income, place of residence, being smoker and ex-smoker, the forced expiratory volume in 1s (FEV1) in both samples. There were also significant differences in all domains and the total SGRQ and in all WHOQoL-Bref domains except the Environment. Brazilian patients presented higher scores in the SGRQ (worse QoL) while Spanish patients had lower scores in the WHOQoL-Bref (worse QoL).

Conclusions: The differences in the QoL of these patients can be related with the differences in the FEV1 and the socio-demographic characteristics.
Association of Paid Sick Leave With Job Retention and Financial Burden Among Working Patients With Colorectal Cancer
Authors: Christine M. Veenstra, Scott E. Regenbogen, Sarah T. Hawley, Paul Abrahamse, Mousumi Banerjee, Arden M. Morris
Journal: JAMA (2015)

This study uses data from the Surveillance, Epidemiology, and End Results database to examine the association between access to paid sick leave and job retention and personal financial burden among patients with colorectal cancer.
Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study
Authors: Xiaoxu Huo, Leili Gao, Lixin Guo, Wen Xu, Wenbo Wang, Xinyue Zhi, Ling Li, Yanfeng Ren, Xiuying Qi, Zhong Sun, Weidong Li, Qiuhe Ji, Xingwu Ran, Benli Su, Chuanming Hao, Juming Lu, Xiaohui Guo, Hanjing Zhuo, Danyi Zhang, Changyu Pan, Jianping Weng, Dayi Hu, Xilin Yang, Linong Ji
Journal: The Lancet Diabetes & Endocrinology (2015)
Smad4 Deficiency in Smooth Muscle Cells Initiates the Formation of Aortic Aneurysm
Authors: Peng Zhang, Siyuan Hou, Jicheng Chen, Jishuai Zhang, Fuyu Lin, Renjie Ju, Xuan Cheng, Xiaowei Ma, Yao Song, Youyi Zhang, Minsheng Zhu, Jie Du, Yu Lan, Xiao Yang
Journal: Circulation Research (2016)

Rationale: Aortic aneurysm is a life-threatening cardiovascular disorder caused by the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor-β (TGF-β) pathway in aortic aneurysm. Smad4 is the central mediator of the canonical TGF-β signaling pathway. However, the exact role of Smad4 in smooth muscle cells (SMCs) leading to the pathogenesis of aortic aneurysms is largely unknown. Objective: To determine the role of smooth muscle Smad4 in the pathogenesis of aortic aneurysms. Methods and Results: Conditional gene knockout strategy combined with histology and expression analysis showed that Smad4 or TGF-β receptor type II deficiency in SMCs led to the occurrence of aortic aneurysms along with an upregulation of cathepsin S and matrix metallopeptidase-12, which are proteases essential for elastin degradation. We further demonstrated a previously unknown downregulation of matrix metallopeptidase-12 by TGF-β in the aortic SMCs, which is largely abrogated in the absence of Smad4. Chemotactic assay and pharmacologic treatment demonstrated that Smad4-deficient SMCs directly triggered aortic wall inflammation via the excessive production of chemokines to recruit macrophages. Monocyte/macrophage depletion or blocking selective chemokine axis largely abrogated the progression of aortic aneurysm caused by Smad4 deficiency in SMCs. Conclusions: The findings reveal that Smad4-dependent TGF-β signaling in SMCs protects against aortic aneurysm formation and dissection. The data also suggest important implications for novel therapeutic strategies to limit the progression of the aneurysm resulting from TGF-β signaling loss-of-function mutations.
Will Measuring Vasodilator-Stimulated Phosphoprotein Phosphorylation Help Us Optimize the Loading Dose of Clopidogrel?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Neal S. Kleiman
Journal: Journal of the American College of Cardiology (2008)