Microablative fractional radiofrequency for sexual dysfunction and vaginal Trophism: A randomized clinical trial.

OBJECTIVES: To evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. METHODS: This was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). RESULTS: One hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. CONCLUSIONS: Radiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

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.

Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection.

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Microablative fractional radiofrequency for sexual dysfunction and vaginal Trophism: A randomized clinical trial

Abstract Objectives: To evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. Methods: This was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). Results: One hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. Conclusions: Radiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

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.

Near-infrared spectroscopy of blood plasma with chemometrics towards HIV discrimination during pregnancy.

Prevention of mother-to-child transmission programs have been one of the hallmarks of success in the fight against HIV/AIDS. In Brazil, access to antiretroviral therapy (ART) during pregnancy has increased, leading to a reduction in new infections among children. Currently, lifelong ART is available to all pregnant, however yet challenges remain in eliminating mother-to-child transmission. In this paper, we focus on the role of near-infrared (NIR) spectroscopy to analyse blood plasma samples of pregnant women with HIV infection to differentiate pregnant women without HIV infection. Seventy-seven samples (39 HIV-infected patient and 38 healthy control samples) were analysed. Multivariate classification of resultant NIR spectra facilitated diagnostic segregation of both sample categories in a fast and non-destructive fashion, generating good accuracy, sensitivity and specificity. This method is simple and low-cost, and can be easily adapted to point-of-care screening, which can be essential to monitor pregnancy risks in remote locations or in the developing world. Therefore, it opens a new perspective to investigate vertical transmission (VT). The approach described here, can be useful for the identification and exploration of VT under various pathophysiological conditions of maternal HIV. These findings demonstrate, for the first time, the potential of NIR spectroscopy combined with multivariate analysis as a screening tool for fast and low-cost HIV detection.

Microablative fractional radiofrequency for the genitourinary syndrome of menopause: protocol of randomised controlled trial.

INTRODUCTION: Menopause is a physiological and progressive phenomenon secondary to decreased ovarian follicular reserve. These changes have consequences: vaginal dryness, dyspareunia, discomfort, burning and irritation, vulvovaginal pruritus, dysuria and increased frequency of genitourinary infections. The therapy more suitable for vaginal symptoms in postmenopause yet is the use of a topical hormone. However, the prescription of topical oestrogens should also be avoided in women with a history of breast cancer, oestrogen-sensitive tumours and thromboembolism, emphasising the necessity of alternative treatments. Recently, physical methods, such as laser and radiofrequency (RF), in their non-ablative, ablative and microablative forms have been used in the vaginal mucosa to promote neocolagenesis and neoelastogenesis. This randomised study aims to compare the efficiency of microablative fractional RF (MAFRF) treatment with vaginal oestrogens and no treatment. METHODS AND ANALYSES: This randomised, controlled clinical intervention trial with an open label design comparing the treatment of MAFRF with vaginal oestrogens and no treatment. Four important moments were considered to evaluate treatment results (T0, T1, T2 and T3). The primary outcome includes vulvovaginal atrophy (vaginal pain, burning, itching, dryness, dyspareunia and dysuria), and the secondary outcomes will be sexual function, vaginal health (epithelial integrity, vaginal elasticity, moisture, fluid volume and vaginal pH) and quality of life. ETHICS AND DISSEMINATION: Due to the nature of the study, we obtained approval from the ethics committee. All participants must sign an informed consent form before randomisation. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data. TRIAL REGISTRATION NUMBER: RBR-94DX93.

Physical methods for the treatment of genitourinary syndrome of menopause: A systematic review.

BACKGROUND: Genitourinary syndrome of menopause (GSM) negatively affects sexual function and quality of life. Techniques like laser and radiofrequency are being used to manage GSM, particularly in women with contraindications for hormone therapy. OBJECTIVES: To verify whether the physical methods of laser and radiofrequency can be recommended as safe and effective options for the treatment of GSM/urinary urgency or incontinence in pre- and postmenopausal women. SEARCH STRATEGY: Databases were comprehensively searched using combinations of the following keywords in any language: "postmenopause"; "genitourinary syndrome of menopause"; "vaginal atrophy"; "radiofrequency"; and "laser." SELECTION CRITERIA: Full articles of case-control, cross-sectional, cohort, randomized clinical trials, and quasi-randomized or controlled clinical trials were included. DATA COLLECTION AND ANALYSIS: All authors independently evaluated the design of the studies for quality of reporting, risk of bias, and quality of evidence. MAIN RESULTS: Of the included 49 studies, 37 were on the CO2 laser, 10 on the Erbium laser, and two on radiofrequency. CONCLUSIONS: Laser and radiofrequency therapy could be promising and safe therapeutic options for GSM/urinary incontinence. However, the study findings cannot be generalized until new randomized clinical trials are performed that confirm the strength of the evidence. This review has been registered with PROSPERO: CRD42020141913.

ATR-FTIR spectroscopy in blood plasma combined with multivariate analysis to detect HIV infection in pregnant women.

The primary concern for HIV-infected pregnant women is the vertical transmission that can occur during pregnancy, in the intrauterine period, during labour or even breastfeeding. The risk of vertical transmission can be reduced by early diagnosis. Therefore, it is necessary to develop new methods to detect this virus in a quick and low-cost fashion, as colorimetric assays for HIV detection tend to be laborious and costly. Herein, attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy combined with multivariate analysis was employed to distinguish HIV-infected patients from healthy uninfected controls in a total of 120 blood plasma samples. The best sensitivity (83%) and specificity (92%) values were obtained using the genetic algorithm with linear discriminant analysis (GA-LDA). These good classification results in addition to the potential for high analytical frequency, the low cost and reagent-free nature of this method demonstrate its potential as an alternative tool for HIV screening during pregnancy.

Spectrochemical differentiation in gestational diabetes mellitus based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and multivariate analysis.

Gestational diabetes mellitus (GDM) is a hyperglycaemic imbalance first recognized during pregnancy, and affects up to 22% of pregnancies worldwide, bringing negative maternal-fetal consequences in the short- and long-term. In order to better characterize GDM in pregnant women, 100 blood plasma samples (50 GDM and 50 healthy pregnant control group) were submitted Attenuated Total Reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, using chemometric approaches, including feature selection algorithms associated with discriminant analysis, such as Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) and Support Vector Machines (SVM), analyzed in the biofingerprint region between 1800 and 900 cm-1 followed by Savitzky-Golay smoothing, baseline correction and normalization to Amide-I band (~ 1650 cm-1). An initial exploratory analysis of the data by Principal Component Analysis (PCA) showed a separation tendency between the two groups, which were then classified by supervised algorithms. Overall, the results obtained by Genetic Algorithm Linear Discriminant Analysis (GA-LDA) were the most satisfactory, with an accuracy, sensitivity and specificity of 100%. The spectral features responsible for group differentiation were attributed mainly to the lipid/protein regions (1462-1747 cm-1). These findings demonstrate, for the first time, the potential of ATR-FTIR spectroscopy combined with multivariate analysis as a screening tool for fast and low-cost GDM detection.

Impact of microablative fractional radiofrequency on the vaginal health, microbiota, and cellularity of postmenopausal women.

OBJECTIVES: We aimed to evaluate the effectiveness of microablative fractional radiofrequency (MAFRF) in the non-hormonal treatment of genitourinary syndrome of menopause. METHODS: We examined the cases of 55 postmenopausal women before and after treatment with regard to their vaginal health index (VHI), vaginal microbiota, vaginal pH, and cell maturation. Three applications of MAFRF were performed in the vagina/vaginal introitus. During the treatment, six vaginal smears were obtained and stained with the Papanicolaou stain for determining the degree of cell maturation and with Gram stain for classification of vaginal flora, as per the criteria of Spiegel and Amsel. For vaginal pH determination, pH indicator strips were applied against the vaginal wall. Statistical analysis was performed using SPSS for Windows (version 17.0). Data were reported as mean±standard deviation. The differences were analyzed using the statistical method of generalized estimation equations with autoregressive correlation structure "1" and robust standard errors. RESULTS: The mean age was 59.8±4.2 years, and the mean time of menopause was 15.4±4.5 years. After treatment, there was an increase in the percentage of Lactobacillus spp. (p<0.001). Consequently, there was a progressive decrease in vaginal pH during the treatment (p<0.001). Regarding cell maturation, there was a decrease in the percentage of parabasal cells (p=0.001) and an increase in the rate of superficial cells (p<0.001). Additionally, there was an improvement in the VHI index. The mean VHI values before and after treatment were 13.2±5.6 and 22.5±3.7, respectively (p<0.001). CONCLUSION: MAFRF treatment is well tolerated and leads to improvement in the vaginal microenvironment.

Impact of microablative fractional radiofrequency on the vaginal health, microbiota, and cellularity of postmenopausal women

OBJECTIVES: We aimed to evaluate the effectiveness of microablative fractional radiofrequency (MAFRF) in the non-hormonal treatment of genitourinary syndrome of menopause. METHODS: We examined the cases of 55 postmenopausal women before and after treatment with regard to their vaginal health index (VHI), vaginal microbiota, vaginal pH, and cell maturation. Three applications of MAFRF were performed in the vagina/vaginal introitus. During the treatment, six vaginal smears were obtained and stained with the Papanicolaou stain for determining the degree of cell maturation and with Gram stain for classification of vaginal flora, as per the criteria of Spiegel and Amsel. For vaginal pH determination, pH indicator strips were applied against the vaginal wall. Statistical analysis was performed using SPSS for Windows (version 17.0). Data were reported as mean±standard deviation. The differences were analyzed using the statistical method of generalized estimation equations with autoregressive correlation structure "1" and robust standard errors. RESULTS: The mean age was 59.8±4.2 years, and the mean time of menopause was 15.4±4.5 years. After treatment, there was an increase in the percentage of Lactobacillus spp. (p<0.001). Consequently, there was a progressive decrease in vaginal pH during the treatment (p<0.001). Regarding cell maturation, there was a decrease in the percentage of parabasal cells (p=0.001) and an increase in the rate of superficial cells (p<0.001). Additionally, there was an improvement in the VHI index. The mean VHI values before and after treatment were 13.2±5.6 and 22.5±3.7, respectively (p<0.001). CONCLUSION: MAFRF treatment is well tolerated and leads to improvement in the vaginal microenvironment.

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.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas.

Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

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.

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.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas

Abstract: Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Does 100% Rapid Review Improve Cervical Cancer Screening?

OBJECTIVE: The aim of this work was to evaluate 100% rapid review (100% RR) as a useful tool to detect false negative (FN) results. STUDY DESIGN: A sample of 8,677 swabs was investigated; the unsatisfactory and negative results were referred to 100% RR, concordant results were taken as the final diagnosis, while the discordant results were debated in a consensus meeting to reach a conclusion. The positive results were examined by 2 cytologists. The data were entered into SAS statistical software, and the agreement of the 100% RR results with the final diagnosis was tested with the weighted kappa statistic. RESULTS: There was a significant increase in unsatisfactory results from 348 to 1,927, and of positive results from 174 to 349. On the other hand, there was a substantial decrease in negative results from 8,155 to 6,401. Assessing the relative risk of FN results in smears that were not referred to quality control (100% RR) revealed the following results: atypical squamous cells of undetermined significance (ASC-US), 2.93; low-grade squamous intraepithelial lesion (LSIL), 2.72; high-grade squamous intraepithelial lesion/atypical squamous cells - cannot exclude HSIL (HSIL/ASC-H), 2.25. Evaluating by age group, a higher risk for LSIL (4.90) and ASC-US (3.85) was observed in patients aged under 25 years, whereas patients between 25 and 64 years and those over 64 years presented a higher risk for HSIL and ASC-H: 2.46 and 2.75, respectively. CONCLUSION: 100% RR is an effective screening tool for FN results in countries where molecular tests for DNA-HPV and prophylactic vaccines are not available in cervical cancer screening programs.

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.

High IL-17 expression is associated with an unfavorable prognosis in thyroid cancer.

Previous studies have indicated that cancer may be promoted and/or exacerbated by inflammation and infection. The cytokines produced by activated innate immune cells that stimulate tumor growth and progression are considered as important components in this process. The interleukin (IL)-23/T helper (Th)17 axis, which exerts marked pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. Increasing clinical evidence indicates that Th17 may promote or inhibit tumor progression, however, the function of Th17 in the pathogenesis of benign and malignant thyroid neoplasms remains unclear. The present study investigated the association between the IL-23/Th17 axis and neoplastic and non-neoplastic thyroid lesions using immunohistochemistry. A total of 131 thyroid biopsy specimens were analyzed, which revealed high IL-17 and IL-23 expression in differentiated thyroid cancer and medullary thyroid cancer tissues when compared with benign lesions, including follicular thyroid adenoma and goiter tissues. Furthermore, high IL-17 expression was associated with recurrence and mortality. These results indicate that the IL-23/Th17 axis exhibits a pivotal function in the development of thyroid neoplasms.