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L Kopper

Publications and source records attributed to L Kopper.

At least 55 records · Page 3Linked to original sources

Pheno- and genotypic characteristics of human non-Hodgkin lymphoma xenografts.

The three human non-Hodgkin lymphoma xenografts with different morphological appearance (lymphoblastic, centroblastic, centrocytic) had many common pheno- and genotypic features positivity of B-cell markers, 14q+ chromosomal abnormality, etc.). Furthermore, two lines (HT 58 and 130) expressed lambda light chain monoclonally. The third line (HT 117) showed bigenotypic rearrangement of light genes. A set of new anti-proteoglycan markers, especially anti-chondroitin sulfate mAbs made possible to individualize the xenografts.

Animals↗

Glycosaminoglycans as novel target in antitumor therapy.

Considering the importance of intercellular contacts in the metastasis of malignant tumours drug action on glycosaminoglycan production as one of the underlying mechanisms in metastasis was investigated. 5-hexyl-2-deoxyuridine/HUdR/was shown to inhibit the conversion of glucosamine to UDP-sugars. Consequently various glycoconjugates were affected, especially the synthesis of heparan sulfate was reduced. It is noteworthy that HUdR inhibited the synthesis of glycosaminoglycans in tumour cells with high metastatic capacity. The biological consequence of the alterations in glycosaminoglycan production was studied on measuring HUdR action on cell surface markers, microinvasion and tumour metastasis in experimental systems. It was concluded that HUdR has remarkable antimetastatic activity which by all probability is due to the inhibition of heparane sulfate synthesis.

Animals↗

[Fibrolamellar liver carcinoma].

Four fibrolamellar liver carcinomas were surgically removed and were postoperatively examined. Three patients are alive roughly three years from surgery, and there are no signs of imminent recurrence, while the fourth case was diagnosed only two months back. The carcinomas had developed in non-cirrhotic livers which also produced negative responses to serological tests for hepatitis B. In flow cytometry, DNA indices were indicative of diploidy in two cases and aneuploidy in the other two. The highest DNA index value was recorded from the smallest tumour which could be assigned to the category of "minute HCC". No correlation was found to exist either between age, sex, and DNA index. Positive CEA reaction was immunohistochemically recorded from few tumour cells, whereas negative AFP responses were exhibited by all four tumours. Appearance of AAT in tumour cells was detected in three cases. High degree of differentiation, similarity between tumour and liver cells, and oncocytoid nature of cells were revealed by optical light and electron microscopy. This high degree of differentiation was additionally confirmed by two factors: glucose-6-phosphatase activity was preserved in all four tumours, adenosinetriphosphatase activity was histochemically detectable from certain points of the tumour cell membrane. Gamma-glutamyl-transpeptidase activity, too, was very strongly pronounced in all tumour cells, which, however, cannot be interpreted as a sign of differentiation. Membrane-bordered "dense-core" granules were visible in few tumour cells in two cases. Intensive granular serotonin reactions were immunohistochemically recorded from the majority of tumour cells in the same cases. Our histochemical and ultrastructural parameters have produced clear-cut evidence to the hepatocyte nature of FLC cells. Yet, the presence of secretory granules and positive serotonin reaction might possibly support the assumption that the FLC originates from those pluripotent cells of the liver which may develop in two directions, depending on the individual case, to become either hepatocytes or neurosecretory cells.

Adolescent↗

[Pathobiology of human primary benign and malignant liver tumors].

Authors elaborated 35 surgically removed tumors of liver by morphological and biochemical methods. From tumors 5 proved to be hepatocellular adenoma (HCA), 12 to focal nodular hyperplasia (FNH) and 18 to hepatocellular cancer (HCC). On the basis of enzyme histochemical and biochemical examinations, HCA is characterised by "normal" enzyme pattern. By the above method, FNH can be divided into two groups, characterized with "normal" and "abnormal" (tumor-like) enzyme change, while HCC proved to be very heterogeneous. Majority of HCA and FNH cases, according to data gained by flow cytometer, were of diploid DNA content. In majority of HCC cases, DNA diploid was aneuploid, but in three cases normal DNA content was observed. The above mentioned examination revealed several different characteristics of human hepatic tumors, compared to experimentally created tumors of liver.

DNA, Neoplasm↗

Deoxycytidine is salvaged not only into DNA but also into phospholipid precursors. II. Ara-C does not inhibit the later process in lymphoid cells.

dCTP formed from exogenous deoxycytidine via the salvage pathways was previously shown to serve deoxyliponucleotide synthesis in lymphocytes (Spasokukotskaja et al, Biochem. Biophys. Res. Commun. (1988) 155, 923-929) and now in lymphoma cells. After treatment with 1-beta-D-arabino-furanosylcytosine (ara-C), much more araCTP as well as araCDP-choline was formed in lymphoma cells than in lymphocytes explaining the high sensitivity of lymphoma cells to this drug. Ara-C did not inhibit labeling of 5-3H-dCDP-choline from exogenous 5-3H-deoxycytidine while inhibiting DNA synthesis. Excess of exogenous ribocytidine diminished labeling of araCDP-choline, without any effect on dCDP-choline. These data suggest that araCDP-choline and dCDP-choline were synthesized from separate pools in these cells.

AraC Transcription Factor↗

Two human melanoma xenografts with different metastatic capacity and glycosaminoglycan pattern.

Two human melanoma xenografts were compared with respect to their in vivo growth and metastatic potentials as well as glycosaminoglycan patterns. The less differentiated HT 168 tumor showed faster growth at primary sites and a more pronounced capacity for metastasis into the liver. Although chondroitin sulfate was the dominant glycosaminoglycan subtype in both tumors, the more invasive xenograft had a higher heparan sulfate/chondroitin sulfate (HS/CS) ratio. We suggest that tumor progression is influenced by this ratio in this human melanoma system.

Animals↗

Evidence for a novel gene associated with low tumor metastatic potential.

We describe a gene, NM23, that is associated with the tumor metastatic process. NM23 RNA levels were highest in cells and tumors of relatively low metastatic potential in two experimental systems: (1) murine K-1735 melanoma cell lines, in which the gene was identified, and (2) N-nitroso-N-methylurea-induced rat mammary carcinomas. NM23 RNA levels did not correlate with cell sensitivity to host immunological responses and may, therefore, be associated with intrinsic aggressiveness. The predicted carboxy-terminal protein sequence encoded by the pNM23 cDNA clone is novel compared with Genebank animal, bacterial, and viral sequences.

Amino Acid Sequence↗

Phenotypic characteristics of three human non-Hodgkin lymphoma lines: flow cytometric analysis after long-term maintenance.

Three human non-Hodgkin lymphomas of B-cell origin have been maintained as xenografts in artificially immunosuppressed mice. The long-term maintenance (3-5 years) resulted in no significant change in the morphology, DNA-index or cell surface markers of the tumors. Immunophenotyping revealed many similarities in the morphologically distinct lines. Light chain (lambda) restriction appeared in two lines (HT 58 and 130), but in the third line (HT 117) the co-expression of both light chains indicated the origin from light chain 'uncommitted' B cells. HT 117 was also different, expressing high transferrin-receptor activity, although it proliferates with practically the same rate as the other two lines. This study confirms the value of the xenograft system to approaching many tumor-specific problems.

Animals↗

Chemotherapeutic response of squamous cell carcinoma xenografts (subcutaneous and subrenal capsule assay).

Chemotherapeutic response of two squamous cell carcinoma xenograft lines (established from the primary and metastatic lesion of a tongue carcinoma) was studied using SC and SRC assays (as well as immunocompetent and -suppressed recipients in the latter assay). The two assays provided similar ranking of drugs, in the sense that in each instances two of the three (cyclophosphamide, 5-fluorouracil, vinblastine) most active agents were identical. The host response in immunocompetent recipients supports the need for histology to prove the proper quality of the implanted tumor tissue in order to be used for drug evaluation.

Aged↗

Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments.

The antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9-13 amino acid residues of alpha-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.

Animals↗

Chemotherapy of human non-Hodgkin lymphoma (NHL) xenografts.

Three human NHL (B-cell type) were established successfully as serially transplantable xenografts in artificially immunesuppressed CBA mice. All of them preserved the phenotypic characteristics of the original tumour even after several passages. The transplanted tumours were highly sensitive to cyclophosphamide and methotrexate, reflecting the results obtained in clinical practice, and relatively sensitive to dianhydrogalactitol.

Animals↗

Flow cytometric measurements and electron microscopy of cell surface glycosaminoglycans using acridine orange.

Cell surface glycosaminoglycans (GAGs) were measured, after various treatments, by their binding to Acridine Orange using flow cytometry. Using a critical electrolyte concentration and combining it with specific degradation of individual GAG elements, it was found possible to differentiate between GAG components. The technique was adapted for electron microscopy level to reveal characteristics of membrane-associated GAG. By this means, the cell membrane of the human leukaemic cell line K562 was shown to contain a large amount of GAG; 75% of it was highly sulphated GAG, mostly heparan sulphate. This component was evenly distributed in the outer plasma membrane layer. In the presence of other GAGs, the appearance of complex proteoglycan granules was detected.

Acridine Orange↗

What's new in macrophage-tumor cell interaction?

Macrophages--alone or interacting with other host defense elements--can modify the tumor growth, which usually means a process ending with tumor-cell killing, but in some instances may promote tumor progression. The knowledge on the actual capacity of host extra- and/or intratumoral macrophages to be activated by different kinds of biological modifiers or other effector cells, is necessary in order to design effective immun-manipulation in cancer patients. Progression of malignant tumors can be considered as the outcome of innumerable interactions between tumor cells and host cells with a clear indication on the failure of host defense. Host defense against tumors represents a complex series of interrelated specific and non-specific reactions of different cell types including macrophages. There is little doubt that macrophages--at least in vitro--can effectively destroy tumor cells by cytolytic mechanism, although in few instances their supportive effect on tumor growth is also documented. All of these events require the activation of macrophages.

Animals↗

Characteristics and chemotherapeutic sensitivity of a human testicular cancer grown in artificially immunosuppressed mice.

Seven human testicular tumors were transplanted into artificially immunosuppressed mice. Two of them grew progressively (TT2 and TT6) and a serially transplantable line was developed from TT2. The xenografts maintained only the embryonal carcinoma components of originally mixed (embryonal cell carcinoma and choriocarcinoma) donor tumor. Although the histology did not change remarkably with passages, the xenografts lost their capacity to express human choriogonadotropin and alpha-fetoprotein. The latency period shortened, the growth rate remained similar with subsequent transplantations. The tumor cells of the TT2 line presented the human character according to chromosome analysis and were built up of two subsets of cells with a different DNA index estimated by flow cytometry. The embryonal cell carcinoma line was highly sensitive to CY and cisDDP. PVB combination was also effective, although the tumor growth inhibition proved to be only temporary.

Adult↗

Comparative study on Lewis lung tumor lines with 'low' and 'high' metastatic capacity. I. Growth rate, morphology and resistance to host defence.

A highly metastatic variant (LLT-HH) of liver metastasizing Lewis lung tumor (LLT) has been selected. Comparative studies were made on proliferation rate, morphological characteristics and host cell interaction of these two lines. Increased metastasis formation seemed to result from the selection of cells with increased resistance to nonspecific host effector cells.

Animals↗

Renal cell carcinoma--xenotransplantation into immuno-suppressed mice.

21 human renal cell carcinomas (RCC) were xenotransplanted into artificially immunosuppressed mice. 4 tumors grew successfully retaining some characteristics of the primary tumors (according to morphology and karyotype analysis), but losing metastatic capacity. One of the serially transplantable tumors (HT 40) with hyperdiploid cellular DNA content and estrogen receptor positivity failed to respond to the single maximally tolerated dose of several cytotoxic agents.

Adenocarcinoma↗