RESUMO
Placental dysfunction leads to foetal damage, which jeopardises the exchange between the maternal and foetal systems. We evaluated the effects of tumour growth on the activity of antioxidant enzymes and oxidative stress in placental tissue and cell culture from tumour-bearing pregnant rats compared to non-tumour-bearing pregnant rats that were ascitic fluid injected. Ascitic fluid is obtained from Walker tumour-bearing rats and contains a cytokine called Walker factor (WF), which is a molecule similar to proteolysis-inducing factor (PIF), and induces changes in protein metabolism and oxidative stress. Pregnant Wistar rats were distributed into control (C), tumour-bearing (W) and ascitic fluid injected (A) groups and were sacrificed on days 16, 19 and 21 of pregnancy to analyse the profile of enzyme activities (glutathione-S-transferase (GST), catalase (CAT), alkaline phosphatase (AP)) and malondialdehyde (MDA) content in placental tissue. Meanwhile, placenta samples from all groups were obtained on day 21, placed in primary culture and treated with WF for 72 h. The presence of tumour or ascitic fluid reduced the protein content of the placental tissue. On day 16 there was a significant reduction in AP activity in W rats, and on day 19, CAT activity and MDA content significantly increased. These results indicate that the presence of cancer decreased antioxidant enzyme capacity in the placenta, increasing the amount of oxidation in these cells, which may contribute to irreversible placental damage and compromisefoetal development. WF treatment induces similar changes in placental cells in primary culture, resulting in less cell viability and increased oxidative stress. These results indicate that WF, provided by the tumour or inoculation of ascitic fluid, has negative effects on placental homeostasis, which impairs foetal health.
Assuntos
Estresse Oxidativo/fisiologia , Placenta/metabolismo , Placenta/patologia , Complicações Neoplásicas na Gravidez/patologia , Animais , Antioxidantes/metabolismo , Carcinoma 256 de Walker/metabolismo , Carcinoma 256 de Walker/patologia , Catalase/metabolismo , Células Cultivadas , Feminino , Malondialdeído/metabolismo , Placenta/citologia , Gravidez , Complicações Neoplásicas na Gravidez/metabolismo , Cultura Primária de Células , Ratos , Ratos Wistar , Células Tumorais Cultivadas , Regulação para CimaRESUMO
BACKGROUND: The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. PATIENTS AND METHODS: Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. RESULTS: Metformin pharmacokinetic parameters were: t(½), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). CONCLUSION: Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.
Assuntos
Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Síndrome do Ovário Policístico/metabolismo , Complicações Neoplásicas na Gravidez/metabolismo , Adolescente , Adulto , Feminino , Sangue Fetal , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Troca Materno-Fetal/efeitos dos fármacos , Metformina/efeitos adversos , Metformina/sangue , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Adulto JovemRESUMO
The gynandroblastoma is an extremely rare sexual cord stromal tumor, which contains both male and female elements, characterized by Sertoli or Leydig cells and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old female patient, found accidentally during a cesarean section operation. There is only one reported case in world literature occurring in a pregnant woman. The principal component we found was adult granulose cells, with a microfollicular pattern, and the presence of luteinized cells in some areas; besides we found the presence of well differentiated Sertoli cells elements, in addition to Leydig cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings were performed: citokeratin, which resulted positive in Sertoli cells and negative in granulose cells; and inhibin, which was positive in both components showing its mixed origin.
Assuntos
Cesárea , Neoplasias Ovarianas/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Adulto , Biomarcadores Tumorais/análise , Feminino , Células da Granulosa/patologia , Humanos , Achados Incidentais , Inibinas/análise , Queratinas/análise , Células Intersticiais do Testículo/patologia , Masculino , Proteínas de Neoplasias/análise , Neoplasias Ovarianas/química , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Gravidez , Complicações Neoplásicas na Gravidez/metabolismo , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Células de Sertoli/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/química , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgiaRESUMO
Mouse mammary tumor virus (LA) induces pregnancy-dependent mammary tumors that progress toward autonomy. Here we show that in virgin females, pregnancy-dependent tumor transplants are able to remain dormant for up to 300 days. During that period, these tumors synthesize DNA, express high levels of estrogen and progesterone receptors (ER+PR+) and are able to resume growth after hormone stimulation. Surprisingly, in a subsequent transplant generation, all these tumors are fully able to grow in virgin females, they express low levels of ER and PR (ER-PR-) and have a monoclonal origin; i.e., show all of the features we have described previously in pregnancy-independent tumors. Histologically, mouse mammary tumor virus (LA)-induced tumors are morphologically similar to genetically engineered mouse (GEM) mammary tumors that overexpress genes belonging to the Wnt pathway. Interestingly, in the virus-induced neoplasias, pregnancy-independent passages arising after a dormant phase usually display a lower level of glandular differentiation together with epithelial cell trans-differentiation, a specific feature associated to Wnt pathway activation. In addition, dormancy can lead to the specific selection of Int2/Fgf3 mutated and overexpressing cells. Therefore, our results indicate that during hormone-dependent tumor dormancy, relevant changes in cell population occur, allowing rapid progression after changes in the animal internal milieu.
Assuntos
Neoplasias Mamárias Experimentais/metabolismo , Complicações Neoplásicas na Gravidez/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Apoptose , Sequência de Bases , Diferenciação Celular , Divisão Celular , Progressão da Doença , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Fator 3 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/virologia , Vírus do Tumor Mamário do Camundongo/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Mutação , Transplante de Neoplasias , Neoplasias Hormônio-Dependentes , Gravidez , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Transdução de Sinais , Fatores de Tempo , Proteína Wnt2RESUMO
There is enough evidence that prolactin (PRL), like many other pituitary hormones, is composed by multiple forms that differ from each other by size charge. Although they can be seen in the pituitary glands of a variety of species, their biological significance, identity and chemical nature still remain poorly understood. Recently, a new syndrome characterized by normal ovarian function in the presence of sustained hyperprolactinemia has been reported by our group. In these women, highly abnormal percentages of serum big big PRL have been consistently demonstrated. This observation suggests that big big PRL is immunologically similar, but biologically less active than monomeric or little PRL. In this study we have determined then molecular size heterogeneity of immunoreactive PRL in serum and amniotic fluid from two ovulatory hyperprolactinemic subjects (subjects A and B) who had, under non-pregnant conditions, large amounts of serum big big PRL, throughout different stages of parturition. Control subjects consisted of two women at the end of pregnancy in whom PRL species demonstrated a normal size distribution (subjects C and D). Mean basal levels of PRL were the highest in subjects A and B and remained constant during labor. In the control subjects a remarkable decline in PRL levels was observed during the periparturitional period. This pattern of PRL release was not correlated with changes in steroid hormone concentrations. The relative proportions of PRL size variants throughout delivery showed no apparent changes in all four subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Líquido Amniótico/química , Hiperprolactinemia/metabolismo , Ovário/metabolismo , Complicações na Gravidez/metabolismo , Prolactina/química , Adulto , Córion/metabolismo , Estradiol/sangue , Feminino , Humanos , Hiperprolactinemia/fisiopatologia , Peso Molecular , Complicações do Trabalho de Parto/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Período Pós-Parto/sangue , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações Neoplásicas na Gravidez/metabolismo , Progesterona/sangue , Prolactina/análise , Prolactina/metabolismo , Prolactinoma/complicações , Prolactinoma/metabolismoRESUMO
The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion.