ABSTRACT
AIMS: A growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma. METHODS: Expression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson's X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson's or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis. RESULTS: High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients. CONCLUSION: Our research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.
Subject(s)
Adaptor Proteins, Signal Transducing/analysis , Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Glioma/chemistry , STAT3 Transcription Factor/analysis , Transcription Factors/analysis , Adolescent , Adult , Aged , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Child , Child, Preschool , Female , Glioma/mortality , Glioma/pathology , Glioma/therapy , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Grading , Phosphorylation , Predictive Value of Tests , Progression-Free Survival , Risk Assessment , Risk Factors , Time Factors , Tissue Array Analysis , YAP-Signaling Proteins , Young AdultABSTRACT
PURPOSE: Laparoscopy surgery is the gold standard for the treatment of aldosterone-producing adenomas (APA). However, the effectiveness between laparoscopic total and partial adrenalectomy is controversial. Therefore, we retrospectively analyzed the postoperative and follow-up outcomes of these two procedures. MATERIALS AND METHODS: A total of 96 APA patients underwent laparoscopic surgery in our hospital between January 2012 and December 2017. A total of 65 patients who underwent laparoscopic partial adrenalectomy (group 1) were compared with 31 patients who underwent laparoscopic total adrenalectomy (group 2). The mean follow-up time was 32.3 months and 40.8 months, respectively. Patient's preoperative characteristics, date during surgery, and postoperative clinical results of the two groups were analyzed. RESULTS: In both groups of patients, laparoscopic adrenalectomy was successfully carried out. The laparoscopic partial adrenalectomy group had a shorter operation time when compared to total adrenalectomy (P = .01). However, patients in the laparoscopic total adrenalectomy group were older (P = .04) and had a higher proportion of multiple adenomas (P = .01) compared to partial adrenalectomy. Five patients (7.7%) who underwent partial adrenalectomy did not show improvement in hypertension and/or serum potassium below normal levels, and review of plasma aldosterone concentration (PAC) and/or computerized tomography (CT) indicated that surgery was not successful in these patients. All 31 patients who underwent total adrenalectomy showed improvement or recovery from hypertension, and all PAC and serum potassium levels returned to normal levels after surgery. CONCLUSION: Although both surgical procedures were technically safe and feasible, laparoscopic partial adrenalectomy showed a higher failure rate (7.7%) for patients with APA. Therefore, choosing laparoscopic partial adrenalectomy requires careful consideration, and we selected laparoscopic total adrenalectomy in patients with unilateral APA.
Subject(s)
Adenoma/surgery , Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Laparoscopy , Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Adult , Aged , Aldosterone/biosynthesis , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel. It is commonly used as an expectorant and supplementary anti-cancer drug. ß-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose. Upon their interaction, ß-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid, which inhibits cytochrome C oxidase, the terminal enzyme in the mitochondrial respiration chain, and suspends adenosine triphosphate synthesis, resulting in cell death. Hydrocyanic acid is a cell-cycle-stage-nonspecific agent that kills cancer cells. Thus, ß-glucosidase can be coupled with a tumor-specific monoclonal antibody. ß-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a killing effect. ß-Glucosidase is injected intravenously and recognizes cancer-cell-surface antigens with the help of an antibody. The prodrug amarogentin is infused after ß-glucosidase has reached the target position. Coupling of cell membrane peptides with ß-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein. The Chinese medicine amarogentin and ß-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed.
Subject(s)
Amygdalin/therapeutic use , Antineoplastic Agents/therapeutic use , Prodrugs/therapeutic use , beta-Glucosidase/therapeutic use , Antibodies, Monoclonal/therapeutic use , Cell-Penetrating Peptides/therapeutic use , Humans , Iridoids/therapeutic useABSTRACT
Berberine is a wellknown component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a doseand timedependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostatespecific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway.