tbuckley/cabot-search huggingface dataset:
Abstract 3951: Functional analysis of the 11q23.3 glioma susceptibility locus
Authors: Rebekah Baskin, Nicholas Woods, Gustavo Mendoza-Fandino, Peter Forsyth, Kathleen Egan, Alvaro Monteiro
Journal: Cancer Research (2015)

Abstract Glioma is the most common malignant primary brain tumor and is associated with poor prognosis. Single nucleotide polymorphisms (SNPs) associated with glioma risk have recently been investigated through genome-wide association studies (GWAS). Results of these studies have implicated seven independent glioma risk loci in six chromosomal regions. However, the mechanisms by which these SNPs contribute to cancer risk are still unknown. Here, we performed an in-depth functional analysis of one of these risk loci located near the PHLDB1 gene on 11q23.3. We began by retrieving all SNPs in linkage disequilibrium (LD; r2 ≥ 0.2) with the glioma-associated SNP (rs498872). 61 genes contained in the region defined by a boundary of 1Mb from each end of the LD SNPs were considered candidate targets. A subset of 10 candidate functional enhancer/promoter SNPs was defined by overlap with ENCODE biofeatures and allele specific activity in luciferase and EMSA assays in astrocytes and GBM cells. Functional SNPs in the promoter of PHLDB1 implicated its transcriptional regulation in glioma risk. Chromatin conformation capture (3C) identified a physical interaction between one enhancer SNP and the promoter of the DDX6 gene. We also conducted neurosphere formation assays to evaluate the functional role of two top candidate genes, PHLDB1 and DDX6. We found that knockdown of either gene caused a significant reduction in U87MG neurosphere number and size. Taken together, these studies revealed the functional landscape of the 11q23.3 glioma susceptibility locus and implicated the transcriptional regulatory network of PHLDB1 and DDX6 in the mechanism of increased glioma risk. Citation Format: Rebekah Baskin, Nicholas Woods, Gustavo Mendoza-Fandino, Peter Forsyth, Kathleen Egan, Alvaro Monteiro. Functional analysis of the 11q23.3 glioma susceptibility locus. [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 3951. doi:10.1158/1538-7445.AM2015-3951
Abstract 146: The long noncoding RNA MALAT1 promotes hypoxia-driven angiogenesis by upregulating pro-angiogenic gene expression in neuroblastoma cells
Authors: Andrew E. Tee, Peiyan Liu, Jesper Maag, Renhua Song, Jinyan Li, Belamy B. Cheung, Michelle Haber, Murray D. Norris, Glenn M. Marshall, Marcel Dinger, Tao Liu
Journal: Cancer Research (2015)

Abstract Neuroblastoma is the most common solid tumour during early childhood, and accounts for 15% of all childhood cancer death. One of the key features of neuroblastoma is aggressive progression due to tumour-driven angiogenesis. However, the mechanism through which neuroblastoma cells drive angiogenesis is unclear. Here we showed that the long noncoding RNA MALAT1 was over-expressed in human neuroblastoma cells under hypoxic condition, the condition which triggers pro-angiogenic switch and angiogenesis. In vitro angiogenesis assays demonstrated that conditioned medium from neuroblastoma cells transfected with MALAT1 siRNAs, compared with conditioned medium from neuroblastoma cells transfected with control siRNAs, induced considerably less endothelial cell migration, invasion and vascular sprouting under hypoxic condition. Affymetrix microarray differential gene expression study showed that one of the genes most significantly down-regulated by MALAT1 siRNAs in human neuroblastoma cells under hypoxic condition, was fibroblast growth factor (FGF). RT-PCR and immunoblot analyses confirmed that MALAT1 siRNAs reduced FGF mRNA and protein expression, and in vitro angiogenesis assays demonstrated that forced over-expression of FGF in neuroblastoma cells blocked MALAT1 siRNA-mediated reduction in endothelial cell migration, invasion and vascular sprouting. Taken together, our data suggest that over-expression of MALAT1 in human neuroblastoma cells plays an important role hypoxia-driven angiogenesis by up-regulating FGF mRNA expression. Citation Format: Andrew E. Tee, Peiyan Liu, Jesper Maag, Renhua Song, Jinyan Li, Belamy B. Cheung, Michelle Haber, Murray D. Norris, Glenn M. Marshall, Marcel Dinger, Tao Liu. The long noncoding RNA MALAT1 promotes hypoxia-driven angiogenesis by upregulating pro-angiogenic gene expression in neuroblastoma cells. [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 146. doi:10.1158/1538-7445.AM2015-146
NKG2D-Mediated Marrow Injury in Paroxysmal Nocturnal Hemoglobinuria and Its Related Disorders.
Authors: Nobuyoshi Hanaoka, Tatsuya Kawaguchi, Kentaro Horikawa, Shoichi Nagakura, Sonoko Ishihara, Yasuchika Tsuzuki, Yuji Yonemura, Hideki Nakakuma
Journal: Blood (2007)
Abstract 1508: UV-induced Wnt7a in the human skin microenvironment specifies the fate of neural crest -like cells via suppression of Notch
Authors: Mizuho Fukunaga-Kalabis, Denitsa Hristova, Joshua Wang, Ling Li, Markus Heppt, Zhi Wei, Alexandra Gyurdieva, Marie Webster, Masahiro Oka, Ashani Weeraratna, Meenhard Herlyn
Journal: Cancer Research (2015)

Abstract Multipotent stem cells with neural crest-like properties have been identified in the dermis of human skin. These neural crest stem cell (NCSC)-like cells display self-renewal capacity and differentiate into neural crest derivatives including epidermal pigment-producing melanocytes. NCSC-like cells share many properties with aggressive melanoma cells, such as high migratory capabilities and expression of the neural crest markers. However, little is known about which intrinsic or extrinsic signals determine the proliferation or differentiation of these neural crest-like stem cells. Here, we show that in NCSC-like cells, Notch signaling is highly activated, similar to melanoma cells. Inhibition of Notch signaling reduced proliferation of NCSC-like cells, induced cell death, and down-regulated non-canonical Wnt5a, suggesting that the Notch pathway contributes to the maintenance and motility of these stem cells. In three-dimensional skin reconstructs, canonical Wnt signaling promoted the differentiation of NCSC-like cells into melanocytes. This differentiation was triggered by the endogenous Notch inhibitor Numb, which is up-regulated in the stem cells by Wnt7a derived from UV-irradiated keratinocytes. Together, these data reveal a novel crosstalk between the two conserved developmental pathways in postnatal human skin, and highlight the role of the skin microenvironment in specifying the fate of stem cells. Citation Format: Mizuho Fukunaga-Kalabis, Denitsa Hristova, Joshua Wang, Ling Li, Markus Heppt, Zhi Wei, Alexandra Gyurdieva, Marie Webster, Masahiro Oka, Ashani Weeraratna, Meenhard Herlyn. UV-induced Wnt7a in the human skin microenvironment specifies the fate of neural crest -like cells via suppression of Notch. [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 1508. doi:10.1158/1538-7445.AM2015-1508
R-DHA-Oxaliplatin Versus R-DHA-Cisplatin Regimen in B-Cell Nhl's Treatment: A Eight Years Retrospective Study
Authors: Carole Lacout, Manon De Vries, Valérie Seegers-Thepot, Aline Clavert, Jonathan Farhi, Mélanie Mercier, Marie-Pierre Moles, Norbert Ifrah, Mathilde Hunault, Aline Tanguy-Schmidt
Journal: Blood (2015)
A Pilot Study of Reduced-Intensity Conditioning Stem Cell Transplantation with T-Cell Replete HLA-Mismatched Allograft from Child to Parent Patient for the Treatment of Refractory Adult T-Cell Leukemia.
Authors: Hiroshi Fujiwara, Atsuo Ozaki, Makoto Yoshimitsu, Heiichiro Hamada, Hideaki Kawada, Kakushi Matsushita, Naomichi Arima, Chuwa Tei
Journal: Blood (2006)
Patients with Follicular Lymphoma, Grade 3, Have a Prolonged Relapse-Free Survival Following Aggressive Combination Chemotherapy.
Authors: Apar Kishor Ganti, Dennis D. Weisenburger, Lynette M. Smith, Christine P. Hans, R. Gregory Bociek, Philip J. Bierman, Julie M. Vose, James O. Armitage
Journal: Blood (2004)
714. Use of a Modular Workstation for Reduced Biosafety Risks Also Increased Cellular Yields
Authors: Alicia D. Henn, Shannon Darou, Randy Yerden
Journal: Molecular Therapy (2016)

Cell culture processing in a room-air biologic safety cabinet (BSC), even in a cleanroom, creates multiple risks for both cell cultures and users. Humans can be exposed to genetically-modified cells, viruses, and other biological hazards during suboptimal (open) cell handling in a room air BSC. The cell cultures can also be exposed to suboptimal separation of air during cell handling in the BSC which creates a contamination hazard. In addition, even in the cleanest clean room, cells are exposed to room air temperatures and gas levels. Until cells re-equilibrate with the incubator after handling, cells are chilled, hyperoxic, and hypocapnic compared to physiologic conditions. A barrier isolator (closed cell processing workstation) creates a constant physical barrier between cells and users. This barrier reduces the risks of air mixing between cells and people without dependence upon laminar air flow in a BSC or a costly whole-room HVAC system. We undertook the following study to test the hypothesis that the use of a barrier isolator, during cell handling as well as incubation, could improve cell growth by providing unbroken physiologic conditions to cells. We used K562 cells, an undifferentiated leukemic cell line that has been used for T cell bioprocess optimization. We divided a single culture into two sets of triplicate cultures in T-75 flasks, three for growth in a barrier isolator and three for growth in a standard room-air incubator equipped with an inner chamber (C-chamber) for control of gasses. Both sets of cultures were incubated at 5%CO2, 5%O2, 37 C, and tracked for cell growth and viability over two weeks. For routine subculturing twice weekly, the cultures in the isolator were handled in the processing chamber of the isolator in physiologic conditions identical to the incubator. The cultures in the room-air incubator and C-chamber were handled in a standard room-air BSC (open). While cell viability was high in both sets of cultures, we found that handling cells under continuous physiologic conditions produced statistically higher cell yields over time (p=0.00086, Day 14, two-tailed paired T test, assuming unequal variances). No contamination events occurred and particle count data indicated no breach of functional separation between room air and isolator cell culture workspace. We concluded that cell handling in unbroken physiologically relevant conditions produced better cell growth over time while reducing risks to both cells and cell culturists. We predict that as cells become increasingly valuable, controlled workspaces for better cell growth and lower biosafety risks will become increasingly valuable as a part of a total quality approach to cell culture.
Abstract 5176: Chemotherapy alters the natural history of metastatic progression
Authors: Nicole M. Aiello, David L. Bajor, Minh N. Pham, Robert H. Vonderheide, Ben Z. Stanger
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of less than 6%. Metastatic disease accounts for a majority of PDAC-related deaths, even for patients with no evidence of metastasis at the time of resection. In this study we sought to understand the natural history of metastatic colonization and the cellular mechanisms governing the metastatic cascade. Using an autochthonous PDAC mouse model combined with a lineage-labeling approach, we have tracked and characterized the various stages of metastatic progression, from single cells to macroscopic lesions. PDAC tumors primarily metastasize to the liver, where small lesions of 10 cells or less reside closest to portal veins and exhibit a high frequency of epithelial-mesenchymal transition (EMT). Larger metastatic lesions exhibit reduced EMT and are hypovascular, resembling primary PDAC tumors. Metastases gradually accumulate desmoplasia as they grow, which consists of myofibroblasts, leukocytes and extracellular matrix components including collagen, hyaluronic acid, fibronectin and SPARC. Treatment with gemcitabine and nab-paclitaxel reduces overall metastatic burden and shifts the size distribution of metastases toward small lesions of 10 cells or less. Single seeded cells in particular seem to be protected from chemotherapy-induced killing, while larger lesions that have accumulated a desmoplastic stroma are more susceptible. Our results demonstrate that chemotherapy has direct measurable effects on metastatic burden, which may explain the improved outcomes for PDAC patients who receive adjuvant chemotherapy. Citation Format: Nicole M. Aiello, David L. Bajor, Minh N. Pham, Robert H. Vonderheide, Ben Z. Stanger. Chemotherapy alters the natural history of metastatic progression. [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 5176. doi:10.1158/1538-7445.AM2015-5176
Abstract 5292: Determination of the receptor for advanced glycation end-products in breast cancer patients previous chemotherapy
Authors: Jorge A. Guadarrama-Orozco, Erika B. Ruiz-García, Hector A. Maldonado-Martinez, Lilia P. Barron-Rodríguez, Fernando Mainero-Ratchelous, Horacio Astudillo-delaVega
Journal: Cancer Research (2015)

Abstract The receptor for advanced glycation end-products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. RAGE has recently been recognized as a cancer-associated protein responsible for cancer progression and metastasis in gastrointestinal and epithelial cancers. The aim was to examine the role of RAGE in breast cancer previous to chemotherapy treatment. Methods: A retrospective study in surgical specimens obtained from 68 consecutive patients who underwent surgery for stage II-III breast cancer at the Oncology Hospital at National Medical Center SXXI, between 2008 and 2009. RAGE expression was examined by immunohistochemistry (IHQ) and PCR in 68 patients with stage II or III breast cancer previous chemotherapy treatment. RAGE expression was compared with clinicopathological parameters including clinical stage, invasive depth, nodal metastasis, disease recurrence and disease-free survival. The positive expression rate of RAGE was defined as 50% or more of stain in IHQ. Results: In all 68 samples no RAGE membrane expression was found significantly. Just one specimen was 50% positive in tumor IHQ and no clinicopathological correlation was found. In PCR the results were more significant. Our findings shows suggestive no evidence for the presence of RAGE in membrane, but possibly RAGE gene expression could had relationship in the progression of breast cancer in stages II and III. Citation Format: Jorge A. Guadarrama-Orozco, Erika B. Ruiz-García, Hector A. Maldonado-Martinez, Lilia P. Barron-Rodríguez, Fernando Mainero-Ratchelous, Horacio Astudillo-delaVega. Determination of the receptor for advanced glycation end-products in breast cancer patients previous chemotherapy. [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 5292. doi:10.1158/1538-7445.AM2015-5292
Combination of Transplantation of Haploidentical Human Mesenchymal Stem Cells and Rituximab Therapy in a Patient with Extensive Therapy-Refractory Chronic Graft Versus Host Disease.
Authors: L. Mueller, M. Christopeit, J. Luetzkendorf, K. Reichelt, E. Schlesinger, M. Schulze, G. Behre
Journal: Blood (2006)
OC-084 The targeted use of Taurolock® to reduce central venous catheter sepsis in a home parenteral nutrition cohort
Authors: G P Rafferty, J Nightingale, M Small, J Eastwood, C UgarteCano, S Gabe
Journal: Gut (2010)

<h3>Introduction</h3> Taurolock® (Bio-Implant HealthCare, Winsen, Germany) is an anti-microbial agent (taurolidine) with anticoagulant properties (citrate). There is evidence that Taurolock® is beneficial in reducing catheter-related blood stream infections (CRBSI) in haemodialysis patients, but there are fewer data regarding benefit in home parenteral nutrition (HPN) patients.12 At St Mark9s Intestinal Failure Unit Taurolock® is prescribed for patients with greater than three CRBSI in a 12-month period. The primary aim was to determine the incidence of CRBSI prior and subsequent to Taurolock® use. The secondary aim was to establish cost benefit from Taurolock® prescription. <h3>Methods</h3> Retrospective audit using St Mark9s Intestinal Failure (IF) Database. ::::CRBSI and Taurolock® prescription recorded on IF database. CRBSI defined as positive central venous catheter blood cultures with fever±rigors. Simple cost analysis calculated at £8340 per hospital treatment for CRBSI (10 day in-patient admission) and Taurolock costing £11 per day. <h3>Results</h3> All 16 patients (male 56.3%, mean age 44.8 years (range 23–73)) prescribed Taurolock® were selected. In the pre-treatment group mean duration from first CRBSI episode to Taurolock® prescription was 602±317 days. This pre-treatment group had a mean 9.8±6.5 CRBSI rate per 1000 catheter days. The treatment group (mean duration 557±269 days) had a mean 3.3±3.4 CVC related sepsis rate per 1000 catheter days. There was a significant difference (p&lt;0.001) in CRBSI rate prior and subsequent to Taurolock® prescription. Treating CRSBI for 1 year in these 16 patients pre-Taurolock® cost approximately £367 000 (440 in-patient days and antibiotic costs). Approximate treatment group costs were £228 240 (£164 000 hospital costs for treating CRBSI and £64 240 for Taurolock treatment). One year cost savings of Taurolock® prescription was £138 760. <h3>Conclusion</h3> Taurolock® significantly decreases CRBSI rate in HPN patients. These results are in keeping with a Canadian group that managed to decrease CRBSI following treatment in seven patients. (2) Taurolock® prescription generates considerable cost savings in this cohort of patients.
Outcomes of c Hematopoietic Stem Cell Transplantation (HCT) after Non-Myeloablative Conditioning in Relapsed, Refractory, or Transformed Indolent Non-Hodgkin Lymphoma (NHL).
Authors: Andrew R. Rezvani, Brenda M. Sandmaier, Barry Storer, Michael Maris, Edward Agura, Richard Maziarz, James C. Wade, Thomas Chauncey, Stephen J. Forman, Dietger W. Niederwieser, Judith Shizuru, Amelia Langston, Michael Pulsipher, Rainer F. Storb, David G. Maloney
Journal: Blood (2006)
Efficacy of robotic-assisted surgery in colorectal cancer: A systematic review and meta-analysis.
Authors: D. Chow, B. E. Stabile, B. Lee
Journal: Journal of Clinical Oncology (2011)

e14125 Background: Laparoscopic assisted colorectal surgery is an accepted mode of treatment for colorectal cancer. The addition of robotics has been reported by some to improve technical aspects of minimally invasive surgery. The aim of this review was to evaluate surgical and oncological parameters in robotically assisted colorectal surgery for malignancy. Methods: The study was a retrospective analysis of a publicly available database and exempt from Institutional Review Board approval. A systematic review of publications concerning robotically assisted surgery and colorectal cancer was performed for the years 1993 to 2011. Numbers of patients, mean age, TNM staging, mean lymph node extraction, margin status, mean operating time, and conversion rates were recorded. Results: Initial search yielded a total of 254 articles, of which 12 were selected for data extraction. A total of 518 patients were identified from these studies as having a robotically assisted surgery for their malignancy. Mean operative time was 262.3 minutes. 12 operations were converted to an open procedure. 5 (0.9%) patients had a positive margin, 4 of which were the circumferential radial margins in rectal cancer. The mean lymph node retrieval was 16.1. Anastomotic complications occurred in 29 patients. Conclusions: Robotically assisted surgery for colorectal cancer can be performed safely. Review of the literature resulted in acceptable morbidity rate, lymph node retrieval rate, and positive margin rate. These outcomes should be interpreted with caution until results of survival and recurrence rates are reported.
Abstract 4811: Pro-oncogenic role of NOTCH1 in early tongue squamous cell carcinoma
Authors: Pawan Upadhyay, Jyotirmoi Aich, Vidyalakshmi Sethunath, Prachi Dani, Sadhana Kannan, Pratik Chandrani, Kavitha Sonawane, Beamon Agarwal, Shubhada Kane, Sudhir Nair, Amit Dutt
Journal: Cancer Research (2015)

Abstract Notch pathway play a context-dependent tumor-suppressive or pro-oncogenic role in solid tumors and hematological malignancies. In head and neck cancer, inactivating mutations in NOTCH1 are associated with poor prognosis. Here we perform meta-analysis of DNA copy number and gene expression profiling of NOTCH signaling pathway genes in 35 paired primary T1 and T2 stage tongue tumors, comprising of Notch ligands, receptors and target genes. We find 32% of primary tongue squamous cell carcinoma (TSCC) tumors amplify NOTCH signaling pathway components; and over express activated NOTCH1based on immuno-histochemical staining in an additional series of 50 surgically resected paired TSCC tumors. Interestingly, these alterations: amplification at Notch ligand DLL3 (χ2 = 7.575, P = 0.023); over expression of Notch pathway target gene HEY2 transcript (χ2 = 9.885, P = 0.007); and expression of activated NOTCH1 (χ2 = 7.575, P = 0.023) positively correlate with N+ve and non- smoking status of patients. In a parallel effort, we characterized four HNSCC cell lines– NT8E, OT9, AW13516, and AW8507– established from Indian patients using whole exome, whole transcriptome sequencing and SNP array assays. Significant amplification and over expression of NOTCH signaling pathway components were observed in AW13516 and NT8E cells. Inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 could inhibit transformation, survival, migration and invasion of NT8E cells. Taken together, we present that activation of Notch signaling pathway in a subset of TSCC patients is associated with nodal positivity and non-smoking status among early tongue cancer patients. Citation Format: Pawan Upadhyay, Jyotirmoi Aich, Vidyalakshmi Sethunath, Prachi Dani, Sadhana Kannan, Pratik Chandrani, Kavitha Sonawane, Beamon Agarwal, Shubhada Kane, Sudhir Nair, Amit Dutt. Pro-oncogenic role of NOTCH1 in early tongue squamous cell 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 4811. doi:10.1158/1538-7445.AM2015-4811
Natural History of Amyloidosis Isolated to Fat and Bone Marrow Aspirate
Authors: Rajshekhar Chakraborty, Morie A. Gertz, Angela Dispenzieri, Wilson I. Gonsalves, Ronald S. Go, Suzanne R. Hayman, Yi L. Hwa, Prashant Kapoor, Robert A. Kyle, Martha Q. Lacy, Nelson Leung, S. Vincent Rajkumar, Stephen J. Russell, Steven R. Zeldenrust, Shaji Kumar
Journal: Blood (2015)