جستجوی مقالات مرتبط با کلیدواژه « neoplastic stem cells » در نشریات گروه « پزشکی »

Aldehyde dehydrogenase 1 (ALDH1) is an enzyme accountable for the detoxification of aldehydes. Sex-determining region Y-box 9 (SOX-9) plays a role in many biological and pathological processes. In this study, we aimed to evaluate the prognostic significance of ALDH1 and SOX9 expression in early breast cancer.
The expression of ALDH1 and SOX-9 was evaluated through immunohistochemistry derived from 50 eligible patients with early breast cancer included in the current prospective cohort study.
Positive expression of ALDH1 and SOX-9 were detected in 29 (58%) and 34 (68%) patients, respectively. The positive expressions of both markers were statistically significant associated with increasing the stage, lymph nodes metastasis, high Ki67 labeling index, and molecular subtypes (P < 0.001), along with with the biological markers; estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 over-expressions, and large tumor size (P = 0.039, P = 0.022, P = 0.024 and P = 0.003 for ALDH1 expression and P = 0.012, P = 0.007, P = 0.004 , and P = 0.002 for SOX-9 expression, respectively). There is a significant positive association between the expression of ALDH1 and SOX-9, r (correlation coefficient) = +0.806 (P < 0.001). Local recurrence was associated with the positive expression of ALDH1 only (P = 0.045) and the disease progression was statistically significant and associated with the positive expression of both ALDH1 and SOX-9 (P = 0.038, P = 0.023, respectively). There was significant association of positive expression of SOX-9 with reduced 3-y disease-free survival (P = 0.039).
Positive expression of ALDH-1 and SOX9 were associated with aggressive histopathological features and poor outcome in early breast cancer and can be considered potential prognostic markers in this group of patients.

Ionizing radiation (IR) is one of the major therapeutic approaches in the non-small cell lung cancer (NSCLC); however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition (EMT) and the cancer stem cell phenotype. Therefore, we aimed to determine whether IR promote EMT/CSC and to investigate the clinical relevance of EMT/CSC hallmark genes.

In this experimental and bioinformatic study, A549 cell line was irradiated with a high dosage (6 Gy) or a fractionated regimen (2 Gy/day for 15 fractions). The EMT-related features, including cellular morphology, migratory and invasive capacities were evaluated using scratch assay and transwell migration/invasion assays. The mRNA levels of EMT-related genes (CDH1, CDH2, SNAI1 and TWIST1), stemness-related markers (CD44, PROM1, and ALDH1A1) and the CDH2/CDH1 ratio were evaluated via real-time polymerase chain reaction (PCR). The clinical significance of these genes was assessed in the lung adenocarcinoma (LUAD) samples using online databases.

Irradiation resulted in a dramatic elongation of cell shape and enhanced invasion and migration capabilities. These EMT-like alterations were accompanied with enhanced levels of SNAI1, CDH2, TWIST1, CD44, PROM1, and ALDH1A1 as well as an enhanced CDH2/CDH1 ratio. TCGA analysis revealed that, TWIST1, CDH1, PROM1 and CDH2 were upregulated; whereas, CD44, SNAI1 and ALDH1A1 were downregulated. Additionally, correlations between SNAI1-TWIST1, CDH2- TWIST1, CDH2-SNAI1, and ALDH1A1-PROM1 was positive. Kaplan-Meier survival analysis identified lower expression of CDH1, PROM1 and ALDH1A1 and increased expression of CDH2, SNAI1, and TWIST1 as well as CDH2/CDH1 ratio predict overall survival. Additionally, downregulation of ALDH1A1 and upregulation of CDH2, SNAI1 and TWIST1 could predict a shorter first progression.

Altogether, these findings demonstrated that IR promotes EMT phenotype and stem cell markers in A549 cell line and these genes could function as diagnostic or prognostic indicators in LUAD samples.

  Colon tumor is generated and maintained by a small subset of chemo-resistant cancer cells known as Cancer Stem-like Cells (CSCs) that are able to self-renew and differentiate into various cell types within the cancer milieu. CSCs are identified through expression of CD133 that is the most important surface marker of these cells. Epithelial Cell Adhesion Molecule (EpCAM) is another colon CSCs marker. Other markers that are probably involved in colon tumorigenesis are Leucine-rich repeat-containing G-protein-coupled Receptor 5 (LGR5), B cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and Ten-Eleven Translocations (TETs). Here, mRNA expression rates of LGR5, BMI1 and TETs were surveyed by real-time PCR. After collection and digestion, colon samples were used to isolate CD133 and EpCAM positive CSCs through evaluation of AC133 EpCAM by Magnetic Activated Cell Sorting (MACS) and flow cytometry. Real-time PCR was carried out for assessing expressions of LGR5, BMI1 and TETs. High expressions for LGR5, BMI1, TET1 and TET2 in the CD133 and EpCAM positive CSCs (p≤0.05 vs. non-CSCs) were found. TET3, however, showed no significant changes for mRNA expression in the CSCs. In conclusion, high mRNA expressions for LGR5, BMI1, TET1 and TET2 in the CD133 and EpCAM positive CSCs may be a useful criterion for better identification of the cells involved in colon cancer in order to specify therapeutic targets against this type of cancer.

ZFX is a transcriptional regulator in embryonic stem cells and plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood. We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR. The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors, demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants. Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.

Basal cell carcinoma (BCC) is considered to be the most common malignancy in humans and occurs primarily in the skin especially in the head and neck region. Considering the high recurrence rate of the tumor, finding a marker for prediction of recurrence is very important. Cancer stem cells are a small subpopulation in the tumors that are related to tumorigenesis and recurrence and OCT4 is a known stem cell marker. The present study was designed to explore the relation between expres-sion of OCT4 in the head and neck basal cell carcinoma and recurrence of the tumor.
This study was performed on 84 patients with head and neck BCC who were followed up for 24 months. Immunohistochemical expression of OCT4 was assessed in paraffin embedded blocks.
Positive expression of OCT4 was significantly associated with the recurrence rate (P We conclude that the expression of OCT4 can serve as a predictive marker for tumor recurrence in the head and neck basal cell carcinoma.