Epidermal growth factor receptor (EGFR) mutational status is a crucial biomarker for prediction of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Although these mutations have been well characterized in other countries, little is known about the frequency or spectrum of EGFR mutations in Vietnamese NSCLC patients.

As one of the most serious types of primary bone tumor, osteosarcoma (OSA) features metastatic lesions, and resistance to chemotherapy is common. The underlying mechanisms of these characteristics may account for the failure of treatments and the poor prognosis of patients with OSA. It has been reported that inhibition of Cyr61 suppresses OSA cell proliferation as it represents a target of statins. In addition to cystein‑rich protein 61 (Cyr61) and nephroblastoma overexpression, connective tissue growth factor (CTGF) is a member of the CCN family and may therefore exhibit effects on human OSA cells similar to those of Cyr61. In the current study, acridine orange/ethidium bromide staining were used to determine the rate of apoptosis. The present study demonstrated that small interfering RNA‑mediated silencing of CTGF promoted cell death and suppressed OSA cell migration and invasion, as indicated by wound healing and Transwell assays, while lentivirus‑mediated overexpression of CTGF reversed these effects. Furthermore, a colorimetric caspase assay demonstrated that CTGF knockdown enhanced the efficacy of chemotherapeutic drugs. The results of the present study provided a novel molecular target which may be utilized for the treatment of metastatic OSA.

The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. Herein, we investigated the possible role and mechanism of CD24 in cervical cancer. Our results showed that CD24 was overexpressed in cervical cancer tissues compared with that in the adjacent non‑cancerous tissues by qPCR, immunohistochemistry and western blotting technologies. To explore the possible mechanism of CD24 in cervical cancer, we elucidated the effect of CD24 on the proliferation and apoptosis of cervical cancer HeLa cells and found that a considerable increase in cell proliferation was observed in the HeLa cells with CD24 overexpession. The rate of cell apoptosis was decreased in the HeLa/CD24 cells compared with the HeLa or HeLa/vector cells. Cell apoptosis is closely related with a reduction in mitochondrial membrane potential (ΔΨm) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of CD24 in the cervical cancer HeLa cells, led to an increase in ΔΨm and a decrease in intracellular ROS and Ca2+ concentrations. Furthermore, we found that CD24 was correlated with dysregulation of the MAPK signaling pathway in cervical cancer tissues in vitro. At the same time, we found that CD24 overexpression affected the expression of p38, JNK2 and c-Jun in vitro. In summary, our results suggest that CD24 is upregulated in cervical cancer tissues and plays its functions by affecting the MAPK signaling pathway in cervical cancer.

A hypoxic microenvironment is commonly found in the central region of solid tumors, including pancreatic cancer. Our previous study revealed that resveratrol plays an important role in suppressing the proliferation and EMT of pancreatic cancer cells. However, whether resveratrol could suppress hypoxia-induced cancer progression and the underlying mechanisms have not been fully elucidated. The aim of the present study was to evaluate whether resveratrol affects hypoxia-induced reactive oxygen species (ROS) production and the activation of the Hedgehog (Hh) signaling pathway as well as the invasion of pancreatic cancer. The human pancreatic cancer cell lines, BxPC-3 and Panc-1, were subjected to a hypoxic condition and three different concentrations of resveratrol. The intracellular ROS were determined using 2,7-dichlorodihydrofluorecein diacetate. Wound healing and Transwell invasion assays were used to detect the migratory and invasive potential of the cancer cells. Metastatic-related and Hh signaling-related factors were detected by qRT-PCR and western blot analysis. Immunofluorescence staining was used to test the nuclear translocation of GLI1. The results showed that the hypoxia-induced production of ROS was decreased by resveratrol in a concentration-dependent manner. Resveratrol significantly inhibited the hypoxia-stimulated invasion and migration of pancreatic cancer cells. Resveratrol inhibited hypoxia-induced HIF-1α protein expression. Resveratrol also suppressed hypoxia‑induced expression of metastatic-related factors, uPA and MMP2. In addition, resveratrol markedly inhibited hypoxia-mediated activation of the Hh signaling pathway. Furthermore, the antioxidant N-acetylcysteine (NAC) significantly suppressed the invasive and migratory ability of pancreatic cancer cells during hypoxia. Taken together, these data indicate that resveratrol plays an important role in suppressing hypoxia-driven ROS-induced pancreatic cancer progression by inhibiting the Hh signaling pathway, providing evidence that resveratrol may be a potential candidate for the chemoprevention of cancer.

KIF2A is a member of the kinesin-13 family and is involved in cell mitosis and spindle assembly. The abnormal expression and dysfunction of KIF2A are associated with tumorigenesis and the progression of certain human cancer types; however, little is known about the expression and roles of KIF2A in glioma. In the present study, the expression of KIF2A in 35 freshly isolated human glioma tissue samples was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The association between the expression of KIF2A and clinicopathological parameters were assessed using the χ(2) test. The biological functions of KIF2A on the proliferation, apoptosis, migration and invasion of glioma cells were investigated using an A172 cell line. RT-qPCR and IHC results demonstrated that the mRNA and protein expression levels of KIF2A were significantly higher in grade III-IV glioma tissues compared with those in grade I-II glioma tissues (P<0.05). No significant correlation was observed between the expression of KIF2A, and age, gender, tumor location and size (P>0.05). In vitro, KIF2A gene silencing inhibited the proliferation, migration and invasion, and induced apoptosis in cancer cells. The present data suggested that KIF2A may be important in glioma progression and may serve as a novel predictive factor and therapeutic target for glioma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy.

Development of an efficient treatment for triple-negative breast cancer is an urgent issues. Compounds from plant extracts are a potential source of novel cancer treatment. Isolinderalactone, a kind of sesquiterpenoids compound, was purified from the root of Lindera strychnifolia and Neolitsea daibuensis and shows anti-inflammatory and anticancer capacity. In the present study, isolinderalactone induced apoptosis in MDA-MB-231 cells which is a kind of triple-negative breast cancer cell line through induction of an intrinsic mitochondria-mediated and caspase-independent cell death. Treatment of isolinderalactone increased the protein level of the suppressor of cytokine signaling 3 (SCOS3), decreased phosphorylation of the signal transducer and activator of transcription 3 (STAT3), and suppressed expression of the down-stream genes of the X-linked inhibitor of apoptosis protein in MDA-MB-231 cells. Our results further showed that the level of SOCS3 expression was induced by isolinderalactone due to inhibiting the microRNA hsa-miR-30c-5p (miR-30c) expression. In addition, intraperitoneal injection of isolinderalactone induced apoptosis in a xenograft breast tumor while it did not significantly affect the histology of liver, kidney and lung of the treated mice. In conclusion, isolinderalactone induces apoptosis in MDA-MB‑231 cells and suppresses STAT3 signaling pathway through regulation of SOCS3 and miR-30c. It may become a novel treatment for triple-negative breast cancer in the future.

Selenium has received much attention as an anticancer agent, although the mechanisms of action underlying its pro-apoptotic properties remain unclear. Tumors that respond well to antioxidant treatments, such as hepatocellular carcinoma (HCC), may benefit from treatment with selenium as this compound also has antioxidant properties. Furthermore, a major oncogenic driver in HCC is the nuclear transcription co-activator, β-catenin. In the present study, we examined the mechanism by which selenium reduces survival of HCC cells, and whether this was associated with modulation of the β-catenin pathway. Hep3B cell lines and cancer cell xenografted animals were treated with selenium, and apoptotic events or signals such as AMPK, β-catenin and GSK3β were determined. Further interactions among β-catenin, glycogen synthase kinase 3β (GSK3β), and AMPK were explored by applying AMPK small interfering RNA (siRNA) or GSK3β siRNA with western blotting or immunofluorescence microscopic observation. Selenium activated AMPK, which in turn suppressed β-catenin. Selenium induced the translocation of AMPK into the nucleus and prevented the accumulation of β-catenin therein. Upon inactivation of AMPK by AMPK siRNA, selenium no longer modulated β-catenin, implying that AMPK is an upstream signal for β-catenin. We found that the binding between AMPK and β-catenin occurs in the cytosolic fraction, and therefore concluded that the cancer cell antiproliferative effects of selenium are mediated by a GSK3β-independent AMPK/β-catenin pathway, although AMPK-mediated GSK3β regulation was also observed. We primarily discovered that AMPK is a crucial regulator initiating selenium-induced inhibition of β-catenin expression. Taken together, these novel findings help to illuminate the molecular mechanisms underlying the anticancer effect of selenium and highlight the regulation of β-catenin by selenium.

At present, the therapeutic treatment strategies for patients with hepatocellular carcinoma (HCC) remain unsatisfactory, and novel methods are urgently required to treat this disease. Members of the B cell lymphoma (Bcl)-2 family are anti‑apoptotic proteins, which are commonly expressed at high levels in certain HCC tissues and positively correlate with the treatment resistance of patients with HCC. ABT-737, an inhibitor of Bcl-2 anti-apoptotic proteins, has been demonstrated to exhibit potent antitumor effects in several types of tumor, including HCC. However, treatment with ABT-737 alone also activates certain pro-survival signaling pathways, which attenuate the antitumor validity of ABT-737. Curcumin, which is obtained from Curcuma longa, is also an antitumor potentiator in multiple types of cancer. In the present study, the synergistic effect of curcumin and ABT-737 on HCC cells was investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT-737 on HepG2 cells, which was partially dependent on the induction of apoptosis, according to western blot analysis and flow cytometric apoptosis analysis. In addition, the sustained activation of the ROS-ASK1-c-Jun N-terminal kinase pathway may be an important mediator of the synergistic effect of curcumin and ABT-737. Collectively, these results indicated that the combination of curcumin and ABT-737 can efficaciously induce the death of HCC cells, and may offer a potential treatment strategy for patients with HCC.

Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis.

Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro.

In previous studies, we demonstrated that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells derived from breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma. Based on these observations, human glioma U87 cells and a xenograft model in BALB/c nude mice were used to examine the antitumor activity of RHL against human glioma. Notably, RHL statistically significantly suppressed the growth of human glioma U87 xenografts in BALB/c nude mice. In vitro, there was a significant reduction in cell proliferation after treatment with RHL in a dose- and time-dependent manner. The overall growth inhibition was correlated with the increase in reactive oxygen species (ROS) production and cell apoptosis. The apoptosis- and cell cycle-related proteins including BAX and Bim were increased, whereas Bcl-2 and cyclin D were decreased in the RHL-treated cells. The results demonstrated that RHL is highly effective against the growth of human glioma U87 xenografts in BALB/c nude mice. The potent antitumor activity of RHL may be mediated through downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression.

To identify rare mutations and retrospectively estimate the cancer risk of a 45-year old female patient diagnosed with Li-Fraumeni syndrome (LFS), who developed nine primary malignant neoplasms in a period of 38 years, we conducted next-generation sequencing in this patient. Whole-genome and whole-exome sequencing were performed in DNA of whole blood obtained a year prior to the diagnosis of acute myeloid leukemia (AML) and at the time of diagnosis of AML, respectively. We analyzed rare mutations in cancer susceptibility genes using a candidate strategy and estimated cancer risk using the Risk-O-Gram algorithm. We found rare mutations in cancer susceptibility genes associated with an increased hereditary cancer risk in the patient. Notably, the number of mutated genes in p53 signaling pathway was significantly higher than expected (p=0.02). However, the phenotype of multiple malignant neoplasms of the studied patient was unlikely to be caused by accumulation of common cancer risk alleles. In conclusion, we established the mutation profile in a rare case of Li-Fraumeni syndrome, illustrating that the rare mutations rather than the cumulative of common risk alleles leading to an increased cancer risk in the patient.

The sensitization of breast cancer stem cells (BrCSCs) to the inhibitive effects of radiotherapy through adjuvant therapy which targets oncogenic pathways represents a prospective strategy for improving the effect of radiation in patients with triple-negative breast cancer (TNBC). Mammalian target of rapamycin (mTOR) activation is one of the most frequent events in human malignancies, and is critical for sustaining the self‑renewing ability of cancer stem cells (CSCs); inhibition by rapamycin is an effective and promising strategy in anticancer treatments. In the present study, we found that mTOR activity was closely related to the self-renewal ability of BrCSCs, and in triple negative MDA-MB-453 and MDA-MB‑468 cells, rapamycin repression of mTOR phosphorylation decreased the number of mammospheres and helped to sensitize the resistant CSCs to low-dose radiation therapy. By inhibiting mTOR and mitochondrial manganese superoxide dismutase (MnSOD), we confirmed that rapamycin functioned through the mTOR/MnSOD/reactive oxygen species (ROS) signaling pathway, and the existence of Akt governed the rapamycin‑induced asymmetric division (AD) of stem cells in cases of radiation‑treated breast cancer. The synergic effects of rapamycin and low-dose radiation induced the AD of stem cells, which then resulted in a decrease in the number of mammospheres, and both were mediated by MnSOD. Governed by Akt, the consequent inhibition of ROS formation and oxidative stress preserved the AD mode of stem cells, which is critical for an improved radiotherapy response in clinical treatment, as the tumor group is thus easier to eliminate with radiation therapy. We posit that an in-depth understanding of the interaction of radiation with CSCs has enormous potential and will make radiation even better and more effective.

Osteosarcoma (OS) is a primary bone malignancy with a high early metastatic propensity. It is crucial to find specific protein targets to develop therapeutic strategies against this lethal disease. Tetraspanin CD151 is involved in facilitating tumor metastasis. However, the role and molecular mechanism of CD151 in promoting OS metastasis remain enigmatic. In the present study, we used small interfering RNA (siRNA) to inhibit CD151 expression in highly metastatic OS cells and the results demonstrated that CD151 knockdown inhibited their migration, invasion and metastasis. We further investigated the molecular mechanism of CD151 by inhibiting genes known to be involved in metastasis in OS cells and found that CD151 modulated matrix metalloproteinase 9 (MMP9) expression through the glycogen synthase kinase 3 (GSK-3β)/β-catenin signaling pathway. We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS. This suggests that CD151 may be a useful antimetastatic target for OS.

Mutator phenotypes with microsatellite instability (MSI) are observed in a subset of solid tumors including those localized in the brain. MSI arises from impaired DNA mismatch repair. It can be a potential marker of resistance to radiation and chemotherapy, as demonstrated for several cancer types. Our study aims are to investigate MSI incidence in pituitary adenomas (PA) with a currently recommended methodology.

Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed.

In recent years, "liquid biopsy" received enormous attention as a new detecting method. As a non-invasive tumor screening method, the applications of liquid biopsy include early detection, monitoring relapse, assessment of therapy and molecule expression in lung cancer. The main source of liquid biopsy comes from circulating tumor cells (CTCs), ctDNA, and so on. This review will explore the biological characteristics, detection technologies and clinical applications of CTCs, ctDNA and other tumor markers in lung cancer and summarize liquid biopsy which in accord with three important criteria of high sensitivity (high specificity), clinical utility and repeatability, especially a new method of ligand-targeted PCR (LT-PCR) that showed a high sensitivity of 67.2% in stage I lung cancer. We expect that "liquid biopsy" could be really explored from scientific research to clinical application.

Lung cancer is a leading cause of cancer mortality worldwide. Several molecular pathways underlying mechanisms of this disease have been partly elucidated, among which the epidermal growth factor receptor (EGFR) pathway is one of the well-known signaling cascades that plays a critical role in tumorigenesis. The strategies to effectively inhibit EGFR signaling pathway have been used in non-small cell lung cancer (NSCLC) targeted therapy. Patients with EGFR mutations benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, most of TKIs-treated patients eventually suffer drug resistant after 10-month treatments. MiRNAs (microRNAs) is a non coding RNA and protein involved in regulating gene expression in the transcription level. More and more studies have found that miRNAs are correlated with EGFR-TKIs secondary resistance. MiRNAs may serve as novel targets to circumvent the resistance and promising predictive biomarkers for EGFR-TKIs. In this paper, we reviewed briefly advanced research on miRNAs and EGFR-TKIs secondary resistance in NSCLC.