Gramkoch5098

A marked increase in the number of apoptotic cells, together with a significant G1 phase block, were observed at 96 h post‑wo in the cells in which CDKN1A was knocked down, suggesting its involvement in the modulation of the response of RAL cells to the drug combination. On the whole, these data suggest that CDKN1A plays a role in the response to the cisplatin‑pemetrexed combination in advanced KRAS‑mutated NSCLC, thus suggesting that it may be used as a promising predictive marker.Although the effects of stem cells expressing anticancer genes on tumor growth have been demonstrated by many researchers in various types of cancer, relatively few studies have investigated their inhibitory effects on cancer metastasis. In the present study, we examined the inhibitory effects of cytosine deaminase (CD)/5‑fluorocytosine (5‑FC) and interferon‑β (IFN‑β) using genetically engineered neural stem cells (hNSCs) in a cellular and metastasis model of renal cell carcinoma (RCC). The CD/5‑FC method has the advantage of minimizing damage to normal tissues since it selectively targets cancer cells by the CD gene, which converts prodrug 5‑FC to the drug 5‑fluorouracil. Moreover, we used hNSCs as a tool to effectively deliver the anticancer genes to the tumor site. These stem cells are known to possess tumor‑tropism because of chemoattractant factors expressed in cancer cells. Therefore, we ascertained the expression of these factors in A498 cells, a cell line of RCC, and identified the A498‑specific migration ability of hNSCs. We also confirmed that the proliferation of A498 cells was significantly reduced by therapeutic hNSCs in the presence of 5‑FC. Furthermore, we established an A498 metastasis model. In the animal experiment, the weight of the lungs increased in response to cancer metastasis, but was normalized by hNSCs expressing CD and/or IFN‑β genes, while the incidence of liver metastasis was suppressed by the hNSCs. Overall, the results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.BarH‑like homeobox 2 (BARX2), a homeobox gene, is associated with several types of cancers. The present study aimed to determine whether DNA methylation downregulates BARX2 expression and whether BARX2 is associated with suppression of gastric carcinogenesis. BARX2 protein expression in normal and cancerous gastric tissues and various gastric cancer (GC) cell lines was detected using immunohistochemical and western blot assays. BARX2 mRNA levels were detected using both reverse transcription‑polymerase chain reaction (RT‑PCR) and quantitative PCR (qPCR). Promoter hypermethylation in GC cells was detected using methylation‑specific PCR or bisulfite DNA sequencing PCR. Effects of BARX2 expression on GC cell proliferation, clonal formation, and migration were evaluated after lentivirus‑BARX2 transfection. The effect of stable BARX2 transfection on tumor formation was assessed in a nude xenograft mouse model. BARX2 was strongly expressed in the normal gastric mucosa, but weakly or not expressed in GC tissues and most GC cell lines. BARX2 expression was negatively correlated with DNMT (a marker for DNA methylation) expression in the gastric tissues. The BARX2 promoter fragment was hypermethylated in the GC cell lines. Overexpression of BARX2 significantly inhibited GC cell proliferation, clonal formation, and migration. Stable BARX2 transfection inhibited tumor formation in xenograft mice, which was correlated with decreased expression of E‑cadherin, proliferation markers, and matrix metalloproteinases. In conclusion, BARX2 expression is aberrantly reduced in GC, which is associated with increased DNA methylation of its promoter. BARX2 inhibits GC cell proliferation, migration, and tumor formation, suggesting that BARX2 acts as a tumor suppressor in gastric carcinogenesis.Hispidulin is a medicinal natural compound isolated from S. involucrata, which exhibits potent anticancer properties. However, there are few reports on its effects on lung cancer cells. Therefore, the current study investigated the effects of hispidulin on cell viability and apoptosis in human non‑small‑cell lung cancer (NSCLC) cell lines NCI‑H460 and A549 in vitro and in vivo. Methyl thiazolyl tetrazolium, colony formation assay, Hoechst 33342 staining, flow cytometry and western blotting were performed on Human NCI‑H460 and A549 cells. A mouse xenograft model was also established using NCI‑H460 cells. The results showed that the growth of NCI‑H460 and A549 cells was inhibited, while apoptosis was promoted by hispidulin via increased generation of reactive oxygen species (ROS) in a dose‑dependent manner. Furthermore, hispidulin triggered apoptosis in NSCLC cells through upregulating the expression of cleaved caspase‑3 and cleaved poly [ADP‑ribose] polymerase. All these effects were reversed upon pretreatment with glutathione, a selective ROS inhibitor. In addition, endoplasmic reticulum stress (ER stress) in NCI‑H460 cells was activated by hispidulin. Pretreatment with tauroursodeoxycholic acid, a specific ER stress inhibitor, effectively reduced the cell apoptosis induced by hispidulin. In conclusion, hispidulin induces ROS‑mediated apoptosis via activating the ER stress pathway. The current study provides theoretical basis for the antitumor effect of hispidulin in NSCLC.Ketamine is a widely used general anesthetic and has been reported to demonstrate neurotoxicity and neuroprotection. Investigation into the regulatory mechanism of ketamine on influencing neural development is of importance for a better and safer way of relieving pain. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the critical neural associated gene expression, and flow cytometry to detect the neural differentiation effect. Hence, in the present study the underlying mechanism of ketamine (50 nM) on neural differentiation of the mouse embryonic stem cell (mESC) line 46C was investigated. The results demonstrated that a low dose of ketamine (50 nM) promoted the differentiation of mESCs to neural stem cells (NSCs) and activated mammalian target of rapamycin (mTOR) by upregulating the expression levels of phosphorylated (p)‑mTOR. Furthermore, inhibition of the mTOR signaling pathway by rapamycin or knockdown of mTOR suppressed neural differentiation. A rescue experiment further confirmed that downregulation of mTOR inhibited the promotion of neural differentiation induced by ketamine. Taken together, the present study indicated that a low level of ketamine upregulated p‑mTOR expression levels, promoting neural differentiation.Following the publication of this article, the authors have realized that an error was made with the description of the first and fourth listed affiliation addresses "North China University of Science and of Technology", should have been written as "North China University of Science and Technology". This error also affected the Correspondence box information. Therefore, the author affiliations and addresses, and the Corresponding author information, in this paper should have appeared as follows Zheng Bao1,2, Jinqi Hao3, Yuhong li1 and Fumin Feng1,4; 1School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210; 2Child Health Division, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101101; 3School of Public Health, BaoTou Medical College, Baotou, Neimenggu 014040; 4Center‑Laboratory, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China. Correspondence to Dr Fumin Feng, Center‑Laboratory, North China University of Science and Technology, 21 Bohai Road, Tangshan, Hebei 063210, P.R. China. E‑mail hblgffm@126.com; The authors regret this error in the presentation of these addresses, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 20 5190‑5196, 2019; DOI 10.3892/mmr.2019.10788].Multiple mechanisms are involved in regulating hepatic ischemia‑reperfusion injury (IRI), in which Kupffer cells (KCs), which are liver‑resident macrophages, play critical roles by regulating inflammation and the immune response. Suberoylanilide hydroxamic acid (SAHA), a pan‑histone deacetylase inhibitor, has anti‑inflammatory effects and induces autophagy. To investigate whether SAHA ameliorates IRI and the mechanisms by which SAHA exerts its effects, an orthotopic liver transplantation (OLT) rat model was established after treatment with SAHA. The results showed that SAHA effectively ameliorated OLT‑induced IRI by reducing M1 polarization of KCs through inhibition of the AKT/glycogen synthase kinase (GSK)3β/NF‑κB signaling pathway. Furthermore, the present study found that SAHA upregulates autophagy 5 protein (ATG5)/LC3B in KCs through the AKT/mTOR signaling pathway and inhibition of autophagy by knockdown of ATG5 in KCs partly impaired the protective effect of SAHA on IR‑injured liver. Therefore, the current study demonstrated that SAHA reduces M1 polarization of KCs by inhibiting the AKT/GSK3β/NF‑κB pathway and upregulates autophagy in KCs through the AKT/mTOR signaling pathway, which both alleviate OLT‑induced IRI. The present study revealed that SAHA may be a novel treatment for the amelioration of OLT‑induced IRI.Previous studies have shown that calycosin, a natural phytoestrogen which is structurally similar to estrogen, inhibits proliferation and induces apoptosis in estrogen‑dependent cancer types via the estrogen receptor (ER)β‑induced inhibition of PI3K/Akt. Therefore, the aims of the present study were to investigate the effects of calycosin on human osteosarcoma (OS), and to examine the molecular mechanisms associated with ERβ. Human OS MG‑63 cells were treated with various concentrations of calycosin, and MTT and flow cytometry assays were used to assess the effects of calycosin on cellular proliferation and apoptosis. In addition, protein expression levels of ERβ, phosphorylated (p)‑PI3K, p‑Akt, cleaved poly (ADP‑ribose) polymerase 1 (PARP) and cleaved caspase‑3 were evaluated by western blot analysis. The present results suggested that calycosin inhibited proliferation and induced apoptosis in MG‑63 cells. Furthermore, increased ERβ expression was detected in OS MG‑63 cells treated with calycosin, and an ERβ inhibitor (PHTPP) reversed calycosin‑induced cytotoxicity and apoptosis. Moreover, phosphorylation levels of PI3K and Akt were significantly downregulated after calycosin treatment, whereas PHTPP reversed their phosphorylation. ERβ‑mediated PI3K/Akt downstream signaling pathways were found to influence the activity of poly (ADP‑ribose) polymerase 1 and caspase‑3. Thus, the present results indicated that calycosin inhibited proliferation and induced apoptosis in OS MG‑63 cells, and that these effects were mediated by ERβ‑dependent inhibition of the PI3K/Akt pathways.Lung cancer is the most prevalent cancer worldwide and non‑small cell lung cancer (NSCLC) is the most common subtype and accounts for 75% of all lung cancer cases. Although programmed death‑1/programmed death‑ligand‑1 (PD‑1/PD‑L1) blockade has shown good results in the clinic, numerous NSCLC patients still fail to respond to this therapy. In the current study, formalin‑fixed, paraffin‑embedded tumor and matched blood samples from 1,984 Chinese NSCLS patients were collected for detection of genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations and gene rearrangements. The most common mutated genes were tumor protein p53 (55.70%; 1,105/1,984), epidermal growth factor receptor (52.47%; 1,041/1,184), KRAS proto‑oncogene GTPase (13.36%, 265/1084), cyclin dependent kinase inhibitor 2A (12.30%; 244/1,984), LDL receptor related protein 1B (11.09%; 220/1,984) and telomerase reverse transcriptase (10.58%; 210/1,984). Tumor mutational burden was calculated and results revealed that it was associated with PI3K/mTOR pathway gene mutations, and patient's gender, age, smoking status, and tumor stage.