tbuckley/cabot-search huggingface dataset:
US targets companies touting unproven cancer cures
Authors: Michael McCarthy
Journal: BMJ (2017)

The US Food and Drug Administration (FDA) has issued warning letters to 14 companies that the agency says are marketing products fraudulently claiming to diagnose, treat, or cure cancer.1

Under US law it is illegal to market products that claim to prevent, diagnose, mitigate, or cure disease without having demonstrated to the FDA that they are safe and effective for these uses.

Douglas W Stearn, director of the FDA’s Office of Enforcement and Import Operations, said that the use of such products might not only be unsafe but could lead patients to delay seeking appropriate, and …
P09.47 Longterm survival after tumor treating fields (TTFields) therapy
Authors: A. Rulseh, J. Šroubek
Journal: Neuro-Oncology (2017)

Introduction: Glioblastoma multiforme (GBM) is the most common and malignant primary intracranial tumor and traditionally has a median survival of only 10 to 14 months, with only 3 to 5% of patients surviving more than three years. Recurrence (RGBM) is nearly universal, and further decreases the median survival to only 5 to 7 months with optimal therapy. Materials and Methods: Tumor treating fields (TTFields) therapy is a novel treatment technique that has recently shown significant prolonged progression free survival and overall survival in newly diagnosed GBM. The so-called Optune therapy is approved for the treatment of newly diagnosed and recurrent GBM and is based on the principle that low intensity, intermediate frequency alternating electric fields (100 to 300 kHz) have an anti-mitotic effect in specific cell types. The applied fields disrupt the mitotic spindle, microtubule assembly and the segregation of intracellular organelles during cell division, leading to apoptosis or mitotic arrest. Results: Our center was the first in the world to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals (10 GBM and 10 RGBM) in 2004 and 2005, and 4 of the original 20 patients are still alive today (2 GBM, 2 RGBM), in good health and no longer receiving any treatment roughly 12 years after initiating TTField therapy, with no clinical or radiological evidence of recurrence. Conclusions: Our results indicate that TTField treatment may be remarkably successful for both newly diagnosed or recurrent GBM patients. Further investigation is needed to identify any unique characteristics of these patients.
India launches strategy to curb antimicrobial resistance
Authors: Sumi S Dutta
Journal: BMJ (2017)

India’s health ministry has announced the country’s first plan to curb antimicrobial resistance, including measures to prevent misuse of antibiotics by doctors, consumers, and healthcare institutions.

The National Action Plan on Antimicrobial Resistance (2017-21) is the first to assign coordinated tasks to multiple government agencies involving health, education, environment, and livestock to change prescription practices and consumer behaviour and to scale up infection control and antimicrobial surveillance.

Health officials said that the plan aims to tackle longstanding concerns that antibiotic misuse in the human and animal health sectors in India is contributing to antimicrobial resistance that threatens public health in India and other countries.

Releasing …
Response to: ‘The time has come to revisit alternative interpretations of data underlying the EULAR management recommendations for rheumatoid arthritis’ by Pirilä <i>et al</i>
Authors: Josef S Smolen, Robert B M Landewé, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

The views presented by Pirila et al, 1 which focus primarily on the FINnish Rheumatoid Arthritis Combination therapy (FIN-RACo) trial, have been taken into serious consideration by the task force. Indeed, as extensively explained in the text accompanying the updated European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations,2 several committee members referred to the references provided by Pirila et al as well as other publications on this topic. The discussion also included comments that in some countries local societies recommended combination therapy with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (csDMARDs), and this is also mentioned in the publication. Nevertheless, after a long debate regarding csDMARD combinations, the task force arrived at …
OS07.6 A combination of TERT and MGMT improves the prognostication of glioblastomas
Authors: H. Arita, K. Yamasaki, Y. Kanemura, A. Mukasa, M. Nagane, K. Ueki, R. Nishikawa, T. Komori, Y. Narita, K. Ichimura
Journal: Neuro-Oncology (2017)

Intorduction: Recent comprehensive genomic analysis have revealed many genetic alterations in diffuse gliomas, but few markers besides IDH and 1p19q are utilized for diagnosis in the CNS WHO 2016. In particular, diagnostic and/or prognostic markers for IDH-wild tumors are not defined, except for H3.1/3.3. TERT promoter mutation frequently occurs in GBMs among IDH-wild tumors, but its prognostic impact remains controversial. In order to evaluate the influence of TERT, we analyzed a large cohort of IDH wild type tumors. Materials and Methods: One hundred fifty-one grade II-III and 453 GBM cases without IDH mutations were included. All GBM cases were treated with standard radiotherapy and temozolomide. Molecular statuses including IDH, MGMT and TERT were assessed by pyrosequencing and/or Sanger sequencing using frozen tumor tissues for all cases. The survival data were analyzed with the log-rank test and univariate and multivariate Cox regression analyses.Results: In grade II-III cases, TERT mutations were observed in 54% cases and associated with shorter survival (16.1 months for TERT-mutated vs. 34.8 months for TERT-wild cases, p<0.0001). Next, we analyzed a series of GBM cases. In this series, 58% cases harbored TERT mutations and showed slightly but significantly shorter survival (16.3 months for TERT-mutated vs. 20.8 months for TERT-wild cases, p<0.01). A multivariate Cox proportional hazard model incorporating clinical background and MGMT status showed that TERT mutations have adverse impact on survival and that their prognostic impact significantly interacted with MGMT status (p=0.006). When stratified by a combination of TERT and MGMT statuses, the median overall survival was 14.6 months for TERT-mutated/MGMT-unmethylated, 18.8 months for TERT-wild/MGMT-unmethylated, 26.5 months for TERT-wild/MGMT methylated and 30.0 months for TERT-mutated/MGMT-methylated cases. Thus, GBM cases with TERT-mutated/MGMT-unmethylated had the poorest outcome. Conclusions: Our results indicate that TERT mutation is a poor prognostic factor for GBMs as well as grade II-III gliomas. TERT mutations with wild-type IDH indicate under-diagnosed GBMs in grade II-III gliomas. In GBMs, TERT-mutated/MGMT-unmethylated cases show the most unfavorable prognosis, and the combination of TERT and MGMT statuses improves the prognostication.
P2.03b-001 A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis
Authors: Qing Zhou, Bin Gan, Qunying Hong, Mengzhao Wang, Xiaoqing Liu, Liwei Yuan, Ye Hua, Hongcan Ren, Weiguo Su, Yi Long Wu
Journal: Journal of Thoracic Oncology (2017)
Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy
Authors: Laura K. Ferris, Burkhard Jansen, Jonhan Ho, Klaus J. Busam, Kenneth Gross, Doyle D. Hansen, John P. Alsobrook, Zuxu Yao, Gary L. Peck, Pedram Gerami
Journal: JAMA Dermatology (2017)

Expression of long intergenic non-protein coding RNA 518 (LINC00518) and preferentially expressed antigen in melanoma (PRAME) genes, obtained via noninvasive adhesive patch biopsy, is a sensitive and specific method for detection of cutaneous melanoma. However, the utility of this test in biopsy decisions made by dermatologists has not been evaluated.To determine the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in decisions to biopsy a series of pigmented skin lesions.In this secure web-based, multiple-reader-multiple-case study, 45 board-certified dermatologists each evaluated 60 clinical and dermoscopic images of clinically atypical pigmented lesions, first without and then with PLA gene expression information and were asked whether the lesions should be biopsied. Data were collected from March 24, 2014, through November 13, 2015.Participants were given a report for each lesion, which included the results of an assay for expression of LINC00518/PRAME and a PLA score with data on the predictive values of the information provided.Biopsy sensitivity and specificity with vs without PLA data.Forty-five dermatologists (29 male and 16 female) performed the evaluation. After incorporating the PLA into their decision as to whether to biopsy a pigmented lesion suggestive of melanoma, dermatologists improved their mean biopsy sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to 56.9% (P < .001) with PLA data.The noninvasive PLA enables dermatologists to significantly improve biopsy specificity while maintaining or improving sensitivity. This result may increase the number of early melanomas biopsied and reduce the number of benign lesions biopsied, thereby improving patient outcomes and reducing health care costs.
DRES-03. INHIBITION OF HOMOLOGOUS RECOMBINATION RESENSITIZES TEMOZOLOMIDE-RESISTANT GLIOMA CELLS TO TEMOZOLOMIDE
Authors: Shigeo Ohba, Yuichi Hirose
Journal: Neuro-Oncology (2017)

TMZ is a DNA-methylating agent. TMZ-induced O6-methylguanine adducts, in the absence of repair by O6-methylguanine DNA methyltransferase (MGMT), mispair with thymine during the next DNA replication cycle, leading to futile DNA mismatch repair (MMR) by the MMR system, formation of double strand breaks (DSBs) and eventual cell death of glioma cell lines. Several mechanisms have been proposed about the acquisition of resistance to TMZ in glioblastomas, such as changes of expression of MGMT, MMR, nucleotide excision repair and homologous recombination. To clarify the mechanisms of resistance to TMZ and to find the way to overcome the resistance to TMZ, several clones of U251 cells resistant to TMZ were obtained and analyzed. FACS analyses showed several patterns of cell cycle distributions of the cells treated with TMZ. Resistant clone #3 showed G2 arrest at day3 and this arrest was abrogated sooner compared to the G2 arrest of original U251. TMZ-induced DSBs in the resistant cells were rapidly disappeared compared to those in U251 cells. G2 arrest was not found in clone #8 after TMZ exposure. The protein levels of MSH6, which was associated with MMR, was reduced in the cells. By suppression of Rad51, which was a major factor associated with homologous recombination, the resistant clone #3 was re-sensitized to TMZ, however clone #8 was not. These results suggested that inhibition of homologous recombination may be a viable means to resensitize some kinds of TMZ-resistant gliomas to TMZ.
Evolutionary History of Chemosensory-Related Gene Families across the Arthropoda
Authors: Seong-il Eyun, Ho Young Soh, Marijan Posavi, James B. Munro, Daniel S.T. Hughes, Shwetha C. Murali, Jiaxin Qu, Shannon Dugan, Sandra L. Lee, Hsu Chao, Huyen Dinh, Yi Han, HarshaVardhan Doddapaneni, Kim C. Worley, Donna M. Muzny, Eun-Ok Park, Joana C. Silva, Richard A. Gibbs, Stephen Richards, Carol Eunmi Lee
Journal: Molecular Biology and Evolution (2017)

Chemosensory-related gene (CRG) families have been studied extensively in insects, but their evolutionary history across the Arthropoda had remained relatively unexplored. Here, we address current hypotheses and prior conclusions on CRG family evolution using a more comprehensive data set. In particular, odorant receptors were hypothesized to have proliferated during terrestrial colonization by insects (hexapods), but their association with other pancrustacean clades and with independent terrestrial colonizations in other arthropod subphyla have been unclear. We also examine hypotheses on which arthropod CRG family is most ancient. Thus, we reconstructed phylogenies of CRGs, including those from new arthropod genomes and transcriptomes, and mapped CRG gains and losses across arthropod lineages. Our analysis was strengthened by including crustaceans, especially copepods, which reside outside the hexapod/branchiopod clade within the subphylum Pancrustacea. We generated the first high-resolution genome sequence of the copepod Eurytemora affinis and annotated its CRGs. We found odorant receptors and odorant binding proteins present only in hexapods (insects) and absent from all other arthropod lineages, indicating that they are not universal adaptations to land. Gustatory receptors likely represent the oldest chemosensory receptors among CRGs, dating back to the Placozoa. We also clarified and confirmed the evolutionary history of antennal ionotropic receptors across the Arthropoda. All antennal ionotropic receptors in E. affinis were expressed more highly in males than in females, suggestive of an association with male mate-recognition behavior. This study is the most comprehensive comparative analysis to date of CRG family evolution across the largest and most speciose metazoan phylum Arthropoda.
OS11.3 Machine learning for better prognostic stratification and driver genes identification in 1p/19q-codeleted grade III gliomas
Authors: S. Rosenberg, C. Dehais, F. Ducray, A. Alentron, M. Tanguy, A. De Reyneis, N. Elarouci, D. Figarella-Branger, J. Delattre, A. Idbaih
Journal: Neuro-Oncology (2017)

BACKGROUND: Although major advances have been accomplished over the last years in their characterization, 1p/19q-codeleted anaplastic gliomas have variable clinical behavior and mysterious 1p/19q-codeletion “driven” molecular oncogenesis. We have recently shown that the most common alteration (i.e. 9p21.3 allelic loss detected in 42% of cases) is an independent prognostic factor in this tumor type. However, less frequent Genomic Copy Number Variations (CNV) may also have clinical value and may shed light on molecular oncogenesis of this tumor type. METHODS: A cohort of 197, 1p/19q-codeleted grade III gliomas was collected as part of the French POLA network. Clinical, pathological and molecular information were recorded and the patients were clinically followed up. CNV analysis was performed using SNP arrays. Computational biology and machine learning analysis were applied to identify less common additional CNV events associated with overall survival and other clinical-pathological variables Results: Recurrent chromosomal events were identified in chromosomes 4, 9, and 11. 46 focal amplification events and 22 focal deletion events were identified. 12 of the focal events overlapped with known cancer related genomic regions. 24 focal CNV areas were associated with survival and five of them were significantly associated with survival after multivariate analysis. 9/24 signals, detected in 3 to 26 percent of patients, were validated using an external cohort of gliomas of the Cancer Genome Atlas. Five of the validated signals contain a cancer related gene or MIR: CDKN2A deletion, SS18L1 amplification, RHOA/MIR191 copy-neutral loss of heterozigosity, FGFR3 amplification, and ARNT amplification. The CNV profile enables better survival prediction compared to clinical risk assessment. Conclusions: Several recurrent CNV events are characteristics for 1p/19q-codeleted grade III gliomas. These genomic regions are associated with survival and enable better survival prediction. More important, they may help identifying potential genes for understanding oncogenesis and for personalized therapy.
Sustained Minimal Residual Disease Negativity in Newly Diagnosed Multiple Myeloma (NDMM) Patients Treated with Carfilzomib (CFZ), Lenalidomide (LEN), and Dexamethasone (DEX) Followed By 2 Years of Lenalidomide Maintenance (CRd-R): Updated Results of a Phase 2 Study
Authors: Dickran Kazandjian, Neha S Korde, Mark Roschewski, Sham Mailankody, Candis Morrison, Elisabet E. Manasanch, Mary L Kwok, Nishant Tageja, Manisha Bhutani, Adriana Zingone, Rene Costello, Yong Zhang, Marcia Mulquin, Liz Lamping, Ashley Carpenter, Brenda Roberson, Irina Maric, Katherine R. Calvo, Raul C Braylan, Constance M. Yuan, Maryalice Stetler-Stevenson, Diane C. Arthur, Liza Lindenberg, Karen A. Kurdziel, Peter Choyke, Seth M. Steinberg, William Figg, Wyndham H. Wilson, Ola Landgren
Journal: Blood (2016)
a Randomized, Double-Blinded, Placebo Controlled Study of IVIG Vs. IVIG with High Dose Methylprednisolone in Rapidly Augmenting Platelet Counts in Childhood ITP
Authors: Manuel Carcao, Mariana Silva, Michele David, Robert J. Klaassen, MacGregor Steele, Victoria E. Price, Cindy Wakefield, Derek Stephens, Victor S. Blanchette
Journal: Blood (2016)
Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials
Authors: Priscilla S. Briquez, Kristen M. Lorentz, Hans M. Larsson, Peter Frey, Jeffrey A. Hubbell
Journal: Biomaterials (2017)

Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of aprotinin. Here, we aimed to develop a human-derived substitute to aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as aprotinin's is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro, outperforming aprotinin. In vivo, our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which aprotinin did not show efficacy, thus qualifying it as a competitive substitute of aprotinin in fibrin sealants.
Intraventricular pilocytic astrocytomas: Radiology, surgical management and outcome in a series of 8 patients
Authors: Ribhav Pasricha, Chinmaya Dash, Pankaj Singh, Sachin Borkar, Bhawani S Sharma
Journal: Neuro-Oncology (2018)

Intraventricular pilocytic astrocytomas are a rare occurrence, accounting for approximately 4% - 15.6% of all pilocytic astrocytomas. The aim of the study was to describe the radiology, surgical management and outcome in 8 patients with intraventricular pilocytic astrocytoma(ivPA). Between January 2010 and August 2015, 8 patients with histopathologically proven ivPA were identified. The radiological images were obtained from PACS. Patient and surgical details were obtained from the computerized discharge summary, OT records and operative notes, whereas follow up was obtained from the record section. Headache with progressive loss of vision was the most common presentation. Duration of symptoms varied from 4 months to 2 years (mean 9.88 months). Except one patient, all patients with preoperative CT scan revealed calcifications in the lesion, with extensive calcification in 3 patients. All the tumors were predominantly hypointense on T1WI and iso to hyperintense on T2WI. Lesion in all patients showed heterogenous contrast enhancement on post gadolinium images. Mean blood loss in the series was 1969 ml (range 250 ml- 4500 ml).There was one death in this series due to meningitis and septic shock. Preoperative diagnosis of ivPA could not be made on the basis of clinical and radiologic profile in any case. ivPA's are rare tumors and are difficult to diagnose in the preoperative period based on the radiologic profile alone. These tumors can be extremely vascular with potential for massive blood loss. These tumors can be associated with extensive calcification and the calcified tumors have less bleeding as expected.
P17.08 Does adjuvant radiotherapy improve local control rate in intracranial hemangiopericytoma?
Authors: S. Jeon, C. Park
Journal: Neuro-Oncology (2017)

Purpose: This is a single-institution retrospective cohort study designed to investigate the role of adjuvant radiotherapy in intracranial hemangiopericytoma.. Materials and Methods: Between 1995 and 2016, 53 patients received definitive surgery and diagnosed as intracranial hemangiopericytoma at the Seoul National University Hospital. There were 24 males and 29 females and median age of all the patients was 44 years. Of gross total resection (N=30), 14 received adjuvant radiotherapy. Among subtotal resection (N=23), 13 received adjuvant radiotherapy, 6 received stereotactic radiosurgery. Adjuvant chemotherapy was administered in 5 patients. Results: With the median follow-up period of 44 months (range, 3-307 months), 19 patients (36%) had disease relapse (intracranial; 17, extracranial; 7). The 10-year Intracranial and extracranial failure free rate were 44.0% and 62.2%, respectively. In 17 patients with intracranial failure, total of 31 relapsed lesions were observed, 20 of which were at the surgical bed. The other 11 lesions were more than 1.5cm away from the surgical bed. Addition of adjuvant radiotherapy significantly lowered the surgical bed failure rate (p=0.025, 10-year surgical bed control: 58.2% vs. 37.8%). Both non-surgical bed failure and extracranial failure were not associated with adjuvant radiotherapy. The sites of extracranial metastases were bone(4), lung(3), liver(3), inguinal lymph node(1), and Kidney(1). Conclusion: Adjuvant radiotherapy to the surgical bed, obviously with residual tumor if confirmed, seemed to improve local control rate in intracranial hemangiopericytoma.