Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer (CRC), which is one of the leading causes of mortality worldwide. Previous studies have reported altered expression of a mucin-like protein Fc fragment of IgG binding protein (FCGBP) in various types of cancer, but its potential diagnostic, prognostic and immunological roles in CRC remain to be determined. Therefore, the aim of current study was to investigate the potential roles of FCGBP in CRC. The present study investigated FCGBP mutations and changes in its expression levels using a combination of microarray and public dataset analyses, as well as immunohistochemistry. The results demonstrated a 10.5% mutation frequency in the FCGBP coding sequence in CRC tissues, and identified decreased FCGBP mRNA or protein expression levels in colorectal adenoma and CRC (compared with those in normal colorectal tissues from healthy control subjects), including pathologically advanced CRC (stage III+IV vs. I+II). Survival analysis using the GEPIA and Kaplan-Meier Plotter databases revealed that low FCGBP expression levels were associated with short overall, disease-free, relapse-free and event-free survival times in patients with CRC. Notably, analysis using the online Tumor IMmune Estimation Resource database revealed a positive correlation between FCGBP expression levels and the extent of infiltrating immune cells, such as B cells and dendritic cells. Consistently, the expression levels of most markers (51/57) for various types of immune cells were significantly correlated with FCGBP expression levels in CRC tissues. These findings suggested that FCGBP may serve as a diagnostic and prognostic biomarker, and that FCGBP may be associated with immune infiltration in CRC. 相似文献
Study ObjectiveTo demonstrate the procedure and suspension skills of laparoendoscopic single-site (LESS) staging surgery with infrarenal para-aortic lymphadenectomy for early-stage ovarian cancer.DesignA presentation of the surgery through this technical video.SettingA hospital.Patient and InterventionsA 45-year-old woman presented with a pelvic mass on gynecologic examination and a serum cancer antigen 125 level of 5910 U/mL (normal = <35 U/mL). A computed tomographic scan revealed a mixture of solid and cystic components (70 × 77 × 71 mm) arising from the right ovary and characterized by the “ovarian vascular pelvic” sign. Clinically early-stage ovarian cancer was suspected. Subsequently, LESS staging surgery was performed by an experienced surgeon in our department.ResultsThe surgery lasted 280 minutes, and the volume of blood loss was 50 mL; there were no intra- or postoperative complications. We “hid” the incision perfectly for cosmetic purposes. The histopathologic findings supported high-grade serous ovarian cancer of the right ovary with the left fallopian tube involved as well. In addition, a total of 34 negative pelvic and 18 negative para-aortic lymph nodes were identified, and a stage of IIA was diagnosed as a result.ConclusionWe performed an LESS staging surgery for early-stage ovarian cancer successfully. Our video shows that the LESS approach provided feasible, cosmetic, and safe access among the selected malignant gynecologic surgery. Therefore, we have experienced that the effective suspension was an auxiliary measure for LESS lymphadenectomy. In addition, compared with multiport laparoscopy, the LESS approach could provide easier access to infrarenal para-aortic regions; furthermore, it was safe and quick to extract an unknown sample. 相似文献
Alpinetin is a natural flavonoid showing a variety of pharmacological effects such as anti-inflammatory, anti-tumor and hypolipidemic activities. Here, we aim to determine the roles of UDP-glucuronosyltransferases (UGTs) and breast cancer resistance protein (BCRP) in disposition of alpinetin.
Glucuronidation potential of alpinetin was evaluated using pooled human liver microsomes (pHLM), pooled human intestine microsomes (pHIM) and expressed UGT enzymes supplemented with the cofactor UDPGA. Activity correlation analyses with a bank of individual HLMs were performed to identify the main contributing UGT isozymes in hepatic glucuronidation of alpinetin. The effect of BCRP on alpinetin disposition was assessed using HeLa cells overexpressing UGT1A1 (HeLa1A1) cells.
Alpinetin underwent extensive glucuronidation in pHLM and pHIM, generating one glucuronide metabolite. Of 12 test UGT enzymes, UGT1A3 was the most active one toward alpinetin with an intrinsic clearance (CLint?=?Vmax/Km) value of 66.5?μl/min/nmol, followed by UGT1A1 (CLint?=?48.6?μl/min/nmol), UGT1A9 (CLint?=?21.0?μl/min/nmol), UGT2B15 (CLint?=?16.7?μl/min/nmol) and UGT1A10 (CLint?=?1.60?μl/min/nmol). Glucuronidation of alpinetin was significantly correlated with glucuronidation of estradiol (an activity marker of UGT1A1), chenodeoxycholic acid (an activity marker of UGT1A3), propofol (an activity marker of UGT1A9) and 5-hydroxyrofecoxib (an activity marker of UGT2B15), confirming the important roles of UGT1A1, UGT1A3, UGT1A9 and UGT2B15 in alpinetin glucuronidation. Inhibition of BCRP by its specific inhibitor Ko143 significantly reduced excretion of alpinetin glucuronide, leading to a significant decrease in cellular glucuronidation of alpinetin.
Our data suggest UGTs and BCRP as two important determinants of alpinetin pharmacokinetics.
Objective: To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA. Methods: SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. Results: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". Conclusions: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients. 相似文献