tbuckley/cabot-search huggingface dataset:
Abstract 4351: Identification of molecular signature associated with the castration-resistant prostate cancer (CRPC) development by next-generation sequencing (NGS)-based transcriptomic profiling
Authors: Seon-Kyu Kim, Jeong-Hwan Kim, Pildu Jeong, Wun-Jae Kim, Yong Sung Kim, Seok-Joong Yun, Seon-Young Kim
Journal: Cancer Research (2015)

Abstract Backgrounds: Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer produced by disease progression following surgical or pharmaceutical castration. The development process of CRPC becoming castrate resistant is unclear. The objective of this study is to identify a gene set and putative signaling pathway for mediating the development of CRPC. Methods: RNA-seq data was generated using 54 prostate samples [primary prostate cancer (PCa), CRPC, and benign prostatic hyperplasia (BPH)], among which 8 were paired samples of PCa and CRPC obtained from 4 patients. Diverse statistical methods, including a generalized linear model likelihood ratio test, were applied to identify the signature associated with CRPC development. The interconnectivity between genes in the signature was verified by Ingenuity Pathway Analysis TM. We also confirmed a relevance of the signature with experimental assays using prostate cancer cell lines. Results: Unsupervised hierarchical cluster analysis of RNA-seq data revealed a clear gene expression pattern of tumorigenesis in PCa with heterogeneous molecular characteristics of CRPC. Comparing paired cancer samples, 309 genes were differentially expressed between PCa and CRPC samples. We also tested unpaired sample groups (PCa vs. CRPC) and found that 182 genes had significantly differences of expression (a generalized linear model likelihood ratio test, P &amp;lt; 0.001, a 2-fold or greater relative difference). When comparing two gene sets, a total of 15 genes was common in both paired and unpaired CRPC groups. Among them, AR and SPINK1 were significantly increased in the CRPC than in the PCa groups. Gene network analyses and experimental assays of AR and SPINK1 revealed that CRPC development could be mediated by SPINK1-AR pathway. Conclusion: The molecular signature defined by activation of SPINK1-AR may be a genetic determinant of progression from PCa to CRPC. Note: This abstract was not presented at the meeting. Citation Format: Seon-Kyu Kim, Jeong-Hwan Kim, Pildu Jeong, Wun-Jae Kim, Yong Sung Kim, Seok-Joong Yun, Seon-Young Kim. Identification of molecular signature associated with the castration-resistant prostate cancer (CRPC) development by next-generation sequencing (NGS)-based transcriptomic profiling. [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 4351. doi:10.1158/1538-7445.AM2015-4351
Additional Cytogenetic Changes and Prior Genotoxic Exposure Predict Unfavorable Prognosis in Myelodysplastic Syndromes and Acute Myeloid Leukemia with der(1;7)(q10;p10).
Authors: Kazuma Ohyashiki, Hui-Hua Hsiao, Goro Sashida, Yoshikazu Ito, Junko H. Ohyashiki
Journal: Blood (2005)
Abstract RAOS15-03: Pancreatic tumor stroma as a therapeutic target
Authors: Ronald M. Evans
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) occurs in the context of an exuberant desmoplastic response that produces a ‘living chimera’ of tumor and activated stromal components. A prominent feature of the stromal response is the transformation of the Vitamin A storing pancreatic stellate cell (PSC) to activated myofibroblasts. We hypothesized that restoration of the quiescent PSC phenotype could disrupt tumor-stroma crosstalk and thus improve response to chemotherapy. Recently, we have shown that the vitamin D receptor (VDR) is expressed at high levels in activated human pancreatic tumor stroma and, in response to ligand, acts as a master transcriptional regulator of PSCs to reprise the quiescent state. In vivo, a synthetic VDR agonist (Cal) induced signal-dependent transcriptional remodeling of tumor stroma, enhancing the anti-tumor effects of gemcitabine by increasing intra-tumoral concentration 5-fold to reduce tumor growth. A survival study in KPC mice shows that addition of CAL results in a 57% increase in lifespan relative to Gemcitabine treatment alone. An approved IND enables the exploration of CAL in the neo-adjuvant setting in patients with resectable PDAC. This Phase I trial is designed to establish whether CAL (Zemplar) is able to reach the tumor and alter genes and other measurable responses linked to stromal reprogramming. Citation Format: Ronald M. Evans. Pancreatic tumor stroma as a therapeutic target. [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 RAOS15-03. doi:10.1158/1538-7445.AM2015-RAOS15-03
PCR-Based Minimal Residual Disease (MRD) Detection Is a Strong Independent Outcome Predictor Also in Rituximab-Intensive Non-ASCT-Based Programs: Results From the ML17638 Multicenter Randomised Phase III Trial for Elderly Follicular Lymphoma (FL) Patients of the Fondazione Italiana Linfomi (FIL)
Authors: Marco Ladetto, Chiara Lobetti-Bodoni, Barbara Mantoan, Andrea Evangelista, Carola Boccomini, Elisa Genuardi, Barbara Botto, Luca Baldini, Giuseppe Rossi, Alessandro Pulsoni, Francesco Di Raimondo, Luigi Rigacci, Antonello Pinto, Mario Petrini, Stefano Sacchi, Delia Rota-Scalabrini, Luigi Gugliotta, Renato Fanin, Andrea Gallamini, Guido Parvis, Giorgina Specchia, Pellegrino Musto, Barbara Olivero, Enrica Gamba, Giovannino Ciccone, Umberto Vitolo
Journal: Blood (2012)
Bcl-2 Mediated Apoptosis Interacts with p53-Dependent Pathway in Progression of Peripheral T-Cell Lymphoma.
Authors: Dong Hwan Kim, Jin Tae Jung, Eun Kyung Kwak, Young Rok Do, Jong Gwang Kim, Tae In Park, Sang Kyun Sohn, Ki Wyong Kwon, Hong Suk Song, Kyu Bo Lee
Journal: Blood (2004)
Nfkb1 Plays a Tumor-Suppressing Role in BCR-ABL-Induced Leukemias
Authors: Con Sullivan, Yaoyu Chen, Zhiru Guo, Yi Shan, Cong Peng, Haojian Zhang, Jason Bubier, Thomas Sproule, Derry Roopenian, Shaoguang Li
Journal: Blood (2012)
Abstract 2518: Effective vaccination against melanoma in an animal study: Combination of laser-assisted dermal skin delivery and cross-presenting XCR1+ dermal DCs targeting
Authors: Dorothea Terhorst, Even Fossum, Anna Baranska, Samira Tamoutounour, Camille Malosse, Mattia Garbani, Elmira Lechat, Reto Crameri, Roland Winteler, Bjarne Bogen, Bernard Malissen, Sandrine Henri
Journal: Cancer Research (2015)

Abstract Background/Aim/Method The induction of CD8+ cytotoxic T lymphocytes (CTL) is critical to eradicate tumor cells. In mouse skin, a subset of dendritic cell characterised by the expression of the chemokine receptor XCR1 is highly potent to activate CD8+ T cells. By combining PLEASE-assisted laser poration of the skin allowing dermal delivery and the use of dimeric vaccine molecule in which the XCR1 ligand, Xcl1, was fused to the antigen, we targeted specifically this XCR1+ dermal subset. Results Dermal delivery of this vaccine molecule after skin laser-poration induced specific strong T cell proliferation in an XCR1-dependent manner. A single immunization allowed protecting against melanoma in both therapeutic and prophylactic protocols. Discussion &amp; Conclusion Thus, specific targeting of cross-presenting skin DCs represents a promising vaccine strategy for induction of CD8+ T cell responses and protection against cancers. Citation Format: Dorothea Terhorst, Even Fossum, Anna Baranska, Samira Tamoutounour, Camille Malosse, Mattia Garbani, Elmira Lechat, Reto Crameri, Roland Winteler, Bjarne Bogen, Bernard Malissen, Sandrine Henri. Effective vaccination against melanoma in an animal study: Combination of laser-assisted dermal skin delivery and cross-presenting XCR1+ dermal DCs targeting. [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 2518. doi:10.1158/1538-7445.AM2015-2518
Abstract LB-033: FAK promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3ββ
Authors: Chenxi Gao, Guangming Chen, Shih-Fan Kuan, Dennis H. Zhang, Jing Hu
Journal: Cancer Research (2015)

Abstract Aberrant activation of Wnt/β-catenin signaling plays an unequivocal role in colorectal cancer (CRC), but identification of effective Wnt inhibitors for use in cancer remains a tremendous challenge. New insights into the regulation of this pathway could reveal new therapeutic point of intervention, therefore are greatly needed. Glycogen synthase kinase 3β(GSK3β) is a major component of the Wnt/β-catenin pathway, how GSK3β is regulated in Wnt signaling and tumorigenesis remains largely unknown. This study investigated the function and regulation of GSK3β phosphorylation in Wnt/β-catenin signaling and Wnt-driven intestinal tumorigenesis. The function of GSK3β phosphorylation at tyrosine 216 (Y216) in Wnt/-catenin signaling and CRC cells was analyzed by a series of biochemistry experiments and anchorage independent growth assays. Phosphorylation of GSK3βY216 by focal adhesion kinas (FAK) was studied in in vitro reconstitution system and in cells. The role of FAK-mediated phosphorylation of GSK3βY216 was tested by examining adenoma formation and associated molecular changes in control and FAK inhibitor-treated APCmin/+ mice. Immunohistochemistry was used to evaluate the expression levels of FAK, p-GSK3βY216 and β-catenin in CRC patients. Our results showed that GSK3βY216 phosphorylation was required for the activation of the Wnt/β-catenin pathway. Pharmacological inhibition of FAK suppressed adenoma formation in APCmin/+ mice accompanied by reduced intestinal levels of p-GSK3βY216 and β-catenin. FAK, p-GSK3βY216 and β-catenin were elevated and positively correlated in human CRC tissues. Together, our findings indicate that FAK/GSK3βY216 axis is critical for the activation of Wnt/β-catenin signaling in APC-driven intestinal tumorigenesis, thus providing a compelling mechanistic justification for clinical exploration of FAK inhibitors in colorectal cancer patients carrying APC mutations. Citation Format: Chenxi Gao, Guangming Chen, Shih-Fan Kuan, Dennis H. Zhang, Jing Hu. FAK promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3ββ. [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 LB-033. doi:10.1158/1538-7445.AM2015-LB-033
188. Functional Analysis of Human Induced Pluripotent Stem Cell-Derived Cardiac Myocytes
Authors: Matthew Wheelwright, Zaw Win, Patrick W. Alford, Joseph M. Metzger
Journal: Molecular Therapy (2015)

Recent and exciting advances in stem cell biology have made it possible to quickly and efficiently derive induced pluripotent stem cells (iPSCs) from human somatic cell types, as well as differentiate pluripotent cells to committed lineages, such as cardiac myocytes (hiPSC-CMs). The nature of these cells makes them ideal potential candidates for cell therapy treatments, such as implantation of hiPSC-CMs following myocardial infarction. Use in therapy requires optimization of these cells physiologically, which in turn requires appropriate assays to determine cell function beyond gene expression profiles. Difficulty in accurately characterizing hiPSC-CM function comes from large variability in cell size and shape, as well as isotropy of axis of contraction. We utilize here micropatterning techniques, whereby single cell-sized (2500 μm2) rectangles of fibronectin are applied to glass cover slips. The hiPSC-CMs are then cultured on the cover slip at a low density such that one cell occupies the rectangular shaped space. This persuades the cells to assume a rectangular shape, similar to that of an adult myocyte, and causes them to contract along the long axis of the rectangle. By normalizing size, shape, and alignment of hiPSC-CMs, microscopy can be used to determine and compare kinetics of contraction and relaxation, utilizing the IonOptix software and an inverted microscope. Additionally, this technique can be used for traction force microscopy. Here we use fibronectin patterns that are micropatterned onto a polyacrylamide hydrogel, and the hiPSC-CMs are cultured on top of it. Next, 0.2 μm diameter fluorescent beads are embedded in the hydrogel such that when the cell contracts, it pulls on the hydrogel, and movement of the beads is then tracked using confocal microscopy. An ImageJ program analyzes movement of the beads and uses the known Young's modulus of the hydrogel to calculate traction force generated by the individual cells. Preliminary results show that iPSC-CMs will morphologically take the shape of the fibronectin stamp and will contract along the long axis of the rectangle. Additional quantification of these data will be presented and discussed.
Intraperitoneal chemotherapy in pretreated ovarian cancer patients: a retrospective case-control study
Authors: A. Casarin, M.O. Nicoletto, S. Valpione, A. Baldoni, Z. Baretta, G. Artioli, G. Randon, A. Perin, C. Barile, P.F. Conte, C. Aliberti
Journal: Annals of Oncology (2015)
148. AptaMetrics: A Web-Based Aptamer Bioinformatics Platform
Authors: Thomas Bair, Julie S. Wertz, Robert J. Miller, James Schappet, Paloma H. Giangrande, William H. Thiel
Journal: Molecular Therapy (2016)

RNA and DNA aptamer development as a therapeutic moiety and as a diagnostic tool is a rapidly growing field. The discovery process for aptamers involves iterative rounds of selection in a process termed SELEX, Systematic Evolution of Ligands by EXponentional enrichment. The modern SELEX process was revolutionized with the adoption of high-throughput sequencing (HTS), which is able to identify millions of aptamer sequences across multiple rounds of aptamer selection. The scale of aptamer HTS datasets has necessitated bioinformatics algorithms, such as clustering algorithms, to identify candidate aptamers for experimental validation. Herein we describe a web-based aptamer bioinformatics platform, AptaMetrics, which utilizes a collection of programs and algorithms to facilitate the analysis of aptamer HTS datasets. The AptaMetrics platform builds upon our previously described aptamer bioinformatics work (Thiel et. al. PLoSOne, 2012). Central to AptaMetrics is our clustering algorithm, ProcessSeqs, which we engineered to include several novel and distinct features: 1) clustering may be performed using either an "all-versus-all" or a "seed" sequence strategy; 2) clustering may be accomplished through either sequence similarity (edit distance) or structural similarity (tree distance); 3) the output of ProcessSeqs provides a visual and interactive representation of related aptamer networks; and 4) these networks of related aptamers may be analyzed using conventional network analysis tools. We also developed an aptamer structure prediction program, ProcessFold, that provides the predicted structure of millions of aptamer sequences utilizing a variety of proven oligonucleotide structure prediction algorithms (e.g., RNAfold, Mfold, RNAstructure). Integration of these two programs thereby allows users to create networks of structurally related aptamers based on the different structure prediction algorithms. We also created and incorporated an aptamer truncation algorithm, AptmR, into the AptaMetrics platform. The purpose of AptmR is to determine a predicted truncated aptamer sequence based on aptamer sequence and structure information provided by ProcessFold. AptmR can be applied to either a single aptamer sequence or to millions of aptamer sequences. The predicted truncations may then be clustered into networks of related aptamers using the ProcessSeqs clustering algorithm. Importantly, to allow the greatest versatility, each program and algorithm within AptaMetrics may be used independently or as a pipeline. The collection of programs and algorithms within AptaMetrics provide a significant degree of flexibility in analyzing aptamer HTS data while maintaining the ease of accessibility of a web-based environment.
Chronic Eosinophilic Leukaemia (CEL) with FIP1L1-PDGFRalpha Rearrangement (F/P): The Response to Imatinib (IM) Is Durable. A Report of 33 Patients with A Follow –up of 30 to 92 Months.
Authors: Michela Rondoni, Emanuela Ottaviani, Daniela Cilloni, Pier Paolo Piccaluga, Stefania Paolini, Ilaria Iacobucci, Simona Soverini, Serena Merante, Francesca Messa, Francesco Buccisano, Mario Tiribelli, Fabrizio Pane, Giuseppe Saglio, Francesco Lauria, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)
CC-007 Ascites due to unusual cause with unusual mode of therapy
Authors: R L Satarasinghe, K Dias, C Subasinghe
Journal: Gut (2010)

<h3>Introduction</h3> 40 years old married goldsmith presented with features of numbness of both lower limbs, swelling of the neck, bilateral pedal oedema and abdominal distension of 4 months duration. In addition he had asthenia, effort dyspnoea and pigmentation. Systemic inquiry revealed no other significant symptoms and he was on treatment for hypertension. He was a non-alcoholic and a non-smoker. He had many social and psychological problems due to his current illness. Examination revealed mild pallor, pigmentation not involving oral mucosa but involving skin creases, generalised lymphadenopathy in the cervical, supraclavicular and inguinal areas rubbery and non-discrete in certain areas, leuconychia without clubbing, ankle oedema. CVS and respiratory system examination were normal. Abdomen revealed non-tender hepatomegaly 4 cm below right costal margin shifting dullness, while CNS examination revealed presence of peripheral neuropathy with bilateral foot drop without thickened nerves and bilateral papilloedema. Following were the results of laboratory investigations; FBC: Hb-9.3 g/dl, MCV-70.2 fl and rest normal. LFT: normal. Renal profile normal. ESR:40 mm first hour, C-RP 48 mg/dl. FBS-100 mg/dl. Normal ferritin, calcium and ceruloplasmin levels. Clotting profile: INR-1.6, rest normal. UFR normal. HIV screening negative. CXR-PA normal. Abdomen and pelvic USS: minimal hepatomegaly and splenomegaly with ascites. Mantoux negative. OGD: no evidence of portal hypertension. Bone marrow normal. Nerve conduction study and EMG: severe demyelinating sensory and motor neuropathy. 2D echo: moderate LVH and pulmonary hypertension with small pericardial effusion. TSH- 23.8 μiu/l (0.4–4.0 μiu/l) Ascitic fluid analysis: 64.5 g/l, white cells- 344/mm<sup>3</sup> 90% lymphocytes and 10% neutrophils. LDH and amylase levels normal. Screening for mycobacterium negative. Liver biopsy: interphase hepatitis. Immunoglobulin Profile – elevated α 2 Globulins and a mild polyclonal gammopathy Free κ light chains 569.0 mg/dl (138–375) Free λ light chains 258.7 mg/dl (93–242) Lymph node biopsy revealed unifying diagnosis which was compatible with other clinical and laboratory findings. The patient was treated with a single drug for 6 months which resulted in improvement of his clinical features and resolution of ascites. <h3>Conclusion</h3> Ascites is a common condition encountered by a Gastroenterologist with or without other signs, and the aeotiology could be unusually extraordinary as in this report with an unusual therapeutic strategy. <h3>Methods</h3> BSG – interactive case presentation <h3>Results</h3> BSG – interactive case presentation <h3>Conclusion</h3> BSG – interactive case presentation
PTH-051 Vitamin D and bone health in coeliac disease: a district general hospital experience
Authors: A Al-Joudeh, C Raychaudhuri, M Srinivas, R Ellis, P J Willemse, K D Bardhan, P Basumani, B Höroldt
Journal: Gut (2010)

<h3>Introduction</h3> Association between coeliac disease (CD) and osteoporosis is well studied but studies on osteomalacia in CD are lacking. We aimed to determine the prevalence of vitamin D deficiency in CD and its correlation with osteoporosis and osteomalacia in our patients. <h3>Methods</h3> We checked vitamins D and B12, folate and ferritin levels in new and follow-up (FU) patients with proven CD, Calcium profile and Coeliac serology were checked at diagnosis or on annual review. DEXA scan was performed to assess for osteoporosis within 2 months of blood testing. Patients on Calcium and vitamin D or other Vitamin supplements and those on medication interfering with vitamin D metabolism were excluded. P value was calculated using Fisher exact test. Vitamin D (25 OHD) categories: deficient &lt;25 nmol/l, insufficient 25–50 nmol/l, adequate &gt;50 nmol/l. <h3>Results</h3> 143 patients with confirmed CD (65 new, 78 follow-up, 31 male, median (range) age 50.51 (17–83) years; 8 Asian), 75 patients underwent a DEXA scan. A) 69 patients had suboptimal vitamin D level (13% deficient, 35% insufficient). While more common in new than FU patients (17% vs 10%), this did not reach significance (p=0.3). B) Median levels during FU were higher in men (62 vs 47 nmol/l) but not women (52 vs 54 nmol/l); there was no significant difference in deficiency or insufficiency between the sexes either at diagnosis or during FU. C) Median levels of patients &gt;60 years were only slightly lower (52 vs 54 nmol/l). D) Median levels were higher in autumn than spring both for new and FU patients (61 vs 43 nmol/l, p=0.045). E) Median vitamin D levels for patients with T-score of &gt;−1, −1 to −2.5 and &lt;−2.5 were: 60, 47 and 43 nmol/l, respectively. Prevalence of Vitamin deficiency/insufficiency was higher in osteoporotic/oesteopenic patient than in those with normal Dexa scan (p=0.036). F) Only one patient had biochemical evidence of osteomalacia (Ca↓, phosphate↓, ALP↑), in addition 4 Ca↓ (2 vitamin D deficient), 2 phosphate↓ (1 vitamin D deficient), 4 ALP↑ (2 vitamin D deficient). G) Other deficiencies: B12: 15%, folate: 14%, iron (excluding 16 patients found to be coeliac on investigation of iron deficiency anaemia)—32% H) vitamin B12 and folate deficiency were similar among new and FU patients, where as iron deficiency was more common in new patients (45% vs 22%); but this did not reach statistical significance (p=0.07). <h3>Conclusion</h3> Vitamin D deficiency/insufficiency is common in coeliac patients; it appears there is an association between vitamin D deficiency and osteoporosis that can be confirmed in our cohort. Biochemical evidence osteomalacia is not common—but may underestimate the clinical problem. Other vitamin deficiency while less prevalent are still common. Vitamin D testing should be added to the annual screen for coeliac patients.