Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetics of late appearing MSV tumors showing a progressive growth pattern in AKR mice was investigated. The late MSV tumor response in F1 hybrids depended on the genetic background of the non-AKR parent. Within the 4-month observation period following virus injection, (CBA X AKR) F1, (DBA/2 X AKR)F1, and (NIH X AKR)F1 developed progressing MSV tumors, which exhibited latency and growth behavior comparable to that seen in AKR mice, (BALB X AKR)F1, (B6 X AKR)F1, and (B10br x akr)f1 mice did not show any late MSV tumors. In contrast to early regressing M-MSV tumors, whose development is independent of Fv-1 genotype, late MSV tumor progression is largely a function of this gene, since all late tumors which appeared in (B10BR x AKR) x AKR were observed in Fv-1n homozygous mice, H-2k halotype is a further factor in the occurrence of late MSV tumors, at least in (B6 x AKR) x AKR mice. In crosses of AKR with Fv-1 compatible mice, tumor appearance was strongly associated with inheritance of AKR-Mulv, and MSV recovered from late tumors of first back-cross animals appeared to be a new pseudotype with the endogenous AKR-MuLV. It is suggested that the host genetic control in both early and late MSV tumors is exerted mainly on the helper component of the leukemia-sarcoma complex.
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PMID:Genetics of murine sarcoma virus (MSV)--induced tumors in AKR mice: Evidence that late progressing and early regressing tumors are controlled by different gents. 6 12

The levels of expression of histocompatibility antigens on the cell membrane and their gene expression in non-metastatic and in highly metastatic Friend leukemia cells (FLC) were measured and the levels of expression of these antigens were correlated with the different in vivo behaviour of the tumor cells. Highly metastatic in vivo passaged FLC (either interferon-sensitive 745 or interferon alpha/beta-resistant 3Cl-8 cells) expressed higher levels of class I H-2K and H-2D antigens on their cell membrane with respect to the non-metastatic in vitro passaged counterparts. The increased expression of H-2 class I antigens was associated with an increased transcription of H-2K and H-2D genes. As both in vitro and in vivo passaged FLC have been shown to be resistant in vitro to the natural killer (NK) cell activity, we tried to correlate the levels of expression of histocompatibility antigens with the in vivo clearance of [125I]UDR-labeled FLC. However, no correlation was found between the levels of expression of H-2 antigens and the in vivo clearance of tumor cells. In fact, in vivo passaged FLC (tested either after 1 or after 15 in vitro passages) expressed virtually identical levels of H-2 antigens; however, the freshly explanted in vivo passaged FLC exhibited markedly lower levels of clearance from the lung, spleen and liver (when injected i.v. in DBA/2 mice) with respect to the corresponding FLC cultivated for several passages in vitro. Pretreatment of in vitro passaged 745 FLC with either interferon alpha/beta or interferon gamma resulted in the acquisition of some metastatic potential of FLC to the liver when interferon-treated FLC were subsequently injected i.v. in DBA/2 mice; such in vitro treatments resulted in a 2-3-fold increase in the expression of H-2K antigens versus the control untreated FLC. We suggest that such increases could represent some advantages for the homing properties of tumor cells and/or for the tumor progression, by mechanisms different from the resistance to the NK cells.
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PMID:Studies on the expression of H-2 antigens in non-metastatic and highly metastatic Friend erythroleukemia cells: correlation with the in vivo behaviour of tumor cells. 247 72

To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.
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PMID:Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes. 310 13

Viable BCG bacilli, in a lipid emulsion, inoculated intravenously, were capable of reverting the profound humoral immunosuppression induced in adult DBA/2 mice by the mastocytoma P-815. BCG increased not only the number of hemolytic plaque forming cells, but also the serum titers of hemagglutinating IgM antibodies. However, no blocking effect was detected on normal tumor progression.
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PMID:[Influence of BCG in the control of humoral deficiency induced by mastocytoma p-815]. 310 17

Cloned lines of the methylcholanthrene-induced DBA/2 T lymphoma Eb and its highly metastatic variant line ESb were analyzed for differences in the expression of serologically detectable cell surface differentiation markers. Flow cytofluorographic analysis of cells stained with fluorescein isothiocyanate-conjugated monoclonal rate anti-mouse Thy-1, Lyt-1, Lyt-2 and complement-dependent cytotoxicity with mouse alloantisera against Lyt-3.2 and Ly-6.2 revealed, for the parental low metastasizing line, Eb, a phenotype of Thy-1+, Lyt-1-, Lyt-2+, Lyt-3+, Ly-6+, whereas the highly metastasizing variant line typed as Thy-1-, Lyt-1+, Lyt-2-, Lyt-3-, Ly-6-. Analysis of galactose oxidase/NaB3H4-labeled glycoproteins from Eb and ESb clones by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate showed further phenotypic differences. Selective binding of radiolabeled glycoproteins to Helix pomatia or Vicia villosa-Sepharose, respectively, allowed the identification of T130 to be expressed on Eb cells and T145 to be expressed on some ESb clones. The latter antigen is expressed on murine cytotoxic T lymphocytes. Immune precipitation analysis revealed that Eb and ESb bear different molecular forms of the T200 antigen. Comparisons of iodinated surface proteins derived from tumor cells either treated or untreated with tunicamycin indicated that many of the differences in membrane proteins between Eb and ESb cells could be attributed to differences in glycosylation. Our results, derived from a defined tumor system of lymphoid origin, show that the progression from a low to a high malignant tumor line can be associated with changes in the expression of various defined cell surface differentiation antigens. The question of a possible relationship between tumor progression and cell differentiation or dedifferentiation is discussed.
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PMID:Different expression of Lyt differentiation antigens and cell surface glycoproteins by a murine T lymphoma line and its highly metastatic variant. 612 26

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.
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PMID:Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents. 658 1

Previous studies demonstrated that growth in DBA/2 mice of MDW4, a wheat germ agglutinin-resistant (WGAr) mutant of the highly metastatic MDAY-D2 DBA/2 mouse tumor, led to the emergence of WGA-sensitive (WGAs) revertants having higher ploidy levels at the site of inoculation as well as at distant visceral metastases. The results implied that MDW4 was nonmetastatic but progressed to become metastatic in vivo only after a cellular change took place which was accompanied by extinction of the WGAr phenotype and acquisition of a higher number of chromosomes. Results presented here provide strong and direct evidence for the underlying mechanism being spontaneous cell fusion in vivo between the MDW4 (WGAr) tumor cells and normal host cells, at least some of which are of bone marrow origin. Thus, growth of the H-2d MDW4 tumor cells in (C3H X DBA/2)F1 (H-2k X H-2d) or (C57BL/6 X DBA/2)F1 (H-2b X H-2d) mice led to the appearance of WGAs revertants bearing the H-2k or H-2b major histocompatibility complex antigens associated with the C3H or C57BL/6 parental strains, respectively. Similarly, WGAs revertants of MDW4 were found to express H-2k antigens after growth in CBA/HT6T6 (H-2k) leads to DBA/2 bone marrow radiation chimeras. Attempts to mimic the in vivo hybridization process were successful in that in vitro somatic cell fusion between an ouabain-resistant (OuaR), 6-thioguanine-resistant (Thgr) derivative of the MDW4 mutant and either normal bone marrow or spleen cells resulted in loss of the WGAr phenotype in the hybrids (thus showing its recessive character) and increased malignant properties in vivo. An analysis of spontaneous frequencies of re-expression of various drug resistance genetic markers in several hybrid metastatic cells was also consistent with chromosome segregation of the sensitive alleles. The results show that tumor progression and the emergence of metastatic cell variants could arise as a consequence of tumor X host cell fusion followed by chromosome segregation. We also discuss the possibility that this type of event may normally be a very rare one during the growth of tumors, the frequency of which can be artificially amplified by the use of certain classes of lectin-resistant mutants carrying particular cell surface alterations.
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PMID:Spontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor. 668 20

The stability of a cloned murine tumor for sensitivity to NR was examined following growth in vivo in order to test the hypothesis that tumor progression proceeds through the generation and selection of variants. Clonal sensitivity to the [131I]-dUrd elimination assay of NR was assessed for the L5178Y-F9 tumor grown in syngeneic DBA/2 mice or maintained solely in tissue culture. Subclones derived from a tumor obtained from the injection site 3 1/2 weeks after the s.c. inoculation of 25 cells were less sensitive to NR in comparison with subclones derived from cells grown only in vitro. Subclones from the cells grown in vivo exhibited increased heterogeneity in sensitivity to NR in addition to their expanded range of susceptibility to complement-mediated lysis by CBA serum natural antibodies. The extent of the heterogeneity argues against tumor "adaptation" forming the basis for the phenotypic alteration while chromosomal studies eliminate the possibility that a new tumor was induced. These data support the hypothesis that tumor progression proceeds through the random generation of variants and host-mediated selection for the proliferation of clones with an increased ability to survive.
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PMID:In vivo generation and selection of variants with altered sensitivity to natural resistance (NR): a model of tumor progression. 683 50

The properties of an unusual mouse tumor capable of extremely rapid and widespread spontaneous metastatic growth were recently described; this tumor, called MDAY-D2, at first appeared to be an H-2Kk loss variant of an (A X DBA/2)F1 (H-2KkDd) sarcoma called MDAY and was obtained by serial ip passage of MDAY in DBA/2 (KdDd) mice. The studies described here were concerned with the analysis of the origin of MDAY-D2; i.e., was it a true variant or a newly induced DBA/2 tumor? Several approaches were used, most of which exploited defined cell surface alloantigenic systems as natural genetic markers. The results indicated that MDAY-D2 was indeed a newly induced DBA/2 tumor and, furthermore, that MDAY was a homozygous A-strain tumor, probably a T-cell lymphoma. Thus a) MDAY was found to be Ly-1.2+, Ly-2.2+, and Thy-1.2+, but Ly-6.2-, whereas the opposite pattern was observed with MDAY-D2; b) MDAY possessed the private and public H-2 specificities associated with H-2k and H-2Dd, but not H-2Dk [i.e., it typed as an A-strain (H-2a) tumor, not as (A X DBA/2)F1]; c) MDAY-D2 possessed private and public specificities associated with H-2Kd and H-2Dd and was found to be H-2Kk-negative [i.e., it typed as a DBA/2 (H-2d) tumor]; d) serial injection of clonally derived ouabain-resistant H-2Kk-positive MDAY cells into DBA/2 hosts led to the rapid development of an MDAY-D2 (H-2d-positive) tumor that was fully ouabain-sensitive. Several findings did not support a contaminant theory to explain induction of MDAY-D2. The rapid induction of a tumor after injection of allogeneic tumor cells may have importance in relation to oncogenesis, tumor variant formation, and tumor progression. The results showed that tumor cells themselves can be potent carcinogens.
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PMID:Carcinogenicity of tumor cell populations: origin of a putative H-2 isoantigenic loss variant tumor. 692 20

Related tumor lines which represent different stages in their progression towards metastatic capacity were investigated and compared at the chromosomal level. The parental low-metastatic tumor line (L5178Y/Eb) was derived from a long-term transplanted, chemically induced T-cell lymphoma of the DBA/2 mouse. The cytogenetic analysis included this Eb line, a spontaneous high metastatic variant thereof which expressed a distinct tumor-associated transplantation antigen (ESb TATA+), and an immunoresistant TATA-negative variant of the latter (ESb TATA-). All three cell lines were characterized by a near-diploid chromosome count and by some common chromosomal markers derived from Nos. 6, 13 and 16 Large-scale chromosomal rearrangments resulted in the formation of eight marker chromosomes in Eb cells, 16 in ESb TATA+ cells and 18 in ESb TATA- cells. Tumor progression in this system showed a tendency to monosomies, which could bring the corresponding genes to a hemizygous state and possibly to a release from repression. Chromosome 15 was trisomic in Eb cells, monosomic in ESb TATA+ cells and hardly detectable in ESb TATA- cells. The Ig heavy-chain gene-carrying region of both chromosomes No. 12 was found in translocation with chromosomes Nos. 5, 13 and 14 (Eb cells) and with Nos. 1 and 17 (ESb cells). ESb TATA- cells differed from ESb TATA+ cells at four different chromosomes (Nos. 5, 8, 14 and 15).
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PMID:Cytogenetic changes during tumor progression towards invasion, metastasis and immune escape in the Eb/ESb model system. 696 Nov 15


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