tbuckley/cabot-search huggingface dataset:
IMST-20. MAPK PATHWAY BLOCKADE PRIMES BRAFV600E MUTANT GLIOMA FOR IMMUNOTHERAPY
Authors: Stefan Grossauer, Katharina Koeck, Nicole Murphy, Joanna Phillips, Derek Wrainwright, Hideho Okada, Sabine Mueller, C. David James, Theo Nicolaides, Claudia K Petritsch
Journal: Neuro-Oncology (2016)

BRAFV600E mutations are frequent in pediatric gliomas. We previously showed anti-tumor activity when using BRAF and/or MEK inhibitors against BRAFV600E glioma xenografts. While early clinical trial reports suggest an encouraging response rate, a significant fraction of tumors shows no therapy response. Using expression arrays on 30 pediatric gliomas, we noted that CD274 (PD-L1) expression is increased 3-fold and CD8a expression (found on cytolytic T cells and dendritic cells) is elevated in BRAFV600E mutant gliomas compared to KIAA1549-BRAF fusion or BRAF wildtype tumors. We hypothesized that the presence of CD8+ cells may predict BRAFV600Emutant glioma sensitivity to PD-L1 blockade immunotherapy. Immunocompetent, syngeneic FVB/N mice were intracranial-engrafted with luciferase-modified BRAFV600E mutant CDKN2A-deficient murine glioma cell line 2341luc and treated with BRAFV600Eand/or MEK inhibitors, either alone or in combination, and either with or without PD-L1 (Clone 10F.9G2) and CTLA-4 (Clone 9D9) mAbs. While the combination of BRAF and MEK inhibitors significantly increased the median survival from 46 to 70 days (P<0.05), additional treatment with PD-L1 and CTLA-4 mAbs further increased survival to a median of 150 days (P<0.001). Notably, PD-1 and CTLA-4 blockade, alone, only marginally increased survival to 60.5 days (P<0.05). To understand the mechanism underlying the impact on survival, we examined T cell and CD133+ cancer stem cell composition in treated tumors. We found that the survival benefit of quadruple treatment associates with an increased frequency of CD8+ cells and a decrease in T regulatory cells and cancer stem cells. In summary, we report that BRAFV600E mutant gliomas present increased CD8+ and PD-L1 levels at baseline and that when MAPK pathway and immune checkpoint blockades are combined, an immune profile indicative of productive tumor immunity is observed. These data provide rationale for further understanding this therapeutic approach, as well as the potential for clinical consider in the near future.
The Role of Bcl-2 in Apoptosis Induced by khat (Catha Edulis) in Acute Myeloid Leukemia Cell Lines.
Authors: Therese Bredholt, Elisabeth A. Dimba, Anne C. Johannessen, Daniela Costea, G. W. Francis, Olav K. Vintermyr, Bjorn T. Gjertsen5
Journal: Blood (2005)
Unveiling the Regulatory Role of CD8+ T-Cells in the Pathogenesis and Effective Steroid Treatment in ITP
Authors: Li Ma, Elisa K. Simpson, June Li, Min Xuan, Miao Xu, Laura Baker, Yan Shi, Guangheng Zhu, Pingguo Chen, Alan H Lazarus, John J. Freedman, Heyu Ni
Journal: Blood (2014)
14q Deletions Are Recurrent Aberrations in CLL and Other Mature B-Cell Neoplasms and Show a High Coincidence with An Unmutated IgVH Status and Trisomy 12, and Are Associated with An Intermediate Overall Survival and a Shorter Time to Treatment.
Authors: Lena Reindl, Frank Dicker, Tamara Weiss, Wolfgang Kern, Susanne Schnittger, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2009)
OS7.6 Management patterns and outcome of patients with primary CNS lymphoma (PCNSL) in France during 2011–2016. A LOC network study
Authors: C. Houillier, C. Soussain, H. Ghesquières, P. Soubeyran, O. Chinot, L. Taillandier, R. Houot, G. Ahle, E. Gyan, K. Hoang-Xuan
Journal: Neuro-Oncology (2016)
Surgically treated esophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes
Authors: S.R. Markar, C. Gronnier, A. Pasquer, A. Duhamel, H. Behal, J. Thereaux, J. Gagniere, G. Lebreton, C. Brigand, B. Meunier, D. Collet, C. Mariette
Journal: Annals of Oncology (2016)
CBIO-15. VARIATIONS IN CELLULAR PROLIFERATION BY GEOGRAPHIC LOCATION IN PEDIATRIC PILOCYTIC ASTROCYTOMAS
Authors: Albert Tu, Ian Buchanan, Omid Hariri, Harish Babu, Linda Szymanski, Edward Melamed, Mark Krieger
Journal: Neuro-Oncology (2016)

Pilocytic astrocytoma is the most common pediatric brain tumor and frequently found in the cerebellar hemispheres. A significant proportion however, occur in the supratentorial space and along the optic pathway. Behavior of this lesion outside of the cerebellum may have a more aggressive natural history. Ki 67 protein is a cellular marker for proliferation and can predict for more aggressive behaviour. In this study we assess whether there is a difference in Ki-67 expression of pilocytic astrocytomas by the geographic location of the tumor. A retrospective review of pilocytic astrocytomas undergoing surgery at Children’s Hospital of Los Angeles from 2003 – 2015 was carried out. Only patients with complete clinical, pathological, and radiographic documentation were included. Tumor location was determined by reviewing preoperative imaging and stratified into infratentorial, supratentorial (ie. cerebral hemisphere), or optic pathway/suprasellar location. In cases where patients underwent multiple re resections, only the ki-67 from the earliest/initial surgery was recorded. Statistical analysis was carried out using commercially available statistics software. A p value of 0.05 was considered significant. A total of 83 patients were identified for study. 54 had tumor in the posterior fossa, 18 had tumor in the supratentorial space, and 15 had tumors of the optic pathway. The average age of patients at the time of surgery with infratentorial tumors was 6.7 years, while patients with supratentorial and optic pathway tumors were 9.4 and 8.8 years respectively. The average Ki-67 activity of infratentorial tumors was 3.45. Patients with supratentorial tumors had average Ki-67 of 4.15 (p = 0.17), while optic pathway tumors reached 3.31 (p = 0.18). Ki-67 indices are not significantly different when stratified by location, although trends were observed. Supratentorial tumors may grow more aggressively than infratentorial tumors, while optic pathway tumors may behave more indolently. Ongoing study is necessary to validate these findings.
A retrospective study of chemoradiotherapy (CRT) versus chemotherapy (CT) as adjuvant treatment for localized gastric cancer (LGC)
Authors: D.D.M. Girardi, G.C. Pereira, M. Negrão, M.A. Lima, M.M. Felizola, R.N. Fogace, F.C. Capareli, J. Sabbaga, P.M. Hoff
Journal: Annals of Oncology (2016)
P07.09 Textiloma mimicking a recurrent high-grade astrocytoma
Authors: E. Jaramillo-Jiménez, M. Gupta, A. F. Saad, B. S. Cheek, C. B. Michael, A. M. Navarro-Montoya, T. Gómez-Escobar, I. Melguizo-Gavilanes
Journal: Neuro-Oncology (2016)
Risk Factors for Bleeding in Patients with Nonvalvular Atrial Fibrillation Who Are Receiving Anticoagulant Therapy with Ximelagatran or Warfarin: Findings from the SPORTIF III and V Trials.
Authors: James D. Douketis, Karin Arneklev, Samuel Goldhaber, John Spandorfer, Frank Halperin, Jay Horrow
Journal: Blood (2004)
Efficacy and Safety of Prophylactic Use of Darbepoetin Alfa in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: Results of the Interim Analysis of the LNH03-6B GELA Study.
Authors: Richard Delarue, Corinne Haioun, Florence Broussais-Guillaumot, David Sibon, Marion Fournier, Nicolas Mounier, Tony Petrella, Serge Bologna, Christophe Fruchart, Christophe Ferme, Christian Recher, Stephanie Picard, Herve Tilly, Andre Bosly
Journal: Blood (2009)
Provision of spiritual care to advanced cancer patients by doctors and nurses in the Middle East
Authors: G. Bar-Sela, M. Schultz, K. Khader, M. Rassouli, M. Doumit, I. Ghrayeb, R. Kebudi, K. Elshamy, M. Faisal Al-Jadiry, R. Fahmi, H. Charalambous, S. Razaq, N. Gafer, G. Can, R. Obeidat, R. Punjwani, H. Ayyash, M. Khleif, M. Najajreh, M. Silbermann
Journal: Annals of Oncology (2016)
Phase 1b/2, open-label, multicenter, dose escalation and expansion trial of intratumoral SD 101 in combination with pembrolizumab in patients with metastatic melanoma
Authors: A. Ribas, R. Gonzalez, J. Drabick, S. Kummar, S. Agarwala, J. Nemunaitis, R. Coffman, C.J. Berman, E. Schmidt, E. Chartash, C. Guiducci, A. Candia, R. Janssen
Journal: Annals of Oncology (2016)
Phase II study of bevacizumab (B) plus cisplatin (C) plus intensity-modulated radiation therapy (IMRT) for locoregionally advanced head and neck squamous cell cancer (HNSCC): Preliminary results
Authors: D. G. Pfister, N. Y. Lee, E. Sherman, D. Lisa, D. Carlson, H. Stambuk, R. Shen, D. Kraus, J. Shah, M. G. Fury
Journal: Journal of Clinical Oncology (2009)

6013 Background: For patients with locoregionally advanced HNSCC, concurrent high-dose cisplatin + radiation therapy is a historical standard of care. HNSCC tumors expressing high levels of VEGF have been associated with worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. Methods: Percutaneous gastrostomy (PEG) tube was placed pre-treatment for all patients. Planned treatment consisted of definitive IMRT (total, 70 Gy) with concurrent C (50 mg/m 2 days 1, 2, 22, 23, 43, 44) and B (15 mg/kg days 1, 15, and 43). The initial version of the protocol called for an additional 6 months of maintenance B, but this was discontinued in an amendment after a G4 pulmonary hemorrhage event in subject 1 during maintenance treatment. 1 o endpoint was 2-year PFS. Results: 42 previously untreated patients (34 M, 8 F), median age 55 (27–75), with stage III/IV, M0 HNSCC (oropharynx 39, larynx 3) enrolled. HPV status by ISH: 16 pos, 14 neg, 12 unknown). All patients have completed treatment. CTCAE v3.0 toxicities (% patients) have included: functional mucositis G3 (76 %); nausea G3 (24%); vomiting G3 (17%); neutropenia G3 (31%), G4 (10%); hemoglobin G3 (17%); hyponatremia G3 (14%). Median weight loss during treatment was 8.9 kg (2.1–26 kg). There were two deaths within 90 days of last treatment: 1 aspiration pneumonia, 1 sudden death. Median follow up is approximately 9 months (range, &lt;3 to 24 months). Locoregional control rate is 100%. Three patients have developed distant metastasis. Estimated one-year PFS is 83% (± 10%) and estimated 1 year OS is 88% (± 6%). At a median of 8 months after completion of radiation therapy, PSS-HN scores were 100 for eating, speech, and diet in respectively 88%, 76%, and 53% of surveyed patients (n = 17). Conclusions: The addition of B to C + IMRT did not appear to increase toxicity to unacceptable levels, and preliminary efficacy results are encouraging. [Table: see text]
DC-beads loaded with irinotecan combined with systemic chemotherapy for pretreated liver dominant metastatic colorectal cancer: Procedure and outcomes of 49 patients
Authors: A.-L. Pointet, S. Pernot, O. Pellerin, G. Amouyal, A. Berger, P. Rougier, M. Sapoval, J. Taieb
Journal: Annals of Oncology (2016)
Endoscopic ultrasonography-guided antegrade stenting combined with hepaticogastrostomy/hepaticojejunostomy using ultraslim instruments
Authors: Hiroshi Kawakami, Yoshimasa Kubota
Journal: Endoscopy (2017)

Techniques for endoscopic ultrasonography (EUS)-guided biliary drainage (EUS-BD) have been developed, and EUS-guided antegrade stenting (EUS-AGS) and EUS-guided hepaticogastrostomy (EUS-HGS)/hepaticojejunostomy (HJS) are suitable for gastric outlet obstruction (GOO) or surgically altered anatomy. EUS-AGS alone carries the potential risk of causing bile leakage from a fistula; however, EUS-AGS in combination with EUS-HGS or EUS-HJS appears safer, as it can reduce the risk of a bile leak [1] [2].
Treatment of Primary Central Nervous System Lymphoma with a Combination of Intraventricular Administration of Rituximab and Systemic Chemotherapy.
Authors: Shujie Wang, Wei Zhang, Wei Lian, Yongji Wu, Nong Zou, Tienan Zhu, Daobin Zhou, Ying Xu, Ti Shen, Yongqiang Zhao
Journal: Blood (2006)
CSIG-13. ANDROGEN RECEPTOR IS INVOLVED IN GLIOBLASTOMA AND PRESENTS A POTENTIAL THERAPEUTIC TARGET
Authors: Iris Lavon, Nomi Zalsman, Tamar Canello, Hanna Charbit, Bracha Zelikovitch, Anat Mordechai, Yakov Fellig, Stav Rabani, Tal Shahar, Alexander Lossos
Journal: Neuro-Oncology (2016)

To investigate genetic alterations in glioblastoma (GBM), we performed a genome-wide copy number and loss of heterozygosity (LOH) array (OncoScan FFPE Express, Affymetrix) on DNA extracted from 5 formalin-fixed-paraffin-embedded GBM samples of 5 women. It revealed amplification of androgen receptor (AR) region (Xq12) in 4/5 samples, accompanied in 3/5 by LOH in the remaining allele. To examine whether the active or the inactive-X allele was lost, we preformed chromosome inactivation study based on the differential methylation patterns on GBM samples from 35 women. The results indicated that the inactive allele was lost in 34 samples. Quantitative-real-time-RT-PCR and western blot analysis on RNA (n=30) and protein (n=16) extracted from GBM samples from patients of both sexes demonstrated a significant induction of AR RNA (2.76-315,984 induction fold) in 93% and of protein expression (1.7-106 induction fold) in 87%. Oncomine™ (Compendia Bioscience, Ann Arbor, MI) used to analyze AR RNA amplification from several databases including the TCGA database, validated our results and showed a significant AR RNA fold change induction in GBM compared to normal brain. Furthermore, 30% of the tumors also expressed an AR-splice variant lacking the Ligand-Binding-Domain that has been postulated to be a major androgen-independent driver of AR-regulated gene expression. Antagonizing the AR by bicalutamide and enzalutamide on three glioma cell lines induced a dose dependent cell death. Enzalutamide demonstrated a higher efficacy rate than bicalutamide in all tested cell lines. Combination therapy with anti-AR agent and EGFR inhibitor in cell line with ligand independent AR splice variant yielded a better efficacy. We suggest that anti-AR signaling agents alone or combined with other therapies present a novel paradigm in the treatment of glioblastoma. We intend shortly to clinically evaluate efficacy of this approach.
IMST-09. IDENTIFICATION OF A NOVEL H3.3.K27M MUTATION-DERIVED NEOANTIGEN EPITOPE AND CLONING OF A SPECIFIC T-CELL RECEPTOR FOR T-CELL THERAPY IN GLIOMAS
Authors: Gary Kohanbash, Zinal Chheda, John Sidney, Kaori Okada, Shruti Shrivastav, Diego Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian Pollack, Angel Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada
Journal: Neuro-Oncology (2016)

Recent genetic studies have revealed that malignant gliomas in children and young adults often show shared missense mutations, in the gene encoding the replication-independent histone 3 variant H3.3. Approximately 70% of midline gliomas, such as diffuse intrinsic pontine gliomas (DIPG), harbor the amino-acid substitution from lysine (K) to methionine (M) at the position 27 of H3.3. T-cells are normally tolerant to wild-type self-proteins, but can recognize mutated peptide epitopes as non-self. Hence, tumor-specific missense mutations can be suitable targets (i.e. neoantigens) for cancer immunotherapy. We evaluated whether the H3.3 K27M mutation can induce specific cytotoxic T lymphocyte (CTL) responses in human leukocyte antigen (HLA)-A2+ CD8+ T-cells. In vitro stimulation of HLA-A2+ donor-derived CD8+ T-cells with a synthetic peptide encompassing the H3.3 K27M mutation (the H3.3.K27M epitope hereafter) induced CTL lines which recognized not only the synthetic H3.3.K27M epitope peptide loaded on T2 cells but also lysed HLA-A2+ DIPG cell lines which endogenously harbor the H3.3.K27M mutation. On the other hand, CTL lines did not react to HLA-A2+, H3.3 K27M mutation-negative cells or HLA-A2-negative, H3.3 K27M mutation+ cells. A competitive binding inhibition assay indicated that the H3.3.K27M epitope peptide, but not the non-mutant counterpart, has an excellent affinity (Kd 151 nM) to HLA-A2. Furthermore, CTL clones with high and specific affinities to HLA-A2-H3.3.K27M-tetramer were successfully obtained, and α- and β-chain cDNAs from a high-affinity T cell receptor (TCR) were cloned into a lentiviral vector. Human T-cells transduced with the lentiviral TCR demonstrated antigen-specific reactivity. Furthermore, critically important for safety of clinical application, alanine scanning demonstrated that the key amino-acid sequence motif in the epitope for the TCR reactivity is not shared by any known human protein. These data provide us with a strong basis for developing peptide-based vaccines as well as adoptive transfer therapy using autologous T-cells transduced with the TCR.
Efficacy of rikkunshito, a Japanese herbal medicine, on nausea, vomiting and anorexia in patients with uterine cervical or corpus cancer treated with cisplatin and paclitaxel –A randomized phase II study
Authors: S. Ohnishi, H. Watari, M. Kanno, Y. Oba, S. Takeuchi, T. Miyaji, S. Oyamada, E. Nomura, H. Kato, T. Sugiyama, M. Asaka, N. Sakuragi, T. Yamaguchi, Y. Uezono, S. Iwase
Journal: Annals of Oncology (2016)
Vasculae Reactions of Normal and Malignant Tissues in Vivo. I. Vascular Reactions of Mice to Wounds and to Normal and Neoplastic Transplants
Authors: Glenn H. Algire, Harold W. Chalkley, Frances Y. Legallais, Helen D. Park
Journal: JNCI Journal of the National Cancer Institute (1945)

Journal Article Vasculae Reactions of Normal and Malignant Tissues in Vivo. I. Vascular Reactions of Mice to Wounds and to Normal and Neoplastic Transplants Get access Glenn H. Algire, Glenn H. Algire Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold W. Chalkley, Harold W. Chalkley Search for other works by this author on: Oxford Academic PubMed Google Scholar Frances Y. Legallais, Frances Y. Legallais Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen D. Park Helen D. Park Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 6, Issue 1, August 1945, Pages 73–85, https://doi.org/10.1093/jnci/6.1.73 Published: 01 August 1945
Excess BMI in Childhood: A Modifiable Risk Factor for Type 1 Diabetes Development?
Authors: Christine Therese Ferrara, Susan Michelle Geyer, Yuk-Fun Liu, Carmella Evans-Molina, Ingrid M. Libman, Rachel Besser, Dorothy J. Becker, Henry Rodriguez, Antoinette Moran, Stephen E. Gitelman, Maria J. Redondo
Journal: Diabetes Care (2017)

We aimed to determine the effect of elevated BMI over time on the progression to type 1 diabetes in youth.We studied 1,117 children in the TrialNet Pathway to Prevention cohort (autoantibody-positive relatives of patients with type 1 diabetes). Longitudinally accumulated BMI above the 85th age- and sex-adjusted percentile generated a cumulative excess BMI (ceBMI) index. Recursive partitioning and multivariate analyses yielded sex- and age-specific ceBMI thresholds for greatest type 1 diabetes risk.Higher ceBMI conferred significantly greater risk of progressing to type 1 diabetes. The increased diabetes risk occurred at lower ceBMI values in children <12 years of age compared with older subjects and in females versus males.Elevated BMI is associated with increased risk of diabetes progression in pediatric autoantibody-positive relatives, but the effect varies by sex and age.
Physical activity prescription and engaging the entire ‘community of practice’
Authors: Jane Thornton
Journal: British Journal of Sports Medicine (2017)

I welcome the letter from Maiorana et al 1 and am delighted to respond. Thank you for your comments regarding our position statement.2 Referral to certified exercise professionals and other qualified healthcare practitioners can be an important tool to assist patients. The effectiveness of referral schemes has not always been demonstrated3–6; therefore, the search to identify the best …
Gene Expression Profiling of Pediatric MLL-Rearranged Leukemia: Relation between Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Leukemic Cell Lines.
Authors: Masami Ishii, Shuichi Tsutsumi, Tomohiko Taki, Kunihiro Nishimura, Xijin Ge, Masahiro Tsuchida, Misao Ohki, Fumio Bessho, Kanji Sugita, Eiichi Ishii, Hitoshi Ichikawa, Hiroyuki Aburatani, Yasuhide Hayashi
Journal: Blood (2006)
SURG-21. CASE-MATCHED STUDY OF EFFECT OF INTRA-OPERATIVE MRI ON EXTENT OF RESECTION AND CLINICAL OUTCOME IN GLIOMA PATIENTS UNDERGOING SURGICAL RESECTION
Authors: Richard Everson, Alexander Tucker, Matthew Garrett, Logan Marcus, Robert Harris, Robert Prins, Benjamin Ellingson, Linda Liau
Journal: Neuro-Oncology (2016)

Recent studies indicate that increased extent of resection of malignant gliomas correlates with extended survival. Intra-operative MRI (iMRI) has been purported as a tool to aid surgeons in increasing the extent of resection. While several institutions have adopted iMRI, no reports to our knowledge discuss the effects of discontinuing its use. From July 2004 to June 2008, our institution used an intra-operative 1.5T MRI scanner (iMRI) to aid in glioma resection surgery. However, when the institution moved physically into a new hospital, the iMRI unit was discontinued. Using a single surgeon retrospective database, we identified the 68 consecutive patients who underwent iMRI-assisted resection glioma surgery (19 grade II patients, 23 Grade III patients and 26 Grade IV) with. These patients were case-matched with patients undergoing resection by the same surgeon after iMRI was no longer available. The case and control groups were well-matched for age, gender, grade, location of tumor, proximity to eloquent cortex, primary vs. recurrent and preoperative volume. Use of iMRI was not significantly associated with improved extent of resection (mean 96% iMRI vs 94% p=0.3683), rate of gross total resection (60% iMRI vs 65% p=0.4948) or overall survival (3348 iMRI vs >3000 p=0.5488). Gross total resection and extent of resection greater than 90% was associated with improved survival for both groups, regardless of grade. However, patient age, and molecular markers were overall stronger predictors of survival. Gender, KPS, primary vs. recurrent tumor, and preoperative tumor volume were not associated with TTP or OS. While iMRI technology offers many theoretical advantages in the localization and resection of residual tumor that might otherwise be missed, the data in this study indicate that the use of iMRI itself was not significantly correlated with extent of resection or patient survival.