tbuckley/cabot-search huggingface dataset:
P01.05 * ZBTB18 METHYLATION PROMOTES MESENCHYMAL TRANSFORMATION IN GLIOBLASTOMA
Authors: V. Fedele, F. Dai, V. Marinescu, H. Kim, A. Weyerbrock, M. Prinz, M. Bredel, M. Carro
Journal: Neuro-Oncology (2014)

Although studies performed in the past decade have contributed to a better classification and characterization of GBM, the overall survival and outcome of GBM patients have not seen major improvement. The mesenchymal signature is described as the subtype of GBM with the worst prognosis, primarily due to inherent resistance of the tumors to contemporary therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. The Zing Finger And BTB Domain Containing 18 (ZBTB18; formerly ZNF238) is a transcriptional repressor with a crucial role in brain development and neuronal differentiation. Consistent with our previous study, which provided preliminary evidence of a role for ZBTB18 in a network of mesenchymal transformation in GBM, our new data have discovered epigenetic silencing, that is promoter methylation, as a mechanism to downregulate ZBTB18 in these tumors. We show that ZBTB18 functions as a master regulator of a mesenchymal gene signature in GBM and that loss of ZBTB18 contributes to the highly invasive mesenchymal phenotype. Conversely, re-expression of ZBTB18 reverses the phenotype and impairs tumor-forming ability. Overall, our results support a tumor suppressor role of ZBTB18 in the brain and identify promoter hypermethylation as a mechanism to silence ZBTB18 in the mesenchymal subtype of GBM, which provides a new mechanistic opportunity to specifically target this tumor subclass.
Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.
Authors: A López-Guillermo, E Montserrat, F Bosch, M J Terol, E Campo, C Rozman
Journal: Journal of Clinical Oncology (1994)

PURPOSE Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P &lt; .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P &lt; .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P &lt; .0001) and International Index (P &lt; .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.
IgG4 Subclass in Malignant Melanoma
Authors: Maryvonne Daveau, Jeannine Pavie Fischer, Liliane Rivat, Claude Rivat, Claude Ropartz, Hans H. Peter, Jean-Pierre Cesarini, François M. Kourilsky
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article IgG4 Subclass in Malignant Melanoma Get access Maryvonne Daveau, Maryvonne Daveau Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeannine Pavie Fischer, Jeannine Pavie Fischer Search for other works by this author on: Oxford Academic PubMed Google Scholar Liliane Rivat, Liliane Rivat Search for other works by this author on: Oxford Academic PubMed Google Scholar Claude Rivat, Claude Rivat Search for other works by this author on: Oxford Academic PubMed Google Scholar Claude Ropartz, Claude Ropartz Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans H. Peter, Hans H. Peter Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean-Pierre Cesarini, Jean-Pierre Cesarini Search for other works by this author on: Oxford Academic PubMed Google Scholar François M. Kourilsky François M. Kourilsky Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 189–192, https://doi.org/10.1093/jnci/58.2.189 Published: 01 February 1977 Article history Received: 07 January 1976 Revision received: 11 June 1976 Accepted: 16 July 1976 Published: 01 February 1977
Abstract 19213: Establishment of Mechanically-Assisted Primary Bidirectional Cavopulmonary Shunt in Neonates and Infants: An Acute Human Pilot Study
Authors: Osami Honjo, Sandra Merklinger, John Poe, Anne-Marie Guerguerian, Katherine Taylor, Hargen Zhang, Glen Van Arsdell
Journal: Circulation (2012)

Background: One year survival for stage 1 palliation in hypoplastic left heart syndrome (HLHS) is 69%. We hypothesized that primary ‘in-series’ palliation (neonatal bidirectional cavopulmonary shunt - BCPS) with mechanical assist would provide more stable physiology. This is the first human study of an acute intraoperative BCPS model. Methods: Two types of intraoperative, tubing configured, pump-assisted BCPS circulations [superior vena cava (SVC) to pulmonary artery (PA) pump assist at stage I Norwood, and SVC to right atrium (RA) pump with oxygenation at stage II BCPS] were established in the operating room for 20 minutes at the time of modified ultrafiltration (Figure 1A). Hemodynamics and cerebral blood flow were continuously recorded. Arterial and venous blood gases were analyzed every 5-10 minutes. Results: All six patients (3 in each group) completed 20 minutes of mechanical support without hemodynamic compromise. In the SVC-PA pump assist (n=3), the pump generated effective pulmonary blood flow of 335+/-53ml/min while the BT shunt was occluded. Compared to Norwood physiology, the SVC-PA pump-assisted BCPS had a higher mean arterial pressure (median 33 vs. 44 mmHg, p=0.02), lower central venous pressure (CVP) (12 vs. 10 mmHg, p=0.03), and higher cerebral perfusion pressure (33 vs. 46 mmHg, p=0.01) (Figure 1B). In the SVC-RA oxygenation assist (pump and oxygenator assisted BCPS), the pump generated blood flow of 536+/176ml/min with oxygenation. Compared to baseline BCPS physiology, SVC-RA oxygenation-assisted BCPS had a lower CVP (14 vs. 7 mmHg, p=0.05). Conclusion: The study demonstrates the physiologic feasibility of mechanically assisted neonatal in-series single ventricle circulation. Both assist systems attained equivalent or better hemodynamics, stable ventilation and oxygenation, and a more favorable cerebral perfusion profile. This human proof of concept study raises the possibility of a potential paradigm shift for the treatment of HLHS.
Changes in body composition in women with breast cancer on aromatase inhibitors: A two-year trial
Authors: G. J. Van Londen, S. Perera, K. Vujevich, P. Rastogi, B. Lembersky, A. Brufsky, V. Vogel, S. Greenspan
Journal: Journal of Clinical Oncology (2009)

9528 Background: Aromatase inhibitors (AIs), the preferred adjuvant therapy of postmenopausal breast cancer patients, induce severe hypo-estrogenemia which differentiates them from the Estrogen-Receptor-Agonists-Antagonists (ERAAs). Little is known about the effect of AIs on body composition. We sought to examine the impact of AIs on body composition, and whether any changes correlate with gonadal hormone levels. Methods: We analyzed a two year double-blind trial (Risedronate's Effect on Bone loss in Breast CAncer, REBBeCA). 81 chemotherapy-induced newly postmenopausal nonmetastatic breast cancer patients had been randomized to risedronate 35 mg once weekly or placebo and followed, some of whom were on or started AI during the trial. Measures included body composition by whole body DXA-scan and serum sex hormone levels. Combining the two treatment arms, we estimated and compared body composition changes in those on (AI) and not on AIs (no-AI) using a linear mixed model, and examined correlations with serum hormone levels. Results: By 24 months, 41 women were on an AI. Over 2 years, lean mass increased by 1159g (p=0.0003) in women on an AI and did not change (85g; p=0.7684) in the no-AI group (adjusted difference, AD=1047g; p=0.0004). Percent fat did not change (0.0; p=0.9344) in those on an AI and increased (1.2; p=0.0097) in the no-AI group (AD=1.6; p=0.0433). The change in estradiol was associated with changes in lean mass (correlation r=0.42, p=0.0020) and percent fat (r=-0.48, p=0.0003). Conclusions: The use of AIs is associated with a decrease in fat mass and an increase in lean mass. The changes in estradiol are associated with alterations in body composition. The mechanisms and implications of these changes need to be studied further. [Table: see text]
Comparison of allogeneic vs. autologous transplantation for follicular lymphoma after transformation into diffuse large B-cell lymphoma
Authors: F. T. Awan, M. Hamadani, T. S. Lin, P. Porcu, K. A. Blum, D. M. Benson, S. M. Devine
Journal: Journal of Clinical Oncology (2008)

7046 Background: The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of patients (pts). 5yr overall survival (OS) and progression free survival (PFS) rates are 51% and 30% respectively for such patients undergoing autologous (Auto) stem cell transplantation (SCT) (William CD. JCO 2001). Studies comparing outcomes of Auto-SCT with allogeneic (Allo)-SCT in transformed FL have not been previously reported. Methods: FL pts with histologically confirmed transformation to diffuse large B-cell lymphoma undergoing SCT were eligible for this study. Patient characteristics were retrospectively collected. Results: 25 pts with transformed FL underwent SCT between 11/1991 and 7/2007 at our institution. The median age was 54yrs (range 44–68yrs). 17 pts underwent unpurged Auto-SCT. Stem cell source included peripheral blood (n=14), bone marrow (n=1) or both (n=2). Eight pts underwent Allo-SCT (HLA-identical sibling=5, matched unrelated donor=3). 2 Allo-SCT pts received reduced intensity conditioning. The Auto and Allo-SCT groups were matched for age, stage, LDH, number of prior therapies, time from diagnosis to transformation, chemosensitive disease and number of CD34+ cells infused (p-value>0.05). Median follow-up is 56 and 59 mos respectively for Auto and Allo-SCT. Rates of grade II-IV acute and chronic GVHD were 50% each in Allo-SCT group. PFS at 4-yrs by KM method for pts undergoing Auto and Allo-SCT is 23.8% and 56.3% respectively (p-value=0.23). OS at 4-yrs in similar order is 29.8% and 65.6% respectively (p-value=0.15). Cumulative incidence of relapse at 4-yrs was 14.2% and 65.2% respectively in Allo and Auto- SCT groups. 4yr non-relapse mortality rates were 23% and 25% (p-value=0.50) in similar order. Conclusion: Our limited, institutional experience suggests trends of improved PFS and OS in transformed FL pts undergoing Allo-SCT without significantly increased toxicity. Small numbers in our study likely contributed to lack of statistically significant PFS and OS difference between the two groups. These encouraging results warrant further investigation of allografting with matched donors in FL undergoing large cell transformation. No significant financial relationships to disclose.
A multicenter phase II trial of adjuvant erlotinib in patients with resected non-small cell lung cancer (NSCLC) and mutations in the epidermal growth factor receptor (EGFR): Toxicity evaluation.
Authors: J. W. Neal, N. A. Pennell, B. W. Goodgame, M. Lanuti, R. S. Heist, A. T. Shaw, J. S. Temel, P. A. Janne, C. G. Azzoli, L. V. Sequist
Journal: Journal of Clinical Oncology (2010)

7078 Background: Adjuvant chemotherapy for patients (pts) with resected NSCLC provides a modest survival benefit, but a large proportion of pts still relapse, presumably due to inherent chemoresistance. Tumors with activating EGFR mutations are exquisitely sensitive to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib; hence the use of adjuvant TKIs may more effectively prevent recurrences. This trial investigates the safety and efficacy of adjuvant erlotinib in pts with stage I-IIIA NSCLC and somatic EGFR mutations. Methods: Eligible pts have surgically resected stage IA-IIIA NSCLC and activating EGFR mutations. Within 6 months of surgery, and following the completion of routine adjuvant treatment, pts are treated with 150 mg/day of erlotinib for a total of 2 years, with surveillance scans every 6 months. The primary endpoint is disease-free survival at 2 years. Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09. Demographics include: stage I 53%; stage II 19%; stage IIIA 28%; female 75%; never-smokers 56%; exon 19 deletion 61%, L858R 36%. Significant toxicities are listed below (Table). 6 pts have been dose reduced to 100 mg/day and 4 additional pts to 50 mg/day for toxicities including rash, fatigue, diarrhea, transaminitis, and hyperbilirubinemia. 5 pts have withdrawn as a result of toxicity (n=3) or patient preference (n=2), mostly within the first month of treatment (n=4). Current average follow-up time is 8 months. Conclusions: Chronic treatment with adjuvant erlotinib in NSCLC pts with EGFR mutations is feasible. Major observed toxicities are consistent with those previously reported for erlotinib. Based the demonstrated role of EGFR TKIs in advanced NSCLC with EGFR mutations, this trial has been expanded to accrue 100 total patients. Toxicities Event Grade and frequency (%) I II III IV Total Rash 33 36 14 - 83 Diarrhea 58 3 3 - 64 Fatigue 31 17 6 - 53 Alopecia 19 11 - - 31 Nausea/vomiting 22 8 - - 31 Dry skin 25 - - - 25 Mucositis 17 3 - - 19 Pruritis 8 6 3 - 17 Skin erythema 11 6 - - 17 Ocular: dry eye, conjunctivitis 8 8 - - 17 Nail changes 14 - - - 14 AST/ALT 6 - 3 - 8 Bilirubin 3 3 - - 6 Pneumonitis - - - - 0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, GlaxoSmithKline, OSI, Roche Genentech Genzyme
Oxaliplatin plus 5FU/folinic acid (FUFOX Regimen) in 1<sup>st</sup> line metastatic gastric cancer (MGC). Results of the Multicenter Phase II STOMOX Trial
Authors: J. Duyster, S. Lorenzen, F. Kullmann, M. Hentrich, R. Zumschlinge, U. Vehling-Kaiser, T. Seroneit, R. Bredenkamp, C. Peschel, F. Lordick
Journal: Journal of Clinical Oncology (2005)

4016 Background: Phase II trials of biweekly oxaliplatin-5FU protocols demonstrated activity in MGC (Louvet, JCO 2002; Al-Batran, JCO 2004). This trial assessed the efficacy of a weekly protocol which has shown high activity in metastatic colorectal cancer (Grothey, ASCO 2002 abstract 512). Methods: Pts received oxaliplatin 50mg/m2 plus 5FU 2000mg/m2 plus DL-folinic acid 500mg/m2 d1,8,15,22 qd36. The primary endpoint was response according to RECIST. Toxicity was reported according to NCI.CTC v2.0. Median follow-up is 18.1 (11.2–26.2) months. Results: From 8/02 until 10/03 we included 48 pts at 9 study centers: 9 women and 39 men; median age 62 ys, range 41–75. All pts had metastatic disease. Pts received a median of 4 (0–6) cycles. The mean cumulative dosage of oxaliplatin was 674 +/- 270mg/m2. Dose reductions of one or both agents (to <80% of initial doses) were reported in <10% of pts. 2/48 (4.2%) pts died within 60 days after inclusion: one septic diarrhea, one lethal stroke. Severe adverse events (grade 3/4) reported were: neutropenia 4 (8.3%), febrile neutropenia 2 (4.2%), anemia 2 (4.2%), diarrhea 8 (16.7%), nausea 3 (6.3%), emesis 1 (2.1%), fatigue 2 (4.2%), deep vein thrombosis 7 (14.6%), tumor bleeding 2 (4.2%), cardiac ischemia 1 (2.1%), pneumonia 1 (2.1%). Grade 1/2 sensory neuropathy was reported in 32 pts (66.7%) but no grade 3 neuropathy was noted. Intent-to-treat efficacy analysis showed a 54% response rate including 2 CR, 17% SD, 23% PD and 6% NE. Median survival is 11.4 months (95%CI 8.0–14.0). Median time to progression is 6.5 months (95%CI 3.9–9.9). Conclusions: The weekly FUFOX protocol shows notable activity in MGC. The schedule is well tolerated and compares favourably with the previously published biweekly FOLFOX-6 regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Peripheral airway function versus spirometry in childhood asthma
Authors: Sanna Kjellberg, Paul Robinson, Emilia Viklund, Maria Ström, Per Gustafsson
Journal: European Respiratory Journal (2011)

Background:  Tests of peripheral airway function are rarely used in clinical studies of paediatric asthma. The relationships between FEV1 and indices of small airway function from inert gas washout and impulse oscillometry have not been directly compared and are largely unknown.   Methods:  Scond and Sacin (inert gas indices of ventilation inhomogeneity in the conducting and acinar airway zones, respectively) were measured from mass spectrometer multiple breath SF6 washout. Frequency dependence of resistance (R5-R20Hz, a measure of small airway obstruction) was measured using impulse oscillometry (IOS). Both of these tests were performed prior to spirometry, both at baseline and post-bronchodilation (BD) (400 mcg salbutamol inhalation) in 58 subjects aged 8-18 yrs with stable asthma of mild to moderate severity. Reference values for Scond and Sacin were obtained from 45 healthy subjects and for R5-R20Hz from 169 age matched controls. Spirometric reference values were taken from Stanojevic et al 2009 [1]. Results were expressed as z-scores.   Results:  FEV1 was normal (z score >-1.96) in 48/58 (83%) at baseline and 58/58 (100%) subjects post-BD.In those subjects with normal FEV1 abnormal (z-score >1.96) R5-R20Hz, Scond and Sacin were found in 38/48 (79%), 26/47 (55%), and 5/47 (11%) at baseline and 18/58 (31%), 15/56 (27%) and 4/56 (7%) of subjects post BD, respectively.   Conclusions:  Peripheral airway dysfunction is common in school age asthmatics with normal FEV1. This abnormality persists in almost a third despite bronchodilation. The most sensitive indices to detect this peripheral abnormality are R5-R20Hz and Scond.   Reference:   1Stanojevic et al. Am J Respir Crit Care Med. 2009 Sep 15;180(6):547-52.
Abstract P198: Cumulative Abdominal Obese-Years and Arterial Stiffness in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Priya Palta, Michelle Snyder, Hirofumi Tanaka, David Aguilar, Sunil K Agarwal, Gerardo Heiss
Journal: Circulation (2014)

Introduction: Arterial stiffness quantifies subclinical cardiovascular disease (CVD) and is predictive of athero-thrombotic events and mortality. Time-cumulative measures of obesity may more accurately estimate the lifetime burden of CVD due to obesity by accounting for both duration and intensity. Compared to generalized obesity, abdominal obesity is more consistently associated with vascular outcomes and, specifically, arterial stiffness. We examined whether 20-year cumulative abdominal obese-years is associated with greater arterial stiffness in older adults. Methods: We analyzed 5,177 participants from the ARIC cohort. Cumulative abdominal obesity was defined as the product of waist circumference units above the conventional cutpoints for obesity, 88 cm for women and 102 cm for men, and the years of exposure to that waist circumference. This accounts for obesity exposure over 20 years from the five ARIC visits. Arterial stiffness was measured by pulse wave velocity (PWV) at the fifth ARIC visit. Measures of PWV obtained include: carotid-femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and segment-specific measures [heart-femoral (hfPWV) and femoral-ankle (faPWV)]. Multivariable linear regression, adjusted for age, sex, race, systolic blood pressure and smoking, was used to quantify the change in PWV (cm/s) per unit increase in cumulative abdominal obese-years. Subsidiary analyses examined visit five waist circumference. Hypertension and diabetes were explored as effect modifiers. Results: Among the 5,177 participants (mean age: 75, 43% male, 21% African-American), 66% had cumulative abdominal obese-years greater than zero (range: 1-1595), while 34% were not abdominally obese across any ARIC visit and thus had zero cumulative abdominal obese-years. Participants with higher cumulative abdominal obese-years were more often male, African-American and had a history of diabetes and hypertension. Cumulative abdominal obese-years were associated with lower baPWV (beta=-0.19, 95% CI: -0.23, -0.14), lower faPWV (beta=-0.12, 95% CI: -0.15, -0.09) and lower hfPWV (beta=-0.06, 95% CI: -0.10, -0.03). There was no significant association with cfPWV (beta=-0.03, 95% CI: -0.08, 0.01). The cross-sectional association between visit five abdominal circumference and PWV were similar in magnitude to cumulative abdominal obese-years. Hypertension and diabetes did not modify these associations. Conclusions: We observed an inverse association between cumulative exposure to abdominal fat and arterial stiffness in older adults. Survivor bias or the role of sarcopenia may explain these findings.The association of fat deposits with subclinical vascular disease in older adults deserves careful evaluation. Estimation of long-term exposure to abdominal obesity did not reveal associations with arterial stiffness beyond a cross-sectional assessment of abdominal obesity.