tbuckley/cabot-search huggingface dataset:
The skin barrier function gene <i><scp>SPINK</scp>5</i> is associated with challenge‐proven IgE‐mediated food allergy in infants
Authors: S. E. Ashley, H.‐T. T. Tan, P. Vuillermin, S. C. Dharmage, M. L. K. Tang, J. Koplin, L. C. Gurrin, A. Lowe, C. Lodge, A.‐L. Ponsonby, J. Molloy, P. Martin, M. C. Matheson, R. Saffery, K. J. Allen, J. A. Ellis, D. Martino
Journal: Allergy (2017)

Abstract Background A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 ( SPINK 5 ) skin barrier gene have previously been associated with allergic conditions. Objective To determine whether genetic variants in and around SPINK 5 are associated with IgE‐mediated food allergy. Method We genotyped 71 “tag” single nucleotide polymorphisms (tag‐ SNP s) within a region spanning ~263 kb including SPINK 5 (~61 kb) in n=722 (n=367 food‐allergic, n=199 food‐sensitized‐tolerant and n=156 non‐food‐allergic controls) 12‐month‐old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss ( TEWL ) measures were collected at 12 months from a subset (n=150) of these individuals. SNP s were tested for association with food allergy using the Cochran‐Mantel‐Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food‐allergic, n=330 non‐food‐allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value ( PPV ) or challenge, corrected for ancestry by principal components. Results SPINK 5 variant rs9325071 (A⟶G) was associated with challenge‐proven food allergy in the discovery sample ( P =.001, OR =2.95, CI =1.49‐5.83). This association was further supported by replication ( P =.007, OR =1.58, CI =1.13‐2.20) and by meta‐analysis ( P =.0004, OR =1.65). Variant rs9325071 is associated with decreased SPINK 5 gene expression in the skin in publicly available genotype‐tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. Conclusions We report, for the first time, association between SPINK 5 variant rs9325071 and challenge‐proven IgE‐mediated food allergy.
“Was it worth it?” A pilot study of advanced cancer patients’ retrospective perceptions of benefit from phase I trial participation
Authors: J. Y. Bruce, F. J. Hlubocky, C. K. Daugherty
Journal: Journal of Clinical Oncology (2007)

19670 Background: Subjects who enroll in phase I cancer trials generally are those with advanced and terminal disease. Although all such patients (pts) undergo an informed consent process, there is evidence that these pts may not appreciate the primary aims of a phase I trial and have unrealistic expectations of therapeutic benefit. However, these perceptions of benefit have not been described in pts after trial enrollment. Methods: As a pilot study, pts previously enrolled on Phase I trials were interviewed regarding their retrospective perceptions of benefit. A total of 9 pts have been interviewed to date: median age: 72 yr (range: 59–82 yr); 55% male; 77% Caucasian. The interview included open-ended questions assessing patient experiences with the trial, including reasons for enrollment, impressions of quality of life, costs incurred, and other benefits. Pts’ qualitative responses were recorded and analyzed for content and themes. Results: Reasons for enrollment included hope, prior treatment failure, altruism, and family influence. Described perceptions of anticipated benefit included stabilization of disease and close monitoring of their disease. Unexpected costs involved time spent during clinic visits, financial costs, time taken off work by family members, time spent away from family, and additional trial procedures. Issues of quality of life revolved around side effects from the investigational agent. Many interviewed pts (44%) described improved quality of life off the trial as compared to during trial participation. The majority of interviewed pts (67%) believed that the trial had no effect on their survival. Conclusions: Our data suggest that pts’ perceptions of therapeutic benefit after trial enrollment may be different from pre-enrollment expectations. There would also appear to be potentially significant and otherwise undescribed out-of-pocket expenses incurred by subjects as a result of phase I enrollment. Further research is needed to examine how side effects, unexpected costs, and lack of improved survival contribute to these pts’ perceptions of trial benefit. No significant financial relationships to disclose.
Transcriptosome and Serum Cytokine Profiling of B-CLL Identifies Oncogenic Pathways in Pathogenesis and Survival.
Authors: James Choi, Harinder Garewal, Christopher Riley, Laurence Cooke, Thomas Klinkhammer, Sirisha Maddipati, Rohit Sud, Catherine Spier, Daruka Mahadevan
Journal: Blood (2006)
NIMG-54. AMINE CEST MRI, A FAST AMINO ACID AND PH-WEIGHTED MOLECULAR IMAGING TECHNIQUE, CORRELATES WITH 18F-FDOPA PET AND IMAGE-GUIDED BIOPSY IN HUMAN GLIOMA
Authors: Robert Harris, Linda Liau, Kevin Leu, Phioanh Nghiemphu, Whitney Pope, Albert Lai, Timothy Cloughesy, Benjamin Ellingson
Journal: Neuro-Oncology (2016)

Extracellular acidosis and significant amino acid uptake are hallmarks of gliomas. Chemical exchange saturation transfer (CEST) MRI targeted the amine protons on amino acids can serve as a combined amino acid and pH-weighted biomarker with a high specificity for active tumor. We hypothesized that amine CET MRI may provide similar specificity, but higher spatial resolution, compared with 18F-FDOPA PET and that regions of increased amine CEST contrast may contain regions of active proliferating tumor. Eighteen glioma patients underwent pH-weighted amine CEST MRI prior to surgical resection and biopsy. Of these, eight also had 18F-FDOPA PET data acquired prior to surgery. PET and CEST data were registered to anatomical images. ROIs were defined on the highest 20% and lowest 20% of PET uptake values within the FLAIR-enhancing region and the CEST contrast within these ROIs was calculated. Among the larger cohort of eighteen patients, an acidic and non-acidic target was defined by CEST MRI and biopsied during surgery. These samples were stained for Ki67 and HIF1a. Amine CEST MRI and 18F-FDOPA PET uptake showed similar patterns of abnormality and regions of elevated CEST contrast also showed significantly elevated 18F-FDOPA uptake (P=0.002). Elevated CEST contrast showed significantly higher expression of Ki67 compared to non-acidic targets (P=0.034). HIF1a expression was correlated with CEST contrast. Amine CEST MRI provides contrast dependent on both amino acid concentration and pH, provides similar specificity and higher spatial resolution when compared with 18F-FDOPA PET, and is significantly correlated with histological measures of active, hypoxic tumor.
RARE-02. CLINICAL INTERROGATION FOR UNVEILING AN ISOLATED HYPOPHYSITIS MIMICKING PITUITARY ADENOMA
Authors: Jeong Hoon Kim, Young Hoon Kim
Journal: Neuro-Oncology (2016)

A hypophysitis is not a common disease entity mimicking a pituitary adenoma. In spite of the crucial disease involving a pituitary gland, there has been minimal research regarding the hypophysitis. In this study, we described the constellation of the preoperative findings including clinical, radiologic, and endocrinologic features, as well as postoperative outcomes of the hypophysitis. The authors reviewed the data retrospectively of a total of 2,814 patients underwent microsurgery with pituitary mass lesion. As a result, a total 21 cases were enrolled consisting of the 13 cases of tumor-associated and the 8 cases of isolated hypophysitis. In this study, the isolated hypophysitis was focused on the analysis. All patients with isolated hypophysitis were evaluated the clinical, radiologic, endocrinologic tests pre and postoperatively. The 8 cases of isolated hypophysitis were lymphocytic (4 cases), granulomatous (3 cases), and IgG4-related (1case) hypophysitis. The patients presented a wide range of clinical symptoms from general weakness to panhypopituitarism. In addition, the most remarkable radiologic features of the isolated hypophysitis were infundibular thickening and the low signal intensity in T1WI and T2WI. All 8 patients with isolated hypophysitis presented endocrinologic deficiency with a various extent in preoperative biochemistry. After surgery, the profiles of hormonal status were not changed in 4 patients (50 %), however, aggravated in 4 patients (50 %). The 3 patients (37.5 %) complained visual field defects in preoperative ophthalmologic test, improved all after surgery. In this study, the preoperative clinical manifestations, radiologic and endocrinologic features of hypophysitis were described comprehensively. In addition, we also revealed the long-term outcomes of hypophysitis in the aspect of visual function and endocrinologic outcomes. In conclusion, the visual function outcomes were satisfactory, however, the endocrinologic outcomes were vice versa, because the preoperative endocrinologic deterioration was unchanged or aggravated after surgery.
MPTH-13. GENETICALLY-GUIDED TREATMENTS OF GLIOBLASTOMA IN THE ELDERLY POPULATION
Authors: Shota Tanaka, Akitake Mukasa
Journal: Neuro-Oncology (2016)

Based on the two phase III trials (NOA-08 and Nordic trial), adjuvant treatments for newly-diagnosed glioblastoma (GBM) in the elderly population now tend to be stratified by MGMT promoter methylation status. The most recent phase III trial (CE.6), however, demonstrated superiority of concurrent/adjuvant use of temozolomide (TMZ) along with hypofractionated radiotherapy (hRT) over hRT alone, regardless of methylation status. We retrospectively reviewed outcomes of our elderly GBM patients to optimize treatment strategies. Twenty-six patients of age 70 or greater newly diagnosed with GBM were treated at the University of Tokyo Hospital since 2008. Before 2012, 16 patients were treated with Stupp regimen (-2012 group), whereas 10 patients were treated after 2013 according to MGMT methylation status determined by methylation-specific PCR (2013- group): hRT alone when unmethylated and TMZ alone when methylated. Median age was 75.5 years (range, 70-85). There were 13 male patients (50%). Median KPS score was 70 (40-100). Tumors were located most often in the frontal lobe. Gross total resection was achieved in 8 (31%), subtotal/partial resection in 11 (42%), and biopsy in 7 (27%). Tumors were all IDH1-R132H negative. MGMT methylation was noted in 11 patients (48%) among 23 patients whose tumor tissues were available. With the median follow-up of 11 months, median overall survival was 11 and 13 months for -2012 and 2013- groups, respectively, among cases with methylated MGMT, whereas it was 17 and 8 months respectively among those with unmethylated MGMT. For methylated GBM, TMZ alone and Stupp regimen seem equivalent in efficacy. Evaluation of quality of care and neurocognitive function would be important. For unmethylated GBM, Stupp regimen apparently achieves better outcomes than hRT alone. Addition of TMZ and/or higher RT dose may affect outcomes favorably. Further refinement of treatments would be warranted in this subgroup.
OS5.3 Stability of actionable mutations in primary and recurrent glioblastomas
Authors: K. Draaisma, M. Taphoorn, A. Weyerbrock, M. Sanson, T. Gorlia, V. Golfinopoulos, J. M. Kros, P. A. Robe, M. M. J. van den Bent, P. J. French
Journal: Neuro-Oncology (2016)

4 weeks versus 6.7 weeks in the BEV/LOM and LOM arm, respectively; p<0.001), reflecting the difference in time to progression between arms.
Allogeneic Hematopoietic Peripheral Blood Stem-Cell Transplantation From HLA-Identical Siblings Versus Allelic-Matched Unrelated Donors (10/10 high resolution) in Patients with Acute Myeloid Leukemia and Myelodyplasic Syndrome After Reduced Intensity Conditioning,
Authors: Marie Robin, Raphael Porcher, Lionel Ades, Emmanuel Raffoux, Nicolas Boissel, Jérome Larghero, Chantal Himberlin, Claude Gardin, Alain Delmer, Pierre Fenaux, Hervé Dombret, Gérard Socié, Régis Peffault de Latour
Journal: Blood (2011)
Thiopurine Methyl Transferase (TPMT) Activity and Erythrocyte Thioguanine Nucleotide Levels Are Reliable Markers of Tolerability to 6-Mercaptopurine in Adult Acute Lymphoblastic Leukemia
Authors: Manju Sengar, Murari Gurjar, Anand Patil, Vikram Gota, Hasmukh Jain, Hari Menon, Uma Dangi
Journal: Blood (2015)
Graft-Versus-Tumor Activity Against Renal Cell Carcinoma in a Mouse Model of HSCT.
Authors: Teresa Ramirez-Montagut, Andrew Chow, Adam A. Kochman, Vanessa M. Hubbard, David Suh, Odette M. Smith, Hamad Sindhi, Theis H. Terwey, Theo D. Kim, Elisha Waldman, Onder Alpdogan, Marcel R.M. van den Brink
Journal: Blood (2005)
Abstract 8: GTPase-Activating Protein for Rho Associated with FAK (GRAF) Regulates Cardiomyocyte Membrane Integrity
Authors: Thomas J O'Neill, Kaitlin Lenhart, Jason Doherty, Mauricio Rojas, Mack P Christopher, Joan M Taylor
Journal: Circulation Research (2012)

Cardiac myocytes are unique in their requirement to sustain continuous repetitive contraction in the setting of intense mechanical stress while simultaneously maintaining high membrane integrity for an appropriate electrical gradient. The consequence of failure of the membrane repair response has been highlighted in recent reports linking cardiomyocyte membrane fragility with cardiac degeneration in patients as well as in their analogous mouse models. Herein, we describe a novel role for GTPase activator for Rho associated with Focal Adhesion Kinase (GRAF) in regulating cardiomyocyte membrane integrity. We previously published that disruption of GRAF in Xenopus laevis resulted in progressive skeletal muscle degeneration. We now show that GRAF-depleted tadpoles exhibit defective cardiac formation and function. Interestingly, damage of muscle cells in vivo and in vitro led to a translocation of GRAF to the sarcolemma, suggesting that GRAF may be an important component of the cardiac membrane repair machinery. To further explore this possibility, we generated GRAF hypomorphic mice that exhibit greater than 99% reduction of endogenous GRAF expression. While GRAF deficient mice show normal Mendelian birth distribution and are viable, they exhibit a modest skeletal muscle pathology. Although baseline cardiac integrity was not compromised in GRAF deficient mice, treatment either with cardiotoxin or intraperitoneal injection of isoproterenol led to elevated cardiomyocyte membrane damage (assessed by Evan’s blue dye uptake) in GRAF deficient compared to control mice (19% vs 2% of myocytes within afflicted ventricular area for cardiotoxin, 18% vs 8% for isoproterenol respectively). Moreover, cultured GRAF null myocytes exhibited a significantly attenuated membrane resealing response following laser-mediated disruption compared to GRAF-containing control cells as assessed by accumulation of the membrane impermeable dye, FM-143. As well, the survival rate after injury of GRAF-deficient cells was markedly attenuated (20% vs 85% in control cells). While cardiac cell membrane damage is likely a frequent and important event, the repair process is currently understudied, and this is the first report to implicate a Rho regulator in this response.
Non small cell lung cancer (NSCLC) patients harboring BRAF mutation: Clinical characteristics and management in real world setting. Cohort BRAF EXPLORE GFPC 02-14
Authors: J.B. Auliac, S. Bayle, A. Vergnenegre, G. Fraboulet, H. Lecaer, L. Falchero, P. Dô, H. Doubre, P.A. Hauss, A. Vinas, S. Larive, A.M. Chiappa, B. Marin, C. Chouaid
Journal: Annals of Oncology (2016)
Influence of adjuvant chemotherapy on anti-müllerian hormone (AMH) level in patients younger than 35 years treated for an early breast cancer (EBC)
Authors: M. Saint-Ghislain, F. Clatot, M. Degrémont, M. Leheurteur, M. David, C. Veyret, F. Di Fiore, A. Perdrix
Journal: Annals of Oncology (2016)
FALCON: A phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer
Authors: M.J. Ellis, I. Bondarenko, E. Trishkina, M. Dvorkin, L. Panasci, A. Manikhas, Y. Shparyk, S. Cardona-Huerta, K.-L. Cheung, M.J. Philco-Salas, M. Ruiz-Borrego, Z. Shao, S. Noguchi, L.M. Grinsted, M. Fazal, M. Stuart, J.F. Robertson
Journal: Annals of Oncology (2016)
Apurinic/Apyrimidinic Endonuclease 1 Induced Genomic Instability Causes T-Cell Acute Lymphoblastic Leukemia in Zebrafish
Authors: Jianhong Lin, Chun Yang, Ariel Kwart, Jianjun Zhao, Mehmet K Samur, Weihong Zhang, Purushothama Nanjappa, Teresa Calimeri, Xiubao Ren, Dongdong Ma, Xiaofeng Jiang, Yi Zhou, Masood Shammas, Kenneth C. Anderson, Jon C. Aster, Leonard I. Zon, Robert I. Handin, Nikhil C. Munshi
Journal: Blood (2015)
BMET-05. EVALUATION OF SURVIVAL FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM BREAST CANCER
Authors: Tiffanie Do, Andrew Keller, Rahim Ismail, Talayesa Buntinx-Krieg, Jacqueline Babb, Esther Kim, Gurjaspreet Bhattal, Joshua Dajac, Shilpa Kailas, Zoran Pavlovic, Aryan Sarparast, Naren Ramakrishna
Journal: Neuro-Oncology (2016)

We examined the impact of patient- and tumor-specific factors on overall survival in patients with breast brain metastases cancer treated with SRS. We conducted a single-institution IRB-approved retrospective chart review on 47 patients with 158 total breast cancer brain metastases treated with linear accelerator-based SRS between November 2008 and January 2014. Patients included in the study were treated with SRS and had at least one follow-up MRI. Survival was defined as the interval from initial SRS treatment to death. Actual survival was calculated using the Kaplan-Meier method with 95% confidence intervals. Multiple parameters were evaluated for potential relation to survival including prior WBRT, KPS at initial presentation, and histological subtype. Log rank tests were used to evaluate the impact of these parameters on survival. The median follow-up of all metastases was 5.9 months. There was a significant difference in median survival between patients with KPS 90 versus KPS 70 (P=0.032). There was no significant difference in median survival in patients with: prior WBRT (9.59 months, P=0.19); ER positive tumor makers (15.97 months, P=0.56); PR positive tumor markers (20.01 months, P=0.17); HER2 positive tumor markers (14.32 months, P=0.51). Our study supports previous research and further evaluated KPS as significant prognostic factor in brain metastases from breast cancer. Prior WBRT, ER positive, PR positive, and HER2 positive mutation status did not have a significant effect on overall survival following SRS for brain metastases from breast cancer in our study. The assessment of the impact of prior WBRT was limited by the small number of patients with these abnormalities in the study group. These results support the use of SRS for good performance breast cancer patients regardless of marker status.
BMET-37. RADIOSURGICAL TREATMENT FOR ELDERLY PATIENTS WITH BRAIN METASTASES
Authors: Se-Hyuk Kim, Sang Ryul Lee, Mi Ra Seo, Ae Hwa Jang, Tae-Hoon Roh
Journal: Neuro-Oncology (2016)

This study was designed to investigate the treatment results of Gamma Knife radiosurgery (GKRS) for elderly patients (age ≥65) with brain metastases and the relevant factors associated with survival. We retrospectively analyzed the data of 106 patients treated with GKRS for 1 to 15 brain metastases. The median age at the time of treatment was 72 years (65~86), and the median Karnofsky performance status score was 90 (50~100). The most common primary tumor site was the lungs (n =86). The mean lesion volume was 2 cc (0.001~41.2). A median prescription dose of 20 Gy was delivered to the median 50 % isodose line. The median overall survival time was 5.8 ± 1.0 months. During the median follow-up duration of 5.6 ± 1.1 months (0.2~54), 85 patients died of primary cancer progression, and 1 died of uncertain cause. Twenty-two patients underwent repeat GKRS or whole brain radiation therapy for newly developed or progressive brain metastases. Among various factors, primary tumor control (p = 0.001, HR: 0.215, 95% CI: 0.116~0.398) and female (p < 0.001, HR: 0.521, 95% CI: 0.330~0.822) were significant favorable factors for survival after univariate and multivariate analysis. The median survival time of patients with controlled primary tumor vs. uncontrolled was 33.9 ± 12.0 vs. 4.0 ± 0.5 months, and the median survival time of female patients vs. male patients was 14.6 ± 4.1 vs. 4.2 ± 0.6 months. GKRS for elderly patients with brain metastases appears to provide outcomes comparable to younger patients. According to our results, we suggest that radiosurgical treatment should be recommended to female patients with brain metastases when their primary cancer is controlled, even when they are aged 65 years or more. Age should not be an impediment to treatment in this selected group.
Oral vinorelbine in combination with cisplatin or carboplatinin adjuvant chemotherpy of non-small cell lung cancer aprospective multicentre study of feasibility and tolerability
Authors: Vítězslav Kolek, Ivona Grygarová, Jiří Chalupa, Leona Koubková, Jiřina Švecová, Jana Skřičková, Leona Ostřížková, Dimka Sixtová
Journal: Journal of Thoracic Oncology (2009)
Genome-Wide Analysis Reveals MYC-Dependent Cell Death and Identifies Predictive Biomarkers of Ixazomib Sensitivity in Preclinical Models of T-Cell Lymphoma (TCL) and Hodgkin Lymphoma (HL)
Authors: Ravi Dashnamoorthy, Afshin Behesti, Nassera Abermil, Jaya Sharma, Michael Coyle, Irawati Kandela, Andrew Mazar, Lynn Hlatky, Andrew M. Evens
Journal: Blood (2014)
Osteopontin Predicts for Survival and Cystatin C-Based Estimated GFR Predicts for Renal Response to Therapy in Patients with Primary Systemic Amyloidosis
Authors: Evangelos Terpos, Efstathios Kastritis, Evelina Charitaki, Michalis Michail, Georgios Boutsikas, Eurydiki Michalis, Sosana Delimpasi, Marie-Christine Kyrtsonis, Meletios A. Dimopoulos
Journal: Blood (2008)