Abstract COX7A1, a subunit of cytochrome c oxidase, holds an important position in the super-assembly which integrates into multi-unit heteromeric complexes peripherally in the mitochondrial electron transport chain (ETC). Recently, some studies indicated the significant potential of COX7A1 in cancer metabolism and therapy. However, the underlying metabolic process and therapy mechanism remain unclear. In this study, COX7A1-overexpressed cell line was established via lentivirus transduction. The relationship between COX7A1 and ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, was further analyzed in different human non-small-cell lung carcinoma (NSCLC) cells respectively. Our results showed that COX7A1 increased the sensitivity of NSCLC cells to the ferroptosis induced by cysteine deprivation via enhancing the tricarboxylic acid (TCA) cycle and the activity of complex IV in mitochondrial ETC. Meanwhile, COX7A1 suppressed mitochondrial dynamics as well as mitochondrial biogenesis and mitophagy through blocking autophagic flux. The autophagy activator, rapamycin, relieved the autophagic blockage and further strengthened the sensitivity to cysteine deprivation-induced ferroptosis of NSCLC cells in vitro and in vivo. Taken together, our data indicate the close association of COX7A1 with cysteine deprivation-induced ferroptosis, and provide a novel insight into the therapy mode against human NSCLC.
Ampelopsis sinica root is widely used in Chinese folk medicine for treating liver disorders caused by the hepatitis B virus (HBV). The present study was performed in order to investigate the anti‐HBV activity and mechanisms of the ethanol extract from A. sinica root (EASR) in vitro. The antiviral activity of EASR was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNAs in stable HBV‐producing human hepatoblastoma HepG2 2.2.15 cells. We found that EASR effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose‐dependent manner, and it also suppressed the amount of extracellular HBV DNA. After EASR treatment, the percentage of apoptotic cells was found to be significantly higher than that of control by flow cytometric analysis. A luciferase reporter gene assay was used to determine the effects of EASR on the activities of HBV promoters and intracellular signaling pathways. The results showed that EASR selectively inhibited the activities of HBV promoters (Cp, S1p and Fp) and the p53 signaling pathway in HepG2 cells significantly. These data indicate that EASR exerts anti‐HBV effects via inhibition of HBV promoters and the p53‐associated signaling pathway, which helps to elucidate the mechanism underlying the potential therapeutic value of EASR.
Existence of cancer stem cell is regarded as a main reason for metastasis and/or recurrences. In this study, the cancer stem-like cell derived from TJ905 glioblastoma multiforme cell line was isolated successfully. However, it was observed that generating rate of the cancer stem-like cells was lower than that of TJ905 cells, that expression of the anti-apoptotic and multidrug resistance-associated protein (MRP) genes were paradoxical to the literatures, which showed the uncertainty of cancer stem cells, and that some stem cell was not the solo factor to maintain tumor growth and resist apoptosis and anti-tumor drugs.
The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood. We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry. The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections. Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD.
Objective
To evaluate the curative efficacy and adverse events of in vitro hyperthermia in combination with chemotherapy for treating patients with advanced pancreatic carcinoma.
Methods
Seventy-five patients with advanced pancreatic carcinoma by pathologic diagnosis admitted in Beijing Friendship Hospital were enrolled and randomly divided into Group Combination (hyperthermia and chemotherapy) and Group Chemotherapy at the ratio of 1∶1. All the patients were treated for 4 cycles and the clinical efficacy were evaluated.
Results
After being treated for 4 cycles, the number of the patients in Group Chemotherapy who had complete response(CR), partial response(PR), stable disease(SD), progressive disease(PD) was 0, 10, 10 and 17, the objective response rate(ORR) was 27.0%, and the disease control rates(DCR) was 54.1%, which in Group Combination was 0, 18, 15 and 5, and 47.4% and 86.8%, respectively. DCR between the two groups was statistically significantly different (P=0.002), but there was no statistical significance on DCR(P=0.069). In Group Combination, the pain relief rate and physical fitness improvement rate was 92.1% and 84.2%, which were significantly higher than 21.6% and 27.0% in Group Chemotherapy, which had statistical significance (both P<0.05). The median survival time and 1-year survival rate in Group Combination was 8.8 months and 31.6%(12/38), which in Group Chemotherapy was 17.86 months and 27.0%(10/37), and there was no statistically significant difference between the two groups. The adverse events in two groups were mild, and no digestive tract reaction with III and IV degree and bone marrow suppression with IV degree were observed.
Conclusions
DCR and symptom improvement rate in Group Combination were higher than those in Group Chemotherapy, while the adverse events were mild, and patients could tolerate. This combination therapy was worthy of clinical application.
Key words:
Pancreatic neoplasms; Drug therapy, combination; Hyperthermia
The aim of the present study was to observe the effect of siRNA-Livin on the expression of multidrug resistance-associated protein (MRP) genes in a U251 cell line and U251 stem cells. CD133+ cancer stem cells were identified and isolated from the U251 glioblastoma cells, and morphological observations were used to detect the cell survival conditions. In addition, quantitative polymerase chain reaction was used to detect the mRNA expression levels of Livin, MRP1 and MRP3. Following transfection with the lentivirus containing the siRNA-Livin, the expression of Livin was significantly inhibited in the U251 cells and stem cells (P<0.01). Following temozolomide intervention, the proliferation of the U251 cells and U251 stem cells was restrained, with a lot of cell debris present and the structure of the cell spheres destroyed. The inhibitory effect was more significant following transfection with siRNA-Livin. Prior to siRNA-Livin transfection, the expression of MRP1 presented an increasing trend in the U251 cells and U251 stem cells with increasing drug concentrations and intervention times (P<0.05). Following siRNA-Livin transfection, the expression of MRP1 decreased in the U251 cells and U251 stem cells under the same drug concentration and intervention time (P<0.05), while the expression of MRP3 increased in the U251 stem cells under the same intervention concentration and time (P<0.05). Therefore, siRNA-Livin was shown to decrease the expression of MRP1 in U251 cells and U251 stem cells, increase the expression of MRP3 in U251 stem cells and decrease the proliferation of U251 cells and U251 stem cells. Thus, Livin may be associated with the high expression of MRP1, and siRNA-Livin may be used to lower the expression of MRP1 in order to reduce the drug resistance to chemotherapy in cases of glioblastoma.
To date, several positron emission tomography/computed tomography (PET/CT) radiotracers including fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 labeled choline (11C-choline), 18-F fluorocholine (18F-FCH) and carbon-11 acetate (11C-acetate) have already been assessed in the application of prostate cancer (PCa) diagnosis to some extent, the diagnostic efficiency of these radiotracers still remain controversial. As a result of this, we carried out this meta-analysis for the purpose of comparing the diagnostic accuracy among four PET/CT radiotracers.A systematical literature search for articles was performed until July 3, 2015. We implemented all analysis using the statistical software of STATA12 and quality assessment was performed using QUADAS-2.A total of 56 studies containing 3,586 patients were included in this meta-analysis. Parameter estimates of the overall analysis are as follows: sensitivity, 0.80 (95% CI: 0.74-0.85); specificity, 0.84 (95% CI: 0.77-0.89) and area under roc curve-AUC of SROC, 0.89 (95% CI: 0.86-0.91), indicating a relatively high level of accuracy in diagnosis of PCa. When different radiotracers of PET/CT were compared, 18F-FCH-PET/CT was ranked as the most favorable with the highest value of AUC (AUC = 0.94; 95% CI: 0.92-0.96) whereas 18F-FDG was the least favorable (AUC = 0.73, 95% CI: 0.69-0.77).This study suggested that PET/CT imaging plays an invaluable role in the diagnosis of PCa and 18F-FCH-PET/CT was considered as a superior diagnostic tool over other radiotracers. More attention should be paid to the diagnostic efficiency of the four radiotracers particularly for PCa patients with different clinical stages.
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