GLI-1 polymorphisms of Hedgehog pathway as novel risk and prognostic biomarkers in melanoma patients

xlomafota13 shared this article with you from Inoreader GLI-1 polymorphisms of Hedgehog pathway as novel risk and prognostic biomarkers in melanoma patients Via Melanoma Research - Current Issue In adult organisms, deregulation of the sonic hedgehog (SHH) signaling pathway is significantly correlated with different malignancies. Currently, data associating genetic polymorphisms in the SHH pathway with melanoma are scarce and largely unknown. The objective of our study was to elucidate an association between gene polymorphisms in the SHH pathway and prognosis of melanoma skin cancer patients. The current study investigated the association of PTCH1 (rs357564), SMO (rs2228617) and GLI1 (rs2228224, rs2228226), polymorphisms with melanoma predisposition and prognosis. Single-nucleotide polymorphisms were assessed by TaqMan SNP Genotyping Assays. The study involved 93 melanoma patients and 97 individuals in the control group. Melanoma patients with the variant mutant genotype GG of GLI1 rs2228226 polymorphism had poorer overall survival and recurrence-free survival (P = 0.0001 and P = 0.037, respectively). The multivariate analysis revealed that disease progression [hazard ratio (HR) = 14.434, P = 0.0001] and the GLI1 rs2228226 polymorphism (HR = 4.161, P = 0.006) persisted as independent prognostic factors. Mutated allele carriers (combined heterozygous and mutated genotypes) for GLI1 rs2228224 G and GLI1 rs2228226 G allele significantly increased melanoma risk [odds ratio (OR) = 2.261, P = 0.007; OR = 2.176, P = 0.010]. Our study demonstrated that genetic variants in GLI1, downstream member of the HH signaling pathway, are the risk factors for melanoma susceptibility and it can be a novel marker for melanoma prognosis. As a crucial SHH signaling member, GLI1 can also be regarded as a novel drug target for anti-cancer treatment in melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization

xlomafota13 shared this article with you from Inoreader Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization Via Melanoma Research - Current Issue Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which serum MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen de privation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Leptomeningeal dissemination as a first sign of progression in metastatic melanoma: a diagnostic lesson

xlomafota13 shared this article with you from Inoreader Leptomeningeal dissemination as a first sign of progression in metastatic melanoma: a diagnostic lesson Via Melanoma Research - Current Issue One of the most serious complications of advanced melanoma is the diffusion of cancer cells to the central nervous system. The diagnosis of leptomeningeal metastasis (LMM) is notoriously challenging and requires a combination of consistent MRI and cerebrospinal fluid (CSF) cytology. In ambiguous cases, mutations like BRAF V600E in CSF-cell-free (cf)DNA may help to clarify diagnosis of LMM. Here we present the case of a young woman who developed isolated LMM after the diagnosis of a node-positive primary melanoma with normal LDH. The CSF was negative for tumour cells by cytology but positive for cfDNA BRAF V600E mutatio n, thus allowing us to diagnose LMM. To our knowledge, this is the first case where CSF sampling for the detection of BRAF mutation was used to identify leptomeningeal disease in the presence of negative MRI and without involvement of any other distant sites. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-β signaling

xlomafota13 shared this article with you from Inoreader Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-β signaling Via Cellular and Molecular Biology Histol Histopathol. 2021 Dec 27:18416. doi: 10.14670/HH-18-416. Online ahead of print. ABSTRACT BACKGROUND: Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. METHODS: The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. RESULTS: The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-β signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. CONCLUSION: Our study reports the miR-485-3p/TGFBR2/ TGF-β signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC. PMID:34958117 | DOI:10.14670/HH-18-416 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multiple Sclerosis Masquerading as Post Septorhinoplasty Complication: A Case Report

xlomafota13 shared this article with you from Inoreader Multiple Sclerosis Masquerading as Post Septorhinoplasty Complication: A Case Report Via leak of cerebrospinal fluid Cureus. 2021 Nov 15;13(11):e19591. doi: 10.7759/cureus.19591. eCollection 2021 Nov. ABSTRACT This is a case report of a young woman, who after a successful septorhinoplasty procedure, sustained repeated nasal trauma with a subsequent diagnosis of multiple sclerosis (MS) at a large tertiary hospital in Riyadh, Saudi Arabia. A 24-year-old woman with a history of childhood trauma presented with difficulty in breathing and dissatisfaction with her nasal appearance. After a successful and uneventful septorhinoplasty, she required numerous hospital admissions due to multiple episodes of blunt nasal trauma, culminating in clear nasal discharge and neurological symptoms, including dizziness, right-sided paresthesia and difficulty walking. Cerebrospinal fluid (CSF) leak was ruled out by CT brain; however, magnetic resonance imaging (MRI) of the brain and spinal cord showed demyelinating areas in the brain and cervical region of the spinal cord. CSF ex amination revealed the presence of oligoclonal bands. A neurologist confirmed the diagnosis of MS and initiated treatment, which was well tolerated. The patient is in remission with mild paresthesia in the right hand. Despite the repeated nasal trauma, the septorhinoplasty procedure had an excellent outcome. In conclusion, repeated nasal trauma, especially in the early postoperative period, in addition to procedure failure, may also point to the presence of an uncommon underlying neurological disorder, hitherto undiagnosed. It is therefore important to have an open mind when it comes to the differential diagnosis in such unusual scenarios. In addition, while investigating recurrent nasal trauma, it is extremely important to keep in mind rare neurological conditions, especially in younger patients. PMID:34956744 | PMC:PMC8675578 | DOI:10.7759/cureus.19591 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Breathy Dysphonia, Not Just a Pain in the Neck

xlomafota13 shared this article with you from Inoreader Breathy Dysphonia, Not Just a Pain in the Neck Via ear nose throat Ear Nose Throat J. 2021 Dec 27:1455613211069919. doi: 10.1177/01455613211069919. Online ahead of print. ABSTRACT We describe a rare occurrence of unilateral vocal fold paralysis associated with a cervical osteophyte abutting the course of the recurrent laryngeal nerve. Trans-nasal laryngoscopy is vital in diagnosing vocal fold paralysis, but often does not provide insight into etiology. This case highlights the importance of radiographic imaging in newly diagnosed vocal fold paralysis, and underscores the principle that a diagnosis is not idiopathic until all sources have been ruled out. PMID:34958270 | DOI:10.1177/01455613211069919 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An Intramolecular Ionic Interaction Linking Defective Sodium/Iodide Symporter Transport to the Plasma Membrane and Dyshormonogenic Congenital Hypothyroidism

xlomafota13 shared this article with you from Inoreader An Intramolecular Ionic Interaction Linking Defective Sodium/Iodide Symporter Transport to the Plasma Membrane and Dyshormonogenic Congenital Hypothyroidism Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.