Haymoses8519

served in our study, suggesting that SC is more prevalent than previously reported. Clinicians should be familiar with the characteristics of these tumors. Furthermore, the established nomogram could accurately predict the 3-/5-year survival rate of patients with SC, which may be of value for patient counselling and risk stratification.Cancer stem cells (CSCs) are a small population among cancer cells, defined as capable of self-renewal, and driving tumor growth, metastasis, and therapeutic relapse. The development of therapeutic strategies to target CSCs is of great importance to prevent tumor metastasis and relapse. Increasing evidence shows that shikonin has inhibiting effects on CSCs. This study was to determine the effect of shikonin on prostate CSCs, and on drug resistant cells. Sphere formation assay was used to enrich prostate CSCs. The effect of shikonin on viability, proliferation, migration, and invasion was studied. Typical CSCs markers were analyzed by flow cytometry and RT-qPCR. The cytotoxic mechanism of shikonin was analyzed by staining for annexin V, reactive oxygen species (ROS) and mitochondrial membrane potential. To study the effect of shikonin on drug-resistant cells a cabazitaxel resistant cell line was established. Shikonin inhibited the viability, proliferation, migration, and invasion of prostate CSCs. Shikonin enhanced the antitumor effect of cabazitaxel, which is a second-line chemotherapeutic drug in advanced prostate cancer. Shikonin induced apoptosis through generating ROS and disrupting the mitochondrial membrane potential. Furthermore, shikonin suppressed the expression of ALDH3A1 and ABCG2 in prostate CSCs, which are two markers related to drug-resistance. When inhibiting the expression of ABCG2 and ALDH3A1, the cabazitaxel resistant cells acquired more sensibility to cabazitaxel. Shikonin enhances the cytotoxic activity of cabazitaxel in prostate CSCs and reverses the cabazitaxel-resistant state.The Cdc2-like kinases (CLKs) regulate RNA splicing and have been shown to suppress cell growth. Knockdown of CLK2 was found to block glioma stem-like cell (GSC) growth in vivo through the AKT/FOXO3a/p27 pathway without activating mTOR and MAPK signaling, suggesting that these pathways mediate resistance to CLK2 inhibition. We identified CLK2 binding partners using immunoprecipitation assays and confirmed their interactions in vitro in GSCs. We then tested the cellular viability of several signaling inhibitors in parental and CLK2 knockdown GSCs. Our results demonstrate that CLK2 binds to 14-3-3τ isoform and prevents its ubiquitination in GSCs. Stable CLK2 knockdown increased PP2A activity and activated PI3K signaling. Treatment with a PI3K/mTOR inhibitor in CLK2 knockdown cells led to a modest reduction in cell viability compared to drug treatment alone at a lower dose. However, FGFR inhibitor in CLK2 knockdown cells led to a decrease in cell viability and increased apoptosis. Reduced expression of CLK2 in glioblastoma, in combination with FGFR inhibitors, led to synergistic apoptosis induction and cell cycle arrest compared to blockade or either kinase alone.TAS-102/Lonsurf is a new oral anti-tumor drug consisting of trifluridine and tipiracil in a 10.5 molar ratio. Lonsurf has been approved globally, including US, Europe Union, and China, to treat patients with advanced colorectal cancer. Ongoing clinical trials are currently conducted for the treatment of other solid cancers. However, the therapeutic potential of TAS-102 in hematological malignancies has not been explored. In this study, we investigate the therapeutic efficacy of TAS-102 in multiple myeloma both in vitro and in vivo. We demonstrate that TAS-102 treatment inhibits tumor cell proliferation in six human myeloma cell lines with IC50 values in a range from 0.64 to 9.10 μM. Dot blotting and immunofluorescent staining show that trifluridine is predominately incorporated into genomic DNAs of myeloma cells. TAS-102 treatment induces myeloma cell apoptosis through cell cycle arrest in G1 phase and activation of cGAS-STING signaling in myeloma cells. In the human myeloma xenograft models, TAS-102 treatment reduces tumor progression and prolongs mouse survival. TAS-102 has shown its efficacies in the drug-resistant myeloma cells, and the combination of TAS-102 and bortezomib has a synergistic anti-myeloma activity. selleck chemicals llc Our preclinical studies indicate that TAS-102 is a potential novel agent for myeloma therapy.Circular RNAs, a special class of non-coding RNA with closed circular structure, have been increasingly proven to be involved in the progression of various tumors. However, the biological functions of circular RNAs in epithelial ovarian cancer (EOC) tissues remain a mystery. In this study, we detected the function of circEEF2 (has-circ-0048559) in EOC tissues. Firstly, the basic characteristics including closed circular structure and spliced mature sequence length of circEEF2 were confirmed. The location and expression in EOC tissues was detected by fluorescence in situ hybridization (FISH). The regulatory effect of circEEF2 on autophagy, proliferation, and invasion were investigated in SKOV3 and A2780 cells. The relationship between circEEF2 and mir-6881-3p was confirmed using dual-luciferase reporter gene assay. The binding of circEEF2 with ANXA2 was confirmed using RNA-pulldown assay and MALDI-TOF-MS. We found that the expression level of circEEF2 was higher in EOC tissue than in normal tissue. CircEEF2 promoted autophagy, proliferation, and invasion. CircEEF2-regulated EOC proliferation and invasion are closely related to the occurrence of autophagy. Mechanistically, circEEF2 harbor miR-6881-3p to upregulate the latter's targets ATG5 and ATG7. Moreover, circEEF2 could directly bind with ANXA2 to inhibit the expression of p-mTOR. In conclusion, findings of the current study illustrate that circEEF2 promoted autophagy, proliferation, and invasion of EOC by interacting with miR-6881-3p and ANXA2.Breast cancer (BCa) has the highest incidence and mortality among malignant diseases in female worldwide. BCa is frequently caused by estrogen receptor α (ERα), a ligand-dependent receptor that highly expressed in about 70% of breast tumors. Therefore, ERα has become a well-characterized and the most effective target for treating ERα-expressing BCa (ERα+ BCa). However, the acquire resistance was somehow developed in patients who received current ERα signaling-targeted endocrine therapies. Hence, discovery of novel anti-estrogen/ERα strategies is urgent. In the present study, we identified butein as a potential agent for breast cancer treatment by the use of a natural product library. We showed that butein inhibits the growth of ERα+ BCa both in vitro and in vivo which is associated with cell cycle arrest that partially triggered by butein-induced ERα downregulation. Mechanically, butein binds to a specific pocket of ERα and promotes proteasome-mediated degradation of the receptor. Collectively, this work reveals that butein is a candidate to diminish ERα signaling which represents a potentially novel strategy for treating BCa.