A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice

Surgery Today ◽  
1993 ◽  
Vol 23 (5) ◽  
pp. 420-423 ◽  
Author(s):  
Toshiharu Furukawa ◽  
Tetsuro Kubota ◽  
Masahiko Watanabe ◽  
Tsong-Hong Kuo ◽  
Hideki Nishibori ◽  
...  
2019 ◽  
Vol 316 (1) ◽  
pp. H245-H254 ◽  
Author(s):  
Ninna C. S. Voss ◽  
Henrik Kold-Petersen ◽  
Ebbe Boedtkjer

Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K+-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.


1990 ◽  
Vol 416 (5) ◽  
pp. 393-396 ◽  
Author(s):  
Koji Sekikawa ◽  
Jan W. Arends ◽  
Kees Verstijnen ◽  
Joop Kate ◽  
Bert Schutte ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1913
Author(s):  
Noëlle Dommann ◽  
Daniel Sánchez-Taltavull ◽  
Linda Eggs ◽  
Fabienne Birrer ◽  
Tess Brodie ◽  
...  

Colorectal cancer, along with its high potential for recurrence and metastasis, is a major health burden. Uncovering proteins and pathways required for tumor cell growth is necessary for the development of novel targeted therapies. Ajuba is a member of the LIM domain family of proteins whose expression is positively associated with numerous cancers. Our data shows that Ajuba is highly expressed in human colon cancer tissue and cell lines. Publicly available data from The Cancer Genome Atlas shows a negative correlation between survival and Ajuba expression in patients with colon cancer. To investigate its function, we transduced SW480 human colon cancer cells, with lentiviral constructs to knockdown or overexpress Ajuba protein. The transcriptome of the modified cell lines was analyzed by RNA sequencing. Among the pathways enriched in the differentially expressed genes, were cell proliferation, migration and differentiation. We confirmed our sequencing data with biological assays; cells depleted of Ajuba were less proliferative, more sensitive to irradiation, migrated less and were less efficient in colony formation. In addition, loss of Ajuba expression decreased the tumor burden in a murine model of colorectal metastasis to the liver. Taken together, our data supports that Ajuba promotes colon cancer growth, migration and metastasis and therefore is a potential candidate for targeted therapy.


Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2522 ◽  
Author(s):  
Sanaz Koosha ◽  
Zahurin Mohamed ◽  
Ajantha Sinniah ◽  
Mohammed A. Alshawsh

Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 518-518
Author(s):  
Luo Cong

518 Background: Anti-angiogenic therapy is an important therapeutic strategy in advanced colorectal cancer. However, the anti-angiogenic drug,such as bevacizumab(avastin) is expensive. So, clarifying whether different doses of avastin play the same effect in vivo is urgently needed. The aim of the study was to observe the different doses of avastin in combination with irinotecan in human colon tumor growth in nude mice and tumor angiogenesis. Methods: 21 nude mice inoculated with DLD-1 human colon cancer cells were randomly divided into four groups: sterile saline control (group A), 5mg/kg avastin plus irinotecan chemotherapy group (group B), 10mg/kg avastin plus irinotecan group (group C), and irinotecan chemotherapy group (group D). Drugs were administered in the first 1,5,9 days, mice were sacrificed in the 10th day after treatment, the tumor growth inhibitory rate was calculated and the tumor microvessel density (MVD) were detected by immunohistochemistry. Results: The tumor inhibition rate in groups B, C, and D were 62.85%, 47.91%, 39.59% respectively. A, B, C, and D groups’ MVD were 7.000 ± 0.71, 4.940 ± 0.58, 5.080 ± 1.25, 5.557 ± 2.04, The MVD in group B and C were significant different compared with group A by Dunnett's test, and the MVD expression difference between D, A groups and B, C groups did not reach statistical significance (P values were 0.086,0.083). Tissue necrosis was found in each group after HE staining of tumor tissue. Among them, the control group, mostly mild to moderate necrosis, and the necrosis area were increased after drug treatment. But there were no statistical differences of the necrotic area in drug treated groups graded by rank sum test (χ2 = 4.73, P = 0.193). And cell apoptosis was obviously seen in treated groups. Conclusions: Different doses of avastin with irinotecan inhibited the tumor growth on DLD-1 xenografted nude mice, Synergistic effects were observed in combination therapy, From cell morphology changes after staining with HE, we speculated that the mechanism may be related to the inhibition of tumor angiogenesis, and cell apoptosis increasing. The effect of 5mg/kg and 10mg/kg bevacizumab on tumor volume and MVD had no significant differences.


2018 ◽  
Author(s):  
Pornsuda Maraming ◽  
Sompong Klaynongsruang ◽  
Patcharee Boonsiri ◽  
Surachai Maijaroen ◽  
Sakda Daduang ◽  
...  

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