scholarly journals Antitumor Activity of Ficus deltoidea Extract on Oral Cancer: An In Vivo Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
May Al-koshab ◽  
Aied M. Alabsi ◽  
Marina Mohd Bakri ◽  
Rola Ali-Saeed ◽  
Manimalar Selvi Naicker
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Oral Cancer ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Cellular Adhesion ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Mesenchymal Transition ◽  
Ficus Deltoidea

Background. The aim of this study is to evaluate the chemopreventive and chemotherapeutic activities of Ficus deltoidea (FD) in an animal model induced for oral cancer using 4-nitroquinoline-1-oxide (4NQO). Methods. Male Sprague-Dawley (SD) rats were randomized into six groups (n = 7 per group): Group 1 (untreated group); Group 2 (control cancer group) received 4NQO only for 8 weeks in their drinking water; Groups 3 and 4 (chemopreventive) received 4NQO for 8 weeks and were simultaneously treated with FD extract at 250 and 500 mg/kg, respectively, by oral gavage; Groups 5 and 6 (chemotherapeutic) received 4NQO for 8 weeks followed by the administration of FD extract at 250 and 500 mg/kg, respectively, for another 10 weeks. The incidence of oral cancer was microscopically evaluated. Moreover, immunohistochemical expression was analysed in tongue specimens using an image analyser computer system, while the RT2 profiler PCR array method was employed for gene expression analysis. Results. The results of the present study showed a beneficial regression effect of the FD extract on tumor progression. The FD extract significantly reduced the incidence of oral squamous cell carcinoma (OSCC) from 100% to 14.3% in the high-dose groups. The immunohistochemical analysis showed that the FD extract had significantly decreased the expression of the key tumor marker cyclin D1 and had significantly increased the expression of the β-catenin and e-cadherin antibodies that are associated with enhanced cellular adhesion. Based on the gene expression analysis, FD extract had reduced the expression of the TWIST1 and RAC1 genes associated with epithelial-mesenchymal transition (EMT) and had significantly downregulated the COX-2 and EGFR genes associated with cancer angiogenesis, metastasis, and chemoresistance. Our data suggest that the FD extract exerts chemopreventive and chemotherapeutic activities in an animal model induced for oral cancer using 4NQO, thus having the potential to be developed as chemopreventive and chemotherapeutic agents.

scholarly journals Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lydia Ntari ◽  
Christoforos Nikolaou ◽  
Ksanthi Kranidioti ◽  
Dimitra Papadopoulou ◽  
Eleni Christodoulou-Vafeiadou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Therapeutic Effect ◽  
Expression Analysis ◽  
Mode Of Action ◽  
Gene Expression Analysis ◽  
Kinase Inhibitors ◽  
High Dose ◽  
Dependent Manner ◽  
Combination Therapies ◽  
Number Of Patients

Abstract Background New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients. Methods We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy. Results Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy. Conclusion Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.

Microarray-based gene expression analysis of an animal model for closed head injury

Injury ◽  
2012 ◽  
Vol 43 (8) ◽  
pp. 1264-1270 ◽  
Author(s):  
T. Colak ◽  
N. Cine ◽  
B. Bamac ◽  
O. Kurtas ◽  
A. Ozbek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
Head Injury ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Closed Head Injury ◽  
Closed Head

scholarly journals ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aline Simoneti Fonseca ◽  
Anelisa Ramão ◽  
Matheus Carvalho Bürger ◽  
Jorge Estefano Santana de Souza ◽  
Dalila Lucíola Zanette ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Sequencing ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Sequencing Analysis ◽  
Microarray Gene Expression ◽  
Mesenchymal Transition ◽  
Paired Samples

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. Methods Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. Results Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples. Conclusion Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

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