Ribonuclease MCPiP1 contributes to the loss of micro-RNA-200 family members in pancreatic cancer cells.

The microRNA-200 (miR-200) family is frequently down-regulated in tumors, including pancreatic adenocarcinomas (PDACs). In this study we have examined the mechanisms involved in the loss of miR-200s in tumoral pancreatic cells. Whereas miR-200 gene promoters appear methylated in mature miR-200 deficient cell lines, miR-200 precursors are detected in nuclear but not cytoplasmic compartment of these cells, indicating that promoter hypermethylation is not sufficient to explain the deficit of mature miR-200s.

Differential expression of miR200a-3p and miR21 in grade II-III and grade IV gliomas: evidence that miR200a-3p is regulated by O⁶-methylguanine methyltransferase and promotes temozolomide responsiveness.

Glioblastoma multiforme (GBM) is the most common primary brain tumor and is among the deadliest of human cancers. Dysregulation of microRNAs (miRNAs) expression is an important step in tumor progression as miRNAs can act as tumor suppressors or oncogenes and may affect cell sensitivity to chemotherapy. Whereas the oncogenic miR21 has been shown to be overexpressed in gliomas, the expression and function of the tumor-supressor miR200a in GBMs remains unknown.

Association of matrix metalloproteinase 2 plasma level with response and survival in patients treated with bevacizumab for recurrent high-grade glioma.

Background: A predictive marker of bevacizumab activity is an unmet medical need. We evaluated the predictive value of selected circulating prebiomarkers involved in neoangiogenesis and invasion on patient outcome in recurrent high-grade glioma treated with bevacizumab.

Methods: Analyzed in plasma were a set of 11 prebiomakers of interest (vascular endothelial growth factor receptor [VEGF]; VEGF receptor 2; basic fibroblast growth factor; stromal cell derived factor 1; placenta growth factor; urokinase-type plasminogen activator; plasminogen activator inhibitor 1; matrix metalloproteinases 2, 7, and 9; and adrenomedulline), using ELISA, at baseline and 2 weeks after bevacizumab initiation in a prospective cohort of 26 patients (Cohort 1).

Adrenomedullin blockade suppresses growth of human hormone-independent prostate tumor xenograft in mice.

Purpose: To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth.

Experimental Design: Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis.

Results: Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score >7), suggesting a role of the adrenomedullin system in prostate cancer growth.

Adrenomedullin expression and regulation in human glioblastoma, cultured human glioblastoma cell lines and pilocytic astrocytoma.

Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Glioblastoma (GBM) and pilocytic astrocytoma (PA), both angiogenic tumours display strong contrast enhancement associated with peripheral oedema in GBM but not in PA indicating differences in vascular permeability in these two types of gliomas. Here we show that expression of adrenomedullin (AM) mRNA is induced in GBM whereas is barely detectable in PA.

Targeting adrenomedullin receptors with systemic delivery of neutralizing antibodies inhibits tumor angiogenesis and suppresses growth of human tumor xenografts in mice.

Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). Previously, we reported on the development of an anti-AM antibody that potently inhibits tumor cell proliferation in vitro and tumor growth in vivo. Here, we report the effect of anti-AM receptor antibodies (alphaAMRs) on angiogenesis and tumor growth.

Adrenomedullin, an autocrine/paracrine factor induced by androgen withdrawal, stimulates 'neuroendocrine phenotype' in LNCaP prostate tumor cells.

Neuroendocrine (NE) differentiation in prostate cancer (CaP) has been reported to be an early marker associated with the development of androgen independence. The mechanisms by which CaP acquires NE properties are poorly understood. In this study, a putative role of adrenomedullin (AM) in the NE differentiation was investigated.

Expression of adrenomedullin in adipose tissue of lean and obese women.

Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity.

Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes.

Identification of secondary structure in the 5'-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation.

Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5'-untranslated region (5' UTR) of human AM mRNA. Reverse transcriptase-polymerase chain reaction of the 5' UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an approximately 65-bp deletion from the central region of the 5' UTR, suggesting the presence of a secondary structure.

[Role of adrenomedullin in glioblastomas growth].

Glioblastoma multiforme is the most malignant of the primary brain tumors and is almost always fatal. The treatment strategies for this disease have not changed appreciably for many years and most are based on a limited understanding of the biology of the disease. Growth factors are potential targets for therapeutic strategies because they are essential for tumor growth and progression.

Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors.

Recently, we demonstrated that U87 glioblastoma xenograft tumors treated with anti-adrenomedullin (AM) antibody were less vascularized than control tumors, suggesting that AM might be involved in neovascularization and/or vessel stabilization. Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, is a multistep process that involves migration and proliferation of endothelial cells, remodeling of the extracellular matrix and functional maturation of the newly assembled vessels. In our study, we analyzed the role of AM on human umbilical vein endothelial cell (HUVEC) phenotype related to different stages of angiogenesis.

Molecular cloning and tissue distribution of the ovine somatostatin receptor subtype 5: osst5.

The sheep is a valuable model to study growth hormone (GH) neuroregulation since its GH secretion pattern is close to that in humans and an integrated physiological approach is possible in this species. Somatostatin receptor subtype 5 (sst5) appears to be important in GH regulation but the ovine sst5 gene (osst5) has not yet been cloned. We report here the cloning of sst5 in that species.

Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines.

After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop androgen-independent growth through not-well-defined mechanisms. The presence of neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal prostate, and the frequency of NE cells correlates with tumor malignancy, loss of androgen sensitivity, increase of autocrine-paracrine activity, and poor prognosis. In some CaPs, neuropeptides have been previously implicated as growth factors.

Characterization and regulation of peptidylglycine alpha-amidating monooxygenase (PAM) expression in H9c2 cardiac myoblasts.

Peptidylglycine alpha-amidating monooxygenase (PAM), which catalazyes the two-step formation of bioactive alpha-amidated peptides from their glycine-extended precursors, has been found in H9c2 myoblasts. The expression of PAM has been evaluated in H9c2 cells. Northern blot analysis and amplification of fragments derived from rat PAM by the reverse transcription/polymerase chain reaction method has demonstrated the presence of rPAM-1, -2, -3, -3a and -3b mRNA transcripts.

Alpha1-adrenergic regulation of peptidylglycine alpha-amidating monooxygenase gene expression in cultured rat cardiac myocytes: transcriptional studies and messenger ribonucleic acid stability.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.

Effect of corticotrophin-releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease.

Objective: To evaluate the effect of CRH administration on plasma AVP and ANF concentration in patients with Cushing's disease and healthy subjects.

Subjects: Fifteen patients with Cushing's disease and 15 sex- and age-matched healthy subjects entered the study.

Study Design: All subjects were randomly given i.

Evidence of high expression of peptidylglycine alpha-amidating monooxygenase in the rat uterus: estrogen regulation.

In the present study, high levels of peptidylglycine alpha-amidating monooxygenase (PAM), which catalyzes the two-step formation of bioactive alpha-amidated peptides from their glycine-extended precursors, have been found in the uterus. Expression of PAM was evaluated in the uterus of intact cycling adult female rats and after experimental manipulation of the estrogen status of the rats. During the estrous cycle, PAM mRNA levels exhibited striking changes inversely related to the physiological variations of plasma estrogen levels.

Identification of a novel cis-element in the 3'-untranslated region of mammalian peptidylglycine alpha-amidating monooxygenase messenger ribonucleic acid.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.

Estrogen regulation of peptidylglycine alpha-amidating monooxygenase messenger ribonucleic acid levels by a nuclear posttranscriptional event.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.

Estrogen regulation of peptidylglycine alpha-amidating monooxygenase expression in anterior pituitary gland.

The pituitary is a rich source of peptidylglycine alpha-amidating monooxygenase (PAM). This bifunctional protein contains peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase catalytic domains necessary for the two-step formation of alpha-amidated peptides from their COOH-terminal glycine extended precursors. Expression of PAM was evaluated in the anterior pituitary of intact cycling adult female rat and after experimental manipulation of estrogen status.

Effect of thyroid hormones on peptidylglycine alpha-amidating monooxygenase gene expression in anterior pituitary gland: transcriptional studies and messenger ribonucleic acid stability.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.

Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin-releasing hormone and comparison with patients without Cushing's disease.

Background: Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease.

Design: In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation.

Patients: Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes.

Corticotropin-releasing hormone administration increases alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinuses in a subset of patients with Cushing's disease.

The effect of corticotropin (ACTH)-releasing hormone (CRH) administration on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta-endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing's disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to alpha-MSH response. CRH bolus did not modify alpha-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole.