scholarly journals Heterogeneity of circulating tumor cell dissemination and lung metastases in a subcutaneous Lewis lung carcinoma model

2020 ◽  
Vol 11 (7) ◽  
pp. 3633 ◽  
Author(s):  
Jessica E. Fitzgerald ◽  
Brook K. Byrd ◽  
Roshani A. Patil ◽  
Rendall R. Strawbridge ◽  
Scott C. Davis ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lung Metastases ◽  
Circulating Tumor Cell ◽  
Tumor Cell Dissemination ◽  
Lewis Lung ◽  
Lewis Lung Carcinoma Model ◽  
Cell Dissemination

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

1979 ◽  
Vol 65 (6) ◽  
pp. 657-664 ◽  
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.

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

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.

Paracrine Suppression of VEGF Secretion by Erythropoietin Inhibits Tumor Growth.

Blood ◽  
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.

scholarly journals Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

2019 ◽  
Vol 25 (10) ◽  
pp. 1534-1539 ◽  
Author(s):  
Francesca Chemi ◽  
◽  
Dominic G. Rothwell ◽  
Nicholas McGranahan ◽  
Sakshi Gulati ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Resection ◽  
Circulating Tumor Cell ◽  
Tumor Cell Dissemination ◽  
Disease Relapse ◽  
Cell Dissemination

scholarly journals Novel pyrazolopyrimidine derivatives inhibit angiogenesis and tumor growth in a mouse Lewis lung carcinoma model

2015 ◽  
Vol 26 ◽  
pp. ii36 ◽  
Author(s):  
M. Michailidou ◽  
V. Giannouli ◽  
I. Kostakis ◽  
V. Kotsikoris ◽  
P. Marakos ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lewis Lung ◽  
Lewis Lung Carcinoma Model

scholarly journals EFFECT OF DICHLOROACETATE ON LEWIS LUNG CARCINOMA GROWTH AND METASTASIS

2015 ◽  
Vol 37 (2) ◽  
pp. 126-129 ◽  
Author(s):  
D L Kolesnik ◽  
O N Pyaskovskaya ◽  
I V Boychuk ◽  
O I Dasyukevich ◽  
O R Melnikov ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Tumor Tissue ◽  
Control Group ◽  
Lewis Lung ◽  
Antimetastatic Activity ◽  
Apoptosis Level

A hallmark of malignancy is excessive tumor glycolysis, even in the presence of oxygen, which causes lactacidosis in the tumor microenvironment and favors tumor cell proliferation and survival. For this reason antimetabolic agents which target tumor cell metabolism are being researched extensively as promising anticancer drugs. Aim: To study the effect of lactacidosis on survival of Lewis lung carcinoma (LLC) cells at the conditions of nutritional substrate deficiency in vitro and evaluate antitumor and antimetastatic activity against LLC/ R9 in vivo. Materials and Methods: LLC variant LLC/R9 was used as experimental tumor model. Tumor cell viability was determined using trypan blue staining. Apoptosis level was counted with the use of Hoechst 33258 dye. Lactate content in the tumor tissue was evaluated by enzyme method with the use of lactate dehydrogenase. Reactive oxygen species was determined using 2.7-dichlorofluorescein diacetate. Effects of dichloroacetate (DCA) on the growth and metastasis of LLC/R9 were analyzed by routine procedures. Evaluation of DCA effect toward electron-transport chain (ETC) components was performed using EPR. Results: It has been shown that at the conditions of lactacidosis and glucose deficiency, LLC/R9 cell viability in vitro was higher by 30% (р < 0.05) and apoptosis level was triply lower (р < 0.05) than these indices at the conditions of glucose deficiency only. In mice with transplanted LLC/R9 tumors treated for 3 weeks per os with DCA at the total dose of 1.5 g/kg of body weight starting from the next day after tumor transplantation, the primary tumor volume was just by 30% lower than that in control group. At the same time, the number and volume of lung metastases in animals treated with DCA were by 59% (р < 0.05) and 94% (р < 0.05) lower, respectively, than these indices in the control group. DCA treatment resulted in nearly 30% increase (р < 0.05) of lactate content in tumor tissue compared to that in the control, but did not affect significantly the levels of heme iron complexes with NO (at gmed = 2.007) in mitochondrial ETC proteins and Fe-S cluster proteins (at g = 1.94) in tumor cells. Conclusions: It has been shown that lactacidosis significantly promoted LLC/R9 cell survival at the conditions of glucose deficiency in vitro. If LLC/R9 developed in vivo, DCA as the compound with antilactacidosis activity did not suppress significantly the primary tumor growth but exerted significant antimetastatic activity.

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

2015 ◽  
Vol 37 (4) ◽  
pp. 255-261 ◽  
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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