tbuckley/cabot-search huggingface dataset:
NIMG-43DUAL VOLUME VISUALIZATION (3D-DSA AND CROSS-SECTIONAL IMAGING) FOR SURGICAL PLANNING OF INTRACRANIAL MENINGIOMAS
Authors: Young Il Kim, Seung Ho Yang, Sang Won Lee
Journal: Neuro-Oncology (2015)

INTRODUCTION: Many techniques about planning for the surgery of intracranial brain tumors have been considered for getting more information about the relationship between tumors and adjacent vasculatures. Especially for the surgery of meningiomas, it is essential to distinguish passing arteries from feeders. It is also very important to preserve venous structures. Dual volume visualization is apt and powerful method to know about these vascular structures. METHODS: Between Feb. 2012 and Dec. 2014, a total of 20 patients underwent brain tumor surgery after undergoing dual volume visualization. The tumors comprised of 1 glioblastoma, 1 medulloblastoma, and 18 meningiomas. The locations of meningiomas were as follows : 6 parasagittal; 4 falx; 2 convexity; 1 tentorial; 1 foramen magnum; 2 sphenoid wing; 1 petroclival; and 1 olfactory groove. RESULTS: In cases involving glioblastoma and medulloblastoma, the boundary between the distinctive tumor mass of the intrinsic tumor and the normal brain is unclear, resulting in post-operative assessments showing greater direct damage done to the normal brain than that caused by vessel injury. Vascular supply and disfiguring observed in preoperative dual volume visualization images closely resembled the actual observations made during the surgery of meningiomas. Three out of eighteen meningioma cases demonstrated new deficits. One case exhibited tumor bed bleeding and perilesional edema leading to aggravation of motor weakness and deterioration. One exhibited venous infarction and a separate delayed hemorrhage leading to motor weakness and deterioration. One developed facial palsy. CONCLUSIONS: The advantages of this technique are as follows: 1. It enables the visualization of arteries and veins, individually; 2. the 3D rotation allows for convenient presurgical orientation; 3. it permits simulating craniotomies. This technique could reduce the incidence of newly developed neurological deficits as a result of identifying which veins to preserve during surgery and predicting the arteries that may shift.
Optimal First-Line and Maintenance Treatments for Advanced-Stage Nonsquamous Non-Small Cell Lung Cancer
Authors: Ryan D. Gentzler, Jyoti D. Patel
Journal: Journal of the National Comprehensive Cancer Network (2014)

During the past 10 years, the treatment of advanced-stage non-small cell lung cancer (NSCLC) has become increasingly complex, and debate continues regarding the optimal chemotherapeutic agents and duration of treatment. The addition of bevacizumab to platinum doublet chemotherapy, the use of pemetrexed for nonsquamous histology, and the introduction of maintenance chemotherapy are strategies that have been shown to improve overall survival beyond 12 months. Many acceptable treatment options are recommended in the NCCN Clinical Practice Guidelines in Oncology for NSCLC. This article discusses the first-line treatment of NSCLC with no identifiable mutations with FDA-approved targeted therapies for patients treated outside a clinical trial, particularly focusing on difficult clinical decisions, such as when the use of bevacizumab is appropriate, choosing a platinum partner, and treatment of patients with an ECOG performance status of 2. Data are summarized from several recent maintenance clinical trials, such as PARAMOUNT, AVAPERL, and PointBreak, and the implications these trials have on practical decisions oncologists must make when choosing an optimal treatment strategy for patients with advanced NSCLC are discussed.
Abstract 226: GGF2 Requires Activation Of PI3 Kinase Pathway To Mediate Cytoprotective Effects In The Mouse Atrial-derived Hl-1 Cardiomyocyte-like Cell Line
Authors: Maya Srinivas, Jing Cao, Roni Zilinski, Anthony O Caggiano, Donald Button
Journal: Circulation Research (2014)

Glial growth factor (GGF2) is a Neuregulin-1 (NRG-1), which binds ErbB receptors and activates downstream cell signaling processes. NRG-1 ligands and their receptors are required for cardiac development and adult cardiac function. GGF2 has been shown to improve left ventricular function in several models of heart failure though the mechanisms by which GGF2 is efficacious are poorly understood. GGF2 is currently in clinical trials for treatment of congestive heart failure. Many studies have focused on GGF2 regulation of PI3 kinase (PI3K) as measured by formation of pAKT in vivo and in numerous cell lines, including HL-1 cells, neonatal rat ventricular myocytes (NRVMs) and human iPSC-derived cardiomyocytes. NRG-1s also activate the MAP kinase (MAPK) pathway as measured by pERK1/2 formation. To better understand GGF2 action in the stressed heart, we have developed in vitro systems to study GGF2 protection of cardiomyocytes from doxorubicin induced toxicity. After serum starvation, cells were pre-incubated with GGF2 (0.15 pM to 9.5 nM) for 1 hr followed by exposure to 1 μM doxorubicin for 18 hrs. After doxorubicin treatment MTT labeling index of cultures was used as an endpoint measurement of cell metabolic status. Doxorubicin decreases MTT labeling index by 90% while GGF2 prevented this toxicity by almost 50% compared to untreated cells, with an EC 50 of 83.3±19.4 pM . This effect appears to be dependent upon AKT signaling and not MAPK as assessed using inhibitors of both pathways. Inhibition of MAPK increases pAKT formation without changing extent of GGF2 protection. Blocking ErbB4 receptor, highly expressed in cardiomyocytes, causes a decrease in pAKT formation, suggesting that this receptor is important for mediating GGF2 action in these cells. Our results demonstrate that, in HL-1 cells, GGF2 mediates cytoprotective responses which require PI3K activation. Similar studies are being pursued in doxorubicin-treated NRVMs and human iPS derived cardiomyocytes. Initial results indicate GGF2 also mediates cytoprotective effects in these cell types. Future efforts will be aimed at elucidating potential roles for PI3K-dependent GGF2 regulation of mitochondrial function, Ca 2+ signaling or REDOX regulation in the observed cytoprotective actions.
Pd-L1 Expression and Survival Among Advanced Non–Small Cell Lung Cancer (Nsclc) Patients Treated with Chemotherapy
Authors: S. Sorensen, W. Zhou, M. Dolled-Filhart, J.B. Georgsen, Z. Wang, K. Emancipator, D. Wu, M. Busch-Sorensen, P. Meldgaard, H. Hager
Journal: Annals of Oncology (2014)
Lessons From Peglispro: IMAGINE How to Improve Drug Development and Affordability
Authors: Matthew C. Riddle
Journal: Diabetes Care (2016)

Imagination is more important than knowledge.—Albert Einstein, 1931

On 4 December 2015, Eli Lilly announced it was ceasing development of its basal insulin peglispro, a new long-acting insulin analog (1). This was not entirely unexpected, given that in February 2015 Lilly announced a delay in submitting this product for regulatory review due to signs of liver injury apparently related to fat accumulation (2). The company presumably made this difficult decision because peglispro’s prospects for regulatory approval and commercial success were dimmed by potential hepatic toxicity in the context of a market already including several other basal insulins, among them Lilly’s biosimilar version of insulin glargine. Still, the story behind this costly, late-stage failure of a new product offers several messages for the diabetes community.

Part of this story concerns an unusual property of peglispro. The active component is insulin lispro, an analog of human insulin, which is linked to a large hydrophilic polyethylene glycol polymer (3). Due to its structure, peglispro is slowly absorbed after injection and also slowly cleared from circulation. Early studies—including a clinical development program named IMAGINE—showed that peglispro has a long and stable profile of action (4) and causes less hypoglycemia than insulin glargine (5). Moreover—and herein lies its novelty—peglispro was as effective as regular human insulin (6) or glargine (7) in suppressing hepatic glucose production but had less effect on peripheral tissues. A possible explanation for its hepatic specificity is better access of the large peglispro molecule to liver tissue through windows (fenestrae) in portal vessels than to peripheral tissues. Thus, peglispro might control glucose through the reduction of hepatic glucose release with less risk of hypoglycemia caused by variable peripheral uptake by muscle and might favor weight loss rather than gain (8). Surely, the investigators working on peglispro were intrigued by these possibilities. …
FDG-PET is a predictor of metabolic response to chemotherapy in metastatic colorectal cancer (mCRC)
Authors: Nancy Van Damme, Sylvie De Bruyne, Jeroen Mertens, Christophe Van De Wiele, Wim Ceelen, Peter Smeets, Liesbeth Ferdinande, Stéphanie Laurent, Karen Geboes, Marc Peeters
Journal: Journal of Clinical Oncology (2011)
Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells.
Authors: C Libetta, T Rampino, G Palumbo, C Esposito, A Dal Canton
Journal: Journal of the American Society of Nephrology (1997)

Previously, the authors reported that the serum of patients with immunoglobulin (Ig) A nephropathy stimulated peripheral leukocytes, and this effect was inhibited by nominal haptens for lectins. In vitro studies have shown that lectins can bind to rat mesangial cells and cause their activation. This study was performed to investigate whether the serum of IgA nephropathy patients contains lectins that activate mesangial cells, i.e., induce release of interleukin (IL)-6, a nephritogenic cytokine. The serum of patients was adsorbed by affinity chromatography on resins loaded with lectin-binding sugars. After adsorption, serum supernatant was collected and the resins were then eluted. Human mesangial cells were conditioned with native serum, post-adsorption supernatant, and eluate (all three at 10%) for 24 h, and the release of IL-6 was determined by ELISA. Normal serum was used as control. Incubation of mesangial cells with IgA nephropathy patients serum raised average IL-6 release from 8.5 pg/mL to 274.1 pg/mL. Adsorption in beta-D-glucose and N-acetyl-D-glucosamine caused a fall in the activity of patients' serum, to 17.0 and 63.7 pg/mL, respectively, and the activity lost was recovered in the eluate (185.2 and 142.7 pg/mL, respectively). Neither adsorption on N-acetyl-D-galactosamine nor on fucosylamine was associated with any effect on serum activity; accordingly, no activity was found in the eluates. Serum of patients with non-IgA mesangiocapillary nephritis did not stimulate mesangial cells. These results show that the serum of IgA nephropathy patients contains specific lectins that stimulate IL-6 nephropathy by mesangial cells and are, therefore, potential nephritogenic.
MITO (Multicentre Italian Trials in Ovarian cancer): CERV 2 trial—A randomized phase II study of carboplatin and paclitaxel +/- cetuximab, in advanced and/or recurrent cervical cancer.
Authors: Sandro Pignata, Giovanni Scambia, Domenica Lorusso, Ugo De Giorgi, Maria Ornella Nicoletto, Rossella Lauria, Anna Maria Mosconi, Cosimo Sacco, Claudia Omarini, Pierosandro Tagliaferri, Gabriella Ferrandina, Saverio Cinieri, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Vanda Salutari, Maria Carmela Piccirillo, Gennaro Daniele, Ciro Gallo, Francesco Perrone
Journal: Journal of Clinical Oncology (2015)

5520 Background: Carboplatin (C) plus paclitaxel (P) is among standard options for treatment of advanced or recurrent cervical cancer (ARCC) patients (pts). Cervical cancer cells often express Epidermal Growth Factor receptor (EGFR). Cetuximab (CET), an anti-EGFR monoclonal antibody, can be safely combined with CP. MITO-CERV 2 is a comparative randomized phase 2 study, testing the addition of CET to CP. Methods: ARCC pts, < 2 previous chemotherapy, ECOG PS≤1, were randomized to CP (C AUC5 + P 175 mg/m², d1q21) for 6 cycles +/- CET (400 mg/m² one week before starting CP, then 250 mg/m² weekly) until disease progression or unacceptable toxicity. Primary endpoint was event-free survival (EFS), i.e. time from randomization to progression, death, definitive discontinuation of the whole treatment or loss to follow-up, whichever occurred first. With a 4.5 mos expected median EFS and a 6.4 mos auspicated EFS (HR 0.70), 0.20 one-tailed α and 80% power, 89 events were required for the final intent-to-treat analysis. Results: 108 pts were randomly assigned to CP (n = 53) or to CP-CET (n = 55). Median age was 50, 69% were PS0, 76% had recurrent disease, 91% had distant metastasis and 57% had received previous chemotherapy. A median number of 6 CP cycles was given in both arms. After a median follow-up of 23 mos (95% CI:20-26), 102 pts had an event, 97 progressed and 61 died. Median EFS was 4.7 and 6.0 mos (one-tail p = 0.43), median PFS was 5.2 and 7.6 mos (one-tail p = 0.20) and median OS was 17.7 and 17 mos (one-tail p = 0.27), with CP and CP-CET, respectively. One patient died for a stroke during standard treatment. There was no difference in the occurrence of severe side-effects, except grade 3-4 skin toxicity reported only with CP-CET (8 cases, 6 with acneiform rash, p = 0.004). Out of 86 patients eligible for RECIST, objective response rate was 43% and 38% with CP and CP-CET respectively (p = 0.63). Conclusion: The addition of CET to CP is not worthy of further investigation in unselected ARCC pts. Efforts are ongoing to retrospectively collect tumor samples for an exploratory biomarker analysis. ClinicalTrials.gov NCT00997009. Partially supported by Merck Serono. Clinical trial information: NCT00997009.
Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: A feasible and active approach
Authors: E E Vokes, D J Haraf, J M McEvilly, R Mick, M F Kozloff, M D Goldman, W J Moran, N J Clendeninn, M A Collier, R R Weichselbaum
Journal: Annals of Oncology (1992)
Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with “Ultracentral” Non–Small Cell Lung Cancer
Authors: Hilâl Tekatli, Niels Haasbeek, Max Dahele, Patricia De Haan, Wilko Verbakel, Eva Bongers, Sayed Hashemi, Esther Nossent, Femke Spoelstra, Adrianus J. de Langen, Ben Slotman, Suresh Senan
Journal: Journal of Thoracic Oncology (2016)
Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel
Authors: Ho Jeong Lee, Masaki Hanibuchi, Sun-Jin Kim, Hyunkyung Yu, Mark Seungwook Kim, Junqin He, Robert R. Langley, François Lehembre, Urs Regenass, Isaiah J. Fidler
Journal: Neuro-Oncology (2016)

We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases.The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy.Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases.Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases.
Squirrel Monkey Retrovirus and &lt;italic&gt;Herpesvirus saimiri&lt;/italic&gt;: Observation in the Same Cell Following Isolation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G C Smith, R L Heberling, S T Barker, S S Kalter
Journal: JNCI Journal of the National Cancer Institute (1979)

Electron microscopic examination of mink lung cells previously cultured with a squirrel monkey (Saimiri sciureus) throat swab suspension revealed the presence of squirrel monkey retrovirus (SMRV) and Herpesvirus saimiri (HVS) coexisting within the same cells in culture. HVS was identified by serum neutralization, and the retrovirus isolate was identified as SMRV by a morphologic examination, microimmunodiffusion analysis, and demonstration of an Mg2+ preference for the RNA-directed DNA polymerase.
Physiotherapy for pain: a meta-epidemiological study of randomised trials
Authors: Elisabeth Ginnerup-Nielsen, Robin Christensen, Kristian Thorborg, Simon Tarp, Marius Henriksen
Journal: British Journal of Sports Medicine (2016)

Objectives To empirically assess the clinical effects of physiotherapy on pain in adults. Design Using meta-epidemiology, we report on the effects of a ‘physiotherapy’ intervention on self-reported pain in adults. For each trial, the group difference in the outcome ‘pain intensity’ was assessed as standardised mean differences (SMD) with 95% CIs. Stratified analyses were conducted according to patient population (International Classification of Diseases-10 classes), type of physiotherapy intervention, their interaction, as well as type of comparator group and risks of bias. The quality of the body of evidence was assessed based on GRADE methodology. Data sources Systematic searches were carried out in MEDLINE and PEDro from 1 January 2004–31 December 2013. 174 trials (224 comparisons) met the inclusion criteria for the meta-analysis. Eligibility criteria for selecting studies Randomised trials using ‘no intervention’ or of a sham-controlled design were selected. Only articles written in English were eligible. Results An overall moderate effect of physiotherapy on pain corresponding to 0.65 SD-units (95% CI 0.57 to 0.73) was found based on a moderate inconsistency (I 2 =51%). Stratified exploration showed that therapeutic exercise for musculoskeletal diseases tended to be more beneficial than multimodal interventions (difference 0.30 95% CI 0.03 to 0.57; p=0.03). Trials with a ‘no intervention’ comparator tended to have a higher overall effect size than trials with a sham comparator (difference 0.25; 95% CI 0.09 to 0.41; p=0.004). In general, our confidence in the estimates was low, mainly due to high risk of performance biases and between-study heterogeneity. Conclusions Physiotherapy reduces pain in adults, but standardisation of interventions and focus on trial research with low risks of bias and reproducible treatment modalities are needed. Trial registration number CRD42014008754.
A randomized pilot study comparing aprepitant to olanzapine for treatment of chemotherapy-induced nausea and vomiting
Authors: N. M. Shumway, S. E. Terrazzino, C. B. Jones
Journal: Journal of Clinical Oncology (2009)

9633 Background: Chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) is prevalent. The NK 1 antagonist, aprepitant (APR), has been shown to decrease CINV and with increased use, cost of supportive care is rising. Recent studies have shown that olanzapine (OLN) is safe and effective for CINV when used in combination with dexamethasone and palonosetron. We conducted a randomized, double-blind, placebo controlled pilot study to evaluate the use of OLN compared to APR for prevention of CINV in patients receiving HEC. Methods: Chemotherapy naïve patients receiving HEC were randomized to an APR containing arm or an OLN containing arm [see Table ] for the first 2 cycles of treatment. Patients recorded episodes of emesis and use of rescue meds using a daily diary and symptoms using the M.D. Anderson Symptom Inventory(MDASI). 18 patients consented to the protocol and 17/18 (OLN=8, APR=9) patients were evaluable (1 lost daily diary) with a median age 60 (range 24–71) 11/18 were females. Results: Chemo regimens for OLN group included (AC=50%, cisplatin=25%, ABVD=25%, and ifos=25%) and for APR (AC=55%, cisplatin=33%, and ABVD=11%) For both cycles (C1+C2) the complete response (CR=no emesis, no rescue) during the anticipatory period (D-2, D-1) was 87.5% in the OLN group compared to 77.8% in the APR group. Acute period (D1) CR rates were 75% in OLN vs. 44% in the APR group. Delayed (D2–4) CR rates were 62.5% in OLN vs. 55.6% in the APR group. Rates of nausea (score ≥ 1 on scale of 0–10, MDASI) were 25% OLN vs. 22.2% APR for anticipatory period, 62.5% OLN vs. 44.4% APR for acute period, and 62.5% OLN vs. 66.7% APR for delayed period. There were no grade 3 /4 toxicities. Conclusions: OLN containing antiemetic regimens were well tolerated and offered similar efficacy as APR containing regimens in preventing CINV in patients receiving HEC. Larger studies are needed to evaluate non-inferiority and potential cost savings of OLN containing regimens. [Table: see text] No significant financial relationships to disclose.