Promyelocytic leukemia zinc finger (PLZF) plays important roles in tumorigenic and developmental processes of various types of cancers. However, the expression of PLZF in gastric cancer (GC) has not been reported. The aim of the present study was to investigate the expression level and potential status of PLZF in GC as well as its possible mechanism. In the present study, we found that PLZF was downregulated in the majority of GC cell lines and tumor tissues and that alteration of PLZF expression was closely correlated with a malignant phenotype, epithelial-mesenchymal transformation and overall survival. Evaluation of in vitro proliferation, colony information, migration and invasion indicated that PLZF gene transduction induced a less malignant phenotype, which was also confirmed through in vivo studies performed in athymic nude mice. Furthermore, we assessed the expression levels of the lncRNA ANRIL in GC and found that it was negatively associated with the level of PLZF and that ANRIL indirectly methylated PLZF to suppress its expression via binding with polycomb repressive complex 2. When GC cells were treated with the methylation inhibitor 5-Aza-2'-deoxycytidine, the expression of PLZF increased, which further confirmed that PLZF was methylated. These results indicated that constitutive ANRIL activation was a possible cause of the lack of PLZF expression in GC cells. Coupled deregulation of PLZF and ANRIL may account for most of the alterations described in GC, and PLZF may become a potential target of GC therapy.
Interleukin-33 (IL-33), a newly-discovered cytokine belonging to the IL-1 family, serves an important role in inflammation. However, it is not clear whether IL-33 is of clinical significance in hepatocarcinogenesis. The present study was designed to investigate the role of IL-33 during oncogenesis and development of hepatocellular carcinoma (HCC). IL-33 protein expression was detected in 76 HCC (including 36 para-carcinoma), 33 cirrhosis, 30 hepatitis, and 20 normal liver tissues using immunohistochemistry. IL-33 mRNA expression in carcinoma and para-carcinoma tissues was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The possible correlation between IL-33 and clinicopathological parameters of HCC was also analyzed. Significant differences in IL-33 expression were not observed among normal, hepatic, and cirrhotic tissues (P>0.05), whereas the level of protein positive rate was markedly reduced in HCC tissues (P<0.01). Positive staining of IL-33 in non-cancerous liver (NCL) tissues (i.e. normal, hepatitis, and liver cirrhosis) was located predominantly in the nucleus and occasionally in the cytoplasm of hepatocytes; however, the expression in HCC tissues was mostly restricted to the cytoplasm. A significant alteration in protein localization was observed in HCC tissues as compared with NCL tissues (P<0.01). In comparison with HCC tissues, cytoplasmic staining of IL-33 was increased in para-carcinoma tissues. RT-PCR assay further confirmed relatively high mRNA expression levels of IL-33 in para-carcinoma tissues. IL-33 expression was significantly negatively associated with tumor histological grade (r=−0.279, P=0.015), but not with year, gender, tumor size, clinical stage, HCC with hepatitis and cirrhosis background, lymph node metastasis or intrahepatic vascular embolism (P>0.05). Therefore, the aberrant expression of IL-33 is associated with oncogenesis and progression of HCC and the cytoplasmic accumulation of the protein may serve a role in hepatocarcinogenesis.
To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.
BackgroundThis study aimed to compare the efficacy and safety of vinorelbine plus cisplatin (NP regimen) vs. gemcitabine plus cisplatin (GP regimen) for treatment of metastatic TNBC after failure with anthracyclines and taxanes.Material/MethodsA total of 48 patients with metastatic TNBC that failed in anthracyclines and taxanes treatment were enrolled and randomly grouped. Patients in the NP group (n=22) were given 25 mg/m2 vinorelbine on days 1 and 8 and 25 mg/m2 cisplatin on days 2–4 of each 21-day cycle, while subjects in the GP group (n=26) were administered 1000 mg/m2 gemcitabine on days 1 and 8 and 25 mg/m2 cisplatin on days 2–4 of each 21-day cycle. The treatment response and adverse events were compared between the 2 groups every 2 cycles.ResultsThe ORR, DCR, and median TTP were 45.5%, 77.3%, and 5 months in the NP group, and 46.2%, 80.8%, and 5.2 months in the GP group, and no significant differences were observed in ORR, DCR, and median TTP between the 2 groups (P>0.05). The major adverse events included grade I–II bone marrow inhibition, gastrointestinal reactions, and phlebitis, and a lower incidence of thrombocytopenia and rash and a higher incidence of phlebitis was found in the NP group than in the GP group (P<0.05).ConclusionsEither NP or GP regimen is active and tolerated in treatment of metastatic TNBC with anthracyclines and/or taxanes resistance, which may be used as a salvage treatment for metastatic TNBC.
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