tbuckley/cabot-search huggingface dataset:
PDTB-07. CO-CLINICAL STUDY OF PANOBINOSTAT IN AN IMMUNOCOMPETENT GENETICALLY ENGINEERED BRAINSTEM GLIOMA MOUSE MODEL
Authors: Tammy Hennika, Guo Hu, Oren Becher
Journal: Neuro-Oncology (2016)

Diffuse intrinsic pontine glioma (DIPG) is one of the major causes of brain tumor-related death in children. Its prognosis has remained poor despite numerous efforts to improve survival. Panobinostat, a histone deacetylase inhibitor, is a targeted agent that has recently entered a phase I clinical trial for the treatment of children with recurrent or progressive DIPG. A co-clinical study using a transgenic mouse model of DIPG driven by PDGF-B signaling, p53 loss, and ectopic H3.3-K27M or H3.3-WT expression to investigate the efficacy of Panobinostat both in vitro and in vivo. In vitro, Panobinostat significantly reduced cell proliferation and viability, and induced apoptosis (average IC50s from 3 separate H3.3-K27M and H3.3-WT brainstem glioma cell lines: cell proliferation- 0.08 µM H3.3-K27M & 0.06 µM H3.3-WT; cell viability- 0.04 µM H3.3-K27M & 0.08 µM H3.3-WT). In vivo, pharmacokinetic analysis after systemic administration of Panobinostat at 20mg/kg daily for 3 days via intraperitoneal (i.p.) injections demonstrated an average drug concentration of 0.07 µM in normal cortex and 0.56 µM in tumor tissue. In addition, pharmacodynamics analysis showed increased levels of H3 acetylation in tumor tissue demonstrating that at this dosing schedule target inhibition can be achieved. Short-term in vivo treatments with Panobinostat at 20mg/kg daily for 5 days showed a significant decrease in tumor cell proliferation by 50% compared to vehicle, but did not induce apoptosis. Treatment with Panobinostat at 20mg/kg daily for > 5 days resulted in drug toxicity. At a well-tolerated dose of Panobinostat at 20mg/kg daily given twice a week, overall survival was not prolonged compared to vehicle-treated mice. Our co-clinical study demonstrates that Panobinostat is an effective targeted agent against DIPG tumor cells in vitro and in short-term in vivo efficacy studies, but survival benefit was not observed due to toxicity necessitating dose de-escalation.
A microbial signature for Crohn's disease
Authors: Victoria Pascal, Marta Pozuelo, Natalia Borruel, Francesc Casellas, David Campos, Alba Santiago, Xavier Martinez, Encarna Varela, Guillaume Sarrabayrouse, Kathleen Machiels, Severine Vermeire, Harry Sokol, Francisco Guarner, Chaysavanh Manichanh
Journal: Gut (2017)

<h3>Objective</h3> A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. <h3>Design</h3> We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. <h3>Results</h3> In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. <h3>Conclusions</h3> Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.
CLL-Cell Proliferation Measured by In Vivo Deuterium Labeling in Early Stage Patients and Correlation with Other Prognostic Markers.
Authors: Elizabeth J. Murphy, G. Hayes, L.Z. Rassenti, J. Voogt, C.S. Zent, T. Lin, W. Weirda, A. Greaves, K. Prado, M.K. Hellerstein, N. Chiorazzi, T.J. Kipps, Kanti R. Rai
Journal: Blood (2007)
Non-Cardiopulmonary Factors Affecting the Six-Minute Walk Distance in Patients with Sickle Cell Disease: Results From the Walk-PHaSST Study
Authors: Ruchika Goel, Kathryn L. Hassell, Roberto F Machado, Robyn J. Barst, Nancy Yovetich, Gregory J. Kato, Victor R. Gordeuk, Jane A Little, J Simon R Gibbs, Dean E. Schraufnagel, Reda E. Girgis, Erika Berman Rosenzweig, Claudia R. Morris, David B. Badesch, Sophie Lanzkron, Onyinye Onyekwere, Mehdi Nouraie, Oswaldo L Castro, Vandana Sachdev, Myron Waclawiw, Robert Woolson, Jonathan C. Goldsmith, Mark T Gladwin, Lakshmanan Krishnamurti
Journal: Blood (2011)
A randomized trial of atorvastatin versus placebo in women at high risk for breast cancer.
Authors: M. E. Wood, F. Kingsley, J. A. Ellerton, J. N. Atkins, S. S. Grubbs, H. B. Muss, J. E. Garber
Journal: Journal of Clinical Oncology (2010)

TPS141 Background: Chemoprevention studies are long and expensive. Gaining information about the feasibility of an agent using biomarker endpoints can save money and ensure that only the most promising agents move forward. This clinical trial will evaluate the effect of a statin on several breast cancer biomarkers (breast density, IGF1, cytologic atypia/proliferation). Statins have been chosen as they are safe, tolerable and there is epidemiologic and laboratory evidence to suggest that statins, specifically lipophilic statins, have breast cancer prevention properties. This study will provide important information regarding the feasibility of a larger chemoprevention study of statins using cancer development as the endpoint. Successful completion of this study will also validate this design of biomarker testing of potential chemoprevention agents within a cooperative group setting and add to data validating these specific biomarkers. Methods: Eligibility: Premenopausal women ≥ 35 years and at increased risk (due to family history, BRCA positivity, prior biopsy history or history of chemoradiotherapy for Hodgkins disease). Since 2005, 55 of 100 planned women have enrolled in this study. Randomization: Placebo or 40 mg of atorvastatin daily for 1 year. Participating Institutions: This study is being carried out at several CALGB institutions (both main member and CCOP sites). Monitoring: Women are monitored for sensitivity to statins (liver enzymes, CPK, and muscle injury) regularly. Information on medical, diet, physical activity, and body mass index are obtained at baseline and 12 months. Breast cancer biomarkers (mammographic density, serum IFG1, cytologic atypia and proliferation) are analyzed at baseline and 12 months. Mammographic density will be determined using the visual analogue scale. Endpoints: The primary endpoint of this study is to determine the effect of statins on mammographic density. This study has 80% power to detect a 3.5% difference in density (p=0.05). Secondary endpoints are to examine the influence of statin on IFG1 and tissue biomarkers (cytologic atypia and proliferation) and look at the interaction between biomarkers. Funding: This study is sponsored by the BCRF and CALGB. No significant financial relationships to disclose.
398PD PD-L1 status in Taiwanese lung adenocarcinoma patients: Comparison of PD-L1 immunohistochemical assays using antibody clones 22C3, SP142 and SP263 with clinicopathological correlation
Authors: Y-C. Yeh, S-F. Lin, C-H. Chiu, Y-C. Wu, W-Y. Hsieh, H-L. Ho, T-Y. Chou
Journal: Annals of Oncology (2016)
Concurrent chemotherapy immediately following erlotinib (E) or gefitinib (G) induced apoptosis in previously untreated patients with advanced or metastatic non-small cell lung cancer (NSCLC)
Authors: R. B. Natale, R. B. Natale
Journal: Journal of Clinical Oncology (2009)

e19014 Background: The EGFR-TKIs, E and G, block EGFR-mediated proliferative and anti-apoptotic signaling. The predominance of anti-proliferative effects over the latter mechanism is postulated as the reason that no additional benefit was observed when either agent was given concurrently with 1 st line chemotherapy in unselected NSCLC pts (INTACT 1 &amp; 2, TALENT &amp; TRIBUTE trials). However, a subset analysis of TRIBUTE pts with a never smoking history suggested that improved survival may occur when the pt population is partially enriched to increase the proportion with an EGFR-TKI induced apoptotic effect (Miller VA. Proc ASCO, 2004). We therefore hypothesized that pts demonstrating rapid tumor regression within a 3–4 week exposure to E or G represented a population highly enriched for the apoptotic effect and that immediate concurrent administration of chemotherapy would produce prolonged survival. Methods: Forty-one stage IIIB/IV pts, including 27 women and 14 men, median age 67 (range 41 to 88) with limited smoking history (21 never smokers, 20 former light smokers) were treated with E 100–150 mg/day (39 pts) or G 250 mg/day (2 pts) for an average of 26 days (range, 21–34) before response assessment. Twenty-two pts achieved objective tumor responses (2 CRs, 20 PRs) and immediately received 4–6 cycles of platinum-based chemotherapy concurrently with continued E or G (group A). E or G was discontinued in 19 pts not achieving objective response and platinum-based chemotherapy alone was given after a 10–14 day washout. Results: With a median follow-up of 24 mos, the median TTPs are 21+ mos and 7 mos and the median survivals are 31+ and 12 mos in groups A and B, respectively. Thus far, only 5 deaths have occurred in 22 group A pts. Results of EGFR mutation and other analyses in tumor tissue from 27 pts will be presented. Conclusions: These data suggest that EGFR-TKI induced apoptosis may act synergistically with concurrent 1 st line chemotherapy in pts with advanced or metastatic NSCLC and a new paradigm for incorporation of biologically targeted agents into chemotherapy regimens. [Table: see text]
Intravenous C1-INH [C1-INH(IV)] Use Among Patients with Hereditary Angioedema (HAE) in the United States (US) and Associated Health Care Resource Utilization (HCRU)
Authors: Marc A. Riedl, Aleena Banerji, Michael E. Manning, Earl Burrell, Namita Joshi, Dipen Patel, Thomas Machnig, Ming-Hui (Mindy) Tai, Douglas Watson
Journal: Journal of Allergy and Clinical Immunology (2017)
Her2/Neu expression in consecutive resected primary breast cancers in a community hospital
Authors: S. Welt, C. Miller, J. Irwin, L. Stripe, B. Holman, C. C. Lanning, D. A. Kostyal, W. R. Flesher
Journal: Journal of Clinical Oncology (2005)

9669 Background: The determination of breast cancer tissue Her2/neu receptor expression status has both prognostic and therapeutic implications for the patient. The scoring of receptor amplification has involved primarily two assays, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The latter methodology has been determined to correlate best with prognosis and response to Herceptin treatment, but is more costly. A compromise strategy is to carry out IHC and to repeat FISH analysis only on those of intermediate staining as up to 24% of these are true positives, while the +1 are essentially all negative and the +3 are all true positives. Methods: We have collected 131 consecutive surgical specimens in a community hospital where referral bias is minimal. US Labs, Irvine, CA, carried out all assays. Results: Of these 131 cases, 129 (98.5%) had Her2/neu testing by IHC. Of these, there were 7 (+3) positives (5.4%) and 20 intermediate, consisting of 6 scored as (+2) and 14 scored as (+1-+2). Four of the 6 samples scored as (+2) were further tested by FISH and found to be negatives. The weaker staining (+1-+2) samples were considered and treated as true negatives. Using this strategy only the 7 (+3) staining cases and the 2 (+2) staining cases were considered true positives, 0.0698 (0.0258,0.1138) or 7%, statistically different (p<0.05) from prior reported values. Conclusions: These data suggest that the true positivity rate for Her2/neu gene amplification will be grossly underestimated utilizing IHC to screen samples for FISH and only FISH analysis should be done. Alternatively, the true positivity rate in the general population may be much lower than has been estimated from data collected at tertiary hospitals where high risk patients are more likely to be referred. No significant financial relationships to disclose.
Initial first-in-human phase 1 results of PTC596, a novel small molecule that targets cancer stem cells (CSCs) by reducing BMI1 protein levels
Authors: G. Shapiro, J. Infante, T.M. Bauer, A. Prawira, P. Bedard, O. Laskin, M. Weetall, J. Baird, E. O'Mara, R. Spiegel
Journal: Annals of Oncology (2016)
<i>Notes from the Field:</i> Mortality Associated with Hurricane Matthew — United States, October 2016
Authors: Alice Wang, Anindita Issa, Tesfaye Bayleyegn, Rebecca S. Noe, Christine Mullarkey, Julie Casani, Craig L. Nelson, Aaron Fleischauer, Kimberly D. Clement, Janet J. Hamilton, Christopher Harrison, Laura Edison, Kathrin Hobron, Katie M. Kurkjian, Ekta Choudhary, Amy Wolkin
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Acceptability and Safety of Hydroxyurea for Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria
Authors: Michael R. DeBaun, Najibah Aliyu Galadanci, Shehu U. Abdullahi, Musa A. Tabari, Shehi Abubakar, Raymond Belonwu, Auwal Salihu, Kathleen A Neville, Fenella J. Kirkham, Baba PD Inusa, Yu Shyr, Sharon Phillips, Adetola A. Kassim, Lori C. Jordan, Muktar H. Aliyu, Brittany V. Covert
Journal: Blood (2014)
Oral Food Challenge Outcomes in Nut and Seed Allergy
Authors: Schweta R. Arakali, Daniel G. Winger, Li Wang, Todd D. Green
Journal: Journal of Allergy and Clinical Immunology (2017)

A need remains to define prognosticating factors among potentially nut and sesame seed allergic patients, to reduce volume of risky, time consuming oral food challenges (OFC). Retrospective chart review of patients undergoing peanut (PN), tree nut (TN), or sesame seed (SS) OFC in Children's Hospital of Pittsburgh of UPMC allergy/immunology clinic between 2006-2016. Quantitative/qualitative data were analyzed. Among eighty-three challenges reviewed to date (analysis ongoing), larger SPT wheal sizes were associated with failed PN challenges (median 6.0 mm [interquartile range 4-7.25] versus 0 mm [IQR 0-3.5] in passed, p<0.001), while this relationship was not seen with TN/SS (median 4.0 mm [IQR 0-6.5] vs 0 mm [IQR 0-4.75], p=0.209). There was no difference between sIgE levels in those who passed and failed PN/TN/SS challenges. Males were more likely to fail TN/SS challenges than females (50% vs. 12.5%, p=0.010), with a similar but not statistically significant trend for PN (42.1% vs. 16.7%, p=0.240). No association seen between failure and having first degree family members (regardless of number) with atopic disease, or a personal history of asthma, allergic rhinitis, or atopic dermatitis. Preliminary findings suggest that, among patients deemed to be low risk for OFC to TN/SS, neither SPT nor sIgE result is associated with outcome. While sIgE levels appear to be similarly nondiscriminatory in potentially PN-allergic patients, larger PN SPT results are associated with a higher proportion of failed challenges, potentially reducing OFC demand. At this point OFC remain an essential part of food allergy diagnosis, particularly for TN/SS allergy.
Quality Of Life (QoL) in Canadian Children With Peanut (PA), Sesame (SA) And Seafood Allergy (SFA)
Authors: Alexander Lyttle, Ann E. Clarke, Rick Chin, Lianne Soller, Moshe Ben-Shoshan, Stephen T. Cheuk, Yuka Asai, Edmond S. Chan
Journal: Journal of Allergy and Clinical Immunology (2017)
Tubastatin A, a Selective HDAC6 Inhibitor, Enhances Antigen-Presenting Cell (APC) Function and Restores the Responsiveness of Anergic CD4+ T Cells
Authors: Hongwei Wang, Zi Wang, Fengdong Cheng, Karrune V. Woan, Jennifer Rock-Klotz, Eva Sahakian, John Powers, Pinilla Javier, Joel Bergman, Alejandro Villagra, Alan Kozikowski, Eduardo M. Sotomayor
Journal: Blood (2011)
Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor Redirected-T Cells Against Multiple Myeloma
Authors: Xiuli Wang, Ryan Urak, Miriam Walter, Lihong Weng, Laura Lim, Ching Wong, Wen-Chung Chang, Sandra H. Thomas, Myo Htut, Amrita Krishnan, Stephen J. Forman
Journal: Blood (2016)
Predominant Reconstitution of B Lymphoid Precursors (hematogones) Following Cord Blood Stem Cell Transplantation Is Associated with Less Occurrence of Acute Graft-Versus-Host Disease and Superior Overall Survival.
Authors: Takahiro Shima, Toshihiro Miyamoto, Yoshikane Kikushige, Kenjirou Kamezaki, Katsuto Takenaka, Takanori Teshima, Koichi Akashi
Journal: Blood (2009)
KIF3A genetic Variation Is Associated with a Pediatric Asthma Phenotype Characterized By Past or Current Eczema Independent of Allergic Rhinitis
Authors: Elisabet Johansson, Jocelyn M. Biagini Myers, Lisa J. Martin, Hua He, Valentina Pilipenko, Tesfaye B. Mersha, Matthew T. Weirauch, Nathan Salomonis, Patrick H. Ryan, Grace K. LeMasters, David I. Bernstein, James E. Lockey, Gurjit (Neeru) K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2017)
Relationship Between Sputum TWEAK Levels and Childhood Asthma
Authors: Soo Yeon Kim, Jong Deok Kim, In Suk Sol, Min Jung Kim, Mi Seon Oh, Yun Seon Kim, Mina Kim, Jung Yeon Hong, Young A. Park, Yoon Hee Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
Journal: Journal of Allergy and Clinical Immunology (2017)
CD98hc expression to predict prognosis in renal cell cancer.
Authors: Gerald Prager, Marina Poettler
Journal: Journal of Clinical Oncology (2012)

26 Background: CD98, a transmembrane protein, has a heteromeric structure, consisting of a heavy subunit (CD98hc) and a light subunit, extracellular linked together via disulfid bounds. A genetic knockout of CD98hc is embryonic lethal and overexpression of CD98hc in somatic cells led to malignant transformation. CD98hc is highly expressed in low differentiated papillary, clear cell and chromophobe RCC, but not in benign tumors. Notably, CD98hc expression directly correlated with grade of differentiation. Methods: To evaluate a potential functional role of CD98hc in renal cancer cell metastatic behavior, we generated a stable low CD98hc clear cell RCC cell line (Caki2) via lentiviral shRNA infection and compared tumor cell behavior with a high expressing mock transfected control. Results: We found that tumor cell behavior such as proliferation (52 ± 3% less 3[H] thymidin – incorporation in low CD98hc/Caki2 cells), cell survival upon anoikis (46% late and 45% early apoptosis in low CD98hc/Caki2 cells compared to high/CD98hc/Caki2 cells with 18% late apoptosis and 64% early apoptosis) and invasion/transmigration (520 ± 67 cells / field after 24h in low CD98hc/ Caki2 cells and 1257 ± 346 cells / field in high CD98hc/Caki2 cells analyzed in a modified boyden chamber) were considerably impaired whenever CD98hc expression was downregulated. To examine the mechanism by which CD98hc affected metastatic tumor cell behavior, we introduced two mutations in a reconstitution (silent mutation). A truncation mutant interfered with integrin interaction and a two point mutations (Cys109Ser and Cys330Ser) mutant affected amino acid transporter activity. Whenever integrin/CD98hc interaction was impaired tumor cell behavior including cell proliferation, cell survival, invasio/transmigration, and cell spreading as well as signal transduction pathways including FAK, c-src, MEK/ERK pathways were significantly compromised resembling the low CD98hc phenotype. Conclusions: For these data we conclude that metastatic tumor cell behavior such as cell survival, invasion and proliferation are dependent on CD98hc expression in renal cancer cells.
Non–clear cell histology in patients with metastatic RCC as a prognostic indicator in the targeted therapy era.
Authors: Edward N. Rampersaud, Frederic Birkhauser, Joshua E Logan, Geoffrey Sonn, Yvonne Chan, Christine Anterasian, David Li, Frederic Pouliot, Fairooz F. Kabbinavar, Allan J. Pantuck, Arie S. Belldegrun
Journal: Journal of Clinical Oncology (2012)

454 Background: The role of targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) having non-clear cell histology (non-ccRCC) is still being defined. We sought to examine the factors associated with survival outcomes in patients presenting with various histological subtypes in the TT era. Methods: The UCLA Kidney Cancer Program database containing records of over 2000 patients was queried. The clinicopathologic factors between patients with clear cell subtype (ccRCC) and those with non-clear cell histology were compared using the Student’s T-test and the chi-square test for continuous and categorical variables, where appropriate. Survival outcomes were estimated using Kaplan-Meier (log rank). Univariate and multivariate Cox regression models were used to identify independent associations with survival. Results: Of 157 patients treated with FDA-approved TT, 132 (84%) had ccRCC while 25 (16%) had non-ccRCC. The two groups were balanced for baseline demographic variables, including gender, race, BMI, pack-years of smoking, T-stage, Fuhrman grade, performance status and UCLA Integrated Staging System (UISS) risk category. Median survival of patients with ccRCC and non-ccRCC was 41.6 and 18.1 months (p&lt;0.001). In univariate analysis, non-ccRCC was associated with a 2.7-fold risk of cancer specific death compared to ccRCC patients. Among patients receiving TT-only, median survival of patients with ccRCC and non-ccRCC was 35 and 15.4 months (p=0.007). A subset of ccRCC patients treated sequentially with IMT followed by TT had a median survival of 73 months. Worsening UISS risk class and non-ccRCC histology, but not age, gender, race, tobacco exposure history, or tumor size, were independently associated with the risk of cancer death. Conclusions: Non-clear cell histology remains a significant and independent risk factor for cancer specific death for mRCC patients treated by TT even after controlling for UISS risk category. [Table: see text]
A Phase III study of atezolizumab with carboplatin plus etoposide in patients with extensive-stage small cell lung cancer (IMpower133)
Authors: L. Horn, M. Reck, T.S.K. Mok, M. Johnson, D. Waterkamp, S. Lam, X. Tang, A. Sandler, A. Lopez-Chavez, G. Giaccone, S.V. Liu
Journal: Annals of Oncology (2016)