Evaluation of Exosomal miRNA as Potential Biomarkers in Cervical Cancer.

Different studies show that small non-coding RNAs, such as microRNAs (miRNAs) obtained from exosomes, are considered potential biomarkers in several types of cancer, including cervical cancer (CC). Therefore, the present study seeks to present an overview of the role of circulating exosomal miRNAs with the potential to act as biomarkers for the diagnosis and prognosis of CC and to analyze the presence of these miRNAs according to the stage of CC. For this purpose, a review was developed, with articles consulted from the electronic databases MEDLINE/PubMed, Scopus, and Web of Science published between 2015 and 2021. Seven articles were included after a selection of studies according to the eligibility criteria. In addition to the methods used for sample analysis, detection, and isolation of miRNAs in each article, clinical data were also extracted from the patients studied, such as the stage of cancer. After analyzing the network of the seven miRNAs, they were associated with the immune system, CC progression and staging, and cisplatin resistance. With the belief that studies on miRNAs in cervical cancer would have major clinical implications, in this review, we have attempted to summarize the current situation and potential development prospects.

Histomorphometric analysis in HPV-induced cervical lesions

SUMMARY Introduction: squamous intraepithelial lesions (SIL) of the cervix involve dysplastic change, or abnormal cell maturation and their progression can result in cervical carcinoma. Some studies have reported the importance of the immune system in the process of tumor progression. Therefore, it is important to characterize the inflammatory infiltration as a possible marker of prognosis. Aim: to analyze density of the inflammatory infiltrate in different degrees of SIL and in cervical cancer to under-stand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system. Methods: one hundred and eight (108) cervical biopsy specimens were obtained from patients treated at the tertiary hospital and were stratified into four groups: Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC) and negative for intraepithelial lesion and malignancy (NILM). Histomorphometric analysis was performed from the identification and quantification of inflammatory cells in ten (10) fields per sample in images captured by a digital system and analyzed using the software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. Differences between groups were evaluated by Anova followed by Tukey test. Tests yielding p values < 0.05 were considered significant. Results: we found a significant increase in the average number of lymphocytes (cells/mm2 and cells/field) in samples of CC in relation to the other groups. No statistical difference was observed in relation to neutrophils, plasma cells and eosinophils. Conclusion: cervical cancer specimens had significantly more lymphocytes than NILM, or LSIL and HSIL, suggesting that this cell type plays a central role in cellular immunity against cervical carcinoma.

Introducción: las lesiones escamosas intraepiteliales (SIL) del cuello uterino implican cambios displásicos o maduración celular anormal y su progresión puede resultar en carcinoma cervical. Algunos estudios han informado de la importancia del sistema inmunológico en el proceso de progresión tumoral. Por tanto, es importante caracterizar la infiltración inflamatoria como un posible marcador de pronóstico. Objetivo: analizar la densidad del infiltrado inflamatorio en diferentes grados de SIL y en cáncer de cuello uterino para comprender los cambios locales y sistêmicos en las interacciones entre las lesiones cervicales asociadas al VPH y el sistema inmunológico. Métodos: se obtuvieron ciento ocho (108) muestras de biopsia cervical de pacientes tratados en el hospital terciario y se estratificaron en cuatro grupos: Lesión intraepitelial escamosa de bajo grado (LSIL), Lesión intraepitelial escamosa de alto grado (HSIL), cáncer de cuello uterino (CC) y negativo para lesiones intraepiteliales y malignidad (NILM). El análisis histomorfométrico se realizó a partir de la identificación y cuantificación de células inflamatorias en diez (10) campos por muestra en imágenes capturadas por un sistema digital y analizadas utilizando el software Leica Qwin Pro-V 3.5.1, Leica Microsystems Ltd. Anova seguido de la prueba de Tukey. Las pruebas que arrojaron valores de p <0,05 se consideraron significativas. Resultados: encontramos un aumento significativo en el número medio de linfocitos (células/mm2 y células/campo) en muestras de CC en relación con los otros grupos. No se observó diferencia estadística en relación con neutrófilos, células plasmáticas y eosinófilos. Conclusión: las muestras de cáncer de cuello uterino tenían significativamente más linfocitos que NILM o LSIL y HSIL, lo que sugiere que este tipo de células juega un papel central en la inmunidad celular contra el carcinoma de cuello uterino.

Introdução: Lesões intraepiteliais escamosas (SIL) do colo do útero envolvem alteração displásica ou maturação celular anormal e sua progressão pode resultar em carcinoma cervical. Alguns estudos relatam a importância do sistema imunológico no processo de progressão tumoral. Portanto, é importante caracterizar o infiltrado inflamatório como um possível marcador de prognóstico. Objetivo: analisar a densidade do infiltrado inflamatório em diferentes graus de SIL e no câncer cervical para compreender as alterações locais e sistêmicas nas interações entre as lesões cervicais associadas ao HPV e o sistema imunológico. Métodos: Cento e oito (108) espécimes de biópsia cervical foram obtidos de pacientes tratados no hospital terciário e foram estratificados em quatro grupos: Lesão intraepitelial escamosa de baixo grau (LSIL), Lesão intraepitelial escamosa de alto grau (HSIL), câncer cervical (CC) e negativo para lesão intraepitelial e malignidade (NILM). A análise histomorfométrica foi realizada a partir da identificação e quantificação das células inflamatórias em dez (10) campos por amostra em imagens capturadas por um sistema digital e analisadas no software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. As diferenças entre os grupos foram avaliadas por Anova seguida do teste de Tukey. Os testes com valores de p <0,05 foram considerados significativos. Resultados: encontramos um aumento significativo no número médio de linfócitos (células/mm2 e células/campo) nas amostras de CC em relação aos demais grupos. Não foi observada diferença estatística em relação aos neutrófilos, plasmócitos e eosinófilos. Conclusão: as amostras de câncer cervical tinham significativamente mais linfócitos do que NILM, ou LSIL e HSIL, sugerindo que este tipo de célula desempenha um papel central na imunidade celular contra o carcinoma cervical.

Tityus serrulatus Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines.

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells.

Bothrops jararaca (BJ) and Bothrops erythromelas (BE) are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123), nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that both Bothrops venoms could be used as prototypes for the development of new therapies.