tbuckley/cabot-search huggingface dataset:
Detection and Viability of Colorectal Liver Metastases After Neoadjuvant Chemotherapy
Authors: Vincent Dunet, Nermin Halkic, John O. Prior, Anass Anaye, Reto A. Meuli, Christine Sempoux, Alban Denys, Sabine Schmidt
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to compare combined gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced and diffusion-weighted (DW) MRI with IV contrast-enhanced F-FDG PET/CT to detect and assess the viability of colorectal liver metastases (CLMs) after neoadjuvant chemotherapy (NAC).After NAC, 45 patients with CLMs were prospectively enrolled and underwent combined Gd-EOB-DTPA-enhanced and DW-MRI and contrast-enhanced F-FDG PET/CT. Forty patients subsequently underwent surgery based on intraoperative ultrasound, which served as the reference standard for the presence of CLMs. The number of metastases detected by each technique was then compared. In 69 resected metastases, the SUVmean and SUVmax, mean and maximum target-to-background ratio (TBR), total lesion glycolysis, metabolic tumor volume, and mean and minimum apparent diffusion coefficient (ADC) were examined to identify correlations with the corresponding tumor viability (TV) determined from histological specimens.Intraoperative ultrasound revealed 153 CLMs, 122 of which were resected. The detection rate of MRI and contrast-enhanced F-FDG PET/CT were similar (P = 0.61). The SUVmax and minimum ADC were negatively correlated (r = -0.34, P = 0.005) on preoperative imaging after NAC. However, TV was significantly correlated with the maximum TBR (r = 0.33, P = 0.006) and mean TBR (r = 0.37, P = 0.002), but not with the minimum ADC (r = -0.02, P = 0.9) or mean ADC (r = 0.01, P = 0.9).Combined Gd-EOB-DTPA-enhanced and DW-MRI and contrast-enhanced F-FDG PET/CT allow confident detection of CLMs, but only F-FDG PET metrics are associated with TV after NAC.
Restoration of CCAAT Enhancer Binding Protein Alpha P42 Overcomes Myeloid Differentiation Block and All-Trans Retinoic Acid Resistance in Human Acute Promyelocytic Leukemia NB4-R1 Cells
Authors: Limengmeng Wang, Haowen Xiao, Xing Zhang, Weichao Liao, Shan Fu, He Huang
Journal: Blood (2015)
The European Leukemia Net CML Registry - Objectives, Achievements and First Results.
Authors: Joerg Hasford, Gianantonio Rosti, Michele Baccarani, Rudiger Hehlmann, Joelle Guilhot, Phillippe Rousselot, Francisco Cervantes, Andrzej Hellmann, Juan L. Steegmann, Adriana Colita, Gertraud Markl, Markus Pfirrmann, Bengt Simonsson
Journal: Blood (2006)
The impact of the 21-gene assay in the Czech Republic on adjuvant chemotherapy (CT) recommendations and costs in estrogen receptor positive (ER+) early stage breast cancer (ESBC) patients with grade 2 tumors and risk factors
Authors: K. Petrakova, L. Petruzelka, M. Holanek, T. Svoboda, M. Palacova, Z. Bielcikova, Z. Zbozinkova
Journal: Annals of Oncology (2016)
A Successful Syngeneic Bone Marrow Transplant after an Ortotopic Liver Transplantation for Fulminant Hepatitis - Case Report.
Authors: Lucia Silla, Alessandra Paz, Claudia Astigarraga, Alethea Zago, Caroline Brum, Rosane Bittencourt, Laura Fogliatto, João R. Friederich, Denise Leugeur, Themis R. Silveira
Journal: Blood (2005)
Reduction of psoas muscle volume during chemotherapy for esophageal cancer may be a negative predictor of the outcome
Authors: Hideyuki Ohzawa, Kentaro Kurashina, Atsushi Miki, Yasunari Okuda, Misuzu Mori, Masuzu Ueda, Yoshinori Hosoya, Joji Kitayama, Naohiro Sata, Hirofumi Fujii
Journal: Annals of Oncology (2016)
MPTH-58. PEMETREXED: A POTENTIAL NEW THERAPEUTIC OPTION FOR THE TREATMENT OF THYMIDYLATE SYNTHASE (TS) NEGATIVE RECURRENT PRIMARY AND SYSTEMIC MALIGNANCIES WITH CNS METASTASIS
Authors: Lyndon Kim, Kevin Judy
Journal: Neuro-Oncology (2016)

Fluoropyrimidine analogues, 5FU, Capecitabine and Pemetrexate, inhibit thymidylate synthase and they have been widely used for the treatment of systemic malignancies. Capecitabine can penetrate CNS and has shown some efficacy in the treatment of breast cancers with CNS metastasis. The role of Pemetrexed in the treatment of recurrent primary and systemic malignancies with CNS metastsis is not known. We have treated 33 pts with previously heavily-treated recurrent primary and systemic malignancies with CNS metastasis based on the results of the molecular profiling. 16/33 pts were found to have TS-negative and 9/16 TS-negative patients were treated with Pemetrexed. MRI was performed every 2-3 months for tumor evaluation. Total pts: 9. M:F 5:4, Age: 48-88 yo. Median age 70.7 yo. Treatment period: 7/14 - 6/16. 1/1 GBM pt: SD for 4 mo. 1/2 anaplastic astrocytoma pts: SD for 4 mo. 1 Gr. II astrocytoma pt: SD for 7 mo. 2/2 meningioma pts: SD for 2 mo (still on treatment) and 4 mo. Both pts also received concurrent cisplatin based on ERCC1 and BRCA1 markers. 2/2 pts with squamous cell Ca of skin with skull base/brain metastasis: 1 PR for 24 mo, 1 SD for 18 mo respectively and still receiving treatment. 1 chordoma pt involving cervical/skull base: SD for 11 mo: still receiving treatment. Toxicities were very mild except 2 meningioma pts (Gr. 3-4) who also received cisplatin. Pemetrexed treatment for TS-negative recurrent primary and systemic malignancies with CNS metastasis demonstrated an excellent response rate of 89% (PR:1, SD:7, TP:1). Toxicities were minimal and tumor responses were durable. Particularly in the elderly population, in light of excellent toxicity profile, Pemetrexed should be considered as a part of the first treatment options for TS-negative CNS malignancies. A TS directed trial for pts with TS-negative recurrent CNS malignancies is warranted.
TMIC-20. STEM-CELL PHENOTYPE WITH DNA HYPOMETHYLATION IS INDUCED BY HYPOXIA IN GLIOBLASTOMA
Authors: Yasuo Iwadate, Tomoo Matsutani
Journal: Neuro-Oncology (2016)

Since the existence of necrosis is a hallmark of the diagnosis of glioblastoma, a hypoxic microenvironment may be a main cause of epithelial-mesenchymal transition (EMT) in glioblastoma (GBM). This biological process leads to an increased motility and a resistance to genotoxic insults. We examined the correlation between the methylation status of stem cell-related genes and the treatment outcomes in patients with glioblastoma (GBM) with special reference to the pseudopalisading necrosis. Tumor cells around necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor-β (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between groups of patients with high expression of TGF-β around necrosis and hypoxia inducible factor-1α(HIF-1α). The genomic DNAs in GBMs with high expression of TGF-β around necrosis and high HIF-1α were more hypomethylated than in other GBMs. Stem cell-related genes including ALPL and CD133 were also significantly hypomethylated in GBMs with high high expression of TGF-β around necrosis. Accumulation of stem cell properties due to aberrant DNA hypomethylation caused by hypoxia is associated with the refractory nature of GBM. Hypoxia is an important therapeutic target of GBM.
Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment
Authors: Amanda Vannitamby, Huei Jiunn Seow, Gary Anderson, Ross Vlahos, Michelle Thompson, Daniel Steinfort, Louis B Irving, Steven Bozinovski
Journal: Thorax (2017)

Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.
SURG-06. OUTCOMES OF SECOND SURGERY FOR RECURRENT GLIOBLASTOMA MULTIFORME: A RETROSPECTIVE CASE CONTROL STUDY
Authors: Alysson Wann, Patrick Tully, Liz Barnes, Zarnie Lwin, Lindy Jeffree, Kate Drummond, Hui Gan, Mustafa Khasraw
Journal: Neuro-Oncology (2016)

There is variable evidence on the effect of surgery for recurrent glioblastoma multiforme (GBM) on overall survival. Data on this has been marred with patient cohorts that were not exclusively with GBM and been staggered across three decades. There has also not been a case control approach to looking at this data. Retrospective data on all patients with recurrent GBM in two tertiary hospitals from Jan 2010 – Dec 2014 was collected. At each centre, non-resected patients were matched with resected patients on extent of resection and age, and a case-control matched study was conducted. Survival was assessed as from initial diagnosis (OS1) and from date of recurrence (OS2). Functional outcomes of patients post resection was also analysed. There were 60 patients in each cohort with a median age of diagnosis was 56.8 years. The most common location for tumour was the temporal location (n=49 at first resection, n=46 at second resection). Median progression free survival was 8.35m (95% CI: 7.2 - 9.6m). Median OS1: 14.17m (95% CI: 11.5 - 15.72m) versus 21.54m (95% CI 18 - 24.67m). There was a difference in OS2 of 4.9m (4.6 vs 9.5m). Surgery at recurrence correlated with a better OS2 outcome (p=<0.001, HR 0.523, 95% CI 0.378 - 0.724). Other factors such as chemo at recurrence had a positive impact on OS2 (HR 0.468, p=0.0284, 95% CI 0.237-0.923). Frontal lobe recurrence didn’t have an impact on OS2 (HR 0.815, p=0.4094, 95% CI 0.501-1.325). Post surgery; 78% didn’t require rehabilitation and 61% were independent with their mobility. Second surgery for recurrent GBM is beneficial with a survival advantage. There is also a survival advantage in having chemotherapy (with or without surgery) at recurrence. Outcomes post surgery was also promising. More studies are required in the era of improved surgical techniques and new anti-neoplastic therapies.
P09.37 Photodynamic therapy using Talaporfin sodium and semiconductor laser combined with maximum tumor resection improves prognosis of patients with glioblastoma
Authors: M. Nitta, Y. Muragaki
Journal: Neuro-Oncology (2017)

Photodynamic therapy (PDT) is a local therapy that utilizes biochemical reactions between photosensitizer, light and tissue oxygen. PDT using Talaporfin sodium has shown dramatic anti-tumor effects for various cancers including esophageal cancer. We have conducted a prospective phase II trial of PDT for malignant brain tumors between 2009 and 2012, and it was approved in 2013 in Japan. Since the approval, our institute has performed a prospective post-marketing surveillance study of PDT and we have treated 90 patients with malignant brain tumors. Here, we analyzed clinical results of this prospective study on PDT for glioblastoma patients. 41 patients (23 males and 18 females) with 16 newly diagnosed and 25 recurrent glioblastoma were treated with PDT between March 2009 and August 2015. A maximum resection of the enhanced lesion using intraoperative MRI was followed by PD laser irradiation of the cavity wall for 6 locations on average. Fractionated radiotherapy (60 Gy) and concomitant temozolomide chemotherapy were given for patients with newly diagnosed glioblastoma. The median PFS and OS were 19.6 and 31.5 months, respectively. Compared to other 76 patients with glioblastoma who underwent surgical resection in the same period in our institute, their median PFS and OS were 6.9 and 21.0 months, respectively. There was statistically significant difference in PFS between two groups (P=0.018, HR= 0.49), however there was no statistical significance in OS (P=0.08, HR=0.51), probably because of the small size of the PDT group. There was no significant adverse effect apparently related to PDT in any of the patients. Among 12 patients who recurred, only 5 (41.7%) showed local recurrence and the rest (58.3%) showed distant recurrence or dissemination, suggesting good local control by PDT. The median PFS and OS after PDT in patients with recurrent glioblastoma was 4.3 and 15.0 months, respectively. As conclusion, PDT appears to provide survival benefit for patients with both newly diagnosed and recurrent glioblastomas. A randomized clinical trial is justified and is under planning.
Molecular Remission to Imatinib in Patients with Chronic Myeloid Leukaemia (CML) Is Less Durable Compared to Patients after Allografting.
Authors: Thoralf Lange, Thomas Bumm, Marc Mueller, Sandra Otto, Haifa K. Al-Ali, Leanthe Grommisch, Scarlet Musiol, Christina Franke, Rainer Krahl, Dietger W. Niederwieser, Michael W. Deininger
Journal: Blood (2004)
Hematopoietic Progenitor Cell (HPC) Mobilization after Initial Therapy of Multiple Myeloma Including Velcade: Ability to Collect HPC as a Function of Velcade Dosing.
Authors: Michele Cottler-Fox, David Holley, Linda Whigham, Julie Stover, Erik Rasmussen, Maurizio Zangari, Guido Tricot, Barthel Barlogie
Journal: Blood (2004)
Endoscopic ultrasound-guided, through-the-needle forceps biopsy in the assessment of an incidental large pancreatic cystic lesion with prior inconclusive fine-needle aspiration
Authors: Alexander Huelsen, Caroline Cooper, Nivene Saad, Saurabh Gupta
Journal: Endoscopy (2017)

A 68-year-old man underwent endoscopic ultrasound (EUS) and fine-needle aspiration of a large cystic lesion of the pancreatic neck seen incidentally on computed tomography (CT). CT demonstrated a nonenhancing, exophytic, multilocular cystic mass, measuring 82 × 72 mm ([Fig. 1], [Video 1]). A mural calcific focus was noted posteroinferiorly and a more solid component posteriorly. The CT density averaged 19 HU for the cystic component and 40 HU for the solid component.
Modeling of pharmacokinetics, thrombocytopenia, plasma GDF-15 levels and tumor kinetics in response to treatment with the p53-HDM2 protein-protein interaction inhibitor NVP-CGM097
Authors: C. Meille, N. Guerreiro, S. Bauer, P. Cassier, G. Demetri, R. Dummer, D.S. Tan, L. Van Bree, T. Ramkumar, E. Halilovic, S. Jeay, A. Jullion, F. Hourcade-Potelleret, J.U. Wuerthner
Journal: Annals of Oncology (2016)
Paclitaxel plus carboplatin (PC) in patients with metastatic melanoma (MM): Experience in a single institution
Authors: C. Diaz Romero, N. Olvera, H. Martínez, J. Mtz Cedillo, M. Cuellar, R. Morales, M. Álvarez, B. Segura, J. De la Garza, P Aguilar
Journal: Journal of Clinical Oncology (2009)

e20019 Background: The number of agents active in patients with metastatic melanoma is limited and cure is not an objective for treatment at this stage, so that clinical benefit in these patients is the most important. The aim of the study was to evaluate the efficacy and safety of combination regimen consisting of paclitaxel and carboplatin as second-line chemotherapy, in patients with MM. Based on reports of responses to PC, 17 patients with MM was treated at the National Cancer Institute of Mexico. Methods: We evaluated retrospectively the combination of PC in patients with MM. Data regarding patient characteristics and outcomes were abstracted from medical records of NCI of Mexico from 01/05 to 12/08. The regimen was weekly paclitaxel (at a dose of 80 mg/m2) received on days 1, 8, and 15 of a 21-day cycle and carboplatin (AUC 5) on day 1. Response evaluation was using RECIST and toxicity was according to National Cancer Institute Common Toxicity Criteria. This study was approved by the hospital ethics committee. Results: Seventeen patients with MM were treated with PC. All patients were previously treated (and failed) with dacarbazine (DTIC). Sixteen were assessable for response with three cycles of chemotherapy and seventeen for toxicity. One patient was deemed to be ineligible because they presented severe hypersensitivity reaction to paclitaxel at beginning. Objective partial response were obtained in 4 patients (25%); 8 stable disease (50%) at least four months. No patient had a complete response to therapy. Progression disease was in 4 patients (25%). In 12 (75%) we noted clinical benefit. The median time to disease progression for the entire group was 4.2 months (range, 1–11 mos), with a median overall survival of 8.1 months (range, 5.6–10.5 mos). The toxicity grade 3 reported was thrombocytopenic in 2 patients (11%) and anemia in one patient (6%). Additional patients had reversible toxicities grade 3 including alopecia, nausea and fatigue; 2 of them presented moderate hypersensitivity reactions to paclitaxel. No toxic death was noted. Conclusions: The PC combination appears to be safety and well tolerated in second line chemotherapy in MM, however we need more patients to demonstrate a true clinical benefit, we outcomes are according with other clinical reports. No significant financial relationships to disclose.
Generation of Influenza HA-Specific Lymphocytes from Autologous Umbilical Cord Blood-Derived Dendritic Cells.
Authors: William K. Decker, Sufang Li, Dongxia Xing, Simon N. Robinson, Hong Yang, David Steiner, Catherine M. Bollard, Elizabeth J. Shpall, Amar Safdar
Journal: Blood (2007)
Transcription Factors and MicroRNAs Expression Profiles in Reticulocytes From Beta Thalassemia Intermedia and Sickle Cell Anemia Patients,
Authors: Regiane Ferreira, Marcos André Cavalcanti Bezerra, Fernanda Marconi Roversi, Dulcinéia Martins Albuquerque, Aderson S Araujo, Fernando Ferreira Costa
Journal: Blood (2011)
MPTH-48. INTER-INTERPRETER CONSISTENCY IN REVIEWING HISTOPATHOLOGY FROM PATIENTS WITH GLIOBLASTOMA AND RADIOGRAPHIC PROGRESSION FOLLOWING STANDARD RADIATION AND TEMOZOLOMIDE
Authors: Anna F. Piotrowski, Xiaobu Ye, Yao Lu, Roy Strowd, Shannon Seopaul, Fausto Rodriguez, Stuart A. Grossman, Peter Burger, Matthias Holdhoff
Journal: Neuro-Oncology (2016)

As clinical and imaging assessments are often insufficient to determine if glioblastoma patients after standard treatment have true progression versus pseudo-progression, surgery is frequently recommended to obtain tissue to answer this critical question. However, inter-interpreter consistency of pathologic interpretation in this setting has never been formally addressed. 101 neuropathologists from 50 NCI-designated Cancer Centers were identified, mailed a case scenario, and asked to review histologic sections. The scenario involved a patient who underwent surgery within one year of diagnosis for progressive symptoms and imaging changes. Tissue sections were provided from 13 different cases. Neuropathologic evaluations requested the (1) percent active tumor, (2) percent treatment effect, (3) degree of cellularity, (4) degree of mitotic activity, and (5) overall assessment of disease activity (‘active tumor’ vs. ‘pseudo-progression’ vs. ‘unable to classify’). Fleiss’ kappa statistics were assessed for inter-interpreter consistency among all readers. The patterns of pathologists’ readings per patient case were also characterized. Responses were received from 48 pathologists (48%) at 30 centers (44 were neuropathologists). The kappa score for agreement in overall assessment of disease activity was 0.228 (95% CI: 0.22-0.24), which indicates marginal agreement. Percentages of maximum agreement in pathology assessment among the 13 cases ranged from 36%-98%. The pathology reading diversity in the overall assessment of disease activity (5) was highly consistent with the pathology reading diversity on percent active tumor (1) and percent treatment effect (2) with p=0.03 and 0.001, respectively. However, it was less consistent with cellularity (3) and mitotic activity (4). These data demonstrate marginal inter-interpreter consistency when experienced neuropathologists review the same images with an identical clinical scenario. This study strongly suggests that efforts to standardize pathologic interpretation in patients with glioblastoma with progressive imaging abnormalities post-therapy are critical to improving patient care and conduct of clinical research.
Phylodynamic Inference across Epidemic Scales
Authors: Erik M. Volz, Ethan Romero-Severson, Thomas Leitner
Journal: Molecular Biology and Evolution (2017)

Within-host genetic diversity and large transmission bottlenecks confound phylodynamic inference of epidemiological dynamics. Conventional phylodynamic approaches assume that nodes in a time-scaled pathogen phylogeny correspond closely to the time of transmission between hosts that are ancestral to the sample. However, when hosts harbor diverse pathogen populations, node times can substantially pre-date infection times. Imperfect bottlenecks can cause lineages sampled in different individuals to coalesce in unexpected patterns. To address realistic violations of standard phylodynamic assumptions we developed a new inference approach based on a multi-scale coalescent model, accounting for nonlinear epidemiological dynamics, heterogeneous sampling through time, non-negligible genetic diversity of pathogens within hosts, and imperfect transmission bottlenecks. We apply this method to HIV-1 and Ebola virus (EBOV) outbreak sequence data, illustrating how and when conventional phylodynamic inference may give misleading results. Within-host diversity of HIV-1 causes substantial upwards bias in the number of infected hosts using conventional coalescent models, but estimates using the multi-scale model have greater consistency with reported number of diagnoses through time. In contrast, we find that within-host diversity of EBOV has little influence on estimated numbers of infected hosts or reproduction numbers, and estimates are highly consistent with the reported number of diagnoses through time. The multi-scale coalescent also enables estimation of within-host effective population size using single sequences from a random sample of patients. We find within-host population genetic diversity of HIV-1 p17 to be 2Nμ=0.012 (95% CI 0.0066–0.023), which is lower than estimates based on HIV envelope serial sequencing of individual patients.
MLN4924, a Novel Investigational NEDD8 Activating Enzyme Inhibitor, Exhibits Preclinical Activity In Multiple Myeloma and Waldenström's Macroglobulinemia through Mechanism Distinct From Existing Proteasome Inhibitors
Authors: Douglas W. McMillin, Zachary Hunter, Jake Delmore, Val Monrose, Peter G Smith, Ann Birner, Paul G Richardson, Kenneth C. Anderson, Steven P. Treon, Andrew L. Kung, Constantine S. Mitsiades
Journal: Blood (2010)