tbuckley/cabot-search huggingface dataset:
Melanoma MicroRNA Signature Predicts Post-Recurrence Survival
Authors: Miguel F. Segura, Ilana Belitskaya-Lévy, Amy E. Rose, Jan Zakrzewski, Avital Gaziel, Douglas Hanniford, Farbod Darvishian, Russell S. Berman, Richard L. Shapiro, Anna C. Pavlick, Iman Osman, Eva Hernando
Journal: Clinical Cancer Research (2010)

To identify a melanoma microRNA (miRNA) expression signature that is predictive of outcome and then evaluate its potential to improve risk stratification when added to the standard-of-care staging criteria.Total RNA was extracted from 59 formalin-fixed paraffin-embedded melanoma metastases and hybridized to miRNA arrays containing 911 probes. We then correlated miRNA expression with post-recurrence survival and other clinicopathologic criteria.We identified a signature of 18 miRNAs whose overexpression was significantly correlated with longer survival, defined as more than 18 months post-recurrence survival. Subsequent cross-validation showed that a small subset of these miRNAs can predict post-recurrence survival in metastatic melanoma with an estimated accuracy of 80.2% (95% confidence interval, 79.8-80.6%). In contrast to standard-of-care staging criteria, a six-miRNA signature significantly stratified stage III patients into "better" and "worse" prognostic categories, and a multivariate Cox regression analysis revealed the signature to be an independent predictor of survival. Furthermore, we showed that most miRNAs from the signature also showed differential expression between patients with better and worse prognoses in the corresponding paired primary melanoma.MiRNA signatures have potential as clinically relevant biomarkers of prognosis in metastatic melanoma. Our data suggest that molecularly based models of risk assessment can improve the standard staging criteria and support the incorporation of miRNAs into such models.
High-Dose Therapy Improves Progression-Free Survival and Survival in Relapsed Follicular Non-Hodgkin’s Lymphoma: Results From the Randomized European CUP Trial
Authors: Harry C. Schouten, Wendi Qian, Stein Kvaloy, Adolfo Porcellini, Hans Hagberg, Hans Erik Johnsen, Jeanette K. Doorduijn, Matthew R. Sydes, Gunnar Kvalheim
Journal: Journal of Clinical Oncology (2003)

To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin's lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS.Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P).Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were.0037 and.079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively.HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.
Increased Sentinel Lymph Node Lymphangiogenesis is Associated with Nonsentinel Axillary Lymph Node Involvement in Breast Cancer Patients with a Positive Sentinel Node
Authors: Gert G. Van den Eynden, Melanie K. Vandenberghe, Pieter-Jan H. van Dam, Cecile G. Colpaert, Peter van Dam, Luc Y. Dirix, Peter B. Vermeulen, Eric A. Van Marck
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Lymph node (LN) lymphangiogenesis has recently been shown to be important in the premetastatic niche of sentinel LNs. To study its role in the further metastatic spread of human breast cancer, we investigated the association of angiogenesis and lymphangiogenesis in sentinel LN metastases with the presence of nonsentinel LN metastases in breast cancer patients with a positive sentinel LN. Experimental Design: Angiogenesis and lymphangiogenesis—quantified as endothelial cell proliferation fraction (ECP%) and lymphatic ECP fraction (LECP%)—were assessed in sentinel LN metastases of 65 T1/T2 patients with breast cancer using CD34/Ki67 and D2-40/Ki67 immunohistochemical double stains. Correlations were analyzed between nonsentinel LN status, LECP%, and other clinicopathologic variables (number of involved sentinel LNs, size of the primary tumor and LN metastasis, presence of lymphovascular invasion in the primary tumor, and of extracapsular growth in the sentinel LN metastasis). Results: Thirty seven out of 65 patients (56.9%) had at least one involved nonsentinel LN. Size of the sentinel LN metastasis (P = 0.001), lymphovascular invasion (P = 0.02), extracapsular growth (P = 0.02), and LECP% (P = 0.01) were correlated with a positive nonsentinel LN status. The multivariate logistic regression model retained high LECP% (odds ratios = 4.2, P = 0.01) and the presence of extracapsular growth (odds ratios = 3.38, P = 0.04) as independently associated with the presence of nonsentinel LN metastases. Conclusions: Increased sentinel LN metastasis lymphangiogenesis is associated with metastatic involvement of nonsentinel axillary LNs. These are the first data sustaining the hypothesis that sentinel LN lymphangiogenesis is involved in further metastatic spread of human breast cancer.
The Effect on Melanoma Risk of Genes Previously Associated With Telomere Length
Authors: Mark M. Iles, D. Timothy Bishop, John C. Taylor, Nicholas K. Hayward, Myriam Brossard, Anne E. Cust, Alison M. Dunning, Jeffrey E. Lee, Eric K. Moses, Lars A. Akslen, Per A. Andresen, Marie-Françoise Avril, Esther Azizi, Giovanna Bianchi Scarrà, Kevin M. Brown, Tadeusz Dębniak, David E. Elder, Eitan Friedman, Paola Ghiorzo, Elizabeth M. Gillanders, Alisa M. Goldstein, Nelleke A. Gruis, Johan Hansson, Mark Harland, Per Helsing, Marko Hočevar, Veronica Höiom, Christian Ingvar, Peter A. Kanetsky, Maria Teresa Landi, Julie Lang, G. Mark Lathrop, Jan Lubiński, Rona M. Mackie, Nicholas G. Martin, Anders Molven, Grant W. Montgomery, Srdjan Novaković, Håkan Olsson, Susana Puig, Joan Anton Puig-Butille, Graham L. Radford-Smith, Juliette Randerson-Moor, Nienke van der Stoep, Remco van Doorn, David C. Whiteman, Stuart MacGregor, Karen A. Pooley, Sarah V. Ward, Graham J. Mann, Christopher I. Amos, Paul D. P. Pharoah, Florence Demenais, Matthew H. Law, Julia A. Newton Bishop, Jennifer H. Barrett
Journal: JNCI Journal of the National Cancer Institute (2014)

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10-9, two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.
603 GUT MICROBIOTA DYSBIOSIS IS ASSOCIATED WITH INFLAMMATION AND BACTERIAL TRANSLOCATION IN MICE WITH CCL4-INDUCED FIBROSIS
Authors: I. Gómez-Hurtado, A. Santacruz, G. Peiró, P. Zapater, A. Gutiérrez, M. Pérez-Mateo, J. Such, Y. Sanz, R. Francés
Journal: Journal of Hepatology (2011)
A Unique Subset of Self-specific Intraintestinal T Cells Maintains Gut Integrity
Authors: Philippe Poussier, Terri Ning, Diponkar Banerjee, Michael Julius
Journal: The Journal of Experimental Medicine (2002)

Lymphocytes residing in the intestinal epithelium are exclusively T cells and account for one of the largest collection of T cells in the organism. However, their function remains obscure. We and others have shown that the development of intestinal intraepithelial T cells is compromised in mutant mice prone to chronic intestinal inflammation. These results led us to directly assess their role in regulating the development of colitis secondary to transfer of primary splenic TCRalphabeta(+)CD4(+)CD45RB(hi) T cells into severe combined immunodeficiency (SCID) mice. Here we demonstrate that prior reconstitution of SCID recipients with intraintestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells prevents disease, and does so in an interleukin (IL)-10-dependent fashion. In contrast, reconstitution with either TCRgammadelta(+) or TCRalphabeta(+)CD4(-) CD8alpha(+)beta(+) intestinal T cells did not prevent colitis. TCRalphabeta(+)CD4(-)8alpha(+)beta(-) T cells are unique to the intestinal epithelium of both rodents and humans. Previous repertoire analyses of TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells revealed a high proportion of cells expressing high affinity, self-specific TCR within this subset. We demonstrate that monoclonal, self specific TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) cells derived from TCR transgenic mice also prevent the onset of colitis. Thus, intestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells, selected based on their self-reactivity, maintain gut integrity in a IL-10-dependent fashion.
Cytolytic T cell granules. Isolation, structural, biochemical, and functional characterization.
Authors: E R Podack, P J Konigsberg
Journal: The Journal of Experimental Medicine (1984)

The cytoplasmic, dense granules of cloned T cell lines were isolated and analyzed for their functional and biochemical properties. Isolated granules of approximately 90% homogeneity, in the presence of Ca, effect strong tumoricidal and hemolytic activity. Tumor cell lysis is complete in less than 30 min, with less than 2 micrograms granule protein corresponding to a killer/target ratio of 3-6:1 by assuming 50% yield for granule isolation. The granules contain a set of unique proteins, responsible for cytolytic activity and designated K1 to K6, in the molecular weight range of 14,000 to 75,000, as defined by sodium dodecyl sulfate (SDS) polyacrylamide slab gel analysis under reducing and nonreducing conditions. Cytolysis mediated by isolated granules is accompanied by the assembly of tubular complexes of 160 A (poly P1) and of approximately 70 A width (poly P2) that are inserted into membranes and form ultrastructural membrane lesions. As shown by immunofluorescence and by Percoll gradient fractionation, cytolytic granules are detected in cells of cytolytic T cell lineage and not in the T cell lymphomas E14 and S194. Poly perforin 1 assembled by CTLL-2 upon stimulation with concanavalin A (Con A) and phorbol myristate acetate (PMA) was isolated by detergent extraction and gel filtration. Poly P1 is composed of disulfide-linked subunits that, after reduction, co-migrate with certain granule proteins. The results are compatible with the hypothesis that the dense granules of cytolytic T cells contain cytolytic proteins that polymerize to disulfide-linked tubular poly perforins in a Ca-dependent reaction and may cause cytolysis by membrane insertion and transmembrane channel formation.
Short-term increase of plasma free fatty acids does not interfere with intrinsic mitochondrial function in healthy young men
Authors: Myrte Brands, Joris Hoeks, Hans P. Sauerwein, Mariette T. Ackermans, Margriet Ouwens, Nicolette M. Lammers, Mart N. van der Plas, Patrick Schrauwen, Albert K. Groen, Mireille J. Serlie
Journal: Metabolism (2011)
SRST2: Rapid genomic surveillance for public health and hospital microbiology labs
Authors: Michael Inouye, Harriet Dashnow, Lesley-Ann Raven, Mark B Schultz, Bernard J Pope, Takehiro Tomita, Justin Zobel, Kathryn E Holt
Journal: Genome Medicine (2014)

Rapid molecular typing of bacterial pathogens is critical for public health epidemiology, surveillance and infection control, yet routine use of whole genome sequencing (WGS) for these purposes poses significant challenges. Here we present SRST2, a read mapping-based tool for fast and accurate detection of genes, alleles and multi-locus sequence types (MLST) from WGS data. Using >900 genomes from common pathogens, we show SRST2 is highly accurate and outperforms assembly-based methods in terms of both gene detection and allele assignment. We include validation of SRST2 within a public health laboratory, and demonstrate its use for microbial genome surveillance in the hospital setting. In the face of rising threats of antimicrobial resistance and emerging virulence among bacterial pathogens, SRST2 represents a powerful tool for rapidly extracting clinically useful information from raw WGS data. Source code is available from http://katholt.github.io/srst2/.
Capillary fluid filtration. Starling forces and lymph flow.
Authors: A E Taylor
Journal: Circulation Research (1981)

STARLING (1894STARLING ( , 1896) ) described the basic forces responsible for producing fluid shifts between the circulating blood and the surrounding tissue spaces.On page 324 of his classical article entitled "On the absorption of fluids from the connective tissue spaces," Starling described how capillary pressure determines transudation into the tissues and the osmotic pressure of the proteins determines absorption from the tissues.The paper also investigated how tissue pressure affects absorption, and Starling came to the correct conclusion that tissue pressure would not cause fluid to be absorbed from the tissue unless this pressure was not transmitted to the veins.Starling also recognized that a small amount of fluid was lost continually from the circulation ("frictional resistance of the capillary wall") and formed lymph, but believed that this was small and that the forces tending to move fluid out of and into the circulation were almost balanced.Finally, Starling postulated that tissue colloidal osmotic pressure decreased following elevation of capillary pressure and provided the opposing forces to limit transudation of fluid into interstitial spaces.Thus, Starling defined the basic forces responsible for maintaining fluid balance between the microcirculation and interstitium, and physiologists have termed tissue pressure (P t ), capillary pressure (P c ), plasma colloidal osmotic (TT P ), and tissue colloidal osmotic (wt) pressure as Starling forces.However, a mathematical relationship between those forces was not formulated by Starling in his original papers.Staub (1978) presents a delightful discourse concerning the historical development of the mathematical description of the Starling hypothesis
Extent of Resection of Glioblastoma Revisited: Personalized Survival Modeling Facilitates More Accurate Survival Prediction and Supports a Maximum-Safe-Resection Approach to Surgery
Authors: Nicholas F. Marko, Robert J. Weil, Jason L. Schroeder, Frederick F. Lang, Dima Suki, Raymond E. Sawaya
Journal: Journal of Clinical Oncology (2014)

Approximately 12,000 glioblastomas are diagnosed annually in the United States. The median survival rate for this disease is 12 months, but individual survival rates can vary with patient-specific factors, including extent of surgical resection (EOR). The goal of our investigation is to develop a reliable strategy for personalized survival prediction and for quantifying the relationship between survival, EOR, and adjuvant chemoradiotherapy.We used accelerated failure time (AFT) modeling using data from 721 newly diagnosed patients with glioblastoma (from 1993 to 2010) to model the factors affecting individualized survival after surgical resection, and we used the model to construct probabilistic, patient-specific tools for survival prediction. We validated this model with independent data from 109 patients from a second institution.AFT modeling using age, Karnofsky performance score, EOR, and adjuvant chemoradiotherapy produced a continuous, nonlinear, multivariable survival model for glioblastoma. The median personalized predictive error was 4.37 months, representing a more than 20% improvement over current methods. Subsequent model-based calculations yield patient-specific predictions of the incremental effects of EOR and adjuvant therapy on survival.Nonlinear, multivariable AFT modeling outperforms current methods for estimating individual survival after glioblastoma resection. The model produces personalized survival curves and quantifies the relationship between variables modulating patient-specific survival. This approach provides comprehensive, personalized, probabilistic, and clinically relevant information regarding the anticipated course of disease, the overall prognosis, and the patient-specific influence of EOR and adjuvant chemoradiotherapy. The continuous, nonlinear relationship identified between expected median survival and EOR argues against a surgical management strategy based on rigid EOR thresholds and instead provides the first explicit evidence supporting a maximum safe resection approach to glioblastoma surgery.
Pharmacokinetics and Antitumor Efficacy of XMT-1001, a Novel, Polymeric Topoisomerase I Inhibitor, in Mice Bearing HT-29 Human Colon Carcinoma Xenografts
Authors: Mark D. Walsh, Suzan K. Hanna, Jeremy Sen, Sumit Rawal, Carolina B. Cabral, Alex V. Yurkovetskiy, Robert J. Fram, Timothy B. Lowinger, William C. Zamboni
Journal: Clinical Cancer Research (2012)

To evaluate the pharmacokinetics and tissue disposition of macromolecular camptothecin (CPT) drug conjugate, XMT-1001, and irinotecan (CPT-11) in mice bearing HT-29 xenograft tumors.The antitumor efficacy of XMT-1001 was evaluated in the mouse HT-29 human colon carcinoma xenograft model. XMT-1001 was administered intravenously to female athymic nude (nu/nu) mice bearing established HT-29 xenograft tumors (n = 10) at 15, 30, and 60 mg CPT equivalents/kg on weekly or biweekly schedules. The tumor growth inhibition and tumor growth delay endpoints were used for efficacy evaluation. In the pharmacokinetic study, XMT-1001 was administered intravenously at a pharmacologically relevant dose of 60 mg CPT equivalents/kg × 1 via tail vein or an equimolar dose of CPT-11 at 100 mg/kg i.p. × 1. Mice (n = 3 per time point) were euthanized from 0.083 to 336 hours after XMT-1001 administration and from 0.083 to 24 hours after CPT-11. Plasma, tumor, and tissues were collected from all animals. A liquid chromatography-tandem mass spectrometry assay was used to measure XMT-1001, conjugate release products, CPT-20-O-(N-succinimido-glycinate; CPT-SI) and CPT-20-O-(N-succinamidoyl-glycinate; CPT-SA), and CPT.After XMT-1001 administration, the majority of the plasma exposure is accounted for by conjugated CPT. XMT-1001 exhibited a prolonged exposure of conjugated drug, active conjugate primary release products, CPT-SI and CPT-SA, and active CPT, which was associated with greater antitumor response compared with CPT-11.XMT-1001 provides an extended systemic and tumor exposure of conjugated drug and shows improved antitumor effect compared with CPT-11.
First-in-Human Phase 0 Trial of Oral 5-Iodo-2-Pyrimidinone-2′-Deoxyribose in Patients with Advanced Malignancies
Authors: Shivaani Kummar, Larry Anderson, Kimberly Hill, Eva Majerova, Deborah Allen, Yvonne Horneffer, S. Percy Ivy, Larry Rubinstein, Pamela Harris, James H. Doroshow, Jerry M. Collins
Journal: Clinical Cancer Research (2013)

Iododeoxyuridine (IdUrd), a halogenated nucleoside analog, produced clinical responses when administered as a radiosensitizer via continuous intravenous (c.i.v.) infusion over the course of radiotherapy. We conducted a phase 0 trial of 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR), an oral prodrug of IdUrd, in patients with advanced malignancies to assess whether the oral route was a feasible alternative to c.i.v. infusion before embarking on large-scale clinical trials. Plasma concentrations of IPdR, IdUrd, and other metabolites were measured after a single oral dose of IPdR.
Computer-Aided Decision Support Systems for Endoscopy in the Gastrointestinal Tract: A Review
Authors: Michael Liedlgruber, Andreas Uhl
Journal: IEEE Reviews in Biomedical Engineering (2011)

Today, medical endoscopy is a widely used procedure to inspect the inner cavities of the human body. The advent of endoscopic imaging techniques-allowing the acquisition of images or videos-created the possibility for the development of the whole new branch of computer-aided decision support systems. Such systems aim at helping physicians to identify possibly malignant abnormalities more accurately. At the beginning of this paper, we give a brief introduction to the history of endoscopy, followed by introducing the main types of endoscopes which emerged so far (flexible endoscope, wireless capsule endoscope, and confocal laser endomicroscope). We then give a brief introduction to computer-aided decision support systems specifically targeted at endoscopy in the gastrointestinal tract. Then we present general facts and figures concerning computer-aided decision support systems and summarize work specifically targeted at computer-aided decision support in the gastrointestinal tract. This summary is followed by a discussion of some common issues concerning the approaches reviewed and suggestions of possible ways to resolve them.
Lymphatic Mapping and Sentinel Lymph Node Biopsy in Patients with Breast Cancer
Authors: Charles E. Cox, Siddharth S. Bass, Christa R. McCann, Ni Ni K. Ku, Claudia Berman, Kara Durand, Monica Bolano, Jessica Wang, Eric Peltz, Sarah Cox, Christopher Salud, Douglas S. Reintgen, Gary H. Lyman
Journal: Annual Review of Medicine (2000)

▪ Abstract The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to the SLN. In addition to reviewing the literature, this chapter describes our lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute with 1147 breast cancer patients. Our results, in addition to a meta-analysis of data from 12 institutions comprising an additional 1842 patients undergoing complete axillary dissection, demonstrate that SLN biopsy is an accurate method of axillary staging. Although the results from small series may exaggerate the probability of false negative results, the risk of nodal disease based on tumor size and other risk factors should be evaluated when considering the results of SLN sampling.
Aortic valve replacement for severe aortic regurgitation caused by idiopathic giant cell aortitis.
Authors: A S Soorae, F McKeown, J Cleland
Journal: Thorax (1980)

Giant cell aoritis occurred in a 25-year-old woman, with absent pulses in the left arm and severe aortic regurgitation from dilatation of the valvar annulus. The aortic valve was replaced by a Starr-Edwards prosthesis, and the patient was treated with steroids. Five years later, she continues asymptomatic and haemodynamically stable. The left brachial and radial pulses have returned.