RESUMO
The heterogeneity of tumor cell mass and the plasticity of cancer cell phenotypes in solid tumors allow for the insurgence of resistant and metastatic cells, responsible for cancer patients' clinical management's main challenges. Among several factors that are responsible for increased cancer aggression, metabolic reprogramming is recently emerging as an ultimate cancer hallmark, as it is central for cancer cell survival and self-renewal, metastasis and chemoresistance. The P2X7 receptor, whose expression is upregulated in many solid and hematological malignancies, is also emerging as a good candidate in cancer metabolic reprogramming and the regulation of stem cell proliferation and differentiation. Metabostemness refers to the metabolic reprogramming of cancer cells toward less differentiated (CSCs) cellular states, and we believe that there is a strong correlation between metabostemness and P2X7 receptor functions in oncogenic processes. Here, we summarize important aspects of P2X7 receptor functions in normal and tumor tissues as well as essential aspects of its structure, regulation, pharmacology and its clinical use. Finally, we review current knowledge implicating P2X7 receptor functions in cancer-related molecular pathways, in metabolic reprogramming and in metabostemness.
Assuntos
Carcinogênese/metabolismo , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Oncogenes/fisiologia , Receptores Purinérgicos P2X7/metabolismo , Diferenciação Celular/fisiologia , Humanos , Células-Tronco Neoplásicas/patologiaRESUMO
Introduction A foreign body (FB) is an object or substance foreign to the location where it is found. FBs in the ear, nose, and throat are a common problem frequently encountered in both children and adults. Objective To analyze FBs in terms of type, site, age, and gender distribution and method of removal. Methods A retrospective study was performed in a tertiary care hospital in the central part of Nepal. The study period was from June 2013 to May 2014. The information was obtained from hospital record books. Results A total of 134 patients had FBs in the ear, nose, or throat; 94 were males and 40 were females. Of the 134 patients, 70 (52.23% ) had FB in the ear, 28 (20.89% ) in the nose, and 36 (26.86% ) in the throat. The FB was animate (living) in 28 (40% ) patients with FB in the ear and 1 (3.5% ) patient with FB in the nose, but the FB was inanimate (nonliving) in any patient with FB in the throat, in 42 (60% ) patients with FB in the ear FB, and in 27 (96.4% ) patients with FB of the nose. The FB was removed with or without local anaesthesia (LA) in 98 (73.13% ) patients, and only 36 patients (26.86% ) required general anaesthesia (GA). The most common age group affected was <10 years. Conclusion FBs in the ear and nose were found more frequently in children, and the throat was the most common site of FB in adults and elderly people. Most of the FBs can be easily removed in emergency room or outpatient department. .
Assuntos
Animais , Humanos , Genes Supressores de Tumor/fisiologia , Oncogenes/fisiologia , Receptores Notch/fisiologia , Eritrócitos/fisiologia , Genes de Troca , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Hematopoese/genética , Células-Tronco Hematopoéticas/fisiologia , Megacariócitos/fisiologia , Transdução de Sinais/fisiologiaRESUMO
Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.
Assuntos
Neoplasias Encefálicas/metabolismo , Glutaminase/metabolismo , Glutamina/metabolismo , Oncogenes/fisiologia , Neoplasias Encefálicas/fisiopatologia , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Ciclo do Ácido Cítrico/fisiologia , Glicólise/fisiologia , Humanos , Via de Pentose Fosfato/fisiologia , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.
Assuntos
Humanos , Neoplasias Encefálicas , Glutaminase , Glutamina , Oncogenes/fisiologia , Neoplasias Encefálicas , Proliferação de Células , Transformação Celular Neoplásica , Ciclo do Ácido Cítrico/fisiologia , Glicólise/fisiologia , Via de Pentose Fosfato/fisiologia , Células-Tronco , Células-TroncoRESUMO
The role of inflammation in human papillomavirus (HPV) infection and disease is complex since it involves responses capable of preventing initial infections, clearing those ongoing as well as promoting persistence and progression of associated lesions. Avoiding the immune response has been considered a key aspect of HPV persistence which is the main factor leading to HPV-related neoplasia. HPVs have evolved different ways of targeting immune signaling pathways. Moreover, host inflammatory response may promote lesion progression and affect tumor fate by diverse mechanisms including the direct participation of inflammatory cells. In this review, we discuss the interplay between HPV oncogenic proteins and an array of inflammatory responses that ultimately may lead to cancer.
Assuntos
Inflamação/imunologia , Neoplasias/imunologia , Oncogenes/fisiologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/imunologia , Transformação Celular Neoplásica , Humanos , Neoplasias/virologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologiaRESUMO
A given cancer is produced by a unique combination of genetic alterations that target specific genes, most often leading to activation of oncogenes and inactivation of tumor suppressor genes. Traditional oncogenes, such as RasV12, are involved in maintaining pro-survival and proliferation signals activated in the cell. Several evidences suggest that cancer cells are addicted to oncogenes and that their inhibition has dramatic effects on cancer cells. Here, the hypothesis that oncogenes may be activated only transiently and that this short activation may be important for cancer formation by affecting the differentiation state of the cancer cells is presented. These "transient oncogenes" are overlooked in genomic or proteomic analysis due to their transient nature. Here we argue that transcription factors, such as the so called Yamanaka factors, capable of reprogramming cells to a less differentiated state, which normally happens to cancer cells, can function as transient oncogenes. Several published evidences are used to support the proposed hypothesis. Analysis and even targeting of this new class of oncogenes could have a great impact on cancer biology, treatment and, most importantly, prevention.
Assuntos
Diferenciação Celular/genética , Neoplasias/genética , Oncogenes/fisiologia , Fatores de Transcrição/fisiologia , Ativação Transcricional/fisiologia , Humanos , Oncogenes/genética , Fatores de Tempo , Fatores de Transcrição/genética , Ativação Transcricional/genéticaRESUMO
Understanding of visual system function and the development of new therapies for corneal diseases and damages depend upon comprehension of the biological roles of the tissue. The in vitro cultivation of corneal epithelial cells and cell lines derived from them has become a powerful tool to analyze and understand such issues. Currently, researchers have developed well-defined and precisely described culture protocols and a collection of corneal epithelial cell lines. These cell lines have been obtained through different experimental approaches: (1) the ectopic expression of oncogenes, (2) the inactivation of p16 and p53 pathways and hTERT expression, and (3) the spontaneous establishment after serial cultivation of cells. The advantages or disadvantages for these approaches are discussed. In conclusion, the availability of several culture protocols and immortalized cell lines that express corneal epithelial phenotype will be useful for investigating issues such as gene regulation and tissue development, or for validating alternative methods in toxicology.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Epitélio Corneano/citologia , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Epitélio Corneano/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Oncogenes/fisiologiaRESUMO
Las evidencias epidemiológicas, virológicas y clínicas demuestran que hay una estrecha asociación entre tipos específicos de HPV y cáncer cervicouterino. La infección por HPV precede el desarrollo de la enfermedad cervical. Los HPV están presentes en las lesiones precursoras. La infección por HPV es una condición necesaria pero no suficiente, se requiere de factores que participan en la oncogénesis cervical. No se conoce la función que ejercen algunos factores asociados. Una pequeña proporción de las infecciones por HPV de alto riesgo desarrollan una neoplasia maligna.
Assuntos
Humanos , Feminino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Oncogenes/fisiologia , Oncogenes/genética , PapillomaviridaeRESUMO
La endometriosis es una enfermedad cuya etiología no se conoce y sobre la cual existen diferentes teorías que a la fecha no han sido totalmente demostradas. Está claramente demostrado que las mujeres que presentan dicha enfermedad cursan con infertilidad y que la recurrencia de aparición de los focos endometriósicos es alta, y al parecer no dependientes del estímulo estrogénico. Este fenómeno se ha atribuido a otros factores de crecimiento y algunos oncogenes los cuales son expresados para contrarrestar la falta del estímulo estrogénico. Sin embargo, pocos estudios existen en relación a los oncogenes u otros receptores hormonales, por lo que el presente trabajo tuvo por objetivo el evaluar su expresión tanto en tejido eutópico como en ectópico de mujeres con diagnóstico previo de endometriosis. El análisis de la expresión tanto de c-myc, neu y el receptor de prolactina (PRLr) se realizó por la técnica de RT-PCR. Nuestros resultados demuestran que tanto myc como el PRLr se expresan de manera distinta entre los diferentes tejidos, en tanto que neu se expresa de la misma manera entre los dos tejidos. Con estos datos concluimos que las células que conforman el foco endometriósico presentan un estado diferencial en relación a la expresión de algunos de sus genes, lo cual favorece el desarrollo y mantenimiento de los mismos en un ambiente hormonal diferente al de la cavidad uterina.