Biomedical subjects

K Oliva

Publications and source records attributed to K Oliva.

6 recordsLinked to original sources

PubMed2003

Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta1 integrin complex in colon cancer cells.

Cancer invasion is regulated by cell surface proteinases and adhesion molecules. Interaction between specific cell surface molecules such as urokinase plasminogen activator receptor (uPAR) and integrins is crucial for tumour invasion and metastasis. In this study, we examined whether uPAR and beta1 integrin form a functional complex to mediate signalling required for tumour invasion. We assessed the expression of uPAR/beta1 integrin complex, Erk signalling pathway, adhesion, uPA and matrix metalloproteinase (MMP) expression, migration/invasion and matrix degradation in a colon cancer cell line in which uPAR expression was modified. Antisense inhibition of the cell surface expression of uPAR by 50% in human colon carcinoma HCT116 cells (A/S) suppressed Erk-MAP kinase activity by two-fold. Urokinase plasminogen activator receptor antisense treatment of HCT116 cells was associated with a 1.3-fold inhibition of adhesion, approximately four-fold suppression of HMW-uPA secretion and inhibition of pro-MMP-9 secretion. At a functional level, uPAR antisense resulted in a four-fold decline in migration/invasion and abatement of plasmin-mediated matrix degradation. In empty vector-transfected cells (mock), uPA strongly elevated basal Erk activation. In contrast, in A/S cells, uPA induction of Erk activation was not observed. Urokinase plasminogen activator receptor associated with beta1 integrin in mock-transfected cells. Disruption of uPAR-beta1 integrin complex in mock-transfected cells with a specific peptide (P25) inhibited uPA-mediated Erk-MAP kinase pathway and inhibited migration/invasion and plasmin-dependent matrix degradation through suppression of pro-MMP-9/MMP-2 expression. This novel paradigm of uPAR-integrin signalling may afford opportunities for alternative therapeutic strategies for the treatment of cancer.

Colonic Neoplasms↗

PubMed2001

Glucose-induced release of tumour necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus.

AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of insulin resistance in Type 2 diabetes mellitus, but limited data are available in relation to gestational diabetes mellitus (GDM), a disease in which similar biochemical abnormalities exist. We investigated the effect of exogenous glucose on the release of TNF-alpha from placental and adipose (omental and subcutaneous) tissue obtained from normal pregnant women, and women with GDM. METHODS: Human tissue explants were incubated for up to 24 h and TNF-alpha concentration in the incubation medium quantified by ELISA. The effect of normal (5 mmol/l) and high (15 and 25 mmol/l) glucose concentrations on the release of TNF-alpha was assessed. RESULTS: In placental and subcutaneous adipose tissues obtained from women with GDM (n = 6), TNF-alpha release was significantly greater under conditions of high glucose compared with normal glucose (placenta, 25 mmol/l 5915.7 +/- 2579.6 and 15 mmol/l 4547.1 +/- 2039.1 vs. 5 mmol/l 1897.1 +/- 545.5; subcutaneous adipose tissue, 25 mmol/l 423.5 +/- 207.0 and 15 mmol/l 278.5 +/- 138.7 vs. 5 mmol/l 65.3 +/- 28.5 pg/mg protein; P < 0.05). In contrast, there was no stimulatory effect of high glucose on TNF-alpha release by tissues obtained from normal pregnant women (n = 6) (placenta, 25 mmol/l 1542.1 +/- 486.2 and 15 mmol/l 4263.3 +/- 2737.7 vs. 5 mmol/l 5422.4 +/- 1599.0; subcutaneous adipose tissue, 25 mmol/l 189.8 +/- 120.4 and 15 mmol/l 124.5 +/- 32.3 vs. 5 mmol/l 217.9 +/- 103.5 pg/mg protein). CONCLUSIONS: These observations suggest that tissues from patients with GDM release greater amounts of TNF-alpha in response to high glucose. As TNF-alpha has been previously implicated in the regulation of glucose and lipid metabolism, and of insulin resistance, these data are consistent with the hypothesis that TNF-alpha may be involved in the pathogenesis and/or progression of GDM.

Adipose Tissue↗

PubMed1997

Analysis of chorionic gonadotrophin secreted by cultured human blastocysts.

Embryos produced in an in-vitro fertilization (IVF) programme, but which were unsuitable for transfer to patients because they originated from one (1PN) or three pronuclear (3PN) oocytes or because they originated from two pronuclear (2PN) oocytes but cleaved normally, were maintained in tissue culture. The embryos that progressed to blastocytes were cultured to day 14 of development in order to study their daily output of human chorionic gonadotrophin (HCG). Blastocysts that released large amounts of immunoreactive HCG, which continued to increase daily during the study period, provided the culture supernatants used in the present studies. The heterogeneity of HCG released by blastocyst tissues on days 11 and 14 of development was studied by a chromatofocusing method which separates the isoforms of the gonadotrophin based on differences in their isoelectric points. It was found that the secreted HCG was composed of several molecular forms and that this heterogeneity changed from day 11 to 14 of development. The early blastocyst tissues produced more acidic HCG isoforms than the more advanced embryonic tissues. Differences in the apparent ploidy of the blastocyst tissues studied did not affect significantly the distribution of the HCG isoforms secreted either on day 11 or day 14 of development. These results suggest that the bioactivity of the HCG secreted by blastocytes may change with time and with differentiation of the trophectoderm. In addition, the results suggest that the ploidy of early blastocytes does not influence the nature of the HCG secreted.

Blastocyst↗

PubMed1993

Chorionic gonadotrophin secretion by human blastocysts.

Abnormal embryos that arose in our in-vitro fertilization programme were cultured in serum-free minimum essential medium (MEM), and those that developed into blastocysts were cultured up to day 14 after fertilization to study the influence of various supplements on chorionic gonadotrophin (CG) secretion. Human cord serum, at a concentration of 1%, was found to be one of the most effective stimulants for initiating and maintaining CG production. A mixture of insulin+transferrin+selenium (ITS) stimulated CG secretion in serum-free MEM, although the output of hormone began to decline after approximately 3 days. Platelet-derived growth factor (PDGF) produced a similar response to ITS. Stimulation of blastocyst CG secretion in the absence of serum could also be induced with 8-bromo-cAMP. All stimulants were able to evoke CG secretion in day 7-8 blastocysts. These studies have shown that multiple factors were capable of inducing CG production by early blastocysts. On the basis of these and other studies it was postulated that receptors for insulin, transferrin and PDGF were expressed in preimplantation blastocysts.

Blastocyst↗

PubMed1990

A loving will.

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Aged↗

PubMed1982

Embryonic development and blastocyst implantation following in vitro fertilization and embryo transfer.

A sensitive and specific radioimmunoassay was used to measure human chorionic gonadotropin (hCG) excretion in serial overnight urine samples in women having embryo transfer, in an in vitro fertilization program. Elevated hCG excretion suggestive of blastocyst implantation was detected in 17 of 121 women studied. When the results were corrected for interference by luteinizing hormone and other immunoreactive substances, implantation was detectable 8 to 9 days after fertilization in 20% of conceptual cycles, in 80% by days 12 to 13, in 93% by days 14 to 15, and in 100% by days 16 to 17. From a life table of human embryo development in culture, it was estimated that 37% of four-cell and 43% of eight-cell embryos reached the blastocyst stage. On the basis of these estimates and the elevated hCG from implanting blastocysts, it was concluded that 60% to 65% of uterine blastocysts either failed to implant or failed to produce measurable hCG.

Blastocyst↗