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

We report the chromosomal localization of the cellular oncogene SKI, the putative oncogene of the Sloan-Kettering viruses (SKVs), a group of transforming retroviruses that had been isolated from chicken embryo cells infected with the avian leukosis virus tdB77. Southern blot analysis of DNA from mouse X human somatic cell hybrids with the v-SKI probe established synteny with chromosome 1, but excluding the region 1pter----q21. In situ hybridization of the same probe both to human spermatocyte pachytene and lymphocyte metaphase chromosomes enabled precise localization of the gene to the region 1q22----q24, a region that frequently is involved in translocations and other rearrangements in diverse human tumor types. In situ hybridization studies of metaphase spreads from a small noncleaved cell lymphoma that exhibited a t(1;14)(q21;q32) translocation showed that SKI translocates to the der(14) chromosome. Cytogenetic analysis of 65 prospectively ascertained non-Hodgkin's lymphomas revealed that the SKI region undergoes nonrandom breakage leading to translocations. Further analysis of the chromosome breaks in this group of lymphomas suggested that those involving the SKI site probably are of importance in tumor progression.
 ...
PMID:The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22----q24. 302 37

The therapeutic use of unmodified monoclonal anti-idiotypic antibody for human B cell malignancies has met with limited success. Some factors thwarting antibody attack can be identified, such as the presence of extracellular idiotypic immunoglobulin (Ig), and the escape of the target cell by antigenic modulation. Another possibility is a change in idiotypic determinants due to somatic mutation. For direct attack on tumor cells in vivo it might be necessary to use antibody derivatives: univalent antibodies will avoid modulation, and chimeric univalent antibodies consisting of mouse Fab' gamma linked to host Ig of appropriate subclass can be engineered to mediate particular effector functions while reducing immunogenicity. Another approach is to use toxin or isotope-bearing antibodies. However, the final eradication of tumor might involve the natural non-specific, and specific anti-idiotypic mechanisms of the host which should not be damaged by antibody therapy, and which appear to be involved in control of tumor progression in patients in long-term remission. Rapidly growing animal lymphomas presently available as models cannot mimic more than a small fraction of human lymphoma but they provide useful information for design of passive anti-idiotype therapy. However host anti-idiotypic immunity must be induced in such models by pre-immunization with purified idiotype. Such a procedure can generate effective anti-idiotypic immunity which is highly protective in mouse and guinea pig lymphomas. Analysis of mechanisms involved should give insight into the role of the idiotype networks in the behavior of human disease.
 ...
PMID:Therapeutic strategies for B cell malignancies involving idiotype-anti-idiotype interactions. 333 51

A case of diffuse large cell lymphoma with t(2p-;8q+) is reported. Immunologically the lymphoma cells were shown to be of B-cell origin and positive for surface gamma and kappa chains, B4, CALLA, and Ia1 markers. Karyotypically three major clones were detected: 47,XX, + 12,t(2;8)(p11-13;q24) (52%); 47,XX, + 12 (26%); and 46,XX,t(2;8)(p11-13;q24) (15%). A t(2p-;8q +) has been exclusively reported in cases of Burkitt's lymphoma or Burkitt-type acute lymphocytic leukemia. The present case is the first one with t(2p-;8q +) observed in non-Burkitt-type lymphoid malignancy of the B-cell lineage. The t(2p-;8q +) may play a primary role in the early stage of transformation of B cells, and trisomy 12 may provide them secondarily with an advantage for tumor progression. The phenotypic pictures provided by 8q24 rearrangements seem to be heterogeneous, as previously suggested.
 ...
PMID:A variant Burkitt-type translocation (2p-;8q+) in a patient with diffuse large cell lymphoma. 379 Nov 76

Loss of sensitivity to drugs following tumor progression constitutes the main reason for failure of treatment in advanced cancer. In view of the dynamic nature of neoplasms, models of tumor progression should be used for the testing of drugs. In the present study, two variants of malignancy of AKR lymphoma were used as a model of tumor progression to test various treatment modalities. The two variants, TAU-39 (of low-malignancy) and TAU-38 (of high-malignancy) differed in the pattern of local tumor growth as well as in the rate of metastatic spread and mice killing capacity. The efficiency of chemotherapy, immunotherapy and hyperthermia on the two variants was compared. The low-malignancy tumor was more sensitive to adriamycin than the high-malignancy one. Administration of levan-activated macrophages at the tumor site inhibited the growth of TAU-39. However, growth of the high-malignancy variant was stimulated by macrophages. Hyperthermic treatment was, in contrast to the other treatments, more effective against the high - than against the low-malignancy tumor. Models of tumor progression used in tests for antitumoral drugs may help in the discovery of treatment modalities effective also for advanced stages of cancer.
 ...
PMID:A model for cancer treatment in advanced compared to early cancer. 380 Mar 29

AKR lymphoma cells derived from primary s.c. tumors (PT) and cells from their metastases (MT) were inoculated into recipient mice in order to compare their malignant behavior. A higher malignant potential of MT compared to PT cells was found. The results support the hypothesis that metastasis is a process of selection of cells possessing a potential to metastasize, which preexist in the primary tumor. In the model used, both the selection of 'variants' of malignancy and the assay of malignancy were as close as possible to natural tumor progression.
 ...
PMID:Different biological behavior of AKR lymphoma cells from primary and metastatic tumors. 397 88

An examination of the variant generation and selection hypothesis of tumor progression was undertaken using the NK-sensitive, NAb-sensitive SL2-5 lymphoma in the threshold inoculum model of tumor progression. Tumor cells obtained from the i.p. injection site expressed increased heterogeneity for sensitivity to syngeneic NAb and to NR measured in the 131IUdR-labelled tumor elimination assay. Cells retrieved from the s.c. injection site exhibited reductions in sensitivity to NR which correlated with decreases in sensitivity to syngeneic NAb and NK cells in vitro. These data confirm and extend our previous observations with the NK-resistant L5178Y-F9 lymphoma and further substantiate the evidence for the participation of NAb and NK cells in host-mediated anti-tumor resistance. Characterization of the model revealed that the selection for reduced sensitivity to NR in thymus-depleted AT x BM mice and normal animals could not be distinguished, suggesting that thymus-independent mechanisms may be major contributors to the surveillance of nascent tumors. The decreases in susceptibility to NR occurred in a stepwise and time-dependent manner in accord with the sequential multistage concept of progression. Furthermore, the selection for tumor cells which exhibited reductions in sensitivity to NR correlated with selection for increased tumorigenicity, in keeping with the idea that progression is associated with development towards an increasingly autonomous tumor.
 ...
PMID:Characterization of tumor progression from threshold tumor inocula: evidence for natural resistance. 397 73

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.
 ...
PMID:Different expression of Lyt differentiation antigens and cell surface glycoproteins by a murine T lymphoma line and its highly metastatic variant. 612 26

Bursal lymphomas induced in chickens by avian leukosis viruses (ALVs) harbor proviral insertions that augment expression of an adjacent cellular oncogene, c-myc. To analyze such insertionally mutagenized c-myc genes in greater detail, we isolated molecular clones from two independent tumors. Precise proviral integration has occurred within the transcribed region of the c-myc gene in both mutant alleles. The proviruses bear different internal deletions that preclude the expression of the gag, pol, and env genes. The c-myc gene from bursal lymphoma LL4 contains a single copy of an ALV long terminal repeat (LTR), presumably the product of homologous recombination between LTRs at the ends of a normal provirus; the "solo" LTR is positioned in the correct orientation to act as a promoter for the c-myc gene. Bursal lymphoma LL3 contains an ALV provirus positioned upstream in the opposite transcriptional orientation to the coding exons of c-myc and deleted from a site within the leader region into the gag gene. In addition, the nucleotide sequence of the c-myc gene from tumor LL3 differs from the published sequence of the normal c-myc coding region at 3 positions of 180 determined. One of these changes, a silent nucleotide transition, is documented as a somatic mutation by restriction endonuclease mapping. It is flanked by two other candidate tumor-specific point mutations, one of which predicts an amino acid replacement, Pro----Thr at position 63. Thus, additional lesions that may affect the expression of viral genes and the quantity and nature of the putative c-myc gene product occur in provirally mutated c-myc alleles and may contribute to tumor progression.
 ...
PMID:Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to the progression of avian bursal tumors. 632 73

An ouabain- and thioguanine-resistant subline (TIKAUT) of spontaneous AKR lymphoma, TKA, was trisomic for chromosome 15 and contained a single 33 kb EcoRI fragment, containing the oncogene c-myc. The original TKA lymphoma and derived in vitro line contained the same 33 kb fragment, as well as a normal 22 kb fragment. It has been concluded that the original 15-trisomic TKA tumor has duplicated a 15-chromosome that contained the changed fragment, while maintaining the normal fragment as well. Subsequently, in the derived TIKAUT line, the changed chromosome duplicated again, giving rise to three copies, and the normal homologue was eliminated altogether. This confirms our earlier somatic hybrid study showing that the duplicated 15-chromosome of a T-cell leukemia confers an advantage on the cell that favors tumorigenicity, whereas the normal homologue exerts a counteracting influence. Therefore, in the course of tumor progression, the changed chromosome tends to be amplified, whereas its normal homologue tends to be eliminated.
 ...
PMID:Triplication of one chromosome No. 15 with an altered c-myc containing EcoRI fragment and elimination of the normal homologue in a T-cell lymphoma line of AKR origin (TIKAUT). 632 25

Intravenous inoculation of the AKR mouse-strain-derived BW lymphoma into CBA recipients resulted in a case of liver metastasis; cells derived from this metastatic nodule were termed BW-Li cells. BW-Li cells, upon reinoculation, generated metastases in the spleen, liver, kidney and ovaries in 100% of CBA recipients. Furthermore, BW-Li cells, in contrast to BW cells, were found to infiltrate in vitro monolayers of hepatocytes, thus confirming their inherent invasive potential. Analysis of the alloantigenic phenotype of BW-Li cells revealed that such cells were Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2- and H-2Dk+, as compared to BW cells which exhibited the membrane phenotype Thy 1.1+, Thy 1.2-, Lyt 1.2-, Lyt 1.1-, Lyt 2-, H-2Dk-. BW-Li cells also differed functionally from BW cells since these cells secreted IL-2 upon stimulation with Concanavalin A. BW tumor transplantation experiments were repeated in a semi-allogeneic F1 strain combination, i.e. (AKR X CBA)F1, and again a case of massive liver metastasis was observed. Cells derived from these liver metastases (termed BW-O-Li) manifested an invasive and metastatic potential similar to that of BW-Li cells. Furthermore, BW-O-Li cells secreted IL-2 upon stimulation with Con A and manifested the following alloantigenic phenotype: Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2-, H-2Dk+ and H-2Kk+. These results indicate that BW-Li and BW-O-Li cells are functional T-cell hybrids which express T-cell markers derived from BW cells and Thy 1.2+ CBA host cells. The acquisition of host-derived T-cell properties may have led to the expression of metastatic and invasive capabilities. From these results we conclude that the acquisition of metastatic properties following somatic cell fusion with normal lymphoreticular cells may represent a mechanism for tumor progression in vivo.
 ...
PMID:Generation of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells. 633 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>