ABSTRACT
Colorectal cancer (CRC) is one of the leading causes of death worldwide. Recently, the role of cancer stem cells (CSCs) has been highlighted as a crucial emerging factor in chemoresistance, cancer relapse, and metastasis. CD133 is a surface marker of CSCs and has been argued to have prognostic and therapeutic values in CRC along with its related pathways such as Wnt, Notch, and hedgehog. Several studies have successfully applied targeted therapies against CD133 in CRC models namely bispecific antibodies (BiAbs) and anti-Wnt and notch pathways agents. These studies have yielded initial promising results in this regard. However, none of the therapeutics have been used in the clinical setting and their efficacy and adverse effects profile are yet to be elucidated. This review aims to gather the old and most recent data on the prognostic and therapeutic values of CD133 and CD133-targeted therapies in CRC.
Subject(s)
AC133 Antigen/antagonists & inhibitors , AC133 Antigen/metabolism , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Molecular Targeted Therapy , Neoplastic Stem Cells/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Humans , Neoplastic Stem Cells/pathologyABSTRACT
BACKGROUND: Colorectal cancer (CRC) is attributed as one of the most common malignancies worldwide. CD133 molecule, as a pentaspan transmembrane glycoprotein, confers stem cell-related characteristics, including self-renewal and multi-directional differentiation capability. CD133 plays important roles in the progression of CRC by conferring apoptotic resistance and migration ability. OBJECTIVE: To investigate the anti-apoptotic and anti-angiogenic effect of CD-133 targeted siRNA in a colorectal cancer cell line. METHODS: In this study, CD133-targeted siRNA transfection was conducted into HT-29 cells. MTT assay was employed to evaluate the cytotoxic effects of transfection on the cells. Flow cytometry was used to evaluate the apoptosis rate. The mRNA expression of apoptosis and metastasis related genes were assessed by quantitative Real-Time PCR (qRT-PCR). Wound healing assay was used to assess the migration potency of the infected cells. RESULTS: Expression of CD133 was significantly downregulated after transfection of CD133-specific siRNA. Moreover, the rate of apoptosis was significantly increased after transfection. The migration potential of cells was diminished after transfection. siRNA delivery resulted in the modulation of expression of apoptosis and metastasis-related genes. CONCLUSION: siRNA mediated targeting of CD133 could be considered as a promising approach to treat CRC through suppressing the cancerous behavior of tumor cells.
Subject(s)
AC133 Antigen/metabolism , Colonic Neoplasms/metabolism , Colorectal Neoplasms/metabolism , AC133 Antigen/genetics , Apoptosis , Cell Movement , Cell Proliferation , Cell Survival , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Gene Silencing , HT29 Cells , Humans , Molecular Targeted Therapy , Neoplasm Metastasis , Neovascularization, Pathologic , RNA, Small Interfering/geneticsABSTRACT
Adrenocortical carcinoma (ACC) is a rare tumor and usually a fatal disease which can develop at any age in either sex. Differential diagnosis between malignant and benign adrenal mass is not easy which leads to significant clinical challenge for optimal treatment. Here we report a 22-year-old woman diagnosed with primary hyper aldostronism initially but disease relapsed during six months and magnetic resonance imaging revealed tumor with metastasis to the liver.
