tbuckley/cabot-search huggingface dataset:
Interleukin-10 as a prognostic factor in patients treated with autologous melanoma cell vaccine.
Authors: A. Mahipal, D. Berd, I. Chervoneva, M. Terai, M. J. Mastrangelo, T. Sato
Journal: Journal of Clinical Oncology (2010)

8588 Background: Interleukin-10 (IL-10) downregulates the T cell-mediated immune response. We studied the association between IL10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients who were treated with cancer vaccine consisting of the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). It was assumed that production of IL-10 in tumor cell suspensions reflect the degree of IL-10 in tumor microenvironment. Methods: Tumor cells were extracted from metastatic tissues and cryopreserved until vaccine production. Small fraction of melanoma cell suspensions were separated prior to vaccine production and cultured overnight for the production of IL-10 in the culture supernatants. After inactivation with radiation and modification with DNP, autologous melanoma cells were injected to patients as a cancer vaccine. The final vaccine products did not produce IL-10. Forty four patients including 29 stage III and 15 stage IV disease were evaluated. The cut-off of 200 pg/mL was used to differentiate high versus low IL-10 producers based on scattergram. Cox regression model was used for multivariate analysis. Overall survival was calculated using Kaplan and Meier method and survival curves were compared with log-rank tests. Results: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The overall survival (OS) was significantly longer for low versus high IL-10 producers (median OS 42 vs. 10.5 months, p = 0.02). In stage III patients, median OS for low and high IL-10 producers was 84 months and 9.7 months respectively (p = 0.07). In stage IV patients, the corresponding values were 13.7 months and 10.5 months (0.62). In multivariate analysis, the hazard ratios for stage III and stage IV patients were 2.92 (1.04-8.20) and 0.92 (0.28-3.00). Conclusions: Our study suggests that high IL-10 production in tumor cells is associated with worse prognosis in stage III melanoma patients receiving autologous vaccine. It has been shown that delayed-type hypersensitivity to autologous tumor cells is associated with longer OS. By downregulating the T cell mediated immune response, IL-10 in tumor microenvironment may decrease the effectiveness of the vaccine. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AVAX
TCT-526 An in-vivo multi-modality imaging study of the Absorb everolimus-eluting bioresorbable scaffold in complex coronary bifurcations
Authors: Johan Bennett, Nina Vanden Driessche, Maarten Vanhaverbeke, Walter Desmet, P. Sinnaeve, Tom Adriaenssens, Christophe Dubois
Journal: Journal of the American College of Cardiology (2015)
Rare recurring chromosomal abnormalities. Report of an international workshop on the relationship of prior therapy to balanced chromosome rearrangements in treatment-related leukemia and myelodysplasia
Authors: AW Block, Baer, AJ Carroll, Anne Hagemeijer-Hausman, Lucienne Michaux, K van Lom, R Espinosa, T Karrison, JD Rowley
Journal: Blood (2000)
Current results of studies of immunophenotype-, age- and leukocyte-based therapy for children with acute lymphoblastic leukemia
Authors: W. Crist, J. Shuster, T. Look, M. Borowitz, F. Behm, Paul Bowman, L. Frankel, J. Pullen, R. Krance, P. Steuber, B. Camitta, M. Amylon, M. Link, V. Land
Journal: Leukemia (1992)
Preliminary data on weekly irinotecan (CPT) with continuous capecitabine (X) in metastatic colorectal cancer (MCRC) patients (pts)
Authors: N. Anderson, J. Lokich, L. Kalman, L. Bertoli, R. Foulke, L. Ratner, A. Weitberg, H. Burris
Journal: Journal of Clinical Oncology (2004)

3755 Background: X (Xeloda) has superior activity and improved safety compared to bolus 5-FU/LV in 1st-line MCRC. Addition of irinotecan (CPT) to 5-FU/LV improves efficacy. In combination, X should preserve the safety advantages of protracted infusions of 5-FU while improving convenience for pts. Continuous X monotherapy (666 mg/m2 twice-daily) is safe and effective in MCRC (Van Cutsem, JCO 2000). Methods: X was given as a fixed dose of 1000 mg twice daily plus intravenous CPT 75 mg/m2 weekly, for the 1st 4 weeks of each 6-week cycle. Pts ≥65 years old received reduced doses (CPT 60 mg/m2; X 750 mg twice-daily). Study objectives were efficacy and safety. Results: Of 52 pts enrolled, all were evaluable for safety and 49 for response: 35 men (67%), 17 women (33%); median Karnofsky PS 90 (70–100), median age 65 (39–78). 36 pts (69%) had colon cancer, 11 rectal (21%) and 5 both (10%). Most common metastatic sites were liver (79%), nodes (58%), lung (33%), and soft tissue (13%). At diagnosis, 63% of pts had metastases. 14 pts (27%) had received prior adjuvant 5-FU. Mean treatment duration is 112 days. Most common grade 3/4 clinical adverse events were diarrhea (19% G3), nausea/vomiting (12% G3). Overall, G3/4 toxicity was more frequent in pts ≥65 years (38 vs 27%) as was GI toxicity (35 vs 23%). Only 1 pt experienced grade 3 HFS and there was no G3/4 stomatitis. Responses (PR+CR) were seen in 9 pts (1 CR) with an additional 5 unconfirmed responses, producing an overall response rate of 29%. Disease control (CR+PR+SD) was seen in 65% of pts. Disease control rates were similar in pts <65 and ≥65 years (63% vs. 68%). Median progression-free and overall survival in the elderly also compare favorably (TTP 5.3 vs. 5.2 months; OS 13.2 vs. 14.9 months). Conclusion: Safety and efficacy of X with CPT is now established in several schedules, with intermittent X + CPT (Patt, ASCO 2003) favored for phase III development. The continuous fixed-dosing regimen described here may be suited to elderly pts as efficacy was not compromised despite the initial 25% dose reduction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; GlaxoSmithKline Genentech GlaxoSmithKline Hoffmann La Roche
Wilms’ Tumor 1 Gene Mutations in Childhood Acute Myeloid Leukemia: A New Prognostic factor with Implications for MRD Detection
Authors: Iris H.I.M. Hollink, Marry M. van den Heuvel-Eibrink, Martin Zimmermann, Brian V. Balgobind, Susan T.C.J.M. Arentsen-Peters, Mariel Alders, Andre Willasch, Gertjan J.L. Kaspers, Jan Trka, Andre Baruchel, Siebold S.N. de Graaf, Ursula Creutzig, Rob Pieters, Dirk Reinhardt, C. Michel Zwaan
Journal: Blood (2008)
Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias
Authors: Brittany Knick Ragon, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi, Jorge Cortes, Gautam Borthakur, LaKiesha DeBose, Zhihong Zeng, Heather Schneider, Naveen Pemmaraju, Guillermo Garcia‐Manero, Steven Kornblau, William Wierda, Jan Burger, Courtney D DiNardo, Michael Andreeff, Marina Konopleva, Naval Daver
Journal: American Journal of Hematology (2016)

Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day. The MTD was 80 mg/day. Of the 14 patients treated, the best response was stable disease in one patient that lasted 82 days. The median survival for all patients was 75 days (range 10-568). Three patients with a 3q26 chromosome abnormality had a significantly improved median survival of 360 days (range 278-568) as compared to a median survival of 57 days (range, 10-125) among the 11 other patients. The most frequent drug-related toxicities included confusion, mucositis, dysphagia, and fatigue. Western blot profiling revealed a decrease in p-pS6K/total pS6K in 5/7 (71%) available patient samples with a mean quantitative inhibition of 65% (range, 32-100%) and a decrease in p-FOXO3/total FOXO3 in 4/6 (67%) samples with a mean quantitative inhibition of 93% (range, 89-100%). BKM120 administered at 80 mg/day showed modest efficacy and was tolerable in advanced acute leukemias. Am. J. Hematol. 92:7-11, 2017. © 2016 Wiley Periodicals, Inc.
Use of integrated genomics to identify three high-grade glioma subtypes with distinct genetic profiles, pathway signatures, and clinicopathologic features.
Authors: S. Puget, C. Philippe, E. De Carli, R. Grundy, B. Job, P. Varlet, C. Richon, C. Sainte-Rose, G. Vassal, J. Grill
Journal: Journal of Clinical Oncology (2010)

e12500 Background: Molecular pathogenesis of pediatric malignant glioma (pMG) is poorly described and the histo-prognostic classifications used for their adult counterparts may not apply completely. Our study aimed to identify specific genomic abnormalities to generate a new biological classifier. Methods: After histopathologic review, aCGH profiles and gene expression (GE) signature of 45 frozen samples of pMG including pontine tumors were analysed by oligonucleotide microarrays (Agilent 44K); 36 paraffin-embedded samples from an independent group were used to validate the aCGH classifier. Candidate genes were validated using real-time polymerase chain reaction and immunohistochemistry (IHC). Results: Amplifications and deletions were relatively rare concerning N-myc, KIT, PDGFRA and CDKN2A/B, MTAP, TUSC1, respectively. The unsupervised hierarchical clustering identified 3 patterns of aCGH profile that were associated with survival but not with histology or tumor location. The addition of the 36 external samples did not modify the clustering and confirmed the prognostic implication of the new aCGH-based classification. The poor prognosis group consisting in the oldest patients (p = 0.007) showed some similarities with adult high-grade gliomas: chromosomal imbalances (gain of 7 and loss of 10q) and adult glioma GE pattern with proliferative profile on gene set enrichment analysis (GSEA). However, EGFR amplification was rare and no PTEN mutation were found in tumors with 10q loss. Another group was characterized by a simultaneous gain of chromosome 1q and 17q. Its GE profile showed an enrichment for proliferation and neural patterning genes. The last group consisting in the youngest patients had a balanced aCGH profile and a significantly better prognosis than the first group. It showed an overexpression of CDKN1A. Potential prognostic markers on IHC (p53, PTEN, EGFR and nuclear betacatenin) were distributed among the 3 groups. Conclusions: We have identified 3 subgroups of pMG with survival correlates. Their molecular profiling did fit neither with the histopathologic classification nor with the genomic signature of their adult counterparts. No significant financial relationships to disclose.
Chlamydia pneumoniae induces a change in type of atherosclerotic lesions in ApoE3 Leiden transgenic mice
Authors: Rajaa Ezzahiri, Marjorie Nelissen-Vrancken, Harrie Kurvers, Inge Vliegen, Gert Grauls, Cathrien Bruggeman, Peter Kitslaar
Journal: Circulation (2000)
How to follow-up advanced-stage serous borderline tumors of the ovary: Analysis of the mode of diagnosis of recurrence in patients with stage II-III disease.
Authors: A. Kane, C. Uzan, S. Gouy, P. Pautier, C. Balleyguier, C. Haie-Meder, C. Lhomme, P. Duvillard, P. Morice
Journal: Journal of Clinical Oncology (2010)

e15525 Background: The aim of this study was to describe how recurrences has been diagnosed in the largest series of patients treated for advanced-stage serous borderline ovarian tumors. Methods: From 1969 to 2006, 45 patients with a serous borderline and peritoneal implants recurred out of the 162 patients with a follow up > 1 year. Datas about recurrences and its mode of diagnosis were reviewed. Results: The median duration of follow-up was 98 months (range, 19-286). The mode of diagnosis was imaging (n = 19), clinical symptoms (n = 8), rising CA125 level (n = 7), a secondary surgery (n = 5) and unknown (n = 6). The median time-to-recurrence was 31 months (range, 4-242). Type of recurrence was invasive disease for 14 patients. Five patients died of their recurrence. Among the 39 patients with identified mode of diagnosis, the most frequent diagnostic tool of invasive recurrence was raised CA125 blood (6/13) and majority of non invasive recurrences was diagnosed by imaging (16/23). Conclusions: This study demonstrates that ultrasounds is the most relevant procedure for the follow-up in this context. Nevertheless, the CA125 blood test has an interest, particularly to point out invasive recurrent diseases, which are the most crucial event to detect. No significant financial relationships to disclose.
Evolution of Protein Domain Repeats in Metazoa
Authors: Andreas Schüler, Erich Bornberg-Bauer
Journal: Molecular Biology and Evolution (2016)

Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution.
MYO5B mutations cause cholestasis with normal serum gamma‐glutamyl transferase activity in children without microvillous inclusion disease
Authors: Emmanuel Gonzales, Sarah A. Taylor, Anne Davit‐Spraul, Alice Thébaut, Nadège Thomassin, Catherine Guettier, Peter F. Whitington, Emmanuel Jacquemin
Journal: Hepatology (2016)

Some patients with microvillus inclusion disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
IMPACT OF GERIATRIC ASSESSMENT ON TREATMENT DECISIONS IN OLDER LUNG CANCER PATIENTS
Authors: Leen Vanacker, Cindy Kenis, Katrien Van Puyvelde, Johan Flamaing, Dennis Schallier, Johan Vansteenkiste, Godelieve Conings, Kristiaan Nackaerts, Jean Pierre Lobelle, Koen Milisen, Jacques De Greve, Hans Wildiers, Lore Decoster
Journal: Journal of Thoracic Oncology (2013)
Fine tuning metabolism of biochemically active abiraterone metabolites to optimize anti-androgen therapy in prostate cancer.
Authors: Nima Sharifi, Zhenfei Li, Mohammad Alyamani, Jianneng Li, Sunil Upadhyay, Steven P. Balk, Mary-Ellen Taplin, Richard J. Auchus
Journal: Journal of Clinical Oncology (2016)

5016 Background: Abiraterone inhibits CYP17A1 and blocks androgen synthesis, prolonging survival in castration-resistant prostate cancer (CRPC). Abiraterone is metabolized in patients to D4A, which has even greater anti-tumor activity and structural similarities to endogenous steroidal 5α-reductase substrates, such as testosterone. Other steroidal abiraterone metabolites might also harbor biochemical activity that could be relevant to clinical response or resistance to abiraterone. Furthermore, clinical manipulation of abiraterone metabolites might be an approach to optimizing anti-androgen therapy. Methods: We synthesized 3 5α-reduced and 3 5β-reduced abiraterone metabolites as standards for mass spectrometry analysis and to interrogate biochemical function. Serum was analyzed by mass spectrometry in 12 patients treated with abiraterone acetate plus prednisone for CRPC and in 16 patients treated on a clinical trial of abiraterone acetate (1000 mg) plus prednisone for 2 cycles, followed by the addition of dutasteride (3.5 mg) for 4 cycles. The activity of selected novel abiraterone metabolites was tested in assays for steroidogenic enzymes, androgen receptor binding studies, gene expression studies and xenograft models. Results: D4A is converted to at least 3 5α-reduced and 3 5β-reduced metabolites. The initial 5α-reduced metabolite, 5α-abi, is more abundant than D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor (AR) agonist, which promotes prostate cancer progression. In a clinical trial of abiraterone alone, followed by abiraterone plus dutasteride, 5α-abi and downstream metabolites are depleted, while D4A concentrations rise, effectively blocking production of a tumor promoting metabolite and permitting D4A accumulation. Furthermore, dutasteride does not deplete three 5β-reduced metabolites, which were also clinically detectable, demonstrating the specific biochemical effects of pharmacologic 5α-reductase inhibition on abiraterone metabolism. Conclusions: Our findings suggest a previously unappreciated and biochemically specific method of clinically fine tuning abiraterone metabolism to optimize therapy.
Rapid systematic review: The case for evaluating pretreatment CA 19–9 as a stratification factor in randomized clinical trials (RCT) in advanced pancreatic cancer (APC)
Authors: E. D. Saad, R. C. Gansl
Journal: Journal of Clinical Oncology (2008)

15617 Background: Since 2000, we and others have suggested that the pretreatment serum level of CA 19–9 is one of the strongest prognostic factors in APC. We sought to investigate the current use of CA 19–9 and other factors for prognostic stratification in RCT in APC. Methods: We reviewed RCT of systemic antineoplastic treatments for APC appearing in Medline-indexed journals between 01/2003 and 11/2007. Eligible trials were analyzed with respect to stratification factors and the results of multivariable analyses (MVA) of prognostic factors. In addition, we searched the reference lists of retrieved articles, as well as ASCO meetings 2006 and 2007 (excluding ‘publication only’ abstracts). Studies investigating other interventions (such as anticoagulation) were excluded. Results: The Medline search and the reference lists yielded 27 eligible RCTs, and the ASCO meetings yielded an additional 10 RCTs (total=37). Of the 37 RCTs, 24 were phase III, and 13 were randomized phase II. Stratification factors were reportedly used in 26 trials, most commonly disease stage and performance status (N=19 each), and center (N=12). CA 19–9 in stratification was used in none of the trials. MVA was reported in 9 trials and included pretreatment CA 19–9 in only 1 case, in which it was statistically significant (Louvet et al, JCO 2005). The most frequently significant factors in MVA were stage and performance status (N=5 each), and treatment (N=3). Conclusions: Our study shows that CA 19–9 has not been used as a stratification factor in most of the recent RCTs in APC. We suggest that investigators responsible for future studies attempt to examine the prognostic role of pretreatment CA 19–9 vis-à-vis other prognostic factors, and consider its use as a stratification factor in RCTs. No significant financial relationships to disclose.
Risk and impact of pulmonary complications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Andrew Charles Dietz, Yan Chen, Kirsten K. Ness, James S Hagood, Eric Jessen Chow, Yutaka Yasui, Marilyn Stovall, Joseph Philip Neglia, Kevin C. Oeffinger, Ann Mertens, Leslie L. Robison, Gregory T. Armstrong, Daniel A. Mulrooney
Journal: Journal of Clinical Oncology (2014)

10022 Background: Pulmonary complications from exposure to radiation, bleomycin and the nitrosureas have been well-documented among adult survivors of childhood cancer. However, the magnitude of condition-specific risks, compared to a non-cancer population, and the long-term impact on physical activity have not been well described. Methods: This analysis includes 13,208 five-yr survivors of childhood cancer (53% male, age 8 yrs [range: 0-21] at diagnosis, 33 yrs [6-59] at last follow-up), diagnosed ≤ 21 yrs between 1970-1986. Self-reported pulmonary outcomes were compared to a sibling control group (N=4,023) using Poisson regression to estimate rate ratios (RR) and 95% confidence intervals (CI) adjusted for attained age, sex, race, body mass index, congestive heart failure, and smoking status. Logistic regression was used to estimate associations (odds ratios, OR) between pulmonary outcomes and daily physical activity (walk one block, carry groceries, climb stairs, etc). Results: Compared to siblings, fewer survivors ever smoked (21.2% vs. 34.3%, p<0.001) but were more likely to report asthma (RR 1.4, CI 1.2-1.6), bronchitis (RR 1.2, CI 1.1-1.3), chronic cough (RR 2.2, CI 1.9-2.5), emphysema (RR 2.5, CI 1.2-5.2), need for extra oxygen (RR 2.2, CI 1.8-2.6), pulmonary fibrosis (RR 3.9, CI 2.7-5.8), pleurisy (RR 1.3, CI 1.1-1.7), and recurrent pneumonia (RR 2.8, CI 1.9-4.0). Cumulative incidence of any pulmonary condition by age 40 was 78.7% (CI 78.3-79.2). Lung cancer was reported in 17 (0.1%) with a standardized incidence ratio of 3.9 (CI 2.3-6.2). The standardized mortality ratio for death due to a pulmonary condition was 9.1 (CI 7.4-11). Limited daily physical activities were more likely among survivors with a pulmonary condition vs. those without: asthma (OR 1.6, CI 1.4-1.8), bronchitis (OR 1.5, CI 1.4 - 1.7), chronic cough (OR 2.8, CI 2.5 - 3.1), emphysema (OR 2.6, CI 1.5 - 4.3), need for extra oxygen (OR 3.3, CI 2.9 - 3.7), lung fibrosis (OR 2.3, CI 1.9 - 2.8), pleurisy (OR 1.9, CI 1.6 - 2.3), and recurrent pneumonia (OR 3.6, CI 2.9 - 4.4). Conclusions: Pulmonary complications are substantial among cancer survivors, significantly impacting daily activity and increasing risk of death.
Frequent rearrangement of the BCL6 gene in lymphocyte predominance Hodgkin's lymphoma and its absence in classical Hodgkin's disease provides further evidence for their genetic diversity
Authors: Iwona Wlodarska, B Maes, P Pauwels, P Noyen, R Van Hezik, Sabine Franke, Chris Peeters, Anne Hagemeijer-Hausman
Journal: Blood (2001)