Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Transplant ; 34(3): e13805, 2020 03.
Article in English | MEDLINE | ID: mdl-32003076

ABSTRACT

BACKGROUND: Transplant candidates are reluctant to accept kidneys from high Kidney Donor Profile Index (KDPI) donors. Incomplete understanding can lead to transplant delays for older transplant candidates. Patients need access to understandable information to make more informed decisions about KDPI. METHODS: We developed a KDPI-specific animation with input from six stakeholder groups and conducted a one-group pre-post study with 60 kidney transplant candidates for feasibility and acceptability to improve participant KDPI knowledge, understanding, decisional self-efficacy, and willingness to accept a KDPI > 85% kidney. Data were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: Compared with pre-animation scores, post-animation scores were significantly higher for KDPI knowledge for the entire cohort (4.6 vs 6.1, P < .001) and across different levels of age, educational attainment, health literacy, vintage, and technology access. The frequency of positive responses increased pre-post animation for KDPI understanding (55% vs 83%, P < .001) and decisional self-efficacy (47% vs 75%, P < .001). However, willingness to accept KDPI > 85% kidneys (32% vs 36%, P = .83) increased by 2%. After viewing simplifyKDPI, >90% indicated positive ratings on ease of watching, understanding, and engaging. CONCLUSION: In collaboration with stakeholders, an educational animation about KDPI was developed that was well-received and is promising to impact knowledge.


Subject(s)
Kidney Transplantation , Tissue and Organ Procurement , Cohort Studies , Humans , Kidney , Tissue Donors
2.
Transplantation ; 104(2): 326-334, 2020 02.
Article in English | MEDLINE | ID: mdl-31107826

ABSTRACT

BACKGROUND: Current educational interventions about increased risk donors (IRDs) are less effective in improving knowledge among African American (AA) kidney transplant candidates compared to other races. We aimed to develop an IRD educational animated video culturally responsive to AAs and conduct feasibility testing. METHODS: Between May 1, 2018, and June 25, 2018, we iteratively refined a culturally targeted video for AAs with input from multiple stakeholders. We then conducted a one group pre-post study between June 28, 2018, and October 29, 2018, with 40 kidney transplant candidates to assess the feasibility and acceptability of the video to improve participant knowledge and obtain feedback about IRD understanding, self-efficacy, and willingness. A mixed population was chosen to obtain race-specific acceptability data and efficacy estimates to inform a larger study. RESULTS: Three themes emerged and informed video development; misattribution of IRD to kidney quality, IRD terminology as a barrier to meaningful understanding, and variable reactions to a 1:1000 risk estimate. The study cohort was 50% AA. Median IRD knowledge increased from 5 to 7.5 (P = 0.001) overall and from 5 to 7 (P < 0.001) among AAs. The frequency of positive responses increased pre-post video for understanding of (23% vs 83%, P < 0.001), self-efficacy to decide about (38% vs 70%, P < 0.001), and willingness to accept IRD kidneys (25% vs 72%, P < 0.001). Over 90% of participants provided positive ratings on each of the 6 acceptability items. CONCLUSIONS: A culturally responsive IRD educational video was developed in collaboration with key stakeholders. Quantitative results indicate the video was acceptable and promising to impact IRD knowledge among AA and non-AA kidney transplant candidates.


Subject(s)
Decision Making , Kidney Transplantation/methods , Patient Education as Topic/methods , Risk Assessment/methods , Tissue Donors , Video Recording/methods , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
3.
J Biol Chem ; 287(46): 38569-79, 2012 Nov 09.
Article in English | MEDLINE | ID: mdl-23027863

ABSTRACT

CCN1 is a matricellular protein and a member of the CCN family of growth factors. CCN1 is associated with the development of various cancers including pancreatic ductal adenocarcinoma (PDAC). Our recent studies found that CCN1 plays a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. CCN1 mRNA and protein were detected in the early precursor lesions, and their expression intensified with disease progression. However, biochemical activity and the molecular targets of CCN1 in pancreatic cancer cells are unknown. Here we show that CCN1 regulates the Sonic Hedgehog (SHh) signaling pathway, which is associated with the PDAC progression and poor prognosis. SHh regulation by CCN1 in pancreatic cancer cells is mediated through the active Notch-1. Notably, active Notch-1is recruited by CCN1 in these cells via the inhibition of proteasomal degradation results in stabilization of the receptor. We find that CCN1-induced activation of SHh signaling might be necessary for CCN1-dependent in vitro pancreatic cancer cell migration and tumorigenicity of the side population of pancreatic cancer cells (cancer stem cells) in a xenograft in nude mice. Moreover, the functional role of CCN1 could be mediated through the interaction with the αvß3 integrin receptor. These extensive studies propose that targeting CCN1 can provide a new treatment option for patients with pancreatic cancer since blocking CCN1 simultaneously blocks two critical pathways (i.e. SHh and Notch1) associated with the development of the disease as well as drug resistance.


Subject(s)
Carcinoma/metabolism , Cysteine-Rich Protein 61/physiology , Gene Expression Regulation, Neoplastic , Hedgehog Proteins/metabolism , Pancreatic Neoplasms/metabolism , Animals , Cell Line, Tumor , Cysteine-Rich Protein 61/chemistry , Disease Progression , Drug Resistance, Neoplasm , Humans , Integrins/metabolism , Male , Mice , Mice, Nude , Models, Biological , Neoplasm Transplantation , Proteasome Endopeptidase Complex/metabolism , Receptors, Notch/metabolism , Signal Transduction
4.
J Biol Chem ; 286(50): 43475-85, 2011 Dec 16.
Article in English | MEDLINE | ID: mdl-22020939

ABSTRACT

MicroRNAs (miRNAs) are naturally occurring single-stranded RNA molecules that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in regulating processes commonly altered during tumorigenesis and metastatic growth. These include cell proliferation, differentiation, apoptosis, migration, and invasion. Among the several miRNAs, miRNA-10b (miR-10b) expression is increased in metastatic breast cancer cells and positively regulates cell migration and invasion through the suppression of the homeobox D10 (HOXD10) tumor suppressor signaling pathway. In breast metastatic cells, miR-10b expression is enhanced by a transcription factor TWIST1. We find that miR-10b expression in breast cancer cells can be suppressed by CCN5, and this CCN5 effect is mediated through the inhibition of TWIST1 expression. Moreover, CCN5-induced inhibition of TWIST1 expression is mediated through the translational inhibition/modification of hypoxia-inducible factor-1α via impeding JNK signaling pathway. Collectively, these studies suggest a novel regulatory pathway exists through which CCN5 exerts its anti-invasive function. On the basis of these findings, it is plausible that reactivation of CCN5 in miR-10b-positive invasive/metastatic breast cancers alone or in combination with current therapeutic regimens could provide a unique, alternative strategy to existing breast cancer therapy.


Subject(s)
Breast Neoplasms/metabolism , CCN Intercellular Signaling Proteins/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MicroRNAs/metabolism , Nuclear Proteins/metabolism , Repressor Proteins/metabolism , Twist-Related Protein 1/metabolism , Animals , Blotting, Western , Breast Neoplasms/genetics , CCN Intercellular Signaling Proteins/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Immunohistochemistry , In Vitro Techniques , JNK Mitogen-Activated Protein Kinases/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , Laser Capture Microdissection , Mice , Mice, Nude , MicroRNAs/genetics , Nuclear Proteins/genetics , Real-Time Polymerase Chain Reaction , Repressor Proteins/genetics , Twist-Related Protein 1/genetics
5.
Mol Cancer ; 10: 8, 2011 Jan 13.
Article in English | MEDLINE | ID: mdl-21232118

ABSTRACT

BACKGROUND: Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood. RESULTS: We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1. CONCLUSIONS: In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.


Subject(s)
Adenocarcinoma/pathology , Cysteine-Rich Protein 61/biosynthesis , Epithelial-Mesenchymal Transition , Pancreatic Neoplasms/pathology , Adenocarcinoma/metabolism , Animals , Biomarkers, Tumor , Cell Movement , Cysteine-Rich Protein 61/genetics , Gene Expression Profiling , Humans , Male , Mice , Mice, Nude , MicroRNAs/biosynthesis , MicroRNAs/genetics , Neoplasm Transplantation , Neoplastic Stem Cells/pathology , Pancreatic Neoplasms/metabolism , Paracrine Communication , RNA Interference , Side-Population Cells , Up-Regulation
6.
Mol Cancer ; 9: 209, 2010 Aug 05.
Article in English | MEDLINE | ID: mdl-20687910

ABSTRACT

BACKGROUND: New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process. RESULTS: We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells. CONCLUSION: These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.


Subject(s)
Mesenchymal Stem Cells/cytology , Neuropilin-1/physiology , Pericytes/cytology , Proto-Oncogene Proteins c-sis/physiology , Animals , Cell Differentiation , Cell Line , Culture Media, Conditioned , Mice , Mice, Inbred C3H
7.
Mol Cancer Ther ; 9(3): 523-34, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20197389

ABSTRACT

The purpose of this study was to evaluate whether 2-methoxyestradiol (2-ME(2)), a promising anticancer agent, modulates Barrett's esophageal adenocarcinoma (BEAC) cell growth and behavior through a cellular pathway involving beta-catenin in partnership with E-cadherin, which seems to play a critical role in the induction of antitumor responses in cancer cells. We found that 2-ME(2) markedly reduced the BEAC cell proliferation through regulating apoptotic machinery such as Bcl-2 and Bax. It may nullify the aggressive behavior of the cells by reducing the migratory behavior. Expressions of beta-catenin and E-cadherin and binding of these two proteins is activated in a 2-ME(2)-dependent fashion in Bic-1 cells. Moreover, overexpressions of these two proteins may be due to the stabilization of these proteins by 2-ME(2). We found that 2-ME(2)-induced antimigratory effects are mediated through the beta-catenin-E-cadherin signaling pathways. In view of these results, we determined whether 2-ME(2) reduces BEAC tumor growth. Administration of 2-ME2 significantly decreased the growth of BEAC cells xenografted on the flank of nude mice. The evidence presented points out that the effect of 2-ME(2) on beta-catenin-orchestrated signal transduction plausibly plays a multifaceted functional role to inhibit the proliferation and cell migration of 2-ME(2)-treated malignant cells and it could be a potential candidate in novel treatment strategies for Barrett's esophageal adenocarcinoma.


Subject(s)
Adenocarcinoma/pathology , Barrett Esophagus/pathology , Cadherins/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Esophageal Neoplasms/pathology , Estradiol/analogs & derivatives , beta Catenin/metabolism , 2-Methoxyestradiol , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Barrett Esophagus/drug therapy , Barrett Esophagus/metabolism , Cadherins/physiology , Cell Transformation, Neoplastic , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Estradiol/pharmacology , Estradiol/therapeutic use , Female , Humans , Male , Mice , Mice, Nude , Signal Transduction/drug effects , Signal Transduction/physiology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , beta Catenin/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...