tbuckley/cabot-search huggingface dataset:
Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan
Authors: Y. Ohe, Y. Ohashi, K. Kubota, T. Tamura, K. Nakagawa, S. Negoro, Y. Nishiwaki, N. Saijo, Y. Ariyoshi, M. Fukuoka
Journal: Annals of Oncology (2006)

To compare the efficacy and toxicity of three platinum-based combination regimens against cisplatin plus irinotecan (IP) in patients with untreated advanced non-small-cell lung cancer (NSCLC) by a non-inferiority design.A total of 602 patients were randomly assigned to one of four regimens: cisplatin 80 mg/m(2) on day 1 plus irinotecan 60 mg/m(2) on days 1, 8, 15 every 4 weeks (IP) carboplatin AUC 6.0 min x mg/mL (area under the concentration-time curve) on day 1 plus paclitaxel 200 mg/m(2) on day 1 every 3 weeks (TC); cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1000 mg/m(2) on days 1, 8 every 3 weeks (GP); and cisplatin 80 mg/m(2) on day 1 plus vinorelbine 25 mg/m(2) on days 1, 8 every 3 weeks (NP).The response rate, median survival time, and 1-year survival rate were 31.0%, 13.9 months, 59.2%, respectively, in IP; 32.4%, 12.3 months, 51.0% in TC; 30.1%, 14.0 months, 59.6% in GP; and 33.1%, 11.4 months, 48.3% in NP. No statistically significant differences were found in response rate or overall survival, but the non-inferiority of none of the experimental regimens could be confirmed. All the four regimens were well tolerated.The four regimens have similar efficacy and different toxicity profiles, and they can be used to treat advanced NSCLC patients.
Combined Effects of Obesity and Chronic Obstructive Pulmonary Disease on Dyspnea and Exercise Tolerance
Authors: Josuel Ora, Pierantonio Laveneziana, Dror Ofir, Athavudh Deesomchok, Katherine A. Webb, Denis E. O'Donnell
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Severity of lung hyperinflation is known to influence the extent of dyspnea and exercise intolerance among patients with chronic obstructive pulmonary disease (COPD) with similar degrees of airway obstruction. Lung volume components are consistently affected by body mass index (BMI) in health and in disease.Objectives: To explore the complex interactions between obesity, lung hyperinflation, dyspnea, and exercise performance in COPD.Methods: We compared dyspnea intensity ratings and ventilatory responses (breathing pattern, operating lung volumes, and gas exchange) during symptom-limited incremental cycle exercise in well-characterized groups of 18 obese (mean BMI ± SD, 35 ± 4 kg/m2) and 18 normal-weight (mean BMI ± SD, 22 ± 2 kg/m2) patients with moderate to severe COPD.Measurements and Main Results: Groups were well matched for FEV1 (mean 49% predicted) and diffusing capacity (means >70% predicted), but resting lung hyperinflation (end-expiratory lung volume [EELV]) was significantly reduced in association with increasing BMI (P < 0.005). In the obese patients, peak symptom-limited oxygen uptake was increased (P < 0.01) and dyspnea ratings at a standardized ventilation were decreased (P < 0.01) compared with normal-weight patients. Ratings of dyspnea intensity at a standardized ventilation during exercise correlated well with the concurrent dynamic EELV/total lung capacity (TLC) ratio (r = 0.68; P < 0.00001) and with the resting EELV/TLC (r = 0.67; P < 0.00001).Conclusions: The combined mechanical effects of obesity and COPD reduced operating lung volumes at rest and throughout exercise with favorable influences on dyspnea perception and peak oxygen uptake during cycle ergometry.
Targeted Drug Delivery via the Transferrin Receptor-Mediated Endocytosis Pathway
Authors: Z. M. Qian
Journal: Pharmacological Reviews (2002)

The membrane transferrin receptor-mediated endocytosis or internalization of the complex of transferrin bound iron and the transferrin receptor is the major route of cellular iron uptake. This efficient cellular uptake pathway has been exploited for the site-specific delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that overexpress the transferrin receptors. This is achieved either chemically by conjugation of transferrin with therapeutic drugs, proteins, or genetically by infusion of therapeutic peptides or proteins into the structure of transferrin. The resulting conjugates significantly improve the cytotoxicity and selectivity of the drugs. The coupling of DNA to transferrin via a polycation or liposome serves as a potential alternative to viral vector for gene therapy. Moreover, the OX26 monoclonal antibody against the rat transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain.
Race and risk of lung cancer
Authors: K Ward
Journal: Thorax (2005)

▴ Cote ML, Kardia SLR, Wenzlaff AS, et al . Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer. JAMA2005;293:3036–42 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The investigators collected interview data on 692 patients with early onset lung cancer, 773 matched controls, and 7576 first degree relatives of cases and controls. Patients were diagnosed between 1990 and 2003 in Detroit, USA and all were aged less … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DCote%26rft.auinit1%253DM.%2BL.%26rft.volume%253D293%26rft.issue%253D24%26rft.spage%253D3036%26rft.epage%253D3042%26rft.atitle%253DRisk%2Bof%2BLung%2BCancer%2BAmong%2BWhite%2Band%2BBlack%2BRelatives%2Bof%2BIndividuals%2BWith%2BEarly-Onset%2BLung%2BCancer%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.293.24.3036%26rft_id%253Dinfo%253Apmid%252F15972566%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.293.24.3036&link_type=DOI [3]: /lookup/external-ref?access_num=15972566&link_type=MED&atom=%2Fthoraxjnl%2F60%2F9%2F753.atom [4]: /lookup/external-ref?access_num=000229945200019&link_type=ISI
Endoscopic measurement of oesophageal transmucosal potential difference in reflux oesophagitis.
Authors: B J Collins, R J McFarland, J M Sloan, A H Love
Journal: Gut (1984)

Oesophageal transmucosal potential difference (PD) was measured in 76 patients during endoscopy. Twelve patients with no symptoms of gastro-oesophageal reflux, and normal oesophageal appearance on endoscopy and mucosal biopsy had a PD of -18.3 +/- 3.8 mV (mean +/- SD). Thirty three patients had reflux symptoms but the oesophagus appeared normal at endoscopy. Eighteen of these patients had reflux change on oesophageal suction biopsies and the PD in the same region of the oesophagus in this group was -18.1 +/- 7.5 mV. In 15 of the patients, mucosal biopsies were normal and the PD in this group was -18.8 +/- 9.9 mV. Thirty one patients had erosive oesophagitis and PD values in this group were markedly reduced. Twenty seven of these patients had PD values less than -10 mV. We conclude that PD measured by our technique is abnormal in erosive oesophagitis but that it is of no value in the diagnosis of mild mucosal damage in patients with reflux symptoms when endoscopic findings are normal.
An Intensive Treatment Program of Interpersonal Psychotherapy Plus Pharmacotherapy for Depressed Inpatients: Acute and Long-Term Results
Authors: Elisabeth Schramm, Dietrich van Calker, Petra Dykierek, Klaus Lieb, Sabine Kech, Ingo Zobel, Rainer Leonhart, Mathias Berger
Journal: American Journal of Psychiatry (2007)

Objective: The purpose of this article was to determine the relative efficacy of a psychotherapy program when combined with pharmacotherapy versus medication and clinical management in more severely depressed patients. Method: A randomized controlled trial was conducted in 124 hospitalized patients with DSM-IV major depressive disorder that compared 5 weeks of interpersonal psychotherapy modified for depressed inpatients (15 individual and eight group sessions) plus pharmacotherapy with a regimen that involved medication plus intensive clinical management. The study included a prospective, naturalistic follow-up 3 and 12 months after acute treatment in 97 of 105 treatment completers. The 17-item version of the Hamilton Depression Rating Scale (HAM-D) was the primary outcome measure. Results: For the intent-to-treat cohort (N=124), analysis of covariance (ANCOVA) showed that patients treated with interpersonal psychotherapy had a significantly greater reduction of depressive symptoms at week 5. Response rates differed significantly between the two treatment conditions, favoring the group that received adjuvant interpersonal psychotherapy (70%) versus clinical management (51%). Remission rates also tended to be higher for patients in the interpersonal psychotherapy group (49% versus 34%). Patients who initially responded to interpersonal psychotherapy exhibited greater treatment gains at the 3-month follow-up evaluation, since only 3% of these subjects relapsed, compared with 25% of the clinical management subjects. Nine months later, this difference lost statistical significance. Conclusions: An inpatient treatment program with both brief and intensive psychotherapy plus pharmacotherapy is superior to standard treatment. The results, which add to a growing body of evidence, suggest that this combination treatment may offer an advantage over treatment with medication and clinical management for more severely depressed patients.
Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle Cell Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG)
Authors: Georg Lenz, Martin Dreyling, Eva Hoster, Bernhard Wörmann, Ulrich Dührsen, Bernd Metzner, Hartmut Eimermacher, Andreas Neubauer, Hannes Wandt, Hjalmar Steinhauer, Sonja Martin, Else Heidemann, Ali Aldaoud, Reza Parwaresch, Joerg Hasford, Michael Unterhalt, Wolfgang Hiddemann
Journal: Journal of Clinical Oncology (2005)

Purpose Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL. Patients and Methods One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNα). All patients older than 65 years received IFNα maintenance. Results R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups. Conclusion The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
The fertility potential of women with a single ovary
Authors: A Lass
Journal: Human Reproduction Update (1999)

The incidence of having a single ovary is quite common in infertile patients and can reach up to 17% of women with severe tubal disease who require in-vitro fertilization (IVF) treatment. Data on the short- and long-term implications of having only one ovary are scarce, and patients in this situation are naturally concerned. This article reviews the effect of possessing a single ovary on the fertility potential and ovarian reserve of the women and their performance in assisted reproduction treatment.
Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis <i>In vitro</i> and <i>In vivo</i>
Authors: Joell J. Gills, Jaclyn LoPiccolo, Junji Tsurutani, Robert H. Shoemaker, Carolyn J.M. Best, Mones S. Abu-Asab, Jennifer Borojerdi, Noel A. Warfel, Erin R. Gardner, Matthew Danish, M. Christine Hollander, Shigeru Kawabata, Maria Tsokos, William D. Figg, Patricia S. Steeg, Phillip A. Dennis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents. Experimental Design: HIV protease inhibitors were screened in vitro using assays that measure cellular proliferation, apoptotic and nonapoptotic cell death, endoplasmic reticulum (ER) stress, autophagy, and activation of Akt. Nelfinavir was tested in non–small cell lung carcinoma (NSCLC) xenografts with biomarker assessment. Results: Three of six HIV protease inhibitors, nelfinavir, ritonavir, and saquinavir, inhibited proliferation of NSCLC cells, as well as every cell line in the NCI60 cell line panel. Nelfinavir was most potent with a mean 50% growth inhibition of 5.2 μmol/L, a concentration achievable in HIV patients. Nelfinavir caused two types of cell death, caspase-dependent apoptosis and caspase-independent death that was characterized by induction of ER stress and autophagy. Autophagy was protective because an inhibitor of autophagy increased nelfinavir-induced death. Akt was variably inhibited by HIV protease inhibitors, but nelfinavir caused the greatest inhibition of endogenous and growth factor–induced Akt activation. Nelfinavir decreased the viability of a panel of drug-resistant breast cancer cell lines and inhibited the growth of NSCLC xenografts that was associated with induction of ER stress, autophagy, and apoptosis. Conclusions: Nelfinavir is a lead HIV protease inhibitor with pleiotropic effects in cancer cells. Given its wide spectrum of activity, oral availability, and familiarity of administration, nelfinavir is a Food and Drug Administration–approved drug that could be repositioned as a cancer therapeutic.
Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease.
Authors: E Beutler, W Kuhl, F Matsumoto, G Pangalis
Journal: The Journal of Experimental Medicine (1976)

Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: "acid" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested.
Proteomics: improving biomarker translation to modern medicine?
Authors: Paul C Guest, Michael G Gottschalk, Sabine Bahn
Journal: Genome Medicine (2013)

Biomarkers are defi ned as ‘measurable characteristics that refl ect physiological, pharmacological, or disease processes’ according to the European Medicines Agency [1]. Th e ideal platforms for biomarker discovery include genomic, transcriptomic, proteomic, metabonomic and imaging analyses. However, most biomarkers used in clinical studies are based on proteomic applications as the majority of current drug targets are proteins, such as G protein-coupled receptors, ion channels, enzymes and components of hormone signaling pathways [2]. Furthermore, linking the results of biomarker studies using protein-protein interaction approaches can assist in systems biology approaches and could lead to hypo thesis generation and identifi cation of new drug targets [3]. Proteomic-based approaches for biomarker investigation can be employed in diff erent aspects of medicine, such as elucidation of pathways aff ected in disease, identifi cation of individuals who are at a high risk of developing disease for prognosis and prediction of response, identifi cation of individuals who are most likely to respond to specifi c therapeutic interventions, and
Surface antigenic phenotypes of human T‐cell leukemia corresponding to those of post‐thymic T cells
Authors: Yoshifumi Ishii, Junichiro Fujimoto, Shinichiro Kon, Minoru Ogasawara, Hirofumi Koshiba, Chikara Mikuni, Kokichi Kikuchi
Journal: American Journal of Hematology (1982)

Abstract Leukemic cells from eight adult patients with various types of T‐cell leukemias, including one patient with lymphosarcoma cell leukemia (T‐LSL), two patients with chronic lymphocytic leukemia (T‐CLL), and five patients with adult T‐cell leukemia (ATL), were analyzed for their surface antigenic phenotypes with a series of monoclonal antibodies directing to human T‐cell differentiation antigens. All of the leukemic T cells studied were regarded as being of post‐thymic T‐cell origin because of their ability to form rosettes with sheep red cells under the condition at 4 o C but not 37 o C as well as the expression of human Ly‐1‐like but not TL‐like antigen on their cell surfaces. By using monoclonal antibodies to a variety of human T‐cell antigens (Leu‐1, Leu‐2a, and Leu‐3a), all eight cases could be divided into either group of three distinct categories. Thus, one patient with T‐LSL had cells with Leu‐1 + 2a + 3a + phenotype, which might reflect possible post‐thymic precursor T cells, whereas one patient with T‐CLL had cells with the same phenotype (Leu‐1 + 2a + 3a ‐ ) as normal cytotoxic/suppressor T cells. The latter cells also expressed Ia antigens as defined by monoclonal antihuman Ia antibody. The remaining six cases, including one T‐CLL and five ATL patients, had leukemic cells with the same phenotype (Leu‐1 + 2a ‐ 3a + ) as normally found on helper/inducer T cells, despite distinct clinical and immunological features between T‐CLL and ATL. Some clinical findings observed in those patients may reflect functional activities retained by their leukemic T cells.
Mother Rotors and the Mechanisms of D600-Induced Type 2 Ventricular Fibrillation
Authors: Tsu-Juey Wu, Shien-Fong Lin, Ali Baher, Zhilin Qu, Alan Garfinkel, James N. Weiss, Chih-Tai Ting, Peng-Sheng Chen
Journal: Circulation (2004)

Two types of ventricular fibrillation (VF) have been demonstrated in isolated rabbit hearts during D600 infusion. Type 1 VF is characterized by the presence of multiple, wandering wavelets, whereas type 2 VF shows local spatiotemporal periodicity. We hypothesized that a single mother rotor underlies type 2 VF.One (protocol I) or 2 (protocol II) cameras were used to map the epicardial ventricular activations in Langendorff-perfused rabbit hearts. Multiple episodes of type 2 VF were induced in 22 hearts by high-concentration (> or =2.5 mg/L) D600 (protocol I). During type 2 VF, a single spiral wave (n=19) and/or an epicardial breakthrough pattern (n=11) was present in 14 hearts. These spiral waves either slowly drifted or intermittently anchored on the papillary muscle (PM) of the left ventricle. Dominant-frequency (DF) analyses showed that the highest local DF was near the PM (12.5+/-1.1 Hz). There was an excellent correlation between the highest local DF of these spiral waves and breakthroughs (11.8+/-1.7 Hz) and the DF of simultaneously obtained global pseudo-ECG (11.2+/-1.8 Hz, r=0.97, P<0.0001) during type 2 VF. We also successfully reproduced the major features of type 2 VF by using the Luo-Rudy action-potential model in a simulated, 3-dimensional tissue slab, under conditions of reduced excitability and flat action-potential duration restitution.Either a stationary or a slowly drifting mother rotor can result in type 2 VF. Colocalization of the stationary mother rotors with the PM suggests the importance of underlying anatomic structures in mother rotor formation.
Wear resistance of artificial hip joints with poly(2-methacryloyloxyethyl phosphorylcholine) grafted polyethylene: Comparisons with the effect of polyethylene cross-linking and ceramic femoral heads
Authors: Toru Moro, Hiroshi Kawaguchi, Kazuhiko Ishihara, Masayuki Kyomoto, Tatsuro Karita, Hideya Ito, Kozo Nakamura, Yoshio Takatori
Journal: Biomaterials (2009)
A Small System—High-Resolution Study of Metabolic Adaptation in the Central Metabolic Pathway to Temperate Climates in Drosophila melanogaster
Authors: Erik Lavington, Rodrigo Cogni, Caitlin Kuczynski, Spencer Koury, Emily L. Behrman, Katherine R. O’Brien, Paul S. Schmidt, Walter F. Eanes
Journal: Molecular Biology and Evolution (2014)

In this article, we couple the geographic variation in 127 single-nucleotide polymorphism (SNP) frequencies in genes of 46 enzymes of central metabolism with their associated cis-expression variation to predict latitudinal or climatic-driven gene expression changes in the metabolic architecture of Drosophila melanogaster. Forty-two percent of the SNPs in 65% of the genes show statistically significant clines in frequency with latitude across the 20 local population samples collected from southern Florida to Ontario. A number of SNPs in the screened genes are also associated with significant expression variation within the Raleigh population from North Carolina. A principal component analysis of the full variance–covariance matrix of latitudinal changes in SNP-associated standardized gene expression allows us to identify those major genes in the pathway and its associated branches that are likely targets of natural selection. When embedded in a central metabolic context, we show that these apparent targets are concentrated in the genes of the upper glycolytic pathway and pentose shunt, those controlling glycerol shuttle activity, and finally those enzymes associated with the utilization of glutamate and pyruvate. These metabolites possess high connectivity and thus may be the points where flux balance can be best shifted. We also propose that these points are conserved points associated with coupling energy homeostasis and energy sensing in mammals. We speculate that the modulation of gene expression at specific points in central metabolism that are associated with shifting flux balance or possibly energy-state sensing plays a role in adaptation to climatic variation.