tbuckley/cabot-search huggingface dataset:
Impact of <i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (G) vs gemcitabine alone on Karnofsky performance status (KPS) in metastatic pancreatic cancer.
Authors: E. Gabriela Chiorean, Yin Wan, Scott Whiting, Louis Kayitalire, Marc Botteman, Xiang Ji
Journal: Journal of Clinical Oncology (2015)

e15275 Background: A randomized phase III clinical trial (MPACT) found that the addition of nab-P to G significantly increased response rate and survival. This analysis sought to determine whether the addition of nab-P also affected KPS, a performance status metric that has been used historically to help measure clinical benefit (Rothenberg et al, Ann Oncol 1996;7(4)) and is correlated with quality of life (eg, Schag et al, Qual Life Res 1994;3(2)). Methods: The main outcome measure was the difference between treatment arms in cumulative change over time from baseline in age- and sex-adjusted KPS scores (with 0 = death and 100 = normal), estimated using a generalized linear model with 95% CIs obtained via bootstrapping. Missing values between observed KPS scores were imputed using the midpoint of the last and next observed values. The impact of this imputation method was tested via a sensitivity analysis, wherein the last observation carried forward (LOCF) method was used instead. Death (KPS = 0) was carried forward to the end of follow-up. Separately, a mixed-effect model was applied to 1 year of follow-up data (without any imputation) to examine the impact of time on KPS change across treatments. Results: Baseline KPS scores were 87.1 and 86.7 for patients receiving G (n = 428) and nab-P + G (n = 429), respectively. Patients on nab-P + G had a lower cumulative reduction from baseline in KPS score than those on G at every time point. This difference became significant between 100 and 200 days after starting the treatments (mean difference, 95% CI, by day 100: 2.9 [−0.1-5.7]; by day 200: 5.7 [2.2-9.1]) and remained significant thereafter. By day 400, the cumulative difference reached 6.9 (95% CI, 3.2-10.6) and remained stable thereafter. The LOCF method yielded similar results. The mixed-effect model showed that patients on nab-P + G experienced less KPS degradation per month than patients on G alone (ie, the rate of decline in KPS score for nab-P + G patients was, on average, 3 points [P < 0.001] less per month than that for G patients). Conclusions: The addition of nab-P to G results in significantly better performance scores than G alone in patients with metastatic pancreatic cancer. Clinical trial information: NCT00844649.
Gene Expression Changes in CD34+ Cells Precede Development of Therapy-Related Leukemia (t-MDS/AML) After Autologous Hematopoietic Cell Transplantation (aHCT) for Hodgkin (HL) or Non-Hodgkin Lymphoma (NHL).
Authors: Liang Li, Min Li, Can-Lan Sun, Melanie D. Sabado, Liton Francisco, Tinisha McDonald, Karen L. Chang, Shirong Wang, Jerald Radich, Lue Ping Zhao, Stephen J. Forman, Smita Bhatia, Ravi Bhatia
Journal: Blood (2009)
Relationship between HER-2 amplification and tumor infiltrating lymphocytes in breast cancer patients treated with neoadjuvant trastuzumab
Authors: C. Masini, G. Bisagni, M. Ragazzi, A. Bisagni, K. Dallaglio, G. Falco, G. Ferrari, C. Bassano, G. Gardini, A. Bologna, G. Moretti, C. Boni, L. Baldi, C. Pinto
Journal: Annals of Oncology (2016)
CSIG-29. CELL EXTRINSIC REGULATION OF OLIG2-MEDIATED GLIOMA INVASION
Authors: Laura Belmont, Shiv Singh, Emily Szeto, Jennifer Eschbacher, Nader Sanai, Shwetal Mehta
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is the most aggressive, infiltrative, and lethal brain tumor in adults with high mortality rates. GBM patients have an overall survival of <1 year, despite major research efforts in diagnosis and treatment. The poor survival is attributed to their highly invasive nature and resistance to conventional therapies. Hence, the tumors almost always recur, and there is no standard-of-care for recurrent GBM. In glioblastoma, it has been proposed that migrating tumor cells undergo a switch from proliferation to invasion. However, the molecular mechanism involved in the regulation of this switch from proliferation to invasion/migration in GBM is poorly understood. We have recently shown a novel role for lineage-specific transcription factor, Olig2 in promoting glioma invasion. We found that glioma cells expressing low levels of phosphorylated OLIG2 (pOLIG2low) are highly invasive while those with high pOLIG2 (pOLIG2high) are less invasive but proliferate at higher rate. In addition, modulating the phosphorylation status of OLIG2 was sufficient to switch the cellular phenotype from invasive to proliferative. Here, we demonstrate how cell intrinsic factors determine OLIG2 phosphorylation levels and cell extrinsic factors that can trigger dephosphorylation of OLIG2 and lead to invasion. We have employed patient-derived xenograft models and short-term glioma stem-like cultures to address how signals from the surrounding tumor cells and the microenvironment can induce a switch in glioma cells from proliferation to invasion.
Primed for Death: Hypoxia Sensitizes Primary CLL Cells towards Compounds Targeting Mitochondrial Integrity
Authors: Lukas P. Frenzel, Malte Huelsemann, Julia Claasen, Reinhild Brinker, Sebastian Theurich, Hans Jiro Becker, Michael S. von Bergwelt-Baildon, Christian P. Pallasch, Michael Hallek, Clemens Wendtner
Journal: Blood (2011)
Circulating tumor cell number predicts time to progression (TTP) in patients with heavily pretreated gynecological cancers treated with selinexor (SEL)
Authors: M. Crochiere, I.B. Vergote, B. Lund, H. Havsteen, Z. Ujmajuridze, E. Van Nieuwenhuysen, C. Haslund, T. Juhler-Nøttrup, M. Mau-Sørensen, P. Berteloot, A. Kranich, J. Meade, G. Wright, E. Shacham, T. Rashal, J.-R. Saint-Martin, S. Shacham, M. Kauffman, M. Raza Mirza, Y. Landesman
Journal: Annals of Oncology (2016)
PP52. RAMAN SPECTROSCOPY FOR THE IDENTIFICATION OF ISOCITRATE DEHYDROGENASE (IDH) MUTATED GLIOBLASTOMAS
Authors: Mr James Livermore, Dr Katherine Lau, Mr Connor Scott, Mr Puneet Plaha, Prof Claire Vallance, Prof Olaf Ansorge
Journal: Neuro-Oncology (2017)

INTRODUCTION: Raman spectroscopy is an emerging biophotonic tool for the identification of disease. By probing the unique molecular vibrations that depend on the composition and structure of samples, it provides a wealth of information on a cellular and molecular level of both solid and liquid specimens without the use of external agents such as dyes, stains or radioactive labels. Glioblastomas can be stratified by the presence or absence of mutations in isocitrate dehydrogenase (IDH) 1 or 2. Determination of IDH status is critical for histological diagnosis and clinical decision-making with evidence that the presence of IDH mutation confers better prognosis and a better response to chemotherapy. Mutation-positive tumours accumulate high concentrations of D-2-hydroxyglutarate, resulting in metabolic and epigenetic changes which we hypothesize will be reflected in a change in Raman scattering. In this study, we investigate the feasibility of using Raman spectroscopy to differentiate between IDH1 positive (IDH1+) and negative (IDH1-) tumours through classification modelling. METHOD: Forty biopsies of glioblastoma (WHO grade IV) in patients under the age of 40 years were classified into either IDH1+ (n=20) or IDH1- (n=20) using IDH-1(R132H) and BCAT-1 immunohistochemistry. 6µm thick sections were prepared from formalin fixed paraffin embedded specimens. Based on the hematoxylin and eosin stained contiguous section, high tumour density areas in the unstained sections were identified and subjected to analysis. Raman maps of ca. 1mm2 were acquired from up to two locations on each sample using an inVia Raman microscope (Renishaw, UK) configured with a 785nm excitation laser source. RESULTS: 30 spectral maps (60,325 spectra) from a total of 16 biopsy samples (8 IDH+ and 8 IDH-) have been collected to date. Principal component analysis (PCA) demonstrated good separation of the IDH1+ and IDH1- groups (see figure). A PCA-linear discriminant analysis classification model demonstrated 96.98% sensitivity and 90.1% specificity for predicting the presence of an IDH1 mutation. CONCLUSIONS: The results demonstrate the feasibility of using Raman spectroscopy to accurately distinguish IDH1 mutated glioblastomas from their IDH1- counterparts. Raman spectroscopy could provide a powerful tool to aid neuropathological diagnosis and genetic classification of glial tumours in the future.
Juvenile Myelo-Monocytic Leukemia (JMML): the Effect of Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF) on Wilms Tumor Gene (WT1) by Quantitative Real Time-Polymerase Chain Reaction (q-RT-PCR) and Flow Cytometry
Authors: Morris Kletzel, Sana Khan, Wei Huang, Marie Olszewski
Journal: Blood (2010)
Risk factors for <i>clostridium difficile</i> infection in children with malignancy.
Authors: P. M. K. De Blank, T. Zaoutis, B. Fisher, A. B. Troxel, J. Kim, R. Aplenc
Journal: Journal of Clinical Oncology (2011)

9533 Background: Clostridium difficile, the most common cause of nosocomial diarrhea, can lead to significant morbidity and mortality. 25% of all pediatric nosocomial C. difficile Infections (CDI) occur in children with cancer. Although the epidemiology of CDI in adults is well described, risk factors for CDI in children with malignancy have not been fully studied. Methods: Using the PHIS database, we created a retrospective cohort of patients ≥1 year old with an ICD-9 code for malignancy who were admitted to participating children’s hospitals from 2001-09. CDI was defined by an ICD-9 code, a charge for C. difficile toxin assay and antibiotic treatment for CDI. Pharmaceutical data was analyzed for the 7 days prior to each CDI. A Cox proportional hazards model, adjusted by site and clustered by patient, was created to measure the risk of developing CDI for each hospital admission. The model censored on discharge, stem cell transplantation or death. Results: Of 40,638 admissions of 21,248 children among 41 hospitals, 1,048 CDIs occurred. Analysis by drug class showed that exposure to 3rd and 4th generation cephalosporins was associated with increased risk of CDI. Exposure to 1st generation cephalosporins, macrolides, and H2 acid blockers showed a protective effect. Proton pump inhibitors, fluoroquinolones and clindamycin were not significantly associated with CDI. Individual drug analyses were also performed (Table). Conclusions: This study reports the first risk factor analysis for CDI among children with cancer in an administrative database. Similar to adult studies, risk of CDI increased with broad spectrum antibiotics. Unlike prior studies, ciprofloxacin showed a protective effect against CDI in children with cancer. Further study and confirmation of risk factors for CDI in children with malignancy may help guide antibiotic use and CDI screening programs. Risk factors for CDI. Risk factor Hazard ratio P value 95% confidence interval Ceftizoxime 14.4 <0.001 5.4 – 38.2 Ticarcillin 8.9 0.033 1.2 – 66.2 Cefepime 2.1 <0.001 1.8 – 2.5 Cefotaxime 1.6 0.032 1.04 – 2.4 Ceftazidime 1.5 <0.001 1.2 – 1.8 Hospital days in last month 1.04 <0.001 1.03 – 1.05 Ranitidine 0.86 0.047 0.73 – 0.998 Cefazolin 0.72 0.015 0.55 – 0.94 Ciprofloxacin 0.59 0.019 0.37 – 0.92
BMET-07. PROGNOSTIC DIFFERENTIAL GENE EXPRESSION PROFILING FOR DEVELOPMENT OF BRAIN METASTASIS IN CUTANEOUS MELANOMA VARIES BASED ON SITE OF TISSUE SAMPLED
Authors: Ryan Lee, Nathan Johnson
Journal: Neuro-Oncology (2016)

Our ability to predict brain metastasis in melanoma is poor. Gene expression profiling (GEP) of tumor samples could provide prognostic information by identifying genes that are differentially expressed between melanoma patients who do and do not develop metastasis. Since primary tumor is not always available for molecular testing, we sought to identify potentially prognostic differentially expressed genes (DEGs) at each type of site that may be sampled--primary tumor, lymph nodes, and locoregionally-invaded tissue--and evaluate if these DEGs differed significantly between sites. We then sought to identify site-independent DEGs with potential prognostic or pathophysiologic relevance. We obtained RNA-sequencing data for 470 patients from The Cancer Genome Atlas and identified patients that developed brain metastasis on follow-up. Stratifying by site of tissue sample tested, we identified DEGs using R/Bioconductor/EBSeq (FDR-corrected p<0.01, fold change >2). Proportions of site-total DEGs to shared DEGs were then compared using Chi Square test for each combination of site. Comparing samples from patients that developed brain metastasis to those that did not, there were 600-1000 DEGs at each of the three sampled sites. The numbers of shared DEGs were significantly fewer (range 97-204, p<0.001). Only 17 DEGs were shared between all three site-wise analyses. CHRNA9, CWH43, EFCAB1, ELFN2, FAM83F, FERMT1, HAPLN1, LCE1F, PAGE2B, PCDH15, PRSS3, PSAPL1, SCEL, SIX3, and SPRR2D were down-regulated in samples from patients that would later develop brain metastasis. GFRA2 and PRB1 were upregulated. The variability in DEGs based on sample site should be accounted for when developing prognostic GEP protocols for this clinical scenario. However, the 17 shared DEGs identified had potential prognostic relevance independent of site and serve as candidates for GEP. Many of these have potential pathophysiologic relevance as well. For example, GFRA2 is a RET pathway activator and neurotrophic factor receptor.
Vitamin D replacement in children, adolescents and pregnant women in the Middle East and North Africa
Authors: Marlene Chakhtoura, Sara El Ghandour, Khaled Shawwa, Elie A. Akl, Asma Arabi, Ziyad Mahfoud, Robert Habib, Hassan Hoballah, Ghada El Hajj Fuleihan
Journal: Metabolism (2017)
STMC-24. NOVEL INHIBITOR OF CDK5 SIGNALING AXIS SUPPRESSES SELF-RENEWAL PROPERTIES OF GBM STEM CELLS AND INDUCES APOPTOSIS
Authors: Subhas Mukherjee, Monica Chau, Carol Tucker-Burden, Changming Zhang, Jun Kong, Renee Read, Daniel Brat
Journal: Neuro-Oncology (2016)

Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. To uncover mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model in which brat-RNAi is driven by the neuroblast specific promoter inscuteable. Suppressing Brat in this population led to accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. Using adult Drosophila brain tumor, we performed a suppressor screen for kinases and found brain specific dCdk5 partially reverses the tumor phenotype. dCdk5 and its human ortholog CDK5 (79% identity) are different than other CDKs because they do not regulate cell cycle in normal cells, but are critical for neurogenesis and survival of mature neurons. Interestingly, many cancers show overactivation of CDK5 signaling, regulating cell cycle and leading to uncontrolled proliferation. To date, not much is known about the role of CDK5 in glioblastoma GBM) and glioma stem cell self-renewal. Our analysis of TCGA data shows that IDH wt GBM has significantly high level of CDK5 compared to the IDH wt lower grade glioma. Using patient-derived (GBM) neurosphere cultures and in vivo xenograft tumors in mice, we further demonstrated that a novel pharmaceutical suppressor of CDK5 signaling axis was capable of suppressing self-renewal properties and glioma stem cell viability by inducing apoptosis. Together, our results show that the CDK5 signaling pathway is important for glioma stem cell survival and that suppressing CDK5 could be a novel therapeutic approach to eliminate glioma stem cells.
Immunodiffusion Studies of Lymphoblast Cell Antigens
Authors: Angel Guerra, Ursula Koldovsky, Werner Henle
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Immunodiffusion Studies of Lymphoblast Cell Antigens Get access Angel Guerra, M.D., Angel Guerra, M.D. The Children's Hospital of Philadelphia 34th Street and Civic Center BoulevardPhiladelphia, Pennsylvannia 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ursula Koldovsky, Ph. D., Ursula Koldovsky, Ph. D. The Children's Hospital of Philadelphia 34th Street and Civic Center BoulevardPhiladelphia, Pennsylvannia 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar Werner Henle, M.D. Werner Henle, M.D. The Children's Hospital of Philadelphia 34th Street and Civic Center BoulevardPhiladelphia, Pennsylvannia 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 2, August 1975, Page 229, https://doi.org/10.1093/jnci/55.2.229-a Published: 01 August 1975
Abstract 5940: Pttg1 Regulates Cardiac Hypertrophy
Authors: Nalini Rajamannan, Thomas C Spelsberg, Malayannan Subramaniam
Journal: Circulation (2008)

Genetic Hypertrophic cardiomyopathy (HCM) is the most common identifiable cause of sudden cardiac death. However, the cellular mechanisms are not well known. The triad of HCM is ventricular hypertr...
Fcμ-Receptor (FcμR; TOSO/FAIM3) Mediated Internalization of Antibody-Drug Conjugates: A Novel Approach to Selectively Target Chronic Lymphocytic Leukemia Cells
Authors: Berengere Vire, Alexandre David, Joshua D Thomas, Terrence R Burke, Christoph Rader, Adrian Wiestner
Journal: Blood (2011)
First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.
Authors: Gerrard Teoh, Kihyun Kim, Alok Srivastava, Vasant Pai, Sung-Soo Yoon, Cheolwon Suh, Yeo-Kyeoung Kim
Journal: Blood (2009)
Bone biomarkers and overall survival (OS) in men with castrate resistant prostate cancer (CRPC) and skeletal metastases: Updated results from SWOG 0421, a phase III trial of docetaxel +/- atrasentan
Authors: P.N. Lara, M. Plets, C. Tangen, E. Gertz, N.J. Vogelzang, D.I. Quinn, I. Thompson, M. van Loan
Journal: Annals of Oncology (2016)
Polymorphisms in CD31/PECAM-1 and CD38 Genes Are Associated with Susceptibility to Multiple Myeloma
Authors: Krzysztof Jamroziak, Zofia Szemraj, Janusz Szemraj, Olga Grzybowska-Izydorczyk, Katarzyna Oszajca, Grazyna Janiszewska, Ewa Balcerczak, Marek Mirowski, Halina Urbanska-Rys, Tadeusz Robak
Journal: Blood (2008)
RBIO-03. IMPROVING GEMCITABINE-MEDIATED RADIO-SENSITIZATION USING MOLECULARLY TARGETED MENINGIOMA THERAPY
Authors: Arabinda Das, Daniel G. McDonald, William Alexander Vandergrift, Abhay K. Varma, Scott M. Lindhorst, Jeffrey Raizer, Pierre Giglio, Sunil J. Patel, Michele L Decandio, Naren L Banik, Kenneth N Vanek, Joseph M Jenrette, David Cachia
Journal: Neuro-Oncology (2016)

Of the many treatment options, gemcitabine has been currently used clinically to a variety of solid tumors types both as a chemotherapeutic agent and as a radiation sensitizer. However, it has been speculated that the gemcitabine plus relatively high dose of radiation increased the toxicity. Therefore, our current approaches to integrate of molecularly targeted agents, which potentially produce less toxicity than standard chemotherapy, and with gemcitabine-radiation improve chemo-radiation sensitivity. We combined HDACs or Chk1 inhibitors with gemcitabine and radiation using three meningioma cell lines (Ben Men 1, CH157 MN, and IOMM-Lee). These cell lines were treated with the 1 µM of HDAC inhibitor (Ganoderic Acid A and DM) or 1 µM of Chk1 inhibitor (UCN-01 and SB218078) with 1 µM of gemcitabine plus irradiation (1 Gy single dose) for 72 hr. Cell proliferation (SRB assay), cell survival (clonogenic assay) and apoptosis (Western blot) were analyzed following treatments. Our in vitro studies demonstrated that HDAC inhibitors Ganoderic Acid (A and DM) andChk1 inhibitor UCN-01 and SB218078 enhances gemcitabine + radiation activity, likely via disruption of HDAC activities and Chk1 signaling and inducing caspase-3 activities. These studies also indicate that timing of drug administration strongly influences response to gemcitabine + radiation activity plus HDAC inhibitor or Chk1 inhibitor in all three meningioma cells. Furthermore, this sequence combination was more effective in cell lines with dysfunctional Chk1 signaling or low level of HDAC activity. Addition of HDAC inhibitor or Chk1 inhibitor to gemcitabine significantly enhanced inhibition of cell proliferation and inhibited the gemcitabine and RT mediated apoptotic cascade.
ACTR-22. ANALYSIS OF BEVACIZUMAB UTILITY IN THE MANAGEMENT OF ADULT DIFFUSE BRAINSTEM GLIOMAS
Authors: Abdulrazag Ajlan, Abdullah Feroze, Seema Nagpal, Lawrence Recht
Journal: Neuro-Oncology (2016)

Both pediatric and adult diffuse brainstem gliomas (DBG) share notably poor prognoses. Currently, radiotherapy remains a mainstay of treatment algorithms. Thus far, the institution of adjuvant chemotherapeutic regimens such as coupled with radiotherapy has demonstrated no clear advantage in rates of overall free survival versus upfront radiotherapy alone. However, the utility of chemotherapy utilizing bevacizumab (BEV) has not yet been evaluated systematically in adults presenting with diffuse BSG. We retrospectively extracted all DBG cases treated at the Stanford University Medical Center from January 2007 through August 2014). Inclusion criteria comprised of patients ages greater than or equal to 18 years of age upon initial presentation with confirmed cases of DBG who received bevacizumab along the course of their therapy. A total of 46 patients with brainstem involvement were identified in our brain tumor database registry. 13 patients with DBG met imposed inclusion. Median age at diagnosis was 35 years (range, 22–56 years) with a median follow-up of 19 months (range, 5–115 months). The overall survival of the full cohort was 41 months (5–115). Three had radiation as the initial treatment, the rest had radiation and chemotherapy. The BEV was given in cases of progression in 11 patients, the other two patients received BEV upfront with chemo radiation because of symptomatic mass effect. On the 1st follow-up, 4 patients had Partial response (PR), 4 had stable disease (SD), and three had Progressive disease (PD). The PR seen was sustained for 2 months. The SD was sustained for 2.25 months. The OS after initiating BEV was 8 months. In three cases, BEV was discontinued because of severe toxicity. Our limited case series of 13 adult patients afflicted with diffuse brainstem gliomas suggests potential role for the bevacizumab in the management of such neoplasms.
Safety of Lanreotide 120 mg ATG in combination with metformin in patients with progressive advanced well-differentiated gastro-intestinal (GI) or lung carcinoids. A pilot, one-arm, open-label, prospective study: the MetNET-2 trial
Authors: R. Buzzoni, D.B. Filippo, D. Femia, N. Prinzi, L. Concas, M. Milione, E. Tamborini, F. Perrone, G. Lo Russo, C. Vernieri, I. Pulice, F. Piras, G. Dinoi, S. Pusceddu
Journal: Annals of Oncology (2016)
Diagnostic performance of liquid biopsy for pancreatic solid lesion as alternative to endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)
Authors: D. Sefrioui, F. Blanchard, P. Basile, E. Toure, C. Dolfus, L. Beaussire, N. Vasseur, A. Perdrix, A. Gangloff, L. Schwarz, F. Clatot, J.-J. Tuech, J.-C. Sabourin, T. Frebourg, P. Michel, F. Di Fiore
Journal: Annals of Oncology (2016)
An Analysis of the Incidence, Risk Factors and Prognosis of Acute Promyelocytic Leukemia Following Mitoxantrone Therapy in Patients Affected by Multiple Sclerosis.
Authors: Chiara Cattaneo, Erika Borlenghi, Cinzia Cordioli, Samantha Ferrari, Antonio Regazzoli, Giuseppina Ruggeri, Elena Gobbi, Maria Adele Capucci, Moira Micheletti, Ruggero Capra, Giuseppe Rossi
Journal: Blood (2006)