Coatesorr1773

To evaluate the mechanism underlying the communication between myeloid malignant and bone marrow (BM) microenvironment cells in disease progression, the current study established BM mesenchymal stromal cells (MSCs) and assessed extracellular vesicle (EV) microRNA (miR) expression in 22 patients with myelodysplastic syndrome (MDS) and 7 patients with acute myeloid leukemia and myelodysplasia-related changes (AML/MRC). Patients with MDS were separated into two categories based on the revised International Prognostic Scoring System (IPSS-R), and EV-miR expression in BM-MSCs was evaluated using a TaqMan low-density array. The selected miRs were evaluated using reverse transcription-quantitative PCR. The current study demonstrated that the expression of BM-MSC-derived EV-miR was heterogenous and based on MDS severity, the expression of EV-miR-101 was lower in high-risk group and patients with AML/MRC compared with the control and low-risk groups. This reversibly correlated with BM blast percentage, with which the cellular miR-101 from BM-MSCs or serum EV-miR-101 expression exhibited no association. Database analyses indicated that miR-101 negatively regulated cell proliferation and epigenetic gene expression. The downregulation of BM-MSC-derived EV-miR-101 may be associated with cell-to-cell communication and may accelerate the malignant process in MDS cells. Copyright © 2020, Spandidos Publications.Activation of antiapoptotic genes has been indicated as one of the factors that contributes to hepatitis B virus (HBV) infection-induced liver cancer. The cellular inhibitor of apoptosis protein 2 (cIAP2), a member of the IAP family, is upregulated in various types of cancer and serves as a potential treatment target. However, to the best of our knowledge, the importance of cIAP2 in HBV-induced liver cancer has not been investigated. In the present study, cIAP2 expression in liver cells in response to HBV infection and the underlying mechanism involved was investigated. Western blot analysis of clinical liver samples showed that higher cIAP2 expression was detected in HBV-positive non-cancerous tissue compared with that in HBV-negative non-cancerous tissue, and the expression was further increased in HBV-positive liver cancer tissue. Reverse transcription-quantitative PCR and western blot experiments performed on two liver cell lines also confirmed that cIAP2 expression was increased upon HBV infection at both the mRNA and protein levels. Promoter analysis revealed that HBV could activate cIAP2 promoter in an infection dose-dependent manner, and this activation involved a NF-κB-binding site in the cIAP2 promoter. Further analysis demonstrated that HBV enhanced NF-κB phosphorylation and nuclear translocation via the PI3K/AKT signaling pathway, leading to the binding and activation of cIAP2 promoter. The present data demonstrates that HBV-infection induces cIAP2 expression in the liver by activation of the PI3K/AKT/NF-κB signaling pathway through promoting the binding of NF-κB to cIAP2 promoter, which may lead to carcinogenesis. The findings from the present study provide more information for understanding HBV-induced liver cancer and also offer a potential target for treatment or diagnosis of this disease. Copyright © 2020, Spandidos Publications.Dysregulated expression of long non-coding RNAs has been determined to be important in cancer development; however, their role in tongue squamous cell carcinoma (TSCC) progression and carcinogenesis, to the best of our knowledge, is yet to be elucidated. The present study revealed that long intergenic non-coding RNA 00152 (LINC00152) expression was significantly increased in human TSCC tissues compared with in tissues from matched controls using RT-qPCR. In TSCC cell lines, CAL-27 and SCC-9, LINC00152 was revealed to promote TSCC cell proliferation, enhance cell cycle progression and inhibit cell apoptosis. Additionally, migration and invasion of TSCC cell lines was increased in response to LINC00152 overexpression. Mechanistically, LINC00152 was determined to be localized in the cytoplasm and acted as a microRNA (miR)-193b-3p sponge, and LINC00152 knockdown or miR-193b-3p mimics both inhibited PI3K signaling pathway activation and downstream AKT phosphorylation; therefore, promoting TSCC progression in vitro. Overall, the results of the present study suggested that increased LINC00152 expression in TSCC tissues may act as a sponge of miR-193b-3p to promote cancer progression in vitro. Copyright © 2020, Spandidos Publications.Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with poor outcomes in patients ineligible for autologous stem cell transplantation. In this setting, novel treatment approaches are urgently required and the innovative agent pixantrone has shown some promising results in terms of disease-free and overall survival (OS). The present study retrospectively analyzed 12 patients routinely treated with pixantrone in monotherapy or in combinations at the Institute of Oncology Ljubljana, Slovenia, between January 2016 and October 2018. All 12 patients had refractory lymphoma to last treatment and a large proportion of them had other high risk features (high proliferation index, high disease stage, high international prognostic index (IPI) score, high percentage of primary refractory disease and high percentage of refractoriness to anthracyclines) at initiation of pixantrone. All patients progressed during treatment and none of the patients were alive at the time of analysis due to progressive lymphoma. Pixantrone specific median OS was 3.5 months (range, 0.5-10 months). A somewhat superior median OS (P=0.065) was observed in patients primarily sensitive to anthracyclines. Pixantrone has shown only limited efficacy in the present real world study comparable to the results of another real world UK retrospective analysis and substantially worse than the efficacy observed in the PIX301 registration trial. Therefore, an appropriate selection of patients for this treatment is crucial. Despite the limited experience due to a small number of patients, it was recommended to consider only patients with relapsed (and not refractory) disease, patients with non-primary refractory disease and those with fewer lines of prior therapy. Copyright © Novakovic et al.Multidrug resistance in cancer cells is a primary factor affecting therapeutic efficacy. Heat shock 27 kD protein 1 (HSP27) is associated with cell apoptosis and resistance to chemotherapy. However, the mechanisms underlying HSP27-associated pathways in colon cancer cells remain unclear. Therefore, the present study used short hairpin (sh) RNA to inhibit HSP27 expression in colon cancer cells in order to investigate the effects in vitro and in vivo. Flow cytometry was used to investigate cell apoptosis and a xenograft model was employed to examine the tumorigenesis. Protein expression was measured by Western blotting. The results revealed that suppression of HSP27 expression significantly increased cell apoptosis, inhibited tumor growth and enhanced sensitivity to the anti-cancer agents 5-fluorouracil (5-FU) and vincristine (VCR). shHSP27 significantly decreased the expression of notch receptor 1 and the phosphorylation level of Akt and mTOR, and enhanced the effect of 5-FU and VCR. In conclusion, HSP27 suppression enhanced the sensitivity of colon cancer cells to 5-FU and VCR, and increased colon cancer cell apoptosis with and without chemotherapy. Therefore, the development of novel therapeutic agents that inhibit the expression of HSP27 may offer a new treatment option for colon cancer. Copyright © 2020, Spandidos Publications.Hepatocellular carcinoma (HCC) remains an intractable disease despite numerous advancements made in the available treatments over recent decades. Therefore, investigation of the underlying pathogenesis of HCC is urgently required. Our previous microarray result showed that SCIN was generally downregulated in 23 paired tumor/normal tissues. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed in the present study in order to detect the expression of scinderin (SCIN). Lentivirus-mediated gene delivery was used in order to produce SCIN-manipulated cell lines. MTT and crystal violet assays were performed in order to investigate cell growth, and fluorescence-activated cell sorting analysis was used in order to determine cell cycle distribution. SCIN was downregulated in HCC samples, and low SCIN expression predicted the poor prognosis of patients with HCC. Notably, SCIN may have the potential to serve as an independent risk factor for overall survival (3-year overall survival rate of 28.6 and 10.3% in high SCIN expression and low SCIN expression groups, respectively) and disease-free survival (3-year recurrence rate of 71.4 and 84.6% in high SCIN expression and low SCIN expression groups, respectively) in HCC. SCIN inhibited HCC cell proliferation both in vitro and in subcutaneous tumor formation assay. Furthermore, SCIN decreased the levels of phosphorylated STAT3, thereby downregulating cyclin A1 levels in HCC cells. The results of the present study demonstrate the tumor suppressive role of SCIN in HCC, providing a candidate strategy to treat this disease. Copyright © 2020, Spandidos Publications.The numbers of abnormal findings incidentally detected in adjacent regions are increasing with advances in imaging modalities. The present study aimed to examine the prevalence and characteristics of incidental findings in the thyroid gland on computed tomography (CT) images of the oral and maxillofacial region. CT scans of the oral and maxillofacial region in patients obtained between January 2012 and December 2016 were retrospectively reviewed. Images that revealed incidental findings in the thyroid gland, including nodules, were recorded, together with the sizes and characteristics of the findings. The Japan Association of Breast and Thyroid Sonology (JABTS) guidelines were used for classification. The rate of descriptions of these findings in the radiographic interpretation reports were also examined. Of the 1,135 patients examined, 326 (28.7%) had several types of incidental findings. In particular, 169 (14.9%) of the 1,135 patients had nodules >5 mm in diameter, for which further careful examination is recommended in the JABTS guideline. The description rate for nodules >5 mm in diameter in the radiographic interpretation reports was 30.8% (52/169 patients), of whom 17.3% (9/52 patients) were referred to the endocrinology department for further careful examination. Incidental findings in the thyroid gland were relatively common on CT images of the oral and maxillofacial region. Oral radiologists tend to focus specifically on the oral and maxillofacial region during diagnosis on oral and maxillofacial CT images, but should pay the same careful attention to observe adjacent regions, such as the thyroid gland. Copyright © 2020, Spandidos Publications.The PI3K/Akt pathway is an attractive therapeutic target in the treatment of pancreatic cancer, as it was demonstrated to be aberrantly regulated in pancreatic cancer cells. click here The present study aimed to investigate the therapeutic potential of the novel Akt inhibitor MK-2206 in human pancreatic cancer cell lines. Pancreatic cancer cell survival following MK-2206 treatment was assessed using the Cell Counting Kit-8 (CCK-8) assay, colony formation and determination of the apoptotic rate by flow cytometry following annexin-V-fluorescein isothiocyanate/propidium iodide staining. The effects of MK-2206 alone or in combination with gemcitabine on pancreatic cell proliferation were assessed using the CCK-8 assay. Western blotting was used to examine the effects of the two drugs on Akt protein expression. The results demonstrated that MK-2206 inhibited the proliferation and induced apoptosis of the Mia PaCa-2 and Panc-1 pancreatic cancer cell lines. In addition, CCK-8 cytotoxicity test showed that combined administration of MK-2206 with gemcitabine enhanced the cytotoxic efficacy of gemcitabine.