tbuckley/cabot-search huggingface dataset:
HGG-08. SURVIVAL OUTCOMES OF PEDIATRIC HIGH-GRADE GLIOMA: RESULTS OF A 20-YEAR SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Cassie Kline, Erin Felton, Isabel Allen, Peggy Tahir, Sabine Mueller
Journal: Neuro-Oncology (2017)

BACKGROUND: Recurrent pediatric high-grade glioma (HGG) is a leading cause of cancer-related death in children. There is currently no standard of care therapy for this population. Limited survival data on pediatric patients with recurrent HGG makes design of novel clinical trials challenging. We report results of a meta-analysis investigating survival outcome in pediatric patients diagnosed with recurrent HGG over the last 20 years. METHODS: MEDLINE/PubMed, EMBASE, Web of Science and Cochrane Review databases were searched for relevant studies reporting on survival outcomes for pediatric patients with first-time recurrent HGG treated between 1996–2016. Included studies were limited to those published in English. Two independent reviewers completed study reviews. Overall survival (OS) and progression-free survival (PFS) were calculated cumulatively over all studies, by therapy subgroup, and by treatment provided pre- and post-2006. Random effects models were used for overall survival and subgroup comparisons to control for heterogeneity as measured by the I2 statistic. RESULTS: A total of 14 studies were included across 3 treatment strategies. Nine studies investigated traditional chemotherapy, 3 investigated targeted therapy, and 1 each investigated immunotherapy and radiotherapy. A total of 150 patients with a median age of 10.5 years were included. Average cumulative PFS was 55 days (95% CI 21, 88). Average cumulative OS was 201 days (95% CI 166,236). OS using targeted therapies was 215 days (95% CI 130,301) compared to 170 days (95% CI 142,198) in studies using traditional chemotherapy. OS in studies done before 2006 was 168 days (95% CI 140, 197) compared to 201 days (95% CI 166, 236) in studies completed after 2006. CONCLUSIONS: Pediatric patients with recurrent HGG suffer from poor progression-free and overall survival, regardless of therapy used. There may be a trend towards improved OS over the last 10 years and with the use of targeted therapies.
Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial
Authors: Martin Markowitz, Ian Frank, Robert M Grant, Kenneth H Mayer, Richard Elion, Deborah Goldstein, Chester Fisher, Magdalena E Sobieszczyk, Joel E Gallant, Hong Van Tieu, Winkler Weinberg, David A Margolis, Krischan J Hudson, Britt S Stancil, Susan L Ford, Parul Patel, Elizabeth Gould, Alex R Rinehart, Kimberly Y Smith, William R Spreen
Journal: The Lancet HIV (2017)
MITIGATION OF ACL RUPTURE IN ALPINE SKIING THROUGH SKI BINDINGS
Authors: Rick Howell
Journal: British Journal of Sports Medicine (2017)

Background ACL-ruptures are the most prevalent injury in alpine skiing competition. Shaped skis produce 2 abduction forces with a centroid that can generate large abduction/valgus-moments and small tibia-torques that cause ACL-rupture before tibia-fracture. Ordinary alpine ski bindings address tibia-fracture. Objective Prove, biomechanically, that ordinary bindings cannot release in response to applied-abduction forces before ACL-rupture, whereas bindings with additional lateral heel release can. Design A ski is affixed to an anthropometrically-correct metallic foot-tibia-femur test-frame that simulates skiing-ACL slip-catch injury-kinematics similar to ISO 9462 Annex-B — also measuring applied abduction force and resultant abduction/valgus-moment. Initially, no ski-bindings are utilized: the ski is bolted beneath the metallic foot. The proximal end of the metallic femur is rigidly attached to the test frame as during maximal internal rotation. Abduction force is applied to a range of positions along the medial edge of the ski while measuring combined peak abduction/valgus-moments and peak tibia-torques—at ACL-rupture—according to a validated ACL-rupture algorithm of an average US male. 2-mode and 3-mode bindings are interposed to quantify their interaction. Setting Biomechanical. Patients (or Participants) None, biomechanical. Interventions (or Assessment of Risk Factors) None, biomechanical. Main Outcome Measurements 3-mode-release bindings can release below the rupture-limit of the ACL; 2-mode bindings cannot. Results An abduction centroid can produce ACL rupture before tibia-fracture when applied to a ski -70 cm to -20 cm aft of the tibia at 155 N to 200 N (21% to 27% of average US male body weight) whereas tibia-fracture is produced when an abduction centroid is applied aft of −70 cm. Conclusions Abduction centroids applied to the medial edge of a ski can produce tibia-fracture or ACL-rupture depending upon the magnitude and the central position of the applied abduction forces. 3-mode bindings with additional lateral heel release can release below the ACL-rupture limit. A prospective intervention study is needed for full-proof.
Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma
Authors: Gustavo Schvartsman, Kristen Perez, Jill E. Flynn, Jeffrey N. Myers, Hussein Tawbi
Journal: Journal for ImmunoTherapy of Cancer (2017)

Immunotherapy plays a key role in the treatment of metastatic melanoma. Patients with autoimmune conditions and/or on immunosuppressive therapy due to orthotropic transplants, however, are systematically excluded from clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus to be approved by the FDA for cancer therapy. To our knowledge, this is the first report of T-VEC being administered in the setting of an organ transplant recipient.Here we present the case of a patient with recurrent locally advanced cutaneous melanoma receiving salvage T-VEC therapy in the setting of orthotropic heart transplantation. After 5 cycles of therapy, no evidence of graft rejection has been observed to date, and the patient achieved a complete remission, and is currently off therapy.This case advocates for further investigation on the safety and efficacy of immunotherapeutic approaches, such as T-VEC, in solid organ transplant recipients.
Effective management of breathlessness: a review of potential human rights issues
Authors: Metin Başoğlu
Journal: European Respiratory Journal (2017)

Chronic breathlessness is a distinct clinical syndrome defined as "breathlessness that persists despite an optimal use of the therapeutic resources available to treat the underlying causative condition" [1, 2]. This is a frequent clinical condition encountered in chronic respiratory diseases, cardiac diseases, neuromuscular disorders, terminal cancers, whether respiratory or not, and in patients receiving mechanical ventilation for acute or chronic respiratory failure. The above definition includes not only chronic conditions, but also acute breathlessness that persists despite maximal pathophysiological treatment. The term "persistent" breathlessness has been proposed to encompass both acute and chronic situations [2]. Persistent or not, breathlessness is under-recognised by respiratory physicians, particularly in settings of advanced palliative care or intensive care, where verbal communication is difficult [3, 4], thereby leading to calls for greater awareness of this problem [5, 6]. Currow et al. [7] have pointed to the need to assess and treat chronic breathlessness with opioids as outlined in specialist clinical guidelines and argued that failure to do so is a breach of human rights. In this editorial, I expand further on this issue in the hope of clarifying potential moral and human rights issues in proper clinical management of chronic breathlessness or breathlessness in general. As breathlessness is an intensely traumatic event, the issue of proper psychological care of patients is also briefly addressed. Failure to assess and treat breathlessness properly may raise moral and human rights issues <http://ow.ly/v2BN30be8a7> Thanks are due to Thomas Similowski for his valuable comments on the manuscript. This article was prepared as part the author's research and knowledge dissemination programme supported by Spunk Fund, Int.
TRTH-01. PRECLINICAL ACTIVITY OF TEMOZOLOMIDE WITH MORPHINE COMBINATION IN THE THERAPY OF GLIOBLASTOMA MULTIFORME
Authors: Anna Lisa Iorio, Martina Da Ros, Lorenzo Genitori, Maurizio De Martino, Iacopo Sardi
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is a highly invasive and aggressive primary brain tumor and is considered one of the deadliest forms of cancer.Despite aggressive therapies, half of GBM patients die within 15 months after diagnosis and only 2% survive more than 5 years.Therefore, effective treatments for Downloaded from https://academic.oup.com/neuro-oncology/article/19/suppl_4/iv51/3859511 by guest on 14 August 2023 *Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IGF-1R, insulin-like growth factor 1 receptor; KPS, Karnofsky Performance Scale; RT, radiotherapy; SOC, standard of care; TMZ, temozolomide.
Transgastric retrograde endoscopic ultrasound sampling of a mediastinal mass in a patient with radiation-induced trismus
Authors: Matheus Franco, Andrew Strong, Prabhleen Chahal, Joseph Veniero, Brian Burkey, John Vargo, Amit Bhatt
Journal: Endoscopy (2017)

Endoscopic ultrasound (EUS) guidance is a safe and effective technique for sampling mediastinal lesions [1] [2] [3]. We report a case where an EUS was done in retrograde fashion through a gastrostomy because of the patient’s limited degree of mouth opening due to trismus.
Co-Occurrence of <i>COMT</i> and <i>BRCA1/2</i> Variants in a Population
Authors: Mercedeh Movassagh, Prakriti Mudvari, Anelia Horvath
Journal: New England Journal of Medicine (2017)

In one database, 5 of 15 women with BRCA1/2 nonsense or frameshift mutations had a synonymous substitution p.L203 in the catechol O-methyltransferase gene. This substitution, present in 1% of 60,418 people, did not occur in 25 women with BRCA1/2-mutated breast cancer.
Vocal laughter punctuates speech and manual signing: Novel evidence for similar linguistic and neurological mechanisms
Authors: Robert R Provine
Journal: Behavioral and Brain Sciences (2017)

Abstract Vocal laughter fills conversations between speakers with normal hearing and between deaf users of American Sign Language, but laughter rarely intrudes on the phrase structure of spoken or signed conversation, being akin to punctuation in written text. This punctuation effect indicates that language, whether vocal or signed, is dominant over laughter, and that speech and manual signing involve similar mechanisms.
TRTH-34. NOVEL ORAL PRODRUGS OF 6-DIAZO-5-OXO NORLEUCINE IMPROVE BRAIN PENETRATION AND DEMONSTRATE EFFICACY AGAINST MYC-DRIVEN ORTHOTOPIC MEDULLOBLASTOMA XENOGRAFTS
Authors: Allison Hanaford, Charles Eberhart, Eric Raabe
Journal: Neuro-Oncology (2017)

Increased MYC levels can alter cellular metabolism, creating a reliance on glutamine. Glutamine PET and MRI spectroscopy demonstrate that aggressive brain malignancies have increased uptake of glutamine and increased glutamate relative to normal brain, suggesting that agents targeting glutamine metabolism may be active in brain tumors. The most aggressive subgroup of medulloblastoma tumors are driven by high expression of MYC, so we hypothesized that these tumors would have altered glutamine metabolism and be sensitive to 6-diazo-5-oxo norluecine (DON), a glutamine analog. Western blotting revealed that expressing MYC in human cerebellar-derived neural stem and progenitor cells (CB NSC) induced the expression of glutaminase (GLS), the enzyme that converts glutamine to glutamate-a critical step in glutamine metabolism. Human neural stem cells transformed with SV40 do not express MYC and thus do not express GLS. MYC-expressing patient-derived medulloblastoma cell lines (D425MED and D283MED) also express GLS. We treated our MYC-transformed CB NSC and medulloblastoma cell lines with DON and observed an increase in apoptosis of up to 450% as determined by cleaved caspase-3 immunofluorescence (p=0.001). DON treatment did not significantly increase apoptosis in SV40-immortablized CB NSC (p=0.65) and had no effect on normal, untransformed human NSC. DON is not orally bioavailable, so we decided to develop DON prodrugs designed for improved oral bioavailability and brain penetration. In non-human primates, our DON prodrug exhibited superior 10-fold enhanced CSF/plasma ratio versus DON. In orthotopic xenograft models, our novel DON prodrugs increased the median survival of mice bearing D425-MED MYC-driven medulloblastoma tumors by 60 percent (22 days for vehicle treated mice compared to 35 days for prodrug treated mice, p<0.01 by log-rank test). DON prodrugs can be engineered to improve oral bioavailability and brain penetration, and these drugs have efficacy in orthotopic xenograft models of aggressive MYC-driven medulloblastoma tumors.
Inhibition of the Mitochondrial Protein Import Machinery Is Selectively Cytotoxic to Acute Myeloid Leukemia (AML) Cells and Stem Cells
Authors: Danny V Jeyaraju, Veronique Voisin, Changjiang Xu, Rose Hurren, Marcela Gronda, Xiaoming Wang, Yulia Jitkova, Joelle Soriano, Neil MacLean, Gary D Bader, Aaron D. Schimmer
Journal: Blood (2016)
Christina Theodoris
Authors: Pam Goldberg Smith
Journal: Circulation Research (2017)

laboratory at Gladstone Institutes, focusing on gene regulatory networks and their disruption in cardiac disease to identify targets for network-correcting therapies.As an artist and a scientist, Christina endeavors to strike a balance between her 2 passions, using her experiences in art to move forward through the setbacks and missteps that are an accepted part of the scientific process as, after all, "there are no mistakes in art." What Can You Say About Your Current Project and What Excites You About It?My research in the Srivastava laboratory harnessed humaninduced pluripotent stem cell-based disease modeling to reveal the transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency in calcific aortic valve disease (CAVD). 2 After mapping the gene networks disrupted by NOTCH1
Outcomes of non-small cell lung cancer patients with adenocarcinoma histology compared with other histologies: SEER registry data 2004-2008.
Authors: Monika Joshi, John M. Varlotto, Suhail M. Ali, Jennifer Toth, Michael Reed, Allan Lipton, Chandra Prakash Belani
Journal: Journal of Clinical Oncology (2012)

e17560 Background: For convenience, the majority of lung cancers are commonly lumped together as non-small lung cancer (NSCLC). Patients with adenocarcinoma of the lung have a higher incidence of driver mutation as compared to those with squamous histology. In addition pemetrexed containing regimens have preferential activity in this histology and agents such as bevacizumab are administered to this subgroup only based on toxicity. The currentanalysis was performed to compare outcomes for patients in the SEER database between 2004 and 2008 with adenocarcinoma (Adenoca), squamous cell carcinoma (SCCA) and NSCLC not otherwise specified (NOS). Methods: Data for 161,175 patients was available in SEER database between 2004 and 2008 with 38 different histology ICD codes. 134,947 patients (83.7%) were included in the study. NSCLC NOS (ICD-3 8046) n=36,408, SCCA (ICD-3 8070) n= 36, 454 and Adenoca (ICD-3 8140) n=62,085. Overall survival (OS) and lung cancer specific survival (LCSS) were analyzed using cox proportional Hazard model for the 3 groups. Results: Patients in the three groups were age-matched. Male gender was more common in patients who had SCCA compared to Adenoca (62.6% vs. 49.5%). Percentage of poorly differentiated tumors was higher in patients with SCCA (35.9%) compared to NSCLC NOS (32%) and Adenoca (27.5%). SCCA had fewer stage IV patients at diagnosis (29.5%) vs. 51.4 % for NSCLC NOS and 45% for Adenoca. OS and LCSS are listed in the table below with Hazard ratio (HR) and p value. Total of 23.54% (n=31,768) patients underwent surgical resection. Stage I patients who underwent surgery (n=18,517) also had similar results. Conclusions: NSCLC patients who have adenocarcinoma histology have significantly better overall outcome when compared to other histologies. The difference is more pronounced in an earlier stage disease. [Table: see text]
PET Tracer <sup>18</sup>F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models
Authors: Shuntaro Oka, Masaru Kanagawa, Yoshihiro Doi, David M Schuster, Mark M Goodman, Hirokatsu Yoshimura
Journal: Theranostics (2017)

18F-Fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid; anti-18F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3H-2-deoxy-2-fluoro-D-glucose (3H-FDG), 3H-choline chloride (3H-choline), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14C-fluciclovine, 3H-FDG, and 3H-choline, but not 99mTc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99mTc-HMDP accumulated mostly in osteoblastic lesions. 14C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14C-fluciclovine and 3H-FDG existed, based on histological differences: low 14C-fluciclovine and high 3H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14C-fluciclovine was not clear, yet clearer than with 3H-FDG. Although half of the osteoblastic lesions with 14C-fluciclovine accumulation showed negligible 3H-choline accumulation in comparison, they were histologically similar to lesions with marked 14C-fluciclovine and 3H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions.
Vitamin E and Selenium Fail to Prevent Dementia in Men
Authors: Anita Slomski
Journal: JAMA (2017)

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A multicenter dose-finding study of irinotecan (CPT-11) based on <i>UGT1A1</i> polymorphisms for metastatic colorectal cancer.
Authors: Hirohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Kozo Yoshikawa, Tomohiko Miyatani, Hideya Kashihara, Chie Mikami, Noriko Matsumoto
Journal: Journal of Clinical Oncology (2013)

e14572 Background: Recent pharmacogenetic studies on irinotecan have revealed significant associations of UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms *28 and *6, the latter being specifically detected in East Asians resulting in severe toxicity such as severe diarrhea and neutropenia. It is necessary that the dose-finding trial that decided the optimal dose according to the gene polymorphism to draw out the maximum therapeutic effect while evading the side effect. Here, we present the final report of prospective trial of safety and efficacy about FOLFIRI ± bevacizumab (Bev) therapy according to each gene type of UGT1A1for Japanese patients with advanced CRC in second-line setting. Methods: Between September 2008 and March 2012, 59 patients were enrolled in this study. Grouping was defined as follows: wild group; both *28 and *6 were wild types, hetero group; *28 and either *6 was hetero type, and homo group; 28/*28 and *6/*6* or a both hetero types. In the 59 patients with advanced CRC treated with FOLFIRI ± Bev as a second line, wild and hetero groups were administered 150mg/m 2 irinotecan, and homo group was 100mg/m 2 . The incidences of severe toxicities according to gene type of UGT1A1, the response rate and progression-free survival were investigated. Results: In the 59 patients, wild group was 28 (47%), hetero group was 26 (44.1%) and homo group was 5 (8.5%). 8 patients (29%) showed severe toxicities (grade 3 or more) in wild group, 5 patients (19%) in hetero group, 1 patient (20%) in homo group (P=0.71). Regarding the response rate, CR, PR, SD, PD was observed in 1 (4.0%), 1 (4.0%), 5 (20.0%) and 18 patients (72.0%), respectively in wild group, 0 (0.0%), 2 (8.3%), 5 (20.8%) and 17 patients (70.8%), in hetero group, 0 (0.0%), 0 (0.0%), 1 (20.0%) and 4 patients (80.0%), in homo group. The overall response rate (CR+PR) was 8.0% in wild group, 8.3% in hetero group, 0% in homo group (P=0.80). As for progression-free survival, the number of cycle to PD was 12.1 cycles (2-35 cycles) in wild group, 8.3 (2-20) in hetero group, 9.8 (6-14) in homo group (P=0.15). Conclusions: The dosages of 150mg/m 2 irinotecan in hetero group, 100mg/m 2 in homo group are safe and effective in FOLFIRI ± Bev therapy in the second line. Clinical trial information: UMIN000004773.