Mir-98 reduces the expression of HMGA2 and promotes osteogenic differentiation of mesenchymal stem cells.

OBJECTIVE: To study effects of microRNA-98 (miR-98) on osteogenic differentiation of mesenchymal stem cells (MSCs). PATIENTS AND METHODS: We predicted target gene of miR-98 with software test, and detected expression changes of miR-98, as well as its target gene HMGA2, in the process of osteogenic differentiation of mesenchymal stem cells. After transfection of miR-98 mimic and HMGA2 siRNA, we induced osteogenic differentiation and detected expression changes of osteogenic differentiation markers (RUNX2, ALP, OCN, and BSP). RESULTS: MiR-98 combined directly with target gene HMGA2 and inhibited its expression. During the process of osteogenic differentiation, expression of miR-98 was up-regulated, while HMGA2 expression was down-regulated. In addition, the expression of osteogenesis maker genes increased in cells being transfected with miR-98 mimics and HMGA2 siRNA. CONCLUSIONS: MiR-98 can promote osteogenic differentiation of mesenchymal stem cells by targeting gene HMGA2.

SEOM clinical guideline for the management of malignant melanoma (2017).

All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams.

[High-Content siRNA Screen of the Kinome Identifies Kinases Involved in Git2-Induced Mesenchymal-Epithelial Transition].

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) programs are involced in the metastatic process. More and more evidence confirms that EMT is vital for the initiation and dissemination of cancer cells whereas MET is critical for successful metastatic colonization of a secondary organ. The regulating mechanism of EMT mediated cancer progression and metastasis has been deeply investigated. However, what processes are dependent on MET in metastatic cascades remains unclear. Here, we created a cell based high-content siRNA screen using the breast cancer cell line 4TO7 to search for kinases that were involved in Git2-induced MET. Our results revealed that 58 kinases including transferase, phosphorylation regulators, ATP/nucleotide partners potentially participate in Git2-induced MET. Our preliminary data is expected to facilitate elucidation of the mechanism on how MET is initiated during cancer metastasis.

[Effect of GTPase activating protein Git2 on metastasis in breast cancer].

OBJECTIVE: To investigate the effect of GTPase activating protein Git2 on metastasis in breast cancer. METHODS: Git2 gene over-expression was induced by Git2 cDNA, and Git2 gene knockdown was induced by Git2 ShRNA lentivirus in four breast cancer cell lines. Six-week old wide type female mice were also used in this study. The cells were tagged with luciferase and injected into wide type female mice by tail vein or 4(th) mammary fat pad, respectively, to establish a cancer metastasis model. In vivo real time imaging system and immunohistochemical staining were used to detect the cancer metastasis. RESULTS: The relative mRNA expression level of Git2 (normalized by GAPDH) in the 4T1, 4TO7, 168FARN and 67NR cells were 0.91±0.03, 0.125±0.06, 0.131±0.04 and 0.92±0.04, respectively. The expression of EMT marker E-cadherin was inhibited and N-cadherin and vimentin were enhanced when Git2 was over-expressed in 168FARN cells and 4TO7 cells expressing low level of Git2, whereas the expression of E-cadherin was increased and N-cadherin and vimentin were decreased when Git2 was knocked down in 67NR cells and 4T1 cells expressing high level of Git2. Furthermore, over-expression of Git2 promoted 4TO7 cells to progress from micro-metastasis to macro-metastasis. The down-regulation of Git2 pushed 67NR cells to intravasate into blood circulation and suppressed the metastatic ability of 4T1 cells. The number of bioluminescence photos of lung metastatic 4T1-Luc-KD cells was (0.4±0.05)×10(6,) compared with (3.0±0.04)×10(6) in the control 4T1-Luc cells, showing a significant difference (P<0.05). CONCLUSION: Our results indicate that Git2 is involved in breast cancer initiation and metastatic colonization.

SEOM guidelines for the management of Malignant Melanoma 2015.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

A preliminary investigation of the relationship between circulating tumor cells and cancer stem cells in patients with breast cancer.

In this study, we explored the relationship between the circulating tumor cells (CTC) and the CTC-cancer stem cells (CSC) in the patients with breast cancer. The magnetic-activated cell separation (MACS) method and flow cytometry (FCM) for selection of epithelial cells from the peripheral blood mononuclear cells (PBMC) were used to analyze the enriched epithelial cells that were labeled with anti-cytokeratin(CK)-fluorescein isothiocyanate, anti-CD44-phycoerythrin (PE) and anti-CD24-PE, respectively. The CK+ cells were attributed to CTC and the CK+CD44+ CD24-/low cells were thought as to CTC-CSC in 26 breast cancer patients, respectively. Our results showed the CK+ tumor cells were detected in 19 of 26 patients, with the CK+ tumor cells varying from 0.11% to 5.42 %. The CTC-CSC were identified in 18 of the 19 patients with CTC and the percentage of CTC-CSC in CTC was 19.01%. The results yet suggested the breast cancer patients with high-rate CK+ tumor cells were at the advanced tumor node metastases (TNM) stage III, and the patients with low-rate CK+ cells were at the modest TNM stage I. The difference between the two groups was statistically significant (p<0.001). We concluded that there is a significant relationship between CTC and CTC-CSC, but not among TNM stages, in breast cancer metastasis.