tbuckley/cabot-search huggingface dataset:
High-dose radiation therapy using photons and carbon ion radiotherapy in patients with atypical and anaplastic meningiomas: Relevance of neuropathologic classification and therapeutic impact of a boost using of carbon ion radiotherapy.
Authors: S. E. Combs, A. von Deimling, J. Debus, D. Schulz-Ertner, C. Hartmann
Journal: Journal of Clinical Oncology (2010)

2071 Background: Histology reevaluation and correlation with outcome after photon and carbon ion radiotherapy (RT) was performed in 73 patients with atypical or anaplastic meningiomas. Methods: Twenty-seven patients were treated with FSRT, 7 with IMRT and 8 patients with a carbon ion boost. All other patients were treated with 3D-conformal photon RT. The tumor specimens of 66 patients were acquired for review and H&E, reticulin, and IHC for Mib1, EMA, CD34, Lu5, INI1, GFAP were performed. In 4 cases the initial diagnosis was not reproducible. Overall survival (OS) and progression- free survival (PFS) were analyzed. Impact of RT dose was evaluated. Results: Re-evaluation resulted in an identical grading in 25 tumors, a downgrading of 1 grade in 28 patient, downgrading of 2 grades in 8 patients, and in upgrading of one grade in 1 tumor. Therefore, 17 patients were graded as benign meningiomas WHO grade I, 32 patients as atypical meningiomas WHO grade II, and 13 patients as anaplastic meningiomas. According to the 1993-classification, OS rates were 95.3% at 5 years for grade II, and 63% at 5 years for grade III meningiomas (p = 0.02). After re-evaluation, tumors of 10 patients were downgraded to grade I. with an OS of 100%; for grade II, OS was 73% at 5 years, and 42% at 5 years for grade III tumors (p = 0.009). Patients initially graded as anaplastic (n = 39) were subdivided after re-evaluation into grade I, II and III, showed a significant difference in OS (p = 0.03). PFS was 60% at 5 years for grade II, and 32% for grade III tumors (p = 0.03). After re-evaluation, PFS for grade II was 43% at 5 years; for grade III, PFS was 8% at 5 years (p = 0.02). In the group treated with carbon ion RT low toxicity and higher survival rates of 75% and 63% at 5 and 7 years was seen. Conclusions: Postoperative RT is recommended for high risk meningiomas. With the new classification, standardized evaluation is possible. Carbon ion RT offers an excellent mode of dose-escalation in patients with high-risk meningiomas and will be evaluated in a prospective trial at the Heidelberg Ion therapy Center (HIT; MARCIE-Trial). No significant financial relationships to disclose.
MOLECULAR PROFILING AS A STRATEGY TO PROSPECTIVELY IDENTIFY PRIMARY SOLID TUMOURS IN METASTATIC CANCER PATIENTS
Authors: E de Azambuja, G Daugaard, C Moulin, M Paesmans, D De Jong, J De Greve, G Ismael, AK Moeller, Lieveke Ameye, A Awada
Journal: Annals of Oncology (2010)
Immunohistochemical expression of Dicer in melanoma.
Authors: C. Capalbo, F. Passarelli, Z. di Rocco, A. Scoppola, P. Marchetti
Journal: Journal of Clinical Oncology (2010)

8591 Background: Little is known about Dicer (D) deregulation in tumour development and/or progression although several recent studies show that a decrease in D expression seems to correlate with several malignant phenotypes. In the present study we investigate the immunohistochemical (IHC) expression of D in melanocytic nevi, in spitz nevi and in malignant melanoma. Methods: D expression levels were examined in 12 melanocytic nevi, in 8 Spitz nevi and in 10 melanomas. IHC staining: Briefly, the slides were incubated at 4°C overnight with anti-D antibodies (Atlas Ab, Sigma) at 1/200 dilution. The epidermidis, adjacent to the malignant tissue, served as an internal positive control. For every specimen, the extent (%) of positive tumour cells and the intensity of D immunoreactivity within tumour cells were recorded. The intensity was graded on a scale from 0 (−) to 3 (+++). A score was calculated for each specimen using the sum between the intensity score and the percentage of tumour cells with that particular intensity. 2 pathologists scored the stained slides. Results: Our results showed loss of D expression in melanoma lesions and differential D expression levels and patterns of immunoreactivity among melanocytic and Spitz nevi. Melanomas failed to express D in 70% of cases (7/10) showed very low D expression levels in 20% of cases (2/10) while only 10% (1/10) showed high expression levels (spitzoid melanoma). Conversely, all the benign lesions expressed D (20/20) The differences in the levels of expression between melanomas and nevi were significant (p = 0.006). In benign lesions expression was high in 87.5% (7/8) of spitz nevi and moderate in 91.5% (11/12) of melanocytic nevi. The differences in the levels of expression between these nevi were statistically significant (p = 0.002). Conclusions: Our results are in agreement with other studies that show reduced D expression levels in different malignant tumours. In fact the present study shows that melanomas do not express D while benign skin lesions do. In particular spitzoid nevi show higher D expression levels than melanocytic nevi. To our knowledge, this is the first study supporting that D is down regulated in malignant melanoma. Further studies are needed to predict the clinical impact of D expression in this disease. No significant financial relationships to disclose.
Phase I radiation dose-escalation trial of intensity-modulated radiotherapy (IMRT) with concurrent fixed dose-rate gemcitabine (FDR-G) for unresectable pancreatic cancer
Authors: E. Ben-Josef, K. Griffith, I. R. Francis, G. Khan, T. S. Lawrence, R. Abrams, W. Leslie, M. Zalupski
Journal: Journal of Clinical Oncology (2009)

4602 Background: Current treatments of non-metastatic, unresectable pancreatic cancer result in poor survival and nearly uniform local persistence of disease. We hypothesized that intensification of local therapy would result in better local control and improve survival. The primary objective of this trial was to determine maximum tolerated radiation dose delivered with IMRT and concurrent FDR-G. Methods: Eligibility included tissue diagnosis of adenocarcinoma, unresectable by radiological criteria, Zubrod performance of 0–2, ANC of ≥ 1500/mm3, platelets ≥ 100,000/mm3, creatinine &lt; 2 mg/dl, bilirubin &lt; 3 mg/dl, ALT and AST ≤ 2.5 x ULN, and informed consent. Patients (pts) received FDR-G (1000 mg/m2, 100-minute infusion) on days -22 and -15. IMRT started day 1 (radiation dose levels [L2-L6] 50, 52.5, 55, 57.5 and 60 Gy, all in 25 fractions) with concurrent FDR-G on days 1, 8, 22, and 29. GTV was defined on pancreas protocol CT in the treatment position. PTV was GTV plus 1 cm expansion. Active Breathing Control was used to reduce breathing motion, except in 3 pts, in whom 4D CT was used to generate an ITV. Post IMRT, up to 4 cycles of FDR-G were given. DLT was defined as GI toxicity ≥ G3, neutropenic fever, or deterioration in Zubrod to ≥3 between day 1 and 126. IMRT dose level was assigned using the Time-to-Event Continual Reassessment Method. With a sample size of 50, the design allows concurrent assessment of efficacy. Results: From 8/06, 27 pts have been accrued. DLTs have been observed in 6 (G3 anorexia, nausea vomiting, and/or dehydration [5 pts]; duodenal bleed [1 pt]). The posterior estimates of probability of DLT are 0.17, 0.21, 0.24, 0.27, and 0.28 for L2 to L6, respectively. The response rate is 52.4% (95% CI 29.8% to 74.3%). The median overall survival and progression-free survival are 23.1 months (95% CI 9–23.1) and 7.2 months (95% CI 5.0–8.0), respectively. Only 1 patient (4%) progressed locally. Two patients have undergone resection (R0), and demonstrated near- and complete pathological responses. Conclusions: High dose radiotherapy and concurrent FDR-G, utilizing the techniques above, is well tolerated and results in highly encouraging response rates, local control rates and overall survival. No significant financial relationships to disclose.
Durable clinical responses in patients (pts) with ovarian carcinoma treated on a phase II trial of autologous dendritic cells (DC) pulsed with MUC1
Authors: P. Mitchell, B. E. Loveland, M. A. Quinn, P. T. Grant, D. G. Allen, T. W. Jobling, S. C. White, D. M. Wall, A. Zhao, V. Karanikas
Journal: Journal of Clinical Oncology (2007)

5515 Background: Mucin 1 (MUC1) is a glycoprotein highly expressed by ovarian carcinoma and is thus a potential antigen for immunotherapy. Following successful phase I results (Loveland et al. Clin Can Res 2006; 12:869), using DC pulsed with mannan-MUC1 fusion protein (DC-MFP), we report a phase II trial in similarly treated pts with ovarian carcinoma. Methods: Eligibility: incurable disease; age = 18 yrs; PS 0–2; no autoimmune disorders; rising CA125 levels (= 25% in 1 mth, confirmed). The primary endpoint was CA125 response (major = 50%, minor = 25%, each confirmed at = 4 wk) or stabilisation (= 3 mths). PBMC were collected by leukapheresis, cultured with IL-4 and GM-CSF to generate DC, and pulsed with MFP on d5. DC were reinjected on d6 as 8 i.d. injections (each 5x10 6 ), given 4-weekly × 3, then 10- weekly to 12 mths. Excess cells were cryopreserved for subsequent injections. Results: 28 pts were recruited, with all evaluable for toxicity and 21 for efficacy (received = 3 vaccinations). Characteristics were: serous histology 24 (86%) pts; median age 58 yrs (34–78); PS 0–1 27 (96%) pts; prior systemic therapy (all pts platinum-treated) 1 line 5 pts, 2 line 4 pts, 3 line 10 pts, = 4 lines 9 pts. Leukapheresis was generally required only 6-monthly. Following ex vivo culture, the proportion of CD86+ cells ranged from 40 - 85%. There was no grade = 3 therapy-related toxicity. Of 21 pts, 4 (19%) showed CA125 response or stabilisation. 2 pts had major response: 1 pt with 4 previous lines of systemic therapy (DC-MFP response duration 12+ mths) and 1 pt treated second line (duration 14 mths). One pt had stable disease of 7 mths duration which included 10 wks classified as minor response and one pt, treated fifth-line, had stable disease for 5 mths. An additional pt, treated fourth-line, had &gt;25% CA125 reduction which was not confirmed by repeat CA125. CT scan results were generally concordant with CA125 status. No relationship was seen between clinical benefit and HLA type. 88% of tumours were MUC1+ on IHC. Conclusions: Study treatment was well tolerated and acceptable to pts. There was clear evidence of clinical benefit, including pts who were heavily pre-treated. This approach warrants further study in ovarian carcinoma. Supported by grants from PrimaBiomed Ltd. No significant financial relationships to disclose.
P0450 : KCa3.1 channels are upregulated in hepatocytes of cirrhotic patients
Authors: L.S. Møller, A.D. Fialla, R. Schierwagen, M. Biagini, W. Reul, S. Klein, M. Rabjerg, L.K. Hansen, O. Schaffalitzky de Muckadell, R. Koehler, J. Trebicka
Journal: Journal of Hepatology (2015)
A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells
Authors: Yulin Xu, Wei Shan, Xia Li, Binsheng Wang, Senquan Liu, Yebo Wang, Yan Long, Ruxiu Tie, Limengmeng Wang, Shuyang Cai, Hao Zhang, Yu Lin, Mingming Zhang, Weiyan Zheng, Yi Luo, Xiaohong Yu, Jiing-Kuan Yee, Junfeng Ji, He Huang
Journal: Journal of Hematology & Oncology (2016)

The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM)-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro. Approximately 70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU) assay showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation. Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic.
Autologous Blood Stem Cell Transplantation Results In Better Relapse-Free Survival Than Consolidation Chemotherapy: Results of a HOVON/SAKK Phase III Trial In 519 AML Patients In First Complete Remission
Authors: Edo Vellenga, Wim van Putten, Gert J. Ossenkoppele, Martin Fey, Jurgen Kuball, Matthias Theobald, Jan J. Cornelissen, Peter Huijgens, Johan Maertens, Alois Gratwohl, Martyn Ronald Schaafsma, Markus G Manz, Carlos Graux, Bob Lowenberg
Journal: Blood (2010)
Lack of virological and serological evidence for continued circulation of highly pathogenic avian influenza H5N8 virus in wild birds in the Netherlands, 14 November 2014 to 31 January 2016
Authors: Marjolein J Poen, Josanne H Verhagen, Ruth J Manvell, Ian Brown, Theo M Bestebroer, Stefan van der Vliet, Oanh Vuong, Rachel D Scheuer, Henk P van der Jeugd, Bart A Nolet, Erik Kleyheeg, Gerhard J D M Müskens, Frank A Majoor, Christian Grund, Ron A M Fouchier
Journal: Eurosurveillance (2016)

In 2014, H5N8 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage emerged in poultry and wild birds in Asia, Europe and North America. Here, wild birds were extensively investigated in the Netherlands for HPAI H5N8 virus (real-time polymerase chain reaction targeting the matrix and H5 gene) and antibody detection (haemagglutination inhibition and virus neutralisation assays) before, during and after the first virus detection in Europe in late 2014. Between 21 February 2015 and 31 January 2016, 7,337 bird samples were tested for the virus. One HPAI H5N8 virus-infected Eurasian wigeon ( Anas penelope ) sampled on 25 February 2015 was detected. Serological assays were performed on 1,443 samples, including 149 collected between 2007 and 2013, 945 between 14 November 2014 and 13 May 2015, and 349 between 1 September and 31 December 2015. Antibodies specific for HPAI H5 clade 2.3.4.4 were absent in wild bird sera obtained before 2014 and present in sera collected during and after the HPAI H5N8 emergence in Europe, with antibody incidence declining after the 2014/15 winter. Our results indicate that the HPAI H5N8 virus has not continued to circulate extensively in wild bird populations since the 2014/15 winter and that independent maintenance of the virus in these populations appears unlikely.
Molecular and clinicopathologic evidence of heterogeneity in KRAS-mutant colon cancers.
Authors: Vlad Calin Popovici, Eva Budinska, Sabine Tejpar, Giovanni d'Ario, Antonio Fabio Di Narzo, John Graeme Hodgson, Arnaud Roth, Fred Bosman, Mauro Delorenzi
Journal: Journal of Clinical Oncology (2012)

3575 Background: The activation of the MEK/ERK signaling cascade by KRAS or BRAF mutations has a high incidence in colorectal cancer (CRC). While these mutations are mutually exclusive, we have identified a highly conserved gene expression pattern, characteristic to BRAF mutants, that can also be observed in KRAS mutants (AACR 2011, JCO 2012), and which defines a distinct subpopulation. Its characterization is important as it may shed a light on the observed survival and treatment response variability of this group of CRCs. Methods: A set of 257 stage II and III KRAS mutant CRCs from the PETACC3 clinical trial and a subset of 150 CRCs from TCGA project were used for this study. Gene expression data was available for all samples and, additionally, CNV and methylation data was available for some of the samples. Due to the limited number of MSI samples, the analyses were focused on MSS subpopulation. Results: The cluster analysis on the genes from the BRAF signature clearly indicated a major split of the KRAS mutants into two subgroups, that were further compared in terms of clinico-pathological and survival parameters. The BRAF-mutant-like (BML) subgroup was clearly enriched in MSI-H (p&lt;0.001), right-sided (p=0.038) and mucinous histology (p&lt;0.001) tumors. The enrichment in mucinous tumors remained significant also in stratified analysis by MSI status. In MSS, the BML subpopulation of KRAS mutants had the worst prognosis for overall survival (p=0.05, HR=1.6) and survival after relapse (p=0.004, HR=2.1). Analysis of differentially expressed genes between BML and the rest of KRAS mutants identified genes responsible for colon crypt differentiation, Wnt pathway activation and, more intriguingly, 50 other genes, all located on chromosome 20q, that had significantly different activation levels in BML tumors. Among these genes, there are a number of important tumor suppressors, like PLAGL2, TP53RK and POFUT1. No differences in type of KRAS mutation nor in PIK3CA mutations were found between BML and the rest of KRAS mutants. Conclusions: We identified a subgroup of KRAS mutants formed of more aggressive, poorly differentiated tumors. All these results prove that KRAS mutant CRCs form a heterogeneous group tumors.
P2.34: Vaxira and CIMAvax-EGF Therapeutic Vaccines Combination in the Advanced NSCLC Treatment
Authors: Amparo E. Macias, Ramon Ortiz, Eduardo Santiesteban, Xitlally Popa, Anet Zayas, Zaima Mazorra, Ivis Mendoza, Elena Garcia, Roberto Gomez, Tania Crombet
Journal: Journal of Thoracic Oncology (2016)
Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial
Authors: Stefan J Schaller, Matthew Anstey, Manfred Blobner, Thomas Edrich, Stephanie D Grabitz, Ilse Gradwohl-Matis, Markus Heim, Timothy Houle, Tobias Kurth, Nicola Latronico, Jarone Lee, Matthew J Meyer, Thomas Peponis, Daniel Talmor, George C Velmahos, Karen Waak, J Matthias Walz, Ross Zafonte, Matthias Eikermann
Journal: The Lancet (2016)
Cardioselective nitric oxide synthase 3 gene transfer reduces endothelial activation, neutrophil infiltration and infarct size following myocardial ischemia-reperfusion injury in pigs
Authors: Z Szelid, Pieter Vermeersch, Peter Pokreisz, H Gillijns, Marijke Pellens, Peter Sinnaeve, Desire Collen, Eric Verbeken, Stefan Janssens
Journal: Circulation (2003)
Lipegfilgrastim: A long-acting, once-per-cycle, glycopegylated recombinant human filgrastim.
Authors: Christian Scheckermann, Karsten Schmidt, Afsaneh Abdolzade-Bavil, Hermann Allgaier, Udo W. Mueller, Wenyan David Shen, Patrick Liu
Journal: Journal of Clinical Oncology (2013)

e13548 Background: Lipegfilgrastim is a once-per-cycle fixed-dose glycoPEGylated granulocyte-colony stimulating factor (G-CSF) under development for the prevention of severe neutropenia in cancer patients receiving chemotherapy (CTx). PEGylation of a molecule extends its half-life in the body, requiring less frequent dosing and allowing for administration of G-CSF once per CTx cycle, making treatment potentially less expensive and enhancing patient compliance and safety. Briefly, traditional PEGylation methods use chemical conjugation through reactive groups on amino acids, which may reduce protein activity and result in non-uniform chemical and pharmaceutical properties. Here, we describe a highly site-specific GlycoPEGylation technology for site-directed PEGylation and summarize preclinical findings compared with pegfilgrastim (Neulasta). Methods: Glycosylation sequon scanning was used to identify the glycoPEGylation site with least impact on protein activity. E. coli-expressed G-CSF was selectively glycosylated at natural O-glycosylation sites and a polyethylene glycol (PEG) sialic acid derivative attached using a sialyltransferase (glycoPEGylation technology). Ligand binding affinity was assessed using the BIACORE 3000 system. Biologic activity of lipegfilgrastim was assessed in an NFS-60 cell line proliferation assay vs filgrastim and pegfilgrastim. PK and PD properties were studied in healthy and neutropenic animal models. Results: GlycoPEGylation produces long-acting G-CSF with improved PK profiles. In vitro, lipegfilgrastim had binding affinity and specific activity comparable to pegfilgrastim, and both were lower than non-PEGylated filgrastim. Comparable increases in leukocytes, neutrophilic granulocytes, and monocytes were seen with lipegfilgrastim and pegfilgrastim in rats and monkeys and were consistent with the effects expected for a long-lasting G-CSF. Conclusions: GlycoPEGylation technology platform is used to produce lipegfilgrastim – a novel, biologically active G-CSF with greater structural homogeneity and comparable pharmacologic properties to conventionally PEGylated G-CSFs.
A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research
Authors: L. B. Grabenhenrich, A. Reich, J. Bellach, V. Trendelenburg, A. B. Sprikkelman, G. Roberts, K. E. C. Grimshaw, S. Sigurdardottir, M. L. Kowalski, N. G. Papadopoulos, S. Quirce, R. Dubakiene, B. Niggemann, M. Fernández-Rivas, B. Ballmer-Weber, R. van Ree, S. Schnadt, E. N. C. Mills, T. Keil, K. Beyer
Journal: Allergy (2016)

Background The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). Methods A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. Recommendations A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. Conclusion The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings.