tbuckley/cabot-search huggingface dataset:
Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.
Authors: Danielle Novetsky Friedman, Suzanne L. Wolden, Zoltan Antal, Chaya S. Moskowitz, Patrick Hilden, Nai-Kong V. Cheung, Brian H. Kushner, Emily S. Tonorezos, Dean Carlow, Kevin C. Oeffinger, Charles A. Sklar
Journal: Journal of Clinical Oncology (2016)

108 Background: Previous reports have suggested an increased risk of Type I and Type II diabetes mellitus (DM) in childhood cancer survivors exposed to abdominal radiotherapy (RT). The mechanisms leading to DM in this population, however, remain unknown. We sought to clarify the pathophysiology leading to these derangements by performing dynamic testing of glucose and insulin in survivors previously treated with abdominal RT. Methods: Cross-sectional pilot study of 2-year survivors of childhood cancer treated with abdominal RT at Memorial Sloan Kettering between 1975 – 2009. Eligible participants were &lt; 21 years of age at exposure to abdominal RT; those with a known diagnosis of DM or prior exposure to brain or total body RT were excluded. Survivors underwent formal 2-hour glucose tolerance testing; auto-antibodies (insulin auto-antibodies, islet cell autoantibody, glutamic acid decarboxylase) typically present in patients with Type I DM and hemoglobin A1c levels were assessed. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Results: 21 survivors were enrolled (male: 47.6%; median age at RT: 3.3 years; median age at study: 14.4 years [range: 8.3 – 46.9]; median time from abdominal RT: 10.7 years). Primary diagnoses included neuroblastoma (n = 15), rhabdomyosarcoma (n = 3), Wilms (n = 1), Hodgkin lymphoma (n = 1), rhabdoid tumor (n = 1). None of the participants were obese (body mass index [BMI] range: 14.7 – 23.2 kg/m 2 ). Five participants (23.8%, 95% confidence interval: 8% – 47%) had glucose derangements at a median of 8.4 years after RT (one with impaired fasting glucose [fasting glucose ≥ 100 mg/dl) and four with impaired glucose tolerance [2-hour glucose 140-199 mg/dl]). Two additional participants with normal glucose tolerance had impaired insulin sensitivity based on an abnormal Matsuda Index and HOMA-IR. None of the participants had abnormal autoantibodies, insulinopenia, or hemoglobin A1c levels. Conclusions: These findings suggest that nonobese childhood cancer survivors treated with abdominal RT may be at high-risk for subclinical derangements of glucose and insulin. Further study is warranted in larger survivor cohorts. Clinical trial information: NCT02248779.
CSIG-08. A REGULATORY CIRCUIT OF miR-125b/miR-20b AND Wnt SIGNALING CONTROLS GBM PHENOTYPES THROUGH FZD6-MEDIATED PATHWAYS
Authors: Tianzhi Huang, Angel Alvarez, Rajendra Pangeni, Craig Horbinski, Songijan Lu, C. David James, Jeffrey Raizer, Cameron Brenann, Erik Sulman, Gaetano Finocchiaro, Ming Tan, Ryo Nishikawa, Xinghua Lu, Ichiro Nakano, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2016)

Molecular profiling of Glioblastomas (GBM) can segregate patients into distinct subtypes associated with tumor phenotype and tumor recurrence. However, the mechanism underlying subtype conversion, that is associated with recurrence, are poorly understood. Here we report that canonical Wnt signaling induces transcription of miR-125b and miR-20b, and both Wnt signaling and their target miRNAs are enriched in proneural (PN) compared to mesenchymal (MES) GBM. Mechanistically, miR-125b and miR-20b enhance Wnt signaling by simultaneously targeting two negative regulators of the Wnt/β-catenin pathway, APC and FZD6, thereby creating a positive feedback loop. Overexpression of miR-125b and miR-20b in MES GBM spheres markedly reduce their capacity for self-renewal in vitro and the in vivo growth of tumor xenografts. Contrastingly, antagonizing miR-125b or miR-20b by specific inhibitory miRZIPs significantly enhances the ability of PN sphere self-renewal and tumor-initiation, while inducing MES-like properties. FZD6 acts as a major downstream effector for miR-125b and miR-20b in regulating phenotypic properties of GBM. Overexpression of FZD6, but not other members of the FZD family, stimulated CaMKII-TAK1-NLK signaling, which attenuates the canonical Wnt pathway, while promoting mesenchymal-enriched Stat3 and NF-kB signaling. These novel findings are further confirmed in vitro and in vivo, with our tumor xenograft models, which demonstrate targeting differentially enriched signaling pathways in PN versus MES GBM effectively inhibits their capacity for self-renewal and tumor growth. Furthermore, analysis of our own patient samples in addition to The Cancer Genome Atlas (TCGA) GBM data sets reveals the expression of the components of TCF4-miR-125b/20b-FZD6 circuit are prognostic for clinical GBM. Our findings provide critical insights for understanding GBM pathobiology and for improving the treatment of GBM.
Uncontrolled Asthma in Specialized Centers in Latin America: Findings from the Asthma Control in Latin America (ASLA) Study
Authors: Hugo E. Neffen, Edith Vallejo-Perez, Marco Chahuan, Eduardo Giugno, Dante D. Hernández-Colín, Fabio Bolivar, Gur Levy, Claudia Vieira, Felipe Moraes, Karynna P. Viana, Cláudia R. Soares
Journal: Journal of Allergy and Clinical Immunology (2017)
The Prognostic Significance of Cytopenia in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL).
Authors: Clive S. Zent, Wei Ding, Karin F. Giordano, Susan M. Schwager, Tait D. Shanafelt, Megan S. Reinalda, James D. Hoyer, Diane F. Jelinek, Renee C. Tschumper, Deborah A. Bowen, Timothy G. Call, Neil E. Kay, Susan L. Slager
Journal: Blood (2007)
Intensification Therapy with Bortezomib-Melphalan-Prednisone Versus Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma: An Intergroup, Multicenter, Phase III Study of the European Myeloma Network (EMN02/HO95 MM Trial)
Authors: Michele Cavo, Meral Beksac, Meletios A Dimopoulos, Lucia Pantani, Francesca Gay, Roman Hájek, Nicoletta Testoni, Ulf-Henrik Mellqvist, Francesca Patriarca, Vittorio Montefusco, Monica Galli, Hans Erik Johnsen, Heinz Ludwig, Sonja Zweegman, Ruth Wester, Ka Lung Wu, Christoph Driessen, Rossella Troia, Petra Cornelisse, Bronno van der Holt, Antonio Palumbo, Pieter Sonneveld
Journal: Blood (2016)
IMST-28. NON-INVASIVE IMMUNE MONITORING FOLLOWING DC VACCINATION EFFECTIVELY DELINEATES IMMUNE RESPONSES IN GLIOBLASTOMA
Authors: Joseph Antonios, Horacio Soto, Richard Everson, Joey Orpilla, Namjo Shin, David Nathanson, Robert Harris, Samuel Sadeghi, Benjamin Ellingson, Linda Liau, Robert Prins
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is a devastating disease with a median survival of 11-14 months following resection with subsequent standard chemotherapy and radiation. As the immunotherapy field has advanced, immune monitoring of patients receiving these treatments has become especially relevant. In the GBM treatment setting, access to tumor is limited only to instances of surgery for initial needle biopsy or resection. As such, non-invasive immune monitoring is of paramount importance. In this study, we hypothesized that non-invasive D-FAC PET and MRI with contrast could be utilized to provide a measure of immune response in GBM using our murine model. To test this, immunocompetent C57BL/6 mice were implanted with GL261 glioma cells in the brain. Mice were stratified into Control, DC vaccine, and DC vaccine + PD-1 mAb treatment groups and imaged post-treatment using a Bruker 7T MR scanner to obtain anatomical, perfusion, and pH-weighted data. Mice were then administered intravenous [18F]-FAC and dually PET/CT imaged with the Genisys 8 scanner to evaluate the tumor-infiltrating lymphocytic response. Tumor-bearing hemisphere was then harvested, processed, and stained for FACS analysis. There was a significant increase in activated tumor-infiltrating lymphocytes in DC vaccine and DC vaccine + PD-1 mAb-treated mice over control mice on FACS analysis. We then co-registered PET and MRI data to delineate subsets of increased contrast signal with areas of PET-denoted inflammatory response. PET signal intensity was significantly increased in treated mice over control mice that positively correlated with activated lymphocyte infiltration identified on FACS analysis and histology. These findings demonstrate a clinically relevant modality to evaluate immune responses non-invasively following DC vaccine treatment.
Interferon Regulatory Factor 4 Is Not Required for Induction of Chronic Myeloid Leukaemia-Like Myeloproliferative Disease by Bcr/Abl in Mice.
Authors: Anna Lena Illert, Cornelius Miething, Rebekka Grundler, Manuel Schmidt, Andreas Burchert, Andreas Neubauer, Claudia Mugler, Christian Peschel, Justus Duyster
Journal: Blood (2005)
Evaluation of estrogen receptor expression as a prognostic factor for very young women (below 35 years) with breast cancer in Taiwan
Authors: C. Lin, C. Huang, Y. Lu, J. Laiu, S. Huang, W. Kuo, W. Kuo, K. Chang, A. Cheng
Journal: Journal of Clinical Oncology (2009)

e22163 Background: In the past two decades, the incidence of very young (&lt;35 years) breast cancer in Taiwanese has been rapidly increasing to quite close to that of Caucasian Americans. However, the clinicopathological features of this group of patients appear to be different from their Western counterpart. Here, we sought to determine the prognostic value of ER expression for this newly emerging population in Taiwan. Methods: We retrospectively collected information on all consecutive very young patients (age &lt;35 years) with stage I-III breast cancer treated at National Taiwan University Hospital between 1997 and 2005. ER expression was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tissue sections. Tumor with more than 10% positive nuclei was considered ER positive. Results: A total of 178 patients with a median age of 32 (range: 21–35) years were included. The median follow-up time was 62.5 (95% confidence interval, 42.0–64.2) months. Univariate analysis showed that ER expression was significantly associated with favorable OS (HR=0.48, P=0.03), but not with DFS (hazard ratio [HR]=0.79, P=0.42). Multivariate analysis showed that stage and ER were independent prognostic factors. Conclusions: In contrast to the findings in Caucasians, ER expression was an independent prognostic factor for favorable overall survival in Taiwanese patients with very young breast cancer. No significant financial relationships to disclose.
NPM Mutations in Adult AML with Normal Karyotype: A Retrospective Study of the Acute Leukemia French Association (ALFA).
Authors: Nicolas Boissel, Aline Renneville, Valeria Biggio, Nathalie Philippe, Xavier Thomas, Jean-Michel Cayuela, Christine Terre, Isabelle Tigaud, Sylvie Castaigne, Emmanuel Raffoux, Stephane de Botton, Pierre Fenaux, Hervé Dombret, Claude Preudhomme
Journal: Blood (2005)
Molecular characterization of HER2-positive (HER2+) metastatic gastric and gastro-esophageal junction cancer patients (mGC): Identification of resistance mechanisms to trastuzumab-based therapy (TTZ)
Authors: M. Alsina, C. Hierro, J. Sastre, R. Guardeño, C. Lopez, E. Pineda, E. Aranda, J.L. Manzano, M. Galán, F. Longo, L. Visa, S. Landolfi, J. Jimenez, J. Sperinde, A. Pandiella, J. Tabernero, J. Hernandez-Losa, J. Arribas, M. Scaltriti, P. Nuciforo
Journal: Annals of Oncology (2016)
The Addition of Rituximab and/or Alpha-Interferon to High Dose Chemotherapy and Autologous Stem Cell Transplantation for Patients with Relapsed Follicular Lymphoma Produces Durable Progression Free Survival and Molecular Remissions
Authors: Sita Bhella, Neil L Berinstein, Nancy Pennell, Matthew Cheung, Kevin R. Imrie, Violet Miliken, Marciano D. Reis, Alden Chesney, David Good, Lisa Hicks, Eugenia Piliotis, Michael Crump, Rena Buckstein
Journal: Blood (2010)
CBIO-13. THE DYNAMIC ROLE OF MARCKS IN THE GROWTH AND PROLIFERATION OF GLIOBLASTOMA
Authors: Nicholas Eustace, Joshua Anderson
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is the most common and deadly form of Glioma, with a median survival of 14 months. GBM remains a deadly disease due to its diffuse nature, high proliferative capacity and therapeutic resistance. Understanding mechanisms of therapeutic resistance and tumor growth allows for the development of new therapeutic strategies. MARCKS is a natively unstructured protein found in the brain that has been shown to electrostatically sequester phosphatidylinositol (4,5)-bisphosphate (PIP2) with its unphosphorylated effector domain (ED). GBM is commonly found with mutations resulting in an over-activation of the Receptor Tyrosine Kinase (RTK)/RAS/PI3K pathway and a loss of PTEN both of which contribute to the conversion of PIP2 into phosphatidylinositol (3,4,5)-triphosphate (PIP3) and subsequent over activation of AKT. AKT activation has been associated with increased tumor growth and proliferation, as-well-as resistance to apoptosis, temozolomide and radiation. MARCKS has the potential to suppress the effects of these mutations by sequestering the common substrate; however, MARCKS ED phosphorylation and regulation in GBM are poorly understood. Using lentiviral overexpression of doxycycline inducible MARCKS ED mutants that mimic the phosphorylated (PP) and unphosphorylated (NP) states of the ED in U87, the effects of ED phosphorylation on tumor growth was assessed in-vitro by colony formation (CF) assays, ATPlite and long term proliferation assays, as-well-as, in-vivo by intracranial injection. Statistically significant decreases in cell proliferation were observed in-vitro in Wild Type and NP MARCKS ED overexpression, while statistically significant increases in proliferation were observed with the PP variant. In-vivo studies are ongoing. In conclusion, the phosphorylation of MARCKS ED appears to have an important function in regulating GBM growth in-vitro. Further investigation into MARCKS function in a cancer stem cell population and its role in GBM’s response to temozolomide and radiation may reveal a novel therapeutic target or uncover a new mechanism of therapeutic resistance.
Drug Provocation Tests in Patients with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Acetaminophen Hypersensitivity Reactions
Authors: Wat Mitthamsiri, Panithan Pradubpongsa, Atik Sangasapaviliya, Tadech Boonpiyathad
Journal: Journal of Allergy and Clinical Immunology (2017)
Analysis of Clinical Characteristics of a Paediatric Population with Rhinitis
Authors: Ana Prieto del Prado, Ibon Eguiluz Gracia, Bogas Gador, Oliver Muñoz Daga, Monica Vidal, Raquel Jurado Escobar, Maria Jose Rodriguez Sanchez, Carmen Rondon Segovia
Journal: Journal of Allergy and Clinical Immunology (2017)
Our act on fertility preservation for young breast cancer patients in our single institute.
Authors: Yasuyuki Kojima, Kyoko Tsuchiya, Chie Nishijima, Nao Suzuki, Koichiro Tsugawa
Journal: Journal of Clinical Oncology (2016)

109 Background: Along with increasing number of newly diagnosed Japanese breast cancer patients, the number of breast cancer survivors in reproductive age is also increasing. Among newly diagnosed Japanese breast cancer patients, 3182(6.6%) are under age 40 in 2011, which was 1610 in 2006. In our institute, we have been cooperating with gynecologists and providing fertility preservation program since 2010. Our aim is to access our team management, clinical impact and outcome of fertility preservation among young breast cancer patients in our institute. Methods: A patient, 1)without distant metastasis, 2)systemic chemotherapy and/or hormonal therapy planned, 3)within reproductive age and 4)willing to preserve fertility, will be referred to oncofertility clinic. Chart review was done retrospectively. Results: Ninety-five patients had consultation to the oncofertility clinic between April 2010 and April 2015. The average age at consultation was 34.1(range 22-44). Almost all patient had invasive cancer; cStage0:4%, cStageI:31%, cStageII:53%, cStageIII:11%. Fifty-five percent had estrogen receptor (ER) positive/HER2 negative, 31% had ER positive/HER2positive, 2% had ER negative/HER2 positive and 12% had ER negative/HER2 negative breast cancer. Forty-five had counseling without any procedure, 22 underwent ovarian tissue cryopreservation, 17 underwent embryo cryopreservation and 8 underwent oocyte cryopreservation. Because observation period is still short, we haven’t had any case that got pregnant or delivered, yet. Conclusions: The number of patient who choose to underwent fertility preservation is increasing. We have actually started facing proposition, when we shall lay aside adjuvant therapy and let them plan to be conceived. Taking risk into account, we are now evaluating the safety of cancer treatment and outcome of each procedure which undergone multidisciplinary deliberate decision-making process.
Acute Myeloid Leukemia
Authors: Margaret R. O'Donnell, Camille N. Abboud, Jessica Altman, Frederick R. Appelbaum, Daniel A. Arber, Eyal Attar, Uma Borate, Steven E. Coutre, Lloyd E. Damon, Salil Goorha, Jeffrey Lancet, Lori J. Maness, Guido Marcucci, Michael M. Millenson, Joseph O. Moore, Farhad Ravandi, Paul J. Shami, B. Douglas Smith, Richard M. Stone, Stephen A. Strickland, Martin S. Tallman, Eunice S. Wang, Maoko Naganuma, Kristina M. Gregory
Journal: Journal of the National Comprehensive Cancer Network (2012)

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations.
Bortezomib in Combination with High-Dose Dexamethasone and Continuous Low-Dose Oral Cyclophosphamide for Relapsed Multiple Myeloma.
Authors: Martin Kropff, Guido Bisping, Peter Liebisch, Orhan Sezer, Hermann Einsele, Christian Straka, Nicolaus Kroeger, Bernd Metzner, Monika Engelhardt, Nicola Lang, Marcus Hentrich, Hans Wolf, Christoph von Schilling, Hans Salwender, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2005)
Gene Expression Profiles with Signatures of Tumor Biology and Chemotherapy Sensitivity May Provide a Novel Approach to Maximize Response to Induction Therapy in Patients with Acute Myeloid Leukemia.
Authors: Arati V Rao, Sascha A Tuchman, Anil Potti, David A. Rizzieri, Hiroyuki Mano, Ruud Delwel, Peter Valk, B. Lowenberg
Journal: Blood (2008)
β7-Integrin and MAdCAM-1 play opposing roles during the development of non-alcoholic steatohepatitis
Authors: Hannah K. Drescher, Angela Schippers, Thomas Clahsen, Hacer Sahin, Heidi Noels, Mathias Hornef, Norbert Wagner, Christian Trautwein, Konrad L. Streetz, Daniela C. Kroy
Journal: Journal of Hepatology (2017)
Th2 Cytokines and IL-17 Have Distinct Effects on Sphingolipid Metabolism in Differentiated Primary Human Keratinocytes
Authors: Elena Goleva, Evgeny Berdyshev, Irina Bronova, Clifton F. Hall, Brittany N. Richers, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2017)
Feasibility of concurrent weekly paclitaxel and radiotherapy in node-positive breast cancer: An experience from India.
Authors: Mohan Kumar, Murali Subramanian, Rajeev AG, Arul Ponni, Nirmala S, Nalini Kilara, Janaki MG
Journal: Journal of Clinical Oncology (2012)

201 Background: Breast cancer patients with positive node and extra nodal spread are at a higher risk for distant metastases and they require immediate adjuvant chemotherapy. Similarly patients after breast conservative surgery or with patholgical T3, T4 disease require adjuvant radiation as early as possible. Taxanes have shown good response in node positive patients and are combined in many adjuvant chemotherapy regimens. Hence the current study was taken to assess the feasibility of concurrent weekly paclitaxel and radiotherapy. Methods: A prospective study was conducted on 22 female breast cancer patients after modified radical mastectomy or breast conservative surgery with pathologically positive node. Chest wall or whole breast radiotherapy was given on Tele Cobalt or Linac for a dose of 50 – 50.4Gy in conventional fractionation. Boost of 16 Gy was given to tumor cavity for those undergone breast conservative surgery. All patients received Inj. paclitaxel 60 mg/m 2 once a week for 5 weeks. After completion of RT, paclitaxel dose was increased to 80mg/m 2 for remaining 7 cycles. This was followed by anthracycline-based treatment sequentially as per standard adjuvant guidelines. Patients assessed weekly and toxicities graded based on CTC version 03. The minimum follow up was 2 months after completion of chemoradiation. Chi-Square test and Fisher exact test were used to interpret the results with literature. Results: See table. Skin reaction was more frequent and severe of all toxicities (p=0.003). With available literatures on adjuvant radiation alone the grade III and higher skin reactions are 3% but in our study it is 28% because of which 5/22 (22%) patients had interruption of both chemotherapy and radiation. Conclusions: Concurrent chemoradiation with weekly paclitaxel in adjuvant treatment of ca breast is associated with more Skin reactions which may result in significant treatment interruptions. It should be practiced cautiously which requires further randomized control studies to assess the toxicities in detail. [Table: see text]
Early Versus Late Administration of Icatibant in Patients With Hereditary Angioedema
Authors: Marcus Maurer, Werner Aberer, Teresa Caballero, Laurence Bouillet, Hilary J. Longhurst, Andrea Zanichelli, Anette Bygum, Anete S. Grumach, Amandine Perrin, Irmgard Andresen
Journal: Journal of Allergy and Clinical Immunology (2017)
Socioeconomic Differences in Rates of Cesarean Section
Authors: Jeffrey B. Gould, Becky Davey, Randall S. Stafford
Journal: New England Journal of Medicine (1989)

Abstract Increasing cesarean-section rates have focused attention on variations in the use of this procedure that appear to be independent of medical indication. We investigated the relation between the rate of primary cesarean section and socioeconomic status in a cohort of 245,854 singleton infants born to non-Hispanic white, black, Asian-American, and Mexican-American residents of Los Angeles County, California. On the basis of birth-certificate data for 1982 and 1983, a significant relation, independent of maternal age, parity, or birth weight, was found between the rates of primary cesarean section and socioeconomic status. Women who lived in census tracts with a median family income of more than $30,000 had a primary cesarean-section rate of 22.9 percent, as compared with 13.2 percent among women residing in areas with a median family income under $11,000. In women between the ages of 18 and 34, the incidence of reported complications of pregnancy or childbirth in the lowest-income group was 10.9 percent, as compared with 17.4 percent in the highest-income group (accounting for 42 percent of the difference in the rate of primary cesarean section between groups); the rate of primary cesarean section in the presence of complications in these two groups was 65.4 percent and 79.3 percent (accounting for 17 percent of the difference); and the primary rate in the absence of reported complications in these two groups was 6.4 percent and 10.5 percent (accounting for 41 percent of the difference). The rates of primary cesarean section were highest among non-Hispanic whites (20.6 percent), intermediate among Asian Americans (19.2 percent) and blacks (18.9 percent), and lowest among Mexican Americans (13.9 percent). Significant socioeconomic differences in these rates were observed in all four groups (P<0.01). We conclude that the rates of primary cesarean section vary directly with socioeconomic status and that this association cannot be accounted for by differences in maternal age, parity, birth weight, race, ethnic group, or complications of pregnancy or childbirth. (N Engl J Med 1989; 321:233–9.)