tbuckley/cabot-search huggingface dataset:
Abstract 4391: Evaluation of tumor targeting activity by elastin like polypeptide containing cell penetrating peptide and IL-4 receptor targeting peptide
Authors: Young-Jin Lee, Vijaya Sarangthem, Yun-Jae Kim, Kuen Hur, Byung-Heon Lee, Rang Woon Park
Journal: Cancer Research (2015)

Abstract The tumor specific internalization of therapeutics drug is been a great importance for cancer therapy. Targeted macromolecular carrier has been used as drug cargos since it improve the cellular uptake of cytotoxic drug in the tumor, while preventing cellular uptake by healthy tissues. Because of favorable pharmokinetic profile, elastin like polypeptide (ELPs) has been used as macromolecular drug carrier for cancer therapy. Fusion with cell-penetrating peptides (CPPs) such as TAT, assist easy penetration and internalization of macromolecular drug conjugates into wide variety of tumor types. For therapeutic peptide to be more penetrable and more effective towards specific tumor tissue, here we have designed a chimeric polypeptide cargo, TAT-AP1-ELP containing TAT, IL-4 receptor (IL4R) targeting peptide AP-1and thermal sensitive elastin-like polypeptides (ELPs). Then it was successfully expressed and purified from E coli using inverse temperature cycling method. Cellular uptake and intracellular localization of TAT-AP1-ELP was monitored through flow cytometry and confocal microscopy. Flow cytometry analysis data shown that both TAT-AP1-ELP and TAT-ELP showed various extends of penetration ability to different cancer cells but not to normal cells. Further a greater cellular uptake was observed in IL4R highly expressing cancer cells when treated with TAT-AP1-ELP compared to TAT-ELP at 37°C in dose-dependent manner. Confocal imaging verified the better cellular accumulation of TAT-AP1-ELP than TAT-ELP in IL4R highly expressing cancer cells. Importantly, the FNR 675-labeled TAT-AP1-ELP polymer showed better tumor accumulation in MDA-MB 231 xenograft mouse model. Thus in this study we demonstrate the improved activity of CPP, fused with targeting modalities in order to enhance intra tumor accumulation of therapeutic peptides. Citation Format: Young-Jin Lee, Vijaya Sarangthem, Yun-Jae Kim, Kuen Hur, Byung-Heon Lee, Rang Woon Park. Evaluation of tumor targeting activity by elastin like polypeptide containing cell penetrating peptide and IL-4 receptor targeting peptide. [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 4391. doi:10.1158/1538-7445.AM2015-4391
Rethinking How We Select Dermatology Applicants—Turning the Tide
Authors: Amy Chen, Kanade Shinkai
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Subtle but critical errors in deriving cancer signatures and markers from high-throughput molecular data: Two high-profile case studies
Authors: Constantin Aliferis, Alexander Statnikov, Chun Li, Jonathan Schildcrout, Ioannis Tsamardinos, Brian Shepherd, Frank Harrell
Journal: Clinical Cancer Research (2007)

B55   Objectives: Molecular high throughput data offers unprecedented opportunities for discovery including new diagnostics and personalized treatments in a wide range of cancers. Given the novel nature of such data, standard analysis principles either do not apply or are not sufficient. On the other hand, recent high-throughput analysis guidelines are not standardized, they have not been independently validated, and there is no consensus regarding best practices. The present study illustrates these problems in two recent cancer studies by identifying subtle yet critical errors that jeopardize the studies9 findings and conclusions. Methods to avoid such errors are proposed.  Methods: We examine the methodological validity and identify subtle errors in the highly-cited studies of [1] and [2] We test the impact of the above errors on study conclusions by re-analyzing the original and simulated data using protocols where the identified errors are systematically removed.  Results: Changes in the error metric, the methods employed for its estimation and statistical testing, and the classifier, allow previously undetected predictive signals to be identified in 6 out of 7 datasets of [1]. This refutes the original study conclusions that microarray data may not predict cancer outcomes and that studies require thousands of patients for the purpose of outcome prediction. Changes in the statistical tests for SNP selection and signature error estimation reveal that all SNPs identified by [2] are not, in fact, statistically significant at the chosen level and that the original study classifier does not perform better than chance.  Conclusions: Critical to fulfilling the promise of omics cancer research is the sound analysis of high-throughput data. The field is in dire need for validated protocols and standardized best practices in order to protect researchers from critical errors and to allow them to use their data effectively and their resources efficiently.  References:  1. Michiels S, Koscielny S, Hill C. Prediction of cancer outcome with microarrays: a multiple random validation strategy. Lancet 2005;365(9458):488-92.  2. Hu N, Wang C, Hu Y, Yang HH, Giffen C, Tang ZZ, et al. Genome-wide association study in esophageal cancer using GeneChip mapping 10K array. Cancer Res 2005 Apr 1;65(7):2542-6.
388. Hypersensitivity of MYH16 Fibers (M Fibers) to Myodegeneration in Canine Muscular Dystrophy
Authors: Yafeng Song, Andy Mead, Mihail Petrov, Phoebe Ingraham, Leon Morales, Shira Rosenblum, Joe Kornegay, Hansell H. Stedman
Journal: Molecular Therapy (2016)

Golden Retriever Muscular Dystrophy (GRMD) dogs frequently develop severe restriction to mouth opening, a condition known as trismus, as one of their earliest physical signs of the disease. Trismus is generally due to fibrosis and/or tonic contraction of the muscles of mastication, the temporalis and the masseter muscle. These muscles are primarily composed of unique myofibers exhibiting a masticatory myosin heavy chain encoded by the MYH 16 gene (M fibers). M fibers have been shown to produce the highest specific force among mammalian myofibers, based on their atypical crossbridge kinetics. Here, we show for a first time a morphological analysis of M fibers for the purposes of their classification, distribution and proportion in the masticatory muscles in normal and GRMD dogs based on immunofluorescence staining by a highly specific anti-MYH16 antibody. Our data demonstrate that in both temporalis and masseter muscles, the predominant M fibers are larger in size when compared to any other striated myofiber. A comparative histological analysis of these and other muscles in GRMD dogs demonstrates a significant relative increase in the proportion of injured, hypercontracted M fibers, a highly significant relative abundance of regenerating fibers expressing the embryonic myosin isoform encoded by the MYH3 gene, and prominent fibrosis when compared to the other affected striated muscles. These results suggest that the higher specific force developed by M fibers, due to the MYH16 encoded MyHC isoform, accelerates the fibers' rate of degeneration in response to myonecrotizing sarcolemmal injury in the absence of dystrophin. Trismus is not seen in Duchenne MD, suggesting that the deletional frameshift in the human MYH16 gene (Nature 428: 373-4, 415-8) dramatically reduces the relative rate of sarcolemmal injury. These observations may offer novel insights into the physiological role of dystrophin in striated muscles, and provide an especially sensitive test for use in experimental therapeutics in the canine models for DMD.
Association of Bax and Bcl-2 polymorphisms in Aggressiveness and Prognosis of Diffuse Large B-Cell Lymphoma
Authors: Angelo Borsarelli Carvalho Brito, Cristiane Oliveira, Marcia Toressan Delamain, Carmino Antonio De Souza, José Vassallo, Carmen Silvia Passos Lima
Journal: Blood (2014)
Abstract 2882: Calorie-induced silencing of the tumor suppressive guanylin-GUCY2C paracrine axis underlies colorectal cancer in obesity
Authors: Erik S. Blomain, Jieru E. Lin, Francheska Colón-González, Gilbert W. Kim, Terry Hyslop, Tingting Zhan, Adam E. Snook, Scott A. Waldman
Journal: Cancer Research (2015)

Abstract Despite a well-characterized epidemiological association, mechanisms underlying the relationship between obesity and colorectal cancer remain incompletely defined. An emerging paradigm suggests that colorectal cancer arises through silencing of the GUCY2C tumor suppressor by loss of the hormone guanylin, a gene product universally lost in colorectal cancer. The present studies demonstrate that obesity is linked to colorectal cancer through suppression of guanylin expression, resulting in silencing of the GUCY2C tumor suppressor and epithelial dysfunction underlying tumorigenesis. In mice, obesogenic diets suppress the expression of guanylin protein, silencing GUCY2C and increasing epithelial dysfunction including DNA damage, crypt hyperproliferation and metabolic reprogramming, associated with amplification of colorectal tumorigenesis. Mouse models uncoupling caloric intake and weight revealed that suppression of guanylin by obesogenic diets reflected ingested calories, rather than the endocrine, adipokine and inflammatory milieu associated with obesity. Further, suppression of guanylin expression by obesogenic diets in wild type mice could be reversed by switching to a lean diet. Importantly, genetically enforced tissue-specific expression of guanylin eliminated epithelial dysfunction and colorectal tumorigenesis in transgenic mice. Taken together, the present studies highlight the guanylin-GUCY2C axis as a principle mechanistic link between colorectal cancer and the increased caloric intake characterizing obesity. Moreover, they highlight a unique opportunity to prevent colorectal cancer in obese patients by oral replacement with FDA-approved GUCY2C ligands. Citation Format: Erik S. Blomain, Jieru E. Lin, Francheska Colón-González, Gilbert W. Kim, Terry Hyslop, Tingting Zhan, Adam E. Snook, Scott A. Waldman. Calorie-induced silencing of the tumor suppressive guanylin-GUCY2C paracrine axis underlies colorectal cancer in obesity. [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 2882. doi:10.1158/1538-7445.AM2015-2882
Single-Dose Pegfilgrastim after Chemotherapy Is Highly Effective in Enhancing the Mobilization of Autologous CD34+ Peripheral Blood Stem Cells in Patients with Lymphoid Malignancies and Solid Tumors.
Authors: Frank Kroschinsky, Kristina Hoelig, Uwe Platzbecker, Eberhard Schleyer, Rainer Ordemann, Astrid Haack, Markus Schaich, Martin Bornhaeuser, Gerhard Ehninger
Journal: Blood (2004)
Abstract 607: Genomic analyses and novel models validate CDK4 as a therapeutic target in imatinib-resistant dermatofibrosarcoma protuberans
Authors: Adrian Marino-Enriquez, Grant Eilers, Jeffrey Czaplinski, Mark Mayeda, Derrick Tao, Meijun Zhu, Jason L. Hornick, Ewa Sicinska, Andrew J. Wagner, Jonathan A. Fletcher
Journal: Cancer Research (2015)

Abstract Dermatofibrosarcoma protuberans (DFSP) is an aggressive PDGFB-dependent cutaneous sarcoma characterized by an infiltrative growth and high rate of local recurrence. Some DFSP progress to a higher-grade fibrosarcomatous form, with rapid growth and increased risk of metastasis. Imatinib provides clinical benefit in ∼50% of patients with unresectable or metastatic DFSP. Efficacious medical therapies have not been developed for imatinib-resistant DFSP. To this end, we established the first patient-derived models of imatinib-resistant DFSP. Cell lines and mouse xenografts were established from DFSP105, an imatinib-resistant fibrosarcomatous DFSP, and were characterized by SNP arrays and sequencing to identify targetable genomic alterations. Findings were validated in vitro and in vivo, and confirmed in a case series including 12 DFSP and 6 fibrosarcomatous DFSP. SNP analysis of DFSP105 revealed a homozygous deletion encompassing CDKN2A. The resultant p16 loss implicated CDK4/6 as a potential therapeutic target in DFSP. In further studies, we demonstrated CDKN2A homozygous deletion in 1 of 12 conventional DFSP vs. 2 of 6 fibrosarcomatous DFSP. In vitro treatment of DFSP105 with two structurally distinct selective CDK4/6 inhibitors, PD-0332991 and LEE011, led to inhibition of RB1 phosphorylation and proliferation (GI50 160 nM and 276 nM, respectively). In vivo treatment of DFSP105 with PD-0332991 (150 mg/kg) inhibited xenograft growth in mice, in comparison with imatinib-treated or untreated tumors. In conclusion, CDKN2A deletion is a novel mechanism of DFSP genetic progression. CDK4/6 inhibition is a preclinically effective treatment against p16-negative, imatinib-resistant fibrosarcomatous DFSP, and should be evaluated as a therapeutic strategy in patients with imatinib-resistant DFSP. Citation Format: Adrian Marino-Enriquez, Grant Eilers, Jeffrey Czaplinski, Mark Mayeda, Derrick Tao, Meijun Zhu, Jason L. Hornick, Ewa Sicinska, Andrew J. Wagner, Jonathan A. Fletcher. Genomic analyses and novel models validate CDK4 as a therapeutic target in imatinib-resistant dermatofibrosarcoma protuberans. [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 607. doi:10.1158/1538-7445.AM2015-607
Abstract 4755: Maximize genomic analysis through dual recovery of DNA and RNA from the same clinical sample
Authors: Angie Cheng, Natalie Hernandez, Mu Li, Charmaine San Jose Hinahon, Susan Magdaleno
Journal: Cancer Research (2015)

Abstract DNA and RNA provide valuable information in order to detect differences such as chromosomal mutations and imbalances in gene expression. Common sample types for these analyses include surgical and needle biopsies, which are very limited in material making the downstream measurement of more than one analyte rather difficult. Obtaining another biopsy, using a different section or splitting the sample can raise issues of tumor heterogeneity. Even adjacent areas of the same tumor tissue can result in a different profile so the ability to isolate multiple analytes from the same sample offer a number of benefits, which include preserving small samples and data consistency eliminating any sample to sample variation. Here we describe the efficient isolation of RNA and DNA from the same starting sample without splitting using the RecoverAll™ Multi-Sample RNA/DNA workflow, followed by versatile and informative downstream analysis. This workflow was applied to FFPE tissue samples, fine needle aspirates, degraded samples as well as fresh cultured cells from a number of different cancer types. As an example, we have shown that DNA and RNA can be isolated from the same non-small cell lung adenocarcinoma FFPE tumor sample and with the recovered analytes, both mutation analysis and fusion transcript detection can be performed by either qPCR or next-generation sequencing (NGS). Citation Format: Angie Cheng, Natalie Hernandez, Mu Li, Charmaine San Jose Hinahon, Susan Magdaleno. Maximize genomic analysis through dual recovery of DNA and RNA from the same clinical sample. [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 4755. doi:10.1158/1538-7445.AM2015-4755
Design of porous Eudragit ® L beads for floating drug delivery by wax removal technique
Authors: Kampanart Huanbutta, Tassanee Nernplod, Prasert Akkaramongkolporn, Pornsak Sriamornsak
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The aim of this study was to design porous matrix beads for floating drug delivery using enteric polymer, Eudragit® L and various amounts of waxes (0, 0.1, 0.5, 1, 2 and 3% w/w). In this study, wax containing cetyl alcohol and white petrolatum was utilized to produce pores using a wax removal technique. To prepare the beads, Eudragit® L, metronidazole and wax were dissolved in acetone and then extruded into dichloromethane. The effect of the amount of wax on the floating and drug release behavior of the Eudragit® L beads was determined. After the extruded product was immersed in dichloromethane, wax dissolved out from the formed beads, resulting in a porous structure. The prepared beads could float in simulated gastric fluid for more than 10 hours. Different amounts of wax had an effect on the drug release. We found that when the percentage of wax increased, the drug release was higher while the beads remained floating. The results suggest that Eudragit® L beads could be used as a carrier for an intragastric floating drug delivery system.
A noncomparative randomized phase II study of two dose levels of itraconazole in men with metastatic castration-resistant prostate cancer (mCRPC): A DOD/PCCTC trial.
Authors: E. S. Antonarakis, E. I. Heath, D. C. Smith, D. E. Rathkopf, A. L. Blackford, D. C. Danila, S. King, A. Frost, M. A. Carducci
Journal: Journal of Clinical Oncology (2011)

4532 Background: The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling, and delays tumor growth in murine prostate cancer xenograft models. Unlike ketoconazole, it does not suppress adrenal androgen synthesis. Methods: A phase II study of oral itraconazole in men with chemo-naïve mCRPC (30% ketoconazole-pretreated) was conducted in 4 PCCTC sites. Men were randomized to low dose (LD) or high dose (HD) itraconazole (200 or 600 mg/d) until disease progression or unacceptable toxicity. The primary endpoint was PSA progression-free survival (PPFS) at 24 wk (PSA progression = 25% PSA rise above baseline/nadir; PCWG2 criteria); a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints were progression-free survival (PFS) at 24 wk (progression = clinical/radiographic progression or death, but not rising PSA; PCWG2 criteria); median PFS; median PPFS; and max PSA decline. Exploratory outcomes were CTC enumeration, and analysis of serum testosterone (T) and DHEA-S. Results: The HD arm enrolled to completion (N=29), but the LD arm closed early (N=17) due to a prespecified futility analysis. After a median follow-up of 21.6 wk (HD arm) and 11.9 wk (LD arm), 24/29 and 17/17 men were evaluable for the primary endpoint. Efficacy results are shown below. In addition, 3/5 men (60%) in the HD arm and 2/3 men (67%) in the LD arm with unfavorable (≥5) CTCs at baseline converted to favorable (<5) CTC counts with treatment. Itraconazole did not reduce serum T or DHEA-S levels. Common toxicities (≥20%) were fatigue, nausea, anorexia, rash, and hypokalemia/hypertension/edema. Conclusions: Only the HD arm met its primary endpoint. Itraconazole 600 mg/d has single-agent activity in men with mCRPC that is not mediated by androgen suppression, and warrants further study. Endpoint Dose Value 95% CI Primary PPFS at 24 wk (%) LD 11.8 3.2–43.2 HD 48.4 32.1–73.0 Secondary PFS at 24 wk (%) LD 18.8 6.8–52.0 HD 61.1 44.1–84.6 Median PFS (wk) LD 11.9 11.9–29.1 HD 35.9 13.0–60+ Median PPFS (wk) LD 11.9 5.6–20.0 HD 17.0 12.4–29.0 ≥30% PSA decline (%) LD 5.9 0.2–28.7 HD 28.6 13.2–48.7 ≥50% PSA decline (%) LD 0 0–19.5 HD 14.3 4.0–32.7
712. Challenges of Production of NanoPlasmid with Large Gene insert using the HyperGRO™ Fermentation Process
Authors: Neha Tiwari, Jill Beilowitz, Carlos Sampson, Dorothy Peterson, Aaron Carnes, Jim Williams
Journal: Molecular Therapy (2016)

Plasmid based DNA vaccines are emerging as a promising alternative to traditional vaccines due to several advantages. One of these advantages is faster production of DNA plasmids using E.coli host cells. However, production of plasmids containing large inserts coding for antigen may have various challenges. Bacterial cell machinery may not be able to produce high cell growth during fermentation due to a large gene insert in the plasmid. A Nanoplasmid™ is a plasmid backbone designed by our collaborators, which contains reduced bacterial sequence and produces a smaller plasmid with the gene insert. With the years of expertise in Plasmid production, our company has successfully implemented the HyperGRO™ Fermentation process (an antibiotic-free, fed-batch system) for Nanoplasmid production. Plasmid pNano1, a Nanoplasmid™ with a gene insert of 3762bp, was produced using a modified HyperGRO™process. The fermentation process was successfully scaled up to 10L scale with high end cell density (OD600) of 90.1 and volumetric yield of 0.696g/L.
Identification of a Region within the Cytoplasmic Domain of Sema4D That Binds Calmodulin and Regulates Shedding of the Sema4D Exodomain in Platelets,
Authors: Peipei Mou, Zhao Zeng, Lijie Ren, Qiang Li, Kenneth M Wannemacher, Xi Mo, Lawrence F. Brass, Li Zhu
Journal: Blood (2011)
Short-term Use of Ginkgo-Flavone Glycosides Increase Risk of Gastrointestinal Bleeding: A Nationwide Population-based Case-Crossover Study
Authors: Wen-Chieh Wu, Kuan Chieh Fang, Bi-Ling Yang, Shun-Ku Lin, Hisao-Yun Hu
Journal: Clinical Gastroenterology and Hepatology (2016)
Abstract 1045: A snapshot of pan-cellular PTM in response to Sorafenib-mediated multikinase inhibition
Authors: Christian M. Loch
Journal: Cancer Research (2015)

Abstract More fundamentally than regulating specific functions or cascades, PTM affords proteins the mechanical complexity necessary to make human cells function. We believe that specifically modified forms of proteins are what conduct the cells business, and that by monitoring these “proteoforms” we can gain unique insight into cellular physiology. To test this, we treated HepG2 hepatocellular carcinoma cells with the multi-kinase inhibitor Sorafenib, and observed pharmacodynamic changes to PTM across the cellular proteome. Our novel approach, referred to as Snapshot Proteomics, revealed changes in phosphorylation to known targets of this drug. Intriquingly, we also observed changes to proteins whose roles make them strong candidates for mediating the clinical side effects of Sorafenib treatment. We also observed that the changes mediating the therapeutic response were far from the most dramatic ones observed, suggesting other, unexpected proteins as better putative pharmacodynamic biomarkers. Finally, we found that manipulating cellular phosphorylation pharmacologically had dramatic and interesting effects on other PTM pathways as well, ubiquitin in particular. This confirmed the already established crosstalk between these pathways, and supports our contention that no PTM occurs in a vacuum. Citation Format: Christian M. Loch. A snapshot of pan-cellular PTM in response to Sorafenib-mediated multikinase inhibition. [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 1045. doi:10.1158/1538-7445.AM2015-1045