Biomedical subjects

N Gibelli

Publications and source records attributed to N Gibelli.

31 records · Page 2Linked to original sources

PubMed1989

Hormonal modulation of brain tumour growth: a cell culture study.

Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.

Aged↗

PubMed1987

In vitro and in vivo studies of poly-L-lysine as inducer of Friend leukemic cells differentiation.

Poly-L-lysine, a synthetic cationic polypeptide known for its ability to bind to cell membranes, was found to induce differentiation of Friend leukemia cells "in vitro". Studies were extended to the same "in vitro" model, in order to examine the therapeutic potential of this new differentiating agent. The i.p. administration of the polymer (Mw 2700) at the maximal tolerated dose resulted in major alterations of disease-related parameters. In particular, a multiple treatment schedule on the advanced disease resulted in a successful reduction of target organ weight and peripheral white blood cell count and appreciable differentiation of spleen and bone marrow cells. Apparently, the effects of poly-L-lysine were superior to those produced by N-methyl-acetamide, a potent inducer of differentiation "in vitro".

Acetamides↗

PubMed1987

Interaction of heat with chemotherapy in vitro: effect on cell viability and protein synthesis in human and murine cell lines.

Cell survival in response to doxorubicin (Dx) and cis-diammine-dichloroplatinum (cis-Pt) administration, either alone or combined with hyperthermic treatment, was analyzed in human osteosarcoma (U-2-OS), murine melanoma (B16V) and murine leukemia (P388) cell lines and in Dx-resistant sublines derived from B16V and P388. In all cell lines tested there was an enhancement of drug toxicity by hyperthermia. In U-2-OS, the increase was more pronounced for cis-Pt than for Dx. In B16V and in P388, the increase in Dx toxicity was of the same degree in Dx-sensitive and Dx-resistant sublines, whereas heat-induced sensitization to cis-Pt was higher in Dx-resistant sublines than in their Dx-sensitive counterpart. Analysis of the protein pattern in the various cell lines showed that the synthesis of heat-shock proteins induced by heat was not influenced by the combined use of drugs and heat. Moreover, in spite of some differences in the overall protein pattern, no significant differences in the basal levels of heat-shock protein synthesis or in the extent of its induction after heat shock were observed between murine cell lines relatively sensitive to Dx and their corresponding selected resistant cells.

Animals↗

PubMed1986

Induction of differentiation of Friend murine erythroleukemia cells by poly-L-lysine and daunorubicin-poly-L-lysine conjugate.

The ability of the synthetic cationic polypeptide poly-L-lysine (PLL) to induce differentiation of Friend murine erythroleukemia cells was examined with the use of polymers of different molecular weights. Like other membrane-interacting agents (polar solvents), all the polymers tested were effective in inducing cell differentiation. This effect was found to be molecular weight dependent, as already reported for other membrane-related actions of these polymers. Since anthracyclines also exert direct effects on the cell membrane, the activity of the daunorubicin-PLL conjugate was also examined. The covalent linking of the drug to the polyamino acid somewhat reduced the differentiation-inducing activity in this system. Indeed, free daunorubicin was found to inhibit the maturational process. Although the inducing effect was observed when the free PLL or daunorubicin-linked PLL was added alone, polymers enhanced differentiation produced by suboptimal concentrations of dimethyl sulfoxide (DMSO). Since PLL was inactive as an initiator of the maturation of a DMSO-resistant line, it is likely that some events (presumably membrane-related effects) involved in the multistep stimulation process are common to polar-planar solvents and the polycationic polymer.

Animals↗

PubMed1985

Influence of calcium and calcium-modulating agents on differentiation of murine erythroleukaemia cells.

Since the involvement of calcium ions in the regulation of cell division and differentiation has been proposed, in this study we have examined the effect of extracellular calcium and of calcium-modulating agents on the DMSO-induced differentiation of murine erythroleukaemia cells. Neither proliferation nor differentiation of these cells was affected by calcium deprivation in the culture medium. Moreover, calcium-chelating agents or agents blocking intracellular calcium uptake induced a marked inhibition of cell differentiation. Intracellular calcium antagonists induced inhibition when cells were grown in a calcium-deprived medium. In contrast, murine erythroleukaemia cell differentiation was unaffected by agents that increased intracellular concentration of calcium. Our results indicate that a mobilization of calcium is indispensable for eliciting full cellular response, but the increase in intracellular level of this cation is not sufficient for complete signal transduction. It is likely that a marked alteration of the intracellular calcium system and availability could be responsible for the independence of our cell system from calcium modulation.

4-Aminopyridine↗

PubMedDate not supplied

[Hepatic hemangioma]

OBJECTIVE: To describe a case of a congenital hepatic hemangioma treated with surgery. METHODS: We report the case of a 6-day-old boy who presented a giant hepatic hemangioma, and describe its evolution. RESULTS: The child developed hemodynamic instability secondary to consumption coagulopathy and respiratory failure. The image studies were inconclusive. He was submitted to surgery with complete resection of the tumor. Pathology confirmed it was hemangioma. The child was discharged after 15 days and is well, without symptoms. CONCLUSIONS: Hepatic hemangiomas should be treated conservatively, with surgery reserved for intractable cardiac failure and/or refractory consumptive coagulopaty.

Journal Article↗

PubMedDate not supplied

Establishment and characterization of two cell lines derived from human glioblastoma multiforme.

We established and characterized two cell lines derived from glioblastoma multiforme. Both cell lines exhibited tumor cell morphology and growth kinetics and showed variable expression of glial fibrillary acidic protein (GFAP), S-100, fibronectin and vimentin. Cytofluorimetrical analysis of tumor samples showed a diploid DNA distribution, whereas permanent culture cells evolved to the hyperdiploid DNA content. Karyotype studies revealed cytogenetical abnormalities described in glial tumors including gain of chromosome 7, loss of chromosome 10 and presence of double minutes (DMs). Enhanced expression of Ha-ras and c-myc genes resulted from high p-21 and p-62 levels. The contemporary presence of TGF-alpha and EGF-Rc transcripts suggested an autocrine mechanism in the cell lines growth.

Cell Division↗

PubMedDate not supplied

Proliferative effect of dexamethasone on a human glioblastoma cell line (HU 197) is mediated by glucocorticoid receptors.

The relationship between Dexamethasone proliferative activity and the presence of glucocorticoid receptors was studied on a human glioblastoma cell line (HU 197). For this purpose, the 17 beta-Carboxamide steroid DXB, a glucocorticoid antagonist that competes with Dexamethasone for binding to the intracellular glucocorticoid receptor but does not trigger the glucocorticoid effect, was used. Concurrent treatments with Dexamethasone and DXB caused an inhibition of the proliferative effect obtained by Dexamethasone. The results obtained demonstrated that the Dexamethasone activity on cell proliferation is a specific receptor-mediated effect.

Cell Division↗

PubMedDate not supplied

Stem cell factor and interleukin-6, alone or in combination with granulocyte colony-stimulating factor, do not affect the growth of solid tumor cell lines.

Hematopoietic growth factors (HGFs) are glycoproteins that control hemopoiesis. They have potential usefulness in a range of clinical conditions including the treatment of patients with myelosuppression induced by chemotherapy. Among HGFs, Stem Cell Factor (SCF) and Interleukin 6 (IL-6) are attracting interest for their capacity to stimulate early hematopoietic progenitors. Furthermore, their use in combination with late-acting growth factors with a more lineage-restricted potential (such as granulocyte colony-stimulating factor, G-CSF) might be expected to offer optimal marrow stimulation and usefulness in clinical oncology. Since non-hematopoietic malignant cells may express receptors for HGFs and respond to these peptides in vitro, we investigated clonal growth 3H-thymidine incorporation and cell cycle analysis by flow cytometry of 5 human solid tumor cell lines under the influence of SCF and IL-6 with or without G-CSF. Our experiments show that these cytokines have no effects on the proliferative capacity of the cell lines tested. Based on our and previously reported data, the use of these HGFs can be considered safe in cancer patients.

Cell Adhesion Molecules↗

PubMedDate not supplied

Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line.

In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp. In our experiments the revertant activity of medroxyprogesterone acetate (MPA) in comparison to that of the well known revertant agent verapamil (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant (CG5/DX) obtained in our laboratory from the parental CG5 human breast cancer cell line by continuous exposure to the drug. The ability of MPA to modulate intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more active than VRP in reversing MDR, suggesting a possible role of this synthetic progestin as chemosensitizing agent in the clinical management of anthracycline-resistant breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Morphological and biochemical features of a medroxyprogesterone acetate (MPA)-resistant MCF-7 breast cancer cell line.

An MCF-7 human breast cancer line variant (MCF-7/MPA), resistant to medroxyprogesterone-acetate (MPA), was obtained by continuous exposure in vitro to the drug. MCF-7/MPA cells were grown in the presence of 12.5 x 10(-6) M MPA and were selected by increasing the concentration of the drug in the growth medium in a stepwise manner from 0.025 x 10(-6) M up to 12.5 x 10(-6) M. Comparative studies of cellular morphology, cytosolic steroid receptor content and P-Glycoprotein expression were performed on both MCF-7 parental line and MCF-7/MPA variant. MCF-7/MPA cells, when compared to the parental line, exhibit a different morphology in terms of membrane alterations, reduced content of cytosolic progesterone receptor, increased expression of P-glycoprotein along with reduction of Doxorubicin (Dx) activity on the growth of MCF-7/MPA resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

CG5/Dx human breast cancer cell line: characterization of a new doxorubicin-resistant variant.

By continuous exposure of CG5 human breast cancer cell line to increasing doxorubicin (Dx) concentrations, a multidrug-resistant (MDR) subline (CG5/Dx) was obtained. The resistant variant showed P-glycoprotein (P-gp) expression and a lower intracellular doxorubicin level than the parental cells. CG5/Dx cells were 19.4 fold more resistant to Dx than CG5 cells and showed a cross-resistance to some structurally related and unrelated compounds. Differences in kinetics, biological and ultrastructural features between the two cell lines were investigated. The CG5/Dx cells grew more slowly, produced higher CEA levels and showed a reduced progesterone receptor (PgR) content than the parental cells. Ultrastructural studies revealed differences involving, polyribosomes, rough endoplasmic reticulum, [mitochondria] and cytoskeleton.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Effects of glycosylated and non-glycosylated G-CSFs, alone and in combination with other cytokines, on the growth of human progenitor cells.

Two recombinant human granulocyte colony-stimulating factors (rHu G-CSF) are clinically available, a glycosylated (lenograstim) and a nonglycosylated from (filgrastim). Since there is accumulating evidence that glycosylation plays a role in the in vitro activity of the G-CSF molecule, we compared the biological potency of lenograstim and filgrastim on human hematopoietic progenitor cells by colony assay in semisolid medium and ex vivo expansion experiments. Leukapheretic products without further processing and CD34-positive purified cells were used as source of human progenitors. Lenograstim demonstrated greater capacity, to stimulate the colony growth of both, purified and CD34+ peripheral blood cells. This effect, which is evident especially at low doses of growth factor, seems not to be mediated by accessory cells. Whether these observations may have clinical relevance is still to be clearly assessed and further investigations are needed.

Antigens, CD↗