Neoplasma最新文献

Existing evidences have revealed the crucial roles of E2 promoter binding factor-1 (E2F1) during the tumorigenesis and progression process of multiple human tumors. However, the expression patterns, biological functions, as well as the underlying molecular mechanism of E2F1 in endometrial carcinoma yet remain largely unclear. The expression patterns and clinical prognostic value of E2F1 in endometrial carcinoma were evaluated using bioinformatics methods. Protein and mRNA, miRNA expression levels in tissues and cells were measured using immunohistochemistry, western blotting, and qRT-PCR assays. Cell viability and cell cycle distribution were examined using CCK-8 assay and flow cytometry, respectively. Scratch healing assay and Transwell assay were applied to measure cell migration and invasion ability. Bioinformatic analysis and luciferase reporter assays were conducted to confirm the targeting relationship between E2F1 and miR-329-3p. Moreover, a series of in vitro and in vivo functional experiments were employed to evaluate the effect of the miR-329-3p/E2F1 axis on cell growth and metastasis. Clinically, E2F1 was aberrantly expressed in endometrial carcinoma tissues and was correlated with advanced FIGO stage, histological type, p53 mutation, poor survival, and degree of tumor cell differentiation. ROC curves analysis also reveals that E2F1 has a high AUC value (up to 0.952, 95% CI: 0.915-0.988), indicating the promising diagnostic value of E2F1 level in endometrial carcinoma. In addition, in vitro gain and loss-of-functional experiments verified that high E2F1 can promote cell proliferation, cell cycle, migration, invasion, and EMT process. In-depth mechanism studies revealed that E2F1 was a downstream target gene of miR-329-3p, and miR-329-3p overexpression could effectively abrogate its promotion of cell malignant biological behavior. Collectively, our findings suggested that the miR-329-3p/E2F1 axis plays a crucial role in the progression of endometrial carcinoma, indicating that E2F1 can be considered a promising diagnostic and prognostic biomarker for endometrial carcinoma patients.

Gut microbial dysbiosis persists months after intensive cancer treatment in children and adolescents. This prospective study compared the intestinal microbiome of children 1-3 years after completion of Berlin-Frankfurt-Münster protocol (BFM)-based pediatric ALL (PALL) treatment and healthy controls. To induce a favorable shift in the bacterial composition of the intestines in PALL with gut microbiome disruptions, 8 weeks of physical activity and probiotic consumption were used. Blood analyses and 16S rRNA sequencing for the gut microbiome were performed on 16 pediatric cases and 16 healthy controls. Significant differences in bacterial diversity were found between pre- and post-intervention, respectively (Shannon index, 3.22±0.45 vs. 3.47±0.24, p=0.04; Simpson index, 0.10±0.05 vs. 0.06±0.02, p=0.02; and Chao1 index, 693.88±238.58 vs. 794.23±116.34, p=0.04). Furthermore, the increase in the relative abundance of Lactobacillus casei (5.04E-03±1.62E-02 vs. 2.92E-02±5.03E-02, p=0.04) and the increase in some strains of Veillonella, a bacterial genus recently linked to improved physical fitness, were identified. Promisingly, the exercise program combined with dairy probiotics increased bacterial richness and diversity.

The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy.

Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase considered a potent tumor suppressor that critically regulates diverse cellular processes, including cell cycle progression, apoptosis, or DNA repair. PP2A is typically downregulated in cancers but mechanisms for its inactivation in human cancers are poorly understood. PP2A represents a family of more than 60 phosphatases. According to cellular context, each heterotrimeric PP2A holoenzyme exerts a unique role in cancer, and PP2A isoforms can act either as tumor suppressors or as promoters. Due to wide structural diversity, PP2A has been considered undruggable. However, increasing knowledge predisposes PP2A diversity to therapeutical targeting for the treatment of a broad range of cancer pathologies, including drug resistance or cloaking immune surveillance. In this review, we discuss the regulatory role of PP2A in cancer, its regulation by microRNA and hypoxia, its contribution to therapy resistance development, and the therapeutic potential of direct and indirect targeting, or combinatory administration with other anti-cancer drugs to improve cancer treatment outcomes.

Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.

Breast cancer metastases are the main reason for women´s highest cancer mortality. Even though tumor cell dissemination via circulating tumor cells (CTC) released from the primary site is a very ineffective process, distant metastases appear in 46% of triple-negative breast cancer (TNBC) patients corresponding to the disease aggressiveness. Laboratory models for functional testing which mimic the spread of metastatic cells are needed for efficient investigation of the underlying mechanisms and therapeutic intervention. Here, we describe novel isogenic variants LMC3 and CTC3 of human TNBC cell line MDA-MB-231 that were derived by repeated injection of tumor cells into the tail vein of immunodeficient mice and subsequent selection of metastatic cells from lung metastases. These variants have increased migration potential, altered expression profiles, and elevated tumorigenic potential. Moreover, cell line CTC3 readily produces metastases in the lungs and bone marrow and detectable viable circulating tumor cells in the blood. This model enables rapid and cost-efficient strategies for biomarker exploration and novel intervention approaches to limit the CTC presence in the blood and hence tumor dissemination.

The purpose of this study was to assess the potential effects of Rhus coriaria L. (sumac) and of Cinnamomum zeylanicum L. bark on the selected serum cytokines as possible serum tumor markers - interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the rat model of mammary carcinogenesis. R. coriaria and C. zeylanicum bark were used as the chemopreventive-therapeutic agents taken by rats in the powder form in the diet at two different concentrations during the entire period of two experiments carried out separately: lower concentration 1 g/kg - 0.1% and higher concentration 10 g/kg - 1%. The serum levels of cytokines of IL-6, IL-10, and TNF-α were determined using an enzyme-linked immunosorbent assay. In the first experiment treated with R. coriaria, a significant decrease in serum levels of IL-6 and TNF-α was present at higher concentrations compared to the chemoprevention-free control group. R. coriaria at lower concentrations non-significantly reduced the serum levels of IL-6 and TNF-α when compared to controls. A significant decrease in serum levels of TNF-α was present at higher concentrations compared to lower concentrations. The significant effect of R. coriaria on the serum levels of IL-10 was not observed. In the second experiment treated with C. zeylanicum bark, a significant decrease in serum levels of IL-6 was observed in lower and higher concentrations compared to the chemoprevention-free control group. C. zeylanicum bark non-significantly reduced the serum levels of TNF-α and had no effect on the serum levels of IL-10. In conclusion, R. coriaria and C. zeylanicum bark demonstrated significant anti-inflammatory effects by analyzing the selected serum cytokine levels in the rat breast carcinoma model. Observed anti-inflammatory effects of both plant-natural substances were associated with their anticancer activities in rats.

Long noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported that lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models. In the present study, bioinformatics analysis showed that the expression level of PVT1 was upregulated in CRC tissues and highly associated with poor prognosis of CRC patients. In cultured CRC cells, knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells. In zebrafish xenografts, the silencing of PVT1 also suppressed the growth and metastasis of CRC cells. For mechanism studies, the binding relationships among PVT1, miR-24-3p, and Neuropilin 1 (NRP1) were predicted by starBase firstly. The luciferase reporter assays verified that PVT1 and NRP1 could bind with miR-24-3p directly. Further studies showed miR-24-3p negatively regulated the progression of CRC cells, the inhibition of miR-24-3p counteracted the repression effects of CRC progression when knocking down PVT1. In addition, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of CRC progression when knocking down PVT1 in vitro and in vivo. Our study reveals that PVT1 promotes the proliferation and metastasis of CRC via regulating the miR-24-3p/NRP1 axis, which provides a prognosis biomarker and a potential therapeutic target for CRC patients.

Silver nanoparticles (AgNPs) exhibit unique physicochemical properties, making these nanomaterials attractive for various medical applications. Among them, AgNPs have shown great potential in the treatment of cancer by inducing apoptosis in cancer cells, inhibiting tumor growth, and enhancing the efficacy of conventional cancer treatments such as chemotherapy and radiation therapy. Despite the promising therapeutical advantage of AgNPs, there are several challenges that need to be addressed. One of the most important is AgNPs' toxicity, which in case of treatment might be extended to non-cancerous cells and tissues. In our study, we therefore investigated the effects of spherical AgNPs with the silver core size of 10, 30, and 45 nm coated with polyacrylic acid (PAA-AgNPs) in an in vitro model using cancer (A549) and non-cancer (HEL299) cells. We estimated the impact of these nanoparticles on cell viability, cell proliferation, and cell actin cytoskeleton remodeling. Moreover, changes in the expression of TNFA, IL-10, FN1, and SOD1 mRNA induced by PAA-AgNPs were determined. Our results suggest that the smallest (10 nm) PAA-AgNPs are the most effective in apoptosis induction, however, they are also the most toxic from the three AgNPs types to both, cancer and non-cancer cells, while bigger (30 and 45 nm) PAA-AgNPs showed fewer undesirable effects in these pulmonary cells.