Biomedical subjects

Elena Allia

Publications and source records attributed to Elena Allia.

8 recordsLinked to original sources

PubMed2006

alpha-fetoprotein expression in a dedifferentiated liposarcoma.

Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. We describe a unique case of relapsing retroperitoneal dedifferentiated liposarcoma with biochemical, immunohistochemical, and molecular evidence of alpha-fetoprotein (AFP) ectopic production. The lesion was associated to elevated AFP plasma levels that subsided after tumor removal. Immunohistochemical studies showed AFP production by a minority of tumor cells and reverse transcriptase polymerase chain reaction confirmed AFP mRNA expression. Finding of MDM2 and CDK4 iperexpression by immunohistochemistry confirmed the diagnosis of dedifferentiated liposarcoma.

Aged↗

PubMed2006

Oxytocin induces proliferation and migration in immortalized human dermal microvascular endothelial cells and human breast tumor-derived endothelial cells.

Oxytocin either increases or inhibits cell growth in different cell subtypes. We tested here the effect of oxytocin on cell proliferation and migration of human dermal microvascular endothelial cells (HMEC) and tumor-associated endothelial cells purified from human breast carcinomas (B-TEC). Oxytocin receptors were expressed in both cell subtypes at mRNA and protein levels. Through oxytocin receptor, oxytocin (1 nmol/L-1 mumol/L) significantly increased cell proliferation and migration in both HMEC and B-TEC, and addition of a selective oxytocin antagonist fully reverted these effects. To verify whether a different expression of adhesion molecule-related genes could be responsible for the oxytocin-induced cell migration, untreated and treated cells were compared applying a microarray technique. In HMEC, oxytocin induced the overexpression of the matrix metalloproteinase (MMP)-17, cathepsin D, and integrin beta(6) genes. In B-TEC, oxytocin significantly switched on the gene profile of some MMP (MMP-11 and MMP-26) and of integrin beta(6). The up-regulation of the integrin beta(6) gene could be involved in the oxytocin-induced cell growth, because this subunit is known to determine activation of mitogen-activated protein kinase-extracellular signal-regulated kinase 2, which is involved in the oxytocin mitogenic effect. In B-TEC, oxytocin also increased the expression of caveolin-1 at gene and protein levels. Because oxytocin receptor localization within caveolin-1-enriched membrane domains is necessary for activation of the proliferative (instead of the inhibitory) response to oxytocin, its enhanced expression can be involved in the oxytocin-induced B-TEC growth as well. Altogether, these data indicate that oxytocin contributes to cell motility and growth in HMEC and B-TEC.

Breast Neoplasms↗

PubMed2006

Oxytocin synthesis within the normal and neoplastic breast: first evidence of a local peptide source.

The role of the neurohypophyseal peptide oxytocin (OT) and its receptor (OTR) in the breast has been described mainly in relation to breast feeding or to neoplastic growth regulation. We demonstrate here the presence of OT synthesis within the breast under both physiological and neoplastic conditions. In order to clarify whether normal epithelial and myoepithelial cells could synthesize OT, the two different cell types were separated using immunomagnetic technique after enzymatic digestion of breast specimens obtained during reductive mastoplasty. The freshly isolated cells as well as primary stabilized cultures derived from purified normal breast epithelial and myopithelial cells were then studied. Both epithelial and myoepithelial cells contained the mRNA for OT and OTR; however, only myoepithelial cells showed an effective OT synthesis and detectable peptide release in the culture medium. Moreover, OT expression was studied at mRNA and protein level in 10 human breast carcinoma cell lines. OT mRNA was present in half (5 out of 10) of the breast carcinoma cell lines tested, and OT was synthesized and released in the cell medium, irrespective of the estrogen receptor status of the different cell lines. However, in the two ER+ cell lines actively producing OT, such synthesis was significantly increased following estradiol (E2) treatment. These data altogether suggest the existence of a local OT source within the normal as well as within the neoplastic breast, and that such synthesis can be modulated by E2.

Breast↗

PubMed2005

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours.

Cortistatin (CST), a novel hormone originally described in the rat, mouse, and human cerebral cortex, displays structural and functional similarities to somatostatin (SRIF). CST binds to all five somatostatin receptors and, differently from SRIF, also binds to MrgX2, which has recently been identified as its specific receptor. Little is known about the distribution of CST and MrgX2 in peripheral non-tumour and neoplastic tissues. The aim of the present study was therefore to determine by immunohistochemistry and mRNA analysis (RT-PCR) the distribution of CST and MrgX2 in 56 human non-tumour and 108 tumour tissues, with special reference to neuroendocrine tissue types. Despite the high level of CST mRNA expression in non-tumour and tumour (both neuroendocrine and non-neuroendocrine) tissues, the presence of immunoreactive CST was confirmed in a subset of gastroenteropancreatic, parathyroid, and pituitary non-tumour cells only, and showed a predominantly focal pattern in most neuroendocrine tumours. Co-localization experiments in the gastroenteropancreatic system demonstrated that the normal CST-producing cells are delta cells, while in the adenohypophysis no preferential co-localization of CST with any of the pituitary hormones was observed. MrgX2 mRNA was variably detected in the hypothalamus, pituitary, thyroid, lung, gastroenteropancreatic tract, testis, and ovary, and was negative in the cerebral cortex, parathyroid, and adrenal, as well as in a variety of tumour types. Conversely, immunolocalization of MrgX2 protein was restricted to neurohypophysis and testis, whilst all tumours analysed were negative. A possible explanation for the discrepancy between RT-PCR and immunohistochemistry is that MrgX2 protein was widely detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia in both normal and neoplastic samples. The findings demonstrate a selective distribution of CST in normal and neoplastic neuroendocrine tissues, suggesting that CST might have a broader functional role than previously assumed, whereas possible autocrine/paracrine actions via its recently described specific receptor MrgX2 are restricted to selected tissues.

Carcinoma, Neuroendocrine↗

PubMed2004

Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines.

BACKGROUND: Ghrelin, a natural growth hormone secretagogue (GHS), has been identified in prostate carcinoma cell lines. OBJECTIVES: To investigate the presence of ghrelin and its receptors in human prostate tumours and in DU-145, PC-3 and LNCaP prostate carcinoma cell lines, and to assess the effects of ghrelin and its more abundant circulating form, des-octanoyl ghrelin, on cell proliferation. METHODS: Ghrelin and types 1a and 1b GHS receptor (GHS-R) were determined at the mRNA and protein levels by RT-PCR, in situ hybridization, immunohistochemistry and enzyme immunoassay in tissues, cell lines and culture medium. Ghrelin binding was determined by radioreceptor assay. The effects on cell proliferation were evaluated by growth curves. RESULTS: Ghrelin mRNA was found in prostatic carcinomas and benign hyperplasias, but immunohistochemistry was negative. GHS-R1a and 1b mRNAs were absent from carcinomas, but GHS-R1b mRNA was present in 50% of hyperplasias. Ghrelin peptide and mRNA were present in PC-3 cells exclusively, whereas GHS-R1a and 1b mRNAs were expressed in DU-145 cells only. Specific [125I]Tyr4-ghrelin binding was detected in prostate tumour, DU-145 and PC-3 cell membranes and the binding was displaced by ghrelin, synthetic GHS and des-octanoyl ghrelin, which is devoid of GHS-R1a binding affinity and GH-releasing activity. Ghrelin and des-acyl ghrelin inhibited DU-145 cell proliferation, displayed a biphasic effect in PC-3 cells and were ineffective in LNCaP cells. CONCLUSIONS: Specific GHS binding sites, other than GHS-R1a and 1b, are present in human prostatic neoplasms. Ghrelin, in addition to des-acyl ghrelin, exerts different effects on cell proliferation in prostate carcinoma cell lines.

Androgens↗

PubMed2004

Evidence of oxytocin/oxytocin receptor interplay in human prostate gland and carcinomas.

Data on the presence of oxytocin receptors (OTR) within the prostate are still controversial and variable among different species. In the present study, OTR expression and localization has been investigated in human hyperplastic and neoplastic prostate at mRNA and protein levels using in situ hybridization (ISH) and immunohistochemistry (ICC) techniques, respectively. In all the cases studied, epithelial cells expressed OTR mRNA and protein. Interestingly, this expression was more intense in neoplastic epithelial cells compared to the hyperplastic ones. In order to determine whether OTR might mediate a biological effect of oxytocin (OT) in prostate cancer cells, OTR expression was studied by RT-PCR and immunofluorescence technique in the human androgen-independent prostate cancer cell line DU145. In addition, a possible heterotopic production of OT by DU145 cells was studied using RT-PCR. The data obtained showed that DU145 cells expressed OTR, whereas no OT mRNA was detected. When DU145 cells were treated with OT (100 nM) a significant inhibition of cell proliferation was observed, while co-incubation with the OT antagonist OTA (100 nm) abolished such an effect. The involvement of apoptosis in the OT effect contrasting cell proliferation was excluded by ISEL technique, which revealed a similar pattern of DNA fragmentation in either untreated or OT-treated cells. Altogether, the data indicate that the OT/OTR system could be involved in the control of prostate neoplastic pathology.

Cell Division↗

PubMed2003

Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth.

Ghrelin, a growth hormone-releasing hormone produced by gastroenteropancreatic endocrine cells, hypothalamus, and pituitary, was recently identified in medullary thyroid carcinomas and derived cell lines. However, no data exist on its expression in either normal or neoplastic thyroid follicular cells. We analyzed ghrelin expression by immunohistochemistry, in situ hybridization, and reverse transcriptase-polymerase chain reaction in 15 fetal, 4 infant, and 10 adult thyroids, and in 54 tumors of follicular origin. We also analyzed the effects of ghrelin on cell proliferation in N-PAP and ARO thyroid carcinoma cell lines. Ghrelin-binding sites were investigated using reverse transcriptase-polymerase chain reaction to detect its growth hormone secretagogue receptor (GHS-R) mRNA and an in situ-binding localization procedure. Strong ghrelin immunoreactivity was found in fetal but not in infant or adult thyroids. Ghrelin protein and mRNA were present, in variable amounts, in benign and malignant tumors. Normal thyroids, thyroid tumors, and cell lines showed ghrelin binding sites by binding localization, in the absence of the specific GHS receptor mRNA (with the exception of one normal thyroid). Moreover, ghrelin induced dose-dependent inhibition of growth in cell lines. In conclusion, ghrelin is expressed in fetal but not in adult thyroid, and is re-expressed in tumors; the presence of ghrelin receptors other than GHS-R in normal and neoplastic adult thyroid is suggested; ghrelin inhibits cell proliferation of thyroid carcinoma cell lines in vitro.

Adenocarcinoma, Follicular↗

PubMed2003

Potential applications of molecular biology in neuroendocrine tumors.

The impact of molecular biology procedures on neuroendocrine (NE) tumor biology is gradually evolving from purely academic and research studies to clinical applications. This review deals with applications of molecular techniques in neuroendocrine tumors, with special reference to their potential for diagnostic, prognostic, or therapeutic impact. Since the cloning of the genes involved in inherited endocrine tumor syndromes, molecular analysis of the responsible genetic alterations has become a routine diagnostic tool to select affected patients and their relatives, and also an interesting approach to investigate the pathogenesis of neuroendocrine tumors. Assessment of the clonal composition of endocrine tumors could be useful to differentiate hyperplastic versus either adenomatous or carcinomatous conditions, as well as to better understand the clonal relationship between different neoplastic populations in mixed tumors. In addition, molecular approaches allow high sensitivity both in defining the neuroendocrine phenotype in poorly differentiated tumors and in searching for micrometastasis during the follow up of patients with endocrine tumors. Finally, the detection of peptide hormone receptors (e.g., oxytocin and somatostatin receptors) and the development of potent synthetic analogs of such peptides, are opening promising applications in the diagnosis and therapy of endocrine tumors.

Biomarkers, Tumor↗