RESUMO

The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.

Assuntos

Transição Epitelial-Mesenquimal/fisiologia , Nucleosídeos/metabolismo , Nucleotídeos/metabolismo , Receptores Purinérgicos/metabolismo , Transdução de Sinais/fisiologia , Animais , Movimento Celular/fisiologia

RESUMO

Extracellular nucleotides are signaling elements present in the tumor microenvironment; however, their role in tumor growth is not completely understood. In the present study, we asked whether nucleotides regulate cell migration in ovarian carcinoma-derived cells. We observed that 100 µM UTP induced migration in SKOV-3 cells (1.57 ± 0.08 fold over basal), and RT-PCR showed expression of transcripts for the P2RY2 and P2RY4 receptors. Knockdown of P2RY2 expression in SKOV-3 cells (P2RY2-KD) abolished the UTP-induced migration. The mechanism activated by UTP to induce migration involves transactivation of the epidermal growth factor receptor (EGFR) since we observed that the EGFR kinase inhibitor AG1478 and the PI3K inhibitor Wortmannin inhibit this response (to 0.76 ± 0.23 and 0.46 ± 0.14 relative to the control, respectively). In agreement with these observations, UTP was able to modify the phosphorylation state of the EGFR; likewise, the induction of ERK1/2 phosphorylation promoted by UTP was abolished by a 30-60 min treatment with AG1478. Our data also suggested that the enhanced cell migration involves the epithelium to mesenchymal transition (EMT) process, since a 12 h stimulation of SKOV-3 cells with 100 µM UTP showed an increase in vimentin and SNAIL protein levels (459.8 ± 132.4% over basal for SNAIL). Interestingly, treatment with apyrase (10 U/mL) reduces the migration of control cells and induces a considerable enrichment of E-cadherin in the cell-cell contacts, favoring an epithelial phenotype and strongly suggesting that the nucleotides released by tumor cells and acting through the P2RY2 receptor are potential regulators of invasiveness.

Assuntos

Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Receptor Cross-Talk/efeitos dos fármacos , Receptores Purinérgicos P2Y2/genética , Uridina Trifosfato/farmacologia , Androstadienos/farmacologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Receptores ErbB/metabolismo , Feminino , Humanos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptores Purinérgicos P2Y2/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirfostinas/farmacologia , Uridina Trifosfato/metabolismo , Vimentina/genética , Vimentina/metabolismo , Wortmanina

RESUMO

Binding and pore formation constitute key steps in the mode of action of Bacillus thuringiensis delta-endotoxins. In this work, we present a comparative analysis of toxin-binding capacities of proteolytically processed Cry3A, Cry3B and Cry3C toxins to brush border membranes (BBMV) of the Colorado potato beetle Leptinotarsa decemlineata (CPB), a major potato coleopteran-insect pest. Competition experiments showed that the three Cry3 proteolytically activated toxins share a common binding site. Also heterologous competition experiments showed that Cry3Aa and Cry3Ca toxins have an extra binding site that is not shared with Cry3Ba toxin. The pore formation activity of the three different Cry3 toxins is analysed. High pore-formation activities were observed in Cry3 toxins obtained by proteolytical activation with CPB BBMV in contrast to toxins activated with either trypsin or chymotrypsin proteases. The pore-formation activity correlated with the formation of soluble oligomeric structures. Our data support that, similarly to the Cry1A toxins, the Cry3 oligomer is formed after receptor binding and before membrane insertion, forming a pre-pore structure that is insertion-competent.

Assuntos

Bacillus thuringiensis/metabolismo , Proteínas de Bactérias/metabolismo , Besouros/metabolismo , Endotoxinas/metabolismo , Animais , Bacillus thuringiensis/patogenicidade , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/química , Proteínas de Bactérias/farmacologia , Toxinas Bacterianas/química , Sítios de Ligação , Ligação Competitiva , Membrana Celular/metabolismo , Besouros/citologia , Endopeptidases , Endotoxinas/química , Endotoxinas/farmacologia , Proteínas Hemolisinas , Microvilosidades/metabolismo , Precursores de Proteínas/química

RESUMO

This article shows the experience in 61 patients with adnexal tumors studied from June 1988 to June 1994; the origin of the patients in private and semiprivate, to whom we practiced a diagnostic and operative laparoscopy (56/61) at the same time. The inclusion and exclusion criteria were determined by clinical history (past history, age, symptoms, size, etc.), vaginal ultrasonography scan (ascites, papillas, cyst's content, etc.), laboratory tests (Ca 125 in postmenopausal patients), the macroscopic assessment during the diagnostic laparoscopy, transoperative biopsy (19/61) was made in order to confirm the benign findings seen before laparoscopy; and the results were accordingly on the 61 cases. The cause of consult was infertility in 24/61; 18/61 were primary infertility; 6/61 were secondary infertility. We did 22 cystectomies and 2 oophorectomies; 10 of them became pregnant. 37 from 61 had pain, nine of this group we did an oophorectomy (2 by torsion, 3 had hemorrhagic cysts that were ruptured and 4 were residual ovary), the rest 28 we performed cystectomy with frank improvement of their symptoms. The postoperative diagnosis of the tumors were: luteomas 13/61; functional cysts 17/61, Hemorrhagic cysts 8/61; endometriomas 9/61; serous cystoadenoma 3/61; mucinous cystoadenoma 1/61; ovaric fibroma 1/61; mature cystic teratoma 2/61; residual ovaries 4/61; paraovaric cysts 2/61 and Morgagni's hydatide 1/61. It is concluded that if one follows all the correct parameters for the evaluation of adnexal tumors, the endoscopic procedure could be safe with the benefits of the laparoscopic procedure.

Assuntos

Doenças dos Anexos/cirurgia , Laparoscopia , Neoplasias Uterinas/cirurgia , Doenças dos Anexos/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Neoplasias Uterinas/diagnóstico

RESUMO

This study was carried out at the General Hospital of Zone N masculine 14 of the IMSS in Jalisco, Mexico, with the goal of designing standardized criteria to handle hospitalized diabetes patients, as a strategy for quality assurance, through the participation of a panel of experts in internal medicine from the hospital. Participation by the attending physician in designing criteria generates a sense of belonging in the staff and makes adherence and application easier. The suggested criteria are subject to further improvement and are not intended for universal application, but to the extent that they have been useful in patient care they have far surpassed the authors' expectations when the goals of this research were originally established.

RESUMO

Nutritional practices of diabetics reflect both human behavior and the health culture of such patients. They also represent how the diabetic deals with the health/illness issue. The purpose of this survey was to identify and relate nutritional practices with metabolic control, age, sex, years of schooling, and time since diagnosis of illness. The sample was taken from 114 cases selected through systematic random sampling in five family practice units in Guadalajara. Using thirteen structured, coded, and quantified questions of the Likert type, the study evaluated nutritional practice with a range of 0-65. Results showed that 21% of the diabetics had appropriate nutritional practices (>31 points), and when related with years of schooling and time since diagnosis of illness, they showed statistically significant differences (p=0.05). Simple regression showed that 9% of metabolic control can be explained by nutritional practices.

RESUMO

This study aims to develop methodological tools to assess and guarantee quality of medical care by investigating satisfaction of expectations by objects of care (patients), medical institutions (directors), and direct providers of care (health personnel). The perspectives of this analysis included the structure, process, and outcomes of medical care. Perhaps the novelty of the research is its democratic approach, i.e., the three main protagonists' freedom of expression regarding medical care and the questioning of such aspects as individual, social, and professional satisfaction and the work environment, ultimately leading to the humanization of the work and thus to quality of care.