tbuckley/cabot-search huggingface dataset:
Abstract 5063: Lysyl oxidase-like 2 (LOXL2) from cancer-associated fibroblasts stimulates the progression of gastric carcinoma
Authors: Hiroaki Kasashima, Masakazu Yashiro, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2015)

Abstract Purpose: Lysyl oxidase families are involved in a variety of pathological processes, including cancer progression. Lysyl oxidase-like 2 (LOXL2) in the tumor stroma was mainly expressed in fibroblasts, which are a major stromal compartment of gastric cancer. Significance of LOXL2 remains unclear in gastric carcinoma. The aim of this study was to clarify the role of fibroblast-derived LOXL2 in the development of gastric cancer. Methods: Two gastric cancer cell lines, OCUM-12 and NUGC-3, and cancer-associated fibroblasts (CAF) were used in this in vitro study. The effect of fibroblast-derived LOXL2 on the motility of gastric cancer cells was analyzed by wound-healing assay, double-chamber invasion assay, and western blot. The correlation between LOXL2 expression and the clinicopathological features of 548 primary gastric carcinomas was examined by immunohistochemistry. Results: LOXL2 mRNA expression of CAF, was significantly higher than that of normal fibroblasts. CAF significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells. This motility-stimulating ability of CAF was inhibited by LOXL2 siRNA. Western blot analysis indicated that phosphorylation of focal adhesion kinase (FAK) in cancer cells was increased by the conditioned medium from CAF, and was not affected by the conditioned medium from LOXL2 siRNA-treated CAF. Immunohistochemical study indicated that LOXL2 expression in stromal cells was significantly associated with tumor invasion depth, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination. The overall survival of all patients with LOXL2-positive stromal cells was significantly poorer than those with LOXL2-negative stromal cells. Multivariable logistic regression analysis revealed that LOXL2 expression in stromal cells was an independent predictive parameter for the overall survival of patients with gastric cancer. Conclusion: LOXL2 from CAF may stimulate the motility of gastric cancer cells. LOXL2 expression in stromal cells may be a useful prognostic factor for patients with gastric cancer. Citation Format: Hiroaki Kasashima, Masakazu Yashiro, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. Lysyl oxidase-like 2 (LOXL2) from cancer-associated fibroblasts stimulates the progression of gastric carcinoma. [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 5063. doi:10.1158/1538-7445.AM2015-5063
No Evidence for Increased Transplant Related Complications in Ph+ Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia with Prior Treatment with Dasatinib.
Authors: Merav Leiba, Avichai Shimoni, Francois Guilhot, Geraldine Martineau, Marc Renaud, Sylvie Francois, Izhar Hardan, Arnon Nagler
Journal: Blood (2006)
The role of palliative care unit co-operating with regional medical systems to provide reliable patient care
Authors: Yoshikazu Hasegawa, Hiroshi Tsukuda, Rikako Iwaya, Tomohiro Suzumura, Takayo Oota, Kimio Yonesaka, Tomi Tanaka, Izumi Kawaguchi, Masatomo Otsuka, Masahiro Fukuoka
Journal: Annals of Oncology (2015)
Mesenchymal Stem Cells From Patients with Acute Myeloid Leukemia (AML) Can Differentiate Into B-Cells in NOD/SCID/IL-2Rγ-/- Mice.
Authors: Rui-Yu Wang, Yue-Xi Shi, Zhihong Zeng, Wendy D. Schober, Teresa J. McQueen, Vicki L. Hopwood, Borys Korchin, Marina Konopleva, Michael Andreeff
Journal: Blood (2009)
Lower Relapse Incidence and Relapse Mortality in Patients Transplanted from a Younger Sibling in HLA-Identical Stem Cell Transplantation: Does Microchimerism Matter?
Authors: Christiane Dobbelstein, Haytham Kamal, Elke Dammann, Eva Mischak-Weissinger, Michael Stadler, Juergen Krauter, Arnold Ganser, Matthias Eder
Journal: Blood (2008)
PWE-037 The clinical outcome of flares of inflammatory bowel disease in patients with concomitant<i>Clostridium difficile</i>infection
Authors: P J Smith, C Banks, B H Hayee, L Langmead, S McCartney, S Bloom
Journal: Gut (2010)

<h3>Introduction</h3> Several studies have highlighted the risks in patients with a flare of colitis and concomitant <i>Clostridium difficile</i> infection: including increased mortality and increased rates of colectomy in patients with ulcerative colitis (UC). Infection control policies, including antibiotic prescribing, have had an impact on rates of <i>Clostridium difficile</i> associated diarrhoea (CDAD) in the general in-patient population but rates of CDAD in inflammatory bowel disease (IBD) have been reported to be as high as 20%. This study was conducted to investigate the current rates of CDAD in IBD in our Trust. <h3>Methods</h3> For January 2007–2009, case notes for patients with a joint diagnosis of CDAD and IBD (UC and all Crohn9s disease (CD)), and hospital audit database for patients with IBD alone, were examined for length of stay, outcomes and medication. Patients were identified by the in-hospital reporting system (Infection Control), as well as discharge diagnoses (Coding). CDAD was diagnosed by positive A/B toxin in standard stool sample testing. <h3>Results</h3> A total of 217 patients with IBD (86 UC) were identified for analysis. 20 patients (12 UC) had CDAD on a pre-existing diagnosis of IBD. This was associated with a dramatically increased average length of stay (38 vs 5.6 days, p&lt;0.001), but not with rates of colectomy (1/12 with UC plus CDAD vs 21/74 with UC alone, p=0.28). Patients with CDAD were older (55.5±20.4 vs 26.8±16.8 years, p&lt;0.05), and 12/20 had received antibiotics for either IBD-related or other pathology, but only 6/20 were on concomitant PPI therapy. Mortality in the CDAD plus UC group was high (2/12), but the deaths occurred in one patient with rectal cancer and another with concomitant chest sepsis. All patients with CDAD received initial therapy with oral or IV metronidazole (in line with Trust practice), and changed to oral vancomycin if diarrhoea had not settled after 10 days (after discussion with the Microbiologist) or if clinical deterioration before this. The use of vancomycin was associated with a longer mean in-patient stay (49.6 vs 28.3 days, p&lt;0.001). <h3>Conclusion</h3> Our rates for CDAD compare favourably with other case series, but do indicate an increased length of in-patient stay for such patients. Neither increased mortality directly attributable to CDAD, nor increased colectomy rates were detected and may reflect early diagnosis and treatment of CDAD in this “at-risk” patient group. Older patients and those receiving antibiotic therapy for other diagnoses remain the highest risk groups identified.
Potent Anti-leukemia Activities of Chimeric Antigen Receptor–Modified T Cells against CD19 in Chinese Patients with Relapsed/Refractory Acute Lymphocytic Leukemia
Authors: Yongxian Hu, Zhao Wu, Yi Luo, Jimin Shi, Jian Yu, Chengfei Pu, Zuyu Liang, Guoqing Wei, Qu Cui, Jie Sun, Jing Jiang, Jue Xie, Yamin Tan, Wanmao Ni, Jifang Tu, Jinping Wang, Aiyun Jin, Hao Zhang, Zhen Cai, Lei Xiao, He Huang
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor–modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. Experimental Design: T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored. Results: We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. In vitro cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 × 106/kg to 9.8 × 106/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day −1 and a higher number of previous relapses. Conclusions: This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. Clin Cancer Res; 23(13); 3297–306. ©2016 AACR.
586. Dimerization Inhibition of HIV-1 RNA by 2’-Deoxy-2’-fluoro-beta-D-arabinose Nucleic Acid (2’-FANA) Modified Antisense Oligonucleotides Results in Potential Inhibition of Viral Expression
Authors: Mayumi Takahashi, Haitang Li, Veenu Aishwarya, Masad J. Damha, John J. Rossi
Journal: Molecular Therapy (2016)

Human immunodeficiency virus-1 (HIV-1) viral particle contains two copies of genomic RNA, which is known to form dimers via intermolecular interactions. The dimerization process is initiated by the formation of a kissing-loop dimer through base pairing of the palindromic loop sequence within dimerization initiation site (DIS). It has been shown that mutation or inhibitions of the DIS severely affect the viral infectivity. Antisense oligonucleotides (AONs) are single-stranded synthetic oligonucleotides that recognize target RNAs via Watson-Crick base pairing and cause post-translational inhibition. The mechanisms are believed to be RNase H cleavage of target RNA, steric hindrance of the translation machinery or prevention of RNA-RNA or RNA-protein interactions. While AONs offer promising solutions for variety of human diseases in preclinical studies and many of these are currently in clinical studies, a number of challenges still hamper their translation from the bench to the bedside, the most significant of which include target accessibility, off target effects, poor extracellular and intracellular stability and effective delivery into target cells. 2'-deoxy-2'-fluoro-beta-D-arabinose nucleic acid (2'-FANA) modification significantly enhances chemical and intracellular stability, as well as binding to the target RNA, forming stable heteroduplex structures. Moreover, 2'-FANA modification has been shown to facilitate gymnotic cellular delivery, a carrier-free method of achieving cellular uptake. Thus, we hypothesized that 2'-FANA modified AONs that bind HIV-1 DIS can inhibit dimerization, and subsequently inhibit viral expression. Firstly, we tested gymnotic delivery of 2'-FANA modified AONs to peripheral blood mononuclear cells (PBMCs) freshly isolated from human blood. Cellular uptake of the 2'-FANA AONs without any transfection reagent were observed in live-cell confocal microscopy analysis as soon as an hour after adding AONs. Next, the HIV-1 inhibitory effect of the 2'-FANA AONs was tested in HIV-1 infected PBMCs. Cell supernatant was collected and HIV-1 expression was measured by HIV-1 p24 ELISA. The 2'-FANA AONs strongly inhibited HIV-1 expression as long as two weeks after 2'-FANA AONs treatment. A mechanism study showed that the 2'-FANAAONs work against HIV by steric blocking of dimerization. Unlike most oligonucleotide therapeutics, 2'-FANA AONs can be gymnotically delivered into PBMCs. This fact makes 2'-FANA AONs great drug candidates for antiretroviral therapy.
Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery <i>in vivo</i>
Authors: Yvonn Heun, Staffan Hildebrand, Alexandra Heidsieck, Bernhard Gleich, Martina Anton, Joachim Pircher, Andrea Ribeiro, Olga Mykhaylyk, Dietmar Eberbeck, Daniela Wenzel, Alexander Pfeifer, Markus Woernle, Florian Krötz, Ulrich Pohl, Hanna Mannell
Journal: Theranostics (2016)

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro. Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo, we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy.
Abstract 3161: Predictive Immunotherapy Models: Overcoming the challenge of T cells gene transfer
Authors: Pascale Bouillé, Christine Duthoit, Régis Gayon, Vincent Feuillet, Cédric Auffray
Journal: Cancer Research (2015)

Abstract The initiation of an appropriate T cell response is a key event in the establishment of efficient anti-tumoral response. In a context of tumor development, different T cell populations are mobilized and understanding the pathways involved in their functions and in their interactions is a major field of research in cancer immunotherapy. Thus, while the activation of antigen-specific naive CD4+ T cells that can differentiate into appropriate effector T cells and home to the tumor might be highly beneficial, regulatory CD4+ T cells are considered as deleterious. Many efforts are thus made to understand the behavior of both CD4+ T cells subsets and to decipher their functions within the tumor micro-environment. A key step to reach this goal is the development of relevant predictive cancer models including genetic modifications of T cell populations in vitro and in vivo, either for gene target studies, or to create new tools for sensitive readouts. While human and activated mouse T cells are easily transduced with lentiviral vectors, transduction of naive and regulatory murine T cells is a technical challenge since these target cells are poorly permissive to transfection or viral transduction. Here, extensive in vitro transduction data show that the use of highly concentrated (1E9 TU/mL) and pure (1E8 TU/mg of proteins) lentiviral vectors increases significantly the transduction level of naive and regulatory CD4+ T cells. Furthermore, transduced T cells exhibit an original cell phenotype without any changes of T cells specific markers expression (CD44, CD69, CD25, Ly-6C) attesting that the composition of this pure batch of lentiviral vector does not have any impact on T cells phenotype. Transduced T cells were then assessed for their properties once adoptively transferred into recipient mice. Analysis of these mice show that not only the genetically modified T cells/regulatory cells can be easily followed thanks to the fluorescent reporter but also their phenotype is not modified by the transduction, as shown in vitro. Our data bring out that the composition of lentiviral vectors in terms of titer, specific activities and purity are the success keys to ensure transduction of murine T cells. This major technological leap will allow to tightly control expression of various modifiers of these cells and thus paves the way to design original tools and develop cell-based cancer. Citation Format: Pascale Bouillé, Christine Duthoit, Régis Gayon, Vincent Feuillet, Cédric Auffray. Predictive Immunotherapy Models: Overcoming the challenge of T cells gene transfer. [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 3161. doi:10.1158/1538-7445.AM2015-3161
Impact of conditioning regimen on outcome of 2-year disease-free survivors of autologous stem cell transplantation (ASCT) for Hodgkin lymphoma (HL).
Authors: B. M. William, F. R. Loberiza, V. Whalen, P. J. Bierman, G. Bociek, J. Vose, J. O. Armitage
Journal: Journal of Clinical Oncology (2011)

8043 Background: ASCT is the standard of care for patients with relapsed HL. Most relapses occur in the first 2 years (y) after ASCT and the long term outcomes for 2 y post-ASCT survivors have not been well described. No prospective trials have compared the impact of different conditioning regimens on outcomes. Methods: We searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with CBV (cyclophosphamide 6000 mg/m2, BCNU 300 mg/m2 and etoposide 600-900 mg/m2) or BEAM (BCNU 300 mg/m2, etoposide 800 mg/m2, cytarabine 800 mg/m2 and melphalan 140 mg/m2). Progression, progression-free survival (PFS) and overall survival (OS) were compared between the 2 regimens while adjusting for significant patient, disease and transplant related characteristics. Results: The median duration of follow up was 8 (2-26) y. Among the 461 transplanted patients, during the study period, 330 received CBV and 131 received BEAM. At 2 y post-ASCT, 225 (49%) were alive and disease-free. Median age of patients was 33 (8-64) y. The PFS at 5 y was 92% for the BEAM and 73% for the CBV group (p=0.002). The OS at 5 y was 95% for the BEAM and 87% for the CBV group (p=0.07). The PFS at 10 y was 79% for the BEAM and 59% for the CBV group (p=0.01). The OS at 10 y was 84% for the BEAM and 66% for the CBV group (p=0.02). The cumulative incidence of progression at 5 y was 4% vs 24% (for BEAM and CBV respectively, p<0.01) and at 10 y was 9% vs 33% (for BEAM and CBV respectively, p<0.001). Higher relative risk (RR) of progression (4.54, p<0.001), treatment failure (2.92; p=0.002) and mortality (2.74; p=0.03) was observed with use of CBV compared to BEAM. Higher RR of mortality was also observed with age of 40 y or older at transplant (1.69, p=0.04) and with chemoresistant disease (1.99, p=0.02). Conclusions: Patients with HL, who are disease-free and alive 2 y post-ASCT, have favorable long-term outcomes. In the dose and schedule used, we observed a lower risk of progression and longer survival associated with use of BEAM, as a conditioning regimen, compared to CBV. With this study design, we cannot rule out a selection bias favoring patients transplanted in more recent years.
A Study of the Role of Antiplatelet Therapy in the Prevention of Thrombosis in Patients with Calr-Mutated Low Risk Essential Thrombocythemia
Authors: Alberto Alvarez-Larrán, Paola Guglielmelli, Eduardo Arellano-Rodrigo, Martin Griesshammer, Chiara Paoli, Ana Kerguelen, Francisca Ferrer-Marin, Juan Carlos Hernández-Boluda, Bjorn Andreasson, Jiri Schwarz, Valentín García-Gutierrez, Rosa M. Ayala, Pere Barba, María Teresa Gómez-Casares, Radek C. Skoda, Carmen Burgaleta, Stefanie Slot, Jan Samuelsson, Alimam Samah, Yan Beauverd, Claire N. Harrison, Francisco Cervantes, Alessandro M. Vannucchi, Carlos Besses
Journal: Blood (2015)
Targeted Cancer Therapy in High-Risk Pediatric Leukemia Using Global Phosphotyrosine Profiling
Authors: Sibasish Dolai, Keith CS Sia, Alissa K Robbins, Ling Zhong, Sue Heatley, Tiffaney Vincent, Falko Hochgräfe, Raushan T. Kurmasheva, Deborah L White, Peter J. Houghton, Malcolm A. Smith, David T. Teachey, Roger J Daly, Mark J Raftery, Richard B. Lock
Journal: Blood (2014)
Multi-Course of Moderate Dose Cytosine Arabinoside and Fludarabin in the Consolidation Therapy of Patients with De Novo Acute Myeloid Leukemia
Authors: Huiying Qiu, Wu Depei, Aining Sun, Zhengming Jin, Miao Miao, XiaoWen Tang, Chengcheng Fu, Yue Han, Guangsheng He
Journal: Blood (2011)
Abstract 5126: Establishment of an esophageal small cell carcinoma cell line (TYUC-1)
Authors: Yutaka Shimada, Tomoyuki Okumura, Yoshinori Takei, Kazuaki Watanabe, Akira Hirasawa, Arito Yamane, Masahiko Nishiyama, Takuya Nagata, Kazuhiro Tsukada, Kazuharu Shimizu
Journal: Cancer Research (2015)

Abstract Background: Small cell carcinoma of the esophagus is rare and its prognosis is extremely poor. However, there is currently no in vitro model of this disease. Methods: After obtaining written informed consent, we obtained a tumor from a 56-year-old female patient with esophageal small cell carcinoma in 2009 and transplanted it into a Severe Combined Immuno Deficiency (SCID) mouse. After successful transplantation, a tumor from the back of this mouse was minced with a sharp scissors without enzymes and was cultured in Ham F12/DMDM supplemented with 5% fetal bovine serum. Results: Culture cells grew as adherent cells during the initial culture phase and gradually grew as floating aggregated cells. We carefully maintained these floating cells and transferred them without enzymes. These cells could passage to another flask with a split ratio of 1/10. We named these cells “TYUC-1”, and passaged them more than 85 times. The population doubling-time of TYUC-1 was approximately 30 hours. The G-band karyotype confirmed that these cells had a human origin. These cells could be transplanted to SCID mice with the same histological features of primary esophageal small cell carcinoma, and were shown to express TrkA, NGF, NSE, FGFRL1, p53, CD56, ALDH1A1, and CD44, but not CD133. A cDNA array also revealed that 9 genes were overexpressed while the expression of 33 genes was significantly lower than that in 28 esophageal squamous cell carcinoma (ESCC) cell lines. Whole exome sequencing revealed that TYUC-1 had TP53, PIK3CA, KMT2D, CACNA1H, NCOR1 and HRAS mutations. Furthermore, TYUC-1 had mutations in 128 genes, whereas 28 ESCC cell lines had no mutations in these genes. Conclusions: We newly established TYUC-1 cells that exhibited neuroendocrine characteristics and expressed several stem cell-related molecules. These cells may be useful for understanding the characteristics of esophageal small cell carcinoma. Citation Format: Yutaka Shimada, Tomoyuki Okumura, Yoshinori Takei, Kazuaki Watanabe, Akira Hirasawa, Arito Yamane, Masahiko Nishiyama, Takuya Nagata, Kazuhiro Tsukada, Kazuharu Shimizu. Establishment of an esophageal small cell carcinoma cell line (TYUC-1). [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 5126. doi:10.1158/1538-7445.AM2015-5126