Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Harding-Passey mouse melanoma (HP) cells (10(6)) were administered i.p. to female BALB/c x DBA/2 F1 (hereafter called CD2F1) mice on Day 0. We showed earlier (H. Z. Hill, et al., Arch Surg., 114: 135-138, 1979) that a single dose of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) administered on Day 0 or on subsequent days was equally effective regardless of the day of administration. We now show that a single dose of 10 mg of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU) per kg was most effective in prolonging survival of HP-bearing CD2F1 mice when administered on Day 0. There was then a decline in effectiveness to Day 10, at which time the increase in survival of the drug-treated animals was no longer significant. The effect of sequential scheduling of DTIC and MeCCNU on HP was studied. The first drug was given on Day 0 or on Day 10. The second drug followed on the same day or on subsequent days. The greatest enhancement of survival was seen when DTIC was administered on Day 0 and MeCCNU on Day 1. Nine of 10 mice on this schedule were cured. When treatment of HP was started on Day 10, the most enhancement was again seen for DTIC on Day 10 and MeCCNU on the next day. Reversal of the order of the two drugs produced less prolongation of survival and fewer cures. The effect of scheduling two doses of DTIC was also studied using the HP model. The first dose was given on Day 0 or on Day 10. The second dose produced the greatest enhancement of survival when administered 3 to 4 days after the first dose, but the enhancement was less than that seen when DTIC was followed by MeCCNU. For comparison, the two drugs were also studied in female DBA/2 mice carrying the Cloudman S91 melanoma. In combination, on Day 0, in only one of three experiments was survival prolonged beyond the controls. Other schedules were ineffective. The enhancement seen when HP-bearing CD2F1 mice are treated with the best combination of the two drugs is clearly not seen with S91. The results imply that dosage scheduling in the treatment of murine melanomas must be individualized. Extrapolation to the human situation suggests the same conclusion.
 ...
PMID:Effect of scheduling of combinations of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea on the Harding-Passey and Cloudman S91 mouse melanomas. 705 82

We have studied the induction of a granulocyte-associated leukocytosis (leukemoid reaction) in C3HA, C57B1/6, and DBA/2 mice by a number of transplantable tumors of different origin. Leukemia L1210, Hepatoma 22, a transplantable mammary carcinoma of spontaneous C3HA origin, and a L929 culture fibroblasts-derived rhabdomyosarcoma, all induced a leukemoid reaction in their specific mouse strain. Melanoma B16 and Lewis lung carcinoma gave no reaction; Adenocarcinoma 755 and Harding-Passey melanoma evoked a leukocytosis but not due to an increase in neutrophils. Some extratumoral factors can influence the hematological response; the intensity of final leukemoid reaction was higher in female mice than in males bearing the same tumor. On the other hand, Ehrlich ascites tumor transplanted in all three inbred mouse strains rendered different levels of leukemoid reaction; response was higher in DBA/2, intermediate in C3HA and lower in C57B1/6.
 ...
PMID:Leukemoid reaction induced by different transplantable tumors in three inbred mouse strains. 707 May 57

Differences in tumour susceptibility between strains of mice (C57Bl/6 and C57Bl/6 X DBA/2 = B6D2F1) could be demonstrated for several tumours of C57Bl origin, both solid tumours (B16 melanoma and Lewis lung carcinoma) and lymphomas (RBL-5, 136-3 and ALC). Serum from mice with high tumour resistance in vivo (B6D2F1) showed an inhibitory effect on tumour colony formation in a soft agar colony assay. Serum from mice with lower tumour resistance (C57Bl/6) had no effect. When other F1 hybrids of C57Bl/6 parental origin were tested, the same correlation between in vitro inhibition of tumour colony formation and in vivo susceptibility was found. The serum factor was species non-specific, since the activity was expressed against in vitro grown cell lines of human origin. The tumour colony inhibitory activity was heat sensitive (56 degrees C for 30 minutes), precipitable by (NH4)2SO4, and not removed by adsorption on tumour cells. These results demonstrate the existance of a naturally-occurring humoral tumerostatic factor(s) which correlates to in vivo susceptibility to tumour cells. Its relationship to NK cell activity is discussed.
 ...
PMID:Inhibitory effect on tumour colony formation of mouse serum associated with tumour resistance in vivo in semi syngeneic mice. 731 58

Studies have been performed using two subcutaneously implanted mouse tumor models to investigate the immunotherapeutic potential of lymphokine-containing culture supernatants from long-term human lymphoblast cell cultures. Human lymphoblastoid cell line, RPMI 1788, was used as a cell culture source of lymphokines. Supernatants were removed from cultures at the stationary phase of growth and concentrated on Amicon filters retaining molecules above 10,000 Daltons. This concentrate was applied to a Sephadex G-25 column, equilibrated with ammonium bicarbonate buffer, for removal of salts and dye from the culture medium. The effluent was lyophilized and reconstituted for use in further purification by affinity chromatography and SDS-PAGE gels. Such preparations were used to inject DBA/2 mice bearing subcutaneous L-1210 tumors. In addition, the B-16 melanoma was used as a model of a solid tumor in C57Bl/l mice. Animals were treated intralesionally and intraperitoneally with lymphokines containing preparations and control solutions. Tumors growing subcutaneously were susceptible to lymphokine-induced inflammation-mediated regression without additional therapy. In the study of L-1210 subcutaneous tumors, reduction in tumor size was followed by complete regression, prolonged survival, immunity to additional inoculation, and cures in 20--40% of the treated mice. Tumor regression and prolongation of survival were also noted in mice bearing B-16 melanomas. These studies support the use of mouse tumors as bioassays for antitumor inflammatory activity of human lymphokine preparations and help to quantitate their potential use in human tumor immunotherapy.
 ...
PMID:Lymphokine-mediated immunotherapy studies in mouse tumor systems. 735 17

The levels of polyamines (putrescine, spermidine and spermine) in erythrocytes and plasma were studied using Cloudman S-91 melanoma grown in the lungs of DBA/2 mice. Polyamine levels and the numbers of tumour-cell colonies in the lungs were determined at weekly intervals. Putrescine levels in both erythrocytes and plasma significantly increased 1 week after tumour inoculation. Three weeks after inoculation, however, putrescine levels in the erythrocytes showed a greater increase than those in plasma. Spermidine and spermine levels were initially high at 2 weeks in plasma and at 4 weeks in erythrocytes. However, by 6 weeks the spermidine levels showed a greater increase in erythrocytes than in plasma. These data suggest that erythrocytes may absorb and store polyamines released into the circulation.This finding was subsequently applied to human studies. Fifty-two untreated patients with solid tumours were examined in the preoperative period. All erythrocyte polyamine levels from patients were significantly higher than those from control subjects. Plasma spermidine levels in patients were significantly higher than those in controls, whereas plasma putrescine and spermine levels showed no significant increase. The frequency of raised levels of putrescine, spermidine and spermine in erythrocytes was significantly greater than in plasma. These results suggest that polyamine levels in erythrocytes may provide useful information for the detection of cancer.
 ...
PMID:Raised polyamines in erythrocytes from melanoma-bearing mice and patients with solid tumours. 742

Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction.
 ...
PMID:Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination. 777 45

The murine B16 melanoma (H-2b) was transfected with a retroviral vector containing the mouse IFN-alpha 1 gene. IFN-alpha 1-transfected cells produced IFN-alpha in vitro and exhibited an altered phenotype characterized by a decreased rate of multiplication, enhanced expression of H-2 antigens, an antiviral state to VSV, and decreased pigmentation. Control and IFN-alpha 1-transfected cells were tested for their ability to grow in syngeneic (H-2b) C57Bl/6 and allogeneic (H-2d) DBA/2 mice. IFN-alpha 1-producing B16 clones were less tumorigenic after s.c., i.p., and i.v. routes of injection than IFN-non-producer B16 clones in syngeneic C57Bl/6 mice. IFN-alpha 1-producing B16 cells were, however, totally rejected by allogeneic DBA/2 mice regardless of the routes and inocula tested, while control B16 cells grew in and killed DBA/2 mice. The total rejection of IFN-alpha 1-transfected B16 cells in allogeneic mice appeared to be dependent on T cells as these cells grew in DBA/2 nude mice. Incubation of IFN-alpha-producing clones with anti-mouse IFN-alpha/beta prior to injection into C57Bl/6 mice did not enhance their tumorigenicity. Likewise, injection of C57Bl/6 and DBA/2 mice with antibody to IFN-alpha/beta did not enhance the tumorigenicity of IFN-alpha 1-transfected cells. C57Bl/6 mice immunized with irradiated IFN-alpha 1 cells were only slightly protected against a subsequent challenge with parental B16 cells. In contrast, DBA/2 mice immunized with irradiated IFN-alpha 1 cells exhibited tumor-specific, long-lasting immunity to subsequent challenge with parental B16 cells.
 ...
PMID:IFN-alpha 1 gene transfection completely abolishes the tumorigenicity of murine B16 melanoma cells in allogeneic DBA/2 mice and decreases their tumorigenicity in syngeneic C57BL/6 mice. 782 20

We have established a model for the immunologic rejection of melanoma cells. Using a receptor-mediated, adenovirus-augmented gene delivery system (transferrinfection) we have shown that, upon transfection with an IL-2 gene construct, MHC class I+/class II- murine M-3 cells lose their tumorigenicity in both athymic and euthymic mice. More importantly, we found that these melanoma cells, which produce high levels of IL-2, can be used to induce a long-lasting anti-tumor immune response in syngeneic euthymic DBA/2 mice but not in athymic animals. This immune response, which can also be elicited by coadministration of nonmodified, irradiated M-3 cells and IL-2-transduced fibroblasts, results in the rejection of a subsequent challenge with M-3 cells or, in the elimination of preexisting M-3 cancer cell deposits. We found that transfer of T cell-enriched, but not of T cell-depleted, splenocytes from immunized mice conferred protection against M-3 cells, but not against unrelated KLN 205 cancer cells. Transfer of either CD4+ or CD8+ T cells led to only partial protection against challenge with wild-type M-3 cells. Our further observations that T cell-enriched, but not T cell-depleted splenocytes of immunized animals are capable of tumor-specific lytic activity and that this activity resides in the CD8+ cell population are compatible with the assumption that MHC class I-restricted T cell cytotoxicity is a biologically relevant effector mechanism in this model. That other mechanisms also contribute to melanoma cell destruction is evidenced by the presence of large numbers of macrophages and granulocytes in addition to T cells at the challenge sites of immunized mice.
 ...
PMID:Elicitation of a systemic and protective anti-melanoma immune response by an IL-2-based vaccine. Assessment of critical cellular and molecular parameters. 789 22

(C57BL/6 x DBA/2)F1 mice were fed antioxidant-matched fish oil (FO) or corn oil (CO) diets for weeks, were challenged with B16.F10 melanoma cells, and lung metastases were enumerated 17 days later. Mice fed FO had fewer lung tumors than mice fed CO. This dietary effect persisted in mice injected with monoclonal antibodies which depleted natural killer cells, CD8+ T cells or CD4+ T cells. Generation of specific anti-B16.F10 cytotoxic cells in vitro by splenocytes from immunized mice was greater in mice fed FO. Even though host resistance to lung metastases by B16.F10 cells is mediated in large part by natural killer cells, CO and/or FO may have affected cells not tested here or tumor cells themselves.
 ...
PMID:Melanoma lung metastases and cytolytic effector cells in mice fed antioxidant-balanced corn oil or fish oil diets. 811 Nov 90

Certain lipophilic cations have been reported to display anticarcinoma activities because of their selective uptake and retention by mitochondria of cancer cells. Thus, these agents may comprise a unique class of agents directed against carcinoma. After screening more than 1000 lipophilic cations, we found that the monovalent lipophilic cation, 2,6-bis(4-amino-phenyl)-4-[4-(dimethylamino)phenyl]thiopyrylium chloride (AA1), displayed remarkable anticarcinoma activity both in vitro and in vivo. Unlike most other lipophilic cations, AA1 is stable and displays minimal light sensitivity. In vitro testing showed that AA1 was 10 times more toxic to the carcinoma cell line CX-1 than to the normal epithelial cell line CV-1. In vivo animal experiments showed that AA1 significantly prolonged the survival of mice implanted with tumors. For C57BL x DBA/2 F1 mice implanted with the mouse bladder carcinoma cell line, MB49, the treated:control ratio was 344%. For Swiss nu/nu mice implanted i.p. with the human melanoma cell line, LOX, the treated:control ratio was 341%. The most significant observation was obtained with Swiss nu/nu mice that were implanted i.p. with the human ovarian cell line, OVCAR-III. The treated:control ratio in this situation was greater than 450%. In all these tumor models, AA1 produced minimal toxicities. AA1 exhibited little inhibition of electron transport in isolated rat liver mitochondria; however, it inhibited mitochondrial ATPase with 50% inhibitory concentration of 6 microM. Compared with previously reported anticarcinoma lipophilic cations such as rhodamine 123 and dequalinium chloride, AA1 appeared to display more effective in vivo anticarcinoma activity. Thus, AA1 could be considered for further clinical development as a candidate for anticarcinoma chemotherapy.
 ...
PMID:AA1, a newly synthesized monovalent lipophilic cation, expresses potent in vivo antitumor activity. 813 49


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