scholarly journals Singer’s Nodules: Investigating the Etiopathogenetic Markers Progressing Their Pathogenesis and Clinical Manifestations

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1268
Author(s):  
Mara Pilmane ◽  
Dins Sumerags ◽  
Nityanand Jain ◽  
Shivani Jain ◽  
Gunta Sumeraga
Keyword(s):  
Vocal Cord ◽  
Clinical Manifestations ◽  
Cellular Level ◽  
Cellular Growth ◽  
Treatment Modalities ◽  
Ki 67 ◽  
Tissue Samples ◽  
Pgp 9.5 ◽  
Vocal Nodules ◽  
Nodule Tissue

Vocal nodules (or Singer’s nodules) are benign vocal cord structures which are commonly encountered by clinicians. Though phonetic trauma/abuse is thought to be the main cause of the development of vocal nodules, the exact etiopathogenesis remains unknown. Hence, we compared the immunohistochemical markers for proliferation (Ki-67), apoptosis (TUNEL), growth (EGFR), ischemia (VEGF), inflammation (IL-1α and 10), and immunoreactive innervation (PGP 9.5), in vocal nodule tissue samples obtained from 10 females (17–56 years) and vocal cord tissue from seven controls. A statistically significant increase in Ki-67, TUNEL, EGFR, VEGF and IL-1α expression was noted (p < 0.05) between nodule tissue and control tissue in both epithelial and subepithelial layers. However, the difference was non-significant for both IL-10 and PGP 9.5 (p > 0.05). All markers demonstrated moderate to strong positive correlations, except for IL-10. These findings suggest increased cellular growth and proliferation in vocal nodules coupled with a persistent presence of inflammatory and ischemic environment. Furthermore, global prevalence of apoptotic cells and decreased anti-inflammatory cytokines highlight the presence of underlying complex mechanisms in the etiopathogenesis of vocal nodules, with age having a negligible impact on the marker levels. Our results could potentially further our knowledge in understanding the effects of different treatment modalities available at the cellular level.

scholarly journals Outcome Analysis in Patients with Benign Vocal Fold Lesions

2016 ◽  
Vol 6 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Arpit Sharma ◽  
Jyoti Dabholkar ◽  
Nitish Virmani
Keyword(s):  
Vocal Cord ◽  
Vocal Fold ◽  
Treatment Modalities ◽  
Outcome Analysis ◽  
Accurate Analysis ◽  
Maximum Phonation Time ◽  
Multidimensional Assessment ◽  
Benign Vocal Fold Lesions ◽  
Sulcus Vocalis ◽  
Vocal Nodules

ABSTRACT Introduction Benign vocal cord lesions cause significant dysphonia by disrupting the normal vibratory function of the vocal fold mucosa. Multidimensional assessment of voice characteristics allows for an accurate analysis of voice impairment and can be used to assess the outcome of different treatment modalities. Aims To evaluate the outcome in patients treated for benign vocal fold lesions using multidimensional voice assessment Materials and methods Thirty adult patients with benign vocal fold lesions were treated according to standard protocols and followed up for 6 months. Voice was evaluated by visual analog scale (VAS), GRBAS (grade, roughness, breathiness, asthenia, strain) scale, maximum phonation time (MPT), S/Z ratio, and acoustic parameters using PRAAT. Pre- and posttreatment voice was compared. Results Benign lesions observed were vocal polyps (16), vocal nodules (7), vocal fold cysts (5), vocal cord papilloma (1), and sulcus vocalis (1). Mean VAS rating improved from 7.5 to 2 at 3 months and 1.6 at 6 months. Mean GRBAS score improved from 7.5 to 2.96 at 3 months and 2.3 at 6 months. Maximum phonation time increased from 9.43 seconds to 14.16 seconds at 3 months and 14.46 seconds at 6 months. S/Z ratio reduced from 1.37 to 1.16 at 3 months and 1.15 at 6 months. Jitter reduced from 1.81 to 1% at 3 months and 0.97% at 6 months; shimmer decreased from 6.07 to 2.19% at 3 months and to 2.03% at 6 months. Harmonic-to-noise ratio values improved from 8.01 to 10.78 dB at 3 months and 10.96 dB at 6 months; mean F0 increased from 207.27 to 217.89 Hz at 3 months and 219.65 Hz at 6 months. Conclusion A single measurement of voice cannot be used as a reliable outcome measure. Perceptual, aerodynamic, acoustic, and self-analysis together allow a multidimensional assessment of voice characteristics. How to cite this article Virmani N, Sharma A, Dabholkar J. Outcome Analysis in Patients with Benign Vocal Fold Lesions. Int J Phonosurg Laryngol 2016;6(1):8-13.

Biomedical applications: Pitfalls in the practice

1994 ◽  
Vol 52 ◽  
pp. 378-379
Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey
Keyword(s):  
Operating Room ◽  
Liquid Nitrogen ◽  
Lung Tissue ◽  
Biomedical Applications ◽  
Microprobe Analysis ◽  
Tissue Sample ◽  
Cellular Level ◽  
Tissue Samples ◽  
Asbestos Fibers

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.

STUDY ON CLINICAL CHARACTERISTICS AND RESULT OF TREATMENT BENIGN VOCAL CORD TUMOR WITH RIGID LARYNGEAL ENDOSCOPIC SURGERY

2012 ◽  
pp. 58-65
Author(s):  
Duy Thai Truong ◽  
Van Dung Phan ◽  
Tu The Nguyen
Keyword(s):  
Vocal Cord ◽  
Endoscopic Surgery ◽  
Clinical Characteristics ◽  
University Hospital ◽  
High Rate ◽  
Treatment Rate ◽  
Reinke’S Edema ◽  
Vocal Nodules ◽  
A Prospective Study

Objective: Study on clinical characteristics and result of treatment benign vocal cord tumor with suspensive laryngeal endoscopic surgery. Materials and Methods: A prospective study was undertaken in 43 patients who had benign vocal cord tumor and performed a suspensive laryngeal endoscopic surgery at ENT Dept. of Hue University Hospital, from 3/2010 to 5/2011. Results: The most common was group was 31 - 45 (44.2%). There was no difference of gender. Moderate hoarness was 67.4%. Classification of benign laryngeal tumor: vocal nodules (13 cases), vocal cyst (18 cases), vocal polyp (10 cases) and Reinke’s edema (2 cases). The successful treatment rate of vocal benign tumor was 88.4%. Conclusions: Suspensive laryngeal endoscopic surgery was the best method to cure benign vocal cord tumor. The surgeon had a clear operative field, easy manoeuver, high rate of cure and less complication.

Vitiligo: An Updated Narrative Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Alexander K. C. Leung ◽  
Joseph M. Lam ◽  
Kin Fon Leong ◽  
Kam Lun Hon
Keyword(s):  
Present Article ◽  
English Literature ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Calcineurin Inhibitors ◽  
Ultraviolet B ◽  
Lower Limbs ◽  
Treatment Modalities ◽  
Topical Corticosteroids ◽  
Topical Calcineurin Inhibitors

Background: Vitiligo is a relatively common acquired pigmentation disorder that can cause significant psychological stress and stigmatism. Objective: This article aims to familiarize physicians with the clinical manifestations, evaluation, diagnosis, and management of vitiligo. Methods: A Pubmed search was conducted in Clinical Queries using the key term "vitiligo". The search included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. The information retrieved from the above search was used in the compilation of the present article. The information retrieved from the above search was used in the compilation of the present article. Results: Approximately one quarter of patients with vitiligo have the onset before 10 years of age. Genetic, immunological, neurogenic and environmental factors may have a role to play in the pathogenesis. Vitiligo typically presents as acquired depigmented, well-demarcated macules/patches that appear milk- or chalk-white in color. Lesions tend to increase in number and enlarge centrifugally in size with time. Sites of predilection include the face, followed by the neck, lower limbs, trunk, and upper limbs. The clinical course is generally unpredictable. In children with fair skin, no active treatment is usually necessary other than the use of sunscreens and camouflage cosmetics. If treatment is preferred for cosmesis, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the mainstays of treatment. Conclusion: The therapeutic effect of all the treatment modalities varies considerably from individual to individual. As such, treatment must be individualized. In general, the best treatment response is seen in younger patients, recent disease onset, darker skin types, and head and neck lesions. Topical corticosteroids and calcineurin inhibitors are the treatment of choice for those with localized disease. Topical calcineurin inhibitors are generally preferred for lesions on genitalia, intertriginous areas, face, and neck. Narrowband ultraviolet B phototherapy should be considered in patients who have widespread vitiligo or those with localized vitiligo associated with a significant impact on the quality of life who do not respond to treatment with topical corticosteroids and calcineurin inhibitors.

scholarly journals Expression and clinical significance of miR-3615 in hepatocellular carcinoma

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Information ◽  
Ki 67 ◽  
Tissue Samples ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

scholarly journals Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
High Risk Group ◽  
Clinical Samples ◽  
Binding Motif ◽  
Ki 67 ◽  
Tissue Samples

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Tert Promoter Mutations ◽  
Formalin Fixed Paraffin Embedded ◽  
Penile Squamous Cell Carcinoma ◽  
Promoter Mutations

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

Antitumor immune response is associated with favorable survival in GEP-NEN G3

2021 ◽  
Vol 28 (10) ◽  
pp. 683-693
Author(s):  
Vivian Rosery ◽  
Henning Reis ◽  
Konstantinos Savvatakis ◽  
Bernd Kowall ◽  
Martin Stuschke ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Spatial Interaction ◽  
Antitumor Immune Response ◽  
Cytotoxic T Cell ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed formalin-fixed paraffin-embedded samples from 37 patients with GEP-NEN G3 by immunohistochemistry and multiplex immunofluorescence to address the abundance and spatial interaction of relevant immune subsets. We focused on the expression of immune checkpoint molecules PD-1 and PD-L1, the cytotoxic T-cell marker CD8, and the tumor-associated macrophage marker CD206. Findings were correlated with overall survival (OS) from the date of a cancer diagnosis. Patients with PD-L1-positive tumors (CPS ≥ 1) and intense PD-1+CD8+ immune cell infiltration showed the most favorable median OS. Multiplex immunofluorescence staining of ten representative tissue samples illustrated intratumoral heterogeneity of PD-L1 expression. Dense PD-1+CD8+ immune cell infiltrates were observed in PD-L1-positive tumor regions but not in PD-L1-negative regions. Proximity analysis revealed a spatial interaction between PD-1+CD8+ cells and PD-L1-positive cells. Our data suggest a pre-existing antitumor immune response in the TME in a subgroup of GEP-NEN G3. This supports a targeted clinical exploration of immunotherapeutic approaches.

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