tbuckley/cabot-search huggingface dataset:
The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer.
Authors: S L Graziano, R Mazid, N Newman, A Tatum, A Oler, J A Mortimer, J J Gullo, S M DiFino, A J Scalzo
Journal: Journal of Clinical Oncology (1989)

Small-cell lung cancer (SCLC), a chemotherapy-responsive disease, is characterized by neuroendocrine properties. In contrast, non-small-cell lung cancer (NSCLC) is at best moderately responsive to chemotherapy, and only 10% to 20% of cases demonstrate neuroendocrine properties. The present study is a retrospective analysis of the use of immunoperoxidase markers for neuron-specific enolase (NSE), Leu-7, and chromogranin A in NSCLC patients treated with chemotherapy. It was designed to determine if the presence of neuroendocrine markers predict for response to chemotherapy. The diagnostic slides and blocks were obtained on 52 NSCLC patients who were treated with chemotherapy (26 responders and 26 nonresponders). Immunoperoxidase studies were performed, and slides were scored without knowledge of the patient's response. Markers were positive in responders and nonresponders, respectively, as follows: NSE, 14 of 26 (54%) versus seven of 26 (27%), P = .04; Leu-7, 11 of 25 (44%) versus five of 26 (19%), P = .08; and chromogranin A, three of 26 (12%) versus 0 of 26 (0%), P = .71. Two markers were positive in 10 of 26 responders (38%) and 0 of 26 nonresponders (0%), P less than .01. Responders with two or more positive markers showed superior survival (median, 79 weeks) compared with responders with fewer than two positive markers (median, 51 weeks) and nonresponders (median, 27 weeks). These data suggest that the presence of neuroendocrine markers in NSCLC is associated with an increased likelihood of response to chemotherapy and may add to the standard parameters (performance status, weight loss) used to select patients for chemotherapy.
Ten-year trend in the prevalence of chronic cough and phlegm among young adults in Italy
Authors: Simone Accordini, Veronica Cappa, Isa Cerveri, Cristina Bombieri, Massimiliano Bugiani, Lucio Casali, Lucia Cazzoletti, Angelo Corsico, Marcello Ferrari, Virginia Ferretti, Alessandro Fois, Francesca Locatelli, Alessandro Marcon, Mario Olivieri, Pietro Pirina, Roberto de Marco
Journal: European Respiratory Journal (2011)

The presence of chronic cough and phlegm (on most days for a minimum of 3 months a year and for at least 2 successive years) identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits. We sought to evaluate the ten-year trend in the prevalence of these symptoms among young adults in Italy.  In 1998/2000, a screening questionnaire was mailed up to 3 times to general population samples of 20-44 year-old subjects, and eventually given over the phone to the remaining non-responders, in the Italian Study on Asthma in Young Adults (ISAYA) (9 centres; response rate = 72.7%). The same procedure was repeated in the Gene Environment Interactions in Respiratory Diseases (GEIRD) study in 2007/2010 (7 centres; response rate = 57.2%).  In the 4 centres (Pavia, Sassari, Turin, Verona) involved in both the studies, the adjusted percentage* of current smokers has decreased (from 34.3 to 27.4%; p  The overall prevalence of chronic cough and phlegm has not changed during the past decade among young adults in Italy, but a decrease is expected due to the observed reduction in the percentage of current smokers. The increase in the prevalence among non-smokers deserves further investigation.
Use of growth factors associated with docetaxel and paclitaxel in patients with early-stage breast cancer in a community oncology center
Authors: S. H. Boklage, L. Chen, N. P. Christiansen, S. D. Sullivan, J. W. Hay, C. D. Mullins
Journal: Journal of Clinical Oncology (2009)

e17548 Background: Docetaxel and paclitaxel are widely used in treating breast cancer (BC), and both have hematologic toxicity commonly managed by costly growth factors (GFs). However, the extent of GFs use in real-world clinical practice has not been well documented. Methods: The Georgia Oncology Specialist Database was used and contained chemotherapy, medical and pharmacy claims, and lab results for nearly 170,000 patients with various types of cancer (2003–2008). Patients with stage I-III BC receiving docetaxel- or paclitaxel-containing regimens as adjuvant therapy were followed from 1 week prior to docetaxel or paclitaxel (index drug) initiation to the earliest of death, loss to follow-up, switch in taxane, or end of 90-day period post last dose of index drug. Incidence of GFs use per person-year was compared using univariate negative binomial (NB) model, median time to first GFs use was compared using Wilcoxon test. Multivariate analyses were performed on number of utilizations and time to first utilization adjusting for potential confounders. Results: Compared with paclitaxel (n = 433), docetaxel cohort (n = 216) had lower incidence per person-year of erythroid stimulating agents (ESAs) use (8.01 vs. 11.72, p = 0.008), while similar incidence of myeloid growth factors (MGFs) use (8.51 vs. 5.07, p = 0.541). Lower MGFs utilization in docetaxel patients (ratio of number of utilization = 0.821, p = 0.033), and similar ESAs utilization (ratio of number of utilization = 0.920, p = 0.305) were found. While descriptive analysis showed paclitaxel patients received first ESAs sooner than docetaxel patients (median length: 23 vs. 7 days, p &lt; 0.001), and no difference in time to first MGFs use (median 8 days for both); multivariate analyses found docetaxel patients received first MGFs sooner (ratio of days = 0.828, p = 0.039), and no difference in time to first ESAs use (ratio of days = 1.091, p = 0.419). Conclusions: This analysis suggests that docetaxel is associated with lower utilization of MGFs. Studies examining the economic impact of GFs use associated with taxanes will need to be conducted. A potential limitation of this study is that the potential selection bias may not be fully adjusted. [Table: see text]
Phase III Comparison of High-Dose Paclitaxel + Cisplatin + Granulocyte Colony-Stimulating Factor Versus Low-Dose Paclitaxel + Cisplatin in Advanced Head and Neck Cancer: Eastern Cooperative Oncology Group Study E1393
Authors: Arlene A. Forastiere, Traci Leong, Eric Rowinsky, Barbara A. Murphy, Daniel R. Vlock, Ronald C. DeConti, George L. Adams
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m 2 (24-hour infusion) + cisplatin 75mg/m 2 + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m 2 (24-hour infusion) + cisplatin 75 mg/m 2 . Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.
Increased renin-angiotensin-aldosteron system activity in lungs of patients with idiopathic pulmonary arterial hypertension
Authors: Frances S. de Man, Christophe Guignabert, Ly Tu, Charlene Francois, Gerard Simmoneau, Elie Fadel, Marc Humbert, Anton Vonk-Noordegraaf, Saadia Eddahibi
Journal: European Respiratory Journal (2011)

Studies have reported over-activation of the sympathetic nerve system (SNS) in patients with idiopathic Pulmonary Arterial Hypertension (iPAH). Since the Renin-Angiotensin-Aldosteron-System (RAAS) is closely related to SNS and the lungs are the major site for angiotensin 2 formation, we hypothesized that RAAS-activity is increased in iPAH.  Pulmonary endothelial cell (P-EC) cultures were generated from lung specimens of iPAH-patients (n=5) and controls (n=5) to assess angiotensin converting enzyme (ACE) activity (Fig. 1A). We determined angiotensin 2 production upon incubation with angiotensin 1 alone and in combination with ACE-inhibitor enalapril. Subsequently, protein levels of the angiotensin 2 receptor type 1 (AT1R) and tyrosine kinase SRC-activity (downstream target of AT1R) were evaluated in pulmonary arteries (PA) homogenates.  P-EC of iPAH-patients produced significantly more angiotensin 2 upon angiotensin 1 incubation, compared to control. Interestingly, enalapril normalized angiotensin 2 production (Fig. 1B). In addition, pulmonary arteries of iPAH-patients exhibited increased AT1R expression and accentuated SRC-activity (Fig. 1C,D)   Conclusion:  This study demonstrates increased RAAS-activity in lungs of iPAH-patients, illustrated by elevated ACE-activity and AT1R signalling. Future studies will focus on the effects of chronic inhibition of RAAS on pulmonary vascular remodelling in iPAH.
Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)
Authors: C. Reading, C. Dowding, B. Schramm, A. Garsd, N. Onizuka-Handa, D. Stickney, J. Frincke
Journal: Clinical Microbiology and Infection (2006)
Distinct phenotypic and pathophysiologic features of elderly asthma
Authors: Min-gyu Kang, Woo-jung Song, Seung-Eun Lee, So-Hee Lee, Kyung-Up Min, Sang-Heon Cho
Journal: European Respiratory Journal (2012)

Background: Recent epidemiologic evidence suggests that asthma is prevalent in the elderly population. Majority of elderly asthma develops in later life, and thus is considered patho-physiologically distinct from young adult asthma.  Objective: To investigate whether elderly asthmatics may have different phenotypic or pathophysiologic features from young adult asthmatics  Methods: Young adult (18-45 years) and elderly (≥65 years) non-smoking, treatment-naive asthmatics were compared cross-sectionally. Asthma was defined if they had typical symptoms and methacholine PC20 ≤ 8 mg /mL. They completed baseline spirometry, induced sputum analyses, inhalant allergen skin prick tests, and anthropometric measurements. As indices of small airway involvements, a FEF25-75% and FEF25-75/FVC were used.  Results: A total of 103 young adult (mean age: 29.9 year) and 120 elderly (mean age: 71.1 year) asthmatics were included. Two age groups had similar degrees of airway hyperresponsiveness (methacholine PC20; 2.7 ± 2.2 mg/mL in the elderly vs. 2.7 ± 2.5 mg/mL in young adults). They also did not differ in gender distribution, FVC%, or FEV1%. However, the elderly asthmatics had higher body mass index (24.9 kg/m2 vs. 23.3 kg/m2, P  Conclusions: Elderly asthmatics had different phenotypic and pathophysiologic features from young adult asthmatics, suggesting their distinct pathogenic mechanisms and therapeutic considerations.
Risk-benefit relationships in cancer clinical trials: the ECOG experience in non-small-cell lung cancer.
Authors: R J Simes
Journal: Journal of Clinical Oncology (1985)

Although there is widespread recognition of the need to critically evaluate risks and benefits for patients participating in clinical trials, the actual implementation can be a difficult task. As an illustration of the analytic difficulties, we reviewed the experience of the Eastern Cooperative Oncology Group (ECOG) in advanced (inoperable) non-small-cell lung cancer over the past ten years (1973 to 1983). Of 2,714 ECOG patients analyzed, 15% showed objective tumor response. Median survival of all patients was 4.2 months, with approximately one half of patient's survival spent on protocol treatment. Thirty-nine percent of patients experienced at least one episode of severe or worse toxicity from therapy. Chemotherapy impact on this disease was assessed by examining trends in patient outcomes over the decade studied and by comparisons with patients receiving no treatment from earlier Veterans Administration Lung Protocols. Introducing more intensive chemotherapy regimens over this period appears to have resulted in some improvement in survival and response to therapy, but at the expense of greater toxicity. Despite modest survival gains achieved by these evolving trials, the community benefit from such trials seems clear, both in identifying ineffective therapies (and avoiding their general use) and as an important step in developing effective regimens. However, the decision for an individual patient to participate in a trial may involve difficult trade-offs between risk and benefit. This study suggests the need to identify subgroups of patients unlikely to benefit from trial participation and stresses the importance of incorporating patient preferences in the final decision. Some of the problems in patient communication are discussed.
EGFR exon in lung cancer: Survival predictors?
Authors: Inês Ladeira, Ana Antunes, Carla Ribeiro, Ana Barroso, Sara Conde, Barbara Parente
Journal: European Respiratory Journal (2012)

EGFR mutations are associated with sensitivity to tyrosine kinase inhibitors(TKI) in patients with NSCLC.Studies point to different outcome to TKI treatment according to exon mutation.   Aim :Understand how different EGFR mutations predict TKI response and affect survival.   Methods : Records review of NSCLC patients with EGFR study(2006-2011). Epidemiological,clinical and outcome information was analyzed using SPSS19.0(p   Results : Of 409 patients studied 53 were EGFR-positive. After exclusion of 1 drug-resistant patient(exon20) and patients who did not use TKI or had TKI as 1st therapeutic,22 patients were considered-50%male,67.5±9.8y,59.1%non-smokers.  Progression-free survival(PFS) was better in exon 19 mutations(p0.04). Survival after TKI(STKI) was better in 18 and 19 mutated patients (no statistical difference-p0.06).  In non-surgical stages(72.8%), exon 19 mutated patients had better global survival(GS),STKI and PFS than others (p>0.05).  Associating patients with exons 18 and 20(described as less predictive of therapeutic outcome) GS29.1, STKI12.2 and PFS8.6 months, all higher than values found for exon21(p>0.05).   Conclusions : Exon 19 mutation confered better prognosis to patients treated with TKI. Exons 18 and 20(22,7%) were not associated with worse prognosis than exon21. Although this is a small group we believe that is worth to maintain analysis of the 4 exon mutation.
Prevalence depression – Anxiety and impact on quality of life, asthma control and asthma severity in adult patients with asthma
Authors: Aysegul Altintop, Haydar Karakus, Zeynep Aytemur, Suleyman Hacievliyagil, Hilal Ermis, Munevver Erdinc
Journal: European Respiratory Journal (2011)

We examined the prevalence of depression and anxiety, and impact of depression and anxiety on quality of life, and treatment response of disease in patients with asthma.  Demographic data, smoking, allergy, atopy, additional diseases, age started asthma, age diagnosed asthma, and body mass index was (BMI) calculated. Hospital-Anxiety Depression Scale (HADS), Asthma Quality of Life Questionnaires (AQLQ) in the subjects were evaluated.  The sample consisted of 414 subjects (73% female) with a mean age of 47,6±13,8 years. Regarding chronic severity, 9,8% were intermittent, 63,2% mild persistent, 24,4% moderate persistent, and 2,6% severe persistent. Furthermore, 44,1% of the subjects were controlled asthma, 47,9% were partly controlled,%8 were uncontrolled. Rates of physician-diagnosed depression and anxiety were 10,4% and 2,9%. Regarding HADS, anxiety score was ≥10 in 37,4% and depression score ≥7 in 50,2% of the subjects. Prevalence of physician-diagnosed depression was significantly higher in women. HADS depression score was significantly higher in women (p  It suggests that depression and anxiety are associated with worse asthma control and quality of life. Physicians should consider depression and anxiety in patients with worse controlled asthma and quality of life in spite of optimal therapy for asthma.
Breast Cancer Risk Reduction
Authors: Therese B. Bevers, Deborah K. Armstrong, Banu Arun, Robert W. Carlson, Kenneth H. Cowan, Mary B. Daly, Irvin Fleming, Judy E. Garber, Mary Gemignani, William J. Gradishar, Helen Krontiras, Swati Kulkarni, Christine Laronga, Loretta Loftus, Deborah J. MacDonald, Martin C. Mahoney, Sofia D. Merajver, Ingrid Meszoely, Lisa Newman, Elizabeth Pritchard, Victoria Seewaldt, Rena V. Sellin, Charles L. Shapiro, John H. Ward
Journal: Journal of the National Comprehensive Cancer Network (2010)
Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis
Authors: Christophe Martinaud, Christophe Desterke, Johanna Konopacki, Lisa Pieri, Frédéric Torossian, Rachel Golub, Sandrine Schmutz, Adrienne Anginot, Bernadette Guerton, Nathalie Rochet, Patricia Albanese, Emilie Henault, Olivier Pierre-Louis, Jean-Baptiste Souraud, Thierry de Revel, Brigitte Dupriez, Jean-Christophe Ianotto, Marie-Françoise Bourgeade, Alessandro M. Vannucchi, Jean-Jacques Lataillade, Marie-Caroline Le Bousse-Kerdilès
Journal: Cancer Research (2015)

Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFβ1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFβ1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFβ1 receptor TGFβR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy.
Overview: research on the psychology of women. I. Gender differences and sexual and reproductive life
Authors: Anne M. Seiden
Journal: American Journal of Psychiatry (1976)

There has been a recent and rapid increase in research literature pertaining to women; this revolution in women's studies may be currently unequaled in any other field related to psychiatry. In this first part of a two-part article the author briefly discusses the social and intellectual contexts of research in this area. She reviews recent research on gender differences in behavior and on women's sexual and reproductive lives, including various aspects of the menstrual cycle, menopause, diseases of the reproductive organs, coitus, rape, childbirth, lactation, and fertility control. The second part will cover research on women in families, communities, work, and psychotherapy; and it will attempt to assess limitations of present knowledge and the anticipated directions and impact of future research.The social and intellectual contexts of research in the area of the psychology of women are discussed. Major findings in aspects of gender differences and sexual and reproductive live are reviewed. The discussion on sexual and reproductive life includes the significance of aspects of the menstrual cycle, menopause, diseases of the reproductive organs, coitus, rape, childbirth, lactation, and fertility control. Today the norm of controlling one's own fertility is experienced as new, and pregnancy is felt to be a matter of choice. However, no contraceptive method except sterilization is 100% effective and many have medical hazards. The safest methods for women are the diaphragm and the condom with back-up abortion, but these methods are psychologically less acceptable. There is a need for research on the psychology of family planning outside of the nuclear family. Data support the conclusion that abortion is safer than normal birth.
Phase I Study of ZD9331 on Short Daily Intravenous Bolus Infusion for 5 Days Every 3 Weeks With Fixed Dosing Recommendations
Authors: B. C. Goh, M. J. Ratain, D. Bertucci, R. Smith, S. Mani, N. J. Vogelzang, R. L. Schilsky, M. Hutchison, M. Smith, S. Averbuch, E. Douglass
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To conduct a phase I study of ZD9331, a potent, nonpolyglutamatable thymidylate synthase inhibitor using a short daily infusion for 5 consecutive days every 21 days. PATIENTS AND METHODS: Patients with refractory cancer or cancer for which no standard therapy was available were treated in escalating doses using an accelerated titration design. Plasma and urine samples were collected at timed intervals in the first cycle for pharmacokinetic analysis. RESULTS: Seventy-four patients were enrolled at 12 dose levels from a starting dose of 0.4 mg/m 2 /d to 16 mg/m 2 /d and 25 mg/d fixed dosing, of which 67 were assessable for toxicity. Maximum-tolerated dose was reached at 16 mg/m 2 /d. Myelosuppression was dose-limiting, consisting of thrombocytopenia associated with neutropenic fever. Body-surface area did not correlate with drug clearance; therefore, fixed daily dosing of 25 mg/d was studied and found to be tolerable, with two of 12 dose-limiting events. Dose-limiting nonhematologic toxicity consisted of grade 3 erythematous maculopapular rash observed in one patient at 12 mg/m 2 /d and one patient at 25 mg/d. Pharmacokinetic analysis showed nonlinearity, with clearance increasing with dose. The mean clearance and terminal half-life of the drug were 6.6 ± 2.0 mL/min and 71.3 ± 27.0 hours, respectively. Area-under-the concentration-time curve was a better predictor of toxicity than dose, using multiple linear regression analyses. Minor response (40% shrinkage of tumor) was observed in one patient with colorectal cancer treated at 12 mg/m 2 /d. CONCLUSION: The recommended dose for ZD9331 on this schedule is 25 mg/d. Neutropenia, thrombocytopenia, and rash were dose-limiting, and efficacy studies in colorectal cancer are indicated.