tbuckley/cabot-search huggingface dataset:
Targeting Wnt pathway in mantle cell lymphoma-initiating cells
Authors: Rohit Mathur, Lalit Sehgal, Frank K Braun, Zuzana Berkova, Jorge Romaguerra, Michael Wang, M Alma Rodriguez, Luis Fayad, Sattva S Neelapu, Felipe Samaniego
Journal: Journal of Hematology & Oncology (2015)

Mantle cell lymphoma (MCL) is an aggressive and incurable form of non-Hodgkin's lymphoma. Despite initial intense chemotherapy, up to 50% of cases of MCL relapse often in a chemoresistant form. We hypothesized that the recently identified MCL-initiating cells (MCL-ICs) are the main reason for relapse and chemoresistance of MCL. Cancer stem cell-related pathways such as Wnt could be responsible for their maintenance and survival.We isolated MCL-ICs from primary MCL cells on the basis of a defined marker expression pattern (CD34-CD3-CD45+CD19-) and investigated Wnt pathway expression. We also tested the potential of Wnt pathway inhibitors in elimination of MCL-ICs.We showed that MCL-ICs are resistant to genotoxic agents vincristine, doxorubicin, and the newly approved Burton tyrosine kinase (BTK) inhibitor ibrutinib. We confirmed the differential up-regulation of Wnt pathway in MCL-ICs. Indeed, MCL-ICs were particularly sensitive to Wnt pathway inhibitors. Targeting β-catenin-TCF4 interaction with CCT036477, iCRT14, or PKF118-310 preferentially eliminated the MCL-ICs.Our results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors.
Resveratrol attenuates cigarette smoke induced oxidative stress: Possible involvement of SIRT1
Authors: Jing An, Yong-Chun Shen, Tao Wang, Ting Yang, Fu-Qiang Wen
Journal: European Respiratory Journal (2012)

Objectives:  Cigarette smoke is known to cause oxidative stress in alveolar epithelial cells. In this study, we investigated the effects of resveratrol, a phytoalexin produced by some spermatophytes, on oxidative stress induced by cigarette smoke in airway epithelial cells.   Methods:  Rats with or without exposure to cigarette smoke were intraperitonealy injected with resveratrol (5,10,20mg/kg·d). TNF-α levels in BALF were determined by ELISA. Total glutathione, SOD and H 2 O 2  levels in rat lungs were detected. Human alveolar epithelial cells (A549) were exposed to cigarette smoke extract (CSE), with or without pretreatment of resveratrol (40μM). The activity of ROS was detected and the expression of SIRT1 protein was evaluated with western blotting.   Results:  Cigarette smoke exposure significantly increased TNF-α expression in BALF and this upregulaion was significantly attenuated by resveratrol (p 2 O 2  was decreased by resveratrol(p   Conclusions:  These results suggest that resveratrol attenuated oxidative stress induced by cigarette smoke. The anti-oxidant effect might act through the expression of SIRT1 proteins.
Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor.
Authors: C R Nichols, E P Fox, B J Roth, S D Williams, P J Loehrer, L H Einhorn
Journal: Journal of Clinical Oncology (1994)

PURPOSE We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature &gt; or = 38.5 degrees C and an absolute neutrophil count &lt; or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.
Brief Report: Main Contribution of DRB1*04:05 Among the Shared Epitope Alleles and Involvement of DRB1 Amino Acid Position 57 in Association With Joint Destruction in Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Chikashi Terao, Koichiro Yano, Katsunori Ikari, Moritoshi Furu, Noriyuki Yamakawa, Shinji Yoshida, Motomu Hashimoto, Hiromu Ito, Takao Fujii, Koichiro Ohmura, Kimiko Yurugi, Yasuo Miura, Taira Maekawa, Atsuo Taniguchi, Shigeki Momohara, Hisashi Yamanaka, Tsuneyo Mimori, Fumihiko Matsuda
Journal: Arthritis & Rheumatology (2015)

The shared epitope is associated with increased joint destruction in rheumatoid arthritis (RA) as well as susceptibility to RA and the production of anti-citrullinated protein antibody (ACPA). However, previous studies addressing whether the association of the shared epitope with joint destruction is independent of ACPA have shown different results in different populations. Different allele distributions in the shared epitope may explain this ethnic heterogeneity. This study was undertaken to assess the associations of the shared epitope and HLA-DRB1*04:05, the most common shared epitope allele in the Japanese population, with joint destruction in patients with ACPA-positive RA.A total of 861 patients with ACPA-positive RA who had not received any biologic agents were recruited from the institute of Rheumatology, Rheumatoid Arthritis cohort (sets 1 and 2) and the Kyoto University Rheumatoid Arthritis Management Alliance cohort (set 3). Joint destruction was assessed using the modified Sharp/van der Heijde score (SHS). The associations of the shared epitope alleles, HLA-DRB1*04:05, and other shared epitope allele groups with the SHS were analyzed in a linear regression analysis. Amino acid variations associated with the SHS were also analyzed.The shared epitope was significantly associated with an increased SHS (P = 0.0017). Although HLA-DRB1*04:05 was significantly associated with an increased SHS (P = 2.7 × 10(-5)), the group of other shared epitope alleles, including HLA-DRB1*01:01, did not show an association with the SHS in spite of sufficient power (P = 0.67). HLA-DRB1*04:05 was associated with joint destruction in a dose-dependent manner. Analyses of amino acid associations of HLA-DRB1 revealed that serine at position 57, recently shown to have a susceptibility effect for ACPA-positive RA in Asian populations, showed a significant association (P = 5.0 × 10(-6)).HLA-DRB1*04:05, characterized by serine at position 57, accounts for the detrimental association between the shared epitope and SHS in Japanese patients with ACPA-positive RA.
Low hypercapnic ventilatory response in long-term lung transplant recipients predicts exercise impairment
Authors: Manuela Weidmann, Bjoern E. Kleibrink, Thomas Rabis, Gerhard Weinreich, Markus Kamler, Helmut Teschler, Urte Sommerwerck
Journal: European Respiratory Journal (2012)

Background:  Only few studies reported findings on CO 2  rebreathing in long-term bilateral lung transplant recipients. Bilateral lung transplantation causes denervation of the donor lung. This might have an impact on control of breathing as measured by the hypercapnic ventilatory response (HCVR). The influence of gender on HCVR and the relation to exercise capacity is unknown yet.   Objectives:  To study HCVR and the relation to exercise capacity after bilateral lung transplantation.   Methods and patients:  Minute ventilation, respiratory rate and HCRV were studied in 24 bilateral lung transplant recipients (12 male). HCVR was measured according to the Read protocol. Exercise testing was performed to evaluate the maximum level of workload. This was expressed as percentage of the corresponding reference value.   Results:  Age and body mass index (BMI) of men and women were similar (age: 56 ± 9 years vs. 54 ± 9 years (n.s.), BMI: 26 ± 3 kg/m 2  vs. 25 ± 6 kg/m 2  (n.s.)). Post-transplant period ranged from 6 months to 9 years. HCVR in lung transplant recipients was 1.71 ± 1.25 l/min/mmHg in men and 0.95 ± 0.38 l/min/mmHg in women (p   Conclusion:  There is a remarkable difference in ventilatory response to carbon dioxide between male and female bilateral lung transplant recipients, suggesting a role for denervation of the lung in the impairment of exercise capacity after bilateral lung transplantation.
Abstract 858: Treatment resistance of colon cancer with low proteasome activity
Authors: Koji Munakata, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
Journal: Cancer Research (2014)

Abstract Background and aims:Emerging evidence indicates that cancer stem cells are resistant to chemotherapy and radiation therapy which result in recurrence after curative intent treatment for solid tumor. Recently, several reports have indicated that some cancer stem cells (CSCs) would be characterized by low proteasome activity. And cell of low proteasome activity could lead to new therapeutic targets. Material and methods: We engineered human colorectal adenocarcinoma cells (HCT116, KM12SM, SW480, LoVo, DLD1, HT29) to express a green fluorescent molecule fused to the degron of ornithine decarboxylase (Gdeg) from a retroviral vector; the fluorescent Gdeg supposed to be accumulated in CSC like cells as a result of low activity of the 26S proteasome. The feature of Gdeghigh cells were analyzed by sphere formation assay, surface marker analysis, reactive oxygen species (ROS) analysis and assessment of chemotherapy and radiation therapy sensitivity. Results: Population of Gdeghigh was up-regurated by chemotherapy (5-FU and oxaliplatin) and radiation therapy. Furthermore CSC markers were increased by chemotherapy and radiation therapy. ROS activity of Gdeghigh was lower than Gdeglow. Conclusions: Low proteasome activity cells suggested eatures of CSCs. Mechanisms of chemotherapy and radiation therapy resistance should be revealed to establish new therapeutic approach based on CSCs hypothesis. Citation Format: Koji Munakata, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori. Treatment resistance of colon cancer with low proteasome activity. [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 858. doi:10.1158/1538-7445.AM2014-858
Who is afraid of a bronchoscopy
Authors: Heinz Borer, Patrick Müller, Franziska Jenzer
Journal: European Respiratory Journal (2013)

Background: To evaluate patient9s (pts) fear of bronchoscopy (BRO), how the procedure itself is rated by the pts and whether the fear of BRO correlates with a suspected diagnosis of malignancy.  Methods: prospective evaluation of all pts undergoing BRO in our hospital during the year 2012 with a standardized questionnaire. The pts had to answer the question for the fear of BRO before the procedure and the question for discomfort they experienced during BRO after the procedure using a visual analog scale (vas: 0-10).  Results: 165 pts were enrolled, mean age 65 years (17-93, SD 15.8), 42% women, 58% men; 60% inpts, 40% outpts; 42% with suspected malignancy before BRO, 36% with proven malignancy by BRO. 23 pts were excluded (mechanical ventilation, missing data). Mean BRO duration was 18.2 min (3-44, SD 8.2), mean propofol dose was 160 mg (0-500, SD 95.5). Fear of BRO was rated 2.82 (SD 2.76) on the vas. Discomfort during BRO was rated 0.43 (SD 1.2) on the vas. Women rated their fear significantly higher than men: 3.82 (SD 2.98) versus 2.14 (SD 2.39) on vas (p=0.001) and we found an inverse correlation between age and rated fear, e.g. the older the pts the lower the rated fear (Pearson9s correlation: -0.273; p=0.001). There was neither a correlation between the fear of BRO and the suspected diagnosis of malignancy, nor between the fear of BRO and the duration of BRO or the amount of propofol used.  Conclusion: younger pts are more anxious before BRO than older pts and women rate their fear of BRO higher than men. The fear experienced before BRO does not correlate with the suspicion of malignancy. BRO is tolerated very well in our institution.
Imaging EGFR and HER2 by PET and SPECT: A Review
Authors: Emily B. Corcoran, Robert N. Hanson
Journal: Medicinal Research Reviews (2013)

Abstract In an effort to discover a noninvasive method for predicting which cancer patients will benefit from therapy targeting the EGFR and HER2 proteins, a large body of the research has been conducted toward the development of PET and SPECT imaging agents, which selectively target these receptors. We provide a general overview of the advances made toward imaging EGFR and HER2, detailing the investigation of PET and SPECT imaging agents ranging in size from small molecules to monoclonal antibodies.
Cell of origin of transformed follicular lymphoma
Authors: Robert Kridel, Anja Mottok, Pedro Farinha, Susana Ben-Neriah, Daisuke Ennishi, Yvonne Zheng, Elizabeth A. Chavez, Hennady P. Shulha, King Tan, Fong Chun Chan, Merrill Boyle, Barbara Meissner, Adele Telenius, Laurie H. Sehn, Marco A. Marra, Sohrab P. Shah, Christian Steidl, Joseph M. Connors, David W. Scott, Randy D. Gascoyne
Journal: Blood (2015)
Allergy and asthma severity
Authors: Svetlana Kamenov, Lozana Markovic, Borislav Kamenov, Aleksandar Kamenov
Journal: European Respiratory Journal (2012)

Background: Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) are multifactorial illnesses determined by complex interplay between genetic and environmental factors with different phenotype expression. The majority of asthmatics have AR and studies have shown that treatment of AR helps control asthma symptoms. The objective of this study was to evaluate if the presence of AR and/or AD interfere with asthma severity.

Methods: We evaluated 1,350 asthmatic children aged 0 – 18 years (median 9 years), attending Health Center Nis. These data were collected by standard protocol and registered in a computer data base. Asthma diagnosis and severity were established by GINA (1995) criteria. Skin prick tests (SPT) were performed with common aeroallergen extracts and tests were considered positive if wheal diameter greater than or equal 3 mm. Data were analyzed by chi square test.

Results: Asthma severity was mild in 61.8%, moderate in 28.0% and severe in 10.2%. Male to female ratio was 1.3:1. AR was present in 59% of the patients, AD in 6.2%., and both AR and AD in 2.1%. Regardless asthma severity there was no difference in the frequency of AR and/or AD among asthmatics. SPT was positive to at least one allergen in 78% of patients. The frequency of SPT positivity was 58% in mild asthma and increased to 85% in severe asthma (p< 0,001).Conclusion: Asthma severity was not related to the presence of AR and/or AD in this group of asthmatic children, but there was a relationship in the frequency of positive skin tests according to asthma severity.
Scolicidal activity of biosynthesized silver nanoparticles against Echinococcus granulosus protoscolices
Authors: Mohammad Taghi Rahimi, Ehsan Ahmadpour, Bahman Rahimi Esboei, Adel Spotin, Mohammad Hasan Kohansal Koshki, Ahad Alizadeh, Soheila Honary, Hamed Barabadi, Milad Ali Mohammadi
Journal: International Journal of Surgery (2015)
PARAMOUNT: Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).
Authors: L. G. Paz-Ares, F. De Marinis, M. Dediu, M. Thomas, J. Pujol, P. Bidoli, O. Molinier, T. P. Sahoo, E. Laack, M. Reck, J. Corral, S. A. Melemed, W. J. John, N. Chouaki, A. Zimmerman, C. M. Visseren Grul, C. Gridelli
Journal: Journal of Clinical Oncology (2011)

CRA7510 The full, final text of this abstract will be available in Part II of the 2011 Annual Meeting Proceedings, distributed onsite at the Meeting on June 4, 2011, and as a supplement to the June 20, 2011, issue of Journal of Clinical Oncology.
A Practical Guide for Medical Teachers
Authors: Christopher Martyn
Journal: Journal of the Royal Society of Medicine (2001)

In medicine our professional self-confidence has lately been eroded by the unrealistic expectations of a consumer society and a shamefully large number of medical disasters. Naturally enough, we wonder if our highly exposed shortcoming have their root in the way we educate doctors. So we traitorously acquiesce in the general derision of the traditional curriculum. You know the sort of thing: the preclinical course is time spent in the company of a cadaver; ward attachments are serial episodes of ritual humiliation; the preregistration year is endurance training in sleep deprivation. And we sit on committees to discuss how to do better.
Cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Fatima Karzai, Ravi Amrit Madan, Marc Robert Theoret, Philip M. Arlen, Nancy Ann Dawson, Inger L. Rosner, David G. McLeod, John Joseph Wright, Lisa M Cordes, Anna Couvillon, Guinevere Chun, Nancy Harold, Seth M. Steinberg, Jane B. Trepel, Douglas K. Price, James L. Gulley, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2015)

235 Background: Docetaxel (D) improves overall survival in metastatic castrate-resistant prostate cancer (mCRPC), but benefits remain short-lived. Clinical data suggests patients (pts) with mCRPC treated with anti-androgen therapy like abiraterone (AA) or enzalutamide (ENZA) have decreased responses to subsequent therapy due to cross-resistance in the androgen pathway targeted by D, AA, or ENZA(van Soest et al, Eur J Cancer 49:18, 2013). Combining D with other agents, like cabozantinib (C), could target different cellular signaling pathways potentially minimizing tumor resistance. Methods: D naive pts receive 75 mg/m2 IV on day 1 of a 21 day cycle, and prednisone (P) 5 mg po q12 hours with C at 3 dose levels: 20, 40, or 60 mg po daily until maximum tolerated dose (MTD) is defined. In phase 2, pts who have progressed on AA or ENZA, enroll on a randomized 2 arm cohort comparing D plus C to D alone. Results: 20 pts have been accrued; 4 at 20 mg C, 8 at 40 mg C, and 7 at 60 mg C. On phase 2, 1 pt is randomized to D alone. Median age is 68 (44-84 yrs). Median baseline PSA is 94.7 (0.01-754.1 ng/mL). Gleason score is 9 (7-10). Median cycles is 9.5 (1-33). 8 pts have bone only disease, 12 pts have bone and soft tissue disease. Common grade 2 and grade 3 adverse events possibly related to C: hand/foot syndrome (4/16), oral mucositis (4/16), hypophosphatemia (4/16), and fatigue (3/16). The MTD of C is 40 mg daily with D. 15 pts were previously treated with AA or ENZA. In 13 patients previously treated with AA, median PFS has not been reached, with a median potential follow up of 12.4 months. Six month PFS is 77.8% and 9 month PFS is 60.5%. Conclusions: D plus P may have limited benefits after disease progression on AA as seen in 3 retrospective analyses demonstrating a median PFS survival of 4.6 months or less (Mezynski J, et al. Ann Oncol 23;11, 2012) (Aggarwal R, et al. Clin Genitourin Cancer 12;5, 2014) (Schweizer MT, et al. Eur Urol 66;4, 2014). PFS results seen in this trial compare favorably to previously published data of treatment with D after AA in mCRPC, suggesting the addition of C to D may help overcome acquired resistance. Further randomized trials will determine if C in combination with D will enhance clinical outcomes. Clinical trial information: NCT01683994.
New feature subset selection procedures for classification of expression profiles
Authors: Trond Hellem Bø, Inge Jonassen
Journal: Genome biology (2002)

Methods for extracting useful information from the datasets produced by microarray experiments are at present of much interest. Here we present new methods for finding gene sets that are well suited for distinguishing experiment classes, such as healthy versus diseased tissues. Our methods are based on evaluating genes in pairs and evaluating how well a pair in combination distinguishes two experiment classes. We tested the ability of our pair-based methods to select gene sets that generalize the differences between experiment classes and compared the performance relative to two standard methods. To assess the ability to generalize class differences, we studied how well the gene sets we select are suited for learning a classifier. We show that the gene sets selected by our methods outperform the standard methods, in some cases by a large margin, in terms of cross-validation prediction accuracy of the learned classifier. We show that on two public datasets, accurate diagnoses can be made using only 15-30 genes. Our results have implications for how to select marker genes and how many gene measurements are needed for diagnostic purposes. When looking for differential expression between experiment classes, it may not be sufficient to look at each gene in a separate universe. Evaluating combinations of genes reveals interesting information that will not be discovered otherwise. Our results show that class prediction can be improved by taking advantage of this extra information.