tbuckley/cabot-search huggingface dataset:
Fulvestrant (FUL) and goserelin (GOS) in premenopausal women with advanced, hormone-sensitive breast cancer: A pilot study
Authors: G. Steger, R. Bartsch, C. Wenzel, D. Hussian, U. Sevelda, U. Pluschnig, R. Mader, C. C. Zielinski
Journal: Journal of Clinical Oncology (2005)

708 Background: FUL is an estrogen receptor (ER) antagonist for the treatment of postmenopausal women with hormone-dependent advanced breast cancer (ABC). Our pilot study evaluated the efficacy and safety of FUL in premenopausal women with hormone-sensitive ABC rendered postmenopausal with continuous GOS treatment. Methods: This prospective trial included 14 patients (pts) with ER and/or progesterone receptor-positive ABC. 2 pts were human epidermal growth factor receptor 2-positive (HER2+). Pts received at least 3 doses of FUL 250 mg i.m. q 4 weeks and continued to receive GOS 3.6 mg sc q 4 weeks until disease progression or intolerability. Tumor assessment and evaluation of time to disease progression (TTP) occurred every 3 cycles. Results: 14 pts (median age 41 years, range 28–49) were included in this evaluation. 1 pt received GOS + FUL as 1st-line therapy, 7 as 2nd-, 5 as 3rd-, and 1 as 4th-line treatment, respectively. 11 pts (78.6%) had received adjuvant chemotherapy and 8 pts (57.1%) adjuvant endocrine therapy (tamoxifen). Prior palliative chemotherapy had been given to 6 pts (42.9%) and prior palliative endocrine therapy to 13 pts (92.9%) (anastrozole and/or exemestane under GOS treatment). 3 pts (21.4%) had only non-visceral metastases, 1 pt (7.1%) only visceral, and 10 pts (71.4%) both. 11 pts are currently evaluable for response: partial remission (PR) was observed in 1/11 pts, stable disease (SD) >3 months but <6 months in 1/11 pts, SD >6 months in 4/11 pts (36.4%), and progression despite treatment (PD) in 5/11 pts (45.5%). Both pts with HER2+ disease experienced SD >6 months. Median TTP is 5 months (2–12+). No local or systemic side effects were reported. Conclusion: Adding FUL to GOS treatment appears to be effective and well tolerated in premenopausal women with ABC including those with asymptomatic visceral disease and HER2+ disease. These preliminary data indicate a clinical benefit rate (PR+SD >6 mo) of 45.5%. FUL activity in pts with visceral disease and HER2+ tumors, and a TTP of 5 months, compares very favorably with data from similar naturally menopausal women with ABC. Thus, FUL in premenopausal women with iatrogenic menopause should be studied in controlled clinical trials. No significant financial relationships to disclose.
Exhaled nitric oxide: A useful adjunct test in assessing asthma control in primary care – A cross-sectional exploration
Authors: Evelien Termeer, Jiska Snoeck-Stroband, Hanneke Nuiten, Persijn Honkoop, Rik Loymans, Bart Thoonen, Ivo Smeele, Jaap Sont, Chris van Weel, Tjard Schermer
Journal: European Respiratory Journal (2011)

Background:  Established markers of asthma control, symptoms and lung function do not measure underlying bronchial inflammation and their results are sometimes contradicting. Measuring fractional exhaled nitric oxide (FeNO) as a marker of eosinophilic airway inflammation might offer benefit.   Aim:  To explore consequences of adding FeNO as an adjunct to symptoms and spirometry for assessing asthma control in primary care.   Methods:  We performed a cross-sectional analysis of two available cohorts of adult asthmatics. We assessed FeNO, lung function and Asthma Control Questionnaire (ACQ) levels in all participants. Pearson correlation coefficients were calculated between FeNO, ACQ,%FEV 1  predicted and%reversibility. In a scenario analysis, patients9 asthma control was categorized according to two established control markers, and with FeNO as an extra marker.   Results:  We included 147 and 160 patients (in total 63% female; mean age 35.4). Correlations between FeNO, symptoms and lung function were weak (max 0.240, between FeNO and%reversibility). All three control markers were consistent in interpretation of asthma control in 25.7% of the population. In 28.1% symptoms and lung function were consistent but FeNO was contradicting and in another 46.3% the two established markers were contradicting.   Conclusions:  We observed weak correlations between FeNO, symptoms and lung function in adults with asthma in primary care, which confirms that FeNO is an independent marker in assessing asthma control.  In almost half the population, results of symptoms and lung function were contradicting regarding assessing asthma control; in this group FeNO may fine-tune categorization of asthma control.
Pneumocystis carinii Pneumonia in Children With Cancer
Authors: H. Durell Johnson
Journal: JAMA (1970)

Pneumocystis carinii<i>pneumonia was diagnosed in 19 children with cancer. The diagnosis was made in 14 children by pulmonary needle aspiration and demonstration of the organism by methenamine silver nitrate stain. Two children had tension pneumothorax and one had postaspiration hemoptysis following needle aspiration, but there was no mortality from the procedure. Seventeen children were treated with pentamidine isethionate; nine recovered. Toxicity to pentamidine consisted of elevated blood urea nitrogen levels and hypoglycemia</i>.
Radiation-Induced Nausea and Vomiting
Authors: Susan Urba
Journal: Journal of the National Comprehensive Cancer Network (2007)

Radiation-induced nausea and vomiting is a common problem for cancer patients. The emetogenic potential of radiation depends greatly on the location of the radiation field, the size of the radiation field, and the fractionation scheme. Radiation fields can be categorized as having high, moderate, low, or minimal emetogenic risk, and treatment differs accordingly. The National Comprehensive Cancer Network, the Multinational Association of Supportive Care in Cancer, and the American Society of Clinical Oncology publish clinical practice guidelines addressing the issue of radiation-induced nausea and vomiting. This article reviews the treatment recommendations for each category of radiation-induced nausea and vomiting from these national and international guideline committees and provides the rationale for these recommendations.
Morning symptoms and acute breathing difficulties in the diagnosis of COPD
Authors: Philip O'Hagan, Beyza Oezel, Niels Chavannes
Journal: European Respiratory Journal (2014)

Introduction  Morning symptoms of COPD can severely compromise the ability to perform activities throughout the day and are associated with an increased frequency of exacerbations (Small M, Broomfield S and Pollard R. Thorax 2012; 67:A155). This survey quantified the reasons patients gave for their attendance at hospital prior to being diagnosed with COPD and the extent to which their daily routines were affected by morning symptoms.  Methods  Approximately 100 patients in each of eight countries completed a structured 20 minute on-line survey which thus had sufficient statistical power to reveal country differences. Patients were recruited from a panel of consumers who had previously expressed an interest in participating in healthcare research. Patients had to have been suffering from at least one of four common symptoms of COPD to a greater extent in the morning.  Results  Nearly two-thirds of patients attended hospital prior to the original diagnosis due to dyspnoea or persistent coughing/wheezing. A quarter attended due to an acute episode of breathing difficulty having experienced on average, four such episodes before diagnosis. Despite treatment, half of all patients had had to make changes to their morning routines.  Conclusions  Awareness of the common symptoms of COPD is key in reaching a diagnosis. Although it is less prevalent, acute breathing difficulty is also of diagnostic importance. Despite treatment, many patients continue to experience symptoms which place them at increased risk of acute breathing difficulties.
Aerobic training inhibits bleomycin-induced pulmonary fibrosis in BALB/c mice
Authors: Ana Roberta Almeida-Oliveira, Paulo Rogério Pereira, Flavia Regina Greiffo, Nicole Cristina Rigonato-Oliveira, Adilson Andrade-Sousa, Jefferson Comin, Manoel Oliveira-Junior, Ricardo Wesley Custodio, Regiane Albertini, Ana Paula Ligeiro Oliveira, Oliver Eickelberg, Rodolfo de Paula Vieira
Journal: European Respiratory Journal (2014)

Idiopatic pulmonary fibrosis (IPF) is a devastating disease with poor prognostic and no effective treatment is available. Although there are a considerable number of studies showing that pulmonary rehabilitation programs for IPF patients results in improved quality of life and disease management, the possible mechanisms involved in this beneficial effects remains to be elucidated. Therefore, the present study investigated the effects of low intensity treadmill aerobic training in an experimental model of pulmonary fibrosis induced by bleomycin in BALB/c mice. The results show that aerobic exercise reduced the number of total cells and neutrophils in bronchoalveolar lavage (pl0.001), reduced the amount of collagen fibers deposition in airways wall (pl0.01), as well as reduced the levels of IL-1beta, IL-6, KC and TNF-alpha in bronchoalveolar lavage fluid, while increased the levels of anti-inflammatory cytokine IL-10 (pl0.01). We conclude that aerobic training inhibits the fibrotic and inflammatory response in a model of pulmonary fibrosis induced by bleomycin.  .  .
ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy.
Authors: R Metzger, C G Leichman, K D Danenberg, P V Danenberg, H J Lenz, K Hayashi, S Groshen, D Salonga, H Cohen, L Laine, P Crookes, H Silberman, J Baranda, B Konda, L Leichman
Journal: Journal of Clinical Oncology (1998)

PURPOSE We have previously shown that relative thymidylate synthase (TS) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and cisplatin are inversely associated with response and survival. This is a presumed function of TS as a target for 5-FU activity. We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing (ERCC1) gene is inversely associated with response and survival as an independent function of cisplatin efficacy. PATIENTS AND METHODS Patients had intact, untreated, primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the beta-actin gene. RESULTS The median ERCC1 mRNA level from 38 primary gastric cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) also segregated responsive versus resistant tumors (P = .024). With both ERCC1 and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) responded (P = .003). CONCLUSION Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC1 mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined.
COPD and pseudomonas aeruginosa , an association
Authors: Tamara Alonso, Rosa Mar Gómez-Punter, Emma Vázquez, Cristina López, Elena García, Rosa María Girón, Julio Ancochea
Journal: European Respiratory Journal (2014)

Introduction:  Isolation of  Pseudomonas aeruginosa  (PA) in patients with COPD seems to be a marker of poor prognosis as it is related to a greater number and severity of exacerbations, increased airflow obstruction and lower BODE index.   Objective:  Describe the main characteristics of our patients with moderate-severe COPD and single or repeated isolation of PA.   Methods:  Observational, retrospective study. 20 patients. Analyzing sex, age, body mass index (BMI), Charlson index, dyspnea on the Medical Research Council (MRC) scale, phenotype according to the Spanish Guideline (GesEPOC), airflow obstruccion, bronchiectasis on High Resolution Computed Tomography (HRCT), number of exacerbations, antibiotic treatment and the BODE and BODEx scales in the previous and the posterior year after treatment.   Results:  90% male; mean age of 73.95 years (SD±9.88), BMI of 19.8, Charlson index 3.40 (SD 1.75). 50% had grade 3 dyspnea of MRC. According to the GesEPOC, 65% phenotype D, 20% phenotype C and 10% phenotype B. 95% of patients presented bronchiestasis. 70% of them had a single isolation and 30% repeated. Antibiotic treatment is shown in   . Exacerbations pre and post treatment were 3.4 (SD±2.13) and 1.7 (SD±1.5) respectively (p   Conclusions:  PA isolation is associated with increased number and severity of exacerbations .  Anti-pseudomonal treatment reduces respiratory exacerbations with better prognosis.
Expression of Apoptosis-Regulating Proteins in Chronic Lymphocytic Leukemia: Correlations With In Vitro and In Vivo Chemoresponses
Authors: Shinichi Kitada, Janet Andersen, Sophie Akar, Juan M. Zapata, Shinichi Takayama, Stanislaw Krajewski, Hong-Gang Wang, Xin Zhang, Florencia Bullrich, Carlo M. Croce, Kanti Rai, John Hines, John C. Reed
Journal: Blood (1998)
Abstract 68: Exomic landscape of uterine leiomyosarcomas
Authors: Netta Mäkinen, Tuomas Heikkinen, Mervi Aavikko, Ralf Bützow, Pia Vahteristo
Journal: Cancer Research (2015)

Abstract Uterine leiomyosarcomas are rare malignant tumors originating from the smooth muscle lining of the uterus, the myometrium. They account for 1-2% of all uterine malignancies with an estimated incidence of 0.3-0.4/100,000 women per year. The symptoms, signs, and histopathological features of uterine leiomyosarcomas widely overlap with those of uterine leiomyomas, their benign counterparts, which can cause diagnostic challenges in daily pathological practice. Because leiomyosarcomas are clinically aggressive tumors with poor 5-year survival and a high recurrence rate, early diagnosis is important for prolonged survival. Currently, the diagnosis of these tumors is often incidental and postoperative. Most leiomyosarcomas are aneuploid with complex numerical and structural chromosomal aberrations and show substantial cytogenetic heterogeneity. Although a few cancer genes have been implicated in uterine leiomyosarcomas, such as TP53, RB1, and CDKN2A, these genes represent, however, common cancer genes not specific for smooth muscle malignancies. The aim of this study is to examine somatic variation in the coding regions of uterine leiomyosarcomas by exome sequencing to identify potential new molecular biomarkers. Altogether 18 formalin-fixed paraffin-embedded tumor samples entered whole-exome sequencing. After the filtering of exome sequencing data, a list of genes which were mutated in at least two tumors was created. The list included over 50 genes TP53 being the most frequently mutated gene. The most prominent candidate variants are validated with Sanger sequencing and the validations are ongoing. Also a series of 35 additional tumors is available on tissue microarray for possible immunohistochemical validations. Identification of novel molecular genetic characteristics in uterine leiomyosarcomas is clinically relevant to further improve the diagnosis and prognosis of the patients. New knowledge on the mechanisms underlying the progression to malignancy is also essential for developing new treatments. Citation Format: Netta Mäkinen, Tuomas Heikkinen, Mervi Aavikko, Ralf Bützow, Pia Vahteristo. Exomic landscape of uterine leiomyosarcomas. [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 68. doi:10.1158/1538-7445.AM2015-68
Abstract 3192: Obesity and Its Relationship to Adverse Cardiovascular Outcomes in Older Patients With Heart Failure and Preserved Ejection Fraction in the I-PRESERVE Trial
Authors: Dalane W Kitzman, Marcus M Haas, Peter E Carson, Scott Hetzel, Michael Komajda, Michael Zile, Ralph H. Johnson, Robert Mckelvie, John J Mcmurray, D. Demets, C Staiger, Agata Ptaszynska, Barry Massie
Journal: Circulation (2009)
Apixaban after Acute Coronary Syndrome
Authors: Laurent Fauchier, Nicolas Clementy
Journal: New England Journal of Medicine (2011)

To the Editor: The results of the APPRAISE-2 trial (Aug. 25 issue) 1 raise doubt about whether combining a long-term anticoagulant (apixaban) with dual antiplatelet therapy in patients with coronary disease can achieve meaningful incre - mental efficacy with an acceptable risk of bleed - ing. However, 15 to 20% of these patients may have atrial fibrillation. 2 Anticoagulation is the best antithrombotic therapy for the prevention of stroke in patients with atrial fibrillation, and apixaban seems a better option than warfarin by offering a lower risk of systemic embolism, less bleeding, and lower mortality. 3 Combined thera -
Commentary: Probably no pain in the absence of "self"
Authors: Z. Szawarski
Journal: BMJ (1996)

What happens if I am stung by a wasp? The first thing is a complex reaction in my body which results in the feeling of sharp pain and my violent reaction to the wasp. The pain is, of course, a specific subjective, qualitative feeling but it would not be possible unless there was a body (organism) which was exposed and reacted to the noxious stimulus. Thus pain has a dual nature. As a subjective, conscious feeling it is always my pain happening inside or on my body and nobody else can experience it. As an objective bodily, neurophysiological phenomenon it can be described and explained in the objective language of science.

The distinction implies several fundamental questions: what is the relation between the objective and subjective aspects …
Expression of RhoC correlates with metastatic disease and survival of prostate cancer patients
Authors: Megumi Iiizumi, Sucharita Bandyopadhyay, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Ken Saito, Misako Watabe, Eiji Furuta, Rui Zhan, Sudha K. Pai, Sonia Mohinta, Kounosuke Watabe
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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RhoC is a member of the RAS superfamily of small GTP-binding proteins. Rho GTPases have previously been shown to be involved in controlling cytoskeletal reorganization through MAP kinase pathway during cell migration and invasion, and they are considered to play key roles in tumor progression. The expression of RhoC appears to be highly up-regulated in various types of cancers including, breast, melanoma, pancreatic and lung. Moreover, inhibition of the expression of this gene was shown to significantly reduce the invasiveness of tumor cells in vitro, suggesting the role of RhoC in tumor metastases, although the molecular mechanism of RhoC action is yet to be examined. In order to understand the functional roles of RhoC in tumor metastases in prostate cancer, we performed immunohistochemical analysis on tumor specimens from 63 prostate cancer patients. RhoC was generally undetectable or only weakly expressed in normal epithelia and stroma cells, however, it was found to be significantly over-expressed in the cytoplasm of high grade tumors. The patients with high Gleason score (>7) had a tendency of higher expression of RhoC, although it was statistically not significant. However, the status of both lymphnode and distant metastatis have significant positive correlation with the RhoC expression (P<0.03). Interestingly, the RhoC expression also showed significant inverse correlation to that of Drg-1 which is a recently identified metastases suppressor gene. Further analysis of five year survival data revealed that the RhoC expression was significantly correlated to patient survival (P<0.02), and that Cox regression analysis indicated RhoC as an independent marker for the prediction of patient outcome. We also examined the effect of RhoC over-expression in prostate tumor cell lines and found that RhoC significantly enhanced both invasion and motility in vitro. Furthermore, results of western blot analysis of these RhoC over-expressed cells indicated that RhoC significantly altered the status of the phosphorylation of the Akt protein. Taken together, our results indicate that RhoC is involved in the process of tumor metastases in prostate cancer by augmenting cell invasiveness through a modulation of the Akt pathway, and that RhoC may serve as a useful prognostic marker.
Abstract 963: IDH2(R140Q) knock-in mouse recapitulating human type II D-2-hydroxyglutaric aciduria
Authors: Fang Wang, Jeremy Travins, Zhizhong Lin, Lee Silverman, Yue Chen, Yuxuan Lu, Hua Yang, Michael Su, Yong Cang, Kate Ellwood-Yen, Shengfang Jin
Journal: Cancer Research (2014)

Abstract A single amino acid substitution, R140Q, in isocitrate dehydrogenase 2 (IDH2) confers a novel enzymatic activity that converts α-ketoglutarate (αKG) to D-2-hydroxyglutarate (D-2-HG). This gain-of-function mutation has been identified in patients with type II D-2-hydroxyglutaric aciduria (D-2-HGA), a rare and severe neurometabolic disorder that presents with a range of clinical findings, including seizures, hypotonia, developmental delay, cardiomyopathy, dysmorphic features and early death. There are no effective therapies for this inherited autosomal dominant disease. Here, we report the generation and characterization of a mouse genetic model that recapitulates key features of type II D-2-HGA. A single amino acid replacement, R140Q, was introduced via homologous recombination into the endogenous mouse IDH2 gene locus, to create heterozygous IDH2(R140Q) knock-in (KI) mice. These KI mice produce significantly elevated levels of D-2-HG in all tissues tested, and exhibit multiple defects consistent with symptoms from D-2-HGA patients, including early mortality, brain lesions, and cardiac hypertrophy. Echocardiogram reveals impaired systolic function with a diffusely hypokinetic left ventricle and low ejection fraction. The IDH2(R140Q) knock-in mouse model provides a valuable tool to elucidate the underlying disease mechanism of D-2-HGA and to evaluate ways to mitigate the disease. Citation Format: Fang Wang, Jeremy Travins, Zhizhong Lin, Lee Silverman, Yue Chen, Yuxuan Lu, Hua Yang, Michael Su, Yong Cang, Kate Ellwood-Yen, Shengfang Jin. IDH2(R140Q) knock-in mouse recapitulating human type II D-2-hydroxyglutaric aciduria. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 963. doi:10.1158/1538-7445.AM2014-963