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)

The adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with the systemic administration of recombinant interleukin 2 (RIL-2) results in the regression of established pulmonary and hepatic micrometastases from a variety of immunogenic and nonimmunogenic murine tumors in syngeneic C57BL/6 mice. Recent studies have shown that this therapeutic approach can mediate the regression of cancer in humans as well. Because of the practical difficulties in obtaining syngeneic or autologous LAK cells for the therapy of cancer in humans we have now evaluated the antitumor efficacy of allogeneic LAK cells generated from different strains of mice. The in vitro lysis of fresh tumor targets by LAK cells is not a major histocompatibility complex-restricted phenomenon since LAK cells of BALB/c-H-2d, DBA/2-H-2d, and C3H-H-2k origin all exhibited lytic activity when tested against allogeneic MCA-102-H-2b tumor cells in short term 51Cr release assays. In vivo, the i.v. transfer of allogeneic LAK cells combined with i.p. injections of RIL-2 reduced the number of established pulmonary metastases induced by either MCA-105 or MCA-101 tumors which are syngeneic to C57BL/6 hosts. The extent of reduction of these pulmonary metastases by the allogeneic LAK cells was directly dependent upon the dose of RIL-2 given; increasing doses of systemically administered RIL-2 resulted in increasingly greater reduction in the numbers of established 3-day pulmonary sarcoma metastases. In dose titration experiments, adoptive transfer of at least 2 doses of 10(8) allogeneic LAK cells was necessary to achieve significant antitumor effect in vivo. Allogeneic LAK cells were also successful in mediating significant regression of hepatic micrometastases. Again, the i.v. transfer of allogeneic LAK cells had a smaller therapeutic benefit compared to i.v. transfer of syngeneic LAK cells. When allogeneic LAK cells were injected intraportally, however, they were as effective as syngeneic LAK cells. Allogeneic LAK cells had little, if any, therapeutic effect on established pulmonary and hepatic metastases when administered to recipients previously immunized to the histocompatibility antigens on the donor cells. Taken together, our results indicate that allogeneic LAK cells from several strains of mice are effective in lysing fresh MCA-102 tumor in vitro and that when given i.v. in sufficient numbers, in conjunction with RIL-2, they can mediate significant reduction in the number of established pulmonary and hepatic micrometastases in nonalloimmunized C57BL/6 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effect of immunotherapy with allogeneic lymphokine-activated killer cells and recombinant interleukin 2 on established pulmonary and hepatic metastases in mice. 348 26

Seven metastasizing small renal cell carcinomas smaller than 30 mm in the greatest diameter were clinicopathologically studied for a better understanding of their characteristic features as compared to those of small tumors without metastases. Grayish-white infiltrating tumors in gross appearance and alveolar or solid microscopic structure consisting of granular or spindle cells and of atypical nuclei were suggestive of having metastases. Two tumors which had positive reactions to the lower nephron markers such as SBA, PNA, and/or DBA were considered to be of lower nephron origin and displayed poor prognosis.
 ...
PMID:Clinicopathological study on small renal cell carcinomas with metastases. 363 Jul 6

Highly resistant (C57BL/10) and intermediately resistant (DBA/2) mice were infected subcutaneously with Leishmania mexicana amazonensis in a hind footpad subsequent to removal of the draining popliteal node. These mice developed greatly exacerbated Leishmania infections as compared to sham-operated controls or to mice infected in the contralateral footpad. The majority of mice in which the draining lymph nodes were removed prior to infection developed metastases, lost their delayed hypersensitivity responses to Leishmania, and some died. Significantly fewer metastases and no deaths were observed in the control groups. The results emphasize the importance of lymphatic control of Leishmania m. amazonensis infection in relatively resistant mouse strains.
 ...
PMID:Leishmania mexicana amazonensis infections in 'resistant' inbred mice following removal of the draining lymph node. 373 29

We showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after the i.v. injection of syngeneic tumor cells in C57BL/6 mice. In this report, we analyzed the factors required for successful therapy. Titration analysis in vivo revealed an inverse relationship between the number of pulmonary metastases remaining after treatment and both the number of LAK cells and the amount of RIL 2 administered. Fresh or unstimulated splenocytes had no anti-tumor effect; a 2- to 3-day incubation of splenocytes in RIL 2 was required. LAK cells generated from allogeneic DBA (H-2d) splenocytes were as effective in vivo as syngeneic, C57BL/6 (H-2b) LAK cells. The anti-metastatic capacity of LAK cells was significantly reduced or eliminated when irradiated with 3000 rad before adoptive transfer. The combined therapy of LAK cells plus RIL 2 was shown to be highly effective in mice immunosuppressed by 500 rad total body irradiation and in treating macrometastases established in the lung 10 days after the i.v. injection of sarcoma cells. Further, reduction of both micrometastases and macrometastases could also be achieved by RIL 2 alone when administered at higher levels than were required with LAK cells. The value of LAK cell transfer and of IL 2 administration for the treatment of tumors established at other sites is currently under investigation.
 ...
PMID:The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. 388 58

The most important target in pharmaceutical therapy against cancer is complete suppression of metastases and recurrence after curative surgical operation. It is fundamentally, a growth inhibition and regression of small number of autochthonous tumors scattering in the host, and coexistence between tumor and host is also important. As immunosuppressive anticancer drugs have detrimental effects for patients in such cases, application of strong immunopotentiators such as lentinan should be expected. Lentinan showed a prominent effect on suppression of metastases in experimental systems of clinical models using MH-134 hepatoma, Madison-109 lung carcinoma and DBA/2.MC.CS-1 fibrosarcoma. Suppression of carcinogenesis may be considered as one of experimental methods to prevent metastases in a viewpoint of regression of small number of autochthonous tumor cells. Lentinan given at suitable timing and schedule showed marked prophylactic effect on chemical and viral carcinogenesis. Mode of action of lentinan as T-oriented adjuvant in its antitumor and metastases-inhibitory effects is also discussed. Considering excellent end-point results of Phase III with advanced and recurrent gastrointestinal cancer, lentinan is the most hopeful substance to prevent micrometastases.
 ...
PMID:[Experimental studies on growth inhibition and regression of cancer metastases]. 400 87

Peritoneal macrophages from normal DBA/2 mice were found to bind significantly more cells of a syngeneic low metastatic lymphoma line (Eb) than cells of a high metastatic variant (ESb) derived therefrom. These differences were observed in three different assays, at 4 degrees C and at 37 degrees C, and at various ratios of macrophages to tumor cells. Upon co-culture with normal macrophages, a tumor cytostatic effect was consistently observed with Eb but not with ESb tumor cells. Further experiments indicated that macrophages exerted their growth inhibitory effect via direct tumor cell contact. Pre-treatment of tumor cells with neuraminidase or pre-treatment of macrophages with lens culinaris lectin increased the numbers of macrophages binding Eb and ESb tumor cells. Addition of D-galactose or D-mannose at 50 mM concentration led to an increase of tumor cell binding and tumor cytostatic activity. Taken together, these results suggest (i) that carbohydrates play a role in tumor cell recognition by macrophages and (ii) that the differences observed between Eb and ESb tumor cells may be due to differences in the expression of carbohydrates. Pre-activation of the macrophages by lymphokine(s) led to a short increase in their tumor cell binding capacity. Lymphokine activation resulted in a strong but also short-lived increase of tumor cytostatic potential. This was effective against both the low and the high metastatic tumor line.
Clin Exp Metastasis
PMID:Interaction of high or low metastatic related tumor lines with normal or lymphokine-activated syngeneic peritoneal macrophages: in vitro analysis of tumor cell binding and cytostasis. 404 55

Administration of highly purified interferon to DBA/2 mice inhibited the growth of interferon-sensitive or interferon-resistant Friend erythroleukemia cells implanted subcutaneously. Injection of interferon at the site of tumor inoculation was more effective than injection of interferon intraperitoneally. Histologic examination of tumors in interferon-treated mice showed extensive areas of tumor-cell necrosis in the absence of an obvious host-cell infiltrate. Interferon inhibited the growth of established subcutaneous tumors and induced complete tumor regression in some mice. Interferon treatment also resulted in an inhibition of tumor metastases in the liver and spleen.
 ...
PMID:Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. III. Inhibition of growth and necrosis of tumors implanted subcutaneously. 618 90

The contribution of natural killer (NK) cells to natural antitumor resistance (NR) in syngeneic DBA/2 mice was examined. Subclones from two NK-resistant tumors, P815 and L5178Y, were selected for tumorigenicity in NR assays measuring the tumor frequency of threshold doses and the elimination of 131IUdR-labelled cells. In vivo variation in sensitivity to NR did not correlate with in vitro NK cytolysis for these clones, but did for a third pair of clones from the SL2 lymphoma selected on the basis of sensitivity or resistance to NK lysis. In another series of experiments it was found that a decrease in NK cytolysis of the (NK-sensitive) SL2-5 lymphoma in aged DBA/2 contrasted with an increased rate of elimination and lower tumor frequency, suggesting that the ontogeny of these phenomena was not related. In addition, while interferon treatment of the (NK-sensitive) SL2-5 produced a corresponding decrease in susceptibility to NK cytolysis in vitro and a reduction in the in vivo elimination of 131I-labelled cells, tumor of the NK-resistant phenotype, interferon-treated in the same way, remained NK-resistant and was more rapidly eliminated. The failure to observe correlative changes in NK cytolysis associated with heterogeneity in tumorigenicity and with age-related or interferon-induced changes in NR suggest that NR cannot be due solely to an NK effector mechanism.
Invasion Metastasis 1981
PMID:Natural resistance to tumors is a heterogeneous immunological phenomenon. Evidence for non-NK cell mechanisms. 620 63

Cloned interferon-sensitive (745) and interferon-resistant (3Cl-8) Friend erythroleukemia cells (FLC) passaged in vitro, are not very tumorigenic when first injected intraperitoneally (i.p.) into syngeneic DBA/2 mice although they do form solid tumors when injected subcutaneously (s.c.). By serially passaging FLC (either 745 or 3Cl-8 cells) i.p. in DBA/2 mice, we obtained two different FLC lines capable of growing i.p. and inducing tumor ascites. The s.c. injection of DBA/2 mice with these in vivo passaged FLC resulted in tumor metastases in the liver and spleen, whereas metastases were not observed in mice inoculated s.c. with in vitro passaged FLC. The capacity of in vivo passaged FLC to metastasize was acquired after several i.p. passages. This highly malignant behavior was a stable characteristic of these cells. All the clones derived from in vivo passaged FLC and passaged more than 14 times in vitro induced hemorrhagic ascites when injected i.p., and metastasized to the liver and spleen when injected s.c. The phenotype of sensitivity or resistance to the inhibitory effect of alpha/beta mouse interferon on virus replication and cell multiplication was conserved during serial i.p. passages and maintained in the clones derived from in vivo passaged cells. These FLC showed a decreased capacity to differentiate in vitro upon treatment with dimethylsulfoxide (DMSO) and a reduced production of Friend leukemia virus with respect to the original clones passaged in vitro.
 ...
PMID:Biologic and biochemical differences between in vitro and in vivo passaged Friend erythroleukemia cells. I. Tumorigenicity and capacity to metastasize. 620 17

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


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