6-O-angeloylplenolin (6-OAP) is a sesquiterpene lactone agent that has been previously demonstrated to inhibit the growth of multiple myeloma (MM) cells through mitotic arrest with accumulated cyclin B1. In the present study, the levels of apoptosis were analyzed in dexamethasone-sensitive (MM.1S), dexamethasone-resistant (U266) and chemotherapy-sensitive (RPMI 8226) myeloma cell lines. Enhanced apoptosis was identified following a 48-h incubation with 6-OAP (0-10 μM) that induced a dose-dependent decrease in pro-casp-3 and the cleavage of its substrate, anti-poly (ADP-ribose) polymerase (PARP). In addition, time-dependent cleavage of PARP was also detected in U266 and MM.1S cells. The mechanism of 6-OAP cytotoxicity in all cell lines was associated with the induction of apoptosis with the presence of cleaved caspase-3 and PARP. In conclusion, 6-OAP-induced apoptosis is caspase-dependent. These observations are likely to provide a framework for future studies of 6-OAP therapy in MM.

Epithelial-mesenchymal transition (EMT) is a critical step in order for epithelial-derived malignancies to metastasize, however, its role in mesenchymal-derived tumors, i.e., osteosarcoma, remains unclear. Cancer stem cells (CSCs) are enriched with cells that undergo EMT. The activity of telomerase is maintained in normal stem cells and a number of malignant tumors. The current study observed the heterogeneity of telomerase activity among individual osteosarcoma cells. We hypothesized that telomerase-positive (TELpos) cells are enriched for stem cell-like and EMT properties. A human telomerase reverse transcriptase (hTERT) promoter-reporter was applied to assess the telomerase activity of individual MG63 osteosarcoma cells and sort them into TELpos and telomerase-negative (TELneg) subpopulations. It was found that the TELpos cells exhibited an enhanced ability to form sarcospheres in vitro. In addition, TELpos cells exhibited a higher expression of vimentin, accompanied by an increased long/short axis ratio. A panel of EMT-related genes was evaluated by quantitative PCR and western blot analysis, and were found to be significantly upregulated in TELpos cells. Next, the in vitro migration capacity was examined by Transwell assay, which confirmed that TELpos cells are more prone to migration (2.6 fold). The results of the present study support the concept that EMT also applies to mesenchymal-derived osteosarcoma and draws a connection between telomerase and EMT characteristics.

Gastric cancer is a major cause of cancer-associated mortality worldwide. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis. Ras proteins transfer information from the extracellular environment to internal cellular compartments and are essential in numerous signal transduction pathways. To investigate the regulation, function and clinical significance of the miRNA377/Ras association domain family (RASSF) 8 signaling axis in gastric cancer, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, cell counting kit-8, western blotting, and Transwell assays were used. The results revealed that expression of RASSF8 was significantly upregulated in normal gastric tissues compared with gastric cancer, which was further confirmed by immunohistochemical analysis, and its expression level was increased in normal gastric cells compared with gastric cancer cell lines. However, the expression of miR-377 was significantly upregulated in gastric cancer compared with normal gastric tissues. In addition, RASSF8 overexpression in BGC-823 gastric cancer cells significantly inhibited the proliferation, apoptosis and invasive abilities of cells. Whereas miR-377 attenuated these effects due to downregulated RASSF8 expression by directly targeting its 3'-untranslated region. Furthermore, in the current study, miR-377 was not able to reverse the effects of RASSF8 overexpression on gastric cancer cells. Collectively, the RASSF8 gene may represent a novel molecular target involved in gastric cancer development and may be useful in targeted therapy of patients with gastric cancer.

The aim of the present study was to explore the classification of the internal iliac artery (IIA) and the diagnostic value of the pelvic tumour-feeding artery by multislice computed tomography angiography (MSCTA) compared with digital subtraction angiography (DSA). A total of 43 patients with pelvic tumours were enrolled between January 2013 and August 2017. The classification of the IIA and the quality of the feeding artery of the pelvic tumours were analysed by Yamaki's classification (Groups A-D according to IIA branching) and the 5-point scoring system. The degree of feeding artery stenosis, caused by tumour compression or invasion, was analysed by a 4-point scoring system. The Wilcoxon signed-rank test was used to determine the vascular diagnostic quality identified by MSCTA and DSA. MSCTA of the pelvic arteries was successfully performed in all patients. The main classifications of the IIA were Group A, followed by Group C, then Group B and with no cases of Group D. There was no significant difference in the classification of the IIA between the left and right sides on MSCTA and DSA. The visualization quality of the IIA and its main branches showed excellent consistency, but the difference in the terminal branches of the feeding arteries in the pelvic tumours was statistically significant between MSCTA and DSA. MSCTA has great advantages in evaluating the classification of the IIA, the imaging quality evaluation of the IIA and its main branches, and in the evaluation of the pelvic tumour-feeding artery. However, in the display of the terminal arterial branches of the pelvic tumours, DSA remains irreplaceable, particularly in cases of interventional embolization.

Although hepatitis B virus (HBV) infection is responsible for liver cancer, the exact mechanism of its action remains unclear. μ1 adaptin is an intrinsic part of the clathrin adaptor AP-1 complex. In addition to its canonical biological function that involves cargo sorting and vesicular transport, recent studies have demonstrated that μ1 adaptin participates in cell growth and proliferation. The aim of the present study was to investigate the effects of the clathrin adaptor AP-1 complex subunit mu-1 (AP1M1) on liver cancer cell proliferation. The present study reports for the first time that AP1M1 is upregulated in the HBV-transfected HepG2.215 liver cancer cells. Silencing of AP1M1 in HepG2.215 cells suppressed their proliferation, while the overexpression of AP1M1 in HepG2 cells promoted cell proliferation. The data suggested that AP1M1 is one of the crucial factors involved in the progression of liver cancer caused by HBV infection. In addition, it was demonstrated that HBV facilitated AP1M1 expression in a JNK-dependent manner. The increased expression levels of AP1M1 enhanced phosphorylation of protein kinase B and accelerated cell proliferation. Unraveling the effects of AP1M1 on liver cancer cell proliferation and the mechanism of AP1M1 transcriptional regulation may provide new therapeutic targets for HBV-positive liver cancer.

The aim of the present study was to investigate the underlying molecular mechanisms of the potent cell cycle inhibition and apoptotic effect of luteolin on LoVo human colon cancer cells. In the present study, Cell Counting kit-8 assay revealed that luteolin exerted notable cytotoxicity on LoVo cells in a dose- and time-dependent manner, with a 50% inhibitory concentration value of 66.70 and 30.47 µmol/l at the time points of 24 and 72 h, respectively. Flow cytometric analysis confirmed that luteolin promoted cell cycle arrest at the G2/M phase, and subsequently induced cell apoptosis. Western blot analysis further revealed that luteolin exhibited an inhibitory effect on the proliferation of LoVo cells by inhibiting cell cycle arrest at the G2/M phase transition, with an inactivation of cyclin B1/cell division cycle 2 and induction of cell apoptosis, in part via cytochrome c- and deoxyadenosine triphosphate-mediated activation of apoptotic protease activating factor 1. In vivo studies revealed that luteolin effectively decreased the colon tumor body weight of mice. Therefore, the evidence suggests that luteolin may be a potential chemopreventive and chemotherapeutic agent against human colon cancer.

Sarcomas represent a heterogeneous group of mesenchymal malignancies arising at various locations in the soft tissue and bone. Though a rare disease, sarcoma affects ~200,000 patients worldwide every year. The prognosis of patients with sarcoma is poor, and targeted therapy options are limited; therefore, accurate diagnosis and classification are essential for effective treatment. Sarcoma samples were acquired from 199 patients, in which TP53 (39.70%, 79/199), CDKN2A (19.10%, 38/199), CDKN2B (15.08%, 30/199), KIT (14.07%, 28/199), ATRX (10.05%, 20/199) and RB1 (10.05%, 20/199) were identified as the most commonly mutated genes (>10% incidence). Among 64 soft-tissue sarcomas that were unclassified by immunohistochemistry, 15 (23.44%, 15/64) were subsequently classified using next-generation sequencing (NGS). For the most part, the sarcoma subtypes were evenly distributed between male and female patients, while a significant association with sex was detected in leiomyosarcomas. Statistical analysis showed that osteosarcoma, Ewing's sarcoma, gastrointestinal stromal tumors and liposarcoma were all significantly associated with the patient age, and that angiosarcoma was significantly associated with high tumor mutational burden. Furthermore, serially mutated genes associated with myxofibrosarcoma, gastrointestinal stromal tumor, osteosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma and Ewing's sarcoma were identified, as well as neurotrophic tropomyosin-related kinase (NTRK) fusions of IRF2BP2-NTRK1, MEF2A-NTRK3 and ITFG1-NTRK3. Collectively, the results of the present study suggest that NGS-targeting provides potential new biomarkers for sarcoma diagnosis, and may guide more precise therapeutic strategies for patients with bone and soft-tissue sarcomas.

Multiple drug resistance remains an unsolved problem in cancer therapy. A previous study has demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of doxorubicin treatment in a mouse tumor model. In the present study, the cross-resistance and sensitivity of HMECd1 and HMECd2 established cell lines to anti-angiogenic drugs, particularly sunitinib, was explored. The results revealed that Dox treatment induced a significant increase in the breast cancer resistance protein (ABCG2) gene transcription and protein expression. This increase gave rise to a 4- to 5-fold increase in the half maximal inhibitory concentration of the HMECd1 and HMECd2 cells in response to sunitinib treatment in vitro. Functionally, the role of ABCG2 in the resistance to sunitinib was confirmed by the use of the ABCG2 inhibitors fumitremorgin C and diethylstilbestrol, which blocked cell resistance. The present study indicates that endothelial cells exhibit cross-resistance between cytotoxic drugs and anti-angiogenic drugs. This suggests that multiple drug resistance induced by chemotherapy in endothelial cells may affect the efficiency of anti-angiogenic drugs.

EphA2 is persistently overexpressed and functionally changed in numerous human cancers. However, to the best of our knowledge, the role that EphA2 plays in prostate cancer is not entirely clear. To investigate the roles of EphA2 in the development and progression of prostate cancer, the present study initially evaluated the roles of the EphA2 protein in LNCaP prostate cancer cells using recombinant plasmid, western blot analysis, flow cytometry, Matrigel invasion chamber and the cell counting kit-8 assay. An immunohistochemistry assay was also conducted to observe the effects of EphA2 in prostate cancer tissues. The results demonstrated that the LNCaP human prostate cancer cells that were transfected with pcDNA3.1(+) plasmid-mediated pcDNA3.1(+)-EphA2, markedly enhanced the cell growth and invasion in vitro. Additionally, EphA2 was overexpressed in prostate cancer specimens and the expression of EphA2 was significantly associated with Gleason grade, total prostate-specific antigen, advanced clinical stage and lymph node metastasis. Collectively, these results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human prostate cancer.

The undetectable onset of glioma and the difficulty of surgery lead to a poor prognosis. Appropriate biomarkers for diagnosis and treatment need to be identified. Interleukin-1 receptor-associated kinase 4 (IRAK4) is involved in the initiation and progression of cancer. However, up until now, no report has revealed the relationship between IRAK4 and glioma. The present study aimed to examine the expression of IRAK4 in glioma, and to determine if there was a relationship between IRAK4 expression and clinical outcomes or survival prognosis. Thousands of glioma tissue samples and corresponding clinical information were obtained from various databases. Then a series of bioinformatics methods were used to reveal the role of IRAK4 in glioma. Finally, reverse transcription-quantitative PCR technology was used to verify the bioinformatics results. The study found that the expression of IRAK4 was significantly increased in glioma compared with the control brain tissue samples, and IRAK4, as an independent prognostic factor, shortened the overall survival time of patients with glioma. Gene Set Enrichment Analysis showed that IRAK4 promoted the activation of cell signalling pathways, such as NOD-like and Toll-like receptor signalling pathways. Co-expression analysis showed that the expression of IRAK4 was correlated with CMTM6, MOB1A and other genes. The present study demonstrated the role of IRAK4 as an oncogene in the pathological process of glioma for the first time, and highlights the potential of IRAK4 as a biomarker for prognostic evaluation and treatment of glioma.

Sphingosine kinase 1 (SPHK1), an ATP-dependent protein, has previously been demonstrated to be upregulated in several types of human cancer and to play an important role in tumor development and progression. However, the role of SPHK1 in predicting long-term prognosis in patients with papillary thyroid carcinoma (PTC) remains unclear. The purpose of the present study was to assess the significance of SPHK1 expression and its associations with clinicopathological characteristics and prognostic outcome in patients with PTC. Immunohistochemistry staining was retrospectively performed to investigate the expression levels of SPHK1 in 92 PTC tumors. Statistical analyses revealed that high levels of SPHK1 expression were associated with tumor size, lymph node metastasis and the Tumor-Node-Metastasis stage. The disease-free survival (DFS) time of patients that exhibited high levels of SPHK1 expression was shorter, whereas patients with lower levels of SPHK1 expression survived longer. Furthermore, multivariate analysis suggested that upregulated SPHK1 was an independent prognostic factor for predicting DFS of patients with PTC. The results of the Cell Counting Kit-8 and invasion assays demonstrated that SPHK1 overexpression significantly enhanced the proliferation and invasion of a PTC cell line, consistent with clinical findings. The results from the present study provide evidence that elevated expression levels of SPHK1 may be involved in the development and progression of PTC, indicating that this protein may act as a potential prognostic marker for patients with this disease.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick sensor involved in the base excision repair (BER) pathway. Olaparib, a PARP inhibitor, has demonstrated antitumor activity in homologous recombination (HR)-deficient cancers. To extend this specific therapy to other types of carcinomas, a panel of 11 different cancer cells were screened in the present study. JF-305, a pancreatic cancer cell line of Chinese origin, demonstrated sensitivity to the PARP inhibitor 6(5H)-phenanthridinone. In the present study, 3 μM olaparib conferred a cell survival rate of 25% following four days of treatment. The colony formation efficiency was 83% at 10 nM, and dropped to 12% at 1 μM following seven days of treatment. Furthermore, olaparib induced cell cycle arrest in the S and G2/M phases prior to the initiation of apoptosis. Although the incidence of double-strand breaks (DSBs) was increased in the olaparib-treated JF-305 cells, the RAD51 foci were well formed at the sites of γ-H2AX recruitment, indicating an activated HR mechanism. Furthermore, tumor growth was reduced by 49.8% following 22 days of consecutive administration of 10 mg/kg olaparib in the JF-305 xenograft mouse model. In summary, the JF-305 cell line was sensitive to olaparib and provided a prospective model for the preclinical assessment of PARP inhibitors in the therapy of pancreatic cancer.

The exact effect of hypoxia on cancer development is controversial. The present study investigates the ability of osteosarcoma to form tumors in the hypoxic microenvironment induced by CoCl(2). MG63 human osteosarcoma cells were cultured with different concentrations (0, 150 and 300 μM) of CoCl(2) for 24 h to simulate hypoxia in vitro. The expression of hypoxia-inducible factor (HIF)-1α was analyzed by western blotting. The proliferation and drug resistance of MG63 cells were examined using the CCK-8 assay, the apoptosis rate was detected by flow cytometry, the ability to form spheroids was assessed by a sarcosphere culture system and invasiveness was determined by a vertical invasion assay. A transplantation assay was used to evaluate the ability to form tumors in vivo. Our results showed that the proliferation of MG63 cells was inhibited by treatment with CoCl(2), while no effect on drug toxicity was observed. The apoptotic rate was increased in a dose-dependent manner, the ability to form sarcospheroids was suppressed, the invasiveness was inhibited and the expression of HIF-1α was upregulated following CoCl(2) treatment. We also found that the ability to form tumors in vivo was inhibited. In conclusion, we provide strong evidence that CoCl(2) has the ability to inhibit osteosarcoma development; the mechanism may be related to the hypoxic microenvironment and HIF-1α may be a critical regulatory factor.

Clinical efficacy of single utility port video-assisted thoracoscopic surgery (VATS) and three-port VATS for patients with non-small cell lung cancer (NSCLC) was compared. A total of 156 patients with NSCLC who underwent VATS in Taizhou Hospital of Zhejiang Province from July 2015 to January 2017 were selected as subjects. They were randomly divided into group A (n=74) and group B (n=82), in which group A was treated with single utility port VATS and group B was treated with three-port VATS. Perioperative indicators such as operation time, intraoperative blood loss, postoperative drainage, removal of drainage tube, lymph node dissection, hospitalization time, postoperative complications, postoperative pain and postoperative quality of life were observed. Expression levels of CRP and IL-6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the operation time, postoperative drainage volume, drainage tube removal time and lymph node dissection between groups A and B (P>0.05). Blood loss and hospitalization time in group A were significantly lower than those in group B (P<0.001). VAS scores at 1-3 days after operation in group A were significantly lower than those in group B (P<0.001). Levels of serum CRP and IL-6 at 1-7 days after operation in group A were significantly lower than those in group B (P<0.001). Incidence of complication in group A was not significantly different from that in group B (P>0.05). Overall quality of life scores of group A and B were significantly lower than the preoperative scores (P<0.001). Overall status score of group A was significantly higher than that of group B (P<0.001). Clinical efficacies of single utility port VATS and three-port VATS were similar. Single utility port VATS can reduce trauma during surgery, reduce stress response, relieve postoperative pain, and facilitate the recovery of postoperative quality of life.