tbuckley/cabot-search huggingface dataset:
Clinical and Serologic Correlates of Anti‐PM/Scl Antibodies in Systemic Sclerosis: A Multicenter Study of 763 Patients
Authors: Julie D'Aoust, Marie Hudson, Solène Tatibouet, James Wick, Michael Mahler, Murray Baron, Marvin J. Fritzler
Journal: Arthritis & Rheumatology (2014)

Objective Anti‐PM/Scl autoantibodies are found in polymyositis, dermatomyositis, systemic sclerosis (SSc), and systemic autoimmune disease overlap syndromes. PM‐1α is a major epitope of the PM/Scl complex, and antibodies against PM‐1α can be detected using a validated enzyme‐linked immunosorbent assay (ELISA). This study was undertaken to determine the prevalence and identify the clinical correlates of anti–PM‐1α antibodies in a large cohort of patients with SSc. Methods Serum samples were obtained from 763 patients with SSc enrolled in a multicenter Canadian cohort. The sera were analyzed by ELISA for the presence of antibodies against PM‐1α. Associations between the presence of anti–PM‐1α antibodies and demographic, clinical, and other serologic manifestations of SSc were investigated. Results Anti–PM‐1α antibodies were present in 55 patients with SSc (7.2%), of whom almost 50% (26 of 55; 3.4% of the overall cohort) had no other SSc‐specific antibodies, namely anticentromere, anti–topoisomerase I, and anti–RNA polymerase III. Features positively associated with the presence of anti–PM‐1α antibodies included younger age at disease onset, skeletal muscle involvement, calcinosis, inflammatory arthritis, and overlap disease. Interstitial lung disease was less frequent and there were fewer gastrointestinal symptoms present in patients with anti–PM‐1α antibodies compared to patients without these antibodies. Conclusion Anti–PM‐1α antibodies are relatively common in SSc and are associated with a distinct clinical phenotype, consistent with that described in association with other anti‐PM/Scl autoantibodies. Although anti–PM‐1α antibodies are not exclusive of other SSc‐specific antibodies, they can be present in the absence thereof. Thus, anti–PM‐1α antibodies may have considerable diagnostic and prognostic relevance in SSc.
A mathematical model of drug resistance applied to treatment for small-cell lung cancer.
Authors: W M Gregory, B G Birkhead, R L Souhami
Journal: Journal of Clinical Oncology (1988)

A mathematical model has been applied to patients with small-cell lung cancer (SCLC) in order to estimate the proportions of resistant and sensitive tumor at presentation, and the efficacy of the treatment, measured in terms of proportions of tumor killed with each cycle of therapy. The model uses estimates of tumor volume obtained from computed tomographic (CT) scans of the chest before each course of chemotherapy. Application of the model to a trial using single-agent high-dose cyclophosphamide (HDC) showed that HDC killed approximately 94% of the sensitive tumor on each application, but that the proportion of tumor resistant to HDC rose from an average of 1% to an average of 15% after the first cycle, assuming a 30-day tumor doubling time. These estimates proved fairly insensitive to different assumptions about tumor doubling time and inaccuracies in volume measurement and may thus provide a useful additional evaluation technique for some clinical trials.
Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum Creatinine
Authors: Delphine S. Tuot, Feng Lin, Michael G. Shlipak, Vanessa Grubbs, Chi-yuan Hsu, Jerry Yee, Vahakn Shahinian, Rajiv Saran, Sharon Saydah, Desmond E. Williams, Neil R. Powe
Journal: Diabetes Care (2015)

Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women and <1.5 mg/dL for men) and eGFR categories: likely safe, ≥45 mL/min/1.73 m(2); contraindicated, <30 mL/min/1.73 m(2); and indeterminate, 30-44 mL/min/1.73 m(2)). Different eGFR equations were used: four-variable MDRD, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl). Diabetes was defined by self-report or A1C ≥6.5% (48 mmol/mol). We used logistic regression to identify populations for whom metformin was likely safe adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S. adult population.Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8 [4.27-51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR <30 mL/min/1.73 m(2). All estimating equations expanded the population of individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to 834,800 (CG). All equations identified larger populations with eGFR 30-44 mL/min/1.73 m(2), for whom metformin safety is indeterminate, ranging from 784,700 (CKD-EPIcr) to 1,636,000 (CG).The use of eGFR or CrCl to determine metformin eligibility instead of sCr can expand the adult population with diabetes for whom metformin is likely safe, particularly among non-Hispanic blacks and men.
Sensitivity of cytology and immunohistochemistry for diagnosis of pancreaticobiliary cancer.
Authors: Atuhani S. Burnett, Joanelle Bailey, Joseph B Oliver, Sushil Ahalawat, Ravi J. Chokshi
Journal: Journal of Clinical Oncology (2015)

TPS490 Background: Biliary strictures present a diagnostic challenge to differentiate benign disease from hepatopancreaticobiliary (HPB) malignancies. ERCP cytology is commonly performed in these patients; however, its sensitivity for diagnosis of HPB malignancy is poor (41.6%). Many adjunctive tests have been investigated to improve the sensitivity of HPB biopsies. In a recent meta-analysis by our group the best immunohistochemical (IHC) stains were a combination of IMP3, S100A4, and standard cytology. IHC stains for S100P and pVHL negativity were also helpful. Based on this meta-analysis we have designed a retrospective analysis of old cell block specimens to demonstrate the sensitivity and specificity of a combination IHC staining panel in detecting HPB maliganancies. Methods: Retrospective IHC staining will be carried out on old cell blocks from ERCP brushings and EUS-FNA. Expression of IMP3, S100A4, S100P, and pVHL will be determined. Using this panel as a combination we will determine its sensitivity and specificity on 200 patient samples. We will further determine how many stains are necessary to achieve maximum sensitivity by subtraction of data from one or more IHC stains followed by repeating sensitivity calculations. Finally, we will calculate the cost of conducting these tests and determine the cost-benefit ratio of employing these tests in the wider clinical setting. Conclusions: Overall we feel these studies will advance the precision with which clinicians can determine the presence of HPB malignancy in patients undergoing biopsy. This will ultimately lead to fewer patients with benign disease undergoing resection unnecessarily.
A phase I study of cediranib in combination with cilengitide in patients with recurrent glioblastoma
Authors: Elizabeth R. Gerstner, Xiaobu Ye, Dan G. Duda, Michael A. Levine, Tom Mikkelsen, Thomas J. Kaley, Jeffrey J. Olson, Burt L. Nabors, Manmeet S. Ahluwalia, Patrick Y. Wen, Rakesh K. Jain, Tracy T. Batchelor, Stuart Grossman
Journal: Neuro-Oncology (2015)

Despite being a highly vascularized tumor, glioblastoma response to anti-vascular endothelial growth factor (VEGF) therapy is transient, possibly because of tumor co-option of preexisting blood vessels and infiltration into surrounding brain. Integrins, which are upregulated after VEGF inhibition, may play a critical role in this resistance mechanism. We designed a study of cediranib, a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, combined with cilengitide, an integrin inhibitor. This phase I study was conducted through the Adult Brain Tumor Consortium in patients with recurrent glioblastoma. Once the maximum tolerated dose was determined, 40 patients enrolled in a dose expansion cohort with 20 being exposed to anti-VEGF therapy and 20 being naive. The primary endpoint was safety. Secondary endpoints included overall survival, proportion of participants alive and progression free at 6 months, radiographic response, and exploratory analyses of physiological imaging and blood biomarkers. Forty-five patients enrolled, and no dose toxicities were observed at a dose of cediranib 30 mg daily and cilengitide 2000 mg twice weekly. Complete response was seen in 2 participants, partial response in 2, stable disease in 13, and progression in 21; 7 participants were not evaluable. Median overall survival was 6.5 months, median progression-free survival was 1.9 months, and progression-free survival at 6 months was 4.4%. Plasma-soluble VEGFR2 decreased with treatment and placental growth factor, carbonic anhydrase IX, and SDF1α, and cerebral blood flow increased. The combination of cediranib with cilengitide was well tolerated and associated with changes in pharmacodynamic blood and imaging biomarkers. However, the survival and response rates do not warrant further development of this combination.
Transforming Growth Factor- β 1 in Asthma
Authors: ANTHONY E. REDINGTON, JACQUELINE MADDEN, ANTHONY J. FREW, RATKO DJUKANOVIC, WILLIAM R. ROCHE, STEPHEN T. HOLGATE, PETER H. HOWARTH
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Airway wall remodeling is an established pathological feature in asthma. Its causes are not well understood, but one mediator of potential relevance is transforming growth factor-beta 1 (TGF- β 1). We have measured levels of immunoreactive TGF- β 1 in bronchoalveolar lavage (BAL) fluid from clinically stable atopic asthmatics and healthy control subjects. We have also examined the influence of allergen exposure on TGF- β 1 release in the airways using a segmental bronchoprovocation model, with BAL performed at two time points following endobronchial allergen and sham saline challenges. Basal concentrations of TGF- β 1 were significantly higher in asthmatics than control subjects (median 8.0 versus 5.5 pg/ml, p = 0.027). Following segmental bronchoprovocation, concentrations of TGF- β 1 at the allergen- and saline-challenged sites were not significantly different after 10 min, (31.3 versus 25.0 pg/ml, p = 0.78), but after 24 h there were significantly higher TGF- β 1 concentrations at the allergen-challenged sites (46.0 versus 21.5 pg/ml, p = 0.017). We conclude that basal TGF- β 1 levels in the airways are elevated in atopic asthma and that these levels increase further in response to allergen exposure. These findings are consistent with the hypothesis that TGF- β 1 is implicated in airway wall remodeling in asthma.
Multiplex Genome-Edited T-cell Manufacturing Platform for “Off-the-Shelf” Adoptive T-cell Immunotherapies
Authors: Laurent Poirot, Brian Philip, Cécile Schiffer-Mannioui, Diane Le Clerre, Isabelle Chion-Sotinel, Sophie Derniame, Pierrick Potrel, Cécile Bas, Laetitia Lemaire, Roman Galetto, Céline Lebuhotel, Justin Eyquem, Gordon Weng-Kit Cheung, Aymeric Duclert, Agnès Gouble, Sylvain Arnould, Karl Peggs, Martin Pule, Andrew M. Scharenberg, Julianne Smith
Journal: Cancer Research (2015)

Adoptive immunotherapy using autologous T cells endowed with chimeric antigen receptors (CAR) has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T cells must be generated on a custom-made basis. Here we show that electroporation of transcription activator-like effector nuclease (TALEN) mRNA allows highly efficient multiplex gene editing in primary human T cells. We use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T cells deficient in expression of both their αβ T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T cells manufactured with this process do not mediate graft-versus-host reactions and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T cells, supporting their engraftment. Furthermore, endowing the TALEN-engineered cells with a CD19 CAR led to efficient destruction of CD19(+) tumor targets even in the presence of the chemotherapeutic agent. These results demonstrate the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies against arbitrary targets. As such, CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biologic immunopharmaceuticals
Use of Complementary/Alternative Medicine by Breast Cancer Survivors in Ontario: Prevalence and Perceptions
Authors: Heather Boon, Moira Stewart, Mary Ann Kennard, Ross Gray, Carol Sawka, Judith Belle Brown, Carol McWilliam, Alan Gavin, Ruth Anne Baron, Dorothy Aaron, Theresa Haines-Kamka
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the prevalence of use of complementary/alternative medicine (CAM) by breast cancer survivors in Ontario, Canada, and to compare the characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A questionnaire was mailed to a random sample of Ontario women diagnosed with breast cancer in 1994 or 1995. RESULTS: The response rate was 76.3%. Overall, 66.7% of the respondents reported using CAM, most often in an attempt to boost the immune system. CAM practitioners (most commonly chiropractors, herbalists, acupuncturists, traditional Chinese medicine practitioners, and/or naturopathic practitioners) were visited by 39.4% of the respondents. In addition, 62.0% reported use of CAM products (most frequently vitamins/minerals, herbal medicines, green tea, special foods, and essiac). Almost one half of the respondents informed their physicians of their use of CAM. Multiple logistic regression analysis determined that support group attendance was the only factor significantly associated with CAM use. CONCLUSION: CAM use is common among Canadian breast cancer survivors, many of whom are discussing CAM therapy options with their physicians. Knowledge of CAM therapies is necessary for physicians and other health care practitioners to help patients make informed choices. CAM use may play a role in the positive benefits associated with support group attendance.
Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.
Authors: V Liengswangwong, J A Bonner, E G Shaw, R L Foote, S Frytak, R T Eagan, J R Jett, R L Richardson, E T Creagan, J Q Su
Journal: Journal of Clinical Oncology (1994)

PURPOSE This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.
A Randomized Phase II Study of Cetuximab Every 2 Weeks at Either 500 or 750 mg/m<sup>2</sup>for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Cancer
Authors: Matthew G. Fury, Eric Sherman, Donna Lisa, Neeraj Agarwal, Kenneth Algazy, Bruce Brockstein, Corey Langer, Dean Lim, Ranee Mehra, Sandeep K. Rajan, Susan Korte, Brynna Lipson, Furhan Yunus, Tawee Tanvetyanon, Stephanie Smith-Marrone, Kenneth Ng, Han Xiao, Sofia Haque, David G. Pfister
Journal: Journal of the National Comprehensive Cancer Network (2012)

Cetuximab is typically administered on a weekly schedule for patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study explores cetuximab administered every 2 weeks (q2w). In this multicenter randomized prospective phase II study, eligible patients (≤2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease; ECOG performance status ≤2) were randomized to receive cetuximab q2w at 500 mg/m2 (Group A) or 750 mg/m2 (Group B). The primary end point was response rate (RECIST 1.0). Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was closed early for lack of efficacy. Confirmed partial response rates were 11% for Group A (4/35) and 8% for Group B (2/26) according to intention to treat analysis. Partial responses occurred only among patients whose primary tumors were in the oral cavity or larynx. Median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0 months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m2, q2w achieves similar efficacy as conventional dosing for patients with recurrent or metastatic HNSCC. Escalating the dose to 750 mg/m2 q2w offers no obvious therapeutic advantage.
Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells
Authors: Honglin Chen, Matteo Gigli, Chiara Gualandi, Roman Truckenmüller, Clemens van Blitterswijk, Nadia Lotti, Andrea Munari, Maria Letizia Focarete, Lorenzo Moroni
Journal: Biomaterials (2015)
Immunotherapeutic and Immunoprophylactic Effects of BCG on 3-Methylcholanthrene-Induced Autochthonous Tumors in Swiss Mice23
Authors: Tohru Tokunaga, Saburo Yamamoto, Reiko M. Nakamura, Tetsuro Kataoka
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Immunotherapeutic and Immunoprophylactic Effects of BCG on 3-Methylcholanthrene-Induced Autochthonous Tumors in Swiss Mice Get access Tohru Tokunaga, Tohru Tokunaga Search for other works by this author on: Oxford Academic PubMed Google Scholar Saburo Yamamoto, Saburo Yamamoto Search for other works by this author on: Oxford Academic PubMed Google Scholar Reiko M. Nakamura, Reiko M. Nakamura Search for other works by this author on: Oxford Academic PubMed Google Scholar Tetsuro Kataoka Tetsuro Kataoka Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 459–463, https://doi.org/10.1093/jnci/53.2.459 Published: 01 August 1974 Article history Received: 28 December 1973 Revision received: 23 April 1974 Accepted: 08 May 1974 Published: 01 August 1974
Pulmonary oxidative stress is induced by smoking in young cigarette smokers
Authors: Shunsuke Taito, Kiyokazu Sekikawa, Makoto Takahashi, Tatsushi Kimura, Hironobu Hamada
Journal: European Respiratory Journal (2014)

Background: Cigarette smoking increases oxidative stress in patients with chronic obstructive pulmonary disease. However, no prior study has examined the effect of smoking in lungs of young smokers.  Aim: This study determines whether pulmonary oxidative stress is induced by smoking in young smokers.  Methods: Hydrogen peroxide (H 2 O 2 ) concentrations in exhaled breath condensate (EBC) were measured. To clarify whether smoking induces pulmonary oxidative stress, EBC samples were collected for 15 minutes before, immediately after, and 1, 2, 4, 8 and 12 hours after smoking. In another experiment, 15 male smokers (mean age: 25.9 ± 2.9 years) and 18 male nonsmokers (mean age: 24.2 ± 4.3 years) performed maximal exercise to induce oxidative stress. EBC samples were collected before and after maximal exercise. Smokers refrained from smoking for 12hr before the experiments.  Results: EBC H 2 O 2  concentrations were increased immediately after and 1 hour after smoking compared to baseline levels. After maximal exercise, EBC H 2 O 2  concentrations were significantly increased in the smokers, but not in the nonsmokers whereas there was no significant difference in baseline EBC H 2 O 2  concentration between smokers and nonsmokers.  Conclusions: These findings suggested that smoking induces pulmonary oxidative stress in young cigarette smokers, which may lead to oxidative damage in the lungs.
Invasive and noninvasive ventilation in adults hospitalized with asthma in Portugal - Nationwide data from 2000-2010
Authors: Daniela Alves, Alberto Freitas, Manuel Vaz, Tiago Jacinto, João Fonseca
Journal: European Respiratory Journal (2012)

Introduction: Few studies have addressed the use and outcomes of invasive (IV) and noninvasive positive pressure ventilation (NPPV) in severe asthma exacerbations. Objective: To describe the use of IV and NPPV in patients hospitalized due to asthma in Portugal from 2000 to 2010. Methods: Retrospective study of inpatient records with principal diagnosis of asthma, age ≥18 years, in acute care hospitals of the national healthcare system (N=85) in mainland Portugal, with discharges between 2000 and 2010 (N=17 446). Analysis of all episodes that included IV and NPPV that were identified using ICD-9-CM (codes 93.9x and 96.7x). The Charlson/Deyo index, a comorbidity risk adjustment measurement, was used. Results: In 1 041 episodes (6%) ventilatory support was needed: NPPV 2.3% and IV 3.6%. NPPV use increased from 17 to 79 cases, mainly after 2007, while IV use decreased over the years. Length of stay (days) was similar in both ventilation procedures. Mortality for IV was significantly higher than for NPPV (15% vs. 2.2%).  Conclusion: NPPV is increasingly used in severe asthma exacerbations. Patients treated with NPPV have a lower mortality rate despite of being older and having an increased comorbidity risk index. Prospective studies are strongly needed.