tbuckley/cabot-search huggingface dataset:
Site of Genetic Regulation on Hypophysial Graft-Induced Mammary Gland Development&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. Wayne Bardin, Annabel G. Liebelt, Robert A. Liebelt
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Site of Genetic Regulation on Hypophysial Graft-Induced Mammary Gland Development Get access C. Wayne Bardin, C. Wayne Bardin Department of Anatomy, Baylor University College of Medicine, Houston, Texas 77025 Search for other works by this author on: Oxford Academic PubMed Google Scholar Annabel G. Liebelt, Annabel G. Liebelt Department of Anatomy, Baylor University College of Medicine, Houston, Texas 77025 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert A. Liebelt Robert A. Liebelt Department of Anatomy, Baylor University College of Medicine, Houston, Texas 77025 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 41, Issue 6, December 1968, Pages 1453–1461, https://doi.org/10.1093/jnci/41.6.1453 Published: 01 December 1968 Article history Received: 01 August 1968 Accepted: 30 August 1968 Published: 01 December 1968
Informed consent for investigational chemotherapy: patients' and physicians' perceptions.
Authors: D T Penman, J C Holland, G F Bahna, G Morrow, A H Schmale, L R Derogatis, C L Carnrike, R Cherry
Journal: Journal of Clinical Oncology (1984)

One hundred forty-four patients and 68 physicians at three cancer centers were studied for their perceptions of the consent procedure, in which they participated one to three weeks earlier, for chemotherapy by one of 65 investigational protocols. Patients recalled the procedure positively and relied heavily on physician's advice. They felt most physicians wanted them to accept; 29% felt their participation in the decision was not encouraged. Primary reasons for accepting were trust in the physician, belief the treatment would help, and fear the disease (viewed as highly serious) would get worse without it. Nearly a fourth did not recall the information given that treatment was investigational. The consent form played no role in decision-making for 69%. Physicians believed therapeutic benefits would exceed potential problems for most patients; they viewed 41% of the patients as less than eager for details of treatment, a third as avoiding the seriousness of the discussion, and a third as passive in decision-making. The perceptual set of both parties places inadvertent constraint on patients' autonomy in decision making.
Laboratory Studies for Every Medicated Outpatient: Are They Really Necessary?
Authors: DARIUS ORNSTON, MARC SCHWARTZ, D. CLINT SMITH, STANLEY STERN
Journal: American Journal of Psychiatry (1974)

Although laboratory tests are useful in some cases, the authors question the value of routine blood studies for every patient who takes psychotropic medication. They report results of a questionnaire distributed to all members of their local psychiatric society concerning usual practice among psychiatrists in regard to laboratory tests. Summarizing the arguments for and against routine laboratory studies for all outpatients, they conclude that routine studies provide little useful information.
Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study
Authors: W C Tan, D D Sin, J Bourbeau, P Hernandez, K R Chapman, R Cowie, J M FitzGerald, D D Marciniuk, F Maltais, A S Buist, J Road, J C Hogg, M Kirby, H Coxson, C Hague, J Leipsic, D E O'Donnell, S D Aaron
Journal: Thorax (2015)

There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population.To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers.We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA).The prevalence of COPD (FEV1/FVC<lower limits of normal) in never-smokers was 6.4%, constituting 27% of all COPD subjects. The common independent predictors of COPD in never-smokers and ever-smokers were older age, self reported asthma and lower education. In never-smokers a history of hospitalisation in childhood for respiratory illness was discriminative, while exposure to passive smoke and biomass fuel for heating were discriminative for women. COPD in never-smokers and ever-smokers was characterised by increased respiratory symptoms, 'respiratory exacerbation' events and increased residual volume/total lung capacity, but only smokers had reduced DLCO/Va and emphysema on chest CT scans.The study confirmed the substantial burden of COPD among never-smokers, defined the common and gender-specific risk factors for COPD in never-smokers and provided early insight into potential phenotypical differences in COPD between lifelong never-smokers and ever-smokers.NCT00920348 (ClinicalTrials.gov); study ID number: IRO-93326.
Challenges in pulmonary fibrosis {middle dot} 2 : Bronchiolocentric fibrosis
Authors: J.-F. Cordier
Journal: Thorax (2007)

Bronchiolocentric fibrosis is essentially represented by the pathological pattern of constrictive fibrotic bronchiolitis obliterans. The corresponding clinical condition (obliterative bronchiolitis) is characterised by dyspnoea, airflow obstruction at lung function testing and air trapping with characteristic mosaic features on expiratory high resolution CT scans. Bronchiolitis obliterans may result from many causes including acute diffuse bronchiolar damage after inhalation of toxic gases or fumes, alloimmune chronic processes after lung or haematopoietic stem cell transplantation, or connective tissue disease (especially rheumatoid arthritis). Airway-centred interstitial fibrosis and bronchiolar metaplasia are other features of bronchiolocentric fibrosis.
Interleukin-17A in the pathogenesis of elastase-induced emphysema in mice
Authors: Nobufumi Kamiishi, Koichiro Asano, Takahisa Takihara, Shizuko Kagawa, Shuichi Yoshida, Naoto Minematsu, Hidetoshi Nakamura, Kyuto Tanaka, Jun Miyata, Yusuke Suzuki, Tetsuya Shiomi, Koichi Fukunaga, Koichi Sayama, Seitaro Fujishima, Yoichiro Iwakura, Tomoko Betsuyaku
Journal: European Respiratory Journal (2012)

Background: Recent studies show that interleukin (IL) -17A is highly expressed in the lungs of patients with chronic obstructive pulmonary disease (COPD) and in the emphysematous lungs of mice after long-term cigarette smoke exposure. However, the role of IL-17A in the pathogenesis of emphysema is still unknown. In the present study, we examined the role of IL-17A in the development of elastase-induced emphysema using Il-17A gene-deficient ( Il-17a -/-) mice.

Methods: Porcine pancreatic elastase (PPE) or phosphate buffered saline (PBS) was administered intratracheally in Il-17a -/- and wild-type (WT, C57BL/6J) mice on day 0. IL-17A mRNA expression in the lungs was assessed with RT-PCR. Lung inflammation was determined by differential cell count in bronchoalveolar lavage fluid. On day 21, we measured lung compliance by forced oscillation method. Emphysema was assessed by alveolar mean liner intercept (Lm) determined by computer-assisted morphometric analysis.

Results: IL-17A mRNA expression was increased in WT mice lungs 6 hours after the administration of PPE. It was accompanied by neutrophilic inflammation in the lungs on day 2 – day 14, whereas neutrophil recruitment was significantly reduced in Il-17a -/- mice (p < 0.05). Lung compliance and emphysema (Lm) on day 21 in PPE-treated WT mice was significantly increased than in PBS-treated ones (p < 0.05). In contrast, Il-17a -/- mice administered with PPE showed significantly less increase in the compliance and Lm (p < 0.05, compared to WT).

Conclusions: These results suggest that IL-17A contributes to the development of elastase-induced neutrophilic inflammation and emphysema in mice.
Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five-drug regimen including etoposide.
Authors: D Kalwinsky, J Mirro, M Schell, F Behm, C Mason, G V Dahl
Journal: Journal of Clinical Oncology (1988)

We tested the value of early intensification of chemotherapy in 68 consecutive children with acute nonlymphocytic leukemia (ANLL) who were admitted to St. Jude Children's Research Hospital from November 1983 through March 1987. Fifty-eight patients (85%) entered complete remission after treatment with etoposide (VP-16)/cytarabine (ara-C) (A), followed by daunorubicin (Dauno)/ara-C/thioguanine (6-TG) (B) and then VP-16/azacytidine (5-AZ) (C). Thirty percent of the complete responders, mainly those with an M4 or M5 leukemia subtype, attained M1 marrow status after component A, 60% after A + B, and 10% after A + B + C. Induction failures resulted primarily from absolute or relative drug resistance; there was only one death during this phase of therapy. Postremission treatment consisted of three pairs of drugs (vincristine [VCR]/amsacrine [m-AMSA], or doxorubicin [Doxo]/6-TG/ara-C, and VP-16/cyclophosphamide [CTX]) administered sequentially in 6-week cycles for 22 months. Despite the high rate of remission induction, only 33% +/- 7% SE of the patients are expected to be failure-free survivors at 2 years. Remission durations were not significantly affected by the majority of factors examined in this study, with the exception of marrow cellularity after VP-16/ara-C induction therapy. Patients with less than or equal to 5% leukemic cells survived relapse-free for a median of 36.1 months, compared with 11.3 months for the group with a larger infiltrate (P = .01). Although postremission therapy did not improve the percentage of long-term failure-free survivors, the induction regimen we used appears highly effective, and its components should be considered for inclusion in other treatment programs.
&lt;italic&gt;N&lt;/italic&gt;-Nitrosodiethylamine-Induced Hepatocarcinogenesis in Estuarine Sheepshead Minnow (&lt;italic&gt;Cyprinodon variegatus&lt;/italic&gt;): Neoplasms and Related Lesions Compared With Mammalian Lesions
Authors: J A Couch, L A Courtney
Journal: JNCI Journal of the National Cancer Institute (1987)

Groups of estuarine sheepshead minnows (Cyprinodon variegatus) were exposed to approximately 57 mg N-nitrosodiethylamine [(DENA) CAS: 55-18-5]/liter for 5–6 weeks. Exposure was stopped and the fish were then transferred to clean, flowing seawater. Induced liver lesions were studied in periodic samples of fish taken during the next 140 weeks of holding. Lesions found following exposure were early altered basophilic and eosinophilic foci, oval cell hyperplasia, clear cell foci, neoplas-tic nodules, hepatocellular carcinomas, cholangiolar carcinomas, possible pericytomas originating in liver, hemangiopericytomas, spongiosis hepatis, and cholangiofibrosis. The relative prevalence of these lesions was given. Most of these lesions morphologically were compared to their counterpart lesions in the rat. Certain lesions in our fish such as hepatocellular carcinomas, cholangiolar carcinomas, pericytomas, hemangiopericytomas, spongiosis hepatis, and cholangiofibrosis have apparent similar cellular origins and morphogenesis to those lesions in rats and perhaps in other mammals. Spongiosis hepatis in the sheepshead minnow apparently arises from perisinusoidal cells and may be a neoplasm of this cell type. The general similarity of response to DENA in sheepshead minnows and rats suggests that this fish has promise as a model subject for studying some hepatocarcinogens and as a sentinel organism for detecting hepatocarcinogens in contaminated coastal waters.
Abstract P354: The “Afro-Cardiac Study” Identifies High Burden of Cardiovascular Disease Risk in West African Immigrants in the United States
Authors: Yvonne Y Commodore-Mensah, Charles A Berko, Maame E Sampah, Joycelyn Cudjoe, Cheryl D Himmelfarb
Journal: Circulation (2015)

Introduction: The African immigrant population grew 40-fold between 1960 and 2007, from 35,355 to 1.4 million with one third coming from West Africa, primarily Ghana and Nigeria. African immigrants have been understudied and, traditionally, lumped into the racial category of Black/African-American. We have examined the prevalence of CVD risk factors (hypertension, overweight/obesity, diabetes, hyperlipidemia, current smoking and physical inactivity), assessed global CVD risk and identified independent predictors of increased CVD risk by sex in West African immigrants (WAI). Methods: Cross-sectional study of WAI (Ghanaians and Nigerians) aged 35-74 years recruited from churches in the Baltimore/ Washington, DC metropolitan area. CVD risk factors were determined per AHA guidelines. Descriptive statistics were performed on participant’s Pooled Cohort Equations (PCE) scores and CVD risk factors with comparison by sex. Participants with PCE scores ≥7.5% and ≥3 CVD risk factors were deemed high risk. A multivariable logistic regression was fitted to identify independent predictors of high CVD risk. Results: The mean age of the 253 participants was 49.5±9.2 years and 58% were female. Males were more likely to be employed than females (90% vs. 72%; p=0.001). Only 52% of participants had health insurance. The majority [54% [137/253)] had ≥3 CVD risk factors and 28% had PCE score ≥7.5%. Smoking was the least prevalent (&lt;1%) and overweight/obesity the most prevalent (88%) risk factor. Although females (64%) were more likely to be treated for hypertension than males (36%), there was no difference in hypertension control by sex. Diabetes was identified in 16% of the participants. Mean total cholesterol (TC) was 180.9±33.9mg/dL and 32% had TC level ≥200mg/dL. In addition, 44% were found to be physically inactive (&lt;150minutes/week of moderate or &lt;75minutes/week of vigorous physical activity). In females, employment [0.18 AOR, 95%CI: 0.075-0.44)] and health insurance [0.35 AOR, 95%CI 0.14-0.87)] were associated with a PCE score ≥7.5%. In males, higher social support was associated with a 0.92 (95%CI: 0.84-0.98) odds of having ≥3 CVD risk factors. Conclusion: The high prevalence of CVD risk among relatively young WAIs is worrisome and suggests that the “healthy immigrant effect” may no longer hold for 21st century African immigrants. Employment and health insurance were protective against high CVD risk in females with social support protective against high CVD risk in males. CVD prevention strategies must be tailored to the unique needs of the WAI with consideration of socioeconomic status and sex.
EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib.
Authors: Andrew X. Zhu, Masatoshi Kudo, Eric Assenat, Stéphane Cattan, Yoon-Koo Kang, Ho Yeong Lim, Ronnie Tung Ping Poon, Jean-Frédéric Blanc, Arndt Vogel, Chao-Long Chen, Etienne Dorval, Markus Peck-Radosavljevic, Armando Santoro, Bruno Daniele, Junji Furuse, Annette Jappe, Kevin Perraud, Ozlem Anak, Dalila B. Sellami, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2014)

172 Background: No effective treatment options exist for advanced HCC following sorafenib failure. Preliminary data suggest everolimus may provide benefit after sorafenib. EVOLVE-1 (NCT01035229) assessed the efficacy and safety of everolimus for advanced HCC after sorafenib failure. Methods: Pts aged ≥18 y with BCLC stage B or C HCC and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were sorafenib intolerant were randomized 2:1 to everolimus 7.5 mg/d or placebo. All pts received best supportive care. Randomization was stratified by region (Asia v rest of world) and macrovascular invasion (yes v no). Study drug was given continuously until disease progression or intolerable toxicity. CT/MRI was performed every 6 wk. Primary endpoint was OS. Secondary endpoints were TTP, disease control rate (DCR; percentage of pts with best overall response of CR, PR, or SD per RECIST 1.0), and safety. Final analysis was performed when 454 deaths occurred. Results: 546 pts from 18 countries enrolled from Apr 2010 to Mar 2012 (everolimus = 362, placebo = 184). Baseline characteristics were balanced between arms; median age was 66.0 y, 84.8% of pts were male, 86.3% had BCLC stage C disease, 16.7% were from Asia, 32.8% had macrovascular invasion, and 74.0% had extrahepatic disease. Prior sorafenib was discontinued for disease progression in 80.8% of pts and intolerance in 19.0%. Median OS was 7.56 mo with everolimus and 7.33 mo with placebo (HR 1.05; 95% CI 0.86-1.27; P = .675). Median TTP was 2.96 mo and 2.60 mo, respectively (HR 0.93; 95% CI 0.75-1.15). DCR was 56.1% and 45.1%, respectively (P = .010). The most common grade 3/4 AEs with everolimus (v placebo) were anemia (7.8% v 3.3%), asthenia (7.8% v 5.5%), decreased appetite (6.1% v 0.5%), and hepatitis B viral load increase or reappearance (6.1% v 4.4%). No pts experienced HCV flare. HBV reactivation was experienced by 39 pts (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. Conclusions: Everolimus did not improve OS in pts with advanced HCC whose disease progressed on or after sorafenib or who were sorafenib intolerant. The safety profile was consistent with that previously observed with everolimus. Clinical trial information: NCT01035229.
Predictive factors of restrictive allograft syndrome after lung-transplantation
Authors: Hendrik Suhling, Sabine Dettmer, Annelies Boemke, Mark Greer, Felix Ringshausen, Gregor Warnecke, Axel Haverich, Tobias Welte, Jens Gottlieb
Journal: European Respiratory Journal (2014)

Background: Chronic lung allograft dysfunction (CLAD) limits the survival after lung transplantation; restrictive allograft syndrome (RAS) was shown to have an even worse prognosis.

Aims and objectives: The study was performed to characterize RAS patients of the Hannover cohort and evaluate parameters predicting RAS.

Methods: Single-centre retrospective study including all patients after double lung- or heart-lung transplantation of the outpatient clinic between September 1987 to July 2012 when CLAD was developed and complete pulmonary function with measurement of lung volumes was available. Patients were classified as severe RAS when irreversible total lung capacity (TLC) decline of more than 19% from TLC baseline (BL) was documented. Survival, time to CLAD and survival after CLAD was investigated.

Results: 215 patients fulfilled inclusion criteria and 29 had a severe RAS with significantly reduced survival (2134 d vs. 3084 d, p=0.001). Patients with TLC decline of 10 – 19 % from TLC BL did show significant different survival compared to severe RAS (p=0.001) but not to non-RAS CLAD patients (3400 d vs. 3044 d, p = 0.8).

A multivariate analysis proved TLC, forced vital capacity (FVC) and residual volume (RV) decline and fibrotic changes in chest x-ray at onset of CLAD being associated with later manifestation of severe RAS.

Conclusion: RAS can be predicted at time point of CLAD onset using FVC, TLC, RV and fibrotic changes in chest x-ray. Furthermore, TLC decline of more than 19% from TLC BL is of clinical relevance, less TLC decline had no impact on survival.
RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Authors: Sherene Loi, Sathana Dushyanthen, Paul A. Beavis, Roberto Salgado, Carsten Denkert, Peter Savas, Susan Combs, David L. Rimm, Jennifer M. Giltnane, Monica V. Estrada, Violeta Sánchez, Melinda E. Sanders, Rebecca S. Cook, Mark A. Pilkinton, Simon A. Mallal, Kai Wang, Vincent A. Miller, Phil J. Stephens, Roman Yelensky, Franco D. Doimi, Henry Gómez, Sergey V. Ryzhov, Phillip K. Darcy, Carlos L. Arteaga, Justin M. Balko
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking. Experimental Design: We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1–targeted immunotherapy in mouse models of breast cancer. Results: Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras–MAPK signaling were significantly correlated with lower TILs. MEK inhibition upregulated cell surface MHC expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PD-L1/PD-1 inhibition enhanced antitumor immune responses in mouse models of breast cancer. Conclusions: These data suggest the possibility that Ras–MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1–targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors. Clin Cancer Res; 22(6); 1499–509. ©2015 AACR.
Chloroma as a mediastinal mass with bronchial infiltration and severe stenosis of the left main bronchus
Authors: Joao Pedro Steinhauser Motta, Axel Tobias Kempa, Franz Stanzel, Jörn Brune
Journal: European Respiratory Journal (2012)

We report the case of a 46 years old women, who presented to our hospital with cough, chest pain and exertional dyspnea for 1 month. The physical examination showed inspiratory stridor located on the left hemithorax. The laboratory tests showed no pathological changes. The thorax computer tomography showed a large mediastinal mass with compression of the left main bronchus.  Bronchoscopy revealed an almost complete obstruction of the left main stem bronchus with extensive infiltration of the mucosa by tumorous tissue. The EBUS-TBNA biopsies demonstrated the suspect of a neoplasm of hematologic origin. The patient was transferred to a referral center for hemato-oncology and underwent a bone narrow biopsy. It could be diagnosed an acute myeloid leukemia. The mediastinal mass and bronchial infiltration corresponded to a chloroma (myeloid sarcoma) as a rare and severe initial manifestation of the disease.  Chloroma is an extramedullary, solid tumor which occurs in association with myeloproliferative or leukemic disorders. It affects 3-8% of patients with acute myeloid leukemia and can present as the initial manifestation of hematologic malignicy. The anatomic distribution includes bone, nerve, lymph node, and skin, but may involve a variety of soft tissues. Pulmonary and mediastinal involvement is rare. Just one case has yet been reported in literature with an identical pattern of airway infiltration.