tbuckley/cabot-search huggingface dataset:
NTOX-09. RECOMMENDED PHASE II DOSE OF INTRA-ARTERIAL MELPHALAN GIVEN WITH INTRA-ARTERIAL CARBOPLATIN, OSMOTIC BLOOD-BRAIN BARRIER DISRUPTION AND DELAYED OTOPROTECTIVE SODIUM THIOSULFATE FOR PATIENTS WITH RECURRENT OR PROGRESSIVE CNS EMBRYONAL OR GERM CELL TUMORS
Authors: Prakash Ambady, Nancy Doolittle, Jenny Firkins, Joao Prola Netto, Dominic Siler, Jessica James, Kirsten Johansson, Amy Huddleston, Rongwei Fu, Edward Neuwelt
Journal: Neuro-Oncology (2017)

Intra-arterial chemotherapy in conjunction with transient osmotic BBB disruption (IA/BBBD) has been shown to increase drug delivery (10-100 folds) to the CNS. We report the maximum tolerated dose of IA melphalan in combination with IA carboplatin with BBBD and delayed IV sodium thiosulfate (STS) otoprotection for patients with recurrent or progressive CNS embryonal or germ cell tumors. In Prior studies, STS has been shown to protect against carboplatin-induced hearing loss. This prospective single-institution phase I/II trial was approved by the institutional review board (NCT00983398). Subjects with embryonal and germ cell tumors of the CNS between 1 and 45 years of age, and met the inclusion/exclusion criteria received IA carboplatin (200 mg/m2/day x two days) and melphalan (starting at 4 mg/m2 x two days with inter-patient 3X3 dose escalation as per protocol until the MTD was reached) in conjunction with osmotic BBBD on two consecutive days every 4-6 weeks for up to 12 treatment cycles. For otoprotection, IV STS was given four and eight hours after carboplatin. 10 males and 4 females (median age 16.3 years, 1.7-28.6 yrs) were enrolled. 11/14(79%) had objective radiographic responses (4 PR, 7 SD). Most frequent grade 3 or 4 toxicities were hematological (64%) with only 1/14 patients developing ototoxicity (Brock’s grade-4). The maximum tolerated dose of IA Melphalan was 6 mg/ m2 x 2 days. The recommended dose phase II dose of melphalan is 6 mg/m2 IA x 2 days when given with IA carboplatin administered with BBBD and delayed IV STS for otoprotection. Favorable safety profile, objective responses and excellent hearing protection compared to IA/BBBD carboplatin without STS warrants proceeding with the phase II part of this study. Phase I study will continue for subjects younger than 10 years due to limited accrual in this age group.
Preventive dose reduction of capecitabine in elderly population
Authors: A. Guidi, A. Luciani, G. Pagliari, B. Bocci, C. Careri, M. Violati, M. Blasi, M. Narracci, V. Bordin, S. Caldiera, G. Zamparelli, S. Zonato, G. Cassinelli, D. Ferrari
Journal: Annals of Oncology (2017)
P3.03-026 Cell-CT® Differential Detection of Dysplastic Bronchial Epithelial Cells from Patient Explants
Authors: D. Sussman, M. Meyer, R. Katdare, C. Presley, T. Bell, J. Reyna, F. Lakers, C. Hamilton, J. Zulueta, Y. Miller, M. Ghosh, A. Nelson
Journal: Journal of Thoracic Oncology (2017)
Quality of end of life care in patients with pancreatic cancer receiving systematic versus on-demand early palliative care at diagnosis: a secondary outcome analysis from a randomized controlled trial
Authors: C. Brunelli, A. Pigni, C. Mandelli, E. Bianchi, L. Ferrigato, M.C. Broglia, O. Nanni, M. Dall'Agata, E. Sansoni, L. Cavanna, V. Dadduzio, F. Garetto, M.S. Pino, R. Bortolussi, M. Luzzani, L. Giaretto, E. Perfetti, C. Autelitano, M.A. Piga, A. Caraceni
Journal: Annals of Oncology (2017)
Government faces legal challenge over data agreement that may put “migrants at risk”
Authors: Anne Gulland
Journal: BMJ (2017)

A charity has launched a legal challenge to the data sharing agreement between the Home Office, Department of Health, and the NHS, which it says puts immigrants’ healthcare at risk by deterring them from seeking care.

The agreement, signed in January, enables the Home Office to access data such as a patient’s home address. The Migrants’ Rights Network says that the agreement was written in secret, without consultation with NHS staff, medical organisations, or the public.

The network says that the agreement …
Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia
Authors: Daniela Di Marcantonio, Esteban Martinez, Simone Sidoli, Jessica Vadaketh, Margaret Nieborowska-Skorska, Anushk Gupta, Jake M. Meadows, Francesca Ferraro, Elena Masselli, Grant A. Challen, Michael D. Milsom, Claudia Scholl, Stefan Fröhling, Siddharth Balachandran, Tomasz Skorski, Benjamin A. Garcia, Prisco Mirandola, Giuliana Gobbi, Ramiro Garzon, Marco Vitale, Stephen M. Sykes
Journal: Clinical Cancer Research (2017)

Purpose: The intracellular redox environment of acute myeloid leukemia (AML) cells is often highly oxidized compared to healthy hematopoietic progenitors and this is purported to contribute to disease pathogenesis. However, the redox regulators that allow AML cell survival in this oxidized environment remain largely unknown.Experimental Design: Utilizing several chemical and genetically-encoded redox sensing probes across multiple human and mouse models of AML, we evaluated the role of the serine/threonine kinase PKC-epsilon (PKCε) in intracellular redox biology, cell survival and disease progression.Results: We show that RNA interference-mediated inhibition of PKCε significantly reduces patient-derived AML cell survival as well as disease onset in a genetically engineered mouse model (GEMM) of AML driven by MLL-AF9. We also show that PKCε inhibition induces multiple reactive oxygen species (ROS) and that neutralization of mitochondrial ROS with chemical antioxidants or co-expression of the mitochondrial ROS-buffering enzymes SOD2 and CAT, mitigates the anti-leukemia effects of PKCε inhibition. Moreover, direct inhibition of SOD2 increases mitochondrial ROS and significantly impedes AML progression in vivo Furthermore, we report that PKCε over-expression protects AML cells from otherwise-lethal doses of mitochondrial ROS-inducing agents. Proteomic analysis reveals that PKCε may control mitochondrial ROS by controlling the expression of regulatory proteins of redox homeostasis, electron transport chain flux, as well as outer mitochondrial membrane potential and transport.Conclusions: This study uncovers a previously unrecognized role for PKCε in supporting AML cell survival and disease progression by regulating mitochondrial ROS biology and positions mitochondrial redox regulators as potential therapeutic targets in AML. Clin Cancer Res; 24(3); 608-18. ©2017 AACR.
Malária importada na França continental, em 1996
Authors: F Legros, M Belkaid, M Danis
Journal: Eurosurveillance (1998)

A malaria deixou de ser endemica em Franca em 1960, ainda que tenham sido notificados alguns casos esporadicos no departamento da Corsega em 1970. Desde entao, nao foi notificado nenhum caso indigena de malaria. Os dados epidemiologicos da malaria em Franca, em 1996, sao apresentados a seguir (1).
Un nouveau relâchement des comportements de prévention chez les homosexuels masculins : rôle des avancées thérapeutiques ?
Authors: A Laporte
Journal: Eurosurveillance (2002)

Les articles presentes dans ce numero d’Eurosurveillance sur l’evolution recente des comportements de prevention chez les homosexuels masculins en Espagne, en Suisse, et aux Pays-Bas font le meme constat d’un recul de la pratique du safer sex. Ils mettent en evidence une augmentation de la pratique de la penetration anale quel que soit le type de partenaire, une augmentation des rapports anaux non proteges et de l’ejaculation dans la bouche, en particulier avec des partenaires occasionnels. L’augmentation des diagnostics de maladies sexuellement transmissibles aigues (gonococcie, syphilis) dans differents pays d’Europe, illustree dans ce numero par les donnees des Pays-Bas, est la premiere consequence objectivable de cette evolution.
ACTR-73. A PHASE II STUDY OF TUMOR TREATING FIELDS IN COMBINATION WITH BEVACIZUMAB AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED, UNRESECTABLE GLIOBLASTOMA
Authors: Ashley Sumrall, Daniel Haggstrom, Stuart Burri, James Symanowski
Journal: Neuro-Oncology (2017)

Patients with newly diagnosed, unresectable glioblastoma multiforme (GBM) will usually receive concurrent temozolomide (TMZ) and radiation therapy. Some patients will also receive bevacizumab (BEV) if clinically indicated. Tumor treating fields (TTFields) have also been shown to be safe and effective for treatment of GBM. The concurrent use of TTFields in newly diagnosed, unresectable GBM patients, with the combination of TMZ and BEV may provide clinical benefit. The primary objective of this phase II study is to assess the efficacy of the administration of TMZ and BEV with concurrent use of TTFields by evaluating the percentage of newly diagnosed unresectable GBM patients who are alive at 12 months. This is an open label, single-arm, phase II protocol. Patients ≥22 years of age with histologically confirmed GBM, planned 6 weeks of concurrent chemo-radiotherapy (45-70Gy) post-biopsy concomitant with TMZ, a KPS score ≥70 and a life expectancy of >3 months are eligible to participate. All patients will complete best standard of care radiation, TMZ and BEV (6 weeks). Within two weeks of completion of this initial treatment period, study patients will be treated continuously with TTFields (OptuneTM). The patients will also continue with maintenance TMZ/BEV. Patients will be followed for evaluation of progression-free-survival, overall survival, quality of life (QoL), safety and exploratory objectives. This study will be carried out in two stages. The first stage will enroll a cohort of 22 patients. Enrollment and interim analysis of the first cohort of patients will be completed within 15 months. The second stage will enroll a cohort of 24 patients and will be completed within 15 months of stage 2 commencements. The duration of the study is expected to be no longer than 30 months (NCT02343549).
Epigenetic Profiling in High-Risk MDS and AML Patients Identifies Pre-Treatment Methylation Patterns That Indicate Response to Hypomethylating Agents: A Pilot Study
Authors: Chetasi Talati, Adam Marsh, Kylie Baggett, Najla Al-Ali, Kendra L. Sweet, David Sallman, Rami S. Komrokji, Alan F. List, Eric Padron, Jeffrey E. Lancet
Journal: Blood (2016)
P3.01-035 Post-Marketing Observational Study of Japanese Patients with EGFR Mutation-Positive (EGFRm+) NSCLC Treated with Daily Afatinib (Final Report)
Authors: N. Yamamoto, T. Nukiwa, Y. Nakanishi, A. Gemma, M. Mizushima, T. Takayama, J. Kumazawa, H. Azuma, K. Tamura
Journal: Journal of Thoracic Oncology (2017)
Margaret McCartney: Pointless paperwork, not patients, is what GPs should avoid
Authors: Margaret McCartney
Journal: BMJ (2017)

Winter’s coming, there’s flu in the southern hemisphere, and the canaries have stopped singing in general practice. I have a visceral sense of dread.

Jeremy Hunt recently spoke to GPs about “the 26% of GP appointments that GPs themselves say are potentially avoidable.”1 He talked about 10 “high impact actions” aimed at releasing capacity, which form part of the Releasing Time for Care programme, put together at a cost of £30m.

Essentially, says NHS England, “most common potentially avoidable consultations were amenable to action by the practice, often with the support of the clinical commissioning group.”2 Some 7% of patients could be diverted elsewhere in the practice, 6% …
Abstract 20540: Dual Mechanisms by Which ANGPTL3 Regulates Low-Density Lipoprotein Cholesterol Levels: Implications for Therapeutic Target of ANGPTL3
Authors: Yu-Xin Xu
Journal: Circulation (2017)

Introduction: ANGPTL3 has emerged as a key regulator of lipoprotein metabolism in humans. Loss-of-function mutations in both ANGPTL3 alleles cause familial combined hypolipidemia characterized by l...
Study pinpoints symptom pattern that indicates endometriosis
Authors: Jacqui Wise
Journal: BMJ (2017)

GPs should look out for a specific pattern of symptoms to enable endometriosis to be diagnosed much earlier, says research in the British Journal of General Practice .1

Endometriosis can be difficult to diagnose clinically as its symptoms are common and non-specific. As a result, often a long time elapses between the first primary care consultation and diagnosis.

Distinct episodes of gynaecological pain and combinations of gynaecological pain with menstrual symptoms …
Recente andamento della gonorrea: un problema emergente di sanità pubblica?
Authors: G Hughes, K. A. Fenton
Journal: Eurosurveillance (2000)

In molti paesi industrializzati, l'infezione da Neisseria gonorrhoeae rimane una delle piu comuni infezioni batteriche a trasmissione sessuale (ITS). Il suo controllo e divenuto una priorita per la sanita pubblica a causa del carico eccessivo sulle popolazioni metropolitane piu povere e delle sue ripercussioni sulla fertilita (1). I nuovi casi d'infezione indicano comportamenti sessuali a rischio relativamente recenti e sono stati utilizzati per monitorare abitudini che, con ogni probabilita, possono facilitare la trasmissione dell'HIV (2). In questo numero di Eurosurveillance, Veronique Goulet e i suoi colleghi riportano un improvviso aumento di gonorrea verificatosi in Francia nel 1998, che e stato identificato grazie alla rete di sorveglianza nazionale basata sui laboratori, RENAGO (Reseau National du Gonocoque). Un simile aumento di gonorrea, osservato in Inghilterra nel 1996, (3) e continuato nel 1997 (4). In entrambi i paesi, gli aumenti osservati sono stati particolarmente allarmanti poiche sono stati successivi ad una costante diminuzione cominciata a meta degli anni '80. Come dovrebbero essere interpretati questi aumenti? Indicano una recrudescenza di comportamenti sessuali a rischio?
NIMG-73. USEFULNESS OF SPINAL MRI AS SCREENING EXAMINATION FOR PATIENTS WITH INTRACRANIAL GLIOMA
Authors: Kenichiro Matsuda, Yuta Mitobe, Kaori Sakurada, Takamasa Kayama, Yukihiko Sonoda
Journal: Neuro-Oncology (2017)

Dissemination of intracranial glioblastoma is seen in 10-20% of cases. They usually appear 6-12 months after treatment and show worse outcome. Otherwise, we have experienced dissemination on first images in rare cases. However, there is mere study on natural course of dissemination. Now, we had investigated frequency and clinical course of spinal dissemination by using pre-treatment and follow-up MRI. 158 cases (GBM: 96, grade 3: 32, grade 2: 30) had examined spinal MRI at pre-treatment period. We had investigation of the presence of intracranial dissemination and ventricular invasion of primary tumor. Furthermore, we examined follow-up spinal MRI on 53 cases harboring GBM. In 96 cases with GBM, 21 (22 %) cases showed intracranial dissemination, and 7 (7 %) cases showed spinal dissemination on pre-treatment examination. In these 7 cases, 6 cases had intracranial dissemination simultaneously. Moreover, all of these 7 cases showed ventricular invasion. There was no spinal dissemination on grade 2 or 3 glioma in pre-treatment examination. In the 7 cases, 5 cases had been resected the primary tumor, but only 4 cases had taken concomitant radiation therapy (resection: 2, biopsy: 2), because of the rapid worsening of general status. These 7 cases showed poor over-all survival of 2-10 months (median: 4 months). Appearance of spinal dissemination on the clinical course had seen in 7 (13.2 %) patients with GBM who had no spinal dissemination on pre-treatment period. Mean interval to detect dissemination was 8.3 months after initial examination. In these cases, 2 cases showed intracranial dissemination on first examination, and others had preceding intracranial dissemination on course. They had worse outcome, and died in 1-7 months after spinal dissemination. Almost all cases with spinal dissemination had preceding intracranial dissemination. Our study suggests that the lower necessity of spinal MRI as screening examination on glioma patients.
IMMU-10. EXPRESSION OF PD-L2, IN GLIOBLASTOMA; IMPLICATIONS AS A BIOMARKER FOR IMMUNOTHERAPY
Authors: Franz Ricklefs, Josie Hayes, Maria Carmela Speranza, Harald Krenzlin, Joseph Costello, Gordon J Freeman, Manfred Westphal, Katrin Lamszus, E Antonio Chiocca, Sean E Lawler
Journal: Neuro-Oncology (2017)

Programmed cell death protein-1 (PD1) expressed on T cells is a key mediator of immune evasion via mediating the inhibition of T-cell function. This occurs via its binding to ligands PD-L1 and PD-L2 on tumor cells and other cells such as macrophages and microglia. Immune checkpoint blockade using anti-PD1 antibodies is of clinical benefit in multiple cancer types and is under investigation in glioblastoma. Tumor PD-L1 expression is currently used to screen for eligibility for anti-PD1 treatment, suggesting that only PD-L1 positive tumors will be included in clinical trials. However, the role of PD-L2 in immune evasion in glioblastoma has not been well studied. To assess the roles of PD-L1 and PD-L2 in glioblastoma, their expression was analyzed in TCGA and IVY Atlas RNAseq data. Genes whose expression was correlated with either PD-L1 or PD-L2 were assessed for pathway enrichment. To compare their effects on patient outcome, Cox regression models for PD-L1 and PD-L2 were fitted. To confirm these findings, western blot and qPCR gene expression was conducted of glioma-patient derived cell cultures (n=19) and fresh tumor samples (n=9). Here we show that PD-L2 is present in glioblastoma at higher levels than PD-L1, and that the level of PD-L2 in the tumor impacts patient survival. Furthermore PD-L2 expression negatively correlated with KPS rho=-0.13 (p=0.007). We show that PD-L2 correlates with retinoic acid receptor and viral induction of apoptosis pathways in glioblastoma. Western blot and gene expression analysis of patient tumor samples and patient-derived cell lines shows that PD-L2 is robustly expressed, while PD-L1 expression is variable. PD-L2 expression was also inducible by IFNy in certain cell lines. These results suggest that PD-L2 should be considered as a biomarker for eligibility of patients in clinical trials for anti-PD1 therapies and widens the net for patient recruitment in these trials.
P1.03-029 Study of Plasma Homocysteine as a Marker of Toxicity and Depression in Patients Treated with Pemetrexed-Based Chemotherapy
Authors: A. Minchom, R. Gunapala, D. Walder, R. Kumar, J. Bhosle, S. Popat, N. Yousaf, M. O’Brien
Journal: Journal of Thoracic Oncology (2017)
SCDT-38. SAFETY AND EFFICACY OF INTRAVENTRICULAR 131I-LABELED MONOCLONAL ANTIBODY 8H9 TARGETING THE SURFACE GLYCOPROTEIN B7-H3 IN PATIENTS WITH CNS/LM DISEASE
Authors: Kim Kramer, Brian Kushner, Shakeel Modak, Neeta Pandit-Taskar, Ursula Tomlinson, Maria Donzelli, Suzanne Wolden, Pat Zanzonico, John Humm, Sophia Haque, Mark Souweidane, Jeffrey Greenfield, Ellen Basu, Stephen Roberts, Jorge Carrasquillo, Jason Lewis, Serge Lyashchenko, Steven Larson, Nai-Kong Cheung
Journal: Neuro-Oncology (2017)

Tumors metastasizing to the central nervous system (CNS) are associated with significant mortality. We tested the toxicity and dosimetry of intraventricular 131I-labeled monoclonal antibody 8H9 targeting surface glycoprotein B7-H3 in patients with CNS. Tumor B7-H3 expression was assessed by immunohistochemistry. CSF flow was determined by 111Indium-DTPA cisternography. 131 patients received 2 mCi tracer of intra-Ommaya 124I- or 131I-8H9 for nuclear imaging followed by a therapeutic injection (10-80 mCi, dose levels 1-8 in 10 mCi increments for phase I patients; expanded cohort 50 mCi/injection) 131I-8H9. Pharmacokinetics were studied by serial CSF and blood samplings over 48 hours. Dosimetry was based on pharmacokinetics and region of interest analyses on serial PET. Toxicity was defined by the CTCAE v.3.0. 8H9 dosimetry and therapy injections were repeated after 1 month if no serious adverse events or progressive disease ensued. Tumor response was determined by clinical, radiographic, cytologic criteria; overall survival was noted. 129 patients with primary or metastatic CNS tumors received 383 injections [median age 5.4 years (1.2- 53.6 years)] Injections were well tolerated and routinely administered in the outpatient setting. Rare self-limited adverse events included grade 1 or 2 fever, headache, vomiting, biochemical elevations in AST or ALT and 1 injection with grade 3 ALT elevation (dose level 3). Although not a dose limiting toxicity, myelosuppression occurred in patients who had received craniospinal radiation and at dose levels 6 and higher (>60 mCi). Of 93 patients treated for metastatic CNS neuroblastoma, an improved overall survival was noted compared to survival reported with conventional therapies. Interpatient variability for total absorbed dose to the CSF and blood was observed; mean absorbed CSF dose was 104.9 cGy/mCi by CSF sampling, and 2.6 cGy/mCi to the blood. We conclude that intraventricular 131I-8H9 is safe, has favorable dosimetry to CSF, and has clinical utility.
QLIF-24. USING FACIAL EXPRESSION AS A SURROGATE INDICATOR FOR QUALITY OF LIFE IN BRAIN TUMOR PATIENTS
Authors: Jennifer Pencek, Stefan Petranek, Mahua Dey
Journal: Neuro-Oncology (2017)

With the increasing complexities of cancer treatment strategies, addressing quality of life (QOL) of cancer patients, is becoming an integral part of comprehensive cancer care. QOL is a multidimensional construct that has been proven difficult to define and measure. Brain tumors have significant impact on patients’ QOL as they can cause considerable impairment in terms of motor and cognitive functioning as well as psychological well-being. Standard method of QOL measurement includes lengthy questionnaires. For brain tumor patients this can be a difficult task to perform. Psychological well-being is not always adequately addressed by clinical intervention. Pet therapy has shown benefits in patients with depression. 1) to determine if facial expression can be used as a surrogate for certain aspects of QOL questionnaires and 2) to evaluate the effect of a therapy dog on patients’ perception of their general well being. First, patients complete the QOL-C30/BN20 questionnaire and have a photograph taken of their face. Following that a therapy dog is brought into the room and the patient spends 10-20 minutes interacting with the dog. Upon completion of the session, patients are again photographed and re-complete the QOL-C30/BN20 questionnaire. For this study, we focused on a few selective scales within the questionnaire. For facial expression analysis, we focused on the upper half of the subjects’ faces from before and after the pet therapy session. The major finding in the questionnaire responses is that all subjects reported an improvement in the future uncertainty category after the pet therapy session. There was notable softening of the facial features in the photographs taken after the session compared to before. In summary our data show that spending as little as 10-20 minutes with a therapy dog improves patients’ outlook on life and this change is reflected in their facial expression.
Evaluating depression in elderly patients with cancer
Authors: S. Parrino, M. Sola, B. Giulio, A. Rosso, O. Cinzia, G. Alessandra, L. Gurrieri, M. Stefano, A. Dicorato, G. Pascoletti, D. Fedele, G. Ceschia, R. Barazzoni
Journal: Annals of Oncology (2017)