Phenotypic Heterogeneity of Cancer Associated Fibroblasts in Cervical Cancer Progression: FAP as a Central Activation Marker.

Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA- FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

HPV and Cervical Cancer: Molecular and Immunological Aspects, Epidemiology and Effect of Vaccination in Latin American Women.

Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores molecular and immunological aspects of HPV infection, its role in cervical cancer development, and the epidemiology in this region, highlighting the prevalence and diversity of HPV genotypes. The impact of vaccination initiatives on cervical cancer rates in Latin America is critically evaluated. The advent of HPV vaccines has presented a significant tool in combating the burden of this malignancy, with notable successes observed in various countries, the latter due to their impact on immune responses. The review synthesizes current knowledge, emphasizes the importance of continued research and strategies for cervical cancer prevention, and underscores the need for ongoing efforts in this field.

Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores.

Prostate cancer (PCa) is the most prevalent cause of death in the male population worldwide. The G Protein-Coupled Estrogen Receptor (GPER) has been gaining relevance in the development of PCa. Hedgehog (Hh) pathway activation is associated with aggressiveness, metastasis, and relapse in PCa patients. To date, no studies have evaluated the crosstalk between the GPER and the Hh pathway along different group grades in PCa. We conducted an analysis of paraffin-embedded tissues derived from patients with different prognostic grade of PCa using immunohistochemistry. Expression and correlation between GPER and glioma associated oncogene homologue (GLI) transcriptional factors in the parenchyma and stroma of PCa tumors were evaluated. Our results indicate that GPER is highly expressed in the nucleus and increases with higher grade groups. Additionally, GPER's expression correlates with pGLI3 nuclear expression across different grade groups in PCa tissues; however, whether the receptor induces the activation of GLI transcriptional factors, or the latter modulate the expression of GPER is yet to be discovered, as well as the functional consequence of this correlation.

HPV-Negative and HPV-Positive Oral Cancer Cells Stimulate the Polarization of Neutrophils towards Different Functional Phenotypes In Vitro.

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV- tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV- and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV- OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets.

Frequency of urinary pesticides in children: a scoping review.

Pesticides are any mix of ingredients and substances used to eliminate or control unwanted vegetable or animal species recognized as plagues. Its use has been discussed in research due to the scarcity of strong scientific evidence about its health effects. International literature is still insufficient to establish a global recommendation through public policy. This study aims to explore international evidence of the presence of pesticides in urine samples from children and their effects on health through a scoping review based on the methodology described by Arksey and O'Malley. The number of articles resulting from the keyword combination was 454, and a total of 93 manuscripts were included in the results and 22 were complementary. Keywords included in the search were: urinary, pesticide, children, and childhood. Children are exposed to pesticide residues through a fruit and vegetable intake environment and household insecticide use. Behavioral effects of neural damage, diabetes, obesity, and pulmonary function are health outcomes for children that are commonly studied. Gas and liquid chromatography-tandem mass spectrometry methods are used predominantly for metabolite-pesticide detection in urine samples. Dialkylphosphates (DAP) are common in organophosphate (OP) metabolite studies. First-morning spot samples are recommended to most accurately characterize OP dose in children. International evidence in PubMed supports that organic diets in children are successful interventions that decrease the urinary levels of pesticides. Several urinary pesticide studies were found throughout the world's population. However, there is a knowledge gap that is important to address (public policy), due to farming activities that are predominant in these territories.

Non-traditional risk factors of progression of chronic kidney disease in adult population: a scoping review.

Chronic kidney disease (CKD) has become a public health concern over the last several years. Nowadays developed countries spend around 3% of their annual health-care budget on patients with CKD. According to the scientific community the most remarkable risk factors for CKD are diabetes and hypertension. Unknown CKD etiology has been reported as a global phenomenon including uncommon risk factors such as: dehydration, leptospirosis, heat stress, water quality, and others. This study aims to report non-traditional risk factors for ESRD based on a scoping review methodology. The scoping review methodology described by Arksey and O'Malley was used by performing an extensive review of the information. A total of 46 manuscripts were reviewed. The non-traditional ESRD risk factors are depicted based on six categories. Gender and ethnicity have been considered as risk factors for ESRD. Erythematous systemic lupus (ESL) is reported as an important risk factor for ESRD. Pesticide use has been an significant risk factor due to its effects on human and environmental health. Some compounds commonly used in homes against insects and plants are related to ESRD. Congenital and hereditary diseases in the urinary tract have been studied as a cause of ESRD in children and young adults. End-stage renal disease is a major concern for public health on a global level. As it can be seen, non-traditional risk factors are several and have different etiologies. It is necessary to put the issue on the table and add it to the public agenda in order to find multidisciplinary solutions.

Cancer-associated fibroblasts in gynecological malignancies: are they really allies of the enemy?

Molecular and cellular components of the tumor microenvironment are essential for cancer progression. The cellular element comprises cancer cells and heterogeneous populations of non-cancer cells that satisfy tumor needs. Immune, vascular, and mesenchymal cells provide the necessary factors to feed the tumor mass, promote its development, and favor the spread of cancer cells from the primary site to adjacent and distant anatomical sites. Cancer-associated fibroblasts (CAFs) are mesenchymal cells that promote carcinogenesis and progression of various malignant neoplasms. CAFs act through the secretion of metalloproteinases, growth factors, cytokines, mitochondrial DNA, and non-coding RNAs, among other molecules. Over the last few years, the evidence on the leading role of CAFs in gynecological cancers has notably increased, placing them as the cornerstone of neoplastic processes. In this review, the recently reported findings regarding the promoting role that CAFs play in gynecological cancers, their potential use as therapeutic targets, and the new evidence suggesting that they could act as tumor suppressors are analyzed and discussed.

Differential modulation of natural killer cell cytotoxicity by 17ß-estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells.

Natural killer (NK) cells play a crucial role in cervical cancer (CC). As estrogens and prolactin (PRL) have been reported to be involved in CC, the present study attempted to elucidate the effects of both hormones on NK cells in CC. For this purpose, NKL cells, as well as CC-derived cell lines (HeLa, SiHa and C33A) and non-tumorigenic keratinocytes (HaCaT cells) were stimulated with 17ß-estradiol (E2; 10 nM), PRL (200 ng/ml), or both (E2 and PRL) for 48 h. The expression of hormone receptors (estrogen receptor α and ß, G protein-coupled estrogen receptor 1 and PRL receptor) and NK cell activating receptors [natural killer group 2D (NKG2D), natural cytotoxicity triggering receptor 3, natural cytotoxicity triggering receptor 2 and natural cytotoxicity triggering receptor 1] were measured using western blot analysis and flow cytometry, respectively. In the HeLa, SiHa, C33A and HaCaT cells stimulated with the hormones, the expression of NKG2D ligands [MHC class I polypeptide-related sequence A/B (MICA/B)] on the membrane and the soluble form of MICA was evaluated using flow cytometry and ELISA. Cytotoxicity assay was performed using GFP-transfected K562 cells as target cells. E2 reduced NKL cell-mediated cytotoxicity, while PRL exerted the opposite effect. NKL cells expressed different hormone receptor forms, of which PRL only induced a decrease in NKG2D expression compared to the untreated control NKL cells. PRL increased MICA/B expression in HeLa cells and E2 and PRL reversed this effect. However, in SiHa cells, the concurrent incubation with the two hormones decreased MICA/B expression. E2 and PRL, either alone or in combination, decreased soluble MICA secretion in all CC cell lines, while E2 solely increased soluble MICA secretion in SiHa cells. On the whole, the present study provides evidence that E2 and PRL mediate the mechanisms through which NK and CC cells mediate a cytotoxic response and these have an antagonistic effect on NK cell-mediated cytotoxicity.

17ß-estradiol modulates the expression of hormonal receptors on THP-1 T. gondii-infected macrophages and monocytes in an AKT and ERK-dependent manner.

Toxoplasma gondii (T. gondii) is a parasite common in pregnancy. Monocytes and macrophages are a significant immunologic barrier against T. gondii by boosting up inflammation. This outcome is highly regulated by signaling pathways such as MAPK (ERK1/2) and PI3K (AKT), necessary in cell growth and proliferation. It may be associated with the hormonal receptors' modulation by T. gondii (Estrogen Receptor (ER)-α, ERß, G Protein-coupled ER (GPER), and Prolactin Receptor (PRLR)), as previously reported by our research group. 17ß-estradiol also activates MAPK and PI3K; however, its combined effect in THP-1 monocytes and macrophages, infected with T. gondii, has not yet been evaluated. This study aimed to evaluate the combined effect of 17ß-estradiol in the activation of signaling pathways using a model of THP-1 monocytes and macrophages infected with T. gondii. THP-1 monocytes were cultured and differentiated into macrophages. Inhibition of AKT and ERK1/2 was performed with specific inhibitors. Stimuli were performed with 17ß-estradiol (10 nM), T. gondii (20,000 tachyzoites), and both conditions for 48 h. Proteins were extracted and quantified, and Western Blot assays were performed. 17ß-estradiol performed activation of ERK1/2 and AKT in T. gondii-infected macrophages. 17ß-estradiol modulated the expression of hormonal receptors in infected cells: increases the PRLR and PrgR in T. gondii-infected macrophages and decreases the PRLR and ERα in T. gondii-infected monocytes. As for GPER, its expression is abolished by T. gondii, and 17ß-estradiol cannot restore it. Finally, the blockage of ERK and AKT pathways modified the expression of hormonal receptors. In conclusion, 17ß-estradiol modifies the receptors of T. gondii-infected THP1 macrophages and monocytes in an ERK/AKT dependent manner.

Exosomal miRNAs and lncRNAs: The Modulator Keys of Cancer-Associated Fibroblasts in the Genesis and Progression of Malignant Neoplasms.

The tumor microenvironment is made up of a universe of molecular and cellular components that promote or inhibit the development of neoplasms. Among the molecular elements are cytokines, metalloproteinases, proteins, mitochondrial DNA, and nucleic acids, within which the ncRNAs: miRNAs and lncRNAs stand out due to their direct modulating effects on the genesis and progression of various cancers. Regarding cellular elements, the solid tumor microenvironment is made up of tumor cells, healthy adjacent epithelial cells, immune system cells, endothelial cells, and stromal cells, such as cancer-associated fibroblasts, which are capable of generating a modulating communication network with the other components of the tumor microenvironment through, among other mechanisms, the secretion of exosomal vesicles loaded with miRNAs and lncRNAs. These ncRNAs are key pieces in developing neoplasms since they have diverse effects on cancer cells and healthy cells, favoring or negatively regulating protumoral cellular events, such as migration, invasion, proliferation, metastasis, epithelial-mesenchymal transition, and resistance to treatment. Due to the growing number of relevant evidence in recent years, this work focused on reviewing, analyzing, highlighting, and showing the current state of research on exosomal ncRNAs derived from cancer-associated fibroblasts and their effects on different neoplasms. A future perspective on using these ncRNAs as real therapeutic tools in the treatment of cancer patients is also proposed.

The Relevant Participation of Prolactin in the Genesis and Progression of Gynecological Cancers.

Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy, cell growth, and differentiation. However, PRL is nowadays known to have a strong implication in oncogenic processes, making it essential to delve into the mechanisms governing these actions. PRL and its receptor (PRLR) activate a series of effects such as survival, cellular proliferation, migration, invasion, metastasis, and resistance to treatment, being highly relevant in developing certain types of cancer. Because women produce high levels of PRL, its influence in gynecological cancers is herein reviewed. It is interesting that, other than the 23 kDa PRL, whose mechanism of action is endocrine, other variants of PRL have been observed to be produced by tumoral tissue, acting in a paracrine/autocrine manner. Because many components, including PRL, surround the microenvironment, it is interesting to understand the hormone's modulation in cancer cells. This work aims to review the most important findings regarding the PRL/PRLR axis in cervical, ovarian, and endometrial cancers and its molecular mechanisms to support carcinogenesis.

The role of estradiol in the immune response against COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen agent causing coronavirus disease (COVID)-19, which was declared a global pandemic in 2020. The spike protein of this virus and the angiotensin-converter enzyme (ACE)-2 in host cells in humans play a vital role in infection and in COVID-19 pathogenesis. Estradiol is known to modulate the actions of immune cells, and, therefore, the antiviral mechanisms of these cells could also be modified by this hormone stimulus. Even though estradiol is not considered a protective factor, evidence shows that women with high levels of this hormone have a lower risk of developing severe symptoms and an even a lower incidence of death. Understanding the mechanism of action of estradiol with regard to viral infections and COVID-19 is essential for the improvement of therapeutic strategies. This review aims to describe the effects that estradiol exerts on immune cells during viral infections and COVID-19.

Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms.

Estrogens are hormones that have been extensively presented in many types of cancer such as breast, uterus, colorectal, prostate, and others, due to dynamically integrated signaling cascades that coordinate cellular growth, differentiation, and death which can be potentially new therapeutic targets. Despite the historical use of estrogens in the pathogenesis of prostate cancer (PCa), their biological effect is not well known, nor their role in carcinogenesis or the mechanisms used to carry their therapeutic effects of neoplastic in prostate transformation. The expression and regulation of the estrogen receptors (ERs) ERα, ERß, and GPER stimulated by agonists and antagonists, and related to prostate cancer cells are herein reviewed. Subsequently, the structures of the ERs and their splice variants, the binding of ligands to ERs, and the effect on PCa are provided. Finally, we also assessed the contribution of molecular simulation which can help us to search and predict potential estrogenic activities.

17ß­estradiol­induced mitochondrial dysfunction and Warburg effect in cervical cancer cells allow cell survival under metabolic stress.

Mitochondria from different types of cancer show bioenergetics and dysfunction that favor cell proliferation. The mechanistic understanding of estrogen in cervical cancer is poorly understood. Therefore, the objective of this study was to determine how 17ß­estradiol (E2) affects mitochondrial function and the Warburg effect in SiHa, HeLa and C33A cervical cancer cells. Mitochondrial compromise was evaluated measuring changes in the membrane permeability by immunofluorescence, calcium concentration, redox status, iron and ferritin reserves. Glucose consumption and lactic acid assays were used to detect the metabolic activity. Results were confirmed at molecular level by analysis of the differential gene expression using RNA sequencing. E2 modified the mitochondrial permeability and produced an alteration in the calcium signaling pathway. In HeLa and SiHa, there was a significant decrease in nitric oxide levels and lipid peroxidation, and an increase in glucose consumption and lactic acid levels when stimulated with E2. Intracellular iron or ferritin reserves were not affected by the E2 treatment. Genes differentially modulated by E2 were involved in the mitochondrial electron transport chain, oxidative phosphorylation system, glycolysis, pentose phosphate pathway and the regulation of metabolic signaling pathways. Herein, we provide evidence for a primary effect of estrogen on mitochondrial function and the Warburg effect, favoring the metabolic adaptation of the cervical cancer cell lines and their survival.

Interaction between 17ß-estradiol, prolactin and human papillomavirus induce E6/E7 transcript and modulate the expression and localization of hormonal receptors.

BACKGROUND: Cervical cancer (CC) is the second most common cancer in less developed countries and the second leading cause of death by cancer in women worldwide. The 99% of CC patients are infected with the Human Papilloma Virus (HPV), being HPV16 and HPV18 infection the most frequent. Even though HPV is considered to be a necessary factor for the development of CC, it is not enough, as it requires the participation of other factors such as the hormonal ones. Several studies have demonstrated the requirement of estrogen and its receptors (ERα, ERß, and GPER) in the precursor lesions progress towards CC. Also, prolactin (PRL) and its receptor (PRLR) have been associated with CC. The molecular mechanisms underlying the cooperation of these hormones with the viral oncoproteins are not well elucidated. For this reason, this study focused on analyzing the contribution of 17ß-estradiol (E2), PRL, and HPV on the expression and localization of hormone receptors, as well as to evaluate whether these hormones may promote greater expression of HPV oncogenes and contribute to tumor progression. METHODS: qPCR was used to evaluate the effect of E2 and PRL on the expression of E6 and E7 oncoproteins in HeLa and SiHa cervical cancer cells lines. HaCaT cells were transduced with the viral oncogenes E6 and E7 from HPV 16 and 18. ERα, ERß, GPER, and PRLR expression and localization were evaluated by qPCR, Western blot and immunofluorescence. RESULTS: E2 and PRL induce E6/E7 oncogenes expression in HeLa and SiHa cells. E6 and E7 oncogenes of HPV16/18 significantly increased the protein expression of ERα, GPER, and PRLR. ERß was positively regulated only by E6 oncogenes of HPV16/18. Besides, some of these oncogenes modify the location of PRLR toward cytoplasm, and ERα, ERß, and GPER mainly to the nucleus. CONCLUSION: Our studies suggest that the mutual regulation between E2, PRL, and HPV oncogenes could cooperate with the carcinogenesis process in CC.

Hormonal modulation of Toxoplasma gondii infection: Regulation of hormonal receptors and cytokine production in THP-1 cells.

BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan able to infect humans and it is common in pregnant women. During pregnancy and lactation, there are changes in the concentration of 17ß-estradiol (E2), progesterone (Prg), and prolactin (PRL). It is known that a proinflamatory response reduces the susceptibility to be infected, and this response may change according to hormonal impairment. Monocytes and macrophages are the main barrier against many intracellular microorganisms, due to their ability to produce cytokines. The aim of this work was to determine the effect of E2, progesterone, and PRL on the infective capacity of T. gondii, proinflamatory immune response modulation and the expression of hormonal receptors on THP-1 cell stimulated with T. gondii. METHODS: The THP-1 cells were infected with 1500 T. gondii tachyzoites, of RH strain. Stimuli were conducted with recombinant PRL (200 ng/mL), E2 (40 nM) y Prg (40 nM). MTT assays were performed to evaluate cellular viability. Western blot assays were carried out to evaluate the expression of the hormonal receptors (PRLR, ERα, and ERß). Cytokines produced were measured with a magnetic bead kit directed to 17 cytokines. RESULTS: Stimuli with E2 and Prg increased T. gondii infection in monocytes after 48 h; however, no differences in infection were observed in PRL stimulus. The E2 decreased the secretion of IL-12 and IL-1ß and PRL did not modify the production of these cytokines in THP-1 cells stimulated with T. gondii; however, both hormones increased the production of IL-10. Besides, PRL augmented the production of IL-4 and IL-13. In contrast, Prg reduced these cytokines. Our results show that T. gondii induces the expression of ERα and ERß and lowers PRLR. The hormones modify the expression of the receptors of other hormones: Prg decreases PRLR, ERß and increases ERα; E2 diminishes PRLR; and PRL decreases ERα and ERß expression. CONCLUSION: The hormones can increase T. gondii infection and could be mediating an anti-inflammatory response in THP-1 cells. T. gondii induces changes in the expression of hormonal receptors.

GPER Overexpression in Cervical Cancer Versus Premalignant Lesions: Its Activation Induces Different Forms of Cell Death.

BACKGROUND: The effect of estrogen has been traditionally studied through the modulation of its alpha and beta nuclear receptors; however, the G Protein-Coupled Estrogen Receptor (GPER) has been recently involved in the pathology of numerous tumors. Although the study of GPER in cervical cancer has begun, its contribution still remains to be completely evaluated. OBJECTIVE: The purpose of this work was to determine the expression of this receptor in different degrees of cervical lesions and whether the stimulation with its specific agonist (G-1) modulated mechanisms of cell survival or cell death in cervical cancer cells. METHODS: Sections of 44 formalin-fixed paraffin-embedded blocks from patients were analyzed by automated immunohistochemistry. After the stimulation with G-1, proliferation was evaluated by the xCELLigence technology, the integrity of the mitochondrial membrane permeability by MitoCaptureTM fluorescence staining, apoptosis by flow cytometry, and senescence by the senescence-associated ß-galactosidase kit. RESULTS: GPER was widely expressed in cervical cancer but not in its precursor lesions. The staining was predominantly cytoplasmic, although it was also important in the nucleus of the epithelial cells. G-1 inhibited proliferation, decreased the mitochondrial permeability, and increased the percentage of apoptosis in SiHa, HeLa, and C-33A. Only in C-33A, an increase of the cells in necrosis was observed, whereas SiHa was the only cell line in which senescence was evidenced. CONCLUSION: GPER is a receptor associated with cervical cancer that inhibits the growth and induces different mechanisms of death in cells derived from uterine cervical cancer. It suggests that GPER can be considered a pharmacological target that prevents the development of cervical carcinogenesis.

Prevalence of Epstein-Barr virus DNA in tonsillar tissue from patients with chronic tonsillitis in Mexican population.

INTRODUCTION: Epstein-Barr Virus (EBV) infection prevails in underdeveloped and developing countries. The tonsils seem to be candidate replication sites for EBV and some studies have exposed a close association among viral infections and chronic tonsillitis. The objective of this study was identifying the EBV prevalence in Mexican patients who had undergone tonsillectomy because of chronic tonsillitis. METHODOLOGY: Frozen tissues and medical records were obtained from 50 Mexican patients. DNA was extracted and subjected to PCR to amplify the EBER-2 region of EBV. Next, the patients were classified according to general and clinical characteristics searching a relation with the EBV-DNA positivity. RESULTS: EBV genome was detected in 46% (23/50) of the analysed tonsil tissues. Trends were found regarding the relationship of viral presence with lower values in terms of age (6.1 ± 2.8 vs 7.6 ± 3.7) , a greater degree of hypertrophy (3.5 ± 0.4 vs 3.0 ± 0.6) and an increase in the number of episodes of tonsillitis (11 ± 7.4 vs 9 ± 6.5). CONCLUSIONS: The prevalence found of EBV-DNA positivity in tonsillar tissues from patients diagnosed with chronic tonsillitis , supports the fact that palatine tonsils can be occupied by EBV and highlights the importance of conducting future studies focused on understanding the role of the EBV infection in chronic inflammatory processes in the population involved in this study.

Effects of 60 kDa prolactin and estradiol on metabolism and cell survival in cervical cancer: Co­expression of their hormonal receptors during cancer progression.

Estrogens and estrogen receptors (ERs), such as ERα and ERß, prolactin (PRL) and prolactin receptor (PRLR) have been reported to be involved in the physiopathology of uterine cervical cancer (UCC). The 60 kDa PRL is an isoform of PRL, which is produced by UCC­derived cells. The present study aimed to evaluate the expression of hormonal receptors in different degrees of cervical lesions, and to determine whether 60 kDa PRL and 17ß­estradiol (E2) modulated cell survival and metabolism in UCC cells, and in HaCaT cells transduced with human papillomavirus (HPV) 16 and 18 E6/E7 oncogenes. ERα, ERß, PRLR, Ki67 and B­cell lymphoma 2 expression levels were analyzed in biopsies of precursor lesions and UCC using immunohistochemistry. In addition, HeLa, SiHa and C33A cells, and transduced HaCaT cells, were stimulated with 60 kDa PRL, E2 or a combination of both. Proliferation was evaluated using the xCELLigence platform, apoptosis was analyzed by flow cytometry and cell metabolism was determined using the MTT assay. The results revealed that ERα, ERß, PRLR and Ki67 expression levels were increased during the progression of cancer. In vitro, 60 kDa PRL alone significantly increased proliferation of SiHa cells. Furthermore, E2 alone or in combination with 60 kDa PRL increased the sensitivity of SiHa cells to cisplatin and increased the percentage of apoptosis; in HaCaT cells, these treatment strategies had the opposite effect on cisplatin sensitivity. Treatment with E2 increased mitochondrial activity in HeLa and SiHa cells, and in HaCaT cells transduced with HPV 16 E6/E7 and HPV 18 E6 oncogenes. PRL had a similar effect on HeLa cells, and on HaCaT cells transduced with HPV 18 E6 and HPV 16 E7. The co­expression of these receptors demonstrated the hormonal dependence of UCC. In addition, E2 and the 60 kDa PRL significantly impacted the metabolism, but not the survival, of cells.

A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production.

Prolactin (PRL) is associated with different types of cancer, such as cervical cancer. Recombinant PRL has antiapoptotic effect on cervical cancer cells, and it can also induce cytokine production on macrophages. A 60 kDa variant of PRL is produced by cervical cancer cells. The aim of the present study was to evaluate this variant's bioactivity, to test its effect on cervical cancer cell apoptosis, and to assess its ability to induce cytokine production on THP-1 macrophages. First, 60 kDa PRL was isolated and used to stimulate Nb2 cells. Later, apoptosis was measured after exposure to 60 kDa PRL. Finally, cytokines were measured on THP-1 stimulated supernatants. Our results show that 60 kDa PRL increased Nb2 cell proliferation. Apoptosis was decreased after stimuli with 60 kDa PRL in cervical cancer cells. IL-1ß and TNF-α are produced by THP-1 macrophages after stimuli. These results suggest that 60 kDa PRL produced by cervical cancer cells is able to reduce apoptosis in HeLa, SiHa and C-33A cells and induce IL-1ß and TNF-α production by THP-1 macrophages.