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Biomedical subjects

L Kopper

Publications and source records attributed to L Kopper.

101 records · Page 6Linked to original sources

Epitopes of cartilage core proteins and GAG pattern in human non-Hodgkin lymphoma xenografts.

Glycosaminoglycan and core protein components of proteoglycans (PGs) have been studied in three human non-Hodgkin lymphoma xenografts of B cell origin. Lymphomas showed similar GAG content, but different composition of GAG subtypes. This variability was accompanied by an individual capacity to adhere to extracellular matrix elements. The core proteins identified by monoclonal antibodies raised against human cartilage chondroitin sulfate PG were also distinctly expressed and released. These proteins shared by different cell types may have biological significance.

Aggrecans↗

New in vitro line from a human (B) non-Hodgkin lymphoma.

An in vitro cell line (HT 58) has been established from a human (B) NHL xenograft. The lymphoma cells in culture retained their lymphoblastic appearance, DNA-content, IgM/lambda monoclonality and many immunophenotypic markers. The clonal chromosomal abnormalities involved the chromosomes 1, 2, 3 and 14. The cells expressed and produced chondroitin sulfate proteoglycans identified with mAbs that were raised against human articular cartilage CSPG. The cells also released IgM into the medium as well as substances that stimulated the proliferation of activated normal peripheral B-cells.

Antibodies, Monoclonal↗

Lectin-binding pattern in human non-Hodgkin lymphoma xenografts.

The glycan profile of cell surface proteins has been studied on three human non-Hodgkin lymphoma xenografts of B-cell origin using a panel of biotinylated lectins. All three lines showed a more heterogeneous lectin-binding pattern than normal peripherial blood lymphocytes (PBLs) involving both the inner core and antenna part of the glycans. The conservative inner core (N-N-acetylchitobiose and oligomannose) was similar but fucosylated to various extents in the different lymphomas. The structure of the antennae of PBLs was characterized by glcNac-gal and galNac-gal-Sa sequences, while in lymphomas additional asialo as well as sialylated galNac containing antennae have been identified. This study suggests that NHLs sharing many immunophenotypic features show intertumoral differences in their lectin-binding pattern.

Animals↗

Effect of interferon-alpha (IFN alpha) on various human tumor xenografts.

The growth of some human tumor xenografts (3 out of 8, melanoma, non-Hodgkin's lymphoma, squamous cell carcinoma) was successfully--but moderately and temporarily--inhibited, when interferon-alpha (EGIS, Hungary) was given for 10 days. The route of administration (intratumoral or intraperitoneal) was usually not a decisive factor. An attempt to potentiate IFNa action with Zymozan or Cyclophosphamide did not succeed.

Animals↗

Transplantable human non-Hodgkin lymphoma line in artificially immunesuppressed mice.

Diffuse non-Hodgkin lymphoma of B-cell origin has been established as a serially transplantable xenograft line in artificially immunesuppressed mice. The take rate and growth rate increased with repeated passages compared to the first transplant generation. However the xenografted tumor preserved many of its characteristics, including morphology, cell surface markers and DNA index. Chromosome analysis proved the human origin of tumors grown in mice and revealed translocation 8,14. Cyclophosphamide, Methotrexate and Vincristine produced substantial inhibition of tumor growth, while Dianhydrogalactitol and Adriamycin were less effective. Human alpha interferon also produced a delay in tumor growth.

Animals↗

Antitumour action of 1,5-dihalogeno-, and 1, 2-4, 5-dianhydro-xylitol derivatives.

The antitumour action of some xylitol compounds possessing alkylating potency at 1 and 5 position of the sugar skeleton was investigated. Unlike the hexitol derivatives, bi-halogenated xylitols showed no antitumour action. The modest therapeutic index of 1, 2-4,5-dianhydroxylitol on the NK/Ly ascites tumour could be substantially increased by the addition of a phenyl-benzoyl group at the 3 position. This latter compound appeared to be active against L1210 leukaemia, S-180, and Yoshida solid sarcoma; and furthermore, against metastasis formation of the Lewis lung tumour.

Animals↗

DNA content of prostatic cancer measured by flow cytometry in patients undergoing radical prostatectomy.

The biological behavior of prostatic cancer is influenced by many host and tumor factors. The proliferative activity of the malignancies can be one of those parameters which serve as the basis to estimate prognosis and design treatment. Here, DNA content and S-phase fraction of prostatic cancer samples obtained by radical prostatectomy from 46 patients were related to other known tumor characteristics (PSA, staging, grading). Nuclei from the paraffin embedded materials were isolated with overnight trypsin-ribonuclease mixture digestion. DNA content and cell cycle distribution were determined by flow cytometry. A correlation was found between the PSA concentration, grading and staging on the one hand and S-phase fraction on the other. DNA content correlated with grading. No kinetic parameter correlated with the nodal involvement. Due to the association between abnormal DNA content plus SPF > 5% with advanced stage and less differentiated appearance of the tumor, we can conclude that these parameters are useful to estimate prognosis.

Aged↗

Antisense tumor therapy (a dream under construction).

Cancer, as a genetic disease, is a logical target for gene-oriented therapy--either by replacing the missing/nonfunctioning gene or by depressing the activity of an unwanted gene. The latter is really the inhibition of gene expression using oligonucleotide-based or "antisense" treatment. There are several strategies to achieve this: anti-gene or anti-code with triplex formation; ribozyme with endogenous catalytic RNase activity; antisense with oligonucleotides through steric inhibition or RNaseH activation; and sense strategy to inhibit or trap proteins by nucleic acids. There are two essential partners of the approach: targeted sequence in the unwanted gene/molecule and the complementary antisense oligo (-ribo- or -deoxyribonucleotide). The antisense sequences require chemical modifications (mostly on the phosphodiester backbone, less in the sugar or in the bases) to avoid nucleases, to form complexes for better delivery (in the organism and also in the cell). The activity of the unwanted target should be non-randomly associated with cancer (e.g. abl/ber). Both aspects of antisense treatment require further improvements to get longer lasting and real sequence-specific antitumor effect which could be competitive with the available therapeutic modalities.

DNA, Antisense↗

Loss of transforming growth factor beta 1 regulatory activity in human non Hodgkin lymphomas.

Since TGF beta 1 inhibits the proliferation of normal B-cells, its disturbed activity in B cell lymphomas is conceivable. We found high expression of TGF beta 1 mRNA in three human B cell non-Hodgkin lymphoma xenografts; also, the gene product (in latent form) was detectable in all lymphoma cells. However, on exposing the cells to exogenously activated TGF beta 1, the incorporation of tritiated thymidine decreased in normal (murine thymocytes, human peripheral mononuclear cells), but not in lymphoma cells. These observations suggest the malfunction of TGF beta 1 mediated regulatory pathway (e.g. insufficient activation or receptor expression) which can contribute to the unlimited expansion of a lymphoid clone. The opposite expression of c-myc to TGF beta and the retained sensitivity to anti-IgM indicate that c-myc and Ig receptor can operate independently of TGF beta in the regulation of lymphoid cell proliferation.

Animals↗

Modulation of apoptosis signaling in etoposide-treated lymphoma cells.

Signals of etoposide (ETO) induced apoptosis were studied in a human (B) lymphoma cell line, HT58. Morphology and DNA fragmentation assays proved the appearance of apoptosis after a short ETO treatment (4 hours). Modulation of signal components of this apoptotic pathway resulted the following a) phorbol ester (PMA) or heat shock inhibited apoptosis, which was prevented by staurosporine b) 3-amino-benzamide, a potent poly(ADP-ribose)polymerase inhibitor, had no significant effect; c) cysteine reactive compounds, such as iodoacetamide and phenylarsine oxide, as well as protease inhibitor TPCK were very active inhibitors of apoptosis; d) protein synthesis inhibitor, cycloheximide, potentiated cell death; e) the ETO-induced p53 protein overexpression had neither enhancing nor protecting effect on the apoptotic process. In conclusion, in the majority of HT58 lymphoma cells the apoptotic machinery is "primed" (the components are already expressed) and ETO-induced apoptosis is regulated by STA sensitive phosphorylation and proteolysis by cystein proteases, but not affected by ADP-ribozylation or p53.

Apoptosis↗

DNA content of parathyroid tumors.

BACKGROUND: The significance of DNA ploidy in indicating the benign or malignant character of parathyroid and other endocrin tumors is controversial. MATERIALS AND METHODS: DNA content of paraffin embedded parathyroid samples from 25 patients was measured with flow cytometry. RESULTS: The DNA index (DI) was 1.0 in all nonneoplastic samples as well as in 50% of adenomas (10/20) and in one carcinoma (1/2). The remaining 45% of the adenoma cases (9/20) and the other carcinoma showed doubled DNA content (DI = 1.9-2.0). The increased DI did not correlate with either clinical data (sex, age, tumor size, preoperative serum Ca++ or parathormone, primary or secondary hyperparathyroidism) or morphology. CONCLUSIONS: These results indicate that the DI has no value in deciding the benign or malignant character of a given sample. However, the prognostic value of tetraploidization (the potentially increased risk for malignancy) could not be ruled out.

Adenoma↗