tbuckley/cabot-search huggingface dataset:
Abstract 079: Estrogen Receptor beta Regulation Of miRNA Expression In The Heart - A Hint For Sex Differences In Hypertrophy
Authors: Ana Queirós, Claudia Eschen, Daniela Fliegner, Vera Regitz-Zagrosek, Hugo Sanchez Ruderisch
Journal: Circulation Research (2013)

Sex differences (SD) in cardiovascular diseases are described and have been attributed to the effects of sex hormones, such as estrogen (E2). Our previous studies in a mouse model of pressure overload revealed SD in fibrosis and apoptosis related genes that were abolished in estrogen receptor β deficient (ERβ-/-) mice. Other studies focus on miRNA regulation by E2, but little is known about sex-specific regulation of miRNAs in heart diseases. We hypothesize that E2 and ERβ are regulators of miRNA expression in the heart potentially contributing to the molecular mechanism of SD observed in cardiovascular diseases. This project aims to identify SD in the expression of miRNAs in a 9-week transverse aortic constriction (TAC) model and the possible role of E2 and ERβ in their regulation in the heart. A Targetscan analysis of 80 sex-specific dysregulated genes in hypertrophy allowed identifying 157 different miRNAs that could target them. Based on their expression in the heart we selected 60 miRNAs for quantification by qRT-PCR. In WT mice, 23 miRNAs showed SD in their expression in hypertrophy, all of them showing a higher expression in males than in females. All these significant SD were abolished in ERβ-/- mice. A direct comparison of some of these miRNAs in WT and ERβ-/- female animals identified nine miRNAs significantly higher expressed in the knock-out animals (let-7e, miR-106b, miR-130a, miR-133a, miR-20a, miR-24, miR-27b, miR-29a and miR-378). In vitro studies performed using a female cardiomyocyte cell line (AC16) showed a down-regulation of eight of these miRNAs after a 48h treatment with E2, being the exception miR-133a. The latter showed however a down-regulation after 48h treatment with an ERβ specific agonist, as well as let-7e, miR-106b, miR-130a, miR-20a, miR-24, miR-27b and miR-29a. The effect of treatment with ERα was only visible as a down-regulation of miR-24, miR-29a and miR-378. The potential of these miRNAs having targets in the same pathway and acting in a synergistic way is still under investigation. ERβ is for the first time identified as a major regulator of miRNA expression in the heart. It may play an important role in determining SD in cardiac hypertrophy, being responsible for the inhibition of miRNA expression in the female heart.
Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.
Authors: D Kelsen, M Karpeh, G Schwartz, H Gerdes, C Lightdale, J Botet, G Lauers, D Klimstra, Y Huang, L Saltz, V Quan, M Brennan
Journal: Journal of Clinical Oncology (1996)

PURPOSE AND METHODS We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography (EUS). Neoadjuvant therapy using the fluorouracil, doxorubicin, and metrotrexate (FAMTX) regimen was given for three courses before planned laparotomy with the intention to perform curative resection. Postoperatively, intraperitoneal (IP) cisplatin and fluorouracil (FU) and intravenous (i.v.) FU were administered to patients undergoing resection. RESULTS Fifty-six assessable patients were treated. Preoperative FAMTX therapy was tolerable, with the major toxicity being neutropenic fever. One treatment-related death was seen. Eighty-nine percent of patients underwent surgical exploration and 61% had potentially curative resections. There were two postoperative deaths. Comparison of pathologic tumor (pT) stage with EUS-predicted tumor stage showed apparent downstaging in 51% of patients. Postoperative IP chemotherapy was delivered to 75% of eligible patients. Toxicity was acceptable. There was no increase in operative morbidity or mortality compared with concurrent nonstudy patients undergoing a similar operative procedure and not receiving preoperative therapy. With a median follow-up time of 29 months, the median survival duration was 15.3 months. For patients who underwent potentially curative resections, the median survival duration was 31 months. Peritoneal failure was seen in 16% of patients. CONCLUSION Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer, without an increase in operative morbidity or mortality. IP therapy can be successfully delivered to most resected patients. The intraabdominal failure pattern appears to be decreased compared with expected. This approach is an appropriate investigational arm to pursue in future studies.
A phase I trial of adoptive transfer of allogeneic natural killer (NK) cells in patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: E. G. Iliopoulou, P. Kountourakis, M. V. Karamouzis, D. Doufexis, A. Ardavanis, C. N. Baxevanis, G. Rigatos, M. Papamichail, S. A. Perez
Journal: Journal of Clinical Oncology (2009)

3001 Background: HLA-mismatched NK cells have been found effective in acute myeloid leukemia pts. Preclinical studies revealed that activated NK cells massively infiltrate lung tissue and improve recipient survival, suggesting a potential role in lung cancer therapeutics. We performed this phase I trial to evaluate safety and antitumor responses of allogeneic, in vitro activated and expanded NK cells in combination with chemotherapy (C) in pts with advanced NSCLC. Methods: Pts with unresectable locally advanced/metastatic NSCLC receiving 1st/2nd line C were eligible. Two relative donors for each pt were selected based on their HLA and KIR typing. CD56 + cells were isolated from 150ml of donor peripheral blood and cultured for 20–23 days with 20ng/ml interleukin-15 and 10 -5 M hydrocortisone. Activated and expanded NK cells, after sterility, phenotype, and function testing, were diluted in 500ml N/S 0.9% with 2% human serum albumin and administered i.v. for 1 hour 2 days after previous and 1 week prior next C. Premedication with corticosteroids and/or H1 inhibitors was allowed. The number of NK cells to be injected was up to 2x10 11 /dose for up to 4 doses. Pts and donors signed detailed informed consent. Results: Between 11/2007 and 11/2008 16 pts (performance status 0–1) were enrolled; 1 pt had rapid disease progression before treatment. Pts characteristics: M/F 12/4; histology: adenocarcinoma/squamous cell carcinoma 13/3; stage IIIb/IV 2/14; 1 st /2 nd line treatment 13/3; median age 64 years (range, 50–71). The number of doses administered was 2 (N=9 pts), 3 (N=2 pts), or 4 (N=4 pts). The number of cells injected varied from 0.2–29x10 6 /Kg (mean 7.4x10 6 ±7.7x10 6 ). During and after injection of NK cells no side effect (local or systemic) was observed. With a median follow-up of 6 months (range, 1–14) 3 pts with partial response and 7 pts with disease stabilization were recorded. Conclusions: Adoptive transfer of allogeneic, in vitro activated and expanded NK cells in combination with chemotherapy is safe, even at the highest dose administered. Based on these encouraging results a randomized phase II trial is further justified. No significant financial relationships to disclose.
Temporal Relationships of Leukemia and Lymphoma Deaths in Neighborhoods
Authors: Frank E. Lundin, Jr., M.D., Dr. P.H., Joseph F. Fraumeni, Jr., M.D., J. William Lloyd, Sc.D., Elizabeth M. Smith, M.Sc.
Journal: JNCI Journal of the National Cancer Institute (1966)

The deaths from leukemia and lymphoma occurring in a metropolitan area over a 10-year period were grouped by spatial proximity into 350 pairs. The temporal distribution of paired deaths revealed an excessive number occurring 6–8 years apart. This excess was not found among control deaths matched by age, sex, race, and year of death. Although leukemia and lymphoma were not found to cluster in time or space, the temporal pattern of deaths suggests that etiologic factors may be transmitted from some cases to others. Alternative explanations, however, could not be excluded. Further study is needed before interpretation of these observations as evidence for the communicability of leukemia.
Spanish Breast Cancer Research Group (GEICAM) hospital-based study on breast cancer outcomes: El Álamo project (1990-2001).
Authors: C. Jara-Sanchez, A. Ruiz, M. Martin, P. Martínez del Prado, A. Santaballa, A. Llombart-Cussac, J. Batista, M. Pollán, E. M. Carrasco, A. Lluch
Journal: Journal of Clinical Oncology (2010)

e12016 Background: El Álamo project is a retrospective analysis of 26833 patients (pts) diagnosed of breast cancer (BC) between 1990 and 2001 across 43 of the main Spanish hospitals. Patterns of BC presentation, treatment and survival in the women population were analyzed. Methods: Three cohorts were analyzed: Álamo I (AI) with 4,532 pts diagnosed between 1990 and 1993; Álamo II (AII) with 10,791 pts diagnosed between 1994 and 1997; and Álamo III (AIII) with 11,277 pts diagnosed between 1998 and 2001. Data were collected by end of year 2000, 2003 and 2007 for AI, AII and AIII respectively. 468 items per pt were recorded, including demographic, therapeutic and outcome data. Results: Pts diagnosed with stage I were 17.6% in AI, 24.3% in AII and 32.7% in AIII; pts diagnosed with stage II were 55.5% in AI, 53.1% in AII and 44.9% in AIII; pts diagnosed with stage III were 18.7% in AI, 15% in AII and 15.7% in AIII; pts diagnosed with stage IV were 7.2% in AI, 5.9 in AII and 4.3% in AIII. Median age at diagnosis and menopausal status was similar in the three cohorts. First treatment option (FTO) for stage I, II, and III disease was surgery in 91% of pts in AI and AII and 89.5% in AIII; breast conserving surgery rate has increased through the cohorts from 19.5% in AI and 24% in AII to 48% in AIII. Neoadjuvant treatment was FTO for 8% of pts in AI and AII and 10.4% in AIII. Adjuvant systemic treatments (chemotherapy and/or hormones) were administered to 87.6% (AI), 92.8% (AII) and 95.7 % (AIII) of pts. Radiation therapy was administered to 38.8% (AI), 50.7% (AII) and 65.2% (AIII) of pts. BC recurrence rate has decreased from 36.6% (AI) to 22.5% (AII) and 15.9% (AIII). Six-year survival rate has increased from 72.50% (CI95%: 71.2-73.8) in AI, and 80,4% (CI95%: 79,6-81,2) in AII to 85.0% (CI95%: 84.3%-85.7%) in AIII. Conclusions: BC screening programs in Spain seem to accomplish the objectives as more patients are diagnosed with stage I disease and a higher amount of them are undergoing breast-conserving surgery. BC outcomes have improved through the consecutive cohorts. The main reason for that improvement is likely to be the BC screening program, nevertheless the impact of better surgical techniques, radiotherapy and new systemic therapies cannot be ruled out. No significant financial relationships to disclose.
Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumor: Being younger and getting less benefit from adjuvant tamoxifen treatment
Authors: K. Yu, G. Di, Z. Shao
Journal: Journal of Clinical Oncology (2008)

22032 Background: Most receptor-negative/progesterone receptor-positive (ER-/PgR+) patients are premenopausal cases, with few adjuvant endocrine therapeutic alternatives but tamoxifen(TAM). The efficacy of adjuvant TAM on patients with ER-/PgR+ tumor is still controversial. In this study, we evaluated the efficacy of adjuvant TAM on patients with ER-/PgR+ tumor. Methods: Among all 1836 consecutive operable patients with primary breast cancer, 798 cases were with ER+/PgR+ tumor and 205 with ER-/PgR+ tumor. In order to investigate the differences of survivals between groups, we sub-grouped the patients according to ER/PR phenotypes and whether the patient had been treated with adjuvant TAM therapy. Results: Patients with ER-/PgR+ tumor were younger than those with ER+/PgR+ tumor (P=0.021), and were mainly premenopausal (P=0.013). ER-/PgR+ patients were related to more involved lymph nodes and later stage. In the absence of TAM treatment, ER+/PgR+ group had a similar survival to ER-/PgR+ group in terms of 5-year DFS, as well as OS. After TAM treatment, both groups had increased survival rates comparing with the baseline of non-TAM-treated groups. In addition, significant survival differences were observed between the TAM-treated ER+/PgR+ group and ER-/PgR+ group either in DFS (P=0.016) or OS (P=0.007). Of the TAM-treated patients, by sub-dividing the chemotherapy-treated population into CMF group and CA(E)F group, we found that ER-/PgR+ group got more benefits from CMF regimen than from CA(E)F. STEPP analysis showed that the ER-/PgR+ group had an obvious worse survival in younger patients (younger than 55 ys) than ER+/PgR+ group. Axillary lymph nodes involvement was unique independent prognostic factor for ER-/PgR+ group. Conclusions: Patients with ER-/PgR+ tumor are mainly premenopausal and young. Although patients with ER-/PgR+ tumor are generally considered as candidates for endocrine therapy clinically, they gain less benefit from adjuvant TAM treatment than ER+/PgR+ group. No significant financial relationships to disclose.
Treatment of multiple myeloma: an Argentine Group for the Treatment of Acute Leukemia Study.
Authors: K Dhingra
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.11.1784 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3054007 Treatment of multiple myeloma: an Argentine Group for the Treatment of Acute Leukemia Study. K DhingraxK DhingraSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.11.1784 PDF "Treatment of multiple myeloma: an Argentine Group for the Treatment of Acute Leukemia Study.." Journal of Clinical Oncology, 6(11), pp. 1784–1785© 1988 by American Society of Clinical Oncology
Community health worker-based intervention for adherence to drugs and lifestyle change after acute coronary syndrome: a multicentre, open, randomised controlled trial
Authors: Denis Xavier, Rajeev Gupta, Deepak Kamath, Alben Sigamani, P J Devereaux, Nisha George, Rajnish Joshi, Janice Pogue, Prem Pais, Salim Yusuf
Journal: The Lancet Diabetes & Endocrinology (2016)
Medulloblastoma histological variants as the most powerful prognostic indicator: A 10-year mono-institutional experience.
Authors: M. Massimino, L. Gandola, V. Biassoni, P. Collini, B. Pollo, F. Giangaspero
Journal: Journal of Clinical Oncology (2010)

9556 Background: Histological classification in medulloblastoma has aroused in importance and newer treatment protocols will include histology as risk factor. We centrally revised all our medulloblastoma cases of the last ten years and highlighted their histology to identify its prognostic importance. Methods: Patients' samples were reviewed according to the two subsequent WHO classifications 2000 and 2007. Consecutive patients were 127. Results: Male were 91, M0 were 88, primary tumor was completely resected in 99, 11 patients were under 3-years of age. Median follow-up was 54 months. Treatment applied was institutional driven, hyperfractionated accelerated radiotherapy (HART) based for 38 non metastatic cases before 2003, applied European PNET IV protocol in 30, was institutional and HART based for 40 high risk children, infants tailored in 11 (mostly with HDCT), patient condition tailored in 7. Six years PFS/EFS/OS were 75, 72 and 79.5%, respectively. Histology was classic in 93 cases, desmoplastic in 21, anaplastic/large cell in 6/4 and desmoplastic nodular in the last three. PFS was 76.4% for M0 cases and 72.6% for M0 ones; 78% for NED cases and 66.4% for those with tumor residual; further sratification according to both presence of residual disease and metastases was not prognostic either, as were not the main different protocols adopted. Histology showed 83.5% PFS for desmoplastic variant, 79% for classic, 50% for nodular variant and 0% for anaplastic/large cell one (P < 0.0001). Conclusions: “Tailored” treatment to recognized risk factors has flattened prognostic differences while histologic variants, that were not considered when designing previous trials, remained the most powerful prognostic factors. No significant financial relationships to disclose.
<i>Annals</i> Graphic Medicine - Atrial Flutter
Authors: Judy G. Swanson
Journal: Annals of Internal Medicine (2016)

Web Exclusives2 February 2016Annals Graphic Medicine - Atrial FlutterFREEJudy G. Swanson, MDJudy G. Swanson, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-0013 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G15-0013.Author/Illustrator Information: Judy G. Swanson, MD, a faculty attending for Providence Internal Medicine Residency Spokane and WWAMI Site Clerkship Director for University of Washington. She integrates art and literature into medical education to ensure that today's physicians in training see the relevance of the humanities in medicine.Corresponding Author: Judy G. Swanson, MD; e-mail, [email protected]Author Contributions: Conception and design: J.G. Swanson.Drafting of the article: J.G. Swanson.Final approval of the article: J.G. Swanson.Collection and assembly of data: J.G. Swanson. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 February 2016Volume 164, Issue 3Page: W11KeywordsConflicts of interestDisclosureHealth careMedical educationResidency ePublished: 2 February 2016 Issue Published: 2 February 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD
Authors: Alexandra Montagner, Arnaud Polizzi, Edwin Fouché, Simon Ducheix, Yannick Lippi, Frédéric Lasserre, Valentin Barquissau, Marion Régnier, Céline Lukowicz, Fadila Benhamed, Alison Iroz, Justine Bertrand-Michel, Talal Al Saati, Patricia Cano, Laila Mselli-Lakhal, Gilles Mithieux, Fabienne Rajas, Sandrine Lagarrigue, Thierry Pineau, Nicolas Loiseau, Catherine Postic, Dominique Langin, Walter Wahli, Hervé Guillou
Journal: Gut (2016)

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).We constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing.Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα(hep-/-) mice when compared with Pparα(-/-) mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα(-/-) mice became overweight during ageing while Pparα(hep-/-) remained lean. However, like Pparα(-/-) mice, Pparα(hep-/-) fed a standard diet developed hepatic steatosis in ageing.Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD.
Systemic inflammation, diet, and place of residence modify lung function in Greenland Inuit
Authors: Katherine Baines, Vibeke Backer, Peter Gibson, Powell Heather, Celeste Porsbjerg
Journal: European Respiratory Journal (2014)

Background: The preservation of lung health requires an understanding of the modifiable risk factors involved in airflow limitation. We aimed to determine the association between lung function, diet and systemic inflammation in a genetically homogenous population of Inuits residing in the arctic (Greenland) or Western Europe (Denmark).  Methods: Two unselected Inuit populations were recruited, one living in Greenland (Urban (Nuuk) n=288; Rural (Uummannaq) n=183) and the other in Denmark (n=613). Lung function was measured using spirometry, and expressed as forced expiratory volume in one second (FEV 1 )/height (Ht). Systemic inflammation was measured by commercial enzyme linked immunoassay of serum C reactive protein (CRP), interleukin (IL)-6 and soluble CD163. Diet was assessed by food frequency questionnaire. Predictors of airflow limitation were assessed using multiple linear regression models.  Results: The dietary composition differed significantly in the two regions, with high fish intake and low fruit intake in the arctic region and the reverse in Denmark. Consumption of wild meat (p=0.020), fish (p=0.025), and fruit (p=0.020); were positive predictors of FEV 1 /Ht ratio. Whereas systemic inflammation, determined by a high CRP (p=0.0001), IL-6 (p=0.003) and sCD163 (p=0.001), was associated with lower lung function.  Conclusions: Among Greenlandic Inuits, lung function is associated with potentially modifiable risk factors including systemic inflammation and dietary intake. Specifically, high wild meat, fish and fruit intake had independent positive effects on lung function. These factors may play an important role in determining overall lung health.