Strong Correlation Between mRNA Expression Levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in Laryngeal Carcinoma

Popov, T.; Stancheva, G.; Goranova, Teodora; Rangachev, J.; Konov, D.; Todorov, Sp.; Stoyanov, O.; Kaneva, Radka; Попова, Д.

doi:10.1007/s12253-016-0059-4

Cited by 7 publications

(4 citation statements)

References 19 publications

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“… 14 While the HIF switch is quite evident and documented during the evolution of renal cell carcinoma, literature data regarding laryngeal carcinoma are inconclusive. 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

“…14 the HIF switch is quite evident and documented during the evolution of renal cell carcinoma, literature data regarding laryngeal carcinoma are inconclusive. 15,16 Study on oral carcinomas showed that the expression of HIF-1α is an early event in carcinogenesis. 17 The explanation behind this theory is that HIF-1α expression reflects the level of oxygen reduction in tumor tissue, which is a characteristic of fast-growing tumors, particularly early forms of carcinomas.…”

Section: Discussionmentioning

confidence: 99%

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The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

et al. 2022

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Introduction The association between the expression of HIF-1α in the laryngeal carcinoma and the prognosis of disease is quite well documented, but the significance of HIF-1α C1772T polymorphism and its relation to disease phenotype have to be clarified. The aim of this study was to investigate the influence of C1772T polymorphism on the clinical-pathological characteristics and disease-free survival after initial surgical treatment of patients with laryngeal carcinoma. Materials and methods The prospective cohort study included 65 patients with laryngeal carcinoma. Two representative tumor tissue specimens were taken in each patient during surgery; 1 specimen was used to asses HIF-1α C1772T polymorphism and the other 1 to determine the immunohistochemical expression of HIF-1α, VEGF, as well as CD 34 proteins. The comparison of polymorphism frequency between study and control population was conducted by collecting a 5 mL of peripheral venous blood samples in each subject. Results Clinicopathological characteristics of laryngeal carcinoma didn’t affect the expression of hypoxia-related biomarkers, such as HIF-1α, VEGF or MVD. The statistically significant association between HIF-1α and VEGF expression was found ( P = .034), but not between HIF-1α expression and MVD value ( P = .696). The expression of HIF-1α was significantly higher among CT heterozygotes ( P = .029). We found a significantly more recurrence among CT heterozygotes compared with patients with CC homozygous alleles (57.10% and 24.30%, respectively; P = .007). Patients with C1772T polymorphic variants had significantly worse disease-free survival compared with patients without polymorphism (Log-rank test, P = .007). Conclusion HIF-1α C1772T polymorphism was significantly associated with worse disease-free survival which nominates it as a predictor of laryngeal carcinoma relapse. The preoperative assessment of hypoxia-related biomarkers should be used in everyday practice in order to determine the treatment modalities for laryngeal carcinoma.

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“… 14 While the HIF switch is quite evident and documented during the evolution of renal cell carcinoma, literature data regarding laryngeal carcinoma are inconclusive. 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

et al. 2022

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“…MMPs comprise a multigene family of endopeptidases that are involved in remodeling of extracellular matrix during fibrosis. Moreover, MMPs are implicated in pathological processes, including cancer [ 69 ]. The activity of these proteins plays a pivotal role in tumor growth, invasion and metastasis [ 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Estarás

Gonzalez

Fernandez–Bermejo

et al. 2021

IJMS

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In certain diseases of the pancreas, pancreatic stellate cells form an important part of fibrosis and are critical for the development of cancer cells. A hypoxic condition develops within the tumor, to which pancreatic stellate cells adapt and are able to proliferate. The consequence is the growth of the tumor. Melatonin, the product of the pineal gland, is gaining attention as an agent with therapeutic potential against pancreatic cancers. Its actions on tumor cells lead, in general, to a reduction in cell viability and proliferation. However, its effects on pancreatic stellate cells subjected to hypoxia are less known. In this study, we evaluated the actions of pharmacological concentrations of melatonin (1 mM–1 µM) on pancreatic stellate cells subjected to hypoxia. The results show that melatonin induced a decrease in cell viability at the highest concentrations tested. Similarly, the incorporation of BrdU into DNA was diminished by melatonin. The expression of cyclins A and D also was decreased in the presence of melatonin. Upon treatment of cells with melatonin, increases in the expression of major markers of ER stress, namely BIP, phospho-eIF2α and ATF-4, were detected. Modulation of apoptosis was noticed as an increase in caspase-3 activation. In addition, changes in the phosphorylated state of p44/42, p38 and JNK MAPKs were detected in cells treated with melatonin. A slight decrease in the content of α-smooth muscle actin was detected in cells treated with melatonin. Finally, treatment of cells with melatonin decreased the expression of matrix metalloproteinases 2, 3, 9 and 13. Our observations suggest that melatonin, at pharmacological concentrations, diminishes the proliferation of pancreatic stellate cells subjected to hypoxia through modulation of cell cycle, apoptosis and the activation of crucial MAPKs. Cellular responses might involve certain ER stress regulator proteins. In view of the results, melatonin could be taken into consideration as a potential therapeutic agent for pancreatic fibrosis.

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“…Previous investigations demonstated important relationships between the serum level/mRNA tissue immunostaining for MMP-2/MMP-9 and clinical stage, nodal status and survival rates in patients with LSCC. [19][20][21]…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 expression in laryngeal squamous cell carcinoma

Rašić

Perić

Vukomanovic-Djurdjevic

et al. 2021

VOJNOSANIT PREGL

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Introduction/Aim. Previous investigations suggest that matrix metalloproteinases (MMPs) have ability to degrade extracellular matrix components and play important role in malignant tumour progression and metastasis. The aim of this prospective study was to investigate matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in tissue of laryngeal squamous cell carcinoma (LSCC) and to evaluate their clinical significance. Methods. The samples of tumour tissue of seventy (n=70) patients with LSCC, 45 glottic and 25 supraglottic, and samples of laryngeal mucosa of 70 chronic laryngitis patients were immunohistochemically stained for MMP-2 and MMP-9. We studied the relationships between MMPs tissue expression and clinical and histological characteristics of LSCC in comparison to patients with chronic laryngitis. Results. MMP-2 and MMP-9 expression was significantly higher in tissue of both glottic and supraglottic SCC than in chronically inflamed laryngeal mucosa (p<0.001; p<0.001, respectively). There were positive correlations between epithelial MMP-2 expression and the presence of perineural invasion (r=0.515, p=0.008), lymphovascular invasion (r=0.559, p=0.004) and disease recurrence (r=0.415, p=0.039) in supraglottic SCC, as well as between MMP-2 expression and the presence of exophytic type of tumour growth (r=0.347, p=0.020) in glottic SCC. Epithelial MMP-9 expression is associated with lymphovascular invasion (r=0.331, p=0.026) and the presence of exophytic tumour growth (r=0.474, p=0.001) in glottic SCC. Conclusion. MMP-2 and MMP-9 can be used as potential biomarkers for assessment of LSCC progression.

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Strong Correlation Between mRNA Expression Levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in Laryngeal Carcinoma

Cited by 7 publications

References 19 publications

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 expression in laryngeal squamous cell carcinoma

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