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BackgroundCancer is a life-threatening disease that affects approximately 18 million individuals worldwide. Breast cancer is the most common female neoplasm globally with more than 276,480 new cases of invasive breast cancer expected to be diagnosed in women in the U.S. alone in 2020. Genetic and epigenetic factors play role in the carcinogenesis and progression of this disease. In this study, MCF-7 adenocarcinoma cells were transfected with CRISPR/Cas9 plasmid to either knock out CDK11 or to activate CDH1. Treated cells were allografted into the mammary glands of female rats (150–190 g, 6–8 weeks) to evaluate the capability of these cells to control cancer progression and metastasis.ResultsqPCR data revealed a significant downregulation of CDK11 and upregulation of CDH1. Cell cycle analysis and apoptosis assays indicated the knockout of CDK11 and simultaneous activation of CDH1 resulted in cell cycle arrest at G2/M phase and accumulation of cells at G2. Meanwhile, the percentage of cells that underwent late apoptosis increased in both genome editing hits. Histopathological sectioning data indicated that untransfected MCF-7 cells were capable of developing tumors in the mammary gland and initiation g angiogenesis. Transfected cells significantly restricted cancer cell infiltration/invasion by minimally localizing tumors and inhibiting angiogenesis.ConclusionsAlthough further investigation is needed, the present data indicate the potentiality of using CRISPR/Cas9-based therapy as a promising approach to treat breast cancer. Impact: these data indicate targeting cancer-related genes via any genome editing tool might represent a novel approach to combat cancer.How to cite: Al-Mulhim F, Alqosaibi AI, Al-Muhnna A, et al. CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.06.002 相似文献
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BackgroundButyrate is a histone deacetylase inhibitor that induces apoptosis and inhibits cell proliferation of colorectal cancer cells. To improve its anticancer activity, butyrate has been evaluated mixed with drugs and different molecules. Plant antimicrobial peptides are attractive anticancer alternative molecules because they show selective cytotoxic activity against different cancer cell lines. In this work, we explore if the plant defensin γ-thionin (Capsicum chinense) can improve butyrate activity on Caco-2 cell line and we also determined the mechanism of death activated.ResultsThe combined treatment of γ-thionin (3.5 µM) and butyrate (50 mM) showed higher cytotoxicity on Caco-2 cells with respect to single treatments. Also, the combined treatment reduced cell proliferation and exhibited a higher rate of apoptosis than single treatments. Combined treatment induced caspases 8 and 9 activation to an extent comparable with that of butyrate while γ-thionin did not activate caspases. Additionally, reactive oxygen species generation preceded the onset of apoptosis, and superoxide anion production was higher in cells treated with the combined treatment.ConclusionsThe γ-thionin from Habanero chili pepper improved the butyrate cytotoxicity on Caco-2 cells. This effect occurred through apoptosis induction associated with reactive oxygen species production. Therefore, the combination of butyrate with cytotoxic antimicrobial peptides could be an attractive strategy for cancer therapy.How to cite: Velázquez-Hernández ME, Ochoa-Zarzosa A, López-Meza JE, Defensin γ-thionin from Capsicum chinense improves butyrate cytotoxicity on human colon adenocarcinoma cell line Caco-2. Electron J Biotechnol 2021;52. https://doi.org/10.1016/j.ejbt.2021.04.009 相似文献
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本文应用银染细胞核仁组成区(AgNORs)技术,对34例胃腺癌(GAC),96例不同病理类型胃炎进行 AgNORs 颗粒计数。结果显示:胃腺癌与各型胃炎均有显著性差异;胃粘膜癌前病变(本文指胃炎伴不典型增生(CGAH)。胃炎伴肠化(CGIM)慢性萎缩性胃炎(CAG))均与慢性浅表性胃炎(CSG)有显著性差异。故 AgNORs 在胃粘膜良恶性疾病的鉴别及癌前病变的诊断上具有一定意义。 相似文献
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Purpose: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kipl and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. Methods: Cyclin D 1 and p27kip 1 protein were detected by immunohistochemical En Vision method in 43 BACs. Results: The positivity of cyclin D 1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P＜0.01. No statistically significant association was found between cyclin D1 expression data and sex, age, tobacco-use history, histologic subtype (mucinous vs nonmucinous), stromal fibrosis, lymph node metastasis, clinical stage or postoperative survival period (P＞0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P＜0.05). The positivity of p27kipl in BACs was 51.2% (22/43), significantly lower than that in normal pulmonary tissue (12/13), P＜0.01. p27kipl expression level was not associated with sex, age, tobacco-use history, tumor size or histologic subtype (P＞0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P＜0.05); and positively associated with postoperative survival period (P＜0.01). The survival rate of p27kipl positive group was significantly higher than that of p27kipl negative group (P＜0.01). No statistically significant correlation was found between cyclin D 1 and p27kipl expression. Conclusions: Increased cyclin D1 expression and decreased p27kip 1 expression are related to the pathogenesis of BAC;decreased p27kipl expression is associated with metastasis progression; immunodetection ofp27kip 1 is useful for assessment of prognosis. 相似文献
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INTRODUCTION Bronchioloalveolar carcinoma (BAC) is a par-ticular subtype of pulmonary adenocarcinoma de-rived from clara cell and type II pneumocyte. BAC cells grow along and within alveolar spaces while the alveolar framework of the lung is preserved. The incidence of BAC appears to be rising recently. The etiology and pathogenesis of this unique neoplastic disease are still unclear; many studies of oncogene and tumor suppressor gene expression include BAC with all adenocarcinoma o… 相似文献
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Li-duan Zheng Xiu-ping Yang Hua-xiong Pan Xiu Nie Jun He Qing Lv Qiang-song Tong 《Journal of Zhejiang University. Science. B》2009,10(3):237-241
Gastric carcinoma with osteoclast-like giant cells (OGCs) is an extremely rare tumor. So far, only six cases have been reported in the literature. Here we report an additional case of this tumor in a Chinese 78-year-old man presented with abdominal pain, vomiting, and hematemesis. Physical examination and gastroscopy revealed a tumor in the gastric antrum. The biopsy and pathological findings indicated a gastric adenocarcinoma with OGCs, which were present in both the tumor and the metastatic lymph nodes. Further immunohistochemical staining indicated that OGCs were reactive with CD68, CD45, and vimentin protein, but not with pancytokeratin, carcinoembryonic antigen, or epithelial membrane antigen, suggesting the monocytic/histiocytic derivation of these OGCs. In situ hybridization for Epstein-Barr virus showed no nuclear positivity in either adenoearcinoma or OGCs. Postoperative follow-up showed that the patient had survived for at least 6 months without recurrence. Further investiga-tion is warranted to clearly define the prognostic significance of OGCs in gastric carcinoma. 相似文献
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