tbuckley/cabot-search huggingface dataset:
Association of hypersensitivity reactions to oxaliplatin with cumulative dose of oxaliplatin.
Authors: M. Saito, T. Yoshino, Y. Kawamoto, H. Bando, Y. Arimura, N. Fuse, M. Tahara, T. Doi, A. Ohtsu
Journal: Journal of Clinical Oncology (2011)

584 Background: The incidence of hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) in colorectal cancer patients (CRC) receiving the 5-fluorouracil/leucovorin plus L-OHP (FOLFOX) regimen is reported to be 10 to 17%. There are several reports of clinical features of HSRs to L-OHP, but the relationship between HSRs and the cumulative dose of L-OHP has not been clarified. Methods: From August 2005 to July 2009, a total of 54 CRC patients who developed HSRs during treatment with mFOLFOX6 or mFOLFOX6 plus bevacizumab regimen as first-line treatment, were reviewed retrospectively. Within this patient group, sixteen patients had an L-OHP-free interval of at least three months or more. We investigated the clinical features of HSRs associated with L-OHP in our institution, and evaluated the degree to which its occurrence is dependent upon the cumulative dose of L-OHP in patients who had an interruption of L-OHP. Results: Within the sample of 54 patients, HSRs occurred after a median treatment course number of 8 (range 2-19), and the median cumulative dose of L-OHP being 700 mg/m 2 (range 170-1615). In these subjects, grade1/2/3 HSRs developed in 33/20/1 patients, respectively. Re-challenge of L-OHP combined with prophylactic agents was performed in 42 patients (78%). There were 16 patients who had an L-OHP- free interval, in whom the major reason for L-OHP withdrawal was neurotoxicity, with reintroduction because of tumor progression or recurrence. Of these 16 patients, 10 developed the first HSRs after reintroduction of L-OHP. Among these 10 patients, grade1/2/3 HSRs developed in 6/3/1 patients, respectively, and occurred at a median course number of 2.5 following re-infusion of L-OHP, or 12 treatments after the initial infusion. The median cumulative dose of L-OHP at HSRs in this patient group was 213 mg/m 2 after the re-introduced infusion, and a total of 1088 mg/m 2 since initial onset of treatment. Conclusions: Our results suggest that the development of HSRs during L-OHP treatment depends on the cumulative dose from the initial administration even in patients who experienced an L-OHP-free interval. No significant financial relationships to disclose.
Conversion of external percutaneous transhepatic biliary drainage to endoscopic ultrasound-guided hepaticogastrostomy after failed standard internal stenting for malignant biliary obstruction
Authors: Woo Paik, Nah Lee, Yousuke Nakai, Hiroyuki Isayama, Dongwook Oh, Tae Song, Sang Lee, Dong-Wan Seo, Sung Lee, Myung-Hwan Kim, Do Park
Journal: Endoscopy (2017)

Abstract Background and study aim Percutaneous transhepatic biliary drainage (PTBD) is a rescue procedure after a failed endoscopic retrograde cholangiopancreatography. As PTBD causes patient discomfort, conversion of the PTBD to internal biliary stenting (PTBDS) may be required; however, PTBDS is sometimes difficult because of the tight stricture. We evaluated the efficacy and safety of conversion of external PTBD to endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) after failed PTBDS. Patients and methods A total of 16 patients with malignant distal biliary obstruction who underwent conversion of external PTBD to EUS-HGS after failed PTBDS were enrolled from two institutions in Korea and Japan. Data were analyzed retrospectively. Results The technical and clinical success rates were 100 % and 81 %, respectively. Early adverse events developed in two patients: proximal stent migration (n = 1), and cholecystitis (n = 1). Stents were occluded or migrated distally in five patients. The mean duration of stent patency was 402 days. Conclusions Conversion of external PTBD to EUS-HGS may be a good rescue option after failed PTBDS.
Circulating vascular endothelial growth factor (VEGF) as prognostic factor of progression-free survival in patients with advanced chordoma receiving sorafenib: An analysis from a phase II trial of the French Sarcoma Group (GSF/GETO)
Authors: L. Lebellec, F. Bertucci, E. Tresch-Bruneel, E. Bompas, Y. Toiron, L. Camoin, O. Mir, V. Laurence, S. Clisant, E. Decoupigny, J.-Y. Blay, A. Gonçalves, N. Penel
Journal: Annals of Oncology (2016)
MYC Protein Expression, but Not High Grade Morphology, Is Associated with Poor Outcome in Non-Burkitt Diffuse Aggressive B-Cell Lymphomas: A SWOG S9704 Correlative Study
Authors: James R. Cook, Bryan H. Goldman, Raymond R. Tubbs, Michael LeBlanc, Lisa M. Rimsza, Patrick Stiff, Richard I Fisher
Journal: Blood (2012)
P11.01 Patient-reported outcome measures in meningioma research - lack of the patients perspective
Authors: A. H. Zamanipoor Najafabadi, L. Dirven, M. L. D. Broekman, W. C. Peul, M. J. B. Taphoorn, W. R. van Furth
Journal: Neuro-Oncology (2016)

AbstractBackground:A vast number of generic and disease specific questionnaires are used to measure health-related quality of life (HRQoL) in meningioma research. We aimed to assess the relevance of issues mentioned in these questionnaires and to compare the patient’s perspective with the perspective of the health care professional (HCP) on meningioma-related symptoms and problems.Methods:A systematic literature search was conducted to identify all HRQoL items and questionnaires. Both patients and HCPs had to rate the relevance of each item on a 4-point Likert scale (ranging from ‘not at all’ to ‘very much’): items were relevant when ≥ 30% of patients or HCPs scored the items as relevant. For each questionnaire the percentage of relevant items was assessed. All identified items were categorized into different domains of HRQoL, which were discussed in semi-structured interviews with both groups. The aim of these interviews was to reveal all issues of meningioma patients, including issues not present in the existing questionnaires.Results:Included in this study were 14 patients (mean age 56 years, 71% female) and 7 HCPs (2 neurosurgeons, 2 neurologists, 2 radiotherapists, 1 rehabilitation specialist, mean experience 15 years). Fourteen different questionnaires were found in the literature, including 140 unique issues. Patients and HCPs considered 25–60% and 90–100% of the items of each questionnaire as relevant, respectively. When comparing the 12 most relevant issues as assessed by meningioma patients and HCPs, only 5 issues were the same. Issues missing in the already existing questionnaires were mostly issues in the psychological and cognitive domains (e.g. multitasking and stress-management).Conclusion:Existing HRQoL questionnaires do not fully cover the problems of meningioma patients. Patients and HCPs differ in opinion what the most relevant issues are of meningioma patients. Both findings support the need to develop and validate an HRQoL questionnaire specific for meningioma patients.
Prognostic impact of tumor-infiltrating lymphocytes (TILs) in male breast cancer
Authors: S. Abdeljaoued, I. Bettaieb, O. Adouni, A. Goucha, O. El Amine, A. Chabchoub, H. Bouzaiene, J. Ben Hassouna, R. Makhlouf, T. Ben Dhiab, H. Boussen, K. Rahal, A. Gamoudi
Journal: Annals of Oncology (2016)
Prognostic factors and survival in germ cell cancer (GCC) patients treated with bleomycin, etoposide, and cisplatin (BEP): A population-based study
Authors: M.G.G. Kier, J. Lauritsen, M.S. Mortensen, M. Bandak, K.K. Andersen, M.K. Hansen, M. Agerbaek, N.V. Holm, S.O. Dalton, C. Johansen, G. Daugaard
Journal: Annals of Oncology (2016)
Coagulation Factors in Therapeutic Apheresis Plasma Held for 18 Hours at Ambient Temperature Prior to Pathogen Inactivation (INTERCEPT™).
Authors: Jean-Pierre Cazenave, Hervé Isola, Marie-Louise Wiesel, Daniel Kientz, Michel Laforêt, Marc Slaedts, Linda Pinkoski, Yasmin Singh, Laurence Corash
Journal: Blood (2006)
Gemcitabine and pegylated liposomal doxorubicin as salvage therapy in metastatic breast cancer (MBC)
Authors: M. Ghosn, F. El Karak, J. Kattan, F. Farhat, F. Nasr, F. Younes, G. Chahine
Journal: Journal of Clinical Oncology (2006)

10645 Background: Doxorubicin and Taxanes are the most used drugs in front-line therapy for MBC. Patients with progressive disease refractory to these drugs are candidate to different salvage regimens. We investigated the combination of gemcitabine and pegylated liposomal doxorubicin as salvage option for these patients. Methods: This phase II study included gemcitabine (Gemzar) 1000 mg/m 2 day 1, day 8 and pegylated liposomal doxorubicin (Caelyx) 25 mg/ m 2 day 1 every 21 days. Inclusion criteria included measurable disease, performance status &lt;2 according to the Zubrod scale, and no prior Gemzar or Caelyx treatment. Patients had to have one line of chemotherapy for metastatic disease. Responses were evaluated according to the RECIST criteria. Study Objectives were response rate, time to progression, and toxicity profile. Results: Between March 2003 and September 2005, 30 patients were enrolled. Mean age was 54 years [32–72]. 22 patients had two or more metastatic sites. Mean metastatic sites were liver (17), bone (12), lung (10) and pleura (5). 26 patients have had prior taxane treatment, and 21 prior anthracyclines. 144 cycles were delivered with a median of 6 per patient. There were 13 partial response, 11 stable disease, 5 progression and 1 unknown. Overall response rate was 43% with median response duration of 7 months (4–20+). 12 among the 13 objective responses were noted at visceral sites. During follow-up, 14 patients died. Median Survival time was 7 months. Median Time to progression was 7 months [0.5–20+]. The most encountered grade 3 or 4 toxicities were anemia in 5 pts, thrombopenia in one pt, neutropenia in 7 pts, neutropenic fever in 2 pts, hand-foot syndrome in 4 pts and stomatitis in 3 pts. No cardiotoxicity was noted. Conclusion: Salvage therapy for MBC could be successfully achieved by the combination of Gemcitabine and Pegylated liposomal doxorubicin (43% OR) according to our schedule. The tolerability was also acceptable. This schedule warrants further investigation. No significant financial relationships to disclose.
PDTB-06. SUPPRESSION OF MOLECULAR CIRCUIT OF MULTI-CILIATE DIFFERENTIATION IS CRITICAL FOR CHOROID PLEXUS CARCINOMA DEVELOPMENT
Authors: Haotian Zhao, Li Li
Journal: Neuro-Oncology (2016)

Choroid plexus (CP) tumors are rare primary brain tumors predominantly found in children. While surgery is the primary treatment for the mostly benign CP papilloma, safer and more effective therapies are yet established for CP carcinomas which are frequently lethal. Multiple factors such as TP53 mutations, abnormal NOTCH signaling, receurrent genomic and epigenetic alterations have been described in CP carcinomas. Accurate preclinical models that recapitulate human diseases are of vital importance to understand underlying mechanims of CP tumors and to evaluate potential therapeutics. We showed that sustained Notch1 expression or constitutive Sonic Hedgehog (Shh) signaling drives the formation of CP papilloma. Vertebrate Shh signaling depends on the primary cilium. Unlike CP epithelial cells which possess multiple primary cilia, tumor cells in our animal models are characterized elevated Notch pathway activities and a solitary primary cilium that uniquely mediates pro-proliferative Shh signaling, suggesting a synergistic interaction where Notch-mediated suppression of multi-ciliate differentiation allows Shh-driven proliferation of CP tumor cells. Indeed, constitutive activation of both pathways leads to aggressive CP carcinoma in mice. Molecular and histology analyses revealed that these murine CP tumors closely resemble their human counterparts, which also display aberrant SHH and NOTCH signaling, suggesting they may represent potential therapeutic avenues. Consistently, treatment with vismodegib, an ­FDA-approved Shh pathway inhibitor, suppressed CP tumor growth. Importantly, most human CP tumors, especially aggressive papillomas and carcinomas, consist of tumor cells with a solitary primary cilium. CP tumors in mice and humans exhibit a distinct repression of a conserved molecular circuit of multi-ciliate differentiation shown to be sensitive to inhibition by Notch. Together, these results indicate that maintenance of a solitary primary cilium is crucial for CP tumor development, whereas formation of multiple cilia subsequent to Notch inhibition has tumor suppressive functions and represents a novel therapeutic target in CP tumors.
The Histone Methyltransferase DOT1L Promotes Neuroblastoma by Regulating Gene Transcription
Authors: Matthew Wong, Andrew E.L. Tee, Giorgio Milazzo, Jessica L. Bell, Rebecca C. Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Hüttelmaier, Jason W.H. Wong, Jenny Wang, Patsie Polly, Giovanni Perini, Christopher J. Scarlett, Tao Liu
Journal: Cancer Research (2017)

Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyzes H3K79 methylation. Here, we show that N-Myc upregulates DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2 DOT1L bound to the Myc Box II domain of N-Myc protein, and knockdown of DOT1L reduced histone H3K79 methylation and N-Myc protein binding at the ODC1 and E2F2 gene promoters and reduced neuroblastoma cell proliferation. Treatment with the small-molecule DOT1L inhibitor SGC0946 reduced H3K79 methylation and proliferation of MYCN gene-amplified neuroblastoma cells. In mice xenografts of neuroblastoma cells stably expressing doxycycline-inducible DOT1L shRNA, ablating DOT1L expression with doxycycline significantly reduced ODC1 and E2F2 expression, reduced tumor progression, and improved overall survival. In addition, high levels of DOT1L gene expression in human neuroblastoma tissues correlated with high levels of MYCN, ODC1, and E2F2 gene expression and independently correlated with poor patient survival. Taken together, our results identify DOT1L as a novel cofactor in N-Myc-mediated transcriptional activation of target genes and neuroblastoma oncogenesis. Furthermore, they characterize DOT1L inhibitors as novel anticancer agents against MYCN-amplified neuroblastoma. Cancer Res; 77(9); 2522-33. ©2017 AACR.
First-in-human study of AC0010, a novel irreversible, mutant-selective EGFR inhibitor in patients with 1st generation EGFR TKI-resistant non-small cell lung cancer (NSCLC)
Authors: L. Zhang, H. Zhao, B. Hu, J. Jiang, X. Zheng, Y. Zhang, Y. Ma, J. Ge, B. Zou, X. Fang, W. Xu, X. Xu
Journal: Annals of Oncology (2016)
Updated Results of a Phase I Study of Flavopiridol in Acute Leukemias Using a Novel, Pharmacokinetically Derived Schedule: Clinical Activity Including Hyperacute Tumor Lysis Syndrome (TLS), Pharmacokinetics (PK), and Pharmacodynamics (PD).
Authors: William Blum, Rebecca B. Klisovic, Cheryl Kefauver, Amy Johnson, Mitch Phelps, James T. Dalton, David Lucas, LeNguyen Huynh, Shujun Liu, Michael R. Grever, A.D. Colevas, Guido Marcucci, John C. Byrd
Journal: Blood (2006)
OS5.2 Health-Related Quality of Life (HRQoL) in patients with progressive glioblastoma treated with combined bevacizumab and lomustine versus lomustine only (randomized phase III EORTC study 26101)
Authors: M. J. B. Taphoorn, A. Bottomley, C. Coens, J. C. Reijneveld, T. Gorlia, A. A. Brandes, J. Domont, A. Idbaih, M. J. van den Bent, W. Wick
Journal: Neuro-Oncology (2016)
Early Performance in Medicaid Accountable Care Organizations
Authors: K. John McConnell, Stephanie Renfro, Benjamin K. S. Chan, Thomas H. A. Meath, Aaron Mendelson, Deborah Cohen, Jeanette Waxmonsky, Dennis McCarty, Neal Wallace, Richard C. Lindrooth
Journal: JAMA Internal Medicine (2017)

Several state Medicaid reforms are under way, but the relative performance of different approaches is unclear.To compare the performance of Oregon's and Colorado's Medicaid Accountable Care Organization (ACO) models.Oregon initiated its Medicaid transformation in 2012, supported by a $1.9 billion investment from the federal government, moving most Medicaid enrollees into 16 Coordinated Care Organizations, which managed care within a global budget. Colorado initiated its Medicaid Accountable Care Collaborative in 2011, creating 7 Regional Care Collaborative Organizations that received funding to coordinate care with providers and connect Medicaid enrollees with community services. Data spanning July 1, 2010, through December 31, 2014 (18 months before intervention and 24 months after intervention, treating 2012 as a transition year) were analyzed for 452 371 Oregon and 330 511 Colorado Medicaid enrollees, assessing changes in outcomes using difference-in-differences analyses of regional focus, primary care homes, and care coordination. Oregon's Coordinated Care Organization model was more comprehensive in its reform goals and in the imposition of downside financial risk.Regional focus, primary care homes, and care coordination in Medicaid ACOs.Performance on claims-based measures of standardized expenditures and utilization for selected services, access, preventable hospitalizations, and appropriateness of care.In a total of 782 882 Medicaid enrollees, 45.0% were male, with mean (SD) age 16.74 (14.41) years. Standardized expenditures for selected services declined in both states during the 2010-2014 period, but these decreases were not significantly different between the 2 states. Oregon's model was associated with reductions in emergency department visits (-6.28 per 1000 beneficiary-months; 95% CI, -10.51 to -2.05) and primary care visits (-15.09 visits per 1000 beneficiary-months; 95% CI, -26.57 to -3.61), improvements in acute preventable hospital admissions (-1.01 admissions per 1000 beneficiary-months; 95% CI, -1.61 to -0.42), 3 of 4 measures of access (well-child visits, ages 3-6 years, 2.69%; 95% CI, 1.20% to 4.19%; adolescent well-care visits, 6.77%; 95% CI, 5.22% to 8.32%; and adult access to preventive ambulatory care, 1.26%; 95% CI, 0.28% to 2.25%), and 1 of 4 measures of appropriateness of care (avoidance of head imaging for uncomplicated headache, 2.59%; 95% CI, 1.35% to 3.83%).Two years into implementation, Oregon's and Colorado's Medicaid ACO models exhibited similar performance on standardized expenditures for selected services. Oregon's model, marked by a large federal investment and movement to global budgets, was associated with improvements in some measures of utilization, access, and quality, but Colorado's model paralleled Oregon's on several other metrics.
Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group retrospective analysis
Authors: A. Kollar, R.L. Jones, S. Stacchiotti, H. Gelderblom, M. Guida, P. Boccone, N. Steeghs, A. Safwat, D. Katz, F. Duffaud, S. Sleijfer, W. van sder Graaf, N. Touati, S. Litière, S. Marreaud, A. Gronchi, B. Kasper
Journal: Annals of Oncology (2016)
Specific cutaneous infiltrates in children with acute lymphoblastic leukemia or lymphoblastic lymphoma
Authors: F Millot, A Robert, Y Bertrand, F Mechinaud, Genevieve Laureys, A Ferster, P Brock, P Rorlich, F Mazingue, D Plantz, H Pacquement, C Behar, X Rialland, Jm Chantraine, E Tokaji, F Guilhot
Journal: Blood (1995)
A prognostic model using inflammatory response markers in metastatic gastric cancer (GC) pts before first-line chemotherapy
Authors: A. Petrillo, M.M. Laterza, J. Ventriglia, B. Savastano, G. Tirino, L. Pompella, A. Diana, E. Martinelli, F. Morgillo, M. Orditura, F. Ciardello, F. De Vita
Journal: Annals of Oncology (2016)
Changing trends in HIV and cancer
Authors: A. Fernández Ruiz, R. Lastra del Prado, P. Iranzo Gomez, A. Rodrigo, A. Callejo Perez, E. Quilez Bielsa, M. Cruellas Lapeña, M.J. Crusells Canales, A. Yubero Esteban, N. Galan Cerrato, J.J. Lambea Sorrosal, L. Murillo Jaso, R. Andres Conejero, P. Escudero Emperador, E. Pujol Obis, A. Saenz Cusi, D. Isla Casado
Journal: Annals of Oncology (2016)
DDIS-15. SPECIFIC SPHINGOSINE KINASE 1 INHIBITORS FOR MALIGNANT GLIOMA TREATMENT
Authors: Sang Lee, Jeremy Hengst
Journal: Neuro-Oncology (2016)

Gliomas account for 28% of all primary brain and central nervous system tumors, and 80% of gliomas are malignant. Among the sphingolipid metabolic enzymes, sphingosine kinase 1 (SK1) is a key regulator of the sphingolipid metabolism and is up-regulated in malignant glioma, glioblastoma multiforme (GBM). Elevated expression of SK1 correlates with poor survival in GBM patients. We hypothesize that SK1-selective inhibitors can be a therapeutic option for malignant brain tumors. We determined the cytotoxicity and cell death mechanisms of two SK1 selective inhibitors (SKI) on the human brain tumor cells in in vitro. We also evaluated whether SKI have anti-tumor effects in orthotopic nude mouse brain tumor models. The two SK1 inhibitors (SKI-178, SKI-349) are selective SK1 inhibitors. In the in-vitro SK1 activity assay, SKI-349 (IC50 ≈2μM) is more potent towards SK1 than SKI-178 (IC50 ≈35 μM). SKI-349 showed almost 10 fold lower LC50 (50% cell growth inhibition concentration) to the GBM cell lines and GBM stem cells than SKI-178 (4-74 nM vs 272-506 nM). There are combination effect of SKI and Temozolomide on GBM and GBM stem cells. SKI-349 dose dependently induced apoptosis and an accumulation of cells in mitosis in GBM stem cells. These results suggest that SKI could potentially be efficacious in mouse models of GBM. However, SKI-349 did not significantly affect the average survival time for tumor-bearing mice relative to the vehicle treated control group. The lack of therapeutic efficacy suggests that SKI-349 is not able to cross the blood-brain-barrier (BBB) given the efficacy of SKI-349 in xenograft models of other cancer types. Together, these studies suggest that SKI-349 would not be an effective therapy for GBM in its current state. Future studies will be to overcome the BBB permeability of SKI-349 by conjugation of SKI-349 to carrier molecules capable of crossing the BBB.
Radiation Resistance in KRAS-Mutated Lung Cancer Is Enabled by Stem-like Properties Mediated by an Osteopontin–EGFR Pathway
Authors: Meng Wang, Jing Han, Lynnette Marcar, Josh Black, Qi Liu, Xiangyong Li, Kshithija Nagulapalli, Lecia V. Sequist, Raymond H. Mak, Cyril H. Benes, Theodore S. Hong, Kristin Gurtner, Mechthild Krause, Michael Baumann, Jing X. Kang, Johnathan R. Whetstine, Henning Willers
Journal: Cancer Research (2017)

Lung cancers with activating KRAS mutations are characterized by treatment resistance and poor prognosis. In particular, the basis for their resistance to radiation therapy is poorly understood. Here, we describe a radiation resistance phenotype conferred by a stem-like subpopulation characterized by mitosis-like condensed chromatin (MLCC), high CD133 expression, invasive potential, and tumor-initiating properties. Mechanistic investigations defined a pathway involving osteopontin and the EGFR in promoting this phenotype. Osteopontin/EGFR-dependent MLCC protected cells against radiation-induced DNA double-strand breaks and repressed putative negative regulators of stem-like properties, such as CRMP1 and BIM. The MLCC-positive phenotype defined a subset of KRAS-mutated lung cancers that were enriched for co-occurring genomic alterations in TP53 and CDKN2A. Our results illuminate the basis for the radiation resistance of KRAS-mutated lung cancers, with possible implications for prognostic and therapeutic strategies. Cancer Res; 77(8); 2018-28. ©2017 AACR.