Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study.

Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Globally Vibrio cholera antibiotics resistance to RNA and DNA effective antibiotics: A systematic review and meta-analysis.

BACKGROUND: Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics. METHOD: A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR). RESULTS: The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin. CONCLUSION: V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.