tbuckley/cabot-search huggingface dataset:
Abstract 5127: The most common mistakes in cancer cell pharmacology
Authors: Guido Lenz, Andrew O. Silva
Journal: Cancer Research (2015)

Abstract Background: Cancer cell culture has contributed with pivotal discoveries for cancer biology and pharmacology. However, cancer cells in culture have not provided a good test method for patient´s response to chemotherapy to a similar extent as antibiograms have been useful to predict response to antibiotics. Although the reason for this is multifactorial, some very common mistakes in cancer cell pharmacology are made in most studies that, if corrected, could improve the overall results. Methods: We systematically tested key conditions such as concentration, time of exposure and analysis, methods of analysis and number of cells analyzed in glioma cell lines. Results: We found that time of exposure to the drug and time of analysis have a large impact on the outcome, with some drugs producing in vitro “relapse” only after 20 days of analysis. Additionally, the initial number of cells plated is also central for the outcome, with resistance being uncovered only after a certain number of cells is treated. Finally, a direct comparison between the MTT viability assay with population doubling assay clearly indicates that the former is not suited for studying effective anticancer drugs and resistance due to its low sensitivity. By systematically analyzing concentration, time of exposure and analysis, number of initial cells and method of analysis we showed that for more meaningful in culture cancer pharmacology, drug exposure should mimic the patient´s exposure time, (5 days for gliomas), analysis should be for at least one treatment cycle (28 days for gliomas), the number of cells tested should be at least more than 15 thousand and the method for analyzing cell number should be repetitive direct counting instead of viability assays such as MTT. Conclusion: Despite not addressing other very fundamental issues in cancer cell culture such as medium, adhesion, 3D culture and presence of other cell types, these simple improvements should aid to produce more significant in culture cancer pharmacology. Financial support: FAPERGS, CNPq e CAPES. Citation Format: Guido Lenz, Andrew O. Silva. The most common mistakes in cancer cell pharmacology. [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 5127. doi:10.1158/1538-7445.AM2015-5127
Adverse Prognostic Impact of GAS6 Expression in De Novo Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) (CALGB 8461, 9665, 20202; Alliance)
Authors: Susan Whitman, Jessica Kohlschmidt, Kati Maharry, Deedra Nicolet, Sebastian Schwind, Heiko Becker, Klaus H. Metzeler, Krzysztof Mrózek, Jason H. Mendler, Ann-Kathrin Eisfeld, Stefano Volinia, Bayard L. Powell, Thomas H. Carter, Jonathan E. Kolitz, Richard M. Stone, Il-Kyoo Park, Michael A. Caligiuri, Guido Marcucci, Clara D. Bloomfield
Journal: Blood (2012)
CC-004 Unexpected cause of colitis in a middle-aged Caucasian female
Authors: S Isse, D Lambo, Z Mangera, B Krishnan, D Lindo
Journal: Gut (2010)

<h3>Introduction</h3> We report on a common clinical problem with an unexpected aetiology in a middle aged Caucasian female. <h3>Methods</h3> N/A. <h3>Results</h3> The initial blood results were unremarkable apart from a CRP of 145 and albumin of 27. A plain abdominal x-ray showed extensive distal colon wall oedema. The patient went on to have a flexi-sigmoidoscopy, which demonstrated a congested recto-sigmoid mucosa with two discrete ulcers and florid, tender anal tags. Overall, the appearances were suggestive of a diagnosis of Crohn9s and the patient was continued on intravenous steroids and pentasa. Biopsies taken proved indeterminate. However, the CRP continued to increase, peaking at 304, the albumin continued to fall and the symptoms persisted. Failure to respond to treatment prompted alternative causes to be investigated. All seven stool specimens sent for microscopy and cultures were positive for leucocytes but failed to isolate any infective causes. Amoebic serology was also negative. <h3>Conclusion</h3> This unusual case highlights the need for a thorough history, including travel and sexual history, in any patient presenting with chronic diarrhoea in order to avoid delay in diagnosis and minimise the risk of further transmission. Furthermore, vigilance is required when reviewing the response to treatment in a newly diagnosed colitis. Finally, unusual endoscopic appearance should be biopsied and sent to microbiology in addition to pathology.
The Evolutionary Relationship of the Domain Architectures in the RhoGEF-containing Proteins
Authors: Qing-Lan Sun, Hong-Jun Zhou, Kui Lin
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract Domain insertions and deletions lead to variations in the domain architectures of the proteins from their common ancestor. In this work, we investigated four groups of the RhoGEF-containing proteins from different organisms with domain architectures RhoGEF-PH-SH3, SH3-RhoGEF-PH, RhoGEF-PH, and SH3-RhoGEF defined in the Pfam database. The phylogenetic trees were constructed using each individual domain and/or the combinations of all the domains. The phylogenetic analysis suggests that RhoGEF-PH-SH3 and SH3-RhoGEF-PH might have evolved from RhoGEF-PH through the insertion of SH3 independently, while SH3-RhoGEF of proteins in fruit fly might have evolved from SH3-RhoGEF-PH by the degeneration of PH domain.
Phase 1B Results of Ricolinostat (ACY-1215) Combination Therapy with Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (MM)
Authors: Dan T. Vogl, Noopur Raje, Parameswaran Hari, Simon S Jones, Jeffrey G Supko, Gina Leone, Catherine Wheeler, Robert Z. Orlowski, Paul G. Richardson, Sagar Lonial, David Tamang, Sundar Jagannath
Journal: Blood (2014)
Characterization of autologous melanoma cell lines for vaccine therapy: Pattern of expression of tumor-associated antigens
Authors: Senthamil R. Selvan, Michelle Sheridan, Abner Fowler, Robert O. Dillman
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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Autologous melanoma cells grown in vitro have been of considerable value for active specific immunotherapy and subsequent monitoring of tumor immune responses as they provide all available antigens of a particular patient. We have been able to reliably establish tumor cell lines from a high percentage of melanoma tissue samples. Between January 2000 and May 2003, 57 tumor tissues were processed and the resulting cell mixtures were cultured in RPMI-1640 medium containing 7.5% fetal bovine serum and 7.5% iron supplemented calf serum. Pure stable melanoma cell lines were established from 43 of 57 (75% success rate) specimens. Here, we examine the pattern of expression of S-100 (15E2E2), HMB45/gp100-cl (HMB45), MART-1/Melan-A (A103; M2-7C10), Tyrosinase (T311), Mel-5 (TRP-1 and TRP-2; Ta99) and MAGE-1 Ab-4 (MA454) in 36 cell lines by immunocytochemistry. All tested antigens were expressed by only 5 of 36 cell lines in the range of few ( 75% cells. As a single major antigen, Tyrosinase was expressed by 35/36 cell lines. MART-1/Melan-A was expressed by 29/36 cell lines with >25% cells in 21 cell lines and few to 25% cells in the rest (8) of the cell lines. Expression of HMB45/gp100-cl was seen in 27/36 cell lines with >25% cells in 20 and few to 25% cells in 7 cell lines. S-100 expressed in 21/36 cell lines with >25% of cells in 14 and few to 25% cells in 7 cell lines. Mel-5 was expressed by 20/36 cell lines with >25% cells in 11 and few to 25% cells in 9 cell lines. MAGE-1 expressed in 20/36 cell lines with > 25% cells in 8 cell lines whereas few to 25% cells in 12 cell lines. In an exclusive pattern, Tyrosinase was expressed by 2 cell lines and MAGE-1 was by one cell line in >75% cells. Both MAGE ( 75% cells) expressed in one cell line and a combination of Melan-A/Mart-1 and Tyrosinase (>75% cells) in another. Three cell lines expressed only S-100 and Tyrosinase (>50% cells). Except for Tyrosinase, all other antigens were expressed by only few cells (<1%) in one cell line. In summary, our findings suggest that melanoma cell line containing heterogeneous tumor cell clones of a given tumor tissue can be reliably established in vitro from high number of tumor tissue samples in order to make patient-specific vaccine. (Supported by Hoag Foundation, Hoag Hospital; *Authors made equal contribution to the work)
116. Overcoming CAR-Dependency of Oncolytic Adenovirus via Adenoviral Fiber Modification with Vesicular Stomatitis Virus Glycoprotein Epitope for Enhanced Antitumor Efficacy
Authors: A-Rum Yoon, Jinwoo Hong, Chae-Ok Yun
Journal: Molecular Therapy (2016)

Utility of traditional oncolytic Ad has been limited due to low expression of coxackies and adenovirus receptor (CAR) in cancer cells which results in poor infectivity of Ads. Here with an aim of improving the efficiency of Ad's entry to the cell, we generated a novel tropism-expanded oncolytic Ad which contains the epitope of vesicular stomatitis virus glycoprotein (VSVG) at the HI-loop of Ad fiber. We generated 9 variants of oncolytic Ads with varying linkers and partial deletion to the fiber. Only one VSVG epitope-incorporated variant, RdB-1L-VSVG, which contains 1 linker and no deletion to fiber, was produced efficiently. Production of 3-dimensionaly stable fiber in RdB-1L-VSVG was confirmed by immunoblot analysis. RdB-1L-VSVG shows a remarkable improvement in cytotoxicity and total viral yield in cancer cells. RdB-1L-VSVG demonstrates enhanced cytotoxicity in cancer cells with subdued CAR-expression as it can be internalized by an alternate pathway. Competition assays with a CAR-specific antibody (Ab) or VSVG receptor, phosphatidyl serine (PS), reveals that cell internalization of RdB-1L-VSVG is mediated by both CAR and PS. Furthermore, treatment with RdB-1L-VSVG significantly enhanced anti-tumor effect in vivo. These studies demonstrate that the strategy to expand oncolytic Ad tropism may significantly improve therapeutic profile for cancer treatment.
Abstract 4092: PDGFRα and β play critical roles in mediating Foxq1-driven breast cancer stemness and chemoresistance
Authors: Fanyan Meng, Cecilia Speyer, Bin Zhang, Yongzhong Zhao, Wei Chen, David Gorski, Fred R. Miller, Guojun Wu
Journal: Cancer Research (2015)

Abstract Many epithelial-mesenchymal transition (EMT)-promoting transcription factors have been implicated in tumorigenesis and metastasis, as well as chemoresistance of cancer. However, the underlying mechanisms mediating these processes are unclear. Here we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. Using an expression profiling assay, we identified Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets. We further show that PDGFRα and β can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β results in more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown of either PDGFRα or β alone. In addition, PDGFRβ is a more potent mediator of Foxq1-promoted stemness traits than PDGFRα. Finally, pharmacological inhibition or gene silencing of PDGFRs sensitizes mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively implicate PDGFRs as critical mediators of breast cancer oncogenesis and chemoresistance driven by Foxq1, and may have important implications for the development of novel combinational therapeutics against breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Fanyan Meng, Cecilia Speyer, Bin Zhang, Yongzhong Zhao, Wei Chen, David Gorski, Fred R. Miller, Guojun Wu. PDGFRα and β play critical roles in mediating Foxq1-driven breast cancer stemness and chemoresistance. [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 4092. doi:10.1158/1538-7445.AM2015-4092
A Standard Set of Value-Based Patient-Centered Outcomes for Breast Cancer
Authors: Wee Loon Ong, Maartje G. Schouwenburg, Annelotte C.M. van Bommel, Caleb Stowell, Kim H. Allison, Karen E. Benn, John P. Browne, Rodney D. Cooter, Geoff P. Delaney, Francois P. Duhoux, Patricia A. Ganz, Patricia Hancock, Reshma Jagsi, Felicia M. Knaul, Anne M. Knip, Linetta B. Koppert, Henry M. Kuerer, Sarah McLaughin, Marc A. M. Mureau, Ann H. Partridge, Dereesa Purtell Reid, Lisa Sheeran, Thomas J. Smith, Mark J. Stoutjesdijk, Marie Jeanne T.F.D. Vrancken Peeters, Yvonne Wengström, Cheng-Har Yip, Christobel Saunders
Journal: JAMA Oncology (2016)

A major challenge in value-based health care is the lack of standardized health outcomes measurements, hindering optimal monitoring and comparison of the quality of health care across different settings globally. The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary international working group, comprised of 26 health care providers and patient advocates, to develop a standard set of value-based patient-centered outcomes for breast cancer (BC). The working group convened via 8 teleconferences and completed a follow-up survey after each meeting. A modified 2-round Delphi method was used to achieve consensus on the outcomes and case-mix variables to be included. Patient focus group meetings (8 early or metastatic BC patients) and online anonymized surveys of 1225 multinational BC patients and survivors were also conducted to obtain patients' input. The standard set encompasses survival and cancer control, and disutility of care (eg, acute treatment complications) outcomes, to be collected through administrative data and/or clinical records. A combination of multiple patient-reported outcomes measurement (PROM) tools is recommended to capture long-term degree of health outcomes. Selected case-mix factors were recommended to be collected at baseline. The ICHOM will endeavor to achieve wide buy-in of this set and facilitate its implementation in routine clinical practice in various settings and institutions worldwide.
Bioactive polymeric scaffolds for tissue engineering
Authors: Scott Stratton, Namdev B. Shelke, Kazunori Hoshino, Swetha Rudraiah, Sangamesh G. Kumbar
Journal: Bioactive Materials (2016)

A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.
OC-082 Spiral enteroscopy—the North Bristol experience
Authors: D Gavin, P Marden, S Hughes
Journal: Gut (2010)

<h3>Introduction</h3> Direct endoscopic inspection of the small bowel is challenging due to limitations of the equipment and techniques available and the anatomy of the small bowel itself. Capsule endoscopy allows visualisation of the small bowel mucosa but does not allow for biopsy or therapeutics. The advent of double balloon enteroscopy (DBE) has overcome many of these hurdles. However, it is a time consuming procedure and requires the purchase of extra equipment to inflate and deflate the balloons. Spiral enteroscopy utilises an over-tube with threaded vanes at the distal end, not unlike an Archimedes screw. It is a single use over-tube which connects with the enteroscope by means of a gentle locking mechanism. Clockwise rotation of the over-tube turns the spiral pleating the small bowel over the tube. This facilitates deep insertion of the enteroscope into the small bowel. <h3>Methods</h3> We describe our experience of 21 patients undergoing spiral enteroscopy. These patients required small bowel investigation for a variety of indications including anaemia, obscure gastrointestinal bleeding and angiodyspalsia. The majority of procedures were performed on a day-case basis with same day discharge, the two exceptions were performed under general anaesthetic on the intensive care unit. An Endoease Endoluminal Advancement System (Spirus) was used in combination with a Fujinon enteroscope. Procedure duration and depth of insertion were recorded. Pathological findings and endoscopic therapy given were recorded. Patient toleration of the procedure was assessed and any immediate complications were recorded. <h3>Results</h3> A total of 22 procedures were performed. 19 via the oral route and three via the anal route. The mean age of the patients was 67.1 years. The mean dosages of sedation used was Pethidine 48.75 mg and Midazolam 7.33 mg. The mean duration of procedure was 44.6 min and mean depth of insertion was 200 cm. In one patient a complete examination of the small bowel to the ileo-caecal valve was achieved. Significant pathology was identified in 11 cases and endoscopic therapy was applied in 10. The procedure was well tolerated in 73% of cases and no major complications were seen. <h3>Conclusion</h3> Our initial experience of spiral enteroscopy has shown that it is an effective method for achieving deep intubation of the small bowel via both the oral and anal routes. The procedure is generally well-tolerated with conscious sedation and appears to be more time-efficient than DBE. In our series the procedure appears safe, with no major complications seen and no evidence of small bowel mucosal trauma.
Abstract 4627: A novel computational re-analysis of published GWAS data suggests new risk loci for melanoma susceptibility
Authors: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski
Journal: Cancer Research (2015)

Abstract Purpose: Multiple melanoma GWAS have identified significant associations between single nucleotide polymorphisms (SNPs) and melanoma. As multiple variants within a given genetic locus may contribute to disease risk in different individuals, a novel computational approach to analyzing GWAS data by ‘wide-locus’ region has been shown to increase analytical power, and, in other diseases, has led to the discovery of new susceptibility loci. To date, this approach has not been applied to the study of germline genetic risk factors for melanoma. We applied this method to publically available melanoma GWAS data to identify novel germline risk factors for melanoma. Methods: We re-analyzed data from the M.D. Anderson Cancer Center melanoma GWAS study (dbGap accession: phs000187.v1.p1). In the original study, 1,977 cases and 1,047 controls of European ancestry were genotyped on an Illumina OMNI1-Quad chip. We age-matched cases and controls using “age-censoring” to account for differences in melanoma risk across different age groups. Biostatistical analysis of ‘wide-loci’ was performed across all SNPs to evaluate risk loci based on the influence of neighboring SNPs. The re-analysis was performed by individuals blinded to specific results of the original study. Genome-wide significance for each wide locus was based on number of regions examined, and was set at p&amp;lt;10−6.16. Results: Using the ‘wide-locus’ approach, we identified 21 risk loci on 16 chromosomes that met genome-wide significance. Firstly, we replicated all of the genome-wide significant findings of the original, single-SNP analysis, identifying specific SNPs at HERC2 and wide loci at MC1R and AFG3L1 that met genome-wide significance. Secondly, we identified additional SNPs not replicated to genome-wide significance in the original analysis but previously discovered in other populations. These additional SNPs reside in the MC1R, OCA2, CPNE7, DBNDD1, and AFG3L1 loci. Finally, we identified 15 new candidate loci meeting genome-wide significance, with the most significant findings located at KLK12 (associated with carcinogenesis in other cancers), PDE8 (involved with cAMP intra-cellular signaling and immune activation), and LY86 (involved in immune cell activation). Conclusion: Applying ‘wide-locus’-based statistical analysis to melanoma GWAS data replicated the findings of prior single-SNP analyses and identified multiple, new candidate risk loci worthy of further investigation. Citation Format: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski. A novel computational re-analysis of published GWAS data suggests new risk loci for melanoma susceptibility. [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 4627. doi:10.1158/1538-7445.AM2015-4627
Plasma ST2 Concentrations Predict Development of Acute Gvhd and Non-Relapse Mortality
Authors: Mark T. Vander Lugt, Thomas M. Braun, Samir Hanash, James L.M. Ferrara, Jerome Ritz, Vincent T. Ho, Joseph H. Antin, Qing Zhang, Alice Chin, Aurelie Gomez, Andrew C. Harris, John E. Levine, Sung W. Choi, Daniel Couriel, Pavan Reddy, Sophie Paczesny
Journal: Blood (2012)