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Hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer, accounting for ~90% of all primary malignancy of the liver. Although various medical treatments have been used as systemic therapies, patient survival time may be extended by only a few months. Moreover, the underlying mechanisms of HCC development and progression remain poorly understood. In the present study, the single-cell transcriptome of one in vivo HCC tumor sample, two in vitro HCC cell lines and normal peripheral blood mononuclear cells were analysed in order to identify the potential mechanism underlying the development and progression of HCC. Interestingly, JunB proto-oncogene was identified to serve a role in the immune response and in development and progression of HCC, potentially contributing to the development of novel therapeutics for HCC patients. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes. Then, the mRNA levels of key genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in U-2 OS cells. Finally, cell apoptosis, proliferation, migration and invasion arrays were performed. In total, 201 DEGs were identified in the curcumin-treated group. EEF1A1 (degree=88), ATF7IP, HIF1A, SMAD7, CLTC, MCM10, ITPR1, ADAM15, WWP2 and ATP5C1, which were enriched in 'biological process', exhibited higher degrees than other genes in the PPI network. RT-qPCR demonstrated that treatment with curcumin was able to significantly increase the levels of CLTC and ITPR1 mRNA in curcumin-treated cells compared with control. In addition, targeting ITPR1 with curcumin significantly promoted apoptosis and suppressed proliferation, migration and invasion. Targeting ITPR1 via curcumin may serve an anticancer role by mediating apoptosis, proliferation, migration and invasion in U-2 OS cells. [ABSTRACT FROM AUTHOR]

The present study assessed whether estrogen receptor (ER)β1 is associated with the survival of patients with advanced lung adenocarcinoma, with or without mutations of the epidermal growth factor receptor (EGFR) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Pathologically confirmed stage IV lung adenocarcinomas were assessed for EGFR mutations and ERβ1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and the log-rank test. A total of 122 out of the 201 (60.7%) patients had EGFR mutations, 64 (31.8%) of which were EGFR Del19 and 58 mutations (28.9%) were EGFR exon 21 L858R mutation. The presence of EGFR mutations was significantly increased in female patients compared with male patients (P<0.001) and in non-smokers compared with smokers (P<0.001). Patients with EGFR mutations had a significantly improved PFS and OS compared with patients without EGFR mutations treated with EGFR-TKIs. Furthermore, ERβ1 expression was significantly increased in patients with EGFR mutations compared with patients without EGFR mutations (P=0.001). However, the median PFS (P=0.005) and OS (P=0.002) of patients carrying the EGFR exon 21 L858R mutation was significantly decreased in patients with tumors where ERβ1 cytoplasmic expression was high. The multivariate analysis demonstrated that ERβ1 expression was the only independent predictor of PFS (P=0.002) and OS (P=0.003) in patients carrying the EGFR exon 21 L858R mutation. The data demonstrated that ERβ1 expression may predict outcomes of patients with lung adenocarcinoma treated with EGFR-TKI. [ABSTRACT FROM AUTHOR]

Locally advanced or metastatic disease accounts for the majority of breast cancer-associated cases of mortality. Treatment options for patients with locally advanced or metastatic disease are limited. The current study aimed to explore the efficacy and safety of apatinib combined with chemotherapy in patients with previously treated advanced breast cancer in real-world clinical practice. A total of 85 patients with advanced breast cancer, who had previously been exposed to anthracyclines or taxanes, received combined treatment. Tumor response was evaluated by a computed tomography scan based on the Response Evaluation Criteria in Solid Tumors. Adverse events were graded based on the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method and a log-rank test were used to analyze the univariate discrimination of progression-free survival (PFS) and overall survival (OS) by demographic data, baseline clinical information and toxicities. The combined effects of these variables were analyzed by a Cox proportional hazards regression model. At a median follow-up time of 9.7 months, 73 patients exhibited disease progression and 48 had succumbed to the disease. During the follow-up, 19 patients demonstrated a partial response (PR) and 53 patients achieved stable disease (SD), with an objective response rate of 23.2%. Additionally, 39 patients demonstrated a PR or SD for ≥24 weeks, with a clinical benefit rate of 47.6%. The median PFS was 4.4 months [95% confidence interval (CI)=2.8–6.0] and the median OS was 11.3 months (95% CI=8.9–13.8). No treatment-associated mortalities occurred. The most common adverse events of all grades included myelosuppression (49.4%), gastrointestinal reaction (45.9%) and fatigue (43.5%). Proteinuria was an independent predictive factor for PFS and OS. Apatinib combined with chemotherapy appeared to be efficacious for pretreated advanced breast cancer, with acceptable toxicity for real-world clinical practice. [ABSTRACT FROM AUTHOR]

The objective of the present study was to screen the key genes of ribavirin in hepatocellular carcinoma (HCC) and provide novel therapeutic targets for HCC treatment. The mRNA expression datasets of GSE23031 and GSE74656, as well as the microRNA (miRNA) expression dataset of GSE22058 were downloaded from the Gene Expressed Omnibus database. In the GSE23031 dataset, there were three HCC cell lines treated with PBS and three HCC cell lines treated with ribavirin. In the GSE74656 dataset, five HCC tissues and five carcinoma adjacent tissues were selected. In the GSE22058 dataset, 96 HCC tissues and 96 carcinoma adjacent tissues were selected. The differentially expressed genes (DEGs) and differentially expressed miRNAs were identified via the limma package of R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed with the Database for Annotation, Visualization and Integrated Discovery. The target mRNAs of DEMs were obtained with TargetScan. A total of 559 DEGs (designated DEG‑Ribavirin) were identified in HCC cells treated with ribavirin compared with PBS and 632 DEGs (designated DEG‑Tumor) were identified in HCC tissues compared with carcinoma adjacent tissues. A total of 220 differentially expressed miRNAs were identified in HCC tissues compared with carcinoma adjacent tissues. In addition, 121 GO terms and three KEGG pathways of DEG‑Ribavirin were obtained, and 383 GO terms and 25 KEGG pathways of DEG‑Tumor were obtained. A total of five key miRNA‑mRNA regulated pairs were identified, namely miR‑183→CCNB1, miR‑96→DEPDC1, miR‑96→NTN4, miR‑183→NTN4 and miR‑145→NTN4. The present study indicated that certain miRNAs (including miR‑96, miR‑145 and miR‑183) and mRNAs (including NAT2, FBXO5, CCNB1, DEPDC1 and NTN4) may be associated with the effects of ribavirin on HCC. Furthermore, they may provide novel therapeutic targets for HCC treatment. [ABSTRACT FROM AUTHOR]

Fumosorinone (Fumos) isolated from entomogenous fungi Isaria fumosorosea exhibited selective inhibition of Src homology phosphotyrosine phosphatase 2 inhibitor (Shp2) in our previous study. The purpose of the present study was to investigate the effects of Fumos on cell cycle arrest, tumor cell migration and the in vitro antiproliferative activity of Fumos alone or in combination with the commonly used cytotoxic drugs 5‑fluoracil (5‑FU) and p38 inhibitor SB203580. Fumos exhibited cytotoxicity against selected human cancel lines, including HeLa, MDA‑MB‑231 and MDA‑MB‑453 cell lines. Fumos exerted selective cytotoxic effects on the human cell lines. Flow cytometric and DAPI assays showed that Fumos did not induce cell apoptosis, however it induced cell cycle arrest at the G1 phase. Fumos inhibited cell migration though reducing the phosphorylation of focal adhesion kinase (FAK) at tyrosine (Tyr)861 and marginally increasing the phosphorylation of FAK at Tyr397, however, Fumos did not affect the phosphorylation of FAK at Tyr576 or Tyr925. The present study also examined the combination effect of Fumos with other chemical agents, including 5‑FU and p38 inhibitor SB203580. Fumos exhibited a marked synergistic effect with these agents, particularly with 5‑FU. In conclusion, Fumos showed potential anticancer bioactivity, and the combination effect of Fumos with 5‑FU or with p38 inhibitor offers a more effective anticancer strategy for carcinoma treatment. [ABSTRACT FROM AUTHOR]

The seven-amino acid truncated (7ND) protein is an N-terminal deletion mutant of monocyte chemoattractant protein-1 (MCP-1) and it functions as a dominant-negative inhibitor. 7ND and wild-type MCP-1 form a heterodimer, which binds to MCP-1 receptors and inhibits monocyte chemotaxis. In the present study, the 7ND protein was cloned, expressed and purified. An MTT assay revealed that the proliferation of oral squamous cell carcinoma (OSCC) SCC25 cells was not affected following 3 days of treatment with synthetic 7ND protein. Serial dilutions of the 7ND protein were tested for monocyte migration and osteoclast differentiation, and tartrate-resistant acid phosphatase staining demonstrated that significantly fewer osteoclasts were differentiated from cluster of differentiation 14+ (CD14+) monocytes using magnetic activated cell sorting. Immunofluorescence confirmed these results and significantly less F-actin staining was observed in 7ND-treated osteoclasts. Furthermore, bone invasion was examined by subcutaneously injecting SCC25 cells into the area overlaying the calvariae of nude mice. The results demonstrated that the average tumor volume of SCC25 cells with 7ND protein was similar to the average volume of tumors formed by untreated SCC25 cells. Flow cytometric analysis suggested that the CD14+ subpopulation in the bone marrow of 7ND-treated mice was reduced compared with that of untreated mice. Micro-computed tomography imaging revealed significantly less bone resorption in the calvariae injected with SCC25 cells plus the 7ND protein. Taken together, the results of the present study demonstrated the potential therapeutic value of the 7ND protein. The 7ND MCP-1 variant not only functions in vitro to inhibit osteoclast differentiation, but also reduces the progression of bone invasion by OSCC cells in vivo. [ABSTRACT FROM AUTHOR]

Metformin (Met) is a therapeutic agent for the treatment of type 2 diabetes mellitus. There is evidence that Met may reduce the risk of cancer in patients with type 2 diabetes mellitus by inhibiting tumor cell growth, prolonging the overall survival time in patients with various types of malignancy. However, the function and mechanism of Met have not been fully elucidated in osteosarcoma (OS). The present study evaluated the anti-proliferative effect of Met on MG63 and U2OS OS cells, identifying that it acted in a dose- and time-dependent manner. Met also inhibited OS cell migration and invasion, potentially by regulating the epithelial-mesenchymal transition in OS cells. Mechanistically, Met was demonstrated to partly exert these functions through the suppression of Akt phosphorylation, which was associated with increased phosphatase and tensin (PTEN) expression. Silencing PTEN prevented the Met-induced inhibition of the growth and metastasis of OS cells. As Met has anti-proliferative and anti-metastatic effects on OS cells it is a potential candidate, in combination with other chemotherapeutic agents, for use in the treatment of OS. [ABSTRACT FROM AUTHOR]

5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG), a novel synthetic isoflavone derivative, was demonstrated to possess antitumor activity in gastric cancer and breast cancer in vitro, but its antitumor effect and mechanism in ovarian cancer has not been characterized. The aim of the present study was to investigate the effects of HNPG on inhibiting the proliferation and invasion in human ovarian cancer A2780 cell lines of cisplatin resistance (A2780/DDP) and elucidate its underlying molecular mechanism. The results indicated that HNPG presented with marked antitumor activity against A2780/DDP cells in vitro, significantly inhibited the rates of proliferation, clone formation, invasion and metastasis, and markedly induced apoptosis in dose- and time-dependent manner. Simultaneously, levels of reactive oxygen species (ROS) were increased and mitochondrial membrane potential was decreased. In addition, Bcl-2 expression was downregulated, Bax expression was upregulated, and the ratio of Bcl-2/Bax was decreased. Concurrently, levels of Cyt-C were markedly enhanced and the caspase cascade was triggered. Taken together, the results suggested that HNPG exerted anticancer effects through promoting ROS accumulation in cells, triggering mitochondrial apoptotic pathways and ultimately resulting in cells apoptosis. Therefore, HNPG serves as a potential candidate in the chemoprevention and/or treatment of cisplatin-resistant human ovarian cancer. [ABSTRACT FROM AUTHOR]

The effects of NIN1/RPN12 binding protein 1 homolog (NOB1) on the pathogenesis of osteosarcoma and its expression on the chemosensitivity to cisplatin were investigated. Seventy‑four patients with osteosarcoma who received surgical resection in The Affiliated Hospital of Southwest Medical University (Sichuan, China) from September 2013 to September 2016 were enrolled in this study. The expression of NOB1 in cancer and cancer-adjacent tissues of patients was detected by reverse transcription-polymerase chain reaction, and the relationship between NOB1 expression and the pathogenesis of osteosarcoma was analyzed. The expression of NOB1 in osteosarcoma MG-63 cells was interfered with using small interfering ribonucleic acid (siRNA). Western blotting was used to detect the transfection efficiency and changes in apoptosis indicators. Cell Counting Kit-8 (CCK-8) assay was used to examine changes in the sensitivity of cells to cisplatin. The effect of NOB1 knockout on cell apoptosis was examined by flow cytometry. In patients with osteosarcoma, the level of NOB1 mRNA in cancer tissues was significantly higher than that in cancer-adjacent tissues (p<0.05), and the expression of NOB1 was correlated with Ennecking staging and tumor size (p<0.05). The expression level of the apoptotic indicator caspase-3 was activated after siRNA interfered with NOB1 expression, thus reducing the expression level of anti-apoptotic indicator B-cell lymphoma 2. CCK-8 results showed that the downregulation of NOB1 increased the sensitivity of MG-63 cells to cisplatin (p<0.05). In addition, flow cytometry showed that the downregulation of NOB1 significantly promoted the apoptosis of MG-63 cells. NOB1 is significantly upregulated in patients with osteosarcoma, thus reducing the curative effect of cisplatin chemotherapy, which indicates that the prognosis is poor. [ABSTRACT FROM AUTHOR]

Breast metastases from solid non‑breast tumor types are rare; however, they should be always considered in the differential diagnosis of a breast lesion owing to the associated poor patient prognosis and the requirement of different therapeutic strategies compared with those used to treat primary breast cancer. The aim of the current study was to summarize the characteristics of metastases to the breast in a southern Chinese population. The medical records and pathological sections of 22 patients with pathologically confirmed extra‑mammary metastases to the breast that presented to Sun Yat‑sen University Cancer Center between January 2000 and December 2015 were retrospectively reviewed. The median age of onset for breast metastasis was 43 years (range, 10‑62 years) and 19 (86.4%) patients had a known history of a primary tumor. The mean interval from diagnosis of the primary tumor to breast metastasis was 16.5 months (range, 6‑56 months). A unilateral (45.5% left, 36.4% right), upper outer quadrant (15/22, 68.2%) lesion of the breast was most frequently initially detected by self‑checking (63.6%). The most common origin of the primary tumor was the lung (22.7%). Nasopharyngeal carcinoma accounted for a high proportion of the metastases (18.2%). The median duration of survival from the time of diagnosis of a breast metastasis was 14 months (range, 2‑74 months). A total of 10 patients (45.5%) succumbed to the disease. The results also indicated that overall survival in patients that underwent surgery was improved compared with patients who did not undergo surgery. The results of the present study demonstrated that clinical history, imaging findings, pathology from the primary tumor and immunostaining were required in combination to establish an accurate diagnosis. Further investigation into the improvement of the prognosis of patients with metastases to the breast following surgery is required. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the prevalence and prognostic value of myeloid differentiation factor 88 (MYD88) L265P in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We assessed the MYD88 L265P mutation using an allele-specific semi-nested polymerase chain reaction method in 53 DLBCL patients treated with R-CHOP. The MYD88 L265P mutation was detected in 16 of 53 DLBCL (30.19%) samples from patients treated with R-CHOP. Age and location were statistically significantly associated with MYD88 L265P (P=0.025, 0.033, respectively), while treatment response and tumor recurrence were not. Univariate analysis showed that B symptoms (P=0.004) and Ki-67 (P=0.03) were significantly associated with progression-free survival (PFS), while MYD88 L265P showed no significant association with overall survival and PFS. Multivariate analysis showed that B symptoms were significantly associated with PFS. Our study suggests that the prognostic value of MYD88 L265P in DLBCL patients with R-CHOP requires further research. [ABSTRACT FROM AUTHOR]

Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G1 phase, which may b e a result of p oly(ADP-ribose) polymerase cleavage and caspase activation. Furthermore, 3,28-di-(2-nitroxy-acetyl)-oxy-BT-induced apoptosis was mitochondrion-mediated. The results of the present study demonstrated that Bcl-2-associated X protein translocated to the mitochondria from the cytosol following 3,28-di-(2-nitroxy-acetyl)-oxy-BT treatment. Notably, the phosphoinositide 3-kinase/protein kinase B signaling pathway was involved in 3,28-di-(2-nitroxy-acetyl)-oxy-BT-treated Huh7 cells. Therefore, the results of the present study demonstrated that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may inhibit HCC, which may be a possible application to treat HCC. [ABSTRACT FROM AUTHOR]

As an important chemotherapeutic agent for the treatment of osteosarcoma, the effectiveness of cisplatin is considered to be due to its unique properties, which allow it to penetrate the cell membrane and form various DNA-platinum adducts, resulting in genetic alterations or DNA damage. However, chemoresistance to cisplatin remains a major challenge for its use and chemotherapeutic effects. In the present study, an isogenic model of a cisplatin resistant osteosarcoma cell line, MG63-DDP, was generated from the original MG63 cell line. The expression level of microRNA (miR)-133b in the MG63-DDP cisplatin-resistant osteosarcoma cell line was analyzed by reverse transcription-quantitative polymerase chain reaction (PCR). Cisplatin-DNA adduct formation, cell death (carboxyfluorescein succinimidyl ester/propidium iodide staining) and clonogenic survival assays (crystal violet staining) were performed, comparing various cell types. The effect of miR-133b on migration (scratch wound assay) and invasion (Transwell assay) was also evaluated. Characterization studies have previously revealed an increased level of miR-133b in MG63-DDP cells compared with normal MG63 cells. Upregulation of miR-133b was associated with the accumulation of cisplatin-DNA adducts and an increase in cisplatin-induced cell death. Furthermore, increased miR-133b expression levels enhanced the migration and invasion of MG63 cells under cisplatin stress. Concordantly, in MG63-DDP cells the neutralization of miR-133b demonstrated opposite effects, as compared with the upregulation of miR-133b. To the best of our knowledge, the present study demonstrated for the first time that cisplatin-resistant MG63 cells exhibit an increased level of miR-133b expression. The endogenous expression level of miR-133b is sufficient for inducing cisplatin resistance, which suggests that miR-133b may be a biomarker for cisplatin resistance in osteosarcoma. [ABSTRACT FROM AUTHOR]

The aberrant expression of retinoic acid receptor‑α (RARα) has been reported in various types of cancer. However, its association with the prognosis and development of laryngeal squamous cell carcinoma (LSCC) has not yet been determined. Therefore, the present study aimed to examine the expression and function of RARα in patients with LSCC. The expression of RARα in LSCC tissues was investigated using immunostaining. An MTT assay and flow cytometry analysis were also performed to investigate the function of RARα in the proliferation and cell cycle of LSCC cells. The expression of RARα was significantly elevated in LSCC tissues compared with adjacent noncancerous tissues (78.1 vs. 6.3%, P<0.05). The overexpression of RARα was associated with poorly differentiated features of LSCC (P<0.05). Furthermore, the downregulation of RARα inhibited the proliferation of LSCC cells, and arrested the cell cycle at the G1 phase via upregulation of cyclin dependent kinase inhibitor 1A, which may be associated with inhibition of the protein kinase B signaling pathway. Therefore, the overexpression of RARα may contribute to the development of LSCC through the regulation of the cell cycle. The results of the present study provide evidence that RARα serves an important function in LSCC development and may be a potential therapeutic target or prognostic predictor for LSCC. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease that can be classified into several molecular intrinsic subtypes according to hormone markers, including estrogen receptor, progesterone receptor and human epidermal growth factor receptor‑2. Breast cancer cases with different hormone status vary with respect to patient morbidity, metastasis organotropism and disease progression. It is well known that the most preferential relapse site of breast cancer is in the bone, but the metastatic incidence is markedly higher in hormone receptor‑positive cancer compared with that in hormone receptor‑negative cancers. Bone marrow‑derived mesenchymal stem cells (BMSCs) perform important roles at the site of metastasis; however, the effects in different tumors or tumor subtypes are controversial. The present study aimed to explore the various effects of BMSCs on the biological characteristics of different hormone receptor statuses. BMSCs were obtained from female rats and characterized by cell lineage‑specific antigens. The MCF‑7 and MDA‑MB‑231 breast cancer cell lines, which are hormone receptor‑positive and ‑negative, respectively, were employed in the present study. The cancer cells were co‑cultured with BMSCs, and changes in the biological characteristic of cell growth, apoptosis, migration and epithelial‑mesenchymal transition (EMT) were assessed. BMSCs exhibited chemotactic attraction to MCF‑7, promoted the proliferation of MCF‑7 cells and reduced MCF‑7 cell apoptosis. By contrast, BMSCs exerted no marked effects on these behaviors of MDA‑MB‑231 cells. However, following co‑culture with BMSCs, the migratory ability was enhanced in the two cell lines. Furthermore, the expression of epithelial markers (epithelial‑cadherin and occludin) was decreased, and mesenchymal marker vimentin was markedly increased in the two cell lines. Notably, the migratory ability of MDA‑MB‑231 cells was attenuated compared with that of MCF‑7 cells. The results from the present study indicated that BMSCs may favor receptor‑positive cancer cell proliferation in bone and promote enhanced invasiveness of receptor‑negative compared with receptor‑positive cancer cells. [ABSTRACT FROM AUTHOR]

Radiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer. Although cancer cells are usually sensitive to radiotherapy, metastasis and local failure still occur mainly due to developed resistance to radiotherapy. Thus, it is critical to improve therapeutics for cancer treatment. The present study demonstrated that third-generation bisphosphonate zoledronic acid (ZOL), even at a low concentration, augments the radiosensitivity of cancer cells exposed to ionizing radiation (IR) by inducing S-phase arrest and subsequently promoting apoptosis. This function of ZOL was associated with elevated levels of cyclin A and cyclin B in the S and M phases, as well as decreased p21CIP1 expression. In addition, ZOL also inhibited malignant the invasiveness of cancer cells. Notably, these effects could be enhanced concurrently with IR. The present data indicated that combined treatment with ZOL plus IR may be a novel technique to augment the radiosensitivity of cancer cells. [ABSTRACT FROM AUTHOR]

Spalt-like transcription factor 4 (SALL4) is essential for the maintenance of the self-renewal and pluripotent properties in embryonic stem cells. Although the detailed mechanism remains unclear, dysregulation of SALL4 has been detected in various malignancies. Previously, the authors' of the present study reported that the expression level of SALL4 was associated with the poor prognosis of glioblastoma multiforme (GBM). The present study aimed to investigate the function of SALL4 in U251 human glioblastoma cells, including apoptosis and invasion inhibition. It was revealed that knockdown of SALL4 expression through RNA interference induced cell cycle arrest, enhanced early apoptosis and significantly inhibited invasion. Furthermore, downregulation of SALL4 was associated with a significantly lower expression level of the core transcription factors, including POU class 5 homeobox 1, SRY-box 2 and Nanog homeobox. In addition, inhibition of SALL4 significantly reduced the concentration of chemotherapeutic agent temozolomide required to inhibit cell growth by 50%, which decreased from 113.66±23.07 and 114.93±20.91 µg/ml to 68.34±3.52 and 67.44±4.71 µg/ml in two independent short interfering RNA transfected groups. These results indicate that SALL4 serves an important role in the GBM pathophysiology and targeting SALL4 may be a potential approach to the treatment of GBM. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the effects of remifentanil on hemodynamics, liver function, and expression of intercellular adhesion molecule‑1 (ICAM‑1) in patients with liver cancer undergoing surgery. A total of 60 patients who underwent liver cancer resection in The First People's Hospital of Xiangyang, Hubei University of Medicine from January 2014 to January 2016 were selected, including 33 males and 27 females, with an average age of 54.12±4.77 years. Patients were randomly divided into the control group and experimental group (n=30 each). The control group and experimental group were anesthetized with propofol/isoflurane and remifentanil/propofol, respectively. In addition to general parameters, the following parameters were analyzed: mean systolic blood pressure and mean diastolic blood pressure were obtained before treatment, during anesthesia induction and intubation, during blockade of traction reflexes in surgery, and before extubation at the end of surgery. The recovery time from anesthesia withdrawal to spontaneous breathing, time of eye opening, time of extubation, and level of consciousness were recorded. Liver expression of ICAM‑1 was measured with SABC staining, and the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were recorded on the first, third, fifth, and seventh day after surgery. According to hemodynamic parameters, patients in the experimental group experienced a more stable condition than patients in the control group (P<0.05). In addition, the recovery time of the experimental group was shorter than that of the control group (P<0.05). Markers of liver function (AST, ALT and TBIL) of the two groups after surgery were higher than those before surgery, and the increases of the experimental group were significantly lower than those of the control group. ICAM‑1 expression in the experimental group was significantly lower than in the control group (P<0.05). In conclusion, anesthesia with remifentanil better maintained the stability of hemodynamics, played a protective role against hepatic ischemia-reperfusion injury, and reduced ICAM‑1 expression. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and numerous other physiological progresses. The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is a novel caffeic acid amide derivative that was first synthesized in 2013. In the present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse neuron HT22 cell line were used to investigate the anticancer and cytotoxic effects of PT93 in vitro. The cytotoxicity of PT93 was measured using MTT and lactate dehydrogenase assays. The anti-proliferation effect was tested using a cell colony formation assay. Gelatin zymography analysis and a scratch test were used to investigate the anti-migration mechanism of PT93. Western blot analysis was used to measure the expression of MMP-2/-9. The experimental results showed that PT93 suppressed the proliferation of T98G cells, and showed cytotoxicity effects at high concentration in T98G, U87, U251 and HT22 cell lines. Furthermore, PT93 limited the migration ability of the cells and inhibited the extracellular MMP-2 and MMP-9 activity of T98G and U251 cells. Finally, the present study confirmed that PT93 affects the level of MMP-2/-9 expression in T98G cells in a concentration-dependent manner. The present study indicates that PT93, as a novel caffeic acid amide derivative, may be used in the treatment of GBM. [ABSTRACT FROM AUTHOR]

Clinically, temozolomide (TMZ) is widely used in glioblastoma (GBM) treatment. However, the toxicity of TMZ may influence the quality of patient life. Thus, novel treatment options for sensitizing GBM cells to TMZ chemotherapy are necessary. Aurora-A is widely expressed in GBM and correlated with poor prognosis. It has been proven to be an effective target for gene therapy and chemotherapy. In the present study, short hairpin (sh)RNA targeting Aurora-A was employed to knockdown Aurora-A expression in GBM cells. Cell Counting Kit-8 assays, flow cytometry, colony formation assays, invasion assays and tube formation assays were used to determine the effects of Aurora-A knockdown when combined with TMZ treatment. A U251 subcutaneous cancer model was established to evaluate the efficacy of combined therapy. The results of the present study indicated that the proliferation, colony formation, invasion and angiogenesis of GBM cells were significantly inhibited by combined therapy when compared with TMZ treatment alone. In vivo results demonstrated that knockdown of Aurora-A significantly (P=0.0084) sensitizes GBM cells to TMZ chemotherapy. The results of the present study demonstrated that knockdown of Aurora-A in GBM cells enhances TMZ sensitivity in vitro and in vivo. Therefore, Aurora-A knockdown may be a novel treatment option for decreasing TMZ toxicity and improving patient quality of life. [ABSTRACT FROM AUTHOR]

Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo. [ABSTRACT FROM AUTHOR]

The treatment of pharyngeal fistulas is complicated. It is more difficult to deal with pharyngeal fistula following surgical treatment for hypopharynx carcinoma, particularly in cases of pectoralis major muscle flap repair. The present study describes the case of a 56-year-old man who presented with a highly-differentiated pharyngeal squamous cell carcinoma located at the right side of the hypopharynx. The patient underwent a total laryngectomy and a right functional carotid dissection and tracheostomy; this was followed by post-operative radiotherapy. A pharyngeal fistula subsequently developed, but an attempt to repair this with a pectoralis major muscle flap failed. The complicated pharyngeal fistula was treated via continuous negative pressure-flush through a dual tube, without the requirement for incision, daily dressing or antibiotics. The favorable patient outcome represented a positive result, which was also able to reduce the psychological burden of the patient and improve their quality of life. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether dihydroartemisinin (DHA) induces apoptosis in the human cholangiocarcinoma QBC939 cell line through the regulation of myeloid cell leukemia-1 (MCL-1) expression. The inhibitory rates of DHA on QBC939 cell proliferation and the effects of DHA on the cell death rates at various DHA concentrations and following various treatment times were examined. The rate of apoptosis and cell cycle changes following DHA treatment were examined and the changes in the expression of MCL-1 mRNAs and MCL-1 proteins following DHA treatment were also examined. The MTT assay and trypan blue staining demonstrated that DHA significantly inhibited the proliferation (P<0.05) and promoted the death of QBC939 cells (P<0.05). The DNA ladder assay and flow cytometry (FCM) analysis demonstrated that the rate of apoptosis in the experimental group was significantly increased following DHA treatment (P<0.01). FCM analysis also demonstrated that DHA treatment led to a reduction in the percentage of QBC939 cells in the G0/G1 and G2/M phases, and the majority of the DNA-treated cells were arrested in the S phase of the cell cycle (P<0.01). Western blot analysis demonstrated that DHA treatment significantly upregulated the expression of the pro-apoptotic MCL-1S protein. In contrast, no significant difference in the expression of the anti-apoptotic MCL-1L protein was observed following DHA treatment. DHA affected the expression of the apoptosis-associated protein MCL-1 through multiple mechanisms. DHA treatment increased the ratio of MCL-1S/MCL-1L protein, thus inducing apoptosis in cholangiocarcinoma cells. [ABSTRACT FROM AUTHOR]

Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy. Uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT)1A induction is one of the mechanisms that is responsible for the cancer chemopreventive activity of SFN. The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction. These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ), the hydroxylated analog of chloroquine, is an antimalarial lysomotropic agent that inhibits autophagy due to lysosomal acidification, and subsequently blocks the fusion of autophagosomes with lysosomes which leads to the accumulation of autophagosomes that may accelerate tumor cell death. Given these hypothesis the aim of this study was to investigate the effects of HCQ in the inhibition of autophagy and the induction of apoptosis in cervical cancer SiHa cells. Cervical cancer SiHa cells were cultured with Hank's balanced salt solution (HBSS) as positive control of autophagy or treated with HCQ as part of the experimental groups. LC3 and P62/SQSTM1 were detected by quantitative polymerase chain reaction (qPCR) and western blotting, respectively in order to evaluate initially autophagosome formation and their degradation. Specific green fluorescent protein (GFP)-LC3 was subsequently detected by fluorescence microscopy in order to confirm the formation of autophagosomes. MTT and flow cytometry were adopted respectively to assess the proliferation and apoptosis of the SiHa cells. miRNA-9* was also investigated. The results demonstrated that HCQ increased the expressions of LC3 mRNA and LC3 protein and GFP-LC3 signalling but reduced the expression of p62/STSQM1 in cervical cancer SiHa cells. These results indicated HCQ has the ability to inhibit autophagy as incapable of degrading the autophagosome. However, HCQ may promote SiHa cell apoptosis as the MTT, apoptotic assay and miRNA-9* results revealed. HCQ has the ability to inhibit autophagy by blocking the degradation of autophagosomes and subsequently facilitates the apoptosis of cervical cancer SiHa cells. [ABSTRACT FROM AUTHOR]

Intramedullary spinal cord metastases (ISCMs) are rare and account for 4-8.5% of central nervous system metastases. Only one case of biopsy-proven ISCM due to prostate cancer has previously been reported. The current study presents an additional unique case of a 74-year-old male who developed symptoms from an intramedullary conus medullaris metastasis as the first manifestation of prostate adenocarci-noma. To the best of our knowledge, this scenario is even more rare and has not previously been reported. The tumor was radically resected, followed by androgen blockade treatment. The patient's neurological deficit significantly improved, with no tumor recurrence during the follow-up period. In addition, the present study provides an overview of the previous literature concerning ISCMs from prostate cancer, and discusses the treatment options. [ABSTRACT FROM AUTHOR]