tbuckley/cabot-search huggingface dataset:
P11.15 Selective inhibition of BCL-XL increases sensitivity of pediatric tumour models to the anti-mitotic agent MLN8237
Authors: J. Levesley, L. Steele, A. Brüning-Richardson, A. Davison, J. Zhou, S. Lawler, S. C. Short
Journal: Neuro-Oncology (2017)

BACKGROUND: Small molecule inhibitors of the mitotic kinases, including the Aurora kinase inhibitor MLN8237, are being investigated as novel therapeutic agents for the treatment of solid cancers including malignant brain tumours. However, resistance has been observed and anti-apoptotic proteins of the BCL-2 family have been shown to promote cell survival following treatment. In this study, we investigated the effect of disrupting anti-apoptotic protein function in medulloblastoma and pediatric glioblastoma (pGBM) models using BH3-mimetics in combination with MLN8237. METHODS: The effects of single agent and combination treatment on cell viability were determined by MTT/WST-1 assays and flow cytometry. Effects on cell phenotype, cell cycle progression and cellular ploidy were determined by live cell imaging and DNA content analysis. Induction of apoptosis was monitored in real-time, by time-lapse microscopy, using a fluorescent, polarity-sensitive phosphatidylserine probe, and confirmed by measuring caspase-3/7 activity. Knockdown of BAX/BAK was used to confirm these effects. Results: ABT-263 in combination with MLN8237 reduced mitotic slippage and polyploidy, significantly reduced cell viability and promoted the elimination of mitotically defective cells. This occurred through a BAX/BAK-dependent, caspase-mediated apoptotic pathway. The BCL-xL antagonist, WEHI-539, which targets BCL-2, significantly augmented tumour cell killing when used in combination with MLN8237. It also sensitized resistant brain tumour cells to a novel BAX activator, SMBA1. In addition, siRNA mediated knockdown of BCL-xL sensitized pGBM and medulloblastoma cells to MLN8237, and mimicked the effect of combination drug treatment. CONCLUSION: Combination treatment using a pro-apoptotic agent enhanced the cytotoxicity of MLN8237 in paediatric tumours and may overcome an important resistance mechanism.
Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study
Authors: M.E. Pavel, E. Baudin, K.E. Öberg, J.D. Hainsworth, M. Voi, N. Rouyrre, M. Peeters, D.J. Gross, J.C. Yao
Journal: Annals of Oncology (2017)
P09.53 The timing of postoperative chemoradiation treatment (Stupp Protocol) after GBM resection: A systematic review
Authors: A. C. DiRisio, H. Goswami, C. Shi, I. Yunusa, T. R. Smith, R. A. Mekary, M. L. Broekman
Journal: Neuro-Oncology (2017)

Introduction: Standard therapy for glioblastoma (GBM) patients includes surgical resection followed by radiotherapy combined with ­concomitant and adjuvant chemotherapy using temozolomide. However, timing of postoperative chemoradiation has been shown to vary between institutions. Considerations in the timing of therapy include initiating the treatment early to avoid repopulation of the tumor, while avoiding premature initiation of chemotherapy to reduce the adverse effects of treatment. The goal of this study is to understand the factors that contribute to overall and progression free survival as they relate to the timing of postoperative chemoradiation treatment in GBM patients. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Cochrane databases were used to select studies that reported on patients undergoing radiotherapy with concomitant and adjuvant chemotherapy after glioblastoma resection. Time to initiation of chemoradiation, length of treatment, temozolomide dosage, overall survival, and progression-free survival were extracted from the studies that met inclusion criteria. Results: We identified 2309 articles from our search and selected 253 full text articles after the initial review. Timing to start of postoperative chemoradiation as well as duration of chemoradiation varied between studies. Contributors to variability in treatment, survival, and tumor progression included extent of resection, age, and dosage of temozolomide. Conclusion: It is important for physicians to consider the timing of initiation of chemoradiation following GBM resection. While the risk of recurrence is critical to survival, the side effects of treatment also pose a particular burden on patients and are critical to patient outcomes. Taking individual patient characteristics into account when determining timing of chemoradiation can improve patient survival, time to progression, and quality of life.
P01.17 GBMs in striatum are different from thalamic GBMs in gene profiles
Authors: T. Hide, Y. Takahashi, H. Nakamura, K. Makino, H. Kamada, J. Kuratsu, S. Yano
Journal: Neuro-Oncology (2017)

Purpose: Glioblastoma multiformes (GBMs) commonly occur in adult and are one of the most malignant cancer for human. Mean survival time of GBM patients is still about one year, even though they are received surgical maximal resection of tumor and chemo-radiotherapy. Some midline gliomas exist in the area of striatum and thalamus. However, GBMs existing mainly in striatum seemed to differ from those in thalamus in the clinical features. To reveal whether striatum (st) GBMs and thalamic (th) GBMs are different, we investigated clinical features and performed deep sequence analysis. Methods and Results: 9 of stGBMs and 18 of thGBMs were analyzed. Median survival of striatum and thalamic GBM patients were 373 days and 518 days, respectively. DNAs are purified from seven of stGBMs and ­thirteen samples of thGBMs, and also from the blood of five coincident patients of each group. TruSeq Amplicon Cancer Panel (Illumina) were used for deep sequence analysis. EGFR mutations are common in chGBMs (80%) but rare in thGBMs (20%), on the other hand HNF1A mutations are not identified in chGBMs (0%) but frequent in thGBMs (60%). IDH1 mutation was seen in one thGBM patient. Conclusion: There is a possibility that stGBMs are different from thGBMs in midline glioma.
P17.17 Long term results of stereotactic radiosurgery in recurrent oligodendrogliomas
Authors: S. Yang, D. Kim
Journal: Neuro-Oncology (2017)

Background: The treatment of recurrent oligodendrogliomas is challenging given the paucity of effective treatment options and lack of well-designed studies on which to base therapy. We assessed the long-term results of SRS performed as a salvage treatment in patients with recurrent oligodendrogliomas. Methods: Between 1997 and 2010, 40 consecutive patients with recurrent oligodendrogliomas were treated for 52 lesions with SRS. WHO grade 2 Oligodendroglioma was diagnosed in 13 patients, and 27 patients were diagnosed with grade 3 anaplastic oligodendroglioma (AO). The median time between primary diagnosis and SRS was 49.3 months for oligodendroglioma and 51 months for AO. SRS was performed with a median target volume of 3.8 mL and median margin dose of 17.0 Gy. Results: Median overall survival after primary diagnosis was 176.9 months for patients with grade 2 oligodendroglioma and 135.7 months for patients with AO. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection, malignant progression, and age at primary diagnosis. Median survival after SRS was 104.5 months for patients with grade 2 oligodendroglioma and 35.5 months for patients with AO. Median progression-free survival after SRS was 53.0 months for grade 2 oligodendroglioma and 13.4 months for AO. Histologic grading and presented with seizure at SRS were signiﬁcant in inﬂuencing survival and progression-free survival after SRS. Conclusions: SRS offers considerable treatment option as a salvage treatment for patients with smaller lesions of recurrent oligodendroglioma.
Prospective performance study of the liquid-based endometrial cytology with sampling directly from the uterine endometrium for the effective endometrial cancer screening.
Authors: Yasuo Hirai, Fumiko Fukagawa, Maki Kihara, Ken Ishitani, Kenji Yanoh, Yoshiaki Norimatsu, Azusa Hanada, Hideo Matsui
Journal: Journal of Clinical Oncology (2014)

e16548 Background: In Japan, endometrial cytology by intrauterine sampling is one of the most common tests for evaluating the status of the endometrium. This method is usually applied as the initial pathological evaluation and often as endometrial cancer screening tests. However, endometrial cytology with the conventional method needs a lot of training for the diagnosis. Besides, it can cause a lot of pains for the patients, which has resulted in a limited use except in Japan. Under such circumstance, we have developed a new practical and easy endometrial cancer screening system using LBC (BD SurePath) together with an unique safe and painless sampling device by which even a nurse can work for intrauterine sampling. Also included are new OSG reporting format. Methods: Totally 1798 specimens collected from the outpatient cases are used for the study after November 2011 and both endometrial cytology(conventional method and LBC method) and endometrial biopsy were conducted on the same day. The slide is read by one cytotechnologist using standardized OSG(Osaki Study Group) Format and positive cases are checked by the cytopathologist. The final result is reported with descriptive endometrial reporting format presented by Yanoh el al. Results: After pathological results, 15 cases(EGBD), 4 cases (Endometrial Hyperplasia) and 47 cases(Endometrial cancer) were used for the comparison of conventional method and LBC method with the final pathological results respectively. The sensitivity of the endometrial cytology with LBC come up to 79.5%, while that in the conventional method is 72.7%. The specificity of the endometrial cytology with LBC come up to 91.8%, while that in the conventional method is 91.7%. Conclusions: Our method with the liquid based endometrial cytology using BD SurePath showed a good performance to evaluate the status of the endometrium. This cytology method is useful enough for not only the initial endometrial cellular evaluation but also endometrial cancer screening together with cervical cytology. We are going to collect further data for the comparison with the pumped endometrial biopsy and final pathological results.
What is the difference in concussion management in children as compared with adults? A systematic review
Authors: Gavin A Davis, Vicki Anderson, Franz E Babl, Gerard A Gioia, Christopher C Giza, William Meehan, Rosemarie Scolaro Moser, Laura Purcell, Philip Schatz, Kathryn J Schneider, Michael Takagi, Keith Owen Yeates, Roger Zemek
Journal: British Journal of Sports Medicine (2017)

Aim To evaluate the evidence regarding the management of sport-related concussion (SRC) in children and adolescents. The eight subquestions included the effects of age on symptoms and outcome, normal and prolonged duration, the role of computerised neuropsychological tests (CNTs), the role of rest, and strategies for return to school and return to sport (RTSp). Design Systematic review. Data sources MEDLINE (OVID), Embase (OVID) and PsycInfo (OVID). Eligibility criteria for selecting studies Studies were included if they were original research on SRC in children aged 5 years to 18 years, and excluded if they were review articles, or did not focus on childhood SRC. Results A total of 5853 articles were identified, and 134 articles met the inclusion criteria. Some articles were common to multiple subquestions. Very few studies examined SRC in young children, aged 5–12 years. Summary/conclusions This systematic review recommends that in children: child and adolescent age-specific paradigms should be applied; child-validated symptom rating scales should be used; the widespread routine use of baseline CNT is not recommended; the expected duration of symptoms associated with SRC is less than 4 weeks; prolonged recovery be defined as symptomatic for greater than 4 weeks; a brief period of cognitive and physical rest should be followed with gradual symptom-limited physical and cognitive activity; all schools be encouraged to have a concussion policy and should offer appropriate academic accommodations and support to students recovering from SRC; and children and adolescents should not RTSp until they have successfully returned to school, however early introduction of symptom-limited physical activity is appropriate. Systematic review registration PROSPERO 2016:CRD42016039184
P09.07 The use of programmable shunts in patients treated with Tumor Treating Fields: Multicentric Case Series
Authors: L. Schreiber, M. Rapp, M. Sabel, J. Onken, M. Misch, A. Kinzel, C. Thomé, M. Scholz, P. Vajkoczy, C. F. Freyschlag
Journal: Neuro-Oncology (2017)

OBJECTIVE: Tumor Treating Fields (TTFields) are a non-invasive, low intensity, intermediate frequency, alternating electric fields serving as anti-mitotic therapy for treatment of patients with newly diagnosed or recurrent glioblastoma multiforme (GBM). Recently, the Phase 3 EF-14 study demonstrated significantly prolonged overall survival in newly diagnosed GBM patients treated with TTFields + Temozolomide (TMZ) compared to TMZ alone. Although the development of hydrocephalus is a rare complication of GBM treatment, the need for a programmable shunt however, could prevent patients from TTFields treatment as the implantation of a programmable valve is a contraindication. In our multicentric observational cohort, we assessed patients requiring programmable valves during concomitant TTFields treatment with the Optune® System, for safety and feasibility. METHODS: We observed six patients (male=4, female=2) of median age 47.3 years (range 26-59 years) with newly diagnosed or recurrent GBM who had received programmable shunt valves due to different indications such as hydrocephalus, CSF fistula or partial obstruction of ventricles. Shunt indications and valve types implanted differed throughout different neurosurgical departments, according to local standards of care. All patients received antimitogenic treatment with Optune; the shunt valve was radiographically assessed at predefined time points of clinical practice after the initiation of TTFields treatment. Patients were treated at 4 different centers in Germany and Austria, respectively. RESULTS: All programmable shunt types proved functional while undergoing simultaneous treatment with TTFields. We found no influence of alternating electric fields on shunt valve programming during follow-up. For patients’ safety, shunt programming was assessed meticulously. Further imaging (MRI / CT follow-up) included the assessment of shunt valves, showed no dysfunction or unintended reprogramming. CONCLUSION: Our multicentric observational case series demonstrated safety and feasibility of Optune in patients with programmable shunt valves. Additional studies are needed to validate our observations and assess comparable efficacy of TTFields in patients with the need of programmable shunt valves.
P09.33 Feasibility and survival benefit of hypofractionated radiotherapy with concurrent temozolomide and bevacizumab in elderly patients with glioblastoma
Authors: Y. Mitobe, K. Matsuda
Journal: Neuro-Oncology (2017)

BACKGROUND: Hypofractionated radiotherapy (HPRT) was often used for treatment of elderly patients with glioblastoma. This therapy was well tolerated, however, the prognosis was still dismal. Although dose escalation of HPRT (45Gy/15fr) might be effective, incidence of radiation injury could be increasing. In 2014, Bevacizumab (BEV) was approved for newly diagnosed and recurrent glioblastoma in Japan. It has been reported that BEV is effective for cerebral edema and radiation injury as well as suppreression of tumor growth Object. We investigated whether dose escalated HPRT with concurrent temozolomide and bevacizumab would be well tolerant and effective for patients with elderly patients with glioblastoma METHODS: We analyzed 11 elderly (Age >75) patients with newly diagnosed glioblastoma who received the therapy at our hospital from 2014-2016 with HPRT (45Gy/15fr) delivered with concurrent daily TMZ (75mg/m2). Median preoperative KPS was 90 (60-100). All patients who had GBM progression with TMZ were used of BEV for salvage therapy. RESULTS: All patients completed HPRT with concurrent daily TMZ. All patients received BEV for salvage therapy. With a median follow-up of 15.5 months, 4 (36 %) patients were deceased. The median OS was not reached, while the median PFS was 4 months. Median KPS after 6 months after initial therapy was 70 (50-100). CONCLUSION: Dose escalated HPRT with concurrent temozolomide and bevacizumab was well tolerated and effective for elderly patients with glioblastoma.
Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma
Authors: H.R. Kim, H.N. Kang, H.S. Shim, E.Y. Kim, J. Kim, D.J. Kim, J.G. Lee, C.Y. Lee, M.H. Hong, S.-M. Kim, H. Kim, K.-H. Pyo, M.R. Yun, H.J. Park, J.Y. Han, H.A. Youn, M.-J. Ahn, S. Paik, T.-M. Kim, B.C. Cho
Journal: Annals of Oncology (2017)
Contents, Vol. 37, 1982
Authors: Stuart Shipko, I. Modai, A. Bleich, Galia Cygielman, Ranjan Roy, Maurizio Fava, Giovanni A. Fava, Robert Kellner, Emanuela Serafini, Ismaele Mastrogiacomo, Rolf Eide, Reidar Thyholdt, Espen Hamre
Journal: Psychotherapy and Psychosomatics (1982)
Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients With Structural Heart Disease
Authors: Pasquale Santangeli, David S. Frankel, Roderick Tung, Marmar Vaseghi, William H. Sauer, Wendy S. Tzou, Nilesh Mathuria, Shiro Nakahara, Timm M. Dickfeldt, Dhanunjaya Lakkireddy, T. Jared Bunch, Luigi Di Biase, Andrea Natale, Venkat Tholakanahalli, Usha B. Tedrow, Saurabh Kumar, William G. Stevenson, Paolo Della Bella, Kalyanam Shivkumar, Francis E. Marchlinski, David J. Callans
Journal: Journal of the American College of Cardiology (2017)

In patients referred for radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in the setting of structural heart disease, early post-procedural mortality (EM) has not been previously investigated. The purpose of this study was to evaluate EM after catheter ablation of scar-related VT. Associations between clinical and procedural variables and EM (within 31 days of the procedure) were tested in patients with structural heart disease undergoing RFCA of VT at 12 international centers. Of 2,061 patients (mean age 62 ± 13 years; left ventricular ejection fraction [LVEF] 34 ± 13%; 53% ischemic etiology), EM occurred in 100 (5%; 95% confidence interval [CI]: 4% to 6%). A total of 54 (3%) patients died before hospital discharge (median 9 days after the procedure; 25% for refractory VT), including 12 (0.6%) after a major procedure-related complication. In multivariable analysis, the following factors were found to be significantly associated with EM: LVEF (odds ratio [OR] per percent decrease: 1.12; 95% CI: 1.05 to 1.20; p < 0.001), chronic kidney disease (OR: 2.73; 95% CI: 1.10 to 6.80; p = 0.030), presentation with VT storm (OR: 3.61; 95% CI: 1.37 to 9.48; p = 0.009), and presence of unmappable VTs (OR: 5.69; 95% CI: 1.37 to 23.69; p = 0.017). Recurrent VT was also associated with an increased risk of subsequent death (hazard ratio: 7.19; 95% CI: 5.57 to 9.28; p < 0.001) and EM (hazard ratio: 11.45; 95% CI: 7.47 to 17.59; p < 0.001). In a contemporary cohort of patients with scar-related VT undergoing RFCA, EM occurred in 5% of cases. Clinical and procedural variables indicating poorer clinical status (low LVEF, chronic kidney disease, VT storm, and unmappable VTs) and post-procedural VT recurrence may predict EM. Identification of such features may prompt early consideration for hemodynamic support or other care to help mitigate later potential complications.
Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice
Authors: Jiawei Shao, Shuai Xue, Guiling Yu, Yuanhuan Yu, Xueping Yang, Yu Bai, Sucheng Zhu, Linfeng Yang, Jianli Yin, Yidan Wang, Shuyong Liao, Sanwei Guo, Mingqi Xie, Martin Fussenegger, Haifeng Ye
Journal: Science Translational Medicine (2017)

Optogenetically engineered cells maintain blood glucose homeostasis in mice by semiautonomous, wirelessly regulated exposure to far-red light.
Rituximab, Fludarabin and Cyclophosphamide Followed by High Dose Therapy with Autologous Stem Cell Rescue Leads to High Molecular Remission Rate in Chronic Lymphocytic Leukemia patients but Relapses Are Observed.
Authors: Marek Trneny, Jana Salkova, Josef Karban, Jan Cerny, Kyra Michalova, Jan Stritesky, Jiri Schwarz, Robert Pytlik, Alena Slavickova
Journal: Blood (2004)
Abstract P314: Grainyhead-like 3 Plays an Essential Role in Endothelial Cell Function in a NO-Dependent Manner
Authors: Margarete Lukosz, Arne Mlynek, Joachim Altschmied, Judith Haendeler
Journal: Circulation Research (2011)

Aging of human endothelial cells (EC) is associated with reduced nitric oxide (NO) bioavailability, decreased migratory capacity and an increase in Src kinase activation and apoptosis sensitivity. We recently identified the transcription factor grainyhead-like 3 (GRHL3) as a pro-migratory transcription factor in EC. A role for GRHL3 in aging processes was suggested by reduced expression in brains from old mice. Therefore, we wanted to investigate the regulation of GRHL3 by NO and Src kinase and GRHL3 effects on NO-bioavailabilty, apoptosis and migration. We treated EC either with physiological concentrations of NO or the Src kinase inhibitor PP2. In both cases GRHL3 expression was increased (3.75 fold and 4.50 fold, respectively). In addition, both treatments induced migration and inhibited apoptosis. Interestingly, overexpression of GRHL3 activated endothelial nitric oxide synthase (eNOS), its upstream regulator Akt and subsequently increased the S-NO content of EC. This demonstrates that GRHL3 enhances NO-bioavailability in EC, which is inseparably tied to apoptosis protection and migration. Along this line, GRHL3 overexpression reduced apoptosis of EC (1.89 fold reduction of basal apoptosis vs. empty vector transfected cells). Interestingly, this anti-apoptotic effect was dependent on NO synthesis by eNOS, since the eNOS inhibitor L-NMMA completely abrogated the protective effect of GRHL3. Having demonstrated a pro-migratory effect of GRHL3, we wanted to know whether this effect is mediated by induction of vascular endothelial growth factor (VEGF) expression. Surprisingly, GRHL3 overexpression did not change VEGF protein levels. To exclude a bystander effect of GRHL3 in EC migration, we knocked down expression with shRNA. Reduction of GRHL3 mRNA levels decreased basal and NO-induced EC migration (scr: 73 +/− 16 migrated cells; shGRHL3: 26 +/− 12 migrated cells; scr+NO: 149 +/− 19 migrated cells; shGRHL3+NO: 36 +/− 10 migrated cells) demonstrating an essential role in this process. Taken together, these data suggest that GRHL3 is essential for EC functions compromised during aging.