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Biomedical subjects

J Vilches

Publications and source records attributed to J Vilches.

At least 19 recordsLinked to original sources
PubMed2004

Changes in elemental concentrations in LNCaP cells are associated with a protective effect of neuropeptides on etoposide-induced apoptosis.

One of the mechanisms that has been put forward for the development of the androgen-resistant status is neuroendocrine differentiation. Neuroendocrine cells secrete neuropeptides that may represent one of the possible molecular bases by which hormone-dependent prostate cancer cells could escape treatment. LNCaP prostate cancer cells were treated with either etoposide or neuropeptides. Morphological changes related to apoptosis and cell viability were assessed. Changes in intracellular ion content were quantitatively analyzed by electron probe X-ray microanalysis. Etoposide treatment consistently induces a decrease in K and an increase in Na, which are inhibited by bombesin or calcitonin. The Na/K ratio increased markedly after exposure to etoposide, and both bombesin and calcitonin blocked this increase. Etoposide also caused changes in the intracellular P and S concentrations that to a large extent could be blocked by neuropeptides. These results support the hypothesis that neuropeptides confer anti-apoptotic capabilities onto non-neuroendocrine cells in close proximity to neuroendocrine cells.

Apoptosis↗
PubMed2004

Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and recent developments.

It has been suggested that neuroendocrine (NE) cells provide paracrine stimuli for the propagation of local carcinoma cells and that NE differentiation is associated with the progression of prostate cancer toward an androgen-independent state. Apoptosis comprises a critical intracellular defense mechanism against tumorigenic growth and is associated with a number of changes in the elemental content of the cell. The neuropeptides bombesin and calcitonin, which inhibit etoposide-induced apoptosis, also inhibit the etoposide-induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This protective effect on etoposide-induced apoptosis appears to be quite similar in androgen-dependent and androgen-independent cell lines. This confirms that neuropeptides confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to neuroendocrine cells. It can therefore be speculated that certain neuroendocrine peptides can increase the survival and further growth of neighboring cells and may thereby contribute to the aggressive clinical course of prostate tumors containing neuroendocrine elements. In addition, this correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. The culture techniques described were, thus, designed in order to achieve two important goals. First, the development of an in vitro model that allows an approach to neuroendocrine differentiation in prostate cancer and its role in apoptosis blockage. Second, the method has been designed in order to permit rapid cryofixation of intact cell monolayers for subsequent x-ray microanalysis.

Apoptosis↗
PubMed2001

X-ray microanalysis of etoposide-induced apoptosis in the PC-3 prostatic cancer cell line.

Apoptosis comprises a critical intracellular defense mechanism against tumourigenic growth. We have been interested in the relationship between morphological changes and intracellular concentration of several cations after etoposide-induced apoptosis in androgen-independent prostate cancer cells. SEM and X-ray microanalysis were performed on freeze-dried PC3 cells after etoposide treatment, and correlated with the morphological features observed after examination by light and fluorescence microscopy. Cell viability assays were also performed. A significant decrease in intracellular Cl(-) and K(+)and a progressive increase in Mg(2+) and Na(+) were observed, with parallel changes in cellular volume as cells passed through three morphological stages of apoptosis. The use of EPXRMA made it possible to evaluate alterations in element composition in prostate cancer cell apoptosis and may be a helpful tool for further studies on apoptosis in prostate cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines.

BACKGROUND: Neuroendocrine differentiation in prostatic carcinoma has been related to regulation of proliferation and metastatic potential and correlated with prognosis. More than 80% of prostate carcinomas initially respond to androgen ablation, but most relapse, due to the heterogeneous presence of androgen-dependent and independent clones. The pathways of cellular proliferation and apoptosis are inexorably linked to minimize the occurrence of neoplasia, and disfunction of apoptosis is proposed as a pathogenic process in malignant tumors. Androgen-dependent prostatic cancer cells undergo apoptosis after androgen deprivation, but not androgen-independent ones due to a defect in the initiation step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We suggest a possible role of neuroendocrine differentiation in the onset and regulation of apoptosis in prostatic neoplasia. METHODS: LNCaP, PC-3 and DU 145 prostatic cancer cell lines were induced to undergo apoptosis after treatment with etoposide alone or plus androgen ablation. We tested the role of neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis. RESULTS: Etoposide-induced apoptosis in all cancer cell lines was achieved. In LNCaP androgen ablation was also required. Apoptosis is prevented in all three lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3, LNCaP and in an etoposide dose-dependent way in DU 145. CONCLUSION: Neuropeptides bombesin and calcitonin can modulate the apoptotic response of prostate cancer cells by inducing resistance to etoposide-induced apoptosis, suggesting that neuropeptides can be used as a target of therapeutical approach in prostatic carcinoma.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Etoposide sensitivity of human prostatic cancer cell lines PC-3, DU 145 and LNCaP.

Metastatic prostatic cancer is typically refractory to androgen ablation therapy due to the presence of androgen-independent clones in the neoplasia. A therapeutical approach which could effectively control androgen-dependent and independent cells is, thus, needed. Maybe the failure of certain cancer cells to engage in apoptosis could explain the inherent drug resistance of many tumors. Anyway, these cells can retain the ability to undergo apoptosis in response to an adequate stimulus. We tested whether etoposide, a topoisomerase II inhibitor, could induce apoptosis in androgen-dependent (LNCaP) as well as independent (PC-3 and DU 145) human prostate cancer cell lines. Morphological examination was performed, as it is regarded as one of the most reliable parameters for the detection of apoptotic changes. Complementarily, biochemical and flow cytometric studies were also used. Characteristical changes of apoptosis were demonstrated in PC-3, Du 145, and LNCaP cancer cells after treatment with etoposide. These cells, thus, retain the ability to undergo apoptosis under adequate conditions, in a promising approach to hormone refractory prostate cancer therapy.

Androgens↗
PubMed1994

AgNOR and breast cancer. A study by image analysis.

The nucleolar organizer regions are used as a new marker in proliferation cell. AgNOR are loops of DNA actively transcribing to ribosomal RNA and they are associated with nonhistone proteins with strong argyrophil. In the present study we correlated the relationships between number and size of AgNOR measured by an automatic image analysis using CAS-100, in eleven breast carcinomas in different clinical stages and histological grades. We could identify the AgNOR with silver stain; the relationship between the number/size and histological grade/clinical stage shows that in normal breast we find one or two AgNOR but this number is larger when the carcinomas are less differentiated. When studied, the size is larger in the normal breast. We can make the same conclusions with the carcinomas which are lymph-node +.

Breast Neoplasms↗
PubMed1993

Effects of prolactin on explant cultures of rat ventral prostate: morphological and immunohistochemical study.

Specimens derived from rat ventral prostate were cultured by an explant culture technique using differents concentrations of ovine prolactin. Sacrificed explants embedded on paraffin were sectioned for morphologic and immunocytochemical studies using antibodies against prostatic acid phosphatase, prostatic specific antigen, and wide-spectrum monoclonal keratin. Prolactin significantly stimulated the growth of these cells in the concentration range of 1 x 10(-2) ui/ml, but was inhibitory at a concentration of 1 and 0.1 ui/ml. The 1 x 10(-3) and 1 x 10(-4) ui/ml prolactin concentrations demonstrated the preservation of a glandular epithelium with a columnar shape, similar to the normal appearance of ventral prostate from rats.

Acid Phosphatase↗
PubMed1992

[Evaluation of nuclear roundness as a tool for prostatic carcinoma grading].

The microscopic patterns adopted by prostate carcinomas are extraordinarily variable making its histopathological classification and grading extremely complicated. There are numerous systems for prostatic tumours' grading, but many of them lack a truly reproducible character and an acceptable degree of reliability; for this reason, we have studied a series of nuclear microscopic parameters, from a quantitative point of view, in a series of prostatic carcinomas with a minimum follow-up of five years. It was observed that of the morphometric values obtained--area, perimeter, projection on the X- and Y-axis as well as the nuclear roundness factor--the most useful and representative is the latter. Besides, this is an objective parameter to evaluate nuclear anaplasia and can also be considered as a prognostic factor since, in our series, those who died had a greater mean nuclear roundness factor than those who survived.

Aged↗
PubMed1992

[Embryonal development of interstitial Leydig cells in the rat testis].

Blood testosterone concentrations are not constant throughout life, there being a direct correlation with the numbers of cells producing that hormone, for which reason the existence of two Leydig's cells populations has been proposed: one foetal formation, which disappears just prior or immediately after birth, and a subsequent adult generation. In recent studies, however, that withdrawal has not been observed. Considering all the above, we have studied the evolution of these elements during the rat foetal period. From a morphological point of view Leydig's cells do not differentiate from those in the gonadal interstice until day 17 of pregnancy, showing a considerable increase in their numbers by day 21: while from that day onwards their numbers decrease they never disappear completely. We believe those cells become differentiated from the interstitial mesenchymal cells, and that their increase is facilitated by the proliferation of these same elements.

Animals↗
PubMed1992

[The nuclear roundness factor as a parameter in the anatomoclinical correlation of prostatic carcinoma].

This paper correlates the nuclear roundness factor to clinical stage, patient's age and acid phosphatase level at the time of diagnosis in a group of 48 patients with prostate carcinoma and a minimal follow-up of 5 years. It has been demonstrated that, from an anatomo-clinical point of view, the nuclear roundness factor is a good indicator because it presents increasing values as the clinical stage of tumoral extension worsens, and in those stages where the number of patients was relatively high the average of deaths was always higher than that of survivors. On the other hand, a direct correlation to total acid phosphatase, and an inverse correlation to age at the time of diagnosis was shown in patients with changes in these values.

Age Factors↗
PubMed1983

Bioelectrical tissue resistance during various methods of myocardial preservation.

Twenty-one mongrel dogs underwent cardiopulmonary bypass (CPB) and ischemic cardiac arrest for 60 minutes. The bioelectrical tissue impedance, water content, and ultrastructure of the myocardium were studied and correlated with various types of myocardial protection applied. The animals were divided into three groups according to the myocardial protection applied: Group 1, moderate general hypothermia; Group 2, moderate general and local hypothermia; Group 3, moderate general hypothermia and crystalloid cardioplegia. The hearts from 3 normal dogs served as controls. After 35 minutes of ischemic arrest, the difference in bioelectrical impedance of the myocardium of the left ventricle between Groups 1 and 2 was highly significant (p less than 0.001); in Groups 2 and 3, a significant difference was observed after 50 minutes. The heart water content in all three groups increased over that found in the hearts of the control animals, but there was no significant difference between Groups 2 and 3. There was evidence by ultramicroscopic study of ischemic damage to the myocardium in all of the experimental groups. Damage was less evident in Groups 2 and 3. We conclude that measurement of myocardial bioelectrical tissue resistance is a sensitive indicator of myocardial damage due to ischemia and may be useful clinically in determining the need for and type of cardiac resuscitation, particularly following CPB.

Animals↗
PubMed1982

SEM and X-ray microanalysis of human prostatic calculi.

Calculi removed from human prostates affected with nodular hyperplasia were analyzed with scanning electron microscopy and EDAX system. The general spectrum was made up of Na, Al, Mg, S, P, Ca and Zn. Two types of stone were identified morphostructurally and microanalytically: calculi type I of nodular surface with high peaks of S, and calculi type II polyfaceted with high peaks of P and Ca. Their formation from corpora amylacea and/or exogenous constituents is discussed. The superficial deposit of Zn suggests its incorporation from the prostatic liquid and does not seem to play an important role in the genesis.

Calculi↗