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

The effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and human recombinant interleukin 2 (IL2), on palpable intradermal (i.d.) bladder tumor were studied. The murine transitional cell carcinoma MBT-2 was used in C3H mice. IL2 was given intraperitoneally at 5,000 U/injection three times a day for 5 consecutive days beginning on day 10. LAK cells were generated in vitro from normal splenocytes: 10(7)-10(8) LAK cells were transferred intravenously on day 10 and, in some experiments, also on day 13. IL2 alone, LAK cells alone (total 8 x 10(7], and both in combination showed little or no influence on intradermally growing MBT-2 tumors. Cyclophosphamide was also combined with adoptive immunotherapy (IL2 and LAK). CY (100 mg/kg, i.p. on day 9 or 10) alone was able to suppress i.d. MBT-2 growth significantly. The combination treatment of IL2 and LAK cells with CY caused additional tumor growth suppression in a manner dependent on the total number of LAK cells transferred. The amount of the additional tumor growth suppression was, however, relatively small when compared with CY plus IL2-treated groups. In comparison, experimentally induced 3-day and 10-day pulmonary metastases of MBT-2 cells were treated by the same protocol of IL2 and LAK cells but without CY. IL2 alone reduced the number of gross metastatic nodules in the lung. The addition of LAK cells to the IL2 almost entirely eradicated the 3-day metastatic nodules but was less effective against the 10-day metastases. The data suggest that adoptive immunotherapy with IL2 and LAK cells mediates tumor regression of micrometastases at a selected organ (lung), but is ineffective against the same tumor growing in the skin or in gross metastatic nodules. Host immune suppression by CY was not beneficial in this model in creating a successful therapeutic effect of LAK cells and IL2.
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PMID:Ineffectiveness of adoptive chemoimmunotherapy with lymphokine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murine bladder cancer. 325 20

The influence of implantation site on the metastatic behavior of a murine transitional cell carcinoma line (MBT-2) was examined. MBT-2 cells were injected into one of four anatomic sites; subcutaneously, intramuscularly, intravenously or into the footpad, to evaluate the influence of implantation site on the formation and number of metastases. The MBT-2 cell line produced a low incidence of lung metastases after intravenous injection with a mean of 1.1 lung tumors per mouse. Injection of MBT-2 cells into the footpad or subcutaneously did not produce metastases from the primary tumor. Intramuscular implantation, however, resulted in a sixty percent incidence of metastasis with a mean of 8.2 lung nodules per mouse. This study demonstrated a definite implantation site influence on the metastatic ability of the MBT-2 line.
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PMID:Role of the implantation site on metastatic ability of the murine MBT-2 transitional cell carcinoma. 334 61

The influence of the primary implantation site on the metastatic behavior of a murine transitional cell carcinoma line (MBT-2) and three metastatic sublines (L3F1, L3F2, and L3F3) was studied. The parent MBT-2 cell line produced a low incidence of lung metastasis after intravenous injection and no metastases from the primary tumor when injected either subcutaneously in the right hind flank or in the footpad. Intramuscular implantation of the MBT-2 cells in the right hind flank resulted in a significant increase over the subcutaneous, footpad, and intravenous sites in the incidence and number of lung metastases. Three in vivo/in vitro selected metastatic sublines (L3F1, L3F2, and L3F3) were highly metastatic when injected subcutaneously, intramuscularly, and intravenously. A low number of pulmonary metastases was observed after footpad implantation of the three sublines. This study demonstrated a definite implantation site-influence on the metastatic ability of the parent MBT-2 line and the three selected sublines. Intramuscular implantation was the most permissive implantation site for the development of spontaneous metastasis for the MBT-2 line and the L3F1, L3F2, and L3F3 sublines.
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PMID:Influence of transplantation site on metastatic ability of mouse bladder carcinoma sublines. 341 20

Normal Copenhagen rat bone marrow was assayed for growth inhibition of cultured MAT LyLu rat prostate tumor cells. A marrow-derived factor was identified that had significant growth inhibitory activity in vitro against MAT LyLu as well as against DU-145 human prostate tumor and MBT-2 mouse bladder tumor cells but that was noninhibitory to normal rat fibroblasts. The factor was stable to degradation by acid, heat, freezing, trypsin, and carboxypeptidase B. The factor was nonreactive with Coomassie blue, and the molecular weight was estimated as less than 620 daltons. A similar factor was identified in normal human and normal rat sera. The presence of this factor in bone marrow may explain the absence of osseous metastases in the Dunning rat prostate tumor model.
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PMID:In vitro growth inhibition of Dunning rat prostate tumor by bone marrow factor. 356 48

Three chemotherapeutic agents, methotrexate, cyclophosphamide and cis-diamminedichloro-platinum (cis-platinum), were examined for their effectiveness against metastases in a murine transitional cell carcinoma model. Systemic treatment of the drugs was applied against a MBT-2 derived subline which generates 100% incidence of lung metastases in C3H mice by five weeks. The drugs were examined for their effect against the number of metastases, incidence of metastasis and size of the subcutaneously implanted primary tumor. All three compounds significantly reduced both the number of lung metastases and the incidence when compared to untreated animals. None of the agents proved 100% effective against metastatic tumors. These results suggest the existence of a chemotherapeutic resistant population of metastatic cells. Administration of methotrexate and cis-platinum effectively reduced the size of the primary tumor as compared to untreated animals. Cyclophosphamide did not significantly affect primary tumor size. The response of the antineoplastic agents against the metastatic tumor cells indicates that the L3F2 metastatic cell line is an effective model to study agents against metastatic bladder cancer.
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PMID:The efficacy of chemotherapeutic agents against murine bladder metastasis. 368 79

Four sublines of a murine N-[4-(5-nitro-2-furyl)-2-thiazolyl]-foramide (FANFT)-induced transitional cell carcinoma (MBT-2) possessing spontaneous metastatic ability were isolated via in vivo/in vitro serial selection of metastatic lung lesions. Subcutaneous inoculation of the parent cell line (MBT-2) produced primary tumors when injected into C3H mice. These primary tumors rarely metastasize. A subline designated L3F1 was established from 1 MBT-2 pulmonary metastatic tumor. Further in vivo/in vitro selections established three additional sublines designated L3F2, L3F3 and L3F4. Serial selection resulted in MBT-2 sublines of greater metastatic potential in terms of both incidence of metastasis and the number of metastatic tumors per lung. The parent line differed from the four sublines in metastatic potential, in vitro cell morphology, and in vitro growth parameters. The L3F2 subline was examined for the time of onset of metastasis by removal of the primary tumor. Metastasis of the subcutaneously transplanted tumor occurred between 14 and 21 days after injection of the L3F2 subline. The L3F2 primary tumors and lung metastases were morphologically characterized by light and electron microscopy.
Clin Exp Metastasis
PMID:Isolation and characterization of metastatic sublines from a murine transitional cell bladder carcinoma. 369 64

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.
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PMID:[Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)]. 799 Feb 95

Antiangiogenic therapy is a promising strategy for the treatment of cancer since tumor development and metastases require angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important factors in tumor angiogenesis. In the present study, we investigated the antitumor effect of an adenovirus (AdVEGF-ExR) expressing the extracellular domain of the human VEGF receptor (flt-1) using two different urological tumor/mouse systems. RENCA, a renal cell carcinoma of BALB/c origin, and MBT-2, a poorly differentiated transitional carcinoma of C3H/He origin, were used. Both types of tumor were in vitro infected with AdVEGF-ExR and inoculated subcutaneously into the abdomens of syngenenic mice, and tumor growth was measured twice weekly. In some experiments, BALB/c mice with established RENCA tumors were injected intramuscularly with AdVEGF-ExR as a therapeutic model. The cytotoxicity of spleen cells from the tumor-rejected mice was assessed by 51Cr-release assay. Although the in vitro cell growth of either MBT-2 or RENCA was not affected by infection with AdVEGF-ExR, the in vivo growth of both AdVEGF-ExR-infected tumors was significantly suppressed in the syngeneic mice. In addition, although 2 of 5 mice rejected the AdVEGF-ExR-infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from their spleen cells, thus suggesting no cellular immune response. In a therapeutic model, intramuscular injections of AdVEGF-ExR at a remote site also significantly suppressed the growth of the subcutaneously established RENCA. These results indicate that the adenovirus-mediated expression of a soluble VEGF receptor can be an effective therapy for urological cancer treatment; however, such VEGF-targeted gene therapy is not necessarily accompanied by subsequent antitumor T cell immunity.
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PMID:In vivo growth of transitional and renal cell carcinoma cell lines can be suppressed by the adenovirus-mediated expression of a soluble form of vascular endothelial growth factor receptor. 1659 7

Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive bone turnover inhibition. However, little in vivo evidence exists to support this theory. The (99m)Tc-medronate scintigrams of patients with skeletal metastases and BP use (n=40) were individually matched with cancer patients without BP exposure (n=40) and controls with neither malignancy nor BP use (n=40). Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular (MBT) bone turnover was quantified relative to the femur by defining regions-of-interest with correction for background activity. The patients with BP exposure (34 female, 6 male) had a median age of 63 years (range 25-81) and received a median number of 11 zoledronic acid administrations (range 1-44). Most patients suffered from breast cancer (n=30). The mean ratio of the MBT in cancer patients with BP use over non-users was 0.88 (95% CI 0.80-0.96; p=0.003), and 0.83 (95% CI 0.73-0.94; p=0.001) when BP using oncological patients were compared with controls without malignancy or BP use. The ratio of MBT's between BP naive patients was 0.95 (95% CI 0.83-1.07; p=0.8). No dose-response effect between the number of BP administrations and MBT could be demonstrated (r=0.02; p=0.9). These findings suggest that, relative to the femur, BP exert a stronger effect on mandibular bone turnover, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ.
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PMID:Scintigraphic evaluation of mandibular bone turnover in patients with solid tumors receiving zoledronic acid. 2013 70

Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3'UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.
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PMID:MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer. 2728 84


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