Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we reported that rabbit costal chondrocytes in primary culture produced an anti-angiogenic anti-tumor factor. We also established a clonal human chondrosarcoma cell line, HCS-2/8, which had typical cartilage phenotypes. In the present study, we investigated whether HCS-2/8 cells produce an anti-angiogenic anti-tumor factor. Serum-free medium conditioned by exposure to HCS-2/8 cells in culture inhibited the proliferation of bovine pulmonary artery endothelial cells in culture. The inhibition was not due to general cytotoxicity because the endothelial cells started to proliferate after the conditioned medium was removed from the cultures. The factor in conditioned medium also inhibited DNA synthesis in bovine pulmonary artery endothelial cells, but not in B16 melanoma cells, normal rat kidney cells or chick embryo fibroblasts. Production of the factor by HCS-2/8 cells did not change during serial passages. It also inhibited angiogenesis in the chorioallantoic membrane of chick embryos induced by B16 melanoma and growth of the tumor transplanted onto the membrane. Treatment with protease destroyed the inhibitory activities of conditioned medium on angiogenesis and tumor growth. These findings suggest that HCS-2/8 cells produce a peptide factor with anti-angiogenic, antitumor activity and that the cell line should be a useful source of the factor.
...
PMID:A clonal human chondrosarcoma cell line produces an anti-angiogenic antitumor factor. 169 64

An analogue of human platelet factor 4 (PF4) lacking affinity for heparin was specifically designed to evaluate the importance of this property in the antitumor effects of recombinant PF4. The purified protein, recombinant PF4-241 (rPF4-241), failed to bind heparin but retained the ability to suppress the growth of tumors in mice. Daily intralesional injections of rPF4-241 significantly inhibited the growth of the B-16 melanoma in syngeneic mice without direct inhibitory effects on B-16 cell growth in vitro. Similar antitumor effects were observed with the human colon carcinoma, HCT-116, grown in nude mice, indicating that the inhibitory activity was neither tumor-type specific nor T-cell dependent. rPF4-241 inhibited endothelial cell proliferation in vitro with dose dependence similar to the native sequence rPF4. Both rPF4 and rPF4-241 inhibited angiogenesis in the chicken chorioallantoic membrane. The analogue, however, was inhibitory at lower concentrations than rPF4 in the chorioallantoic membrane system and its inhibitory effects were not abrogated by the presence of heparin. The present findings support the conclusion that both rPF4 and rPF4-241 inhibit tumor growth by suppression of tumor-induced neovascularization. The finding that this activity is independent of heparin binding may allow the development of PF4-based angiostatic agents with reduced toxicity and improved bioavailability. These results also suggest that PF4 may play a more specific role in modulation of blood vessel development than previously recognized.
...
PMID:Inhibition of tumor growth in mice by an analogue of platelet factor 4 that lacks affinity for heparin and retains potent angiostatic activity. 170 60

Optimal cancer treatment with cell-cycle-specific agents requires maintenance of a cytotoxic drug level for a prolonged period. We explored the use of multivesicular liposomes as a slow-release depot of bleomycin for systemic administration via the s.c. route. The average volume-adjusted liposome size was 19.1 microns, the half-life of leakage in human plasma was 32.1 h, and the half-life of s.c. liposomal bleomycin was 31.8 h. When tested against the s.c. B-16 melanoma model in BDF1 mice, the therapeutic index of single-dose bleomycin given s.c. was significantly improved when the drug was encapsulated in multivesicular liposomes. The efficacy was improved as assessed by both inhibition of tumor growth and increased life span, and the toxicity appeared to be decreased.
...
PMID:Multivesicular liposomes containing bleomycin for subcutaneous administration. 171 33

Blood flow in six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice was studied and analyzed in relation to tumor growth characteristics. Two different methods were used to measure blood flow, i.e., uptake of 86Rb and clearance of 133Xe. The percentage of the injected 86Rb taken up per g of tumor tissue and the 133Xe clearance rate were used as parameters for blood flow. The results achieved with these two methods were consistent. Blood flow differed significantly among individual tumors of the same line, even for tumors of similar size. All lines showed a decrease in blood flow with increasing tumor volume. This was due to an increase in necrotic fraction as well as a decrease in blood supply per viable tumor cell. Blood flow also differed significantly among the xenograft lines. All lines showed a lower blood flow than the kidney, spleen, liver, and foot. The blood flow was generally lower in the xenograft lines than in the EMT6 and Lewis lung murine tumor lines. There was no correlation between tumor blood flow and volumetric growth rate. The xenograft lines could be divided into two distinct groups of three lines each with respect to blood supply per viable tumor cell. The three lines showing a high blood supply also showed a high fraction of cells in S phase (23-31%), whereas the three lines showing a low blood supply had a low fraction of S-phase cells (11-13%). Thus, blood supply per viable tumor cell was probably decisive for the cell proliferation activity in the tumors. Moreover, necrotic fraction increased with increasing tumor volume, and the magnitude of this increase was largest for the three lines showing the lowest blood supply per viable tumor cell. These observations were possibly consequences of basic differences in vascular architecture between the two groups of xenograft lines.
...
PMID:Blood flow in six human melanoma xenograft lines with different growth characteristics. 173 46

Three model systems involving LOX human malignant melanoma cells in nude rats were used to compare the chemosensitivity of tumors growing in different tissues. Groups of 4-18 rats with either s.c. xenografts, lung tumor colonies, or bone metastases were treated with cisplatin, doxorubicin, dacarbazine, or mitozolomide. The antitumor effect in the s.c. model was expressed as specific growth delay, and in the experimental metastasis studies as relative increase in life span (RILS), calculated on the basis of observed disease-free survival. Cisplatin had a moderate but significant effect on the progression of LOX tumor growth in all three systems. Doxorubicin was clearly more efficacious, but for both drugs tumor-free survivors were rare or absent. Importantly, for each of the compounds the levels of response were roughly the same in all three models, with specific growth delay and RILS values in the range of 0.2-0.3 for cisplatin and 0.5-0.9 for doxorubicin. In contrast, a significant site-dependent difference in sensitivity of the LOX tumors was observed for two alkylating agents. Thus, dacarbazine, which temporarily caused complete regression of s.c. xenografts (specific growth delay = 21.0), showed a moderate activity in the lung tumor model (RILS = 1.0) but had only a limited effect (RILS = 0.4) on bone metastases. Mitozolomide gave a curative effect in 6 of 10 animals with s.c. and in 4 of 4 animals with lung tumors, whereas in the bone metastasis model it was only slightly superior to doxorubicin (RILS = 1.1). In preliminary attempts to elucidate the underlying mechanisms, no site-dependent differences in drug distribution and in two cellular detoxifying systems were detected. The data demonstrate the usefulness of the LOX models for studying the clinically relevant problem of site-dependent tumor response to chemotherapy.
...
PMID:Site-dependent differences in sensitivity of LOX human melanoma tumors in nude rats to dacarbazine and mitozolomide, but not to doxorubicin and cisplatin. 173 96

The ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti-metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum-containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis.
...
PMID:Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis. 173 31

Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.
...
PMID:Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen. 176 Aug 21

Assessment of the function of putative dominantly-acting oncogenes or recessive tumor-suppressor genes in human tumor development and progression must ultimately involve xenografting experiments using immune deficient animals such as nude mice. Most human tumor xenograft experiments have employed conventional subcutaneous injection procedures. However, despite the simplicity of this procedure, it poses some serious potential drawbacks as most types of human tumor will not readily grow or metastasize from a subcutaneous ('ectopic') site of injection. In contrast, 'orthotopic' injection procedures will often enhance the tumorigenic and/or metastatic ability of tumor cell populations. An example of this is summarized in the context of human malignant melanoma where the effects of subcutaneous versus subdermal injection are compared. Despite the seeming subtle and minor change in injection site, superior growth of human melanomas can be obtained by the latter, orthotopic-like, route of injection. It therefore follows that induction of tumorigenic or metastatic properties in a given human cell population by gene transfection may not be detected if the transfected cells are assayed in vivo only by subcutaneous injection procedures. An example of this is provided by experiments involving transfection of normal or mutated ras genes into a low-grade, well-differentiated human bladder carcinoma cell line, called RT-4. Thus overexpression of normal or mutated (valine 12) c-H-ras resulted in acquisition of a clinical-like invasive phenotype. However, this was clearly seen only if the cells were injected into the bladders (i.e. 'intravesically') of nude mice. In contrast, conventional subcutaneous injection of the high ras expressing transfected RT-4 cell lines did not reveal acquisition of invasive properties: all cell lines grew locally as well-encapsulated tumor masses. It is argued that similar orthotopic injection procedures should be employed when assessing the suppressive effects of various wild-type tumor-suppressor genes on human tumor growth in vivo. Utilization of subcutaneous injection procedures may grossly exaggerate the growth suppressive effects of such genes. This could explain the paradox of why, on the one hand, alterations involving many different genes (including different suppressor genes) appear to be involved in human carcinoma tumorigenesis while on the other hand, complete suppression of tumorigenicity can be caused by transfer of a single wild-type suppressor gene. Such complete suppressions might be observed only after ectopic (usually subcutaneous) injection procedures.
...
PMID:Importance of orthotopic transplantation procedures in assessing the effects of transfected genes on human tumor growth and metastasis. 176 65

Laminin, the major glycoprotein component of basement membrane, promotes the malignant phenotype. Cells which are adherent to laminin are more malignant than the non-adherent cells and in certain tumor cells, the number of laminin receptors is positively correlated with malignancy. Laminin also increases collagenase IV activity, an enzyme demonstrated to be critical for tumor spread. A site on laminin, containing the amino acid sequence SIKVAV, has been identified which when injected intravenously with B16F10 melanoma cells, causes an increase in the number of colonies on the surface of the lungs. This peptide does not affect tumor cell arrest in the vasculature or the immune system. It does promote angiogenesis in various in vitro and in vivo models, thereby facilitating tumor cell survival. When a complex mixture of laminin-enriched basement membrane components (Matrigel) is coinjected with tumor cells subcutaneously, tumor incidence and growth increases. Various tumor cell lines and primary isolates, which previously could not form tumors in mice, can be induced to grow rapidly in the presence of Matrigel. Slowly growing tumors or arrested tumors can also be induced to grow more quickly with additional injections of Matrigel. When an SIKVAV-containing synthetic peptide is coinjected with B16F10 tumor cells and Matrigel subcutaneously in mice, larger tumors are formed than that observed with either Matrigel or cells alone. Such studies define the role of laminin in tumor growth and spread and generate new models for studying therapeutic agents. Of particular interest is the ability to grow primary isolates which generally do not grow in mice.
...
PMID:Basement membrane and the SIKVAV laminin-derived peptide promote tumor growth and metastases. 176 67

Murine, antihuman melanoma cell monoclonal antibody (mAb) 16.C8 was generated by fusing the murine myeloma cell line P3X63/Ag8.653 with splenocytes from a nude mouse bearing a human melanoma xenograft, after reconstitution with splenocytes from syngeneic immunocompetent BALB/c mice. The antibody reacted strongly with fresh human melanoma cells and exhibited preferential reactivity with established human melanoma and neuroectodermal tumor cell lines. Electrophoresis and Western blotting experiments indicated that 16.C8 is directed against a sialoglycoprotein antigen with a molecular weight of 110-120 kDa. mAb 16.C8 mediated lysis of melanoma cells in vitro in antibody-dependent cellular cytotoxicity assays using human mononuclear effector cells isolated from normal volunteers or malignant melanoma patients. In addition, the administration of mAb 16.C8 to nude mice bearing established human melanoma lung and liver metastases resulted in significant inhibition of tumor growth as shown by gross and histologic examination. In contrast, animals treated with Hanks' balanced salt solution or nonspecific immunoglobulin exhibited a large tumor burden. These results suggest that mAb 16.C8 may be of value in treatment of metastatic melanoma in humans.
...
PMID:Cell binding and tumor inhibiting functions of a new antihuman melanoma murine monoclonal antibody. 176 67


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

---