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Biomedical subjects

A Albini

Publications and source records attributed to A Albini.

At least 163 records · Page 9Linked to original sources
PubMed1984

Chemotactic response of SV40 virus transformed fibroblasts to conditioned medium: dependence on time and cell number.

The ability of tumor cells to move chemotactically in response to specific stimuli may be one of the many factors which distinguish malignant from non-malignant cells. In this work we demonstrated that a SV 40 virus transformed human fibroblast cell line (SV40/WI26) has an enhanced chemotactic response to fibroblast-conditioned medium (FCM) as compared to control human fibroblasts, and this was true for different migration times and different initial cell numbers. A similar behaviour has been described for SV40 transformed mouse fibroblasts (SV3T3). Furthermore, another SV40 transformed human fibroblast cell line (SV40/WI38) has been reported to have an enhanced chemotactic response to FCM compared to the normal counterpart. We conclude that the increased chemotactic response to FCM could be well correlated with the phenotype induced by fibroblast transformation with SV 40.

Cell Count↗
PubMed1984

Enhanced chemotaxis of tumor-derived and virus-transformed cells to fibronectin and fibroblast-conditioned medium.

SV40 transformants of human embryo fibroblasts showed an enhanced chemotactic response to fibronectin and conditioned medium of fibroblasts in comparison to the non-transformed cells. An even higher chemotactic response was characteristic for a malignant human fibrosarcoma cell line, whereas cells derived from low-grade malignant dermatofibrosarcoma showed a normal response in the Boyden chamber assay. The high stimulation of chemotaxis is paralleled by a reduced synthesis and an altered deposition of fibronectin in the pericellular matrix of these cells. Both high chemotactic response and lack of deposition of fibronectin may play a role in tissue invasion and formation of metastasis by malignant tumors.

Cell Transformation, Viral↗
PubMed1984

A method to select cell populations with enhanced chemotactic activity.

Virus-transformed and tumor cells often show a higher chemotactic activity in comparison to normal cells. Here we show that the blind-well chamber assay is an easy and rapid procedure to select cell populations with enhanced chemotactic activity. Collagen-type-specific antibodies have been applied to analyze the efficiency of cell sorting by the chemotaxis assay.

Cell Separation↗
PubMed1984

Pattern of collagen synthesis and chemotactic response of fibroblasts derived from mucopolysaccharidosis patients.

For comparative studies on the migratory potential we screened fibroblast strains derived from mucopolysaccharidosis (MPS) patients regarding their differential response to chemotactic stimuli and analysed their production of extracellular matrix components. Indirect immunofluorescence staining of MPS-fibroblasts showed the same distribution of type I and type III collagen and of fibronectin as in controls. Biochemical quantification of type I and type III collagen demonstrated an unaltered ratio of these collagen types, although the total amount of newly synthesized collagens was slightly reduced in fibroblasts from MPS patients. Whereas the synthesis of major extracellular matrix components was close to normal, the response of the MPS cells to chemotactic stimuli was greatly affected. Chemotactic migration was improved when fibroblasts were pretreated with medium conditioned by normal fibroblasts, although they never reached normal levels.

Cells, Cultured↗
PubMed1983

Localization of the chemotactic domain in fibronectin.

Fragments derived from human plasma fibronectin by enzymatic degradation were tested in the Boyden chamber for chemotactic activity towards various fibroblast strains. The results provide clear evidence that the chemotactic activity is restricted to a defined region of the fibronectin molecule which is the same for various fibroblast strains. The active domain is localized between the collagen binding site and the major heparin binding site, about 170 kDa apart from the N-terminal and about 70 kDa from the C-terminal ends of the two subunit peptide chains.

Binding Sites↗
PubMed1983

[Chemotactic activity of fibroblasts in mucopolysaccharidoses].

Certain clinical symptoms such as hernias or joint contracture in patients with mucopolysaccharidoses (MPS) cannot be explained as direct consequences of the disturbed glycosaminoglycan metabolism. They may be related to secondary changes of connective tissue components. The glycoprotein fibronectin is a constituent of connective tissue with a high affinity to polyanions such as heparan sulfate or heparin. Fibronectin in addition is a potent stimulus for fibroblasts to migrate chemotactically. We studied this cell property in MPS fibroblasts. The chemotactic activity of all MPS types was diminished. MPS II fibroblasts were chemotactically inactive. When the cells were corrected for the lacking enzyme by adding conditioned medium from control fibroblasts, the chemotactic migration increased except for MPS type II cells. The known enzyme defect in the degradation process of glycosaminoglycans in MPS results in lysosomal storage of degradation products and in addition causes changes of other cell properties.

Chemotaxis↗
PubMed1982

DNA damage in liver, kidney, bone marrow, and spleen of rats and mice treated with commercial and purified aniline as determined by alkaline elution assay and sister chromatid exchange induction.

Aniline of unknown purity has been reported to induce spleen hemangiosarcoma in rats. Aniline has been found to be negative in terms of mutagenicity in both bacteria and yeasts. We have found that both commercial (already rather pure) and repurified aniline are clearly positive to a similar extent in inducing DNA damage in vivo in liver and kidney of rats. Both the commercial and repurified product are also clearly positive in induction of sister chromatid exchanges in vivo in male Swiss mice bone marrow cells. Liver, kidney, and bone marrow DNA damage was absent in male Swiss mice.

Aniline Compounds↗
PubMed1980

[Standardization of a method of determining the thiolic-SH groups in human blood due to kinetic considerations].

Since the reaction of colorimetric titration of the sulphydril groups in human serum with the Ellman method, useful, besides, to follow the course of rheumatic diseases, occurs at 100% only after quite long time, for routine analysis it's necessary to keep to a standard degree of reaction, that is to take the absorbance always after the same time. Referring instead to the plateau of the titration curve it's necessary to put oneself in the conditions to reach the 100% of reaction in a short time. This is possible only by diluting the serum strongly, to the detriment of the precision of the analysis. The best conditions we found for quick and sufficiently precise clinical analysis are obtained by absorbances included between 0,15 and 0,30 u.A., which are reached with a calculated dilution of serum.

Humans↗
PubMedDate not supplied

The in vitro invasiveness and interactions with laminin of K-1735 melanoma cells. Evidence for different laminin-binding affinities in high and low metastatic variants.

The invasive and metastatic characteristics of cloned cells derived from the K-1735 murine melanoma were investigated. Cell lines which are highly metastatic in mice were found to be invasive in vitro, and to show an enhanced attachment to, spreading on and migration toward laminin. As attachment, spreading and directional migration are thought to be receptor-mediated events, the binding of laminin to these cells was studied. Biotinylated laminin was used to evaluate receptor binding by fluorescence activated cell sorting (FACS) and this method was compared with that in which the binding of radioactive laminin is measured. Both studies revealed that metastatic K-1735 cells (a) have more receptors for laminin compared with non-metastatic cells and (b) exhibit a second population of low-affinity binding sites not present on the non-metastatic cells. The differences in receptor number and type may account for the greater interaction of metastatic cells with laminin and their invasive phenotype.

Animals↗
PubMedDate not supplied

KSHV sequences in biopsies and cultured spindle cells of epidemic, iatrogenic and Mediterranean forms of Kaposi's sarcoma.

The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and several factors appear to be involved in the onset of the Kaposi's lesion. Epidemiological studies suggest that a common infective agent may contribute to KS. Sequences which appear to represent a new gammaherpesvirus, currently termed KSHV/HHV8, have recently been identified in KS. To further examine the relationship between this virus and KS, we obtained biopsy samples of KS lesions; these samples, the spindle cells cultured from these lesions and the PBMC of the same patients were tested for the presence of KSHV sequences by PCR. In addition, we tested several "late passage" KS spindle cell lines as well as control samples. The biopsy samples were from lesions of the following forms of KS: one sporadic KS, two epidemic KS and three iatrogenic KS, one of which was in the process of regressing after reduction of immunosuppressive therapy, and two that were at different stages (patch and nodular) from a single patient. The sporadic KS specimen was positive, as were the PBMCs from this patient, and cells grown from this biopsy appeared to contain KSHV viral sequences up to the fifth passage. Both epidemic KS biopsies were positive, but in these cases KSHV sequences were not detected in the cultured cells. The biopsy from the regressing iatrogenic KS lesion was negative, as were the cells cultured from this lesion. However, the PBMCs of this patient were weakly positive for KSHV at the time of biopsy, and PBMCs collected from this patient one month later were completely negative. The samples of both the patch and the nodular KS lesions obtained from another immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs of this patient and primary KS cell cultures from these biopsies were negative. Of the late-passage KS lines tested, only one, IST AIDS KS 12, was positive for KSHV. This line is derived from an early angiomatous-macula lesion. Taken together, these data suggest that an active KSHV infection is associated with KS and that elimination of KSHV from the lesion precedes regression of the lesion, strongly correlating KSHV with KS. In addition, early KS lesions may have a higher KSHV burden, or contain cells more susceptible to KSHV infection, further linking KSHV to KS.

Aged↗
PubMedDate not supplied

Establishment and characterization of two new Kaposi's sarcoma cell cultures from an AIDS and a non-AIDS patient.

We have established and characterized two new Kaposi's sarcoma (KS) cell lines derived from skin biopsies: AIDS-KSISTIV (from an AIDS-associated KS) and KSISTVIII (from a sporadic KS). AIDS-KSISTIV and KSISTVIII are composed mostly of spindle-shaped cells. They show similar patterns of immunohistochemical staining and are positive for smooth muscle (smooth muscle alpha-actin) and fibroblastoid (TE7) markers. Neither of these lines express the endothelial marker von Willebrand factor VIII. These immunohistochemical patterns are similar to numerous other KS lines that we and others have established. When seeded on a reconstituted basement membrane ("Matrigel"), AIDS-KSISTIV and KSISTVIII cells form branching colonies and invade into the Matrigel, as do other KS cultures that we have previously examined. This behaviour on Matrigel is similar to that of malignant sarcoma cells of different origin. The expression of vimentin and the morphology of the invasive colonies on Matrigel suggest that KS-derived cells are poorly differentiated mesenchymal cells. KS lesions are characterized by a conspicuous neovascularization, which appears to be derived from host cell recruitment. We tested the capability of the KS-cell supernatants to induce an angiogenic response in vitro. The new lines are able to stimulate human endothelial cell chemotaxis and invasion through Matrigel-coated filters. No differences in angiogenic potential in vitro were observed between the AIDS and the non-AIDS case, as we previously noted for other established cultures. Our new lines have the properties of true KS cells and confirm that KS spindle cells from HIV-positive or -negative patients have identical phenotypic and behavioural characteristics in vitro.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

DNA damage induced by auramine O in liver, kidney, and bone marrow of rats and mice, and in a human cell line (alkaline elution assay and SCE induction).

Auramine O has been reported to be carcinogenic in rats and mice. It has been reported as positive in some mutagenicity studies and negative in others. We have found that commercial auramine O is positive in inducing DNA damage in vivo in liver, kidney, and bone marrow cells. DNA damage was also induced after treatment in vitro of a human cell line. Commercial auramine O was also clearly positive for sister chromatid exchange (SCE) induction in vivo in bone marrow cells. Purified auramine was negative in terms of DNA damage and SCE induction. Our commercial auramine O had Michler's ketone as a major contaminant. This compound was capable of inducing both DNA fragmentation and an increase of SCE.

Aniline Compounds↗
PubMedDate not supplied

Antiangiogenic activity of chemopreventive drugs.

Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account--at least in part--for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention.

Acetylcysteine↗
PubMedDate not supplied

Angiogenesis at the interface between basic and clinical research.

The field of antiangiogenesis has shown a remarkably rapid evolution from the discovery at the bench to translation into the clinic. Currently a wide variety of compounds are in clinical trial as inhibitors of angiogenesis, and new compounds are being frequently added. The target cell of most angiogenesis inhibitors is the endothelial cell, with inhibitors that selectively affect a number of endothelial cell functions acquired during angiogenesis, including activation, proliferation, migration, invasion and survival. The endothelial cell may also be targeted by chemotherapeutic agents currently in use. The high doses and intermittent treatment schedules used to fight resistant tumor cells may be altered towards lower doses and chronic administration to obtain selective inhibition of angiogenic factor-stimulated endothelial cells as adjuvant therapy. Finally, gene therapy is a promising route for the delivery of novel protein inhibitors of angiogenesis, and is actively being investigated.

Angiogenesis Inducing Agents↗
PubMedDate not supplied

In vitro models of angiogenesis: the use of Matrigel.

Tumor-induced angiogenesis is a key event for neoplastic progression. In vitro assays are important for identification of potential angiogenic agents and rapid screening for pharmacological inhibitors. The increased interest in this field of study has generated several in vitro assays that recapitulate the steps of endothelial cell activation and differentiation. In this short report we emphasize the utility of Matrigel, a reconstituted basement membrane, to define two different steps in the angiogenic process: invasion in response to growth factors and organization of microvessels into a network with branching morphology on a Matrigel substrate.

Chemotaxis↗
PubMedDate not supplied

Generation of expression plasmids for angiostatin, endostatin and TIMP-2 for cancer gene therapy.

Antiangiogenic therapy may represent a promising approach to cancer treatment. Indeed, the efficacy of endogenous angiogenesis inhibitors, including angiostatin, endostatin and TIMPs, has been demonstrated in many types of solid tumors in animal models. In view of the possible problems associated with long-term administration of inhibitors as recombinant proteins, we propose their delivery as nucleic acids through a gene therapy approach. To this end, eukaryotic expression constructs for murine angiostatin and endostatin as well as human TIMP-2 were generated, and characterized in vitro. All constructs carry the relevant cDNAs under the control of the strong HCMV promoter/enhancer, and cleavable leader signals to allow protein secretion. Expression of the angiogenesis inhibitors was detected by in vitro transcription/translation experiments as well as transfection of 293T cells, followed by Western blotting (WB) or radioimmunoprecipitation analysis of both cell lysates and supernatants (SNs). These constructs might be used for in vivo intramuscular delivery of plasmid DNA and as a set of reagents for the development of retroviral as well as adeno-associated viral (AAV) vectors expressing angiogenesis inhibitors.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Inhibition of angiogenesis by type I interferons in models of Kaposi's sarcoma.

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFN alpha and IFN beta are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-1 Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.

Angiogenesis Inhibitors↗