PubMed Health⌕ Search

Biomedical subjects

S Szala

Publications and source records attributed to S Szala.

At least 19 recordsLinked to original sources
PubMed2004

Inhibitors of angiogenesis in therapy of ovarian cancers.

The capacity to induce growth of blood vessels represents one of the phenotypic traits of neoplastic cells. Several preclinical studies prove that the inhibition of growth of peri-neoplastic blood vesssels leads to restricted growth of primary tumours and of metastases. Nevertheless, clinical studies indicate that angiogenesis inhibitors are not such effective drugs as might be expected on the basis of studies conducted on animals. In this article we would like to draw the readers' attention to divergencies between preclinical and clinical results, in particular to those related to ovarian cancers. In the treatment of ovarian cancers, angiogenesis inhibitors combined with other drugs may prove to represent a relatively effective therapeutic approach.

Angiogenesis Inhibitors↗
PubMed2001

Intra-tumoral administration of naked plasmid DNA encoding mouse endostatin inhibits renal carcinoma growth.

Endostatin is a C-terminal fragment of collagen XVIII and has potent anti-angiogenic and anti-tumor activity. Mouse endostatin-coding sequences were obtained using PCR and linked to the signal sequence of influenzavirus hemagglutinin. The signal-sequence endostatin fragment was subcloned into plasmid vectors under the transcriptional control of cytomegalovirus promoter. Murine renal carcinoma (Renca) cells transfected with endostatin-coding plasmid are shown to secrete full-length endostatin. Endostatin-secreting Renca cells demonstrate slower growth in vivo compared to empty vector-transfected cells, but their in vitro growth is unaffected. Anti-angiogenic activity of secreted endostatin was confirmed in a Matrigel angiogenesis assay in vivo. We report growth inhibition of Renca tumors resulting from intra-tumoral delivery of plasmid vector encoding secretable endostatin. Elevated local concentrations of endostatin resulted from multiple intra-tumoral injections of endotoxin-purified plasmid DNA. Local endostatin levels were high enough to obtain growth arrest of Renca tumors.

Animals↗
PubMed2001

Direct in vivo transfer of plasmid DNA into murine tumors: effects of endotoxin presence and transgene localization.

The purpose of this study was to investigate the effect of endotoxin presence in plasmid DNA preparations on the efficiency of transfection achieved in vivo with B16(F10) and Renca tumors and to determine transgene localization. Our data show that endotoxin markedly decreases the efficiency of transfection. Furthermore, the transgene transferred in vivo can be found in both neoplastic and normal (most likely myofibroblast) cells lying in proximity of the administration site.

Animals↗
PubMed2001

Combined delivery of an antiangiogenic protein (angiostatin) and an immunomodulatory gene (interleukin-12) in the treatment of murine cancer.

We investigated the feasibility of a novel therapeutic approach to treat neoplastic diseases in mice. This novel strategy consists in delivering a protein (angiostatin) with strong antiangiogenic properties, followed by administration of the interleukin 12 gene that is strongly immunomodulatory and has also some antiangiogenic effects. When angiostatin-mediated antiangiogenic therapy was used in combination with intratumor delivery of the IL-12 gene (a strategy much safer than IL-12 protein administration), this produced a synergistic therapeutic effect.

Angiogenesis Inhibitors↗
PubMed2000

A new cholesterol derivative suitable for transfecting certain type of cells in the presence of 10% serum.

We developed a new cationic lipid suitable for use as a DNA carrier in the presence of 10% sera. The novel compound (abbreviated as Arg-Chol) contains cholesterol and a dipeptide consisting of glycine and sterically protected arginine. The efficiency of reporter gene transfection using liposomes based on this new reagent was compared with that of liposomes made with other cationic derivatives of cholesterol. Lipoplexes formulated with the newly synthesized lipid mediate in vitro transfection of B16(F10) murine melanoma cells in the presence of 10% sera more efficiently than in other cell lines and compared with other cholesterol derivatives studied.

Animals↗
PubMed2000

Direct transfer of IL-12 gene into growing Renca tumors.

We investigated the feasibility of transferring naked plasmid DNA containing a therapeutic gene (IL-12) into mice harboring growing Renca tumors. We found that naked DNA transferred into growing Renca and B16(F10) tumors gives higher expression level of reporter gene than complexes of DNA with DDAB/DOPE or DC-Chol/DOPE. Transfer of naked DNA carrying the IL-12 gene into growing Renca tumors causes a distinct therapeutic effect that depends on the time span between inoculation of mice with cancer cells and the beginning of the therapy. Therapy started on day 3 resulted in total cure (100%) of mice.

Animals↗
PubMed1998

Combined therapy of B16(F10) murine melanoma using E. coli cytosine deaminase gene and murine interleukin-4 gene.

This paper summarizes preliminary results of combining suicide gene strategy (E. coli cytosine deaminase gene--CD) with immunotherapy (murine interleukin-4 gene) for treatment of experimental B16(F10) melanomas implanted into C57Bl/6 mice. The best therapeutic results, inhibition of tumor growth and prolonged survival time of treated vs. control mice, were obtained when plasmid expression vectors containing therapeutic genes were transferred into mice via DDAB/DOPE cationic liposome carrier on the third or fourth day following inoculation of mice with cancer cells. Extension of survival time has been noted in the case of two-gene therapy (as compared with one-gene therapy) of tumors which originated from cells transfected in vitro with CD gene and which were subsequently injected in vivo with IL-4-secreting cells. However, no improvement of therapeutic effect was obtained in case of mice treated with a combination of two genes transferred intratumorally with DDAB/DOPE cationic liposomes as compared to mice treated with a single gene only.

Animals↗
PubMed1996

On the strategy of using nonviral carriers in cancer gene therapy.

Effectiveness and mode of therapeutic gene delivery in vivo as well as biological safety of such transfer must be improved before widespread application of gene therapy in the clinic becomes possible. Most research has so far focused on recombinant viral delivery systems. Clinical future seems to belong, however, to nonviral delivery systems. Such systems feature DNA complexed to lipid, protein, peptide or polymeric carriers with ligands allowing in vivo tissue targeting by the complex and nuclear translocation of the exogene. Nonviral gene carrier systems are discussed together with strategies of destroying cancer cells.

Genetic Therapy↗
PubMed1996

The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors.

An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cytosine deaminase 'suicide' gene under the control of tissue-specific tyrosinase gene promoter directly into the murine melanoma B16(F10) tumor. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine melanoma B16(F10) tumor growth and, in some cases, rejection of the pre-established tumor. The inhibition of tumor growth expressed as the increased survival of mice is better seen in the case of using DNA-DDAB/DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5-fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), increased transfection efficiency of surviving cancer cells (in this case DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.

Animals↗
PubMed1995

Introduction of murine Il-4 gene into B16(F10) melanoma tumors by direct gene transfer with DNA-liposome complexes.

Il-4 is a highly pleiotropic cytokine which induces cytotoxic activity when present at the tumor site. Death of tumor cells probably depends on the appearance of an inflammatory infiltrate composed of eosinophils and macrophages. Regression of established tumor masses has been readily observed upon direct intratumor implantation of cells which constitutively produce high amounts of Il-4. We now report a similar potent anti-tumor effect achieved via direct gene transfer, i.e. by injecting Il-4 DNA complexed with cationic liposomes into B16(F10) melanoma tumor in vivo.

Animals↗
PubMed1990

Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens.

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.

Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins. Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system. A 1.4-kilobase cDNA species was enriched by immunoselection with monoclonal antibody. The authenticity of individual clones was established by immunologic and sequence criteria. At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4. The amino acid sequence derived from the previously described GA733-related gene, GA733-1, was found to be 49% identical to GA733-2. The positions of 12 cysteine residues in the extracellular domains of the two GA733 antigens are conserved, as is the overall distribution of hydrophobic and hydrophilic residues. A 1.45-kilobase transcript of the GA733-2/KSA gene was found to be expressed in cell lines derived from colorectal and pancreatic carcinoma.

Amino Acid Sequence↗
PubMed1988

Structural changes in DNA of human breast carcinoma.

Rearrangement and loss of genetic material in DNA of human ductal breast carcinoma was analyzed by restriction enzyme digestion, agarose gel electrophoresis and Southern blot hybridization using 32P labeled c-Ha-ras-1 and multilocus, minisatellite 15.1.11.4 as a probe. In several cases an allelic loss of c-Ha-ras-1 locus in heterozygous patients were noticed. Rearrangement of the genetic material in neoplastic tissues was also observed after hybridization with a minisatellite probe. These results provide evidence that loss and redistribution of the genetic material does occur in human ductal breast carcinoma.

Blotting, Southern↗
PubMed1985

Mutagenic activity of radiosensitizers.

Seven radiosensitizers, six derivatives of nitroimidazole (coded P1 to P5 and one imidazole derivative--P6 were investigated for mutagenicity using 3 short-term tests: Ames test, prophage lambda induction and tryptophan reversion test. Out of seven investigated compounds five were not mutagenic. Only P1 derivative induces base pair substitutions. Another derivative of nitroimidazole: metronidazole induces base pair substitution and frameshift mutations. Its positive response in the prophage lambda induction test suggests that metronidazole provokes also epigenetic changes.

Animals↗