Lewis lung

Biological Activity. The maytansinoids possess antitumor activity, particulady against P 388 lymphocytic leukemia, B 16 melanocarcinoma, and Lewis lung carcinoma. A number of semisynthetic esters of maytansinol have been prepared and exhibit good antileukemic activity (52,255). The maytansides lack antitumor activity, indicating that the ester at C-3 is a requirement for activity (50,52). The carbinolamide also appears to be necessary for... 

Poly(DL-lactide) was used as the excipient in microspheres of CCNU, a nitrosourea, prepared by a solvent evaporation procedure (96,97). PLA-CCNU microspheres 3.0 pm in diameter were injected i.v. and leukemia cell survival was determined by spleen colony assay. A 100-fold decrease in leukemia cell survival was observed with the microspheres in both spleen and liver compared to untreated controls. Promising results were also obtained with Lewis lung carcinoma in mice. These studies showed that 2- to 4-ym microspheres were preferentially targeted to the lungs. 

A cytotoxic alkaloid has been isolated from the filamentous species Hapalosi-phon forUinalis strain V-3-1. This isolate was made from soil samples collected in the Marshall Islands in 1981. This strain produces the lipophilic compound hapalindole A, which has a broad range of antialgal and antimycotic activity (9). OscUlatoria acutissima strain B-1, isolated from a freshwater pond in Oahu, was found to produce two novel macrolide compounds termed acutiphycin and 20, 21-didehydroacutiphycin. These macrolides show cytotoxicity (KB and NIH/3T3) and antitumor activity (Murine Lewis lung carcinoma) (10). 

Tumor inhibition rates in mice with Lewis lung carcinoma as well as sarcoma 180 have also been studied. While 52 displayed inhibition rates of 34.1% and 15.3%, respectively, against these two types of tumors, 56 showed inhibition rates of 42.0% and 37.6% respectively [49]. Nevertheless, such inhibition rates are still less than those observed for known antitumor agent cytophos-phane, which had inhibition rates of 88.6% and 87.5% against these same two tumors. Additionally, both 56 and 57 have been found to be neurotoxic [50]. 

Dibutyltin glycylglycinate 44 (where R = butyl) is the most active organotin complex against p388 leukemia, but is inactive against L1210 leukemia, B16 melanoma, and Lewis lung carcinoma in mice (212). 

Morris et al.66 (U.S.A.) induced Lewis lung carcinoma (LLC) in C57 black mice and subjected them to ECT constant current of 20 mA (which gave rise to 8-10 V as the voltage across the electrodes) was applied for 15 minutes. Animals treated with ECT survived longer and exhibited a small primary tumor burden at death as compared to the control group, although no complete regression of the tumor was observed. It would appear that a... 

Rat mammary tumors Lewis lung cancers Mouse mammary tumors Choriocarcinoma cells Anaplastic sarcomas Walker carcinoma cells Rat prostatic carcinomas Rat embryo fibroblasts Different malignant cells... 

Administration of Certain Proteases to Animals Enhances Metastasis. Administration of specific proteases to animals has been found to stimulate the production of metastasis. For example, in rabbits, administration of uPA has been found to enhance the metastasis of V2 carcinomas (K11), while in mice, exogenous uPA increased pulmonary metastasis from Lewis lung carcinomas (Tl). Also, infusion of thrombin into syngenic mice stimulated pulmonary metastasis from both colon carcinoma cells and melanoma cells (N5). This enhanced formation of metastasis in the presence of thrombin may result from increased tumor cell-platelet interaction in the presence of the protease (N5). 

KI5. Kristensen, P., Pyke, C., Lund, L. R., Andreasen, P. A., and Dano, K., Plasminogen activator inhibitor type-1 in Lewis lung carcinoma. Histochemistry 93, 559-566 (1990). 

Tl. Tanaka, N., Ogawa, H., Tanaka, K., Kingo, M., and Kohga, S., Effects of tranexamic acid and urokinase on hematogenous metastases of Lewis lung carcinoma in mice. Invasion Metastasis I, 149-157 (1991). 

Several bis(dioxopiperazines) exhibit antitumor activity. Thus, ICRF 159 122 is an inhibitor of DNA synthesis, blocks the cell cycle in G2-M phase and inhibits metastases in the Lewis lung tumor (3LL) animal model without impeding the... 

These studies were followed by others that demonstrated the potential for therapeutic enhancement by combined cisplatin-radiation treatments with primary murine bladder cancer (60), EMT-6 mammary tumors and KHT and RIF-1 sarcomas (61), and Lewis lung carcinoma (62). 

O Reilly M, Holmgren L, Shing Y, et al. Angiostatin a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994 79 315-328. 

Anderson IC, Shipp M A, Docherty A, Teicher B A. Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine lewis lung carcinoma. Cancer Res 1996 56 715-718. 

---