Interaction between Cigarette Smoke and Human Papillomavirus 16 E6/E7 Oncoproteins to Induce SOD2 Expression and DNA Damage in Head and Neck Cancer.

Even though epidemiological studies suggest that tobacco smoking and high-risk human papillomavirus (HR-HPV) infection are mutually exclusive risk factors for developing head and neck cancer (HNC), a portion of subjects who develop this heterogeneous group of cancers are both HPV-positive and smokers. Both carcinogenic factors are associated with increased oxidative stress (OS) and DNA damage. It has been suggested that superoxide dismutase 2 (SOD2) can be independently regulated by cigarette smoke and HPV, increasing adaptation to OS and tumor progression. In this study, we analyzed SOD2 levels and DNA damage in oral cells ectopically expressing HPV16 E6/E7 oncoproteins and exposed to cigarette smoke condensate (CSC). Additionally, we analyzed SOD2 transcripts in The Cancer Genome Atlas (TCGA) Head and Neck Cancer Database. We found that oral cells expressing HPV16 E6/E7 oncoproteins exposed to CSC synergistically increased SOD2 levels and DNA damage. Additionally, the SOD2 regulation by E6, occurs in an Akt1 and ATM-independent manner. This study suggests that HPV and cigarette smoke interaction in HNC promotes SOD2 alterations, leading to increased DNA damage and, in turn, contributing to development of a different clinical entity.

Ionizing Radiation and Estrogen Affecting Growth Factor Genes in an Experimental Breast Cancer Model.

Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line, MCF-10F, to low doses of high linear energy transfer (LET) α particle radiation (150 keV/µm) and subsequent growth in the presence or absence of 17ß-estradiol. The MCF-10F cell line was analyzed in different stages of transformation after being irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles. In the present report, the profiling of differentially expressed genes associated with growth factors was analyzed in their relationship with clinical parameters. Thus, the results indicated that Fibroblast growth factor2 gene expression levels were higher in cells transformed by radiation or in the presence of ionizing radiation; whereas the fibroblast growth factor-binding protein 1gene expression was higher in the tumor cell line derived from this model. Such expressions were coincident with higher values in normal than malignant tissues and with estrogen receptor (ER) negative samples for both gene types. The results also showed that transforming growth factor alpha gene expression was higher in the tumor cell line than the tumorigenic A5 and the transformed A3 cell line, whereas the transforming growth factor beta receptor 3 gene expression was higher in A3 and A5 than in Tumor2 cell lines and the untreated controls and the E cell lines. Such gene expression was accompanied by results indicating negative and positive receptors for transforming growth factor alpha and the transforming growth factor beta receptor 3, respectively. Such expressions were low in malignant tissues when compared with benign ones. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expressions were found to be present in all BRCA patients that are BRCA-Basal, BRCA-LumA, and BRCA-LumB, except in BRCA-Her2 patients. The results also indicated that the insulin growth factor receptor gene expression was higher in the tumor cell line Tumor2 than in Alpha3 cells transformed by ionizing radiation only; then, the insulin growth factor receptor was higher in the A5 than E cell line. The insulin growth factor receptor gene expression was higher in breast cancer than in normal tissues in breast cancer patients. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expression levels were in stages 3 and 4 of breast cancer patients. It can be concluded that, by using gene technology and molecular information, it is possible to improve therapy and reduce the side effects of therapeutic radiation use. Knowing the different genes involved in breast cancer will make possible the improvement of clinical chemotherapy.

Cell Adhesion Molecules Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model.

Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell-cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17ß-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.

Reticulocyte hemoglobin and hypochromic erythrocytes in the study of erythropoiesis in patients with inflammatory bowel disease.

Anemia due to lack of iron (absolute or functional deficiency) is a common complication of inflammatory bowel disease (IBD). We investigated the potential utility of reticulocyte hemoglobin content (Ret-He) and percentage of hypochromic red cells (Hypo-He) in the assessment of erythropoiesis. We recruited 123 anemic outpatients with IBD. Biochemical tests for iron deficiency were carried out. Full blood counts were performed on a XN 20 system (Sysmex Diagnostics). Differences among groups were studied using analysis of variance and post-hoc tests, considering p < .05 to be significant. Receiver operating characteristic analysis was used to assess the diagnostic performance of Ret-He and Hypo-He for detecting iron-deficient erythropoiesis. The gold standard used for diagnosing iron deficiency was soluble transferrin receptor (sTfR), with a cut-off of >52 nmol/L. Overall, 60 patients had iron deficiency anemia (IDA), 27 anemia of chronic disease (ACD) and 36 mixed ACD + IDA. Ret-He showed the best performance, with an area under curve (AUC) of 0.858 (95% CI 0.816-0.952), considering a cut-off of 30.0 pg, sensitivity of 76.8% and specificity of 99.8% (vs. AUC 0.727 [95% CI 0.624-0.814], considering a cut-off of 4.0%, sensitivity 72.0% and specificity 72.5% for Hypo-He). Ret-He and Hypo-He can be used to assess iron supply for erythropoiesis in patients with IBD, to evaluate long-term (Hypo-He) and short-term (Ret-He) periods.

Salmon cells SHK-1 internalize infectious pancreatic necrosis virus by macropinocytosis.

We have previously shown that infectious pancreatic necrosis virus (IPNV) enters the embryo cell line CHSE-214 by macropinocytosis. In this study, we have extended our investigation into SHK-1 cells, a macrophage-like cell line derived from the head kidney of Atlantic salmon, the most economically important host of IPNV. We show that IPNV infection stimulated fluid uptake in SHK-1 cells above the constitutive macropinocytosis level. In addition, upon infection of SHK-1 cells, IPNV produced several changes in actin dynamics, such as protrusions and ruffles, which are important features of macropinocytosis. We also observed that the Na+/H+ pump inhibitor EIPA blocked IPNV infection. On the other hand, IPNV entry was independent of clathrin, a possibility that could not be ruled out in CHSE 214 cells. In order to determine the possible role of accessory factors on the macropinocytic process, we tested several inhibitors that affect components of transduction pathways. While pharmacological intervention of PKI3, PAK-1 and Rac1 did not affect IPNV infection, inhibition of Ras and Rho GTPases as well as Cdc42 resulted in a partial decrease in IPNV infection. Further studies will be required to determine the signalling pathway involved in the macropinocytosis-mediated entry of IPNV into its target cells.

HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS.

Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset.

[Sexual and reproductive health in young men in Chile: results of a qualitative studySaúde sexual e reprodutiva de jovens do sexo masculino no Chile: resultados de um estudo qualitativo]. / Salud sexual y reproductiva de hombres jóvenes en Chile: resultados de un estudio cualitativo.

OBJECTIVE: To describe, based on the perceptions of adolescents and health service staff, the ways in which adolescent boys interact with sexual and reproductive health services, the changes perceived in this area over time, and the Espacios Amigables strategy ('Friendly Spaces' for adolescent health) to reach out to boys. METHODS: An ethnographic, qualitative study was conducted in Friendly Spaces for adolescent and young adult health in five municipalities belonging to Chile's Metropolitan Region. The research methods used were semi-structured interviews (N = 38), discussion groups (N = 5), and participant observation. RESULTS: A masculinities perspective was [TN: "un enfoque de masculinidades". Or simply: "Masculine perspectives were…"] felt to be missing in adolescent sexual and reproductive health care, which is perceived to be an area geared primarily toward females. Most adolescent boys perceive health services as distant and visit them only in case of emergency. Male attendance is low at sexual and reproductive health services in Friendly Spaces within primary health care centers. However, services outside these centers attract boys in larger numbers, for example, one that is exclusively devoted to providing adolescent health care and integrated services in schools. CONCLUSIONS: Greater provision of adolescent sexual and reproductive health services does not necessarily translate into increased male access. For such an increase to occur, it is important to engage boys in addressing issues that capture their interest, bring health services closer to them, strengthen intersectoral work, and incorporate a masculinities perspectives in their care.

OBJETIVO: Descrever, a partir das percepções dos jovens e do pessoal de saúde, as formas como os adolescentes do sexo masculino se relacionam com a atenção de saúde sexual e reprodutiva, as transformações percebidas neste âmbito e as estratégias para atenção de saúde do adolescente por espaços amigáveis para o alcance deste grupo. MÉTODOS: Foi realizado um estudo qualitativo etnográfico em espaços amigáveis para atenção de saúde de adolescentes e jovens em cinco municípios da região metropolitana do Chile. Foram empregados os métodos de entrevistas semiestruturadas (N = 38) e grupos de discussão (N = 5) e a técnica de observação participante. RESULTADOS: Foi verificada a falta de uma perspectiva de masculinidades na atenção de saúde sexual e reprodutiva para adolescentes, que se percebe como sendo voltada principalmente ao sexo feminino. A maioria dos adolescentes e jovens percebe os serviços de saúde como distantes e recorrem a eles sobretudo em situações de emergência. Foi observada pouca assistência ao sexo masculino nos serviços de saúde sexual e reprodutiva em espaços amigáveis situados em unidades de atenção primária à saúde. No entanto, a frequência dos jovens é maior nos espaços localizados fora destas unidades, como em um centro exclusivo de atenção de saúde do adolescente e serviços integrados em escolas. CONCLUSÕES: Uma maior oferta de serviços de saúde sexual e reprodutiva para adolescentes não implica necessariamente maior acesso do sexo masculino. Para isso, é importante atrair os jovens com assuntos do interesse deles, acercar os serviços de saúde de onde eles estão, reforçar o trabalho intersetorial e incorporar um enfoque de masculinidades à atenção.

Higher prolactin and vasoinhibin serum levels associated with incidence and progression of retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a potentially blinding, retinal neovascular disease. Systemic prolactin accesses the retina to regulate blood vessels. Prolactin is proangiogenic and can be cleaved to antiangiogenic vasoinhibins. We investigated whether circulating prolactin and vasoinhibins associate with incidence and progression of ROP. METHODS: A prospective, longitudinal, case-control study covering postnatal weeks 1 to 9 measured serum prolactin, vasoinhibins, and vascular endothelial growth factor (VEGF) weekly in 90 premature infants diagnosed as ROP or control. RESULTS: Prolactin levels were higher in ROP than in control patients before (106.2 ± 11.3 (SEM) vs. 64.7 ± 4.9 ng/ml, postnatal week 1) and during (120.6 ± 10 vs. 84.7 ± 7.5ng/ml, postnatal week 5) ROP diagnosis. Prolactin, but not gestational age, birth weight, Apgar score, sepsis, or ventilation time, correlated with ROP. The relative risk (RR) of developing ROP increased if Prolactin (PRL) levels were higher than thresholds of 80 ng/ml (RR = 1.55, 95% CI: 1.06-2.28), 100 ng/ml (RR = 1.63, 95% CI: 1.14-2.34), or 120 ng/ml (RR = 1.95, 95% CI: 1.41-2.68). Vasoinhibin levels were 39.7% higher (95% CI: 4.5-77.5) in the circulation of ROP than in control patients at postnatal week 1 and similar thereafter, whereas VEGF serum levels were always similar. CONCLUSION: High serum prolactin and vasoinhibin levels predict and may impact ROP progression.

[Suicide in lesbian, gay, bisexual and trans populations: systematic review of a decade of research (2004-2014)]. / Suicidio en poblaciones lesbiana, gay, bisexual y trans: revisión sistemática de una década de investigación (2004-2014).

UNLABELLED: Lesbian, gay, bisexual and trans (LGBT) populations have a high prevalence of suicide behaviors. AIM: To review the literature on suicide among LGBT populations. MATERIAL AND METHODS: A systematic review of the scientific literature published between 2004 and 2014 on suicidality among LGBT people was conducted. Forty-five articles were selected for a thematic analysis. RESULTS: The research on suicide among LGBT people has increased during the last decade. The vast majority of studies have been conducted in the U.S. and other English speaking countries. At the same time, in a great part, these studies have been published in journals specializing in mental health and public health of sexual minorities. In general, they provide a significant foundation on protective and risk factors for suicide as well as their epidemiology. CONCLUSIONS: The focus of research on suicide among LGBT populations is mainly exploratory. More attention on these at-risk groups is required from the suicide research community in order to provide useful evidence for prevention and development of focalized and effective interventions.

Human papillomavirus infection in oral squamous cell carcinomas from Chilean patients.

Human papillomavirus (HPV) is the causal agent of cervical, anogenital and a subset of oropharyngeal carcinomas. In addition, the role of HPV in oral carcinogenesis has been suggested, although the findings are inconclusive. In this study, using conventional polymerase chain reaction (PCR) and genotyping by specific PCR and DNA sequencing, we analyzed the HPV presence in 80 oral squamous cell carcinomas (OSCCs) from Chilean subjects. In addition, we determined the expression of p16, p53, pRb and Ki-67 using immunohistochemistry (IHC). The CDKN2A (p16) promoter methylation was evaluated using methylation-specific PCR (MSP). HPV sequences were found in 9/80 (11%) OSCCs. Non-statistically significant association with p53, pRb, Ki-67 and p16 levels were found (p=0.77; 0.29; 0.83; 0.21, respectively). HPV-16 and 18 were the most prevalent HPV genotypes in 8/9 (89%) OSCCs. In addition, CDKN2A (p16) was methylated in 39% of OSCCs. No association with HPV presence (p=0.917) was found. These results suggest that HPV positive OSCCs are entities that do not resemble the molecular alterations of HPV-associated tumors in a Chilean population. More studies are warranted to determine the role of HPV in OSCCs.

HPV-associated lung cancers: an international pooled analysis.

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.

An Updated Review of the Marine Ornamental Fish Trade in the European Union.

Wild-caught fish from coral reefs, one of the most threatened ecosystems on the planet, continue to supply the marine aquarium trade. Despite customs and veterinary checks during imports, comprehensive data on this global industry remain scarce. This study provides consolidated data on the largest import market by value, the European Union (EU): a 24-million-euro annual trade value, detailing the main exporting and importing countries, as well as the species and families of the 26 million specimens imported between 2014 and 2021. A watchlist alert system based on the number of specimens traded, import trends, and vulnerability index according to FishBase and the IUCN Red List conservation status is presented, providing key information on which species should require closer scrutiny by authorities. While the European TRAde Control and Expert System (TRACES) electronically monitors the movement of live animals to respond quickly to biosecurity risks, one-third of marine ornamental fish imported lack species-level information. With minor adjustments, TRACES holds the potential to significantly enhance data granularity and the monitoring of wildlife trade, with marine ornamental fish being an interesting case study to validate this approach.

Three cases of kyphoplasty performed in the lateral position due to significant comorbidities.

Background: More than 700,000 people suffer from vertebral compression fractures attributed to osteoporosis, metastatic disease, or trauma each year in the United States, and undergo kyphoplasty. They are typical. These often undergo kyphoplasty to treat resultant pain or new neurological deficits. Here, we present three patients who, due to significant comorbidities, underwent kyphoplasty performed in the lateral decubitus rather than the prone position. Case Description: Three females, two with metastatic cancer and one with osteoporosis, presented with lumbar compression fractures and new accompanying pain and/or neurological deficits. Due to significant accompanying comorbidities, kyphoplasty was safely and effectively performed in all three patients utilizing the lateral decubitus rather than the prone position. Conclusion: Although vertebral kyphoplasties are typically performed in the prone position, here, we present three patients who, due to significant comorbidities, safely and effectively underwent kyphoplasties performed in the lateral decubitus position.

Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.

Breast cancer is frequently the most diagnosed female cancer in the world. The experimental studies on cancer seldom focus on the relationship between the central nervous system and cancer. Despite extensive research into the treatment of breast cancer, chemotherapy resistance is an important issue limiting the efficacy of treatment. Novel biomarkers to predict prognosis or sensitivity to chemotherapy are urgently needed. This study examined nervous-system-related genes. The profiling of differentially expressed genes indicated that high-LET radiation, such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of tumorigenicity in human breast epithelial cells. Bioinformatic tools allowed us to analyze the genes involved in breast cancer and associated with the nervous system. The results indicated that the gene expression of the Ephrin A1 gene (EFNA1), the roundabout guidance receptor 1 (ROBO1), and the kallikrein-related peptidase 6 (KLK6) was greater in T2 and A5 than in the A3 cell line; the LIM domain kinase 2 gene (LIMK2) was greater in T2 than A3 and A5; the kallikrein-related peptidase 7 (KLK7), the neuroligin 4 X-linked gene (NLGN4X), and myelin basic protein (MBP) were greater than A3 only in T2; and the neural precursor cell expressed, developmentally down-regulated 9 gene (NEDD9) was greater in A5 than in the A3 and E cell lines. Concerning the correlation, it was found a positive correlation between ESR1 and EFNA1 in BRCA-LumA patients; with ROBO1 in BRCA-Basal patients, but this correlation was negative with the kallikrein-related peptidase 6 (KLK6) in BRCA-LumA and -LumB, as well as with LIMK2 and ROBO1 in all BRCA. It was also positive with neuroligin 4 X-linked (NLGN4X) in BRCA-Her2 and BRCA-LumB, and with MBP in BRCA-LumA and -LumB, but negative with KLK7 in all BRCA and BRCA-LumA and NEDD9 in BRCA-Her2. The differential gene expression levels between the tumor and adjacent tissue indicated that the ROBO1, KLK6, LIMK2, KLK7, NLGN4X, MBP, and NEDD9 gene expression levels were higher in normal tissues than in tumors; however, EFNA1 was higher in the tumor than the normal ones. EFNA1, LIMK2, ROBO1, KLK6, KLK7, and MBP gene expression had a negative ER status, whereas NEDD9 and NLGN4X were not significant concerning ER status. In conclusion, important markers have been analyzed concerning genes related to the nervous system, opening up a new avenue of studies in breast cancer therapy.

PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.

High-risk human papillomaviruses (HR-HPVs) are the causal agents of cervical, anogenital and a subset of head and neck carcinomas (HNCs). Indeed, oropharyngeal cancers are a type of HNC highly associated with HR-HPV infections and constitute a specific clinical entity. The oncogenic mechanism of HR-HPV involves E6/E7 oncoprotein overexpression for promoting cell immortalization and transformation, through the downregulation of p53 and pRB tumor suppressor proteins, among other cellular targets. Additionally, E6/E7 proteins are involved in promoting PI3K/AKT/mTOR signaling pathway alterations. In this review, we address the relationship between HR-HPV and PI3K/AKT/mTOR signaling pathway activation in HNC with an emphasis on its therapeutic importance.

Cancer Stem Cell and Aggressiveness Traits Are Promoted by Stable Endothelin-Converting Enzyme-1c in Glioblastoma Cells.

Glioblastoma (GBM) is the most common and aggressive type of brain tumor due to its elevated recurrence following treatments. This is mainly mediated by a subpopulation of cells with stemness traits termed glioblastoma stem-like cells (GSCs), which are extremely resistant to anti-neoplastic drugs. Thus, an advancement in the understanding of the molecular processes underlying GSC occurrence should contribute significantly towards progress in reducing aggressiveness. High levels of endothelin-converting enzyme-1 (ECE1), key for endothelin-1 (ET-1) peptide activation, have been linked to the malignant progression of GBM. There are four known isoforms of ECE1 that activate ET-1, which only differ in their cytoplasmic N-terminal sequences. Isoform ECE1c is phosphorylated at Ser-18 and Ser-20 by protein kinase CK2, which increases its stability and hence promotes aggressiveness traits in colon cancer cells. In order to study whether ECE1c exerts a malignant effect in GBM, we designed an ECE1c mutant by switching a putative ubiquitination lysine proximal to the phospho-serines Lys-6-to-Arg (i.e., K6R). This ECE1cK6R mutant was stably expressed in U87MG, T98G, and U251 GBM cells, and their behavior was compared to either mock or wild-type ECE1c-expressing clone cells. ECE1cK6R behaved as a highly stable protein in all cell lines, and its expression promoted self-renewal and the enrichment of a stem-like population characterized by enhanced neurospheroid formation, as well as increased expression of stem-like surface markers. These ECE1cK6R-derived GSC-like cells also displayed enhanced resistance to the GBM-related chemotherapy drugs temozolomide and gemcitabine and increased expression of the ABCG2 efflux pump. In addition, ECE1cK6R cells displayed enhanced metastasis-associated traits, such as the modulation of adhesion and the enhancement of cell migration and invasion. In conclusion, the acquisition of a GSC-like phenotype, together with heightened chemoresistance and invasiveness traits, allows us to suggest phospho-ECE1c as a novel marker for poor prognosis as well as a potential therapeutic target for GBM.

Merkel cell polyomavirus in non-small cell lung carcinomas from Chile.

Lung cancer is a leading pathology strongly associated with the smoking habit. However, a viral etiology for a subset of patients developing lung cancer has been suggested. Polyomaviruses (PyVs) are small double stranded DNA viruses associated with the development of some human diseases. However, a causal role of these viruses in human cancer has been difficult to demonstrate. In this study, eighty-six non-small cell lung carcinomas (NSCLCs), including adenocarcinomas (AdCs) and squamous cell lung carcinomas (SQCs) from Chile were analyzed for the presence of PyVs using polymerase chain reaction (PCR). All of the specimens were positive for a fragment of the betaglobin gene. We found that 4/86 (4.7%) of lung carcinomas were positive for PyVs. After sequencing and BlastN alignment, all four cases were identified as Merkel cell polyomaviruses (MCV) that corresponded to two AdCs and two SQCs. A non-significant statistical association was found between the presence of MCV and clinic-pathological features of the patients and tumors. In addition, 1/4 (25%) of the carcinomas were actively expressing large T antigen (LT) transcripts, as demonstrated by reverse-transcriptase PCR (RT-PCR). Thus a possible role of MCV in a very small subset of patients with lung cancer cannot be ruled out and warrants more investigation.

[Male depression and its symptoms: A qualitative study with Chilean adult men]. / La depresión masculina y sus síntomas: Un estudio cualitativo con hombres adultos chilenos.

In Chile, one out of every ten men presents signs or symptoms of depression each year. However, few studies within Chile or other Latin American countries address the qualitative or narrative aspects of depression in men. Therefore, the objective of this study was to assess the narrative construction of depression and its symptoms in men. This qualitative study was based on interviews with nine Chilean men who had gone through an experience of this nature, which were conducted between June and October 2020. A life history methodology was used to explore depressive processes involved in each individual's biography as well as the symptoms reported in each case. The results show that these men experienced a constellation of symptoms during depression, some of which are atypical as they do not match those described in diagnostic manuals. Three types of narratives were identified, and were termed frustration, breakdown, and insecurity.

En Chile, uno de cada diez hombres presenta indicios o síntomas de depresión cada año. No obstante, tanto en el país como en el resto de América Latina son escasos los estudios que abordan la depresión masculina desde sus aspectos cualitativos y narrativos. El objetivo de este estudio fue, por tanto, analizar la construcción narrativa de la depresión y sus síntomas en hombres, por medio de un estudio cualitativo con entrevistas realizadas entre junio y octubre de 2020 a nueve hombres chilenos que habían pasado por un proceso de esta naturaleza. A partir de una metodología de relato de vida, se exploraron los procesos depresivos en cada biografía, así como los síntomas reportados en cada una de ellas. Los resultados muestran que los hombres experimentan una constelación de síntomas durante una depresión, algunos de ellos atípicos, pues no se corresponden con aquellos descritos en los manuales diagnósticos. Se identificaron tres formas narrativas que fueron denominadas de frustración, de quiebre y de inseguridad.

Epstein-Barr Virus Association with Breast Cancer: Evidence and Perspectives.

Epstein-Barr virus (EBV) is an enveloped DNA virus that belongs to the gamma Herpesviridae family. The virus establishes a latent/lytic persistent infection, though it can be involved in cancer development in some subjects. Indeed, evidence supports an etiological role of EBV in undifferentiated nasopharyngeal carcinoma (NPC), a subset of gastric carcinomas and lymphomas. Additionally, EBV has been detected in breast carcinomas (BCs) although its role has not been established. In this review, we summarize epidemiological information regarding the presence of EBV in BC and we propose mechanistic models. However, additional epidemiological and experimental evidence is warranted to confirm these models.

Human Papillomavirus Detected in Oropharyngeal Cancers from Chilean Subjects.

High-risk human papillomaviruses (HR-HPV) are the causal agents of an important subset of oropharyngeal cancers that has increased considerably in incidence in recent years. In this study, we evaluated the presence of HPV in 49 oropharyngeal cancers from Chilean subjects. The presence of HPV DNA was analyzed by conventional PCR, the genotypes were identified through sequencing, and the expression of E6/E7 transcripts was evaluated by a reverse transcriptase polymerase chain reaction (RT-PCR). Additionally, to determine p16 expression-a surrogate marker for oncogenic HPV infection-a tissue array was constructed for immunohistochemistry (IHC). HPV was detected in 61.2% of oropharyngeal carcinomas, the most prevalent genotype being HPV16 (80%). E6 and E7 transcripts were detected in 91.6% and 79.1% of the HPV16-positive specimens, respectively, demonstrating functional HPV infections. Furthermore, p16 expression was positive in 58.3% of cases. These findings show a high prevalence of HR-HPV in oropharyngeal tumors from Chile, suggesting the necessity of additional studies to address this growing public health concern.