Low-Cost Pseudo-Anthropomorphic PVA-C and Cellulose Lung Phantom for Ultrasound-Guided Interventions.

A low-cost custom-made pseudo-anthropomorphic lung phantom, offering a model for ultrasound-guided interventions, is presented. The phantom is a rectangular solidstructure fabricated with polyvinyl alcohol cryogel (PVA-C) and cellulose to mimic the healthy parenchyma. The pathologies of interest were embedded as inclusions containing gaseous, liquid, or solid materials. The ribs were 3D-printed using polyethylene terephthalate, and the pleura was made of a bidimensional reticle based on PVA-C. The healthy and pathological tissues were mimicked to display acoustic and echoic properties similar to that of soft tissues. Theflexible fabrication process facilitated the modification of the physical and acoustic properties of the phantom. The phantom's manufacture offers flexibility regarding the number, shape, location, and composition of the inclusions and the insertion of ribs and pleura. In-plane and out-of-plane needle insertions, fine needle aspiration, and core needle biopsy were performed under ultrasound image guidance. The mimicked tissues displayed a resistance and recoil effect typically encountered in a real scenario for a pneumothorax, abscesses, and neoplasms. The presented phantom accurately replicated thoracic tissues (lung, ribs, and pleura) and associated pathologies providing a useful tool for training ultrasound-guided procedures.

Feature Ranking by Variational Dropout for Classification Using Thermograms from Diabetic Foot Ulcers.

Diabetes mellitus presents a high prevalence around the world. A common and long-term derived complication is diabetic foot ulcers (DFUs), which have a global prevalence of roughly 6.3%, and a lifetime incidence of up to 34%. Infrared thermograms, covering the entire plantar aspect of both feet, can be employed to monitor the risk of developing a foot ulcer, because diabetic patients exhibit an abnormal pattern that may indicate a foot disorder. In this study, the publicly available INAOE dataset composed of thermogram images of healthy and diabetic subjects was employed to extract relevant features aiming to establish a set of state-of-the-art features that efficiently classify DFU. This database was extended and balanced by fusing it with private local thermograms from healthy volunteers and generating synthetic data via synthetic minority oversampling technique (SMOTE). State-of-the-art features were extracted using two classical approaches, LASSO and random forest, as well as two variational deep learning (DL)-based ones: concrete and variational dropout. Then, the most relevant features were detected and ranked. Subsequently, the extracted features were employed to classify subjects at risk of developing an ulcer using as reference a support vector machine (SVM) classifier with a fixed hyperparameter configuration to evaluate the robustness of the selected features. The new set of features extracted considerably differed from those currently considered state-of-the-art but provided a fair performance. Among the implemented extraction approaches, the variational DL ones, particularly the concrete dropout, performed the best, reporting an F1 score of 90% using the aforementioned SVM classifier. In comparison with features previously considered as the state-of-the-art, approximately 15% better performance was achieved for classification.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2.

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study's aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Global expression profiling of CD10 + /CD19 + pre-B lymphoblasts from Hispanic B-ALL patients correlates with comparative TARGET database analysis.

Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.

Multifrequency Microwave Radiometry for Characterizing the Internal Temperature of Biological Tissues.

The analysis of near-field radiometry is described for characterizing the internal temperature of biological tissues, for which a system based on multifrequency pseudo-correlation-type radiometers is proposed. The approach consists of a new topology with multiple output devices that enables real-time calibration and performance assessment, recalibrating the receiver through simultaneous measurable outputs. Experimental characterization of the prototypes includes a well-defined calibration procedure, which is described and demonstrated, as well as DC conversion from the microwave input power. Regarding performance, high sensitivity is provided in all the bands with noise temperatures around 100 K, reducing the impact of the receiver on the measurements and improving its sensitivity. Calibrated temperature retrievals exhibit outstanding results for several noise sources, for which temperature deviations are lower than 0.1% with regard to the expected temperature. Furthermore, a temperature recovery test for biological tissues, such as a human forearm, provides temperature values on the order of 310 K. In summary, the radiometers design, calibration method and temperature retrieval demonstrated significant results in all bands, validating their use for biomedical applications.

Vitamin A deficiency in K14E7HPV expressing transgenic mice facilitates the formation of malignant cervical lesions.

Infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC), but viral infection alone does not guarantee the development of this malignancy. Indeed, deficiencies of dietary micronutrients could favor cervical cancer development in individuals that harbor HR-HPV infections. The status of retinoid levels, natural and synthetic derivatives of vitamin A, is important in maintaining cellular differentiation of the cervical epithelium. Moreover, many studies show a link between deficient intake of retinoids or alteration of the retinoid receptors and CC development. In spite of this, the effect of vitamin A deficiency (VAD) in presence of HR-HPV oncoproteins on cervical carcinogenesis in vivo has not been reported. Transgenic mice expressing E6 or E7 oncoproteins (K14E6 or K14E7 mice, respectively) were used to evaluate the possible role of VAD in the development of malignant cervical lesions. The survival of the mice in VAD condition was studied, and histopathological analysis and immunohistochemical detection of molecular cancer markers such as the tumor suppressor retinoic acid receptor beta (RARß), proliferating cell nuclear antigen (PCNA), cleaved caspase 3, and the tumor suppressor protein p16INK4A (inhibitor of CDK4) were performed. Our results show that K14E6/VAD mice showed moderate cervical dysplasia; notably, K14E7/VAD mice developed severe cervical dysplasia and cervical in situ carcinoma at an early age. VAD synergizes with HPV16E7 oncoprotein expression favoring cervical carcinogenesis in vivo.

Expression of miR-34a and miR-15b during the progression of cervical cancer in a murine model expressing the HPV16 E7 oncoprotein.

The high-risk human papillomavirus (HR-HPV) E7 oncoprotein appears to be a major determinant for cell immortalization and transformation altering critical processes such as cell proliferation, apoptosis, and immune response. This oncoprotein plays an essential role in cervical carcinogenesis, but other cofactors such as long-term use of hormonal contraceptives are necessary to modulate the risk of cervical cancer (CC). The role of HR-HPVs in the alteration of microRNA (miRNA) levels in persistent viral infections currently remains unclear. The aim of this study was to evaluate the miR-34a and miR-15b expression levels in the murine HPV16K14E7 (K14E7) transgenic model after chronic estrogen (E2) treatment and their involvement in CC. Interestingly, results showed that, although miR-34a expression is elevated by the HPVE7 oncogene, this expression was downregulated in the presence of both the E7 oncoprotein and chronic E2 in cervical carcinoma. On the other hand, miR-15b expression was upregulated along cervical carcinogenesis mainly by the effect of E2. These different changes in the expression levels of miR-34a and miR-15b along cervical carcinogenesis conduced to low apoptosis levels, high cell proliferation and finally, to cancerous cervical tissue development. In this work, we also determined the relative mRNA expression of Cyclin E2 (Ccne2), Cyclin A2 (Ccna2), and B cell lymphoma 2 (Bcl-2) (target genes of miR-34a and miR-15b); Sirtuin 1 (Sirt1), Cmyc, and Bax (miR-34a target genes); and p21/WAF1 (mir15b target gene) and the H-ras oncogene. Given the modifications in the expression levels of miR-34a and miR-15b during the development of cervical cancer, it will be useful to carry out further investigation to confirm them as molecular biomarkers of cancer.

Assessment of Registration Methods for Thermal Infrared and Visible Images for Diabetic Foot Monitoring.

This work presents a revision of four different registration methods for thermal infrared and visible images captured by a camera-based prototype for the remote monitoring of diabetic foot. This prototype uses low cost and off-the-shelf available sensors in thermal infrared and visible spectra. Four different methods (Geometric Optical Translation, Homography, Iterative Closest Point, and Affine transform with Gradient Descent) have been implemented and analyzed for the registration of images obtained from both sensors. All four algorithms' performances were evaluated using the Simultaneous Truth and Performance Level Estimation (STAPLE) together with several overlap benchmarks as the Dice coefficient and the Jaccard index. The performance of the four methods has been analyzed with the subject at a fixed focal plane and also in the vicinity of this plane. The four registration algorithms provide suitable results both at the focal plane as well as outside of it within 50 mm margin. The obtained Dice coefficients are greater than 0.950 in all scenarios, well within the margins required for the application at hand. A discussion of the obtained results under different distances is presented along with an evaluation of its robustness under changing conditions.

Sirtuin GdSir2.4 participates in the regulation of rRNA transcription in the Giardia duodenalis parasite.

Giardia duodenalis is a parasite of great medical interest due to the number of infections it causes worldwide each year. Although research on epigenetic mechanisms in this protist has only begun recently, epigenetic regulation has already been shown to have important roles in encystation, antigenic variation, and resistance to antibiotics in Giardia. In this work, we show that a Giardia ortholog of Sir2, GdSir2.4, is involved in the silencing of rRNA expression. Our results demonstrate that GdSir2.4 localizes to the nucleolus, and its binding to the intergenic spacer region of the rDNA is associated with the deacetylation of the chromatin in this region. Given the importance of the regulation of rRNA expression to maintain adequate levels of ribosomes and genomic stability within the cells, GdSir2.4 can be considered a target to create new therapeutic agents against this parasite.

Segmentation Approaches for Diabetic Foot Disorders.

Thermography enables non-invasive, accessible, and easily repeated foot temperature measurements for diabetic patients, promoting early detection and regular monitoring protocols, that limit the incidence of disabling conditions associated with diabetic foot disorders. The establishment of this application into standard diabetic care protocols requires to overcome technical issues, particularly the foot sole segmentation. In this work we implemented and evaluated several segmentation approaches which include conventional and Deep Learning methods. Multimodal images, constituted by registered visual-light, infrared and depth images, were acquired for 37 healthy subjects. The segmentation methods explored were based on both visual-light as well as infrared images, and optimization was achieved using the spatial information provided by the depth images. Furthermore, a ground truth was established from the manual segmentation performed by two independent researchers. Overall, the performance level of all the implemented approaches was satisfactory. Although the best performance, in terms of spatial overlap, accuracy, and precision, was found for the Skin and U-Net approaches optimized by the spatial information. However, the robustness of the U-Net approach is preferred.

Circulating miR-15b, miR-34a and miR-218 as promising novel early low-invasive biomarkers of cervical carcinogenesis.

Circulating biological markers, such as miRNAs, hold the greatest possibilities to complement tissue biopsy and clinical diagnostic tests. The objective of this study was to evaluate the relative abundance of three circulating miRNAs in serum from 17 HPV16-positive patients with early cervical lesions known as Low-Grade Squamous Intraepithelial Lesions (LSILs). The expression of circulating microRNAs miR-15b, miR-34a and miR-218 in patients with LSILs was compared to 23 HPV-negative individuals showing normal cervical epithelium (healthy women) and 23 Squamous Cell Carcinoma (SCC) samples. The expression levels of miR-15b remained unchanged while those of miRNAs 34a and 218 were relatively high in serum obtained from LSIL patients in comparison with healthy women (results were statistically significant with a p of < 0.01 or < 0.001). According to previous findings, miR-15b was overexpressed and miRNAs 34a and 218 were underexpressed in serum from SCC patients. Additionally, the mRNA expression levels of some selected gene targets were determined [Cyclin D1 (CCND1), Cyclin E1 (CCNE1), B-cell lymphoma 2 (Bcl-2) and MutS homolog 2 (MSH-2)]. All serum results correlated with tissue samples from the same patients. We propose that circulating microRNAs can be valuable as molecular markers for the early follow-up of cervical carcinogenesis risk.

Bimodal microwave and ultrasound phantoms for non-invasive clinical imaging.

A precise and thorough methodology is presented for the design and fabrication of bimodal phantoms to be used in medical microwave and ultrasound applications. Dielectric and acoustic properties of human soft tissues were simultaneously mimicked. The phantoms were fabricated using polyvinyl alcohol cryogel (PVA-C) as gelling agent at a 10% concentration. Sucrose was employed to control the dielectric properties in the microwave spectrum, whereas cellulose was used as acoustic scatterer for ultrasound. For the dielectric properties at microwaves, a mathematical model was extracted to calculate the complex permittivity of the desired mimicked tissues in the frequency range from 500 MHz to 20 GHz. This model, dependent on frequency and sucrose concentration, was in good agreement with the reference Cole-Cole model. Regarding the acoustic properties, the speed of sound and attenuation coefficient were employed for validation. In both cases, the experimental data were consistent with the corresponding theoretical values for soft tissues. The characterization of these PVA-C phantoms demonstrated a significant performance for simultaneous microwave and ultrasound operation. In conclusion, PVA-C has been validated as gelling agent for the fabrication of complex multimodal phantoms that mimic soft tissues providing a unique tool to be used in a range of clinical applications.

Wideband Epidermal Antenna for Medical Radiometry.

Microwave thermometry is a noninvasive and passive technique for measuring internal body temperature. Wearable compact antennas, matched to the specific body area, are required for this method. We present a new epidermal wideband antenna for medical radiometry. The double asymmetric H-shaped slot antenna was designed to be matched to different parts of the body without fat layers. The slots are fed by a short-circuited microstrip line in order to decrease size and back radiation, thus reducing potential interferences. In this way, contribution to radiometric temperature due to back radiation is lower than 4%, versus the 20% of the volume under investigation, over the whole operating frequency band. The designed prototype was manufactured on a flexible substrate. The antenna is a very small size, to make it comfortable and suitable for being used by patients with different body mass indexes. The double H-shaped antenna shows good wideband matching results from around 1.5 GHz up to 5 GHz, in different body locations such as the neck, foot instep and foot sole.

Performance Assessment of Low-Cost Thermal Cameras for Medical Applications.

* Correspondence: evilla@iac [...].

Nicotinamide induces G2 cell cycle arrest in Giardia duodenalis trophozoites and promotes changes in sirtuins transcriptional expression.

Giardia duodenalis is a flagellated unicellular eukaryotic microorganism that commonly causes diarrheal disease throughout the world. Treatment of giardiasis is limited to nitroheterocyclic compounds as metronidazole and benzimidazoles as albendazole, where remarkably treatment failure is relatively common. Consequently, the need for new options to treat this disease is underscored. We predicted by a bioinformatic approach that nicotinamide inhibits Giardia sirtuins by the nicotinamide exchange pathway, and since sirtuins are involved in cell cycle control, they could be related with arrest and decrease of viability. When trophozoites were treated with nicotinamide (NAM), a strong arrest of Giardia trophozoites in G2 phase was observed and at the same time changes in transcriptional expression of sirtuins were produced. Interestingly, the G2 arrest is not related to double-strand breaks, which strengthens the role of sirtuins in the control of the Giardia cell cycle. Results with NAM-treated trophozoites as predicted demonstrate antigiardial effects and thus open new options for the treatment of giardiasis, either with the combination of nicotinamide with another antigiardial drug, or with the design of specific inhibitors for Giardia sirtuins.

Polyvinyl alcohol cryogel phantoms of biological tissues for wideband operation at microwave frequencies.

The aim of this work is to provide a methodology to model the dielectric properties of human tissues based on phantoms prepared with an aqueous solution, in a semi-solid form, by using off-the-shelf components. Polyvinyl alcohol cryogel (PVA-C) has been employed as a novel gelling agent in the fabrication of phantoms for microwave applications in a wide frequency range, from 500 MHz to 20 GHz. Agar-based and deionized water phantoms have also been manufactured for comparison purposes. Mathematical models dependent on frequency and sucrose concentration are proposed to obtain the complex permittivity of the desired mimicked tissues. These models have been validated in the referred bandwidth showing a good agreement to experimental data for different sucrose concentrations. The PVA-C model provides a great performance as compared to agar, increasing the shelf-life of the phantoms and improving their consistency for contact-required devices. In addition, the feasibility of fabricating a multilayer phantom has been demonstrated with a two-layer phantom that exhibits a clear interface between each layer and its properties. Thus, the use of PVA-C extends the option for producing complex multilayer and multimodal phantoms.

Mutant p53R248Q downregulates oxidative phosphorylation and upregulates glycolysis under normoxia and hypoxia in human cervix cancer cells.

Mutations in p53 are strongly associated with several highly malignant cancer phenotypes but its role in regulating energy metabolism has not been completely elucidated. The effect on glycolysis and oxidative phosphorylation (OxPhos) of mutant p53R248Q overexpression in HeLa cells (HeLa-M) was analyzed and compared with cells overexpressing wild-type p53 (HeLa-H) and nontransfected cells containing negligible p53 levels (HeLa-L). p53 R248Q overexpression induced early cell detachment during in vitro growth; however, detached HeLa-M cells showed high viability, shorter generation time and significant diminution in the adhesion proteins E-cadherin and ß-catenin versus HeLa-H and HeLa-L cells. Under normoxia, a lower growth rate of attached HeLa-M cells correlated with decreased levels of proliferating cell nuclear antigen (PCNA), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial proteins (20-80%) and OxPhos flux (69 ± 12%). On the contrary, HeLa-M also showed increased contents of CDKN1A, nuclear factor κB (NF-κB), c-MYC, hypoxia-inducible factor 1-α (HIF-1α; 1-4 times), glycolytic HIF-1α targets (2-4 times), and glycolysis flux (2-fold) versus HeLa-H. In consequence, glycolysis provided ~70% of the cellular adenosine triphosphate (ATP) in HeLa-M cells under normoxia whereas, OxPhos predominated (65-82%) in HeLa-H and HeLa-L cells. Pifithrin-α, a specific p53 inhibitor, did not alter the p53 R248Q target protein contents and OxPhos and glycolytic fluxes, and a poor HIF-1α-p53 R248Q interaction was attained, in HeLa-M cells. These observations suggested that p53 R248Q deficiently interacted with pifithrin-α and HIF-1α. Therefore, lower mitochondrial biogenesis, deficient HIF-1α/mutant p53 interaction, and development of a pseudohypoxic state under normoxia were the apparent biochemical mechanisms underlying glycolysis activation and OxPhos downregulation in HeLa-M cells.

Induction of p53 Phosphorylation at Serine 20 by Resveratrol Is Required to Activate p53 Target Genes, Restoring Apoptosis in MCF-7 Cells Resistant to Cisplatin.

Resistance to cisplatin (CDDP) is a major cause of cancer treatment failure, including human breast cancer. The tumor suppressor protein p53 is a key factor in the induction of cell cycle arrest, DNA repair, and apoptosis in response to cellular stimuli. This protein is phosphorylated in serine 15 and serine 20 during DNA damage repair or in serine 46 to induce apoptosis. Resveratrol (Resv) is a natural compound representing a promising chemosensitizer for cancer treatment that has been shown to sensitize tumor cells through upregulation and phosphorylation of p53 and inhibition of RAD51. We developed a CDDP-resistant MCF-7 cell line variant (MCF-7R) to investigate the effect of Resv in vitro in combination with CDDP over the role of p53 in overcoming CDDP resistance in MCF-7R cells. We have shown that Resv induces sensitivity to CDDP in MCF-7 and MCF-7R cells and that the downregulation of p53 protein expression and inhibition of p53 protein activity enhances resistance to CDDP in both cell lines. On the other hand, we found that Resv induces serine 20 (S20) phosphorylation in chemoresistant cells to activate p53 target genes such as PUMA and BAX, restoring apoptosis. It also changed the ratio between BCL-2 and BAX, where BCL-2 protein expression was decreased and at the same time BAX protein was increased. Interestingly, Resv attenuates CDDP-induced p53 phosphorylation in serine 15 (S15) and serine 46 (S46) probably through dephosphorylation and deactivation of ATM. It also activates different kinases, such as CK1, CHK2, and AMPK to induce phosphorylation of p53 in S20, suggesting a novel mechanism of p53 activation and chemosensitization to CDDP.

Early synergistic interactions between the HPV16­E7 oncoprotein and 17ß-oestradiol for repressing the expression of Granzyme B in a cervical cancer model.

Although high-risk human papillomavirus (HR­HPV) infection has a prominent role in the aetiology of cervical cancer (CC), sex steroid hormones may also be involved in this process; however, the cooperation between oestrogen and HR­HPV in the early stages of cervical carcinogenesis is poorly understood. Since 17ß-oestradiol (E2) and the HPV type 16­E7 oncoprotein induce CC in transgenic mice, a microarray analysis was performed in the present study to generate global gene expression profiles from 2­month­old FVB (non­transgenic) and K14E7 (transgenic) mice who were left untreated or were treated for 1 month with E2. Upregulation of cancer-related genes that have not been previously reported in the context of CC, including glycerophosphodiester phosphodiesterase domain containing 3, interleukin 1 receptor type II, natriuretic peptide type C, MGAT4 family member C, lecithin-retinol acyltransferase (phosphatidylcholine-retinol-O-acyltransferase) and glucoside xylosyltransferase 2, was observed. Notably, upregulation of the serine (or cysteine) peptidase inhibitor clade B member 9 gene and downregulation of the Granzyme gene family were observed; the repression of the Granzyme B pathway may be a novel mechanism of immune evasion by cancer cells. The present results provide the basis for further studies on early biomarkers of CC risk and synergistic interactions between HR­HPV and oestrogen.

Inhibition of RAD51 by siRNA and Resveratrol Sensitizes Cancer Stem Cells Derived from HeLa Cell Cultures to Apoptosis.

Cervical cancer is the second most frequent tumor type in women worldwide with cases developing clinical recurrence, metastasis, and chemoresistance. The cancer stem cells (CSC) may be implicated in tumor resistance to therapy. RESveratrol (RES), a natural compound, is an antioxidant with multiple beneficial activities. We previously determined that the expression of RAD51 is decreased by RES. The aim of our study was to examine molecular mechanism by which CSC from HeLa cultures exhibit chemoresistance. We hypothesized CSC repair more efficiently DNA breaks and that RAD51 plays an important role in this mechanism. We found that CSC, derived from cervical cancer cell lines, overexpress RAD51 and are less sensitive to Etoposide (VP16). We inhibited RAD51 in CSC-enriched cultures using RES or siRNA against RAD51 messenger RNA and observed a decrease in cell viability and induction of apoptosis when treated simultaneously with VP16. In addition, we found that inhibition of RAD51 expression using RES also sensitizes CSC to VP16 treatment. Our results suggest that resveratrol is effective to sensitize cervical CSC because of RAD51 inhibition, targeting high RAD51 expressing CD49f-positive cells, which supports the possible therapeutic application of RES as a novel agent to treat cancer.