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Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases.
Buettner S, van Vugt JLA, Gaspersz MP, Coelen RJS, Roos E, Labeur TA, Margonis GA, Ethun CG, Maithel SK, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Krasnick BA, Weber SM, Salem A, Martin RCG, Scoggins CR, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, IJzermans JNM, van Gulik TM, Pawlik TM, Groot Koerkamp B
(2017) HPB (Oxford) 19: 735-740
MeSH Terms: Aged, Bile Duct Neoplasms, Chemotherapy, Adjuvant, Female, Hepatectomy, Humans, Kaplan-Meier Estimate, Klatskin Tumor, Lymphatic Metastasis, Male, Middle Aged, Netherlands, Proportional Hazards Models, Radiotherapy, Adjuvant, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, United States
Show Abstract · Added April 10, 2018
BACKGROUND - The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.
METHODS - Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.
RESULTS - In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort.
CONCLUSION - Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.
Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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19 MeSH Terms
Quantitative Mass Spectrometry Analysis of PD-L1 Protein Expression, -glycosylation and Expression Stoichiometry with PD-1 and PD-L2 in Human Melanoma.
Morales-Betanzos CA, Lee H, Gonzalez Ericsson PI, Balko JM, Johnson DB, Zimmerman LJ, Liebler DC
(2017) Mol Cell Proteomics 16: 1705-1717
MeSH Terms: Acetylglucosamine, Adult, Aged, B7-H1 Antigen, Biopsy, Cohort Studies, Female, Glycosylation, Humans, Male, Mannose, Mass Spectrometry, Melanoma, Middle Aged, Polysaccharides, Programmed Cell Death 1 Ligand 2 Protein, Programmed Cell Death 1 Receptor, Protein Processing, Post-Translational, Skin Neoplasms, T-Lymphocytes
Show Abstract · Added March 14, 2018
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted MS platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from ∼0.03 to 1.5 fmol/microgram protein and the parallel reaction monitoring (PRM) data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody. PD-1 was measured at levels up to 20-fold lower than PD-L1, but the abundances were not significantly correlated (r = 0.062, = 0.264). PD-1 abundance was weakly correlated (r = 0.3057, = 0.009) with the fraction of lymphocytes and histiocytes in sections. PD-L2 was measured from 0.03 to 1.90 fmol/microgram protein and the ratio of PD-L2 to PD-L1 abundance ranged from 0.03 to 2.58. In 10 samples, PD-L2 was present at more than half the level of PD-L1, which suggests that PD-L2, a higher affinity PD-1 ligand, is sufficiently abundant to contribute to T-cell downregulation. We also identified five branched mannose and N-acetylglucosamine glycans at PD-L1 position N192 in all 22 samples. Extent of PD-L1 glycan modification varied by ∼10-fold and the melanoma with the highest PD-L1 protein abundance and most abundant glycan modification yielded a very low PD-L1 IHC estimate, thus suggesting that N-glycosylation may affect IHC measurement and PD-L1 function. Additional PRM analyses quantified immune checkpoint/co-regulator proteins LAG3, IDO1, TIM-3, VISTA, and CD40, which all displayed distinct expression independent of PD-1, PD-L1, and PD-L2. Targeted MS can provide a next-generation analysis platform to advance cancer immuno-therapeutic research and diagnostics.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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20 MeSH Terms
Scalp-sparing total skin electron therapy in mycosis fungoides: Case report featuring a technique without lead.
Patel CG, Ding G, Kirschner A
(2017) Pract Radiat Oncol 7: 400-402
MeSH Terms: Electrons, Humans, Male, Middle Aged, Mycosis Fungoides, Scalp, Skin Neoplasms, Treatment Outcome
Added April 2, 2019
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MeSH Terms
Treating Flu with Skin of Frog.
Crowe JE
(2017) Immunity 46: 517-518
MeSH Terms: Amino Acid Sequence, Animals, Antimicrobial Cationic Peptides, Humans, Influenza, Human, Peptides, Ranidae, Skin
Show Abstract · Added May 2, 2017
Glands in frog skin secrete substances that possess broad antimicrobial function. Holthausen et al. mined this soup of natural products and discovered a peptide that destroys diverse human influenza strains (Holthausen et al., 2017). This study points the way to the discovery of novel anti-influenza molecules targeting conserved elements on influenza surface proteins.
Copyright © 2017 Elsevier Inc. All rights reserved.
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8 MeSH Terms
The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation.
Luan L, Shi J, Yu Z, Andl T
(2017) Exp Dermatol 26: 497-504
MeSH Terms: 3' Untranslated Regions, Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Carcinoma, Basal Cell, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Cell Survival, Hair Follicle, Homeodomain Proteins, Humans, Intracellular Signaling Peptides and Proteins, Keratinocytes, Mice, Mice, Transgenic, MicroRNAs, Protein-Serine-Threonine Kinases, Skin, Skin Neoplasms, Transcription Factors, Tumor Suppressor Proteins
Show Abstract · Added June 21, 2017
Emerging evidence indicates that even subtle changes in the expression of key genes of signalling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtlety and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes, such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes. This leads to aberrant proliferation, apoptosis, and differentiation that results in altered hair growth, while the loss of miR-31 leads to increased hair growth. Through in vitro and in vivo studies, we have defined a set of conserved miR-31 target genes, including LATS2 and STK40, which serve as new players in the regulation of keratinocyte growth and hair follicle biology. LATS2 can regulate growth of keratinocytes and we have identified a function of STK40 that can promote the expression of key hair follicle programme regulators such as HR, DLX3 and HOXC13.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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22 MeSH Terms
Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.
Lazova R, Yang Z, El Habr C, Lim Y, Choate KA, Seeley EH, Caprioli RM, Yangqun L
(2017) Am J Dermatopathol 39: 689-695
MeSH Terms: Diagnosis, Differential, Female, Humans, Infant, Mass Spectrometry, Melanoma, Nevus, Pigmented, Skin Neoplasms
Show Abstract · Added April 17, 2017
Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.
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8 MeSH Terms
Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis.
Tassone B, Saoncella S, Neri F, Ala U, Brusa D, Magnuson MA, Provero P, Oliviero S, Riganti C, Calautti E
(2017) Cell Death Differ 24: 731-746
MeSH Terms: Acetylcysteine, Animals, Apoptosis, Cell Proliferation, Cells, Cultured, Cellular Senescence, Epirubicin, Glutamic Acid, Hyperplasia, Keratin-14, Keratinocytes, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Radiation Tolerance, Rapamycin-Insensitive Companion of mTOR Protein, Reactive Oxygen Species, Skin, Tetradecanoylphorbol Acetate, Transcriptome, X-Rays
Show Abstract · Added March 7, 2017
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA. Noteworthy, rictor-deficient keratinocytes displayed increased lifespan, protection from senescence, and enhanced tolerance to cellular stressors such as growth factors deprivation, epirubicin and X-ray in vitro and radioresistance in vivo. Rictor-deficient keratinocytes exhibited changes in global gene expression profiles consistent with metabolic alterations and enhanced stress tolerance, a shift in cell catabolic processes from glycids and lipids to glutamine consumption and increased production of mitochondrial reactive oxygen species (ROS). Mechanistically, the resiliency of rictor-deficient epidermal cells relies on these ROS increases, indicating stress resistance via mitohormesis. Thus, our findings reveal a new link between metabolic changes and stress adaptation of keratinocytes centered on mTORC2 activity, with potential implications in skin aging and therapeutic resistance of epithelial tumors.
3 Communities
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22 MeSH Terms
Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patients.
Deger SM, Wang P, Fissell R, Ellis CD, Booker C, Sha F, Morse JL, Stewart TG, Gore JC, Siew ED, Titze J, Ikizler TA
(2017) J Cachexia Sarcopenia Muscle 8: 500-507
MeSH Terms: Adult, Biomarkers, Blood Glucose, Body Composition, Female, Glucose, Humans, Insulin, Insulin Resistance, Leucine, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal, Organ Specificity, Renal Dialysis, Skin, Sodium
Show Abstract · Added April 6, 2017
BACKGROUND - Recent data suggest that sodium (Na ) is stored in the muscle and skin without commensurate water retention in maintenance hemodialysis (MHD) patients. In this study, we hypothesized that excessive Na accumulation would be associated with abnormalities in peripheral insulin action.
METHODS - Eleven MHD patients and eight controls underwent hyperinsulinemic-euglycemic-euaminoacidemic clamp studies to measure glucose (GDR) and leucine disposal rates (LDR), as well as lower left leg Na magnetic resonance imaging to measure Na concentration in the muscle and skin tissue.
RESULTS - The median GDR and LDR levels were lower, and the median muscle Na concentration was higher in MHD patients compared with controls. No significant difference was found regarding skin Na concentration between group comparisons. Linear regression revealed inverse relationships between muscle Na concentration and GDR and LDR in MHD patients, whereas no relationship was observed in controls. There was no association between skin Na content and GDR or LDR in either MHD patients or controls.
CONCLUSIONS - These data suggest that excessive muscle Na content might be a determinant of IR in MHD patients, although the causality and mechanisms remain to be proven.
© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.
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18 MeSH Terms
Sex differences in sodium deposition in human muscle and skin.
Wang P, Deger MS, Kang H, Ikizler TA, Titze J, Gore JC
(2017) Magn Reson Imaging 36: 93-97
MeSH Terms: Adult, Aged, Body Mass Index, Female, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal, Sex Factors, Skin, Sodium
Show Abstract · Added April 6, 2017
The aim of this work was to investigate possible sex differences in the patterns of sodium deposition between muscle and skin using sodium MRI. A total of 38 subjects were examined for comparisons: 20 males, aged 25-79years with a median age of 51; 18 females, aged 38-66years, median age 53. All subjects underwent sodium MRI scans of the calf muscles together with cross sections through four calibration standards containing known sodium contents (10mM, 20mM, 30mM, and 40mM). Tissue sodium concentrations (TSC) in muscle and skin were then calculated by comparing signal intensities between tissues and reference standards using a linear analysis. A Wilcoxon rank sum test was applied to the ΔTSC (=TSC-TSC) series of males and females to examine if they were significantly different. Finally, a multiple linear regression was utilized to account for the effects from two potential confounders, age and body mass index (BMI). We found that sodium content appears to be higher in skin than in muscle for men, however women tend to have higher muscle sodium than skin sodium. This sex-relevant sodium deposition is statistically significant (P=3.10×10) by the Wilcoxon rank sum test, and this difference in distribution seems to be more reliable with increasing age. In the multiple linear regression, gender still has a statistically significant effect (P<1.0×10) on the difference between sodium deposition in muscle and skin, while taking the effects of age and BMI into account.
Copyright © 2016 Elsevier Inc. All rights reserved.
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13 MeSH Terms
Seroprevalence of cutaneous human papillomaviruses (HPVs) among men in the multinational HPV Infection in Men study.
Rahman S, Pierce Campbell CM, Waterboer T, Rollison DE, Ingles DJ, Torres BN, Michel A, Sudenga SL, Pawlita M, Villa LL, Lazcano Ponce E, Borenstein AR, Wang W, Giuliano AR
(2016) J Gen Virol 97: 3291-3301
MeSH Terms: Adolescent, Adult, Aged, Antibodies, Viral, Brazil, Case-Control Studies, Female, Humans, Male, Mexico, Middle Aged, Papillomaviridae, Papillomavirus Infections, Prospective Studies, Seroepidemiologic Studies, Skin Diseases, Young Adult
Show Abstract · Added August 15, 2017
Data on cutaneous human papillomavirus (HPV) seroprevalence are primarily derived from skin cancer case-control studies. Few studies have reported the seroprevalence of cutaneous HPV among healthy men. This study investigated the seroprevalence of cutaneous HPV types and associated risk factors among men residing in Brazil, Mexico and the USA. Six hundred men were randomly selected from the HPV Infection in Men study. Archived serum specimens were tested for antibodies against 14 cutaneous HPV genotypes, β-HPV types (5/8/12/14/17/22/23/24/38/48), α-HPV 27, γ-HPV 4, µ-HPV1 and ν-HPV 41 using a glutathione S-transferase L1-based multiplex serology assay. Risk factor data were collected by a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression to examine factors associated with seropositivity. Overall, 65.4 % of men were seropositive to ≥1 of the 14 cutaneous HPV types, and 39.0 % were positive for ≥1 β-HPV types. Seroprevalence was 8.9, 30.9, 28.6 and 9.4 % for α-HPV 27, γ-HPV 4, µ-HPV 1 and ν-HPV 41, respectively. In multivariate analyses, seropositivity for any cutaneous HPV type was associated with higher education [adjusted odds ratio (AOR) 1.75; 95 % confidence interval (CI) 1.08-2.83], and seropositivity of any β-HPV type was significantly associated with increasing age (AOR 1.72; 95 % CI 1.12-2.63, for men aged 31-44 years vs men aged 18-30 years). Other factors associated with various type-specific cutaneous HPV seropositivity included country, circumcision and lifetime number of male sexual partners. These data indicate that exposure to cutaneous HPV is common. Future studies are needed to assess the role of cutaneous HPV in diseases.
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17 MeSH Terms