scholarly journals EFFECTS OF 5-HYDROXYPYRIMIDINE DERIVATIVE ON GROWTH AND METASTASIS OF MELANOMA B16 IN C57BL/6 MICE

2021 ◽  
Vol 20 (3) ◽  
pp. 66-72
Author(s):  
R. V. Zhurikov ◽  
L. P. Kovalenko ◽  
S. V. Nikitin ◽  
A. D. Durnev
Keyword(s):  
Tumor Growth ◽  
Single Injection ◽  
Tumor Development ◽  
Positive Control ◽  
Significant Inhibition ◽  
Tumor Growth Inhibition ◽  
Antimetastatic Activity ◽  
Melanoma B16 ◽  
Melanoma Model ◽  
Inhibition Of Tumor Growth

Introduction. Suppression of activation of an alternative immune response is promising approach of tumor immunotherapy. In this study we evaluated antitumor and antimetastatic activity of SNK-411.Objective. Evaluation of antitumor and antimetastatic activity of 5-hydroxypyrimidine derivative SNK-411 in mouse melanoma B16 model.Materials and methods. Antitumor and antimetastatic activity of the SNK-411 were studied in tests on male C57BL/6 mice using the B16-F10 melanoma model. SNK-411 was injected intraperitoneally at doses of 10 and 25 mg/kg from day 2 to day 15 of melanoma development. Doxorubicin was injected at dose of 4 mg/kg on day 2 of tumor development to act as positive control. Antitumor and antimetastatic activity were studied by calculation of tumor growth inhibition and metastasis inhibition index (MII).Results. SNK-411 at doses of 10 and 25 mg/kg and in combination with single injection of doxorubicin in dose of 4 mg/kg showed antimetastatic activity. MII in SNK-411 at 10 mg/kg dose was 72 %, at dose of 25 mg/kg was 82,9 %. The combination of 14-day course of intraperitoneal injections of SNK-411 at dose of 10 mg/kg and injection of doxorubicin 4 mg/kg revealed MII 97,1 %, in half of mice in this group metastasis were not observed on 21st day of melanoma development. All results are statistically significant. There was no significant inhibition of tumor growth in all groups.Conclusion. SNK-411 has antimetastatic activity in tests on melanoma B16 model. Further investigation is required. 

scholarly journals new bIologIcal model of moderate InhIbItIon of tumor and metastases growth wIth prolonged leukopenIa In mIce

2016 ◽  
Vol 1 (5) ◽  
pp. 121-125
Author(s):  
Зуева ◽  
Elena Zueva ◽  
Разина ◽  
Tatyana Razina ◽  
Ермакова ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Tumor Therapy ◽  
Biological Model ◽  
Tumor Growth Inhibition ◽  
Lewis Lung ◽  
Inhibition Of Tumor Growth ◽  
Toxic Manifestation ◽  
Cyclophosphamide Dose

A new biological model of moderate inhibition of tumor growth and metastases with prolonged leukopenia on C57Bl/6 mice with the Lewis Lung Carcinoma was designed. The model was created by the injection of cyclophosphamide (dose 83.3mg/kg) on 6th, 12th, 18th days after tumor cells transplantation on animals. Experiment showed that 3-fold cyclo-phosphamide use leads to growth of primary tumor and metastases inhibition. Tumor growth inhibition was 34% on 21st day after cyclophosphamide inject. The number of metastases decreased by 4.7times (p<0,01). Metastatic area reduced. Metastasis frequency made 100%. In addition, the course of cyclophosphamide application caused inhibition of granulocytic and lymphoid hematopoiesis. The reducing the number of segmented neutrophils and lymphocytes was showed on the 3rd day after 1, 2 and 3 injections of cyclophosphamide. The model can be used to study the efficacy of drugs in tumor therapy and in correction of such toxic manifestation of chemotherapy as leukopenia.

The effect of monotherapy and combined therapy with NSC-631570 (Ukrain) on growth of low- and high-metastasizing B16 melanoma in mice

2010 ◽  
Vol 17 (4) ◽  
pp. 339-349 ◽  
Author(s):  
LM Skivka ◽  
YaM Susak ◽  
OO Trompak ◽  
YuI Kudryavets ◽  
N Bezdeneznikh ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Combined Therapy ◽  
Tumor Growth Inhibition ◽  
Cell Cycle Distribution ◽  
Colorimetric Determination ◽  
Chelidonium Majus ◽  
Melanoma B16

Background. NSC-631570 (Ukrain) is a semisynthetic derivative of the Chelidonium majus alcaloids and the alkylans thiotepa. It exerts a selective cytotoxic effect on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte functions. Purpose. The aim of our work was to carry out a comparative investigation of the effects of NSC-631570 alone or in combination with pathogen-associated molecules (PAM) on the growth of low- and high-metastasizing melanoma B16 in mice. Methods. NSC-631570 was administered intravenously and PAM intramuscularly to tumor-bearing mice seven times every third day, starting from the second day after the transplantation of tumor cells. The effect of monotherapy and combined therapy on tumor growth was evaluated by the indices of tumor growth inhibition in experimental animals. Cell cycle distribution of cancer cells was determined by flow cytometry. TAP1 and TAP2 expression was evaluated by RT-PCR. The metabolic activity of phagocytes was determined by NBT-test, phagocytosis was tested by flow cytometry, and arginase activity was estimated by colorimetric determination of urea. Results. Combined therapy and monotherapy with NSC-631570 resulted in significant inhibition of tumor growth in melanoma-bearing mice. Monotherapy with Ukrain was more effective in mice with high-metastasizing tumors. The therapeutic efficacy of NSC-631570 used in combination with PAM was more expressed in mice with low-metastasizing melanoma. Conclusion. The effectiveness of monotherapy and combined therapy with NSC-631570 in the treatment of melanoma B16 depends on the biological properties of the tumor and the immune state of the organism.

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.

scholarly journals Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity

2016 ◽  
Vol 113 (44) ◽  
pp. 12532-12537 ◽  
Author(s):  
Madelon Q. Wentink ◽  
Tilman M. Hackeng ◽  
Sebastien P. Tabruyn ◽  
Wouter C. Puijk ◽  
Klaus Schwamborn ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Binding Site ◽  
3D Structure ◽  
Neutralizing Antibody ◽  
Cd Spectroscopy ◽  
Significant Inhibition ◽  
Surface Plasmon Resonance Analysis ◽  
Signaling Axis ◽  
Melanoma Model ◽  
Neutralizing Monoclonal Antibody

Therapeutic targeting of the VEGF signaling axis by the VEGF-neutralizing monoclonal antibody bevacizumab has clearly demonstrated clinical benefit in cancer patients. To improve this strategy using a polyclonal approach, we developed a vaccine targeting VEGF using 3D-structured peptides that mimic the bevacizumab binding site. An in-depth study on peptide optimization showed that the antigen’s 3D structure is essential to achieve neutralizing antibody responses. Peptide 1 adopts a clear secondary, native-like structure, including the typical cysteine-knot fold, as evidenced by CD spectroscopy. Binding and competition studies with bevacizumab in ELISA and surface plasmon resonance analysis revealed that peptide 1 represents the complete bevacizumab binding site, including the hairpin loop (β5–turn–β6) and the structure-supporting β2–α2–β3 loop. Vaccination with peptide 1 elicited high titers of cross-reactive antibodies to VEGF, with potent neutralizing activity. Moreover, vaccination-induced antisera displayed strong angiostatic and tumor-growth-inhibiting properties in a preclinical mouse model for colorectal carcinoma, whereas antibodies raised with peptides exclusively encompassing the β5–turn–β6 loop (peptides 15 and 20) did not. Immunization with peptide 1 or 7 (murine analog of 1) in combination with the potent adjuvant raffinose fatty acid sulfate ester (RFASE) showed significant inhibition of tumor growth in the B16F10 murine melanoma model. Based on these data, we conclude that this vaccination technology, which is currently being investigated in a phase I clinical trial (NCT02237638), can potentially outperform currently applied anti-VEGF therapeutics.

scholarly journals Significant Inhibition of Tumor Growth following Single Dose Nanoparticle-Enhanced Photodynamic Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shih-Hsun Cheng ◽  
Chia-Hui Chu ◽  
Nai-Tzu Chen ◽  
Jeffrey S. Souris ◽  
Chin-Tu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Human Breast Cancer ◽  
Significant Inhibition ◽  
Oxygen Species ◽  
Human Breast ◽  
Apoptotic Response ◽  
Inhibition Of Tumor Growth

Photodynamic therapy (PDT) for cancer treatment involves the pathology’s uptake of photosensitizers, which produce cytotoxic reactive oxygen species by photoirradiation. The use of nanoparticles as carriers of photosensitizers is one promising approach to this endeavor, owing to their small size, unique physicochemical properties, and easy/diverse functionalization. In the current work, we report on thein vivoassessment of PDT efficacy of these nanoconstructs in a murine model of human breast cancer, following a single (one-shot) nanoparticle dose and photoirradiation. Palladium-porphyrin (PdTPP) was administered intratumorally via injection of aqueous suspensions of either free PdTPP or MSN-conjugated PdTPP (MSN-PdTPP) at a dose of 50 μg. Mice were then exposed to a single photoirradiation session with total energy of 80 J. One month after one-shot PDT treatment, significantly greater reductions in tumor growth were observed in MSN-Pd treated animals than in PdTPP cohorts. Electron microscopy of tumor specimens harvested at various timepoints revealed excellent MSN-PdTPP uptake by cancer cells while immunohistologic analysis demonstrated marked increases in apoptotic response of MSN-PdTPP treated animals relative to PdTPP controls. Taken together, these findings suggest that considerable improvements in PDT efficacy can readily be achieved via the use of nanoparticle-based photosensitizers.

scholarly journals A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4853-4862 ◽  
Author(s):  
Helene Pere ◽  
Yves Montier ◽  
Jagadeesh Bayry ◽  
Francoise Quintin-Colonna ◽  
Nathalie Merillon ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Hematologic Malignancies ◽  
Clinical Development ◽  
Peripheral Tolerance ◽  
Tumor Growth Inhibition ◽  
Inhibition Of Tumor Growth ◽  
Therapeutic Settings ◽  
Small Chemical

Abstract Regulatory T cells (Tregs) may impede cancer vaccine efficacy in hematologic malignancies and cancer. CCR4 antagonists, an emergent class of Treg inhibitor, have been shown to block recruitment of Tregs mediated by CCL22 and CCL17. Our aim was to demonstrate the ability of a CCR4 antagonist (a small chemical molecule identified in silico) when combined with vaccines to break peripheral tolerance controlled by Tregs, a prerequisite for the induction of CD8+ T cells against self Ags. Immunization of transgenic or normal mice expressing tumor-associated self Ags (Her2/neu, OVA, gp100) with a CCR4 antagonist combined with various vaccines led to the induction of effector CD8+ T cells and partial inhibition of tumor growth expressing self Ags in both prophylactic and therapeutic settings. The CCR4 antagonist was more efficient than cyclophosphamide to elicit anti-self CD8+ T cells. We also showed that the population of Tregs expressing CCR4 corresponded to memory (CD44high) and activated (ICOS+) Tregs, an important population to be targeted to modulate Treg activity. CCR4 antagonist represents a competitive class of Treg inhibitor able to induce functional anti-self CD8+ T cells and tumor growth inhibition when combined with vaccines. High expression of CCR4 on human Tregs also supports the clinical development of this strategy.

Combined treatment with the 5 alpha-reductase inhibitor PNU 157706 and the antiandrogen flutamide on the Dunning R3327 prostatic carcinoma in rats.

1999 ◽  
pp. 429-435 ◽  
Author(s):  
T Zaccheo ◽  
D Giudici ◽  
E di Salle
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Prostatic Carcinoma ◽  
Reductase Inhibitor ◽  
Combined Treatment ◽  
Ventral Prostate ◽  
Tumor Growth Inhibition ◽  
Concomitant Treatment ◽  
Inhibition Of Tumor Growth ◽  
Prostatic Tumor

The steroid 5 alpha-reductase enzyme catalyzes the conversion of testosterone to the potent androgen 5 alpha-dihydrotestosterone (DHT). PNU 157706, a novel, potent and selective dual 5 alpha-reductase inhibitor, was reported to be effective in inhibiting the growth of established tumors in the Dunning R3327 rat prostatic carcinoma model. We have studied the efficacy of combined treatment with PNU 157706 and the antiandrogen flutamide in this prostatic tumor in rats. Rats with tumor diameters of about 1 cm were treated orally 6 days a week for 9 weeks with PNU 157706 (10 mg/kg per day) alone or in combination with flutamide (1 and 5 mg/kg per day). Animals were killed 24 h after the last treatment and ventral prostates were removed for testosterone and DHT determination. PNU 157706 reduced the growth of established tumors by 36%; flutamide showed a slight effect at 1 mg/kg per day (24% inhibition), while at the dose of 5 mg/kg per day it reduced tumor growth by 48%. The combination of PNU 157706 with the lower dose of flutamide caused an additive tumor growth inhibition (60%) and the combination with the higher dose of flutamide resulted in a better inhibition of tumor growth (68%) than did either treatment alone. Castration resulted in marked tumor growth inhibition (76%). Ventral prostate weight was more markedly reduced by PNU 157706 treatment than by flutamide; combined treatment was as effective as castration. Prostatic DHT content was markedly reduced by PNU 157706 (93%), whereas prostatic testosterone increased (137%). Concomitant treatment with flutamide partially antagonized the testosterone increase induced by PNU 157706 and did not modify the already considerable suppression of DHT. These data show that the inhibitory effects of PNU 157706 and flutamide on Dunning prostatic tumor growth are additive, thus supporting the rationale of this combination therapy in advanced prostate cancer, in order to achieve adequate androgen blockade with minimal side-effects.

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