scholarly journals Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Igor Sterle ◽  
Daša Zupančič ◽  
Rok Romih
Keyword(s):  
Transient Receptor Potential ◽  
Expression Patterns ◽  
Terminal Differentiation ◽  
Sensory Function ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Apical Surface ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Normal Urothelium

Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

scholarly journals The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3160
Author(s):  
Joseph Bouskila ◽  
Maxime Bleau ◽  
Catarina Micaelo-Fernandes ◽  
Jean-François Bouchard ◽  
Maurice Ptito
Keyword(s):  
G Protein ◽  
Visual Information ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Expression Patterns ◽  
Retinal Function ◽  
Age Related Macular Degeneration ◽  
Transient Receptor Potential Vanilloid ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.

scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Myometrial Invasion ◽  
Staging System ◽  
Stage I ◽  
Low Grade ◽  
List Type ◽  
High Grade ◽  
High Grade Carcinoma ◽  
Concordance Probability ◽  
Grade 3

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

scholarly journals Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Huang ◽  
Fei Ren ◽  
Shujuan Ni ◽  
Cong Tan ◽  
Weiwei Weng ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Expression Patterns ◽  
Biological Behavior ◽  
Low Grade ◽  
High Grade ◽  
Clinicopathologic Characteristics ◽  
Signet Ring ◽  
Cancer Transcriptome ◽  
Male Patients ◽  
Pan Cancer

Abstract Background and aim Amphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. This study characterized the clinicopathologic and survival analysis of this tumor, further compared the genetic diversities among amphicrine carcinoma and other tumors. Materials and methods The clinicopathologic characteristics and survival outcomes of amphicrine carcinoma in this study were analyzed. The pan-cancer transcriptome assay was utilized to compare the genetic expression profile of this entity with that of conventional adenocarcinoma or neuroendocrine tumors. Results Ten cases (all in male patients) were identified in the stomach or intestine, with a median patient age of 62 years. There were characteristic patterns in the tumors: tubular, fusion or single-file growth of goblet- or signet ring-like cells. Four tumors were classified as low-grade and 6 as high-grade according to the histologic architecture. All cases were positive for neuroendocrine markers (synaptophysin and chromogranin A) and showed intracellular mucin in the amphicrine components. Four cases exhibited mRNA expression patterns showing transcriptional homogeneity with conventional adenocarcinomas and genetic diversity from neuroendocrine tumors. During the follow-up period, 3 patients died of disease, all of whom had high-grade tumors. Patients with high-grade amphicrine carcinoma had worse outcomes than those with low-grade tumors. Conclusions This study confirms the morphological, immunostaining and transcriptome alterations in amphicrine carcinoma distinct from those in conventional adenocarcinomas and neuroendocrine tumors, but additional studies are warranted to determine the biological behavior and therapeutic response.

Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma

2002 ◽  
Vol 41 (3) ◽  
pp. 250-259 ◽  
Author(s):  
R H W Simpson ◽  
J S Reis-Filho ◽  
E M Pereira ◽  
A C Ribeiro ◽  
A Abdulkadir
Keyword(s):  
Salivary Glands ◽  
Low Grade ◽  
High Grade ◽  
High Grade Carcinoma

MOLECULAR MARKERS IN OSTEOSARCOMA – A cDNA MICROARRAY AND RT-PCR ANALYSIS

2005 ◽  
Vol 09 (02) ◽  
pp. 77-84
Author(s):  
Meera R. Hameed ◽  
Tao-Zhen Lin ◽  
Frederick Coffman ◽  
Marion C. Cohen ◽  
Helen Fernandes ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Cdna Microarray ◽  
Expression Patterns ◽  
Bone Neoplasms ◽  
Poor Response ◽  
Pcr Analysis ◽  
Low Grade ◽  
High Grade ◽  
Cdna Microarray Analysis ◽  
Response To Chemotherapy

Osteosarcomas account for about 20% of all primary bone neoplasms, and affect predominantly adolescents. Important prognostic factors include the presence or absence of metastases at the time of presentation and tumor response to neoadjuvant chemotherapy. Biological markers predicting metastases and chemoresistance are not well characterized. cDNA microarray analysis enables one to examine the expression of thousands of genes in tumor samples. We performed cDNA microarray analysis of histologically low and high grade areas in osteosarcomas to identify gene expression patterns which may depict aggressive behavior. Microarray analysis with 1.2 K cancer array revealed many differentially expressed genes (both upregulated and downregulated), in histologically high grade tumor samples as compared with a low grade sample. Selected up and down regulated markers in the high grade sarcomas were tested in a group of high grade osteosarcomnas (OS) with varying responses to chemotherapy. Of the multiple markers analyzed, ezrin, a member of the ERM family of membrane-cytoskeleton linkers showed an expression pattern statistically significant between tumors with good response to chemotherapy compared with tumors with poor response (p = 0.036). We discuss our findings, with current review of literature.

Applying the Paris System for Reporting Urine Cytology Increases the Rate of Atypical Urothelial Cells in Benign Cases: A Need for Patient Management Recommendations

2016 ◽  
Vol 61 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Rosario Granados ◽  
Joanny A. Duarte ◽  
Teresa Corrales ◽  
Encarnación Camarmo ◽  
Paloma Bajo
Keyword(s):  
False Positive Rate ◽  
Urine Cytology ◽  
Urinary Cytology ◽  
Low Grade ◽  
High Grade ◽  
Abnormal Cytology ◽  
Positive Rate ◽  
High Grade Carcinoma ◽  
Management Recommendations ◽  
The Impact

The Paris System (TPS) for reporting urinary cytology attempts to unify the terminology in this field. Objectives: To analyze the impact of adopting TPS by measuring nomenclature agreement and cytohistological correlation. Materials and Methods: Voided urine liquid-based cytology samples corresponding to 149 biopsy-proven cases (76 high-grade carcinomas, 40 low-grade carcinomas, and 33 benign lesions), were reclassified by the same pathologist using TPS. Diagnostic agreement and sensitivity for both nomenclature systems was measured. Results: When using TPS, the rate of atypical samples increased 8 times (from 3 to 24.2%) in benign cases, 10 times (from 2.5 to 25%) in low-grade carcinomas, and 2.4 times (from 6.6 to 15.8%) in high-grade carcinomas. The false-positive rate (abnormal cytology in negative or low-grade carcinoma cases) increased from 11 to 34.2%. Sensitivity was higher (63 vs. 49%) with TPS at the expense of a lower specificity (73 vs. 91%). The agreement between both nomenclatures was moderate for negative and high-grade carcinoma cases (k = 0.42 and 0.56, respectively) and weak for low-grade tumors (k = 0.35). Conclusions: Adopting TPS for reporting urine cytology results in a considerable increase in atypical diagnoses, improving sensitivity but lowering specificity. Appropriate management recommendations for patients with an atypical cytological diagnosis are required.

scholarly journals Acute and subacute effects of oropharyngeal sensory stimulation with TRPV1 agonists in older patients with oropharyngeal dysphagia: a biomechanical and neurophysiological randomized pilot study

2019 ◽  
Vol 12 ◽  
pp. 175628481984204 ◽  
Author(s):  
Noemí Tomsen ◽  
Omar Ortega ◽  
Laia Rofes ◽  
Viridiana Arreola ◽  
Alberto Martin ◽  
...  
Keyword(s):  
Older Patients ◽  
Transient Receptor Potential ◽  
Oropharyngeal Dysphagia ◽  
Receptor Potential ◽  
Sensory Stimulation ◽  
Event Related Potential ◽  
Sensory Function ◽  
Transient Receptor Potential Vanilloid ◽  
Laryngeal Vestibule ◽  
Transient Receptor

Background: Older people with oropharyngeal dysphagia (OD) present a decline in pharyngeal sensory function. The aim of this proof-of-concept study was to assess the biomechanical and neurophysiological effects of acute and subacute oropharyngeal sensory stimulation with transient receptor potential vanilloid 1 (TRPV1) agonists (capsaicinoids) in older patients with OD. Methods: We studied the effect of a single dose versus multiple doses (2 weeks) of oral capsaicin treatment (10–5 M) or placebo in 28 older patients with OD (81.2 ± 4.6 years) using videofluoroscopy (penetration-aspiration scale [PAS], timing of swallow response) and electroencephalography (EEG) (latency and amplitude of pharyngeal event-related potential [ERP]). Results: Acute stimulation by capsaicinoids 10–5 M did not improve swallow function and did not produce significant changes in pharyngeal ERP. In contrast, after 10 days of treatment, patients presented a clinically relevant and statistically significant reduction in the laryngeal vestibule closure (LVC) time (22.5%, p = 0.042), and in the PAS (24.2%, p = 0.038), compared with the placebo group. EEG results showed a reduction in the latency of the N1 peak (28.6%, p = 0.007) and an increase of the amplitude of the P1-N2 (59.4%, p = 0.038) and the N2-P2 (43.6%, p = 0.050) peaks. We observed a strong and significant correlation between the reduction in the latency of the N1 peak and change in LVC time after subacute treatment ( r = 0.750, p = 0.003). Conclusions: After 2 weeks of treatment, oropharyngeal sensory stimulation with capsaicinoids induced cortical changes that were correlated with improvements in swallowing biomechanics in older patients with OD. These results further show that sensory stimulation by TRPV1 agonists can become a useful pharmacological treatment for older patients with OD.

scholarly journals Shaoyao-Gancao Decoction Relieves Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome via Inactivating Transient Receptor Potential Vanilloid Type 1 and Reducing Serotonin Synthesis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yun-Yun Shao ◽  
Yi-Ting Guo ◽  
Jian-ping Gao ◽  
Jun-Jin Liu ◽  
Zhuang-Peng Chang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Cell Count ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Visceral Hyperalgesia ◽  
Transient Receptor ◽  
Irritable Bowel ◽  
In Cells

Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.

scholarly journals TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?

2019 ◽  
Vol 7 (8) ◽  
pp. 82 ◽  
Author(s):  
Dorte X. Gram ◽  
Josefine Fribo ◽  
Istvan Nagy ◽  
Carsten Gotfredsen ◽  
Ana Charrua ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oral Glucose ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Oral Glucose Tolerance ◽  
Transient Receptor ◽  
Low Grade Inflammation

With a global prevalence among adults over 18 years of age approaching 9%, Type 2 diabetes mellitus (T2DM) has reached pandemic proportions and represents a major unmet medical need. To date, no disease modifying treatment is available for T2DM patients. Accumulating evidence suggest that the sensory nervous system is involved in the progression of T2DM by maintaining low-grade inflammation via the vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). In this study, we tested the hypothesis that TRPV1 is directly involved in glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1−/−) and their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, Zucker obese rats were given the small molecule TRPV1 antagonist, N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and glucose-stimulated insulin secretion was improved by both genetic inactivation (Trpv1−/− mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, the improved glucose tolerance was accompanied by a reduction in inflammatory markers in the mesenteric fat, suggesting that blockade of low-grade inflammation contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We propose that TRPV1 could be a promising therapeutic target in T2DM by improving glucose intolerance and correcting dysfunctional insulin secretion.

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