A preclinical survey on the efficacy of NSC-290205 in combination with doxorubicin (ADR) in Lewis lung carcinoma (LLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17131-17131
Author(s):  
A. Papageorgiou ◽  
E. Stergiou ◽  
I. Boukovinas ◽  
G. Geromichalos ◽  
I. Stergiou
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Maximum Effect ◽  
Base Pairs ◽  
Chop Regimen ◽  
C57bl Mice ◽  
Inhibition Of Tumor Growth ◽  
Reduced Toxicity ◽  
The Right ◽  
Derivatives Of

17131 Background: NSC-290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. Studies on modified steroidal esters of carboxylic derivatives of N,N-bis(2-chloroethyl)aniline, have shown that they exhibit reduced toxicity and increased antitumor activity and specificity. In this study we investigated the antitumor activity of compound A in combination with ADR (AHOP) in comparison with standard CHOP regimen. Methods: C57Bl mice were used for the antitumor evaluation of AHOP/CHOP. Experiments were initiated by implanting the tumor. LLC cells (purchased by NCI, Bethesda, USA) were implanted intramuscularly into the right hind leg as a suspension of 7 × 106 cells in 0.1 ml. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and the oncostatic parameter T/C % according to the protocol of experimental evaluation of antitumor drugs of the NCI, USA. Treatments were given as a single dose (D) on day 1, intermitted dose (D/2 × 3) on days 1, 5, 9 or consecutive dose (D/4 × 9) on days 1 through 9. Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect (p < 0.05 by the Wilkoxon test). AHOP caused the maximum effect inhibiting the tumor growth by 67.7% and T/C values of 270%. CHOP was less effective producing 54.8% tumor inhibition and T/C values of 238%. Conclusions: It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the -NHCO group, combined with ADR, which intercalates between base-pairs, is the explanation for higher activity of AHOP vs. CHOP. This significant effect of NSC-290205 with the anthracycline adriamycin on LLC adds to NSC-290205 advantage for further clinical development. No significant financial relationships to disclose.

Combinatorial treatment with CTO and temozolomide in sc-implanted human LOX 1MVI melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19006-e19006
Author(s):  
Rashida A. Karmali ◽  
Yulia Maxuitenko ◽  
Greg Gorman
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Calcium Influx ◽  
Dependent Inhibition ◽  
Melanoma Model ◽  
Dose Dependent Inhibition ◽  
Inhibition Of Tumor Growth ◽  
Induction Of Apoptosis ◽  
Oxide Synthase ◽  
Dose Dependent

e19006 Background: Carboxyamidotriazole orotate (CTO) is the orotic acid salt of 5-amino-1.(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1, 2, 3-triazole-4-carboxamide. CTO possesses increased solubility. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor –opertated calcium channel- mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, inhibition of FGF-2-induced tyrosine kinase, VEGF-mediated activation of phospholipase Cγ, generation of IP3 and nitric oxide synthase activation, and induction of apoptosis in imatinib mesylate resistant CML cells by downregulating bcr-abl. Methods: Different combinations of CTO and temozolomide (TEM) were first tested in female athymic NCr-nu/nu mice to evaluate tolerance of the combination. The tolerated combinations were then tested to evaluate the antitumor activity against subcutaneously –implanted human LOX 1MVI melanoma xenografts. Results: Oral CTO at doses of 513 or 342 mg/kg/dose Q1Dx14 resulted in inhibition of tumor growth (p<0.001 and p=0.004). Oral TEM at doses of 90 and 60mg/kg/dose Q4Dx3 resulted in dose-dependent inhibition of tumor growth (p<0.001 and p<0.001). Oral CTO at 513 or 342 mg/kg/dose in combination with TEM 90mg/kg/dose resulted in comparable tumor inhibition to TEM alone. However, oral CTO at 513mg/kg/dose in combination with TEM 60mg/kg/dose resulted in additive antitumor activity compared to each drug alone. Also, CTO at 342mg/kg/dose in combination with TEM 60mg/kg/dose had more than additive antitumor activity and was statistically different from the group treated with TEM 60mg/kg/dose alone (p=0.001). Conclusions: These results suggest that CTO enhances the sensitivity of TEM and may permit use of lower doses of TEM to obtain an optimum antitumor effect in combination therapy thus reducing toxicity of high TEM doses in this melanoma model.

Inhibition of tumor growth by poly(ethylene glycol) derivatives of anti-ErbB2 antibodies

2000 ◽  
Vol 49 (4-5) ◽  
pp. 226-234 ◽  
Author(s):  
Esther Hurwitz ◽  
Leah N. Klapper ◽  
Meir Wilchek ◽  
Yosef Yarden ◽  
Michael Sela
Keyword(s):  
Ethylene Glycol ◽  
Tumor Growth ◽  
Poly Ethylene Glycol ◽  
Inhibition Of Tumor Growth ◽  
Poly Ethylene ◽  
Ethylene Glycol Derivatives ◽  
Derivatives Of

scholarly journals Identification of a variant of gross leukemia virus that induces disease in mice inoculated as adults.

1983 ◽  
Vol 158 (2) ◽  
pp. 629-634 ◽  
Author(s):  
J H Wolfe ◽  
K J Blank
Keyword(s):  
Tumor Growth ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Immune Mechanism ◽  
Thymic Lymphoma ◽  
Adult Mice ◽  
C57bl Mice ◽  
Inhibition Of Tumor Growth ◽  
Murine Leukemia

Gross murine leukemia virus normally induces leukemia (thymic lymphoma) in mice inoculated as neonates, but not as adults. We have isolated an apparent variant of this virus which induces thymomas when inoculated i.p. into susceptible adult mice. Using H-2 congenic BALB and C57BL mice, susceptibility to virus-induced thymomagenesis was found to be linked to the H-2 complex. In addition, a radioresistant immune mechanism leading to inhibition of tumor growth was observed in mice with a C57BL but not a BALB background.

Antitumor activity of poly(ethylene glycol)–camptothecin conjugate: The inhibition of tumor growth in vivo

2005 ◽  
Vol 110 (1) ◽  
pp. 90-102 ◽  
Author(s):  
Deshan Yu ◽  
Ping Peng ◽  
Sonia S. Dharap ◽  
Yang Wang ◽  
Mary Mehlig ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Ethylene Glycol ◽  
Tumor Growth ◽  
Poly Ethylene Glycol ◽  
Inhibition Of Tumor Growth ◽  
Poly Ethylene

scholarly journals Further Studies on Cytostatic Activity of Alkoxymethyl Purine and Pyrimidine Acyclonucleosides

1999 ◽  
Vol 54 (11) ◽  
pp. 923-931
Author(s):  
Hanna Modrzejewska ◽  
Marcin Dramiński ◽  
Anna Zgit-Wróblewska ◽  
Janusz Greger
Keyword(s):  
Tumor Growth ◽  
Dna Polymerase ◽  
Amelanotic Melanoma ◽  
Cytostatic Activity ◽  
Tumor Mass ◽  
Reduce Tumor Growth ◽  
Inhibition Of Tumor Growth ◽  
Derivatives Of ◽  
Tumor Dna

The influence of 14 acyclonucleosides1, derivatives of adenine, guanine, uracil and thymine on the phosphorylation of dAdo, dGuo, dCyd and dThd occurring in the cytosol of growing amelanotic melanoma transplanted to Syrian hamsters, as well as on inhibition of tumor growth were studied. From among the studied ACNs eight were tested earlier (Modrzejewska et al., 1996, The influence of alkoxymethyl purine and pyrimidine acyclonucleosides on growth inhibition of Kirkman-Robbins hepatoma and possible mechanism of their cytostatic activity, Z. Naturforch. 51c, 75 - 80 ) ; from among the newly synthesized ACNs, 1,3-N, N-diallyloxymethylthymine (AMT2), 1-N-allyloxymethyl-5,6-tetramethyIeneuracil (AMUTM ), and tested previously 1-N-allyloxymethylthymine (AMT1), administered i.p. in a dose of 0.2 mmol /kg body weight reduce the tumor mass from 0.98 g to 0.64 g ± 0.11 g (i.e. 35% ± 12% ). 48 hours after i.p. administration of the mentioned ACNs in the same dose a reduction of tumor mass is accompanied by the inhibition of dAMP, dGMP and dTM P synthesis. AMT1 inhibits dThd phosphorylation from 6.2 to 4.22; AMT2 suppresses dAdo, dGuo and dThd phosphorylation by, correspondingly, from 2.8 to 1.7, from 10.8 to 7.5 and from 6.2 to 4.2; AMUTM depresses dAMP synthesis from 2.8 to 1.6 (all data: μmol of 2’dNMP formed per mg of protein per min. × 10-4 ). None of the 14 studied acyclonucleosides influences dCMP synthesis. In vivo, after hydration of allyloxymethyl group to hydroxypropoxymethyl residue (having -CH2OH group), AMT1, AMT2 and AMUTM undergo phosphorylation to corresponding triphosphates. Phosphorylated ACNs are not incorporated into tumor DNA, however they inhibit dAdo, dGuo and dThd incorporation into DNA. It is concluded that ACN triphosphates are not substrates for DNA polymerase but, competing with dATP dGTP and dTTP, inhibit incorporation of these 2’dNTP into DNA and, in consequence, reduce tumor growth, which is presumed to be the main mechanism of cytostatic activity of the studied ACNs.

scholarly journals ANTITUMOR ACTIVITY OF SOME DERIVATIVES OF INDOLO[2,3-A]CARBAZOLES N-GLYCOSIDES WITH XYLOSE CARBOHYDRATE RESIDUE

2020 ◽  
Vol 19 (4) ◽  
pp. 86-93
Author(s):  
I. S. Golubeva ◽  
N. P. Yavorskaya ◽  
L. V. Ektova ◽  
M. V. Dmitrieva ◽  
L. M. Borisova ◽  
...  
Keyword(s):  
Nitrogen Atom ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Antitumor Effect ◽  
Breast Adenocarcinoma ◽  
Tumor Growth Inhibition ◽  
Carbohydrate Residue ◽  
National Medical ◽  
Derivatives Of

Introduction. The search for new antineoplastic agents in a series of indolo[2,3-a]-carbazole derivatives is an urgent and promising direction, since compounds with antitumor activity have been found in this class. In the chemical fusion laboratory, N.N. Blokhin National Medical Research Center оf the Ministry of Health of Russia has developed an original and effective method for the synthesis of glycosides of indolo[2,3-a]-pyrrolo[3,4-c]carbazoles, which makes it possible to synthesize derivatives of N-glycosides of indolo[2,3-a]carbazoles with different substituents in the heterocyclic parts including at the maleimide nitrogen atom and with different carbohydrate residues.The purpose of the study – the primary assessment of the antitumor activity of new derivatives of indolocarbazoles with a carbohydrate residue xylose in models of tumor growth mice.Materials and methods. The compounds studied at transplanted tumors of mice: the Lewis epidermoid carcinoma (LLC), colon cancer ACATOL, cervical cancer RSHM-5, breast adenocarcinoma CA-755. Studies were performed on immunocompetent mice: males and females of BDF1 hybrids (C57Bl/6 × DBA/2), females CBA/Lac and Balb/c. Compound solutions were prepared ex tempore and administered to the mice intraperitoneally at a dose of 60 mg/kg daily for five days. The antitumor effect was evaluated as to of tumor growth inhibition and increase of life span of the treated animals as compared with the control ones.Results. Eight compounds studied, containing D-xylose as a carbohydrate component and various substituents at the maleimide nitrogen atom, showed different degrees of antitumor activity. Two derivatives have been identified: N-[5,7-dioxo-12-(β-D-xylopyranosyl)-indole[2,3-a]pyrrolo[3,4-c]carbazol-6-il]benzamide (compound 4) and N-[5,7-dioxo-12-(β-D-xylopyranosyl)-5,7,12,13-tetrahydro-6H-indole[2,3-a]pyrrolo[3,4-c]carbazole-6-il]pyridin-2-carboxamide (compound 8), which showed high antitumor activity on 4 solid tumors of mice with a duration of effect of 12 days or more. The most pronounced antitumor effect was obtained in compounds 4 and 8 in RSHM-5 and Ca-755, tumor growth inhibition was amounted, respectively: in RSHM-5 – 68–82 % and 80–72 %; for Ca-755 – 57–62 % and 86–68 % (p <0.05).Conclusion. For further research, we chose the compound (N-[5,7-dioxo-12-(β-D-xilopiranosil)-5,7,12,13-tetrahydro-6H-indole[2,3-a] pyrrolo[3,4-c]carbazol-6-il]pyridin-2-carboxamide).

scholarly journals Inhibition of tumor growth by interleukin 10 gene transfer in B16(F10) melanoma cells.

1999 ◽  
Vol 46 (4) ◽  
pp. 967-970 ◽  
Author(s):  
S Walos ◽  
J Szary ◽  
S Szala
Keyword(s):  
Gene Transfer ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Interleukin 10 ◽  
Melanoma Cells ◽  
Murine Melanoma ◽  
Immunosuppressive Cytokine ◽  
Inhibition Of Tumor Growth ◽  
Murine Melanoma Cells

Interleukin 10 (IL-10) is a potent immunosuppressive cytokine with an antitumor activity. The effect of IL-10 on tumor growth was tested in murine melanoma cells manipulated by gene transfer to secrete IL-10. In mice bearing B16(F10) tumors expressing IL-10 tumor growth was decreased depending on the amount of secreted IL-10.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Sign in / Sign up

Export Citation Format

Share Document