RESUMEN
Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.
Asunto(s)
Neoplasias de la Vesícula Biliar , Regulación Neoplásica de la Expresión Génica , MicroARNs , Factor 3 de Transcripción de Unión a Octámeros , ARN Largo no Codificante , Humanos , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/metabolismo , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Femenino , Transición Epitelial-Mesenquimal/genética , Resistencia a Antineoplásicos/genética , Masculino , Invasividad Neoplásica , Cisplatino/farmacología , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fluorouracilo/farmacología , Metástasis LinfáticaRESUMEN
Gastric cancer (GC) represents ~10% of the global cancer-related deaths, increasingly affecting the younger population in active stages of life. The high mortality of GC is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not guide the patient management adequately, thereby new and more reliable biomarkers and therapeutic targets are still needed for this disease. RNA-seq technology has allowed the discovery of new types of RNA transcripts including long non-coding RNAs (lncRNAs), which are able to regulate the gene/protein expression of many signaling pathways (e.g., the PI3K/AKT/mTOR pathway) in cancer cells by diverse molecular mechanisms. In addition, these lncRNAs might also be proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in GC. This review describes important topics about some lncRNAs that have been described as regulators of the PI3K/AKT/mTOR signaling pathway, and hence, their potential oncogenic role in the development of this malignancy.
Asunto(s)
Carcinoma , ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Gástricas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Largo no Codificante/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , BiomarcadoresRESUMEN
The Epstein-Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein-Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Chile/epidemiología , Filogenia , Variación GenéticaRESUMEN
BACKGROUND: A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. METHODS: Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. RESULTS: Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. CONCLUSIONS: In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.
Asunto(s)
Modelos Animales de Enfermedad , Oxigenación por Membrana Extracorpórea/métodos , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Mecánica Respiratoria/fisiología , Índice de Severidad de la Enfermedad , Animales , Femenino , PorcinosRESUMEN
Fucoidans are sulphated polysaccharides that can be obtained from brown seaweed and marine invertebrates. They have anti-cancer properties, through their targeting of several signaling pathways and molecular mechanisms within malignant cells. This review describes the chemical structure diversity of fucoidans and their similarity with other molecules such as glycosaminoglycan, which enable them to participation in diverse biological processes. Furthermore, this review summarizes their influence on the development of metastasis and drug resistance, which are the main obstacles to cure cancer. Finally, this article discusses how fucoidans have been used in clinical trials to evaluate their potential synergy with other anti-cancer therapies.
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Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Polisacáridos/uso terapéutico , Algas Marinas/química , Resistencia a Medicamentos , Humanos , Biología Marina , Metástasis de la NeoplasiaRESUMEN
Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.
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Anticarcinógenos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Catequina/análogos & derivados , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Terapia Combinada/métodos , Fotoquimioterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/farmacología , Carcinoma de Células Escamosas/radioterapia , Catequina/farmacología , Muerte Celular/efectos de la radiación , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/genética , Hipoxia de la Célula/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ferroquelatasa/genética , Ferroquelatasa/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fármacos Fotosensibilizantes/metabolismo , Protoporfirinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Cutáneas/radioterapia , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Estrés Fisiológico/efectos de la radiación , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Survivin/genética , Survivin/metabolismo , Simportadores/genética , Simportadores/metabolismoRESUMEN
BACKGROUND: Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. METHODS: The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. RESULTS: Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. CONCLUSION: CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/ß-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.
Asunto(s)
Antineoplásicos/farmacología , Carboplatino/farmacología , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Ováricas/genética , Transcriptoma/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Fenotipo , Análisis de Secuencia de ARN , Transducción de Señal , Transcriptoma/genéticaRESUMEN
PURPOSE: Cervical cancer is an important health issue among women worldwide. Cervical smear and human papillomavirus detection are the most used screening methods to detect preneoplastic and neoplastic lesions. However, as neither can predict cervical development, new markers are needed for this disease. ZNF516, a potential tumor suppressor gene, has been found altered in cervical cancer. The objective of this study was to determine ZNF516 immunohistochemistry frequency in cervical biopsies and its association with clinicopathological parameters, to evaluate its potential as marker in cervical lesions. METHODS: A retrospective series of 452 formalin-fixed, paraffin-embedded (FFPE) cervical biopsies, obtained between 2002 and 2007, were selected for immunohistochemistry of ZNF516, p16 and Ki-67 markers. Human papillomavirus genotyping was performed on 272 of these samples through reverse line blot assay. RESULTS: An inverse relation between ZNF516 expression and cervical lesions grade (P < 0.001) was observed, given this protein was found mainly expressed in normal tissues, while was decreased in cervical lesions. As expected, the proliferation markers p16 and Ki-67 were found highly expressed in cervical cancer compared to normal tissues, and inversely correlated to ZNF516 expression (P < 0.01). High oncogenic risk-Human papillomavirus presence also was related to the lack of ZNF516 expression in cervical lesions (P < 0.05), and the detection of these two parameters showed a high sensitivity (70.9%) for preneoplastic lesions detection. CONCLUSIONS: The loss of ZNF516 expression was found in cervical lesions, and its detection potentially could be used as a complementary marker of early diagnosis in cervical lesions.
Asunto(s)
Proteínas de Unión al ADN/análisis , Infecciones por Papillomavirus/complicaciones , Lesiones Precancerosas/etiología , Neoplasias del Cuello Uterino/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
BACKGROUND: Human papillomavirus (HPV) is the etiological factor for cervical cancer and its precursor lesions. The characterization of HPV genotypes in preneoplastic lesions and cervical cancer could establishes the effectiveness of vaccination plan in Chilean population. The aim of this study was to determine HPV frequency in a group of women including in a cervical screening program in the public health care system in Chile. METHODS: We analyzed 985 cervical smears samples from women with different histological diagnosis, attending to public health care in Temuco-Chile between 2004 and 2012, to detect HPV genotypes, through PCR followed by reverse line blotting assay. RESULTS: HPV was found present in 80.8% (n = 796) of samples. Only a 5.6% of 985 samples were infected with a low-risk HPV, considering multiple infections. 10.5% (n = 8/76) of normal cervical epithelia, 83.5% (n = 208/249) and 87.6% (n = 557/636) of low and high grade squamous intraepithelial lesions, respectively, and 95.8% (n = 23/24) of squamous cervical carcinomas tested positive for HPV. HPV 16 was the most frequent genotype found (Overall 44.9%, n = 442/985; SCC: 62.5%, n = 15/24). A high variability of HPV types was also found in preneoplastic lesions, whereas there was a selection of genotypes in neoplasia. Also, there was a higher risk of infection with HPV 16 in women ≤26 years and 34-41 years old (p < 0.05), meanwhile infections with HPV 16 or HPV 18 have related with cancer development (p < 0.01). CONCLUSIONS: These data provide further information about the frequency of HPV genotypes in women with cervical lesions in Chile, and the introduction of new targeted vaccines against a wider spectrum of HPV is suggested.
Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Adulto , Biopsia , Cuello del Útero/patología , Cuello del Útero/virología , Chile/epidemiología , Detección Precoz del Cáncer , Femenino , Genotipo , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Clasificación del Tumor , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Prevalencia , Vigilancia en Salud Pública , Neoplasias del Cuello Uterino/diagnóstico , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/etiologíaRESUMEN
Aberrant DNA methylation is a hallmark of many cancers. Currently, there are four intrinsic molecular subtypes in breast cancer (BC): Luminal A, B, Her2-positive, and triple negative (TNBC). Recently, The Cancer Genome Atlas (TCGA) project has revealed that Luminal subtypes have higher levels of genome-wide methylation that may be a result of Estrogen/Estrogen receptor α (E2/ERα) signaling pathway activation. In this study, we analyze promoter CpG-island (CGIs) of the Reprimo (RPRM) gene in breast cancers (n = 77), cell lines (n = 38), and normal breast tissue (n = 10) using a MBDCap-seq database. Then, a validation cohort (n = 26) was used to confirm the results found in the MBDCap-seq platform. A differential methylation pattern was found between BC and cell lines compared to normal breast tissue. In BC, a higher DNA methylation was observed in tissues that were ERα-positive than in ERα-negative ones; more precisely, subtypes Luminal A compared to TNBC. Also, significant reverse correlation was observed between DNA methylation and RPRM mRNA expression in BC. Our data suggest that ERα expression in BC may affect the DNA methylation of CGIs in the RPRM gene. This approach suggests that DNA methylation status in CGIs of some tumor suppressor genes could be driven by E2 availability, subsequently inducing the activation of the ERα pathway.
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Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Islas de CpG , Metilación de ADN , ADN de Neoplasias/metabolismo , Genes Supresores de Tumor , Glicoproteínas/metabolismo , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/genética , ADN de Neoplasias/genética , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Estudio de Asociación del Genoma Completo , Glicoproteínas/genética , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERα(+) tumors showed higher methylation intensity than ERα(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.
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Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/fisiología , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Glicoproteínas/fisiología , Análisis de Varianza , Western Blotting , Neoplasias de la Mama/genética , Ciclo Celular , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular , Metilación de ADN , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Humanos , Invasividad Neoplásica , Reacción en Cadena en Tiempo Real de la Polimerasa , Estadísticas no ParamétricasRESUMEN
Gastric cancer is the third leading cause of cancer mortality worldwide. Unfortunately, most gastric cancer cases are diagnosed in an advanced, non-curable stage and with a limited response to chemotherapy. Drug resistance is one of the most important causes of therapy failure in gastric cancer patients. Although the mechanisms of drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of microRNAs in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of malignancies, including gastric cancer. This review summarizes the current knowledge about the miRNAs' characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant gastric cancer.
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Resistencia a Antineoplásicos/genética , MicroARNs/genética , Neoplasias Gástricas/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , TranscriptomaRESUMEN
CONTEXT: Aberrant hypermethylation of promoter region of tumor suppressor genes could be used as cancer biomarkers. OBJECTIVE: To test methylation status of ZAR1 and SFRP4 promoter regions as potentials biomarkers for diagnosis of preneoplastic and neoplastic lesions of cervix. MATERIALS AND METHODS: Cytobrush samples were evaluated by Methylation specific PCR (MSP) and quantitative MSP (qMSP). RESULTS: ZAR1 and SFRP4 methylation frequency increased as the grade of lesion increased and the differences between normal and cervical cancer (CC) are statistically significant (p < 0.0001). qMSP showed higher ZAR1 and SFRP4 methylation levels in cancer than normal epithelia (p < 0.001) and preneoplastics lesions (p < 0.01). DISCUSSION: qMSP quantify methylation levels and have high sensitivity and specificity. CONCLUSION: ZAR1 and SFRP4 qMSP could be used as potential biomarker for CC diagnosis.
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Biomarcadores de Tumor/genética , Metilación de ADN , Proteínas del Huevo/genética , Proteínas Proto-Oncogénicas/genética , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Neoplasias del Cuello Uterino/genética , Adulto JovenRESUMEN
BACKGROUND: In Chile, cervical cancer (CC) is the second leading cause of death from malignancy in women. The main causal agent of cervical cancer is the human papillomavirus (HPV). This virus is the most common sexually transmitted infection among sexually active youth. An early onset of sexual life increases the chances of HPV infection; this may involve a possible early development of cervical intraepithelial neoplasia and CC, creating a major public health problem. OBJECTIVE: To present HPV frequency in women under the age of 25, treated in the CC screening program and their follow-up after histopathological diagnosis. METHODS: 173 cervical samples were genotyped by polymerase chain reaction and non-radioactive reverse hybridization (line blot). RESULTS: The overall frequency of HPV was 84.8%. HPV16 was the most prevalent. In 12.1% of women the cervical lesion persisted or progressed. 28.9% of women had irregular follow-up; in this group, 88% were HPV(+) and 52% had no record of Pap smear in the past 3 years. DISCUSSION: The results reaffirm the usefulness of complementing the Pap and HPV detection as a primary screening tool in sexually active women. They also suggest the possibility of extending the age coverage of the national screening program.
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ADN Viral/análisis , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Adolescente , Chile , Femenino , Genotipo , Humanos , Tamizaje Masivo/métodos , Prueba de Papanicolaou , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Reacción en Cadena de la Polimerasa , Neoplasias del Cuello Uterino/prevención & control , Adulto JovenRESUMEN
Gastric cancer (GC) ranks fifth globally in cancer diagnoses and third for cancer-related deaths. Chemotherapy with 5-fluorouracil (5-FU), a primary treatment, faces challenges due to the development of chemoresistance. Tumor microenvironment factors, including C-C motif chemokine receptor 3 (CCR3), can contribute to chemoresistance. The present study evaluated the effect of CCR3 receptor inhibition using the antagonist SB 328437 and the molecular dynamics of this interaction on resistance to 5-FU in gastric cancer cells. The 5-FU-resistant AGS cell line (AGS R-5FU) demonstrated notable tolerance to higher concentrations of 5-FU, with a 2.6-fold increase compared with the parental AGS cell line. Furthermore, the mRNA expression levels of thymidylate synthase (TS), a molecular marker for 5-FU resistance, were significantly elevated in AGS R-5FU cells. CCR3 was shown to be expressed at significantly higher levels in these resistant cells. Combining SB 328437 with 5-FU resulted in a significant decrease in cell viability, particularly at higher concentrations of 5-FU. Furthermore, when SB 328437 was combined with 5-FU at a high concentration, the relative mRNA expression levels of CCR3 and TS decreased significantly. Computational analysis of CCR3 demonstrated dynamic conformational changes, especially in extracellular loop 2 region, which indicated potential alterations in ligand recognition. Docking simulations demonstrated that SB 328437 bound to the allosteric site of CCR3, inducing a conformational change in ECL2 and hindering ligand recognition. The present study provides comprehensive information on the molecular and structural aspects of 5-FU resistance and CCR3 modulation, highlighting the potential for therapeutic application of SB 328437 in GC treatment.
RESUMEN
Cytokines are proteins that act in the immune response and inflammation and have been associated with the development of some types of cancer, such as gastric cancer (GC). GC is a malignant neoplasm that ranks fifth in incidence and third in cancer-related mortality worldwide, making it a major public health issue. Recent studies have focused on the role these cytokines may play in GC associated with angiogenesis, metastasis, and chemoresistance, which are key factors that can affect carcinogenesis and tumor progression, quality, and patient survival. These inflammatory mediators can be regulated by epigenetic modifications such as DNA methylation, histone protein modification, and non-coding RNA, which results in the silencing or overexpression of key genes in GC, presenting different targets of action, either direct or mediated by modifications in key genes of cytokine-related signaling pathways. This review seeks insight into the relationship between cytokine-associated epigenetic regulation and its potential effects on the different stages of development and chemoresistance in GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Epigénesis Genética , Citocinas/metabolismo , Resistencia a Antineoplásicos/genética , AngiogénesisRESUMEN
Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells.
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Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , Western Blotting , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular , Supervivencia Celular/fisiología , Técnicas de Silenciamiento del Gen , Células HEK293 , Células HeLa , Humanos , Técnicas In Vitro , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Células Madre/metabolismo , Células Madre/patologíaRESUMEN
Cervical cancer is a leading cause of cancer deaths in women worldwide and infection by high-risk human papillomavirus types is a precursor event. The cellular FLICE-like inhibitory protein (c-FLIP) has been found to be overexpressed in several types of cancers and could be associated with cervical cancer progression because of its ability to inhibit the apoptotic process. To detect c-FLIP expression in cervical cancer, an immunohistochemical staining was performed, using tissue microarrays, on a series of 536 archival biopsy samples, including normal cervical tissues, low-grade and high-grade squamous intraepithelial lesions, and squamous cervical carcinomas. The epithelium in the normal cervix and low-grade squamous intraepithelial lesions mainly stained negatively for c-FLIP, whereas high-grade intraepithelial lesions and cancer samples showed an elevated expression of c-FLIP. A direct association was observed between the increasing grade of the lesion and the intensity of c-FLIP staining, in which the frequency of intense c-FLIP expression increased from 12.5% in the normal tissue to 82.1% in the cervical cancer tissue. An increased expression of c-FLIP may be an important factor in the progression of cervical cancer. This finding could aid in identifying patients with preneoplastic lesions at greater risk of developing cervical cancer. c-FLIP expression in cervical tissue may be a potential cervical cancer progression marker.
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Biomarcadores de Tumor/análisis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/biosíntesis , Carcinoma de Células Escamosas/metabolismo , Displasia del Cuello del Útero/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/análisis , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis de Matrices Tisulares , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Adulto Joven , Displasia del Cuello del Útero/mortalidad , Displasia del Cuello del Útero/patologíaRESUMEN
Globally, human papillomavirus (HPV) is the most frequent sexually transmitted infection (STI) and it affects men and women equally. In men, HPV has been mainly associated with skin lesions like ano-genital warts and intraepithelial neoplasia of penis and anus in recent years. HPV prevalence in men varies extremely due to kind of sample and detection techniques. The most widely used samples to study HPV in men are: penile shaft, glans, prepuce, coronal sulcus, urine and semen, and its detection is usually performed with techniques like reverse line blot (RLB) and hybrid capture (HC). Given that the highest infection rates are in Africa and Latin America, the aim of this review is to describe the pathogenesis of HPV and its main detection techniques in men.
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Enfermedades del Ano/diagnóstico , Enfermedades de los Genitales Masculinos/diagnóstico , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/diagnóstico , Enfermedades Virales de Transmisión Sexual/diagnóstico , Enfermedades del Ano/virología , Enfermedades de los Genitales Masculinos/virología , Humanos , Masculino , Infecciones por Papillomavirus/virología , Enfermedades Virales de Transmisión Sexual/virologíaRESUMEN
BACKGROUND: Chlamydia trachomatis infection is the most commonly reported sexually transmitted bacterial infection worldwide. Between 70 and 90% of women are asymptomatic, however, untreated and persistent infections can lead to the development of urethritis, pelvic inflammatory disease, infertility and ectopic pregnancy. AIMS: To determine C. trachomatis infection frequency in a group of women in Chile, using quantitative real time PCR (qPCR) and to compare the usefulness of endocervical and urine samples for C. trachomatis detection. METHODS: 87 asymptomatic women aged 15-64 years were included. Every woman donated one endocervical sample and one urine sample. Detection and quantification of C. trachomatis was performed by qPCR. RESULTS: Of 87 endocervical samples, the frequency was 11.49% (n = 10). Of these samples, 5 cases were found in women < 35 years old. About urine samples, 16 samples were positive (18.39%). Ten women < 35 years old yielded positive urine samples. Only four women had both samples positive for C. trachomatis (4.6%). There was no statistically significant relationship between age and C. trachomatis infection. Cryptic plasmid quantification was found between 3.55 - 96.050 copies/µL for endocervical samples and 7.22-633.1 copies/µL for urine samples. CONCLUSION: Estimated frequency of C. trachomatis in Chilean women was higher than previous Chilean studies. Both types of samples are complementary for screening and diagnosis strategies using sensitive techniques, because silent infection can be present in either urinary or genital tract or in both in women.