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

The mouse B16 melanoma metastasizes in two stages, first to the lungs and then from lung metastases to systemic organs. Despite widespread dissemination, visible metastases generally occur only in the brain, adrenals, kidneys, ovaries, pancreas, and mesentery. As a novel approach to investigate the basis of metastatic patterning in this system, the possibility was explored that an implantable "artificial organ" could serve as a site for the occurrence and experimental modulation of secondary-stage metastasis. Each implant consisted of a cellulose disc 4 mm in diameter, with a central 1-mm polymer pellet to effect local sustained release of angiogenic or growth factors in a s.c. environment. During the secondary spread of tumors initiated with the B16 melanoma clone G3.12 and with the more metastatic variant G3.12/BM2, metastatic involvement of implants containing angiogenic factors was mainly as invisible micrometastases demonstrable by bioassay; visible metastases were rare and were located in implant blood vessels. Metastasis occurred in about 30% (G3.12) and 50% (G3.12/BM2) of implants with vasculature induced by ethylene-vinyl acetate copolymer alone. Endothelial cell growth factor and heparin promoted greater vascularization but did not significantly alter metastatic involvement of implants. Release of tumor cell mitogenic activity from pellets containing a crude extract of mouse lungs increased the incidence of G3.12/BM2 metastasis in implants to over 70% and stimulated growth of visible metastases within the cellulose matrix. In contrast, liver extract inhibited metastasis growth. Colonization of implants following intracardiac injection of G3.12/BM2 cells was generally similar to metastasis, but visible colonies formed more readily and were less dependent on the influence of lung extract. These results indicate that metastasis and colonization can occur regularly in implants and that the relative favorability of the implant environment for secondary tumor growth can be altered by incorporation of tumor cell growth modulators.
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PMID:B16 melanoma metastasis to an "artificial organ" implant. 170 54

We have examined the ability of bryostatin 1 to inhibit the in vitro growth and in vivo development of a panel of four murine tumors of diverse tissue origins. A wide range of antiproliferative responses was observed for the four tumors. At 100 ng/ml the in vitro growth of the Renca renal adenocarcinoma, the B16 melanoma, the M5076 reticulum cell sarcoma, and the L10A B-cell lymphoma were inhibited by 0, 40, 40, and 94% respectively. All three cell lines sensitive to bryostatin in vitro responded to multiple dose, 1 microgram/injection/day in vivo i.p., bryostatin therapy. Only the in vitro resistant Renca tumor failed to respond to bryostatin in vivo. The correlation between in vitro and in vivo antitumor efficacy suggests a direct mechanism of antitumor activity for bryostatin. Both local regional therapy (M5076 i.p.) and systemic therapy (B16 lung metastases and L10A s.c. tumors) with bryostatin were successful at prolonging survival time. Multiple i.p. doses of bryostatin at a minimum level of 0.5-1.0 microgram/injection were required to observe significant in vivo antitumor effects. The success of in vivo administration of bryostatin in mice bearing 8-10-mm s.c. masses of L10A lymphoma (5-10 x 10(9)) and our further observation that five of a panel of six human B-cell lymphoma cell lines were sensitive to the growth inhibitory effects of bryostatin in vitro suggest that bryostatin may be effective in treating lymphoid malignancies in humans.
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PMID:Preclinical evaluation of bryostatin as an anticancer agent against several murine tumor cell lines: in vitro versus in vivo activity. 172 68

Eighteen patients with disseminated malignant melanoma were treated with a combination of carboplatinum and cytosine arabinoside. There were 14 males and 4 females with median age of 51 years (range 36-68 years). We observed 4 complete responses (CR) and 3 partial responses (PR). Lung metastases, cutaneous and subcutaneous metastases responded more often, while liver and lymph node metastases did not respond. Two groups of toxicities were observed: gastrointestinal and hematological. Only nine grade 3 toxicities were observed. Response rates and low toxicity we observed during this study warrant its use for patients with disseminated malignant melanoma comparing it in a future studies with DTIC containing regimens.
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PMID:Carboplatinum and cytosine arabinoside in patients with disseminated malignant melanoma. A phase II study. 178 29

Several populations of the mouse B16 melanoma that are highly metastatic from subcutaneous transplants but differ in growth characteristics were compared with regard to systemic site patterning of visible metastasis, as well as colonization effected by intracardiac injection of tumor cells. In all cases, metastasis proceeded in two stages, initially to the lungs and secondarily from lung metastases to systemic sites. The relative ranking of systemic site involvement by secondary-stage metastasis was basically similar for all tumor cell populations; the overall hierarchy was: kidneys greater than brain greater than adrenals and ovaries greater than pancreas greater than mesentery. Colonization patterns resulting from intracardiac injection were also generally comparable but differed from metastasis patterning in that the kidneys and brain were poorly colonized while the bones were frequent sites of colonization. Enumeration of fluoresceinated tumor cells or microbeads trapped in various sites following intracardiac injection revealed a ranking of initial involvement that differed markedly from colony formation. These results indicate that the hemodynamics of blood flow is not a critical determinant of colonization patterning. Based on the colonizing behavior of microbead-bound tumor cells, the frequent metastatic involvement of the kidneys and brain appears to result from selective trapping of large multicell tumor emboli within arteries in those organs. The occurrence of metastasis in other systemic sites is, like colonization, not readily explained by hemodynamics.
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PMID:Hemodynamic considerations in organ and tissue patterning of B16 melanoma systemic metastasis and colonization. 180 Apr 50

Female C57BL/6 Jena mice, 3-, 12-, and 18-month-old, were inoculated intravenously (i.v.) with syngeneic melanoma B16 cells. The number of experimental lung metastases, counted 21 days after tumor inoculation, was significantly higher in older hosts. Pretreatment of young adult mice with immunosuppressive dose of cyclophosphamide considerably increased the number of lung nodules. The number of lung metastases was reduced when young and old animals were pretreated or treated with Poly (I:C). Similar treatment of mice with two other immunomodulators (thymalin and diacetyl-splenopentin 5) was practically without effect on metastasis formation. It is suggested that the higher number of experimental metastases of melanoma B16 in aged mice is mediated by immuno-senescence.
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PMID:Age-dependent experimental tumor dissemination of murine melanoma B16. 184 47

While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45 million A-LAK cells, an A-LAK cell/tumor cell ratio higher than 1:1 in most metastases was observed. Surprisingly, approximately 5% of the lung metastases seemed totally resistant to infiltration even though neighboring metastases were highly infiltrated. While substantial infiltration of lung metastases was seen after i.v. injection, significant infiltration of liver metastases was seen only after intraportal injection of the A-LAK cells indicating impaired traffic of intravenous injected A-LAK cells through the lung capillaries. These results present direct evidence that A-LAK cells, upon a proper route of administration, have the potential to migrate to and heavily infiltrate metastases from murine tumors of different origin.
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PMID:Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases. 185 30

The value of resecting pulmonary metastases from malignant melanoma was retrospectively examined. Between 1981 and 1989, 56 patients (35 men and 21 women with a mean age of 49 years) had 65 pulmonary resections for histologically proven metastatic melanoma after treatment of the primary tumor. In patients undergoing thoracotomy, 50% (28/56) had pulmonary metastases as the initial site of recurrence. Twenty-eight patients (50%) had local-regional recurrence before the development of lung metastases. Eight lobectomies, two segmentectomies, and 55 wedge excisions were done. Fifty-four patients (54/56, 96%) underwent complete resection, and there were no operative deaths. The postthoracotomy actuarial survival was 25% at 5 years (median interval, 18 months). Location of the primary tumor, histology, thickness, Clark level, local-regional lymph node metastases, or type of resection was not associated with improved survival. Patients without regional nodal metastases before thoracotomy had a median survival of 30 months compared with 16 months for all others (p = 0.04). Patients with lung as the site of first recurrence had a median survival of 30 months compared with 17 months for patients with initial local-regional recurrence (p = 0.038, log-rank test). Despite systemic spread, patients with isolated pulmonary metastases from melanoma may benefit from metastasectomy.
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PMID:Improved survival after resection of pulmonary metastases from malignant melanoma. 186 35

B16-F10.9 is a highly metastatic clone of the B16-F10 melanoma line, that expresses low levels of MHC class-I antigens. F10.9 cells transfected with H-2Kb are highly immunogenic and consequently exhibit a low metastatic phenotype. Treatment with gamma-IFN elevated H-2Kb and H-2Db cell surface expression of F10.9 cells to levels much higher than did transfection of these genes. Yet, following intravenous injection, the gamma-IFN treated cells generated high loads of lung metastases. However, when tested for their immunogenic effect, they elicited CTL and were sensitive to CTL. Immunization with both the positive transfectant KI and the gamma-IFN-treated F10.9 cells protected in vivo against metastatic spread of a subsequent transplant of parental F10.9 cells. The protection elicited by KI transfectants was more effective than the protection by gamma-IFN-treated cells.
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PMID:Immunization by gamma-IFN-treated B16-F10.9 melanoma cells protects against metastatic spread of the parental tumor. 190 54

Murine macrophages from different anatomical sites were compared for their ability to become tumoricidal and to secrete interleukin-1 (IL-1) and tumor necrosis factor (TNF) following stimulation in vitro by several biological response modifiers (BRM). Peritoneal macrophages (PM), alveolar macrophages (AM), and tumor-infiltrating-macrophages (TIM), isolated from B16F10 melanoma colonies in the lung, were incubated overnight with BRM [recombinant murine interferon gamma (rMulFN-gamma), lipopolysaccharide (LPS), muramyl dipeptide (MDP)], either alone or in combination. PM exhibited an increased cytotoxic response following incubation with LPS or rMuIFN-gamma but not with MDP. Both AM and TIM were induced to become tumoricidal following incubation with rMuIFN-gamma plus LPS or rMuIFN-gamma plus MDP but not after stimulation with any BRM alone; the level of cytotoxicity obtained with TIM incubated with rMuIFN-gamma plus LPS was slightly lower than that observed with PM or AM, while with rMuIFN-gamma plus MDP both AM and TIM had lower cytotoxicity than PM. Secretion of IL-I and TNF was observed in PM stimulated with LPS or MDP but not with rMuIFN-gamma. Likewise, secretion of IL-I by AM or TIM was also induced with LPS, although less than that obtained with PM. AM stimulated with LPS secreted larger amounts of TNF than PM while TIM secreted very low amounts of TNF. However, this result may be a consequence of the enzymatic isolation procedure used to obtain TIM since TNF secretion was also impaired in LPS-stimulated normal lung macrophages isolated by a similar enzymatic procedure, or enzyme-treated PM. Our results suggest that TIM obtained from lung metastases share certain functional characteristics with normal AM and respond to BRM in like manner with respect to induction of tumoricidal activity and cytokine secretion.
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PMID:Tumoricidal activity and cytokine secretion by tumor-infiltrating macrophages. 190 30

Five out of six human melanoma cell lines tested were able to degrade in vitro a smooth muscle cell extracellular matrix in a plasmin-dependent way. In three of these five cell lines, this process was mediated by tissue-type plasminogen activator (t-PA) and in the other two cell lines by urokinase-type plasminogen activator (u-PA). All melanoma cell lines produced t-PA mRNA and protein, whereas only the two cell lines showing u-PA-mediated matrix degradation produced u-PA mRNA and protein. These latter cell lines also produced plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2) mRNA and protein. u-PA receptor (u-PA-R) mRNA and binding of radiolabeled u-PA was found in all melanoma cell lines. The metastatic capacity of these cell lines was studied in nude mice. All cell lines were able to develop primary tumors at the subcutaneous inoculation site. The production of plasminogen activators, their inhibitors and urokinase receptor by subcutaneous tumors corresponded with the production by the parental cell lines in vitro. The two u-PA and PAI-1 producing cell lines showed the highest frequency to form spontaneous lung metastases after subcutaneous inoculation, whereas five of the six cell lines formed lung colonies after intravenous inoculation. In conclusion, u-PA mediated matrix degradation in vitro and production of u-PA and PAI-1 by human melanoma cell lines correlated with their ability to form spontaneous lung metastasis in nude mice. No correlation was found with the ability to form lung colonies after intravenous injection. These findings suggest a role for u-PA and PAI-1 in a relatively early stage of melanoma metastasis.
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PMID:Metastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase-mediated matrix degradation. 191 36


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