tbuckley/cabot-search huggingface dataset:
Prenatal Carrier Screening—Reply
Authors: Wayne W. Grody
Journal: JAMA (2016)

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OS2.6 Identification of IDH1R132H-specific T cell receptors from a humanized mouse model and from glioma patients treated with an IDH1R132H-specific peptide vaccine
Authors: K. Sanghvi, E. Green, T. Bunse, L. Bunse, F. Sahm, T. Omokoko, U. Sahin, M. Schmitt, W. Wick, M. Platten
Journal: Neuro-Oncology (2016)

For malignant gliomas, progress in molecular diagnostics such as genomewide sequencing led to identification of subgroup-defining genetic alterations representing promising immunotherapeutic targets especially for personalized vaccination strategies.One example for an oncogenic mutation occurring in about one half of all pediatric brain stem gliomas and occasionally in adult gliomas is a point mutation in the histon-3.3gene (H3F3A) causing an amino acid exchange from lysine to methionine at position 27 (K27M).Here, we analyzed the immunogenicity of H3.3 K27M and its relevance for a mutation-specific vaccination approach.Vaccination of major histocompatibility complex (MHC)-humanized (A2DR1) mice with a H3.3 K27M-covering 10-mer peptide led to a CD8driven mutation-specific immune response.Using a human leukocyte antigen (HLA) class-I epitope prediction tool, a mutation-containing 10mer peptide sequence with a strong binding affinity compared to the corresponding wild type sequence was identified.In silico, functional presentation of the crucial epitope was predicted for the class-I haplotypes A2.Importantly, peptide vaccination of A2DR1-mice effectively inhibited growth of H3.3 K27Moverexpressing flank tumors.In summary, we demonstrated that a H3.3 K27M-specific and effective antitumor immune response can be induced by a peptide vaccine.Thus, our data provide evidence for a further clinical development of this personalized immunotherapeutic approach.
ONCO-T-PROFIL: treatment of patients with refractory metastatic solid tumors according to a molecular characterization of potential predictive biomarkers
Authors: A. Seeber, G. Gastl, C. Ensinger, V. Forcher, F. Rinderer, E. Willenbacher, W. Willenbacher, W. Eisterer, G. Pall, C. Leitner, G. Spizzo, A. Amann, A. Lang, T. Jaeger, A. Voss, H. Zwierzina
Journal: Annals of Oncology (2015)
Abstract 3283: The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis
Authors: Igor Snapkov, Carl Otto Öqvist, Yngve Anton Figenschau, Per Kogner, John Inge Johnsen, Baldur Sveinbjørnsson
Journal: Cancer Research (2015)

Abstract The formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor with pattern recognition properties and is mainly expressed by myeloid cells. It is involved in a broad range of host defense mechanisms and a variety of host-derived agonists of FPR1 have been identified, including formyl peptides released from disrupted mitochondria of necrotic cells. In the present study, we demonstrate the expression of FPR1 in 7 different neuroblastoma cell lines and in primary tumors. Furthermore, FPR1 is expressed at increased levels in high stage tumors. Addition of the FPR1 agonist N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to neuroblastoma cells in vitro caused enhanced proliferative activity, increase of intracellular calcium response and activation of STAT3 and MAPK/ERK signal transduction pathways. All these signal transduction events were abrogated by the use of Cyclosporin H, a specific FPR1 antagonist. To assess the significance of this receptor in vivo, we developed a set of neuroblastoma cell clones with different expression levels of FPR1. Xenograft models showed that cells with overexpression of the receptor developed tumors significantly faster compared to control group. Our findings so far suggest that FPR1 may play a significant role in neuroblastoma tumorigenesis and that therapeutic intervention of the FPR1 pathway may be an important clinical strategy in neuroblastoma therapy. Citation Format: Igor Snapkov, Carl Otto Öqvist, Yngve Anton Figenschau, Per Kogner, John Inge Johnsen, Baldur Sveinbjørnsson. The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3283. doi:10.1158/1538-7445.AM2015-3283
Impact of interstitial brachytherapy (IB) or radical prostatectomy (RP) on quality of life (QL) of patients (pts) treated for localized prostate cancer (LPC): Medium-term outcomes from a prospective monoinstitutional study.
Authors: O. Caffo, G. Fellin, F. Coccarelli, C. Divan, U. Graffer, V. Murgia, S. Mussari, A. Veccia, E. Galligioni
Journal: Journal of Clinical Oncology (2011)

e15108 Background: Pts with LPC may be treated by different therapies which have similar disease control rates but potentially relevant differences in terms of QL impact. We attempted to evaluate the changes of QL after IB or RP. Methods: From March 2005 to July, 2010, we evaluated a consecutive series of 420 pts treated (on the basis of pts’ preference) with RP (192 pts) or IB (228 pts) for LPC. All pts were requested to fill a self-filled QL questionnaire a week before, one-two months (one for IB, two for RP) and yearly after IB or RP. The questionnaire (listing 64 items) derived from a validated instrument previously used in a prospective study (Int J Radiat Oncol Biol Phys. 2006;66:31-7). The items identify the following QL subscales: physical well-being (PHY), psychological well-being (PSY), relational life (REL), physical autonomy (POW), rectal (REC), urinary (URI), erectile (ERE), and sexual functioning (SEX). Differences in terms of subscales value means between RP and IB at the different assessment time-points were statistically analyzed by one-way variance analysis. Results: In the table are summarized the findings observed at the different assessment time-points, comparing the subscales value means (if no statistically differences were observed we used the symbol =, otherwise it was indicated the treatment with better outcome). Conclusions: In our experience, IB produced a statistically significant better outcome in terms of urinary, sexual, and erectile functions, compared to RP. On the other hand, the rectal function was significantly less impaired after RP. The differences concerning not functional scales favored IB but they were limited to the period immediately after treatment. Further data will be provided from longer follow-up time-point assessments. Basal Post 6 mos 12 mos 24 mos PHY = IB = = = PSY = = = = = REL = = IB = = POW = IB IB = = URI IB IB IB IB = ERE = IB IB IB IB SEX IB IB IB IB IB REC = RP RP RP =
Increased Leukaemia Free Survival (LFS) in Patients with Cytogenetic High Risk AML after Related or Unrelated Hematopoietic Cell Transplantation (HCT) Compared to Chemotherapy in the OSHO 96 and 2002 Studies.
Authors: Dietger Niederwieser, Cornelia Becker, Rainer Krahl, Haifa-Kathrin Al-Ali, Simone Heyn, Michael Cross, Thoralf Lange, Anke Gerhardt, Antje Schulze, Detleff Haehling, Manfred Schulze, Matthias Freund, Erika Kettner, Gottfried Dölken, Michael Assmann, Hans-Heinrich Wolf, Ernst Zschuppe, Norma Peter, Astrid Franke, Ulrich Wedding, Lutz Uharek, Ute Kreibich, Norbert Grobe, Thomas Ittel, Axel Florschuetz, Bernd Opitz, Karin Senftleben, Veronika Schirmer, Friedrich Fiedler, Renate Huhn, Werner Helbig
Journal: Blood (2006)
48. High-Throughput Cloning and Tagging of an Engineered Adenovirus-Library Empowers Vector Diversity for Broad Applications
Authors: Wenli Zhang, Jun Fu, Jing Liu, Hailong Wang, Eric Schulz, Manish Solanki, Philip Boehme, Maren Gebbing, Thorsten Bergmann, Johannes Doerner, Francis A. Stewart, Anja Ehrhardt
Journal: Molecular Therapy (2015)

Adenoviral vectors are the most widely used vectors in gene therapy, largely owing to their high efficacy in gene delivery and the ability to transduce a broad variety of cell types. Although more than 60 human adenoviruses types have been identified, the majority of recombinant adenoviral vectors (AdVs) is based on a small fraction of adenovirus types (Ad2 and 5 from species C) and their genetic modification. Predefined tissue tropism and preexisting immunity considerably limit the application of currently used vectors, making the developing of alternative AdV s mandatory. However, generation of AdVs other than species C was hampered by the lack of convenient cloning methods, for traditional approaches were limited by the low efficiency and complicate procedure. We believe that the engineered adenovirus-library is going to provide spacious novel view to the adenovirus field. As a toolkit, it will bring the AdVs from mono- to multi-types and enables broader applications in molecular medicine including gene therapy and vaccination studies, as well as basic virology studies. Recombineering techniques provide powerful tools for arbitrary engineering of recombinant DNA. Here we established a seamless recombineering pipeline for high-throughput cloning and tagging of adenoviral genomes. We amplified and purified wild type adenoviruses that represent all seven human adenovirus species. Using the recombineering pipeline we generated an engineered adenovirus-library including around half of the currently available adenovirus types. To prove integrity of the cloned adenovirus genomes we performed rescue experiments in respective cell lines permissive for adenovirus infection and we optimized rescue condition by testing different molecular forms of the adenoviral DNA (linear, circular, precise release of the DNA molecule). A limited number of selected types from each species will be tagged with a P2A peptide-mediated bicistronic-expression cassette providing a Turbo Green fluorescent protein as in vitro marker and a NanoLuc luciferase for in vivo studies. These tagged adenoviral vectors will be evaluated in cultured cell lines and mouse model. A summary of the human adenoviral vector-library which can be used for further genetic modification and tagging based on the recombineering technology is shown in figure 1. We believe that the engineered adenovirus-library is going to provide spacious novel view to the adenovirus field. As a toolkit, it will bring the AdVs from mono- to multitypes and enables broader applications in molecular medicine including gene therapy and vaccination studies, as well as basic virology studies.
PTH-056 Enteral nutritional support via the mucous fistula: feasibility and safety in post-operative patients
Authors: C M Lever, L Gregory, J Pratt, T M Trebble
Journal: Gut (2010)

<h3>Introduction</h3> Abdominal surgery with small bowel (SB) resection may require delayed anastomosis with the formation of a temporary defunctioning end stoma and mucous fistula (MF). If sited proximally, this may result in a short bowel in the proximal limb with redundant longer bowel in the distal limb. Oral/nasogastric (NG) intake may induce uncontrolled stomal fluid (&gt;2.5 l/day) and electrolyte losses leading to prolonged hospital admission or parenteral support. The distal bowel can be utilised for absorption of nutrition, fluids and electrolytes if sufficient in length and accessible via the MF. However, the viability and safety of small bowel MF enteral support has been poorly reported. We present a case series of our experience in a busy district general hospital. <h3>Methods</h3> Referred post-operative patients with a MF who demonstrated metabolic and nutritional instability on oral/NG intake due to uncontrolled stoma losses were assessed for MF feeding. A 14 French Foley catheter was inserted into the MF through a universal catheter access port placed into a windowed stoma bag and connected to standard enteral feeding apparatus. Elemental feed, rehydration fluids, electrolytes or nutritional supplements were administered to meet the patient9s requirements using standard methods of jejunal feeding. Proximal stoma output was monitored and oral dietary intake reduced if necessary. <h3>Results</h3> Between February 2007 and October 2008 eight patients were found to be appropriate for a trial of MF feeding. All patients had undergone SB resection with residual proximal small bowel length ranging from 75 to 150 cm (mean 116 cm) from the DJ flexure; all had distal SB length &gt;1 m with a viable large bowel in continuity. Patients reported initial difficulties in assembling the feeding tube and access port via the stoma window, however with training all gained competency allowing home discharge with telephone and clinic support. The universal catheter access port allowed a water tight seal, and leakage around the feeding tube was negligible. There were no major metabolic complications of MF feeding including those patients who remained on controlled oral intake. All patients received enteral support for a minimum of 3 months prior to assessment for surgical anastomosis. In our study group 5 patients had delayed anastomosis and three died of causes unrelated to MF feeding. <h3>Conclusion</h3> MF feeding is a safe and effective method for nutritional support in appropriate patients and may allow home discharge in the presence of a high output proximal stoma. The use of a Foley catheter as a feeding tube and a simple catheter port allowed inexpensive and simple means of access. However, dedicated training, support and monitoring may be required to allow home discharge.
Abstract 1361: The decoy receptor interleukin-1 receptor type 2 acts as an angiogenic factor in human colorectal cancer
Authors: Ai-Chung Mar
Journal: Cancer Research (2015)

Abstract We previously demonstrated that interleukin-1 receptor type 2 (IL1R2), an IL-1 decoy receptor that inhibits exogenous IL-1 signaling, intracellularly activates the expression of several pro-inflammatory cytokines. In this study, we observed that IL1R2 was overexpressed in human colon cancer cells (CRC) compared to normal colon cells. In addition, we observed that the IL1R2 level was higher in late-stage clinical CRC patients and that a high level of IL1R2 was associated with a poor 5-year survival rate in CRC patients. Furthermore, we observed that the levels of IL1R2 and IL-6 were strongly correlated in 40 CRC patients. To elucidate the oncogenic roles of intracellular IL1R2, we modulated its expression levels in human CRC cell lines. We verified that the intracellular level of IL1R2 was correlated with the migration ability of CRC, cells. We observed that the VEGF-A and IL-6 levels were significantly increased in conditioned media harvested from IL1R2-overexpressing cells, and these elevated VEGF-A and IL-6 levels enhanced the proliferation, migration, and tube formation of cultured endothelial cells. We further demonstrated that intracellular IL1R2 levels were positively associated with tumor growth and microvessel density in xenograft mouse models. Furthermore, we observed that IL1R2 formed a complex with c-Fos. This complex bound to the AP-1 site at the IL-6 and VEGF-A promoters. Together, these results reveal that intracellular IL1R2 acts with c-Fos to enhance the transcription of IL-6 and VEGF-A, which promotes tumor malignancy and angiogenesis. Citation Format: Ai-Chung Mar. The decoy receptor interleukin-1 receptor type 2 acts as an angiogenic factor in human colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1361. doi:10.1158/1538-7445.AM2015-1361
Eculizumab Is an Effective Treatment for Atypical Hemolytic Uremic Syndrome in Patients with or without Identified Genetic Complement Mutations or Complement Factor H Auto-Antibodies.
Authors: Samhar I. Al-Akash, Timothy H. J. Goodship, Richard J. H. Smith, Christophe M. Legendre, Christoph Licht, Petra Muus, Camille L. Bedrosian, Veronique Frémeaux-Bacchi, Chantal Loirat
Journal: Blood (2012)
Abstract 3535: A novel tumor-specific oncolytic biological therapy against invasive pancreatic cancer
Authors: Takeshi Koujima, Hiroshi Tazawa, Naoto Hori, Shuta Tamura, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2015)

Abstract Pancreatic cancer is one of the worst prognosis disease all over the world and has an overall 5-year survival rate of less than 5%. At the time of diagnosis, more than 80% of patients are not eligible for curative surgical resection due to extensive local tumor invasion and early systemic metastasis. Moreover, even after curative surgery, pancreatic cancers still show poor prognosis due to local recurrence and systemic metastasis. Gemcitabine is the standard chemotherapeutic agent to treat advanced pancreatic cancers, but median overall survival ranged from 5.0 to 7.2 months, suggesting that standard chemotherapy is less effective to most of pancreatic cancer patients. Therefore, the development of novel therapeutic strategy is needed for the treatment of pancreatic cancers. We developed a novel oncolytic adenovirus, OBP-702, in which a human telomerase reverse transcriptase gene promoter drives viral E1 gene for virus replication, and armed with the wild-type tumor suppressor p53 gene. Precise antitumor effects of OBP-702 have been evaluated in human pancreatic cancer cells. We used four pancreatic cancer cell lines with different invasion ability, including non-invasive type (MIA PaCa-2, Panc-1) and invasive type (BxPC-3, Capan-1). The antitumor effect of OBP-702 for each cell line was assessed using XTT assay. OBP-702 induced profound anti-tumor effect in all human pancreatic cancer cells, whereas OBP-301 lacking the p53 tumor suppressor gene showed differential effects among the cell types. OBP-301 induced moderate anti-tumor effect in MIA Paca-2, BxPC-3 and Capan-1 cells and strong anti-tumor effect in Panc-1 cells in a dose-dependent manner, suggesting the broad spectrum of OBP-702's efficacy. The molecular mechanism of anti-tumor effect was assessed by Western blot analysis. OBP-301 induced autophagy-related cell death, whereas OBP-702 induced autophagy- and apoptosis-related cell deaths. These results suggest that an oncolytic adenovirus, OBP-702, is a promising antitumor agent to induce profound cell death in invasive human pancreatic cancer cells. The clinical trial of intratumoral administration of OBP-702 in patients with invasive pancreatic cancer is warranted. Citation Format: Takeshi Koujima, Hiroshi Tazawa, Naoto Hori, Shuta Tamura, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara. A novel tumor-specific oncolytic biological therapy against invasive pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3535. doi:10.1158/1538-7445.AM2015-3535
Everolimus, an mTOR inhibitor, in combination with docetaxel for second- or third-line therapy of advanced-stage non-small cell lung cancer: A phase II study.
Authors: F. R. Khuri, T. K. Owonikoko, J. Subramanian, G. Sica, M. Behera, N. F. Saba, Z. Chen, M. Tighiouart, D. M. Shin, S. Sun, R. Fu, A. Gal, R. Govindan, S. S. Ramalingam
Journal: Journal of Clinical Oncology (2011)

e13601 Background: mTOR pathway activation is a critical oncogenic event in non-small cell lung cancer. We observed enhanced anti-cancer activity with the combination of docetaxel and everolimus (RAD 001) in pre-clinical and early phase clinical studies. Therefore a phase II study was conducted to evaluate the efficacy of this combination in advanced NSCLC. Methods: Advanced stage NSCLC patients with 1 or 2 prior systemic therapy regimens, ECOG performance status (PS) 0-2, and adequate organ function were eligible. Docetaxel (60 mg/m2) was given on day 1 of each cycle and everolimus (5 mg PO QD) was given on days 2-19 of each 3-week treatment cycle. The primary endpoint was response rate and secondary endpoints included PFS, OS and safety assessment. The Simon two-stage design was utilized. Archived tumor specimens were evaluated for upstream and downstream markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e and 4EBP1). Results: Twenty-eight patients were enrolled (median age- 64 years, male -13, Caucasian 19, adenocarcinoma-17, squamous-8, PS 0/1/2-4/20/2). A median of 3.5 cycles of therapy was administered. Grade 3/4 toxicities (n=11) included neutropenia, anemia, headache, fatigue, hyperglycemia, mucositis, and dyspepsia. Two patients experienced partial response and 13 had stable disease (clinical benefit rate 54%). The median PFS was 2.3 months and the median overall survival was 12 months. The study did not meet the efficacy criteria to proceed to full accrual. High pAkt expression correlated with objective tumor response (p=0.033) but not with PFS (p=0.261) or OS (p=0.467). Conclusions: The combination of everolimus and docetaxel was tolerated well, but there was no clear signal of enhanced efficacy in an unselected population of NSCLC patients. Supported by NCI P01 CA116676. FRK, TKO, SS, and SSR are Georgia Cancer Coalition Distinguished Cancer Scholars.
Chronic Lymphocytic Leukemia (CLL) Cells Are Susceptible to γδ-T Cell Mediated Killing, Provided CLL-Derived γδ-T Cell Dysfunction Can be Reversed
Authors: Iris de Weerdt, Sanne Terpstra, Tom Hofland, Roeland Lameris, Renee C.G. de Bruin, Mark-David Levin, Ester B.M. Remmerswaal, Ineke J.M. ten Berge, Sanne H. Tonino, Tanja D de Gruijl, Hans van der Vliet, Arnon P. Kater
Journal: Blood (2015)