tbuckley/cabot-search huggingface dataset:
O5.04 * PRELIMINARY RESULTS OF THE GALA-5 STUDY: AN EVALUATION OF THE TOLERABILITY AND FEASIBILITY OF COMBINING 5-AMINO-LEVULINIC ACID (5-ALA) WITH CARMUSTINE WAFERS (GLIADEL) IN THE SURGICAL MANAGEMENT OF PRIMARY GLIOBLASTOMA
Authors: C. Watts, K. Wanek, P. Smith, N. Counsell
Journal: Neuro-Oncology (2014)

BACKGROUND: Fluorescence-guided resection of glioblastoma improves surgical cytoreduction. Intra-operative carmustine wafers may enhance survival in patients with good surgical resection. The objective of this study was to establish the safety and tolerability of combining fluorescence-guided surgical resection (5-ALA) with intra–operative chemotherapy (carmustine wafers) in patients with primary glioblastoma (GBM) prior to standard treatment with radiotherapy and temozolomide. METHODS: A single arm design with the following inclusion criteria: • Age 18+ years • Patient reviewed at a specialist neuro-oncology MDT • Imaging evaluated by a neuro-radiologist and judged to be a GBM • Radical resection judged to be realistic by the neurosurgeons (i.e. NICE criteria for the use of Carmustine wafers can be met) • WHO performance status 0 or 1 on clinical review. RESULTS: Seventy-two patients were recruited from 8 UK sites between July 2011 and May 2013; 64 patients received carmustine wafer implants and 59 patients were found to be eligible after surgery. Thirteen patients were found to be ineligible due to: wafers not inserted (n = 8); GBM not diagnosed post-operatively (n = 4); simultaneous diagnosis of unrelated cutaneous sebaceous carcinoma (n = 1). There were 8 surgical complications reported in 6 patients: wound infections were reported in 5 patients (8%) and cerebrospinal fluid leakage in 3 patients (5%). One patient was not able to begin chemoRT (1/33, 3%), and 4 patients (4/33, 12%) were not able to begin chemoRT within 6 weeks of surgery, due to surgical complications. After a median follow-up of 10.8 months, 25 patients (42%) are alive without progression, 16 patients (27%) are alive having progressed and 18 patients (31%) have died. Thirty-three patients (56%) have reported 68 adverse events of grade 3 or higher, 5 of these were reported as being ‘possibly’ related to the combination of 5-ALA and carmustine wafers: sepsis (n = 2), wound infection (n = 2), seizure (n = 1). CONCLUSION: The combination of 5-ALA and carmustine wafers is safe and tolerable in the surgical management of primary glioblastoma. A phase III randomised controlled trial is being designed to evaluate efficacy.
Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome
Authors: Roy G Brower, Paul N Lanken, Neil MacIntyre, Michael A Matthay, Alan Morris, Marek Ancukiewicz, David Schoenfeld, B Taylor Thompson
Journal: New England Journal of Medicine (2004)

Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients.We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen.Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50).These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.
Antigen-Specific Suppressor T Lymphocytes in Human Lymphatic Filariasis
Authors: Willy F. Piessens, Felix Partono, Stephen L. Hoffman, Sutanti Ratiwayanto, Patricia W. Piessens, James R. Palmieri, Iskak Koiman, David T. Dennis, W. Patrick Carney
Journal: New England Journal of Medicine (1982)

Immune responses to parasite antigens are much lower in patients with microfilaremia than in persons with other manifestations of brugian filariasis. To determine whether hyporeactivity is associated with changes in populations of lymphocytes that regulate immune responses, we quantitated helper and suppressor T cells in the blood of patients infected with Brugia malayi. Increased numbers of suppressor T cells were present in 15 of 17 patients with microfilaremia and in six of 11 patients with elephantiasis. This increase correlated with hyporeactivity to filarial antigens but not to nonparasite antigens. Removal of suppressor T cells activated in vivo or in vitro improved reactivity to filarial antigens. These results suggest that immunosuppression induced by filarial parasites is a possible mechanism of survival of these organisms in an immunocompetent host. (N Engl J Med. 1982; 307:144–8.)
522 MAINTAINED VIRAL SUPPRESSION AND EXCELLENT SAFETY PROFILE OF ENTECAVIR MONOTHERAPY IN 418 NUC-NAÏVE PATIENTS WITH CHRONIC HEPATITIS B: A 4-YEAR FIELD PRACTICE, MULTICENTER STUDY
Authors: P. Lampertico, R. Soffredini, F. Invernizzi, M. Viganò, F. Facchetti, E. Minola, O. Fracassetti, F. Suter, S. Zaltron, A. Vavassori, G. Carosi, E. Angeli, G. Gubertini, C. Magni, A. Testa, G. Antonucci, M. Vinci, G. Pinzello, E. Fatta, S. Fargion, P. Del Poggio, B. Coco, M. Brunetto, M. Andreoletti, A. Colli, M. Fasano, T. Santantonio, G. Colloredo, L. Pasulo, S. Fagiuoli, A.E. Colombo, G. Bellati, F. Fumagalli Maldini, M. Milanese, M. Pozzi, N. Terreni, G. Spinzi, M. Quagliuolo, M. Borzio, G. Lunghi, M. Colombo
Journal: Journal of Hepatology (2012)
Subcutaneous Injection of the HIV-1 Fusion Inhibitor Enfuvirtide (FUZEON) May Result in Soft-Tissue Accumulation of Tc-99m MDP
Authors: L. E. Pack, Lionel S. Zuckier
Journal: Clinical Nuclear Medicine (2011)

Bone scintigraphy using Tc-99m methylene diphosphonate (MDP) was performed on a 16-year-old girl as a component of surveillance for recurrence of leimyosarcoma, resected from her right foot 7 years earlier. A symmetric pattern of increased radiotracer uptake was noted in the soft tissues of her upper arms, thighs, and abdomen, corresponding to sites of twice daily rotating subcutaneous injections of Enfuvirtide (FUZEON), a peptide that interferes with fusion of the HIV to host CD4 cells. Use of this medication should be included in the differential diagnosis of causes of soft-tissue uptake of Tc-99m MDP in patients with history of HIV infection.
Abstract 4307: Characterization of a novel lymphoid progenitor population with predictive value in canine non-Hodgkin lymphoma
Authors: Daisuke Ito, Anne C. Avery, Nicola J. Mason, Tim D. O'Brien, Jaime F. Modiano
Journal: Cancer Research (2010)

Abstract Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of lymphoid tumors divided into more than 25 subtypes. Histological classification and clinical stage are used to predict patient outcomes; however, disease progression is variable even within the same NHL subtype. Cancer stem cells (CSCs) are etiologically important cells that can maintain tumors, or whose frequency may reflect individual tumor biology. In terms of patient care and outcome, CSCs are considered to be resistant to conventional therapies. Thus, CSCs are not only etiologically important, but also might mediate treatment failure and relapse, suggesting they have prognostic impact for cancer. The presence and significance of CSCs or CSC-like progenitor cells in NHL has not been conclusively established. The objective of this study was to evaluate the existence and predictive value of lymphoid progenitor cells (LPCs) in dogs with naturally occurring NHL. We previously reported the use of flow cytometry to prospectively identify and enumerate cells in lymph nodes that co-expressed markers associated with hematopoietic progenitors (CD34, c-Kit, and CD133) and the common leukocyte antigen CD45. The number of these cells was inversely correlated (and predictive) for outcome following standard of care with CHOP-based chemotherapy. We now show that these cells represent an atypical lymphoid population, which harbors progenitor markers and lymphoid differentiation markers found within the B-cell phenotype (CD22+) comprising the malignant population. Furthermore, these cells appear to have clonal antigen receptor rearrangements that are related to the principal rearrangement found in the overall (progenitor antigen-negative) malignant cells. The number of progenitor marker- and CD22-positive cells was significantly greater (P=0.0017) in lymphoma samples as compared to lymph nodes from unaffected control dogs, where cells with this phenotype were present in vanishingly small numbers. Together, our results suggest that LPCs in malignant lymph nodes are not only predictive for survival of dogs with spontaneous NHL, but also may represent the CSC compartment for this disease (i.e., “lymphoma-initiating cells”). To confirm their CSC potential, we have adapted an in vitro culture system and a xenotransplantation model that will allow us to expand and serially transplant these primary canine B-cell lymphomas for more detailed studies. This project establishes a useful large animal (canine) model to test the validity of the cancer stem cell theory in non-Hodgkin lymphoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4307.
Neonax: Neoadjuvant Plus Adjuvant or Only Adjuvant Nab-Paclitaxel Plus Gemcitabine for Resectable Pancreatic Cancer: A Phase II Study of the Aio Pancreatic Cancer Group
Authors: Ettrich Thomas, Berger Andreas, Muche Rainer, Lutz Manfred, Prasnikar Nicole, Uhl Waldemar, Tannapfel Andrea, Heinemann Volker, Seufferlein Thomas
Journal: Annals of Oncology (2014)
Pancreatitis Secondary to Endoscopic Retrograde Cholangiopancreatography on a Whole-Body Ga-67 Scan
Authors: KENNETH P. LYONS, SUDHA CHALLA, NORAH MILNE, W. THERON BROWN
Journal: Clinical Nuclear Medicine (1997)

A 65-year-old man who had fever, nausea, vomiting, and elevated liver enzymes for 2 weeks had an abdominal CT and an endoscopic retrograde cholangiopancreatography(ERCP), both of which were normal. Fever and a persistent leukocytosis followed the ERCP. Two days later, a whole-body Ga-67 scan to rule out an intraabdominal abscess showed intense gallium concentration within the pancreas, suggesting pancreatitis secondary to the ERCP. The serum amylase and lipase also were high at this time. A repeated CT of the abdomen showed peripancreatic stranding and an edematous swollen pancreas, confirming the diagnosis of pancreatitis.
INITIATION OF RENAL REPLACEMENT THERAPY FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT IS ASSOCIATED WITH DISMAL OUTCOMES
Authors: Jay Nitin Patel, Sonya Gadhvi, Michael Salama, Liliana Rios-Rojas, Joseph Mattana, John Goncalves, Richard Schwartz, Kevin Marzo, Abdul Moiz Hafiz
Journal: Journal of the American College of Cardiology (2015)
Silent reintroduction of wild-type poliovirus to Israel, 2013 – risk communication challenges in an argumentative atmosphere
Authors: E Kaliner, J Moran-Gilad, I Grotto, E Somekh, E Kopel, M Gdalevich, E Shimron, Y Amikam, A Leventhal, B Lev, R Gamzu
Journal: Eurosurveillance (2014)

Israel has been certified as polio-free by the World Health Organization and its routine immunisation schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunisation campaign using oral polio vaccine (OPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication. This paper reviews the challenges faced by the MOH and the communication strategy devised, in order to facilitate and optimise the various components of the public health response, particularly vaccination. Lessons learned from our recent experience may inform risk communication approaches in other countries that may face a similar situation as global polio eradication moves towards the 'End game'.
Abstract 5395: Mutant oncolytic Herpes simplex virus expressing yeast cytosine deaminase in combination with 5-FC: Viral replication and prodrug bioactivation kinetics in vivo
Authors: Suguru Yamada, Toshihiko Kuroda, Bryan C. Fuchs, Xiaoying He, Jeffrey Supko, Christopher M. McGinn, Anthony Schmitt, Michael Lanuti, Kenneth K. Tanabe
Journal: Cancer Research (2011)

Abstract Background: Herpes simplex virus 1 (HSV-1) expressing yeast cytosine deaminase (yCD) is a well-characterized prodrug/enzyme system that converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). However, a greater understanding of the interactions between the cellular response to 5-FC activation and viral replication is required to establish optimal dosing schedules for virus and prodrug administration. Methods: Using the flip flop BAC system we developed a HSV-1 mutant expressing the yCD gene in the ICP6 locus in the HSV strain Patton, termed bMP6-CMVFcumB. BALB/c mice with MC26 flank tumors were treated by intratumoral injection of bMP6-CMVFcumB and 5-FC was administered intraperitoneally at different initiation times for 6 days. We also investigated different durations of 5-FC administration after initiation on Day 3 after viral injection. To measure viral replication and transgene expression, MC26 tumors on flanks were harvested at different time points between Day 0 and Day 21 following virus injection. Tumor lysates were analyzed by quantitative real-time PCR to assess genomic HSV-DNA, viral plaque assay to assess replicative virions and LacZ staining to assess transgene expression. 5-FU levels in serum and tumor were measured by HPLC at specific time points following administration of 5-FC on Day 3 after viral injection. Results: Intratumoral viral genomic DNA copy number and viral titers peaked on Day 3 after viral injection and gradually decreased afterwards. And consistent with this, 5-FC administration on Day 3 post viral injection was more effective than administration on Day 6. Virus was detected for as long as 2 weeks after viral injection. And consistent with this finding, administration of 5-FC for 12 days was superior to 6 days, and administration for 18 days provided no added benefit over 12 days. The peak level of 5-FU in tumors was seen on Day 6 after viral injection and this value decreased gradually afterwards. Analysis of serum samples demonstrated that 5-FU was present at very low levels on Day 6, but it could not be detected at any other time. Conclusion: Viral replication and transgene expression can be effectively monitored over time and correlated with therapeutic response. Our results suggest that the most potent effect by this combination therapy is observed when 5-FC is initiated at the onset of peak viral and transgene expression and continued for the duration of expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5395. doi:10.1158/1538-7445.AM2011-5395
CHOP and DHAP plus rituximab followed by autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL): A pilot study from the GELA
Authors: R. Delarue, C. Haioun, P. Brice, A. Delmer, V. Ribrag, A. Van Hoof, O. Casasnovas, H. Tilly, G. Salles, O. Hermine
Journal: Journal of Clinical Oncology (2004)

6529 Background: Sequential chemotherapy by CHOP and DHAP regimens followed by ASCT improves complete response (CR) rate and EFS in younger patients with MCL (Lefrère et al, Leukemia, 2002). Since Rituximab (R) may induce significant response in relapsing MCL, we conduct a pilot, multicentric study to determine the impact of the CHOP/DHAP protocol plus R followed by ASCT as a first line therapy in the treatment of MCL at advanced stage. Methods: Patients under 66 years with histologically proven, stage III-IV MCL were included. Treatment consisted of two courses of CHOP, one R-CHOP (Rituximab : 375 mg/m2) and three R-DHAP. Peripheral blood stem cells harvest was performed at the end of the third R-DHAP. Responding pts were eligible for an ASCT after high dose therapy with TBI (10 Gy), Aracytine (6g/m2) and Melphalan (140 mg/m2) (TAM 6) or BEAM if TBI could not be performed. Results: From May 2000 to November 2003, 56 pts were included in this study. Median age is 57 years. Fourty-eight pts are evaluable for treatment response. Characteristics of patients are as follow : bone marrow involvement (42/48), leukemic disease (23/48), PS>1 (3/48), extramedullary involvement (20/48) included gastrointestinal (10/22 tested), LDH > 1N (15/48). Fourty-four pts are evaluable after the three courses of (R)-CHOP. Response rates were as follow : CR (4/44), PR > 50% (37/44) and stable disease (3/44). Fourty patients have completed the three courses of R-DHAP. After the R-DHAP, response rates were : PR (14/40), CR (23/40) and SD (3/40). PBSC harvest was successful in 39/40 patients. Thirty patients were autografted with a TAM 6 (28 pts) or a BEAM regimen (2 pts). After ASCT, all patients but one were in CR. Currently, with a median follow up of 25 months, 28/30 pts were in CR 1 and only one relapse was observed. One patient died from unrelated cause. Conclusions: Chemotherapy with DHAP followed by a Aracytine containing regimen provide a high response rate in untreated MCL. However, longer follow-up is needed to assess impact of Rituximab on EFS and survival. Multicentric European study is currently ongoing to test this approach against R-CHOP induction therapy. No significant financial relationships to disclose.
PWE-280 Ferroportin disease—an important cause of iron overload
Authors: R Mahmood, M Labib, N C Fisher
Journal: Gut (2012)

<h3>Introduction</h3> Ferroportin disease is a recently characterised cause of iron overload. Unlike hereditary haemochromatosis it involves genetic mutations of SLC40A1 gene, and has autosomal dominant transmission. We describe here 3 siblings with typical features. <h3>Methods</h3> All cases had evaluation of liver function, serum iron markers and relevant molecular genotyping. One case (male) had liver MRI scan and two cases (female) had liver biopsy. <h3>Results</h3> Median age was 41. None of them had other risk factors for liver disease. All had normal liver biochemistry, with elevated ferritin levels &gt;1500 μg/l and transferrin saturations consistently below 40%. Liver MRI scan suggested iron deposition. Liver biopsies showed normal architecture with iron deposition mainly restricted to Kuppfer cells with no hepatocellular damage. Molecular genotyping identified SLC40A1 gene mutation in all cases. The male underwent four venesections which were poorly tolerated and have been suspended, while the females accepted an expectant approach. <h3>Conclusion</h3> These cases illustrate features of classical ferroportin disease, with hyperferritinemia, normal transferrin saturation and Kuppfer cells iron loading with no evidence of hepatocyte injury. The natural history of this phenotype is unclear thus require long term follow-up. However, other mutations with a greater likelihood of causing liver injury have been described. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Mayr R</b>, Janecke AR, Schranz M, <i>et al.</i> Ferroportindisease: A systematic meta-analysis of clinical and molecular findings. <i>J Hepatol</i> 2010;<b>53</b>:941–9.
Abstract 1433: Tumor-associated fibroblasts increase HNSCC invasion in the presence of carcinogen NNK via activation of EGFR and c-Met
Authors: Joseph Kim, Mary Panahandeh, Sufi M. Thomas
Journal: Cancer Research (2010)

Abstract Tobacco smoking is a major risk factor for head and neck squamous cell carcinoma (HNSCC); one of the leading causes of cancer mortality. Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) a major product of cigarette smoke and is a well known carcinogen. Approximately 20 − 40% of former smokers continue to smoke 1 year post-HNSCC diagnosis. The role of NNK in tumor progression remains unknown. We hypothesize that exposure to carcinogens such as NNK contributes to the invasive and metastatic ability of HNSCC. In addition we believe it affects the surrounding stromal tissue, facilitating tumor progression. In order to examine the effects of NNK on HNSCC and stomal fibroblast invasion, we used Matrigel-coated transwell invasion chambers, where the cells were plated on top of the Matrigel for 24 h following which the invaded cells were fixed, stained, and counted. Our data demonstrate that NNK (10 nM) increases invasion in both HNSCC cells as well as surrounding stromal fibroblasts though Matrigel. Further, we demonstrate that NNK treatment resulted in activation of the epidermal growth factor receptor (EGFR) and c-met in HNSCC cells. EGFR activates downstream molecules increasing HNSCC invasion. Inhibition of EGFR using the EGFR specific antibody cetuximab abrogates NNK-induced invasion in HNSCC cells. Neutralizing antibodies to HGF abrogates NNK induces invasion in the presence of tumor associated stromal fibroblasts. These findings provide important insights into mechanism whereby NNK contributes to tumor progression. Further, inhibition of EGFR abrogates NNK-mediated invasion of HNSCC and may facilitate loco-regional spread of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1433.
Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group
Authors: D-C Liang, I-J Hung, C-P Yang, K-H Lin, J-S Chen, T-C Hsiao, T-T Chang, C-H Pui, C-H Lee, K-S Lin
Journal: Leukemia (1999)
1292 RESOLVIN D1 PRIMES INFLAMMATION-RESOLUTION PROGRAMMES DURING MODERATE CALORIE RESTRICTION IN OBESITY-INDUCED NASH
Authors: B. Rius, E. Titos, E. Morán-Salvador, C. López-Vicario, V. García-Alonso, A. González-Périz, V. Arroyo, J. Clària
Journal: Journal of Hepatology (2013)