Growth Of Experimental Metastases Research Articles

Application of standardized mistletoe extracts augment immune response and down regulates metastatic organ colonization in murine models

The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extracts from plants grown on fir trees (ME-A) and pine trees (ME-P) were evaluated in BALB/c-mice. Regular subcutaneous (s.c.) and intraperitoneal (i.p.) applications (three times per week for 14 consecutive days; 5 and 50 μg per injection and mouse) upregulated thymus weight and peripheral blood leukocyte counts in tumor bearing mice. To check the influence of ME-A and ME-P treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver and lung colonization. ME-A and ME-P were regularly administered starting 24 h after tumor cell challenge. Organ colonization was investigated on day 14 after tumor cell inoculation and demonstrated statistically significant ( P<0.05) reductions of experimental liver and lung metastases for ME-A and ME-P treated mice.

Thymosin α 1 application augments immune response and down-regulates tumor weight and organ colonization in BALB/c-mice

The immunomodulatory and antimetastatic/antitumor activity of thymosin α 1 (Tα 1) was evaluated in BALB/c-mice. Daily subcutaneous application (7 consecutive days, 0.01–10 μg of Tα 1/injection per mouse) upregulated the number of thymocytes and peripheral blood cells in tumor bearing mice. To check the influence of Tα 1 treatment on growth of experimental metastases, RAW H10 lymphosarcoma cells or L-1 sarcoma cells were intravenously injected into BALB/c-mice to establish liver or lung metastases. Local tumor growth was induced by subcutaneous injection of L-1 sarcoma cells. Tα 1 was subcutaneously administered daily for 7 consecutive days starting 24 h after tumor cell challenge. Organ colonization, as well as local tumor growth, were investigated on day 14 after tumor cell inoculation, and demonstrated a statistically significant ( P<0.05) reduction of experimental liver and lung metastases and local tumor growth for Tα 1 treated mice.

A human fibrosarcoma inhibits systemic angiogenesis and the growth of experimental metastases via thrombospondin-1.

Concomitant tumor resistance refers to the ability of some large primary tumors to hold smaller tumors in check, preventing their progressive growth. Here, we demonstrate this phenomenon with a human tumor growing in a nude mouse and show that it is caused by secretion by the tumor of the inhibitor of angiogenesis, thrombospondin-1. When growing subcutaneously, the human fibrosarcoma line HT1080 induced concomitant tumor resistance, preventing the growth of experimental B16/F10 melanoma metastases in the lung. Resistance was due to the production by the tumor cells themselves of high levels of thrombospondin-1, which was present at inhibitory levels in the plasma of tumor-bearing animals who become unable to mount an angiogenic response in their corneas. Animals carrying tumors formed by antisense-derived subclones of HT1080 that secreted low or no thrombospondin had weak or no ability to control the growth of lung metastases. Although purified human platelet thrombospondin-1 had no effect on the growth of melanoma cells in vitro, when injected into mice it was able to halt the growth of their experimental metastases, providing clear evidence of the efficacy of thrombospondin-1 as an anti-tumor agent.

Inhibition of murine hepatic tumor growth by liposomes containing a lipophilic muramyl dipeptide.

We have investigated the ability of liposomes containing a lipophilic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine glycerol dipalmitate (MDP-GDP) to activate Kupffer cell tumoricidal activity in situ and to inhibit the growth of experimental hepatic micrometastases of tumor cell line H-59, a liver-homing variant of the Lewis lung carcinoma. Liposomes prepared from distearoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DSPC/DMPG) and containing MDP-GDP (1 mumol and 2 micrograms, respectively) were efficiently taken up by the liver after i.v. administration. A single i.v. injection of DSPC/DMPG liposomes containing MDP-GDP was capable of inducing Kupffer cell tumoricidal activity against H-59 tumor cells as measured in vitro. Control liposomes or 100 micrograms free MDP were ineffective in inducing Kupffer cell tumoricidal activity in situ. Two treatment regimens were evaluated in vivo: firstly, C57BL/6 mice were injected with tumor cell line H-59 and subsequently treated with multiple injections of liposomal MDP-GDP. Secondly, treatment with liposomal MDP-GDP was initiated prior to tumor cell injection and continued after tumor cell injection. The ability of liposomes containing MDP-GDP to reduce the number of hepatic micrometastases using the first protocol was related to the tumor cell inoculum, significant inhibition being observed at lower liver tumor burdens (less than 25 tumor nodules). Pretreatment of the mice prior to tumor cell challenge followed by treatment afterwards greatly enhanced the efficacy of liposomal MDP-GDP and brought about a highly significant inhibition of the growth of experimental metastases even at high liver tumor burdens (greater than 50 nodules).

Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen.

B700 is a melanoma-specific glycoprotein antigen, with a m.w. of 65,000 and an isoelectric point of 4.5; this antigen has been shown to bear significant sequence homology to a normally occurring protein, serum albumin. The production of B700 is apparently restricted to all the murine melanomas tested, since a variety of other transformed and untransformed cell lines do not contain detectable levels of this antigen. The capacity of B700 to function as a tumor-specific transplantation antigen (TSTA) is demonstrated in this study. This activity has been titrated, and it is shown that mice immunized with B700 are able to significantly inhibit the growth of B16 F10 melanomas after subcutaneous challenge; immunized mice can also inhibit the establishment and growth of experimental metastases in the lungs after i.v. challenge with B16 melanoma cells. The TSTA was found to cross-protect also against challenge with two other murine melanoma lines, JB/RH and K1735, but was specific in that the growth of two nonmelanoma lines (RBL-5 leukemia and MCA-105 sarcoma) was not affected. B700 is also shown in this study to be unrelated to other known murine tumor antigens, or to murine leukemia virus antigens. It is further shown that mice immunized with B700 produced antibodies specific to B700 that were not cross-reactive with albumins from various mammalian sources.

Low molecular weight dextran and experimental metastasis growth.

AbstractThe effect of low molecular weight dextran (LMD; M 4 × 104) was tested on intravenously‐induced metastases in a syngeneic tumour‐host system in mice. When given as intravenous pretreatment LMD increased the total number of gross extra‐pulmonary metastases, without significantly changing the planimetrically estimated lung and liver metastases. When, on the other hand, the same volume of LMD was given in the cell suspension, there was a further increase in gross extrapulmonary metastases and also in pulmonary metastases.There was an interesting parellelism between these results and the effect of cell and systemic treatment with LMD on the subcutaneous transplantability of tumour cells. Both types of treatment increased the frequency of subcutaneous takes but cell pretreatment with LMD alone increased resulting tumour volumes.The effects of LMD were not reflected in any alteration of the viability index in dye exclusion test or in the aggregability of the tumour cells.