scholarly journals Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats

2016 ◽  
Vol Volume 10 ◽  
pp. 2239-2253 ◽  
Author(s):  
Adel El-Shemi ◽  
Osama Kensara ◽  
Amr Mohamed ◽  
Bassem Refaat ◽  
Shakir Idris ◽  
...  
2018 ◽  
Vol 22 (1) ◽  
pp. 30-39
Author(s):  
Francisco Giner ◽  
José A López-Guerrero ◽  
Antonio Fernández-Serra ◽  
Isidro Machado ◽  
Empar Mayordomo-Aranda ◽  
...  

Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm–4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). Results We observed histological, ultrastructural, and immunohistochemical changes in the xenografted tumor at different times after implantation. Chemokine ligand expression peaked twice, once during the first 48 hours and again in the second week. We observed that tumor cells in contact with murine peritumoral stroma presented higher expression of chemokine ligands as well as more tumor cells around the capillary vessels. Mouse serum vascular endothelial growth factor levels peaked twice, once in the first hours and then in the second week after tumor implantation. Conclusion Chemokines and other angiogenic factors may be relevant in the angiogenic mechanism during tumor growth. This model provides information on the early stages of the angiogenic process and could be a useful tool in researching anti-angiogenic drugs for new therapeutic strategies in EWS.


2020 ◽  
Vol 11 (6) ◽  
pp. 4940-4952 ◽  
Author(s):  
Mingyue Song ◽  
Yaqi Lan ◽  
Xian Wu ◽  
Yanhui Han ◽  
Minqi Wang ◽  
...  

The inhibitory effect of dietary 5-demethylnobiletin on colitis-driven colorectal carcinogenesis and the potential roles of its colonic metabolites were reported.


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 619 ◽  
Author(s):  
Arthur T. Kopylov ◽  
Alexander A. Stepanov ◽  
Kristina A. Malsagova ◽  
Deepesh Soni ◽  
Nikolay E. Kushlinsky ◽  
...  

Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.


2009 ◽  
Vol 69 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Patrick Nasarre ◽  
Markus Thomas ◽  
Karoline Kruse ◽  
Iris Helfrich ◽  
Vivien Wolter ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4243
Author(s):  
Marica Cariello ◽  
Elena Piccinin ◽  
Roberta Zerlotin ◽  
Marilidia Piglionica ◽  
Claudia Peres ◽  
...  

Platelets represent the linkage between tissue damage and inflammatory response with a putative role in tumorigenesis. Given the importance of the microenvironment in colon cancer development, we elucidated the eventual role of platelets-cancer cells crosstalk in in vivo colon cancer models. To evaluate the involvement of platelets in intestinal tumorigenesis, we first analyzed if the ablation of β-integrin P-selectin that drives platelets-cell adhesion, would contribute to platelets-colon cancer cell interaction and drive cancer progression. In a xenograft tumor model, we observed that when tumors are inoculated with platelets, the ablation of P-selectin significantly reduced tumor growth compared to control platelets. Furthermore, in genetic models, as well as in chronic colitis-associated colorectal carcinogenesis, P-selectin ablated mice displayed a significant reduction in tumor number and size compared to control mice. Taken together, our data highlights the importance of platelets in the tumor microenvironment for intestinal tumorigenesis. These results support the hypothesis that a strategy aimed to inhibit platelets adhesion to tumor cells are able to block tumor growth and could represent a novel therapeutic approach to colon cancer treatment.


Nutrients ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 202 ◽  
Author(s):  
Kyung-Sook Chung ◽  
Se-Yun Cheon ◽  
Seong-Soo Roh ◽  
Minho Lee ◽  
Hyo-Jin An

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