tbuckley/cabot-search huggingface dataset:
Phase II study of a fixed dose-rate infusion of gemcitabine associated to cisplatin and UFT in advanced carcinoma of the pancreas, an ONCOPAZ study
Authors: E. Espinosa, J. García Sáenz, A. Rodríguez-Jaráiz, C. Castañón, M. Cruz, E. Fonseca, J. Feliu, M. Lomas, M. González Barón, C. Jara
Journal: Journal of Clinical Oncology (2004)

4099 Background. The efficacy of gemcitabine can be improved by using a fixed dose-rate infusion. Our objective was to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated to cisplatin and UFT in patients with advanced adenocarcinoma of the pancreas. Patients and method. From May 2002 to September 2003, 46 chemotherapy-naïve patients were included, median age 57 years (range 27–77), male/female 30/16. Eleven patients (24%) had locally advanced disease and thirty-five (76%) distant metastases. The Karnofsky score was 80–100 in 34 (74%) and 60–70 in 12 (26%). Treatment consisted of gemcitabine 1200 mg/m2 given as a 120-minute infusion weekly for three consecutive weeks, cisplatin 50 mg/m2 on day 1 and oral UFT 400 mg/m2/day (in 2–3 daily doses) on days 1 to 21. Cycles were given every 28 days. Results. A total of 170 cycles of chemotherapy were delivered with a median of four per patient (range 1–11). There were fourteen partial responses (30%, 95%CI:19–48%), 17patients had stable disease (37%), and fifteen had a progression (33%). The median time to progression was five months and the median overall survival was nine months. Among 33 patients evaluable for clinical benefit, eighteen (55%) experienced a clinical benefit response. Grade 3–4 WHO toxicities per patient were as follows: neutropenia in twenty-six patients (57%), thrombocytopenia in fifteen (33%), anaemia in six (13%), diarrhoea in five (11%), nausea/vomiting in 6 (13%) and asthenia in two (4%). There were no toxic deaths. Conclusion. A fixed dose-rate infusion of gemcitabine associated to cisplatin and UFT is active in patients with advanced carcinoma of the pancreas, although at the cost of considerable toxicity. No significant financial relationships to disclose.
Phase III preliminary results of preoperative fluorouracil (F) and cisplatin (P) versus surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC 94012-FFCD 9703 trial
Authors: M. Ychou, J. P. Pignon, P. Lasser, T. Conroy, O. Bouché, V. Boige, P. Segol, L. Bedenne, B. Saint-Aubert, P. Rougier
Journal: Journal of Clinical Oncology (2006)

4026 Background: The combination of 5FU in continuous infusion and cisplatin (FP) is one of the more active regimen in advanced ASLE. The trial was designed to evaluate the impact on survival of 2–3 cycles of preoperative FP in resectable ASLE. Methods: Patients (pts) with resectable adenocarcima of the stomach (S) without cardia involvement, cardia (C) or lower esophagus (LE), age ≤ 75 yrs, WHO performance status (PS) &lt; 2 were eligible. Pts were centrally randomized between surgery alone (arm 1) and preoperative FP (arm 2). Chemotherapy (CT) included 2–3, cycles of P (100 mg/m 2 ) and F (800 mg/m 2 d1-d5 continuous infusion) every 28 days. Post-operative FP was recommended in arm 2 in case of response to FP preoperative or stable disease with pN+. The main endpoint was overall survival. Sample size was 250 (20 % vs 35 % 5-year rates, two-sided logrank test, α = 5 %, β = 20 %). Results: Between 1995 and 2003, 224 pts (arm 1 = 111 pts, arm 2 = 113 pts) were randomized from 28 centers with early stopping because of low accrual. Initial pts characteristics were equally balanced for age (61 yrs), gender (83 % male), PS (75 % WHO 0), tumor site (S = 25 %,C = 64 %, LE = 11 %). In arm 2, FP was given before surgery in 109 pts (98 pts &gt; 2 cycles) and after surgery in 54 pts. Preoperative FP toxicity : 41 pts with at least one grade 3–4 toxicity (polynuclear, 22 pts, vomiting 10 pts), 9 treatment interruption, 1 toxic death. The number of patients with no surgery / no tumor resection / macroscopic incomplete resection (R2)/ microscopic incomplete resection (R1) by arm were 1/10/12/6 in arm 1 and 4/7/2/4 in arm 2. The number of postoperative deaths were 5 in each arm. Complete resection (R0) rate were 73 % in arm 1 versus 84 % in arm 2 (p=0.04). Among eligible RO, R1 patients (85 &amp; 98 pts in arm 1 &amp; 2): the numbers of pts with T0–2/N0/M+ were 27/17/6 and 41/32/1 en arm 1 &amp; 2, the corresponding p-value were 0.16, 0.05 and 0.05 respectively; 3 pts with complete response in arm 2. For DFS, 160 events are observed so far with a median follow-up of 5 years. Conclusions: Preoperative chemotherapy was well tolerated and led to an increase in R0 resection rate, and a decrease in N+/M+ tumors. Disease-free survival will be presented at the meeting. No significant financial relationships to disclose.
Therapeutically targeting <scp>SELF</scp>‐reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?
Authors: Paolo Bernasconi, Mirko Farina, Marina Boni, Irene Dambruoso, Celeste Calvello
Journal: American Journal of Hematology (2016)

A tight relationship between the acute myeloid leukemia (AML) population and the bone marrow (BM) microenvironment has been convincingly established. The AML clone contains leukemic stem cells (LSCs) that compete with normal hematopoietic stem cells (HSCs) for niche occupancy and remodel the niche; whereas, the BM microenvironment might promote AML development and progression not only through hypoxia and homing/adhesion molecules, but also through genetic defects. Although it is still unknown whether the niche influences treatment results or contains any potential target for treatment, this dynamic AML-niche interaction might be a promising therapeutic objective to significantly improve the AML cure rate.
Changes over time in quality of psychosocial care: Results from the Quality Oncology Practice Initiative (QOPI).
Authors: P. B. Jacobsen, P. Kadlubek
Journal: Journal of Clinical Oncology (2010)

6000 Background: In 2008, ASCO's QOPI added quality measures for psychosocial care to the core set of measures completed by all participating practices. As part of a summary report based on data submitted from medical records, each practice is provided the percentage of its patients and the percentage of all patients audited for whom: 1) current emotional well-being was assessed within one month of the first visit with a medical oncologist; 2) action was taken if a problem with emotional well-being was identified. We sought to determine if performance on these indicators improved between Fall 2008 (when these indicators became part of the core) and Fall 2009 among practices that participated in both rounds of audits. Methods: 166 practices participated in both rounds and provided data on 30,853 patients. The average number of patients per practice was 90 in 2008 and 95 in 2009. Results: Average rates per practice for performing an assessment of emotional well-being improved over time from 64% to 73% (p < 0.001). This change was associated with an increase from 13% to 17% in the percentage of each practice's patients who were identified as having a problem with emotional well-being (p < 0.001). Average rates per practice for taking action if a problem with emotional well-being was identified increased minimally from 74% to 76% (p = 0.41). However, reflecting the higher percentage of patients being assessed, the percentage of each practice's patients for whom action was taken for a problem with emotional well-being increased from 9% to 13% (p < 0.001). Conclusions: Findings suggest that providing feedback to practices produced a marked increase in assessment of emotional well- being. As would be expected, this increase corresponded with more patients being identified as having problems with emotional well-being and more actions being taken to address problems with emotional well-being. Although an increase on this process indicator of quality care is encouraging, additional research incorporating outcome measures is needed to determine if conducting more assessments results into actual improvements in the patients' emotional well-being. No significant financial relationships to disclose.
Abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) and prior therapy with ketoconazole: A Prostate Cancer Clinical Trials Consortium study.
Authors: C. J. Ryan, A. L. Harzstark, A. M. Lin, L. Fong, K. Grycz, R. Z. Szmulewitz, V. K. Weinberg, A. Molina, E. J. Small
Journal: Journal of Clinical Oncology (2011)

4500 Background: AA and ketoconazole (keto) both inhibit CYP 17, the rate limiting enzyme in androgen synthesis. Since mechanisms of resistance to these agents may be overlapping, patients (pts) with prior keto exposure were excluded from the AA randomized phase III trials. In the current study patients with mCRPC who have received prior therapy with keto were treated with AA. Methods: Eligibility required progressive mCRPC and prior keto for >28 days. Prior chemotherapy was not allowed. Pts were required to have normal baseline organ function and ACTH stimulation test. Therapy consisted of a fasting daily dose of AA at 1000 mg with 10 mg of prednisone. Response is defined as a >50% decline in PSA from baseline value. The study is designed to detect a ≥30% PSA decline in ≥30% of patients. Results: Sixteen pts were enrolled in the initial cohort, the median follow up is 13.1 weeks (range 1-18). The median age and baseline PSA are 72.5 years and 62.5 ng/dL, respectively. The median duration of prior keto therapy was 58 weeks (range 9 – 206) and the median duration since last keto therapy was 17 weeks (range 4–187). Ten of 16 (63%) enrolled patients had experienced a ≥50% decline in PSA while on keto. Of the 16 enrolled patients, 11 have completed 12 weeks of therapy, two have completed <12 weeks of therapy and three patients have discontinued therapy (two developed symptomatic progression and one withdrew consent). AA therapy resulted in a confirmed ≥50% decline in PSA at 12 weeks in 3/14 (21%) (95% confidence interval (CI): 5%-51%) and a confirmed ≥30% decline in 6/14 (43%) (95% CI: 18% 71%). Of the pts without a ≥30% PSA decline, one had developed RECIST defined disease progression at 12 weeks and the remainder had stable disease. Grade 3/4 toxicities included hypertension in one patient. Expanded accrual is ongoing. Conclusions: A substantial number of pts with prior ketoconazole exposure respond to AA indicative of the greater CYP 17 inhibition induced by AA and retained CYP 17 dependence in mCRPC. The lower responses observed in this study compared to keto naïve mCRPC suggests the potential for overlapping mechanisms of resistance to AA and keto.
The academic oncology hospitalist—a model for improved teaching and patient care
Authors: A. E. Denes, J. F. DiPersio, M. J. Ellis
Journal: Journal of Clinical Oncology (2007)

19630 Background: The care of hospitalized cancer patients in academic institutions is usually assigned to residents and fellows with supervision by a “rotating” attending oncologist. This approach ensures that, at a minimum, each patient’s care is reviewed and supervised by an attending physician. This model, however, has several shortcomings including: 1) lack of continuity of care 2) limited time for teaching 3) limited knowledge of diseases outside of the research or clinical interests of the attending 4) lack of consistent clinical leadership and 5) communication problems when the attending physician is in clinic, meetings, or research activities. Methods: We felt that a model in which a senior medical oncologist with an interest in patient care, teaching, and clinical research serves as the full time director of the inpatient oncology service would address these challenges. The organizational chart for this model will be presented. In this model, the attending oncologist meets with the “post call” intern/resident team, fellow, and hospitalist each morning to review and discuss all patients admitted to the service in the prior 24 hrs. The afternoons are spent visiting patients, reviewing the status of all patients on the service, and evaluating high acuity new admissions. An oncology core curriculum lecture series was developed with daily lectures. The trainees are encouraged to attend additional conferences as time permits. Results: The program was initiated in November 2005 and has been a universal success. Patient satisfaction has improved significantly and the number of graduating residents pursuing fellowships in oncology has increased from 3–4 to 7–8 per year. The attending physicians are able to continue their clinic schedules and research activities without interruption. We are planning to review this experience to evaluate additional changes in patient outcome such as length of stay, efficacy of symptom control, and readmission rates. Conclusions: Our model of inpatient oncology care has improved patient satisfaction, teaching, and faculty utilization. It lends itself to develop clinical trials of inpatient cancer care. We suggest it be considered in academic cancer centers to achieve similar goals. No significant financial relationships to disclose.
Estimation of right ventricular isovolumic pressure in experimental pulmonary hypertension from a single ejecting beat
Authors: Taco Kind, Gerrina Ruiter, Theo J.C. Faes, Louis M. Handoko, Ingrid Schalij, Anton Vonk Noordegraaf, Nico Westerhof
Journal: European Respiratory Journal (2011)

In pulmonary hypertension (PH), assessment of right ventricle (RV) contractility from end-systolic pressure-volume relationships (ESPVR) is difficult due to the requirement of multiple-beats by alterations in cardiac preload. Several single-beat (SB) methods have been proposed to calculate ESPVR, mostly based on estimation of maximum isovolumic pressure (P max ) using arbitrary wave shapes of isovolumic pressure. The purpose of this study was to derive experimentally the isovolumic pressure wave shape of the RV and to use this curve to compute P max(SB) . Isovolumic pressure curves were determined by clamping the pulmonary artery in 4 control, 3 stable PH and 3 progressive PH rats. PH was induced by monocrotaline (MCT) 40 and 60 mg/kg, respectively. All curves were normalized in amplitude and duration to obtain the typical isovolumic pressure wave shape. This curve was used to estimate P max(SB)  in 9 control, 7 MCT40 and 7 MCT60 rats from ejecting RV pressure curves. P max(SB)  values were compared to values obtained from multiple pressure-volume loops by vena cava occlusion [P max(VCO) ]. Three SB methods from literature were included for comparison. With our method close correlations were found between P max(SB)  and P max(VCO)  (r 2 =0.85, p 2  values of 0.74, 0.82, and 0.85; p max(VCO)  in MCT60 rats, and all three methods resulted in less realistic shapes of isovolumic pressure waves compared to our experimental curves. In conclusion, with our method realistic isovolumic pressure curves can be obtained providing accurate estimates of Pmax over a wide range of RV contractility.
Proteomic analysis of whole saliva may identify patients with high focus score in primary Sjogren’s syndrome
Authors: C Baldini, C. Giacomelli, Donati, L Giusti, Y Da Valle, F Ciregia, F Sernissi, R Talarico, L Bazzichi, G Giannacchini, A Lucacchini, S . Bombardieri
Journal: Annals of the Rheumatic Diseases (2010)
CAP—advancing the evaluation of preclinical Alzheimer disease treatments
Authors: Eric M. Reiman, Jessica B. Langbaum, Pierre N. Tariot, Francisco Lopera, Randall J. Bateman, John C. Morris, Reisa A. Sperling, Paul S. Aisen, Allen D. Roses, Kathleen A. Welsh-Bohmer, Maria C. Carrillo, Stacie Weninger
Journal: Nature Reviews Neurology (2015)
Abstract 14648: The Immune Protein Md-2 is a Novel Independent Predictor for Long Term Mortality in Dilated Cardiomyopathy and Has Stimulatory Capacity in Monocytes and Cardiomyocytes
Authors: Katharina B Wagner, Matthias Hundt, Kerstin Weitmann, Jeannine Witte, Stephan Gross, Marcus Doerr, Klaus Empen, Wolfgang Hoffmann, Stephan B Felix, Alexander Riad
Journal: Circulation (2013)

Myeloid differentiation protein 2 (MD-2) is a known cofactor of Toll-like receptor 4 (TLR4) enhancing lipopolysaccharide (LPS) recognition. Its role in cardiac diseases is unknown. In the present s...
춘계학술대회 : 포스터전시 ; 라미부딘 치료에 의한 YMDD 변이형의 양상과 발생 관련인자
Authors: 도병훈, 김상기, 전성우, 조창민, 탁원영, 권영오, 김성국, 최용환
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 만성 B형 간염에서 라미부딘은 효과적인 항바이러스제로 사용되고 있지만 장기적인 치료에 따른 YMDD 변이형의 발생은 라미부딘 치료효과를 감소시킨다. 따라서 조기에 YMDD 변이형의 발생을 예상할 수 있을 경우 그 치료효과를 높일 수 있으나, YMDD 변이형의 발생과 관련된 인자들에 대한 연구는 아직 미비한 실정이다. 본 연구에서는 YMDD 변이형 발생시기와 관련된 인자, 변이형의 종류 및 특성을 알고자하는 목적으로 진행하였다. 대상 및 방법
New Approaches to Reduce Readmissions in Patients With Heart Failure
Authors: Kumar Dharmarajan, Sarwat I. Chaudhry
Journal: JAMA Internal Medicine (2016)

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Variation in Agar Growth of Transformed 3T3 Cells After Tumor Formation in Nude Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C A Romerdahl, H Rubin
Journal: JNCI Journal of the National Cancer Institute (1985)

Cells from a cloned line of spontaneously transformed 3T3 cells had a colony-forming efficiency in agar (CFEag) of about 10-15% and induced poorly differentiated sarcomas when injected into nude mice. These tumor cells were recultured in vitro and tested for their ability to grow in suspension. Initially, the tumor cells had a CFEag which was a hundredfold to a thousandfold lower than the cells that had been grown only in vitro. After 5-8 further weekly passages, however, the tumor lines recovered their original ability to grow in agar. For determination as to whether this increased CFEag was due to selection of cells with a higher CFEag from the tumor cell population or to adaptation of many of the tumor cells to agar growth, clones were isolated directly from a primary tumor, and each was tested weekly for agar colony formation. All of the tumor clones, as well as the uncloned tumor line, were able to recover their original ability to grow in agar. However, one tumor clone had a relatively high CFEag in the first assay, so the selection hypothesis could not be totally excluded. The initial low CFEag of the recultured cells was not due to the presence of normal nude mouse cells in the population. Before in vivo growth no clones could be isolated from the sublines that had as low a CFEag as the tumor cells isolated after in vivo growth. Tumor cells that had been repeatedly passaged in vivo still had a much lower CFEag than the input cells upon explantation into culture. The results suggest that phenotypic alterations observed during tumor growth and subsequent cultivation have an epigenetic basis.
miR-23∼27∼24 clusters control effector T cell differentiation and function
Authors: Sunglim Cho, Cheng-Jang Wu, Tomoharu Yasuda, Leilani O. Cruz, Aly Azeem Khan, Ling-Li Lin, Duc T. Nguyen, Marina Miller, Hyang-Mi Lee, Ming-Ling Kuo, David H. Broide, Klaus Rajewsky, Alexander Y. Rudensky, Li-Fan Lu
Journal: The Journal of Experimental Medicine (2016)

Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, we show that the miR-23∼27∼24 clusters regulate multiple aspects of T cell biology, particularly helper T (Th) 2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23∼27∼24 clusters revealed that miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, although overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17, and induced regulatory T cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest that tight regulation of miR-23∼27∼24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses.
Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or locally advanced solid tumors: assessment of safety and tolerability in a phase I, open-label expansion study.
Authors: Karen Kelly, Manish R. Patel, Jeffrey R. Infante, Nicholas Iannotti, Petros Nikolinakos, Joseph Leach, Ding Wang, Jason Claud Chandler, Guy Heinrich Maria Jerusalem, Jayne S. Gurtler, Hendrik-Tobias Arkenau, Isabell Speit, Anja von Heydebreck, Kevin M. Chin, Christopher Ryan Heery, James L. Gulley
Journal: Journal of Clinical Oncology (2015)

3044 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. The primary objective of this phase I, open-label, parallel-group expansion study (NCT01772004) was to assess the safety and tolerability of avelumab in patients (pts) with metastatic or locally advanced solid tumors. Methods: Pts with advanced or metastatic disease (including NSCLC, gastric, ovarian, breast, and melanoma; ECOG PS 0-1 at trial entry) were treated with avelumab at 10 mg/kg Q2W until confirmed complete response (CR), progression, unacceptable toxicity, or withdrawal. Adverse events (AEs) were evaluated by CTCAE v4.0. Results: In total, 480 pts treated with avelumab were followed-up for at least 4 weeks (wks) by Nov 5, 2014 and assessed in this interim analysis (median age, 60 years [range 29-85]; ECOG PS 0 [40.6%], 1 [59.0%], 3 [0.2%], or unknown [0.2%]; median of 2 prior treatments [range 1-≥ 4]). Drug-related treatment-emergent AEs (TEAEs; all grades) occurred in 68.8% of pts, with the most frequent being fatigue (20.2%), nausea (12.9%), infusion-related reaction (IRR) (9.8%), diarrhea (6.9%), chills (6.9%), decreased appetite (6.3%), pyrexia (5.6%), influenza-like illness (5.2%), and arthralgia (5.0%). Drug-related TEAEs resulted in treatment discontinuation in 34 pts; of these, 8 were due to an IRR. Drug-related grade ≥ 3 TEAEs were reported in 12.3% (n = 59); the most common of these were anemia (5), fatigue (5), increased GGT (4), IRR (4), increased lipase (4), and decreased lymphocytes (3). AEs that were potentially immune-related were observed in 11.7% of pts, with the most common being hypothyroidism (4.0%) and pneumonitis (1.5%). Conclusions: Avelumab demonstrated an acceptable safety profile in a heavily pretreated population across a range of tumor types. Development of avelumab as a monotherapy and in combination is ongoing. *Proposed INN. Clinical trial information: NCT01772004.