tbuckley/cabot-search huggingface dataset:
Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both
Authors: Nicholas D. James, Sarah J. Pirrie, Ann M. Pope, Darren Barton, Lazaros Andronis, Ilias Goranitis, Stuart Collins, Adam Daunton, Duncan McLaren, Joe O’Sullivan, Christopher Parker, Emilio Porfiri, John Staffurth, Andrew Stanley, James Wylie, Sharon Beesley, Alison Birtle, Janet Brown, Prabir Chakraborti, Syed Hussain, Martin Russell, Lucinda J. Billingham
Journal: JAMA Oncology (2016)

Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival.To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival.The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months.Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89.Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression-free interval, total SREs, and overall survival (OS).Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91).Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy.isrctn.com Identifier: ISRCTN12808747.
Subcutaneous low-dose alemtuzumab as first line therapy for elderly CLL patients with deletion of 17p
Authors: V. Pitini, C. Arrigo, C. Naro, B. Buemi, G. Marabello, M. Santarpia, G. Altavilla
Journal: Journal of Clinical Oncology (2008)

7048 Background: In CLL patients (pts.) the worst disease progression and survival outcome correlate with the deletion of 17p most likely because Chlorambucil and purine analogs induce apoptosis through p53-dependent pathways. In this setting intravenous Alemtuzumab induces significant responses unfortunately associated with reactions and infectious morbidity while subcutaneous low dose Alemtuzumab seems to minimize these adverse effects. Here, we present our results to assess the efficacy and safety of low s.c. Alemtuzumab in elderly B- CLL pts. with del of 17p. Methods: From September 2002 to March 2005, 48 elderly B-CLL pts.( 28 male, 20 female, median age 74) Rai stage II through IV, an evidence of progression according to NCI- WG criteria, no previous chemotherapy, PS of 0 to 2, deletion of 17p detected by FISH, received Alemtuzumab 10mg s.c. three times per week for up to 18 weeks. Results: Out of 48 pts. included in this study 3 pts (7%) obtained a complete response and 16 pts. (33%) a partial response by using the NCI 96 criteria. Furthermore, two pts. achieved a negative minimal residual disease, using a 4-color flow cytometry assay. The median PFS of the responding pts. was 11.8 months (range 5–19 months) while median OS was 30 months for responders and 12.5 for unresponders. Therapy was well tolerated except for some local reactions. Four pts. experienced transient and asymptomatic reactivation of CMV which recoverd without any specific treatment,4 pts had grade 3 anemia and 19 pts had grade 3 to 4 neutropenia. Conclusions: This regimen seems to be as effective as standard intravenous infusions and has a particularly favourable toxicity profile even compared to e.v Alentuzumab administration. No significant financial relationships to disclose.
Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors
Authors: Özge Canli, Yasemin B. Alankuş, Sasker Grootjans, Naidu Vegi, Lothar Hültner, Philipp S. Hoppe, Timm Schroeder, Peter Vandenabeele, Georg W. Bornkamm, Florian R. Greten
Journal: Blood (2015)
Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29)
Authors: D. Koeberle, J.-F. Dufour, G. Demeter, Q. Li, K. Ribi, P. Samaras, P. Saletti, A.D. Roth, D. Horber, M. Buehlmann, A.D. Wagner, M. Montemurro, G. Lakatos, J. Feilchenfeldt, M. Peck-Radosavljevic, D. Rauch, B. Tschanz, G. Bodoky
Journal: Annals of Oncology (2016)
Prospective phenotypic screening for DPD deficiency prior to 5-FU administration: Decrease in toxicity, not in efficacy
Authors: C. Mercier, C. Yang, C. Rosca, J. Ciccolini, L. Padovani, D. Bagarry-Liegey, C. Dupuis, B. Lacarelle, M. Zanaret, F. Duffaud, R. Favre
Journal: Journal of Clinical Oncology (2008)

14556 Background: DPD deficiency is a pharmacogenetics syndrome associated with severe/lethal toxicities upon 5-FU intake. We previously developed a rapid and cost-effective phenotypic method for DPD status estimation. We present here a prospective study using this tool in order to tailor 5-FU administration, and to study its impact on early toxicities and response in head and neck cancer patients (pts). Methods: Fifty-nine pts with non-operable head and neck cancer (43 first-line, 16 relapse) were screened for DPD deficiency prior to the beginning of 5-FU-based chemotherapy (CT) or radio-chemotherapy (RTCT). DPD status was evaluated using the U/UH2 ratio method by UV- HPLC analysis. According to ratio values, 5-FU dose reduction was subsequently proposed as following: no deficiency: standard dose, mild deficiency, 20% dose reduction, severe deficiency, 50% reduction, total deficiency, no 5-FU given. Toxicities were monitored following standard NCI grading after the first course and tumoral response were evaluated 2 months after the end of the scheduled treatment. Results: DPD status evaluated from U/UH2 monitoring in plasma led to detecting 28 out of 59 (47%) pts with mild (25%) to severe (22%) DPD deficiency (U/UH2 ratios >2 and >3, respectively).5-FU doses were subsequently reduced as indicated above, whereas platinum dosage remained unchanged. Twenty five (88%) of the 28 pts with DPD deficiency and dose reduction did not diplayed any severe toxicity after 5-FU administration, and radiation therapy was therefore performed as initially scheduled (no delay >7 days). In first-line therapy, response rates (CR+PR) were respectively 64% (CT) and 81% (RTCT). In pts treated for relapse, response rates were 50% (CT) and 38% (RTCT). Conclusions: 5-FU dose tailoring based upon DPD status evaluation led to 2 fold decrease in occurence of severe toxicities without impairing efficacy. Of note, no toxic-death was observed in our pts. Although non-randomized, this study advocates systematic screening for DPD deficiency in pts scheduled for 5-FU-based therapy. No significant financial relationships to disclose.
Abstract 12106: Long-Term Clinical Outcome in Patients with Angiographically Intermediate Lesion of the Coronary Artery By-Pass Graft Deferred on the Basis of Fractional Flow Reserve Measurement
Authors: Luigi Di Serafino, Fabio Mangiacapra, Aaron Peace, Jozef Bartunek, William Wijns, Bernard De Bruyne, Guy Heyndrickx, Emanuele Barbato
Journal: Circulation (2011)

Purpose. An intermediate stenosis of a native coronary artery can be safely deferred on the basis of non-significant Fractional Flow Reserve (FFR). In addition, deferring a left main stenosis with ...
Analysis of prognostic factors with cervical squamous cell carcinoma after neoadjuvant chemotherapy
Authors: S. Hayashi, T. Fujii, M. Nakamura, N. Hirao, H. Nakagawa, T. Fukuchi, K. Kubushiro, K. Tukazaki, D. Aoki
Journal: Journal of Clinical Oncology (2006)

15060 Background: The purpose of the study was to evaluate retrospectively the clinical effects of neoadjuvant chemotherapy (NAC) given to women with cervical squamous cell carcinoma using the response rates, prognostic parameters, and diagnostic imaging data (CT scan or MRI). Methods: Patients included in the study were 32 women with a mean age of 48.8 ± 10.6 who had stage Ib-IIIb cervical squamous cell carcinoma and was treated initially with platinum-based NAC prior to surgical intervention at our institution between 1994 and 2003. The response rates in these patients were assessed, and a statistical analysis was performed to evaluate the effects of NACT on survival rates and disease recurrence using the following 9 parameters: 1. clinical stage of cancer, 2. lymph node metastasis, 3. blood vessel invasion, 4. parametrial involvement, 5. depth of stromal invasion, 6. tumor diameter, 7. pre- and post-treatment serum levels of the squamous cell carcinoma antigen, 8. age, and 9. rates of response to NAC. CT scan or MRI obtained prior to and after NAC were compared and evaluated for any evidence of lymph node metastasis. Results: Five and 18 patients achieved complete response (CR) and partial response (PR), respectively, with a response rate of 71.8% for these CR and PR patients. A multivariate analysis revealed that lymph node metastasis was the only independent prognostic parameter for survival rates and disease recurrence. In 13 patients in whom lymph node metastasis was found by the was found by the CT scan or MRI prior to NAC, 8 (61.5%) still showed the evidence of metastasis after treatment. Among these, 7 (87.5%) actually had metastatic lymph nodes. In addition, the occurrence of lymph node metastasis was unrelated to rates of response to NAC. Conclusions: The rates of response to NAC dose not predict prognosis in patients with cervical squamous cell carcinoma. The occurrence of lymph node metastasis is unrelated to rates of response to NAC. If metastatic lymph nodes are suspected after NAC, appropriate treatment approaches should be well considered in such patients. No significant financial relationships to disclose.
Brief Communication: Normal Human Mammary Cells in Culture: Evidence for OncornavirusMLike Particles2
Authors: P. Furmanski, C. Longley, D. Fouchey, R. Rich, M. A. Rich
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Brief Communication: Normal Human Mammary Cells in Culture: Evidence for OncornavirusMLike Particles Get access P. Furmanski, P. Furmanski Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Longley, C. Longley Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Fouchey, D. Fouchey Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Rich, R. Rich Search for other works by this author on: Oxford Academic PubMed Google Scholar M. A. Rich M. A. Rich 3Division of Biological Sciences, Michigan Cancer Foundation 110 East Warren Ave., Detroit, Mich. 48201. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 975–981, https://doi.org/10.1093/jnci/52.3.975 Published: 01 March 1974 Article history Received: 15 October 1973 Accepted: 01 December 1973 Published: 01 March 1974
Molecular phylogeny and evolutionary rates of alcohol dehydrogenases in vertebrates and plants.
Authors: S Yokoyama, D E Harry
Journal: Molecular Biology and Evolution (1993)

Phylogenetic relationships and evolutionary rates for 36 alcohol dehydrogenases (ADHs) from vertebrates and plants are described, with ADHs from fission yeast and from baker's yeasts as outgroups. Vertebrate sequences include 15 mammalian, 2 avian, and 1 amphibian ADH, as well as one sequence deduced from a human pseudogene. Plant ADH sequences include 1 from a gymnosperm (loblolly pine) and 16 from angiosperms, in which 9 sequences are from monocots and 7 are from dicots. Phylogenetic analysis shows that ADHs from vertebrates and from plants are classified into two distinct groups, and the latter group is further divided into angiosperm and gymnosperm ADHs. Among three classes of vertebrate ADHs, class I and II ADHs are most closely related and evolved at much faster rates than did class III ADHs. The gymnosperm ADH has evolved more slowly than any angiosperm ADH. However, ADHs within both of the vertebrate classes I and II and class III groups have similar evolutionary rates, as do most of the ADHs within the angiosperm group. The rate of amino acid replacement for the vertebrate and plant ADHs is approximately 0.3-0.6 x 10(-9)/site/year.
Association of Social Determinants With Children’s Hospitals’ Preventable Readmissions Performance
Authors: Marion R. Sills, Matt Hall, Jeffrey D. Colvin, Michelle L. Macy, Gretchen J. Cutler, Jessica L. Bettenhausen, Rustin B. Morse, Katherine A. Auger, Jean L. Raphael, Laura M Gottlieb, Evan S. Fieldston, Samir S. Shah
Journal: JAMA Pediatrics (2016)

Performance-measure risk adjustment is of great interest to hospital stakeholders who face substantial financial penalties from readmissions pay-for-performance (P4P) measures. Despite evidence of the association between social determinants of health (SDH) and individual patient readmission risk, the effect of risk adjusting for SDH on readmissions P4P penalties to hospitals is not well understood.To determine whether risk adjustment for commonly available SDH measures affects the readmissions-based P4P penalty status of a national cohort of children's hospitals.Retrospective cohort study of 43 free-standing children's hospitals within the Pediatric Health Information System database in the calendar year 2013. We evaluated hospital discharges from 2013 that met criteria for 3M Health Information Systems' potentially preventable readmissions measure for calendar year 2013. The analysis was conducted from July 2015 to August 2015.Two risk-adjustment models: a baseline model adjusted for severity of illness and an SDH-enhanced model that adjusted for severity of illness and the following 4 SDH variables: race, ethnicity, payer, and median household income for the patient's home zip code.Change in a hospital's potentially preventable readmissions penalty status (ie, change in whether a hospital exceeded the penalty threshold) using an observed-to-expected potentially preventable readmissions ratio of 1.0 as a penalty threshold.For the 179,400 hospital discharges from the 43 hospitals meeting inclusion criteria, median (interquartile range [IQR]) hospital-level percentages for the SDH variables were 39.2% nonwhite (n = 71,300; IQR, 28.6%-54.6%), 17.9% Hispanic (n = 32,060; IQR, 6.7%-37.0%), and 58.7% publicly insured (n = 106,116; IQR, 50.4%-67.8%). The hospital median household income for the patient's home zip code was $ 40,674 (IQR, $ 35,912-$ 46,190). When compared with the baseline model, adjustment for SDH resulted in a change in penalty status for 3 hospitals within the 15-day window (2 were no longer above the penalty threshold and 1 was newly penalized) and 5 hospitals within the 30-day window (3 were no longer above the penalty threshold and 2 were newly penalized).Risk adjustment for SDH changed hospitals' penalty status on a readmissions-based P4P measure. Without adjusting P4P measures for SDH, hospitals may receive penalties partially related to patient SDH factors beyond the quality of hospital care.
Biometric Findings on Cardiac Neurosis
Authors: Brigitte Stanek, P. Hahn, H. Mayer
Journal: Psychotherapy and Psychosomatics (1973)

Psychoanalytical initial interviews were monitored by cameras while, at the same time, both the patient's and the doctor's ECGs were telemetrically recorded. Changes of heart rate were related to intra- aswell as interpersonal occurrences during the interview. Both concordant and discordant courses were seen: communicative structures of the interview in some cases correlate with the pattern of heart rate. Cardiophobics, with their tendency to cling to the doctor, reveal a corresponding heart rate pattern. In a finally described case, bigeminy attacks during the interview could be related to special transference phenomena.
A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes
Authors: Tongzhi Wu, Tanya J. Little, Michelle J. Bound, Malcolm Borg, Xiang Zhang, Carolyn F. Deacon, Michael Horowitz, Karen L. Jones, Christopher K. Rayner
Journal: Diabetes Care (2016)

OBJECTIVE Nutrient “preloads” given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a 13C-octanoate–labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated. RESULTS Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P &amp;lt; 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P &amp;lt; 0.05 each). CONCLUSIONS In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia.
Pilot study of capecitabine combined with celecoxib (CapCel) for the treatment of far advanced metastatic breast cancer (MBC) patients (pts)
Authors: A. Fabi, M. Milella, P. Malaguti, P. Papaldo, G. Ferretti, P. Carlini, A. Gelibter, A. Felici, I. Sperduti, F. Cognetti
Journal: Journal of Clinical Oncology (2006)

10680 Background: COX-2 is overexpressed during cancer progression in several solid tumors, including breast cancer, and constitutes an attractive therapeutic target. Selective COX-2 inhibitors, such as Celecoxib, have been successfully combined with fluoropyrimidine-based regimens, resulting in a lower-than-expected hematologic, GI, and skin toxicity rate. Methods: MBC pts who had progressed after at least one chemotherapy regimen for metastatic disease were eligible for the study. Capecitabine was administered at the starting dose of 1500–2000 mg/m 2 daily for 14 days q3 wks. Celecoxib was administered at 200 mg b.i.d., continuously, starting on day 1. Dose escalation to Capecitabine 2000 or 2500 mg/m 2 was allowed in the absence of toxicity &gt; G1. Results: To date, 22 pts (median age: 55 yrs, range 35–81; ECOG PS 0: 21 pts) have been accrued; all pts had MBC and the majority had received adjuvant chemotherapy and hormonal treatment in the adjuvant and/or metastatic setting; all pts had been exposed to anthracyclines and/or taxanes. CapCel was administered as 2 nd -, 3 rd -, or ≥ 4 th -line chemotherapy in 3, 10, and 9 pts, respectively. Capecitabine starting dose was 1500 mg/m 2 in 9 pts and 2000 mg/m 2 in 13 pts. Median number of cycles administered was 5 (range: 1–15). Toxicity was negligible: 1 pt experienced G3 neutropenia, 2 pts G3 skin/nail toxicity, and 1 pt G3 liver toxicity; all other toxicities were of grade ≤2. No Celecoxib-related GI or cardiovascular toxicities were observed. Capecitabine dose was escalated from 1500 to 2000 mg/m 2 in 3/9 pts and from 2000 to 2500 mg/m 2 in 2/13 pts, respectively, and reduced from 2000 to 1500 mg/m 2 in 4/13 pts. Twenty pts are currently evaluable for response: 2 pts had PR (duration 48 and 49 wks, respectively), 15 pts had SD (median duration: 20 wks, range 12–44), and 3 pts progressed on therapy, for an overall clinical benefit rate of 40%. Median survival has not been reached. Conclusions: Overall, these preliminary results indicate that CapCel is extremely well-tolerated and has significant anti-tumor activity in a population of far advanced MBC pts. The study will continue to reach the projected accrual of 45 pts. No significant financial relationships to disclose.
Extracellular Adenosine Production by ecto-5′-Nucleotidase (CD73) Enhances Radiation-Induced Lung Fibrosis
Authors: Florian Wirsdörfer, Simone de Leve, Federica Cappuccini, Therese Eldh, Alina V. Meyer, Eva Gau, Linda F. Thompson, Ning-Yuan Chen, Harry Karmouty-Quintana, Ute Fischer, Michael Kasper, Diana Klein, Jerry W. Ritchey, Michael R. Blackburn, Astrid M. Westendorf, Martin Stuschke, Verena Jendrossek
Journal: Cancer Research (2016)

Abstract Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5′-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks postirradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately 3-fold. Histologic evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P &amp;lt; 0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacologic strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. Cancer Res; 76(10); 3045–56. ©2016 AACR.
MET Gene Status in Malignant Mesothelioma Using Fluorescent In Situ Hybridization
Authors: Serena Varesano, Sandra Salvi, Simona Boccardo, Jean Louis Ravetti, Maria Pia Pistillo, Pier Aldo Canessa, Paola Ferro, Franco Fedeli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2016)