tbuckley/cabot-search huggingface dataset:
EPID-08. EFFECT OF HEALTH DISPARITIES ON OVERALL SURVIVAL OF PATIENTS WITH GLIOBLASTOMA
Authors: Jacob Mandel, Michael Youssef, Jooyeon Nam, Akash Patel, Diane Liu, Jimin Wu, Georgina Armstrong, Melissa Bondy, John de Groot
Journal: Neuro-Oncology (2018)

Glioblastoma (GB) is the most common primary malignant brain tumor in adults. It remains uncertain the potential effects of health disparities in this patient population. We conducted a retrospective chart review of newly diagnosed GB patients from 2000–2015 at a free standing dedicated cancer center (MD Anderson Cancer Center - MDACC) and a safety net county hospital (Ben Taub General Hospital - BT) located in Houston, Texas. We obtained demographics, insurance status, clinical variables, extent of resection, treatment, and other known prognostic variables (Karnofsky Score – KPS) to evaluate their role on overall GB survival (OS). We identified 1,073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, primary language, insurance status, marital status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) consisting of concurrent chemoradiation followed by adjuvant temozolomide between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p<0.0176). Of the 177 BT patients, 40 (23%) had KPS KPS <70 at diagnosis, compared to 6 (0.01%) of the 896 MDACC patients. Only 81 (45.8%) of BT patients received SOC compared to 577 (64%) of MDACC patients (p<0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p<0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had a KPS less than 70 at time of diagnosis and 77 (80%) did not have insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance potentially affecting their ability to receive SOC.
NCOG-11. FEASIBILITY AND EFFICACY OF AN IPAD-BASED COGNITIVE REHABILITATION PROGRAM IN BRAIN TUMOR PATIENTS
Authors: Jennie Taylor, Tracy Luks, Angela Jakary, Susan Chang, Jennifer Clarke, Nicholas Butowski, Nancy Ann Oberheim-Bush, Sarah Nelson, Jaap Reijneveld, Karin Gehring
Journal: Neuro-Oncology (2018)

To assess feasibility and effect on cognitive function and Health-Related Quality of Life (HRQoL) of an iPad-based intervention in grade 2 and 3 glioma patients stable off treatment. Patients with lower grade glioma suffer significant cognitive dysfunctions that impact their HRQoL. Formal cognitive rehabilitation is a limited resource that may be more available if deployed with a mobile device such as an iPad. Stable, grade 2 and 3 glioma patients with subjective cognitive complaints, complete a baseline computerized battery of standardized cognitive tests using the NIH Toolbox and HRQOL assessment with the FACT-BR. Patients then completed a novel, evidence-based, iPad based, brain tumor specific, cognitive rehabilitation program called ReMind over the next 3 months (~3 hours per week). NIH Toolbox and HRQOL assessments were repeated after completion of the rehabilitation, and again 9 months after baseline. Primary endpoint was feasibility with secondary endpoints of changes in cognitive scores and HRQOL assessments. To date, 10 patients have enrolled and completed baseline testing, of whom 5 have completed ReMind rehabilitation. Median age is 56 years. Median disease duration is 7.6 years. 5 patients have Oligodendrogliomas (IDH mutated and 1p19q deleted), 3 patients have Astrocytomas, IDH mutated, and 2 patients have Astrocytomas NOS. 5 are grade II and 5 are grade III. 5 had left hemisphere tumors, 4 had right hemisphere tumors, and 1 was bilateral. 10 had prior chemotherapy and 8 prior radiation. We anticipate enrolling another 5 – 10 patients and will present the updated feasibility data as well as changes in cognitive and HRQOL scores. As patients with lower grade tumors live longer, it is important to increase availability of cognitive interventions to improve HRQOL and outcomes. This iPad based approach provides in-home access to cognitive training and compensation strategies for patients with brain tumors.
EXTH-73. TARGETING THE SWEET-TOOTH OF GLIOMA
Authors: Martyn Sharpe, David Baskin
Journal: Neuro-Oncology (2018)

It has long been recognized that sugar transporters are often upregulated in cancers and the upregulation of the Glut3 glucose/galactose transporter in glioma is well described. We have identified that Glut14, the testicular-specific glucose/galactose transporter is also upregulated in GBM, and that levels of Glut3/Glut14 predict patient outcome. We used a Glut3/Glut14 substrate and glucose/galactose analogue, 4-deoxy 4-fluoro Galactose (4D4FG), to inhibit glycan synthesis in glioma, in vitro and in vivo. As 4D4FG is a potent inhibitor of both UDP-glucose 4-epimerase (GALE) and UDP-glucose 6-dehydrogenase (UGDH), we were able to observe aberrant glycan synthesis in glioma exposed to 4D4FG. Perturbation of glycan synthesis correlated with gliomal cell death in vitro, and is accompanied by loss of nuclear localization of glycosylated proteins. In a flank mouse model of primary GBM we compared the effects of three cycles of i.p. 4D4FG with vehicle. We found that 4D4FG initially caused a small shrinkage of tumors, and then slowed tumor growth by 35%, with respect to the controls. Using the upregulation of gliomal sugar transporters to differentially target cancer glycan metabolism is clearly deleterious to glioma. Anti-metabolites like 4D4FG will never be first-line chemotherapeutics in cancer treatment. However, such anti-metabolites may be very usefully used to pre-stress glioma, prior to chemoradiation, to differentially sensitize the tumor to conventional treatment.
STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial
Authors: Matthew J. Reilley, Patricia McCoon, Carl Cook, Paul Lyne, Razelle Kurzrock, Youngsoo Kim, Richard Woessner, Anas Younes, John Nemunaitis, Nathan Fowler, Michael Curran, Qinying Liu, Tianyuan Zhou, Joanna Schmidt, Minji Jo, Samantha J. Lee, Mason Yamashita, Steven G. Hughes, Luis Fayad, Sarina Piha-Paul, Murali V. P. Nadella, Xiaokun Xiao, Jeff Hsu, Alexey Revenko, Brett P. Monia, A. Robert MacLeod, David S. Hong
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL. <h3>Methods</h3> Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2&nbsp;mg/kg and the 3&nbsp;mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells. <h3>Results</h3> Thirty patients were enrolled, 10 at 2&nbsp;mg/kg and 20 at 3&nbsp;mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3&nbsp;mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7&nbsp;months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance. <h3>Conclusions</h3> AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing. <h3>Trial registration</h3> Registered at ClinicalTrials.gov: NCT01563302. First submitted 2/13/2012.
ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis
Authors: Mirja Rotinen, Sungyong You, Julie Yang, Simon G. Coetzee, Mariana Reis-Sobreiro, Wen-Chin Huang, Fangjin Huang, Xinlei Pan, Alberto Yáñez, Dennis J. Hazelett, Chia-Yi Chu, Kenneth Steadman, Colm M. Morrissey, Peter S. Nelson, Eva Corey, Leland W. K. Chung, Stephen J. Freedland, Dolores Di Vizio, Isla P. Garraway, Ramachandran Murali, Beatrice S. Knudsen, Michael R. Freeman
Journal: Nature Medicine (2018)
Low Serum Free Testosterone Association With Cardiovascular Mortality in Men With Stable CAD
Authors: Loukianos S. Rallidis, Christos Kotakos, Stelios Tsalavoutas, Andreas Katsimardos, Alexandros Drosatos, Maria Rallidi, Ekaterini Moustaka, Maria Zolindaki
Journal: Journal of the American College of Cardiology (2018)
Adiposity and Cardiometabolic Outcomes
Authors: Kaitlin H. Wade, George Davey Smith
Journal: JAMA Network Open (2018)

Haris Riaz, MD; Muhammad Shahzeb Khan, MD; Tariq Jamal Siddiqi, MBBS; Muhammad Shariq Usman, MBBS; Nishant Shah, MD; Amit Goyal, MD; Sadiya S. Khan, MD; Farouk Mookadam, MD; Richard A. Krasuski, MD; Haitham Ahmed, MD
Gut-brain axis and addictive disorders: A review with focus on alcohol and drugs of abuse
Authors: Elisabet Jerlhag
Journal: Pharmacology & Therapeutics (2018)

Due to the limited efficacy of existing medications for addictive disorders including alcohol use disorder (AUD), the need for additional medications is substantial. Potential new medications for addiction can be identified through investigation of the neurochemical substrates mediating the ability of drugs of abuse such as alcohol to activate the mesolimbic dopamine system. Interestingly, recent studies implicate neuropeptides of the gut-brain axis as modulators of reward and addiction processes. The present review therefore summarizes the current studies investigating the ability of the gut-brain peptides ghrelin, glucagon-like peptide-1 (GLP-1), amylin and neuromedin U (NMU) to modulate alcohol- and drug-related behaviors in rodents and humans. Extensive literature demonstrates that ghrelin, the only known orexigenic neuropeptide to date, enhances reward as well as the intake of alcohol, and other drugs of abuse, while ghrelin receptor antagonism has the opposite effects. On the other hand, the anorexigenic peptides GLP-1, amylin and NMU independently inhibits reward from alcohol and drugs of abuse in rodents. Collectively, these rodent and human studies imply that central ghrelin, GLP-1, amylin and NMU signaling may contribute to addiction processes. Therefore, the need for randomized clinical trials investigating the effects of agents targeting these aforementioned systems on drug/alcohol use is substantial.
Interactions between the Ig-Superfamily Proteins DIP-α and Dpr6/10 Regulate Assembly of Neural Circuits
Authors: Shuwa Xu, Qi Xiao, Filip Cosmanescu, Alina P. Sergeeva, Juyoun Yoo, Ying Lin, Phinikoula S. Katsamba, Goran Ahlsen, Jonathan Kaufman, Nikhil T. Linaval, Pei-Tseng Lee, Hugo J. Bellen, Lawrence Shapiro, Barry Honig, Liming Tan, S. Lawrence Zipursky
Journal: Neuron (2018)
Anti-CD44 antibody, ARH460-16-2, binds to human AML CD34+CD38- cancer stem cells and demonstrates anti-tumor activity in an AML xenograft model
Authors: Luis da Cruz, Fortunata McConkey, Ningping Feng, Daniel Pereira, Susan Hahn, Daniel Rubinstein, David Young
Journal: Cancer Research (2008)

3976   The CD44 glycoprotein was first identified in cells of hematopoietic origin. CD44 has been found expressed in several hematologic malignancies including AML, ALL, CLL and multiple myeloma. Further, CD44 has been shown to be expressed on the CD34+CD38- cancer stem cells in these malignancies. These findings suggest that targeting CD44 in leukemia may be an effective therapeutic strategy. Using Arius’ FunctionFIRST™ platform, ARH460-16-2, a monoclonal antibody targeting CD44, was discovered. This antibody has potent anti-tumor activity in solid tumor models of breast (CD44+CD24-/lo), liver and prostate cancer. Using flow cytometry, chimeric ARH460-16-2 (chARH460-16-2) was shown to bind to cancer cells from patients with AML, CLL, ALL (B and T), multiple myelomas and to cells from patients with Monoclonal Gammopathies of Undetermined Significance (MGUS), albeit at varying levels of binding. chARH460-16-2 also bound to various leukemia, lymphoma and multiple myeloma cell lines including KG-1, HL-60, CCRF-CEM and OPM, respectively. To determine whether ARH460-16-2 also recognizes CD44 on hemopoietic stem cells, flow cytometry was carried out on peripheral blood samples from patients with AML. The results showed that the antibody bound to all AML CD34+CD38- cancer stem cells. While ARH460-16-2 also bound normal hematopoietic CD34+CD38- stem cells, albeit to a lower degree, these data raise the possibility that ARH460-16-2 can target AML cancer stem cells in a therapeutic setting. Consistent with this notion, a non-GLP cynomolgus dose-ranging toxicology study using chARH460-16-2, did not detect abnormalities in the hematopoietic compartment even though chARH460-16-2 bound to variety of blood cell types. To assess the therapeutic potential in hematologic cancers chARH460-16-2 was tested in two established in vivo subcutaneous models of promyelocytic leukemia (HL-60) and AML (KG-1) in SCID mice. In these experiments, chARH460-16-2 had significant dose-responsive tumor growth inhibition in the KG-1 model (57% at 10 mg/kg) and an increase in the median survival of 62 days compared to 49 days in the control group. The antibody did not have anti-tumor activity in the HL-60 model. Because the maximum levels of binding to KG-1and HL-60, as determined by flow cytometry, were 100 and 4.5 fold above isotype respectively, it is possible that the therapeutic activity of the antibody may directly correlate with CD44 levels.  ARH460-16-2 is being developed as a therapeutic monoclonal antibody for solid tumors and hematologic malignancies based on its effectiveness in pre-clinical models. Its target, CD44, is expressed in a variety of hematologic malignancies and CD34+CD38- cancer stem cells in AML and extends its therapeutic utility.
Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent
Authors: Nicholas L. Opie, Sam E. John, Gil S. Rind, Stephen M. Ronayne, Yan T. Wong, Giulia Gerboni, Peter E. Yoo, Timothy J. H. Lovell, Theodore C. M. Scordas, Stefan L. Wilson, Anthony Dornom, Thomas Vale, Terence J. O’Brien, David B. Grayden, Clive N. May, Thomas J. Oxley
Journal: Nature Biomedical Engineering (2018)
Rate of pathological N2 nodes among patients of NSCLC with cN0/cN1 nodal status on CECT scan: A study from tertiary care hospital in India
Authors: B. Bansal, M. Gowda, V. Kumar, S. Deo, S. Bhoriwal, D. Jain, P. Malik, S. Jee Bharati, M.K. Yadav, S. Kumar
Journal: Annals of Oncology (2018)
Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial
Authors: Ruth Ladenstein, Ulrike Pötschger, Dominique Valteau-Couanet, Roberto Luksch, Victoria Castel, Isaac Yaniv, Genevieve Laureys, Penelope Brock, Jean Marie Michon, Cormac Owens, Toby Trahair, Godfrey Chi Fung Chan, Ellen Ruud, Henrik Schroeder, Maja Beck Popovic, Guenter Schreier, Hans Loibner, Peter Ambros, Keith Holmes, Maria Rita Castellani, Mark N Gaze, Alberto Garaventa, Andrew D J Pearson, Holger N Lode
Journal: The Lancet Oncology (2018)
Disease and Famine as Weapons of War in Yemen
Authors: Amir M. Mohareb, Louise C. Ivers
Journal: New England Journal of Medicine (2018)

Interview with Dr. Amir Mohareb on the humanitarian crisis and violations of medical neutrality in Yemen. (10:45)Download The infliction of suffering in the war in Yemen has particularly toxic characteristics that demand attention from health care providers worldwide: the destruction of health care facilities and the spread of disease and hunger as apparent means of waging war.
Tepotinib + gefitinib (TEP+GEF) in MET+/epidermal growth factor receptor (EGFR)-mutant non-small lung cancer (NSCLC): Phase II data
Authors: Y.-L. Wu, J. Zhou, S. Lu, Y. Zhang, J. Zhao, H. Pan, Y.-M. Chen, C.-F. Chian, R. Bruns, A. Johne, J. Scheele, Y. Cheng
Journal: Annals of Oncology (2018)
Interaction between dietary fat intake and the androgen receptor CAG and GGN repeat polymorphisms in prostate cancer
Authors: Cathryn H. Bock, Christine Neslund-Dudas, Kristin G. Monaghan, Benjamin A. Rybicki
Journal: Cancer Research (2005)

5810  Shorter length androgen receptor CAG repeat (AR CAGr) and GGN repeat (AR GGNr) genotypes and high dietary fat intake are potential risk factors for prostate cancer. A recent study (Zitzmann et al. Diabetologia 46:31-9;2003) has also shown a positive correlation between AR CAGr genotypes and markers of obesity such as body fat mass, leptin and insulin. We stratified the AR genotypes into two groups by base pair length:  20 for CAGr, and  15 for GGNr; the shorter repeat length was considered the risk genotype. Using logistic regression and a case-only approach, we tested for gene-environment interaction by estimating the association between genotype and dietary fat measures (percent of total calories from different types of fat) among 455 incident Caucasian and African American prostate cancer cases, adjusting for age, caloric intake, and race (where appropriate). For the entire sample, a less than multiplicative relationship between AR CAGr risk genotype and percent of calories from polyunsaturated fatty acids (PFA) intake was observed (p=0.015). After stratifying by race, this effect was only observed among the Caucasian men (p=0.020). When the cases were stratified into low and high prostate cancer aggressiveness categories, the effect was observed only in the highly aggressive group (p=0.003). In the entire sample, logistic regression results suggested a possible greater than multiplicative relationship between AR GGNr risk genotype and percent of calories from total fatty acids (TFA, p=0.094) and from saturated fatty acids (SFA, p=0.073), however neither increase was statistically significant. After stratifying by race, a greater than multiplicative relationship between AR GGNr and TFA (p=0.047) and monounsaturated fatty acids (MFA, p=0.035) was observed among African Americans; no interactions between AR GGNr and fat measures were observed among Caucasians. When stratified on aggressiveness, there was a suggestion of a greater than multiplicative relationship between AR GGNr and TFA (p=0.063), and AR GGNr and PFA (p=0.0631), and a statistically significant interaction between AR GGNr and saturated fatty acids (p=0.016) among the cases with highly aggressive disease. Our findings suggest that the AR CAGr and GGNr genotypes and dietary fat intake may be part of a complex interaction in the androgen-dependent pathway of prostate carcinogenesis.
Abstract 21329: Derivation and Validation of Simple Stroke Risk Score in a Thai Population
Authors: Parinya Chamnan, Panpaporn Konepan, Arkhom Arayawichanont, Prasert Boongird, Somsak Laptikultham, Wannee Nitiyanant, Wichai Aekplakorn
Journal: Circulation (2017)

Introduction: Most stroke risk prediction equations were developed in Western populations. These risk scores perform less well in Asian populations, who have different background risk. Hypothesis: This study aimed to develop and validate a new stroke risk algorithm for estimating 5-year risk of developing stroke in a Thai general population using large electronic health records. Methods: This retrospective cohort was derived from the linkage of health checks data with diagnostic information from electronic health records of 483,285 men and women residing in Ubon Ratchathani. It was randomly and evenly divided into the derivation and validation cohorts. An outcome of interest was first recorded diagnosis of stroke over a period of 6 years between January 2006 and December 2012. A Cox proportional hazards model was used to estimate effects of risk factors on stroke risk and to derive a risk equation in the derivation cohort. Measures of discrimination, global model fits and calibration were calculated in the validation cohort. Results: The derivation cohort comprised of 241,643 individuals aged ≥30 years, who contributed 1,393,990 person-years of follow-up and 1,884 incident cases of stroke, while the validation cohort comprised of 241,642 individuals (1,393,420 person-years), with 1,915 incident cases of stroke. The risk equation was 0.0584 x Age (years) + 0.4538 x Sex (Male=1) + 0.0040 x Systolic BP (mmHg) + 0.2886 x Hypertension (present=1) + 0.5214 x Diabetes (present=1) + 0.0266 x Body mass index (kg/m 2 ) - 0.0039 (if exercise 1-2 days/week) or -0.2827 (if exercise 3-5 days/week) or -0.3179 (if exercise &gt;5 days/week). The stroke risk equation had a reasonably good discriminatory ability in the validation cohort, with the area under the receiver operating characteristic curve of 0.756 (95%CI 0.750-0.772). The risk equation had good global model fit as measured by Bayesian information criteria. The Gronnesby and Borgan test showed good calibration, with chi-square statistic of 701.43 (p&lt;0.001). Conclusions: This simple stroke risk score is the first risk algorithm to estimate the 5-year risk of stroke in a Thai general population. The risk score does not need laboratory tests and can therefore be used in clinical settings and also by the public.
Kaposi’s varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab
Authors: David M. Miller, Ryan M. Trowbridge, Anupam Desai, Reed E. Drews
Journal: Journal for ImmunoTherapy of Cancer (2018)

Background: Immune-directed therapies have become front-line therapy for melanoma and are transforming the management of advanced disease.In refractory cases, multi-modal immunoncology (IO) approaches are being utilized, including combining immune checkpoint blockade (ICB) with oncolytic herpes viruses.Talimogene laherparepvec (T-VEC) is the first genetically modified oncolytic viral therapy (OVT) approved for the treatment of recurrent and unresectable melanoma.The use of IO in patients with concomitant malignancies and/or compromised immune systems is limited due to systematic exclusion from clinical trials.For example, a single case report of a solid organ transplant patient successfully treated with T-VEC for metastatic melanoma has been reported.Furthermore, the use of ICB in T-cell malignancies is limited and paradoxical worsening has been described.To our knowledge, this is the first report of dual ICB/T-VEC being administered to a patient with concurrent primary cutaneous anaplastic large cell lymphoma (pcALCL) and melanoma.Case presentation: Here we present the case of a patient with concomitant primary cutaneous ALCL and metastatic melanoma, progressing on anti-programmed death (PD)-1 therapy, who developed Kaposi's varicelliform eruption after receiving the first dose of Talimogene laherparepvec.Conclusion: This case highlights the complexities of care of patients with coexistent cancers, demonstrates rapid progression of primary cutaneous ALCL on nivolumab and introduces a novel adverse effect of Talimogene laherparepvec.