Meth 1 tumor cells

The increased expression of adhesion molecules by the endothelium may activate polymorphonuclear neutrophils (PMN) in rabbits [72], During endotoxic shock, activated PMNs release their granule content and secrete both proinflammatory and cytotoxic molecules. Pickaver et al. [73] were the first to show PMN cytotoxicity against tumor cells. We showed that PMNs are toxic for PROb colon tumor cells [74] in BDEX rats. In vivo, PMNs have been implicated in the Schwartzman reaction [75], and may be involved in LPS-induced tumor necrosis. PMNs, when activated by LPS, synthesize and release NO. The role of NO in tumor growth will be discussed later. The decrease in tumor growth after intradermal injections of LPS is attributed to the induction of TNF-a secretion by PMNs both in intradermal tumors (Meth A sarcoma in BALB/c mice, MH-134 hepatoma in C3H/He mice, Lewis Lung carcinomas in C57BL/6 mice) and pulmonary Meth A metastases [76,77],... 

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

Another structurally related series is the 2-ary 1-1,8-naphthyridin-4-ones (37 to 48, see Table 6.7), which contain a second nitrogen in the aromatic A ring. Compounds with meta-substituted phenyls (methoxy-, chloro-, or fluoro-) or a-naphthyl groups at the C-2 position showed potent cytotoxicity in the NCI 60 human tumor cell line panel with GI50 values in the low micromolar to nanomolar range (Tables 6.7 and 6.8).51 The tumor cell line selectivity varies with the various substituents. 2-(3 -Methoxyphenyl)-naphthyridinone (37) was significantly more cytotoxic in several cancer cell lines than the corresponding 2-(3 -meth-oxyphenyl)-quinolone (36). Both compound classes were potent inhibitors of tubulin polymerization the 2-ary 1-1,8-naphthyridin-4-ones had activity nearly comparable with those... 

CVS displayed a strong antitumor effect against experimental metastasis induced by i.v. tumor rechallenging, Fig. (6)-Protocol B. BALB/c mice were inoculated s.c. with Meth A tumor cells in the right flank on day 0 and rechallenged intravenously with the same tumor on day 9 or 58. The primary tumor was removed on day 11. A significant dose-dependent increase in survival rate was observed when CVS was injected i.t once on day... 

BALB/c mice were injected s.c. with 1 x 10 Meth A cells into the right flank on day 0 and i.v. rechallenged on day 9. The primary tumor was removed on day 11. CVS (50 mg/kg) was injected i.t into the primary tumor on day 3. Subcutaneous injections of CVS (150 mg/kg) were started from day 5. Metastatic foci and lung weight were measured on day 23 (14 days after the rechallenge tumor inoculation). Number of metastatic foci was evaluated as metastatic index (MI 0 no me-... 

We evaluated delayed hypersensitivity to examine the participation of CVS administration on the cellular immunity to Meth A tumor antigens according to the delayed footpad reaction (DFR) [48] in the tumor i.v. rechallenge system. On day 9, 16, or 23, a quantity of 5 x 10 mitomycin C-treated Meth A cells in 0.05 ml PBS were injected into the right hind footpad of each BALB/c mouse. PBS injected into the left hind footpad... 

Fig. (8). Increased infiltration of CD3, CD4 and CDS positive cells into the s.c. rechallenge tumor following CVS treatment [44]. BALB/c mice were injected s.c. with 5 x lCr Meth A cells in the right and left flanks on day 0 and 9, respectively. CVS (50 mg/kg) (B,D,F,H) or PBS (A,C,E,G)was injected i.t. into the primary tumor 3 times every 2 days from day 2. Recnallenge tumor sections, including subcutaneous tissues, were obtained 2 days after tumor rechallenge and stained with hematoxylin-eosin (A,B) or immunohistochemically (C-H). a Subcutaneous muscle layer, b interstitial space, c tumor tissue.

Fig. (13). Effect of a combination of CVS and 5FU on body weight (A) and tumor growth (B) in tumor bearing mice. All mice were inoculated s.c. with 5x10° Meth A tumor cells on day 0. CVS was injected s.c. near the tumor on day 1,3,6,8,11 and 13. 5FU was treated i.p. at a dose of 250 mg/kg on day 14. Solid line means 5FU-nontreated, and dotted line means 5FU-treated mice ( ) means CVS-noninjected and (o) means CVS-injected mice.

Pereira S, Maruyama H, Siegel D, Van Belle P, Elder D, Curtis P, Herlyn D, A model system for detection and isolation of a tumor cell surface antigen using antibody phage display, J. Immunol. Meth., 203(l) ll-24, 1997. 

Adnane L, Trail PA, Taylor I, Wilhelm SM. Sorafenib (BAY 43-9006, Nexavar((R))), a dual-action inhibitor that targets RAF/ MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/ PDGFR in tumor vasculature. Meth.Enzymol. 2005 407 597-612. 

Methylcholanthrene-induced (Meth-A) mouse tumor cells grown in an astaxanthin-supplemented medium had reduced cell numbers and lower DNA synthesis rates 1 to 2 days postincubation than control cultures. Similarly, astaxanthin inhibited murine... 

Sun, S. et al.. Anti-tumor activity of astaxanthin on Meth-A tumor cells and its mode of action, FASEBJ., 12,A966,1998. 

Mice and Tumor Type. Female BALB/c mice, weighing 20 g were used. The Meth-A fibrosarcoma used was maintained in our laboratory in an ascitic form. Tumor cells (2.7 x 10 cells/animal) suspended in Hanks balanced salt solution (Gibco) were implanted intraperitoneally into mice. 

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