Impact of organotin compounds on the growth of epidermoid Lewis carcinoma

Introduction: Search for new compounds with a broad antitumor and antimetastatic potency due to multiple targeting remains important in medicinal chemistry, pharmacology and oncology. We report the efficacy of hybrid organotin agents bis-(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Ме3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Ме5). Materials and methods: The compounds were administered to mice bearing the spontaneously metastatic epidermoid Lewis lung carcinoma (LLC). The efficacy of the treatment was evaluated by mean life span, percentage of tumor growth inhibition, number of lung metastases, frequency of metastasis, tumor weight 21 days after tumor cell inoculation, and a degree of lung damage according to the method of D. Tarin and J.E. Price. Results and discussion: For new organotin compounds containing an antioxidant protective fragment of 2,6-di-tert-butylphenol, moderate antitumor and pronounced antimetastatic effects were revealed in the Lewis model of epidermoid lung carcinoma; more active for Me5. Some features of the development of the process of metastasis were recorded with the introduction of various doses of hybrid organotin compounds. Conclusion: Substances Ме3 and Ме5 possess specific activity on the model under investigation, which allows one to suggest these organotins as promising series of antitumor and antimetastatic agents with multiple targeting mode of action.

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

Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук ◽

10.12737/23406 ◽

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.

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In Vitro and in Vivo Selection of two Lewis Lung Carcinoma Cell Lines

Tumori Journal ◽

10.1177/030089167906500601 ◽

1979 ◽

Vol 65 (6) ◽

pp. 657-664 ◽

Cited By ~ 15

Author(s):

Ada Sacchi ◽

Anna Corsi ◽

Marco Caputo ◽

Gabriella Zupi

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lung Metastases ◽

Tumor Cell Lines ◽

Lewis Lung ◽

Selection Of

Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD 50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.

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Effect of Warfarin, Warfarin Enantiomers and Defibrase on Lewis Lung Carcinoma Metastasis Growth in Mice

10.1055/s-0039-1682748 ◽

1977 ◽

Author(s):

M.B. Donati ◽

A. Poggi ◽

L. Mussoni ◽

L. Kornblihtt ◽

G.de Gaetano ◽

...

Keyword(s):

Lung Carcinoma ◽

Primary Tumor ◽

Lewis Lung Carcinoma ◽

Lung Metastases ◽

Tumor Development ◽

Surgical Removal ◽

Lewis Lung ◽

Complex Activity ◽

Metastasis Growth ◽

Warfarin Enantiomers

The Lewis Lung Carcinoma (3LL) is a spontaneously metastasizing tumor, the development of which is eccompanied by marked hemostatic changes. Acceleration of labelled fibrinogen turnover and fibrin accumulation at the tumor and metastasis sites have been observed in 3LL bearing mice. Both the number and the weight of lung metastases were significantly lower in mice anti-coagulated with racemic sodium warfarin during the whole tumor development period (prothrombin complex activity around 20%). This treatment had less effect on the primary tumor. The anti-metastatic effect was slightly greater with larger doses of warfarin, which lowered the prothrombin complex activity to less than 5%. Continuous anticoagulation also protected the animals from pulmonary growth of blood-borne tumor emboli following intravenous injection of 3LL cells. This effect appeared to be closely associated with the anticoagulant activity of warfarin; indeed experiments performed with the resolved warfarin enantiomers showed that R-warfarin had virtually no anticlotting activity in mice and did not modify the metastatic growth of 3LL cells; the opposite was true for S-warfarin.Lung metastasis growth was increased in mice kept defibrinogenated during the whole period of tumor development by treatment with batrcxobin; in contrast, in mice kept defibrinated only during the period of metastasis growth, with or without surgical removal of the primary tumor, metastasis formation was slightly decreased. This suggests that fibrin may play different roles in various phases of metastaticspreading of the same tumor.

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Paracrine Suppression of VEGF Secretion by Erythropoietin Inhibits Tumor Growth.

Blood ◽

10.1182/blood.v110.11.3909.3909 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3909-3909

Author(s):

Carroll R. Smith ◽

Kenneth J. Salleng ◽

Vaia Y. Sigounas ◽

Adam Asch ◽

George Sigounas

Keyword(s):

Tumor Growth ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lung Metastases ◽

Control Group ◽

Lewis Lung ◽

Average Volume ◽

Primary Tumors ◽

Significant Difference

Abstract Several studies have reported that erythropoietin (Epo) is a pleiotropic cytokine with biological properties in addition to its primary function in regulating maturation, growth and survival along the erythroid lineage. Recently, a number of investigators have reported that various neoplastic tissues and human cancer cell lines express Epo and the Epo receptor (EpoR), raising suspicion for the presence of an autocrine-paracrine Epo-EpoR system. It has been shown that inhibition of vascular endothelial growth factor (VEGF) results in an increase of Epo secretion and increased hematocrit in vivo. In this study, we used an in vivo Lewis lung carcinoma model to examine a converse Epo effect on VEGF production and metastasis. Lewis lung carcinoma (LLC) cells were injected subcutaneously into C57BL mice. The plasma levels of VEGF, the tumor vessel formation, the size of the primary tumors and the extent of lung metastatic disease were determined. In addition, intravenously injected LLC cells seeded in the lungs were assessed. Tumor-bearing animals treated with Epo had 23.6% less VEGF in the plasma compared to saline treated mice (p<0.04). There was no correlation between VEGF concentration and hemoglobin levels in either group of animals. Tumor sections indicated that the number of blood vessels was higher (10.7% for inner and 23.8% for outer, respectively) in tumors obtained from animals treated with saline compared to Epo-treated mice (p>0.05). Using non-parametric analysis, we found that there was a statistically significant difference in tumor growth between saline-treated and Epo-treated animals (p<0.05). However, the number of lung metastases derived from primary tumors was similar in both groups. In assessing size of the metastatic tumors, we found that the average volume of lung nodules was 24.2% higher in saline-injected animals compared to Epo-treated mice. The number of tumors seeded in the lungs following intravenous injection of LLC cells was similar in animals treated with a high dosage of Epo, low dosage of Epo or saline. In addition, the average volume of the nodules was reduced by 42% in animals treated with high and low concentrations of Epo compared to the control group (p = 0.03). In conclusion, Epo exerts a paracrine suppressive effect on VEGF secretion resulting in slower tumor growth in this model.

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EFFECT OF ENTEROSORPTION ON PARANEOPLASTIC SYNDROME MANIFESTATIONS IN MICE WITH HIGHLY ANGIOGENIC VARIANT OF LEWIS LUNG CARCINOMA

Experimental Oncology ◽

10.31768/2312-8852.2015.37(4):255-261 ◽

2015 ◽

Vol 37 (4) ◽

pp. 255-261 ◽

Cited By ~ 1

Author(s):

V V Sarnatskaya ◽

V G Nikolaev ◽

L A Yushko ◽

L M Paziuk ◽

O M Karaman ◽

...

Keyword(s):

Lung Carcinoma ◽

Paraneoplastic Syndrome ◽

Peripheral Blood ◽

Lewis Lung Carcinoma ◽

Lung Metastases ◽

Morphological Structure ◽

Histological Structure ◽

Lewis Lung ◽

Morphological Examination ◽

Biochemical Indices

Aim: To study the correcting effects of microgranulated HSGD enterosorbent on hematological, morphological and biochemical indices of paraneoplastic syndrome in mice with highly angiogenic variant of Lewis lung carcinoma LLC/R9. Methods: The study was performed on male С57/ВL6 mice with transplanted LLC/R9. Enterosorbent HSGD was administered daily at a dose of 0.625 g/kg for 2 weeks starting from 7th day after tumor cell transplantation. When enterosorption was completed, an analysis of peripheral blood, biochemical indices and morphological structure of tumor, lung, liver, spleen and thymus was carried out by standard methods. Results: It has been shown that administration of enterosorbent did not affect LLC/R9 growth but resulted in nearly two fold decrease of the volume of lung metastases (p < 0.05). Erythrocyte number and hemoglobin level were higher by 30.0% (p < 0.05) and 23.3% (p < 0.05), respectively, in mice treated with enterosorbents as compared to untreated animals. In addition sorbent treatment completely normalized the thrombocyte index resulting in elevation of platelet number by 54.5% (p < 0.01) up to their level in intact mice. The morphological examination of liver and biochemical analysis of peripheral blood evidenced on significant positive correcting effect of enterosorption on histological structure of this organ and its functional activ ity. Normalization of total proteins and serum albumin level as well as significant decrease of total lipid concentration by 29% (p < 0.01) in blood of treated mice were observed. Conclusion: Positive influence of microgranulated carbon sorbent on some hematological, morphological and biochemical indices of tumor associated symptoms in LLC/R9-bearing mice denotes that enterosorption-based therapy can be considered as a prospective treatment for correction of some paraneoplastic syndrome signs in cancer patients.

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