Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Host mice bearing pulmonary metastases of B16 melanoma were treated by adoptive immunotherapy with allogeneic donor lymphocytes. Rejection of the allogeneic donor cells by the host was delayed by pretreatment immunosuppression of the host with cyclophosphamide and selection of donors that were matched at the major histocompatibility complex (MHC) but disparate for background minor histocompatibility genes. Adoptively transferred normal nonimmune donor cells exhibited no therapeutic activity. However, allogeneic MHC-matched donor cells that were primed in vivo and secondarily sensitized in vitro to host minor histocompatibility antigens expressed on normal lymphocytes were cytotoxic to B16 tumor cells in vitro and mediated a dose-dependent antitumor effect in vivo following i.v. infusion. The therapeutic activity of sensitized allogeneic cells, which presumably reflected recognition of minor histocompatibility antigens expressed both on normal host tissues and on malignant B16 tumor cells, was not associated with any detectable toxicity to these transiently immunosuppressed tumor-bearing hosts.
 ...
PMID:Adoptive immunotherapy of metastatic B16 melanoma with allogeneic immune cells sensitized to minor histocompatibility antigens. 396 13

Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.
 ...
PMID:Tolerance and autoimmunity to erythroid differentiation (B-G) major histocompatibility complex alloantigens of the chicken. 612 77

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.
 ...
PMID:Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. 620 49

Metastases of ESb lymphoma cells in syngeneic DBA/2 animals frequently are selectively immunoresistant to lysis by syngeneic cytotoxic T-lymphocytes (CTL). This immunoresistance of tumor cells to CTL lysis could be due to a defect in either of two structures: (a) tumor-associated transplantation antigens; or (b) mouse major histocompatibility complex (H-2) antigens serving as restricting elements. In this study, we have analyzed the possible involvement of major histocompatibility complex Class I antigens in the immunoresistance of ESb tumor variant cells. Syngeneic anti-ESb CTL appeared to be H-2Kd restricted since only antibodies to Kd but not D,Ld molecules could inhibit CTL lysis. Comparison of H-2 antigens expressed on immunosensitive and resistant ESb sublines by immunofluorescence and flow cytofluorography, alloreactive CTL, two-dimensional gel analysis did not reveal any differences either qualitatively or quantitatively. Southern blotting of tumor-derived DNA with H-2-specific probes did not reveal differences either. Serologically detectable cell surface differentiation antigens were expressed very similarly on immunosensitive and resistant tumor lines, and only minor differences were noted by biochemical analysis of plasma membrane proteins. C-Type viral Mr 70,000 glycoprotein antigens were also similar in both types of cells. We conclude that cell surface changes on immunoresistant ESb variant cells are very selective and involve only CTL-defined tumor-associated transplantation antigen determinants.
 ...
PMID:Resistance of metastatic tumor variants to tumor-specific cytotoxic T-lymphocytes not due to defects in expression of restricting major histocompatibility complex molecules in murine cells. 633 73

Grafts of the metastatic 3LL Lewis lung carcinoma result in pulmonary metastases in mouse strains which share with the tumor strain of origin (C57BL/6, H-2b) the non-H-2 background genes and the H-2D/H-2L region of the major histocompatibility complex. Lung metastases across H-2K region disparities correlated with low expression of H-2Kb-encoded molecule on the tumor cell surface. We tested whether the 3LL tumor cells lack H-2Kb private and/or public specificities by staining 3LL tumor cells and spleen cells of different recombinant mouse strains with H-2d anti-H-2b and anti-3LL antisera, respectively, following absorption of the antisera on spleen cells from various recombinant mouse strains. The data demonstrated weak expression of H-2Kb public specificities (which could represent H-2Db/H-2Kb biregional encoded molecules) and a complete lack of expression of the H-2.33 H-2Kb private specificity by 3LL tumor cells. The findings provide a possible explanation for the 3LL metastatic potential across H-2Kb region disparities.
 ...
PMID:Loss of the H-2.33 private specificity by 3LL tumor cells correlates with the tumor potential to metastasize across the H-2K region genetic barriers. 640 Oct 4

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.
 ...
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

Intrafootpad inoculation of syngeneic mice with Lewis lung carcinoma (3LL) cells led to the growth of a solid tumor at the site of transplantation, followed by development of metastases in the lungs. Surgical excision of the primary tumor resulted in an accelerated growth and increased incidence of pulmonary metastases. Inasmuch as 3LL tumor cells isolated from the local tumor differed antigenically from the cells isolated from the metastases, the genetic control of the local 3LL tumor growth and that of its lung metastases were tested. The local tumor grew in allogeneic mice, yet its growth rate was higher in syngeneic and semiallogeneic F1 hybrids than in allogeneic recipients. However, lung metastases did not appear in allogeneic animals. By analysis of the rate of growth of the local tumor in congenic mouse strains, the tumor progression appeared to be linked to the host's genetic background rather than to the H-2 region. The generation of lung metastases required compatibility at both background and H-2 haplotype. Tests of the development of metastases in mice of congenic resistant recombinant strains revealed that metastases developed only in animals that shared with the tumor the gene products of the D-end of the major histocompatibility complex. Thus metastasis formation was controlled by both a non-H-2 gene(s) and a gene(s) linked to the H-2D region or another nearby region to the right of H-2D.
 ...
PMID:Control of progression of local tumor and pulmonary metastasis of the 3LL Lewis lung carcinoma by different histocompatibility requirements in mice. 693 34

The ability of two highly metastatic tumor lines of DBA/2 (H-2d) origin to metastasize in various allogeneic normal or nude (nu/nu) mouse strains was investigated. Normal mice differing from DBA/2 at either the major histocompatibility complex or at minor histocompatibility loci were both able to reject rather high subcutaneous inocula of these tumor cells. F1 hybrids between susceptible and resistant strains could not reject the metastatic tumors. This suggests that tumor rejection was dependent on the recognition of allogeneic histocompatibility antigens. Two mouse strains appeared to be selectively resistant to the establishment of tumor metastases but could not prevent the progressive tumor growth at a local site. One was a new variant subline of DBA/2, provisionally designated as DBA/2/HD, the other was C57B1/6 (nu/nu), an athymic 'nude' mouse of C57B1/6 background. 'Nude' mice of BALB/c or C3H background were more or less susceptible to these tumors and their metastases. These studies demonstrate that the establishment of tumor metastasis is greatly influenced by genetic factors of the host. Resistance to local tumor growth seemed to require the presence of mature T lymphocytes while resistance to metastasis formation could be established in T-cell-deficient nude mice of certain genetic backgrounds.
Invasion Metastasis 1981
PMID:Immunogenetic studies on the resistance of mice to highly metastatic DBA/2 tumor cell variants. I. Effect of incompatibilities at H-2 or non-H-2 genes in normal and nude (nu/nu) mice. 718 81

Many neoplasms seem to be heterogeneous in nature, producing metastases by pre-existing variant cells with inherent biochemical and biological properties. The survival and proliferation of metastatic cells depend on various biological properties, such as enzymes which degrade basement membranes, resistance to various host defence systems, association with host cellular components, adhesiveness and expression of certain membrane glycoproteins. Recent studies have indicated that metastatic cells may differ from the local tumour cells in the expression of immune recognizable membrane-associated antigens. Such antigenic differences may result from an immunoselection of cells with distinct antigenic properties due to a specific immune response evoked against the local tumour. In view of the role of the major histocompatibility complex (MHC) system in controlling and restricting the function of immune effector cells against modified self-components, one could assume that the modulation of the expression of MHC-encoded antigens on the membrane of tumour cells influenced the interclonal relationship within a local heterogeneous tumour cell population and the subsequent generation of metastasis. The modulation of the expression of H-2 antigens on several murine tumours is well documented; however, practically no attempts were made to relate H-2 modulation with invasiveness. We now describe principal differences in the expression of H-2 parental haplotypes between a local F1 methylcholanthrene-induced tumour and its descendant pulmonary metastases. These results suggest that both the expression and the immunogenicity of MHC products strongly influence the immune relationship between the tumour and the host's immune system, thus determining the generation and dissemination of metastases.
 ...
PMID:Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties. 743 18

The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.
 ...
PMID:Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene. 786 36


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