Objective To systematically review the prognostic value of perineural invasion (PNI) for patients with early-stage cervical cancer. Methods We searched PubMed, EMbase, The Cochrane Library (Issue 10, 2016), CNKI, WanFang Data, CBM and VIP databases to collect case-control studies about prognostic value of PNI in cervical cancer from inception to October, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results Seven case-control studies from eight articles involving 1 218 patients were included. The results of meta-analysis showed that: (1) On Cox's model multivariate analysis, PNI was not identified as an independent risk factor for disease free survival (DFS) (HR=0.73, 95%CI 0.33 to 1.58,P=0.42) or overall survival (OS) (HR=0.89, 95%CI 0.41 to 1.94,P=0.77) with no significant difference; (2) On Kaplan-Meier-curves, DFS (HR=1.86, 95%CI 1.20 to 2.88,P=0.006) and OS (HR=2.43, 95%CI 1.63 to 3.62,P<0.000 1) were both significantly decreased in patients with PNI positive group. Conclusion PNI represents a decreasing disease-free survival and overall survival in patients with early-stage cervical cancer, and is one of the poor prognosis factors which be informed management decisions regarding adjuvant therapy. However, there is no evidence that PNI is an independent factor affecting the prognosis. In view of the limitation of the studies, a large sample prospective controlled trial is warranted to verify the above conclusion.
Objective To assess the impact of adjuvant chemotherapy (ACH) on the survival of patients with pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). Methods We retrospectively analyzed the clinical and follow-up data of 223 UCB patients who underwent RC between January 2005 and June 2015. None of the patients received neoadjuvant chemotherapy. Of all the patients, 75 (33.6%) were diagnosed as pT3 cancer (including 32 pT3a and 43 pT3b patients). The follow-up data were up to June 2015. Kaplan-Meier method with log-rank test was used to estimate and compare overall survival (OS) and cancer-specific survival (CSS) between groups. Multivariate Cox proportional hazard models were used to identify predictors of OS and CSS. Results The short-term total effective rate of gemcitabine and cisplatin assisted chemotherapy in the treatment of pT3 UCB was 60.0%. Five-year OS rate (47.9%vs. 43.3%) and CSS rate (57.4%vs. 57.6%) were similar in the pT3a and pT3b groups (P=0.682 and 0.796, respectively). In pT3 patients, adjuvant chemotherapy was an independent predictor for OS (P=0.032). On multivariate analysis, according to the pT3 sub-stage, ACH was significantly associated with improved OS [hazard ratio (HR) =0.37; 95% confidence interval (CI) (0.15, 0.68),P=0.006] and CSS [HR=0.34, 95%CI (0.12, 0.86),P=0.022] in the pT3b group only. Conclusion Because pT3b cancer is characterized by macroscopic peri-vesical tissue invasion, patients may obtain an OS benefit from the administration of adjuvant chemotherapy.
ObjectiveTo assess the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM) in evaluating microvessel density (MVD) and microvascular invasion (MVI) of hepatocellular carcinoma (HCC).MethodsRat models were established to be scanned by IVIM. HCC lesions corresponding to IVIM image were examined pathologically to get data of MVD and MVI. Spearman correlation analysis was used to compare the apparent diffusion coefficient (ADC), D, D*, and f with MVD, independent samples t test was used to compare ADC, D, D*, and f between MVI (+) and MVI (–) groups.ResultsFifty HCC lesions were included finally. ADC and D values both showed a negative correlation with MVD (r=–0.406, P=0.003; r=–0.468, P=0.001), D* and f showed no statistical correlation with MVD (P=0.172, 0.074, respectively). The differences in ADC and all the IVIM parameters (D, D*, and f) between MVI (+) and MVI (–) HCCs were not statistically significant (P=0.393, 0.395, 0.221, 0.550).ConclusionADC and D can be used to evaluate MVD of HCC, but ADC and IVIM parameters were limited in evaluating MVI.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.
ObjectiveTo investigate the effects of pipecolic acid oxidase (PIPOX) on the proliferation, apoptosis, migration and invasion of primary liver cancer cells. MethodsImmunohistochemical staining and analysis of The Cancer Genome Atlas (TCGA) database were used to examine the PIPOX expression levels in liver cancer tissues and paired adjacent normal tissues, and studied their relationship with patient prognosis. Liver cancer cell lines stably overexpressing or knocking out PIPOX were constructed to explore PIPOX’s impact on liver cancer cell proliferation, apoptosis, migration and invasion by conducting in vitro functional experiments such as CCK-8, EdU, apoptosis detection, and Transwell assays. In vivo, nude mice subcutaneous tumor models and lung metastasis models were used to verify PIPOX’s effect on liver cancer growth and metastasis. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were both employed to detect the expression of epithelial-mesenchymal transition (EMT) markers in liver cancer cells. ResultsImmunohistochemical staining and TCGA database analysis revealed that PIPOX expression was significantly lower in liver cancer tissues compared to paired adjacent normal tissues (P<0.05). Prognostic analysis indicated shorter overall survival and disease-free survival in PIPOX low expression group (P<0.05). In vitro gain- and loss-of-function experiments showed that PIPOX significantly inhibited liver cancer cell migration and invasion (P<0.05), while having no significant effects on their proliferation and apoptosis (P>0.05). Animal experiments also confirmed that PIPOX significantly inhibited liver cancer lung metastasis (P<0.05), but had no significant effects on tumor growth (P>0.05). Finally, RT-qPCR and western blot results revealed that PIPOX promoted the expression of the epithelial marker E-cadherin (P<0.05) and inhibited the expression of mesenchymal markers (N-cadherin, vimentin, Snail) (P<0.05). ConclusionsPIPOX significantly inhibits liver cancer cell migration and invasion, potentially via suppressing the EMT process. However, PIPOX does not significantly affect liver cancer cell proliferation and apoptosis.
Objective To further comprehend the definition， molecular mechanism， and clinical significance of perineural invasion （PNI） so as to explore new therapy for the tumors. Methods The literatures about the definition， molecular mechanism， and clinical study of PNI were reviewed and analyzed. Results At present， widely accepted definition of PNI was that at least 33% of the circumference of the nerve should be surrounded by tumor cells or tumor cells within any of three layers of the nerve sheath. The newest theory on molecular mechanism of PNI was that PNI was more like infiltration， invasion， not just diffusion. “Path of low-resistance” and “Reciprocal signaling interactions” were the main theories. More recently， the studies had demonstrated that “Reciprocal signaling interactions” could more clearly explain the mechanism of PNI. Stromal elements， including fibroblasts， seemed to play a key role in the complex signaling interactions driving PNI. Neurotrophins and axonal guidance molecules had been implicated in promoting the progress of PNI. PNI was a prognosis index in the cancers of the head and neck， stomach， pancreas， colon and rectum， and prostate， which was positive indicated that the patients would have a poor prognosis and a low 5-year survival rate. Conclusions The mechanism of PNI is very complex， and its clear mechanism is still undefined. Keeping on researching the mechanism of PNI could provide theoretical foundation to disclose the mechanism and the therapy of PNI.
ObjectiveTo explore the predictive value of serum prothrombin induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) detection for the biological characteristics of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).MethodsThis retrospective study included 394 patients with HBV-related HCC who were newly diagnosed and treated with surgical resection in West China Hospital of Sichuan University between June 2017 and December 2018. Their clinical information such as tumor size, tumor number, tumor cell differentiation, presence of microvascular invasion (MVI), distant metastasis, and portal vein tumor thrombus was collected from the medical record. The laboratory test results of patients during diagnosis and before surgery were collected, including alpha-fetoprotein (AFP), PIVKA-Ⅱ, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GGT), etc., and the relationships between PIVKA-Ⅱ levels and tumor biological characteristics were analyzed. Non-normal continuous variables were presented as medium (lower quartile, upper quartile).ResultsCompared with the patients with low HCC serum PIVKA-Ⅱ levels (≤40 mAU/mL), patients with high serum PIVKA-Ⅱ levels (>40 mAU/mL) had larger tumor diameters [5.00 (3.00, 9.00) vs. 2.50 (1.63, 4.95) cm, P<0.001], more severe Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001), and higher AFP [186.05 (6.86, 1 210.00) vs. 17.83 (4.33, 231.95) ng/mL, P<0.001], ALT [38.00 (26.00, 66.25) vs. 32.00 (22.00, 51.00) U/L, P=0.018], AST [42.00 (30.00, 76.00) vs. 34.00 (25.50, 48.25) U/L, P<0.001], and γ-GGT [71.00 (39.00, 165.50) vs. 55.50 (25.00, 93.00) U/L, P=0.005], and were more likely to form portal vein tumor thrombi (16.61% vs. 3.75%, P=0.003) and MVI (43.67% vs. 11.11%, P<0.001). In BCLC stage 0 HCC patients, the positive rate of PIVKA-Ⅱ was only 51.35%. Multivariate logistic regression analysis showed that PIVKA-Ⅱ>40 mAU/mL was an independent predictor of MVI [odds ratio=6.588, 95% confidence interval (CI) (1.645, 26.383), P=0.008]. The area under receiver operating characteristic curve of PIVKA-Ⅱ level predicting MVI was 0.761 [95%CI (0.693, 0.830)], with a sensitivity of 66.22% and a specificity of 79.06%.ConclusionIn HBV-related HCC patients, high PIVKA-Ⅱ is associated with the poor biological characteristics of tumor, and is an independent risk factor for tumor MVI.
ObjectiveTo explore the value of multi-slice CT angiography (MSCTA) in peripancreatic vascular invasion of pancreatic carcinoma. MethodsThirty-eight patients with pancreatic carcinoma were detected by MSCTA technology before operation. The peripancreatic vascular invasion of pancreatic carcinoma was evaluated by multi-planar reconstruction (MPR) and maximum intensity projection (MIP) combined with axial image, and compared with the surgical results. ResultsThe MSCTA results showed that there were 12 patients (31.6%) with vascular invasion in 38 patients with pancreatic carcinoma, and the surgical results showed that there were 16 patients (42.1%) with vascular invasion. There was a b fit goodness of two results (kappa=0.665, P=0.000). The sensibility and specificity of MSCTA was 68.8% (11/16) and 95.5% (21/22), respectively. ConclusionsMSCTA technology has a high correct rate in evaluation of peripancreatic vessel encroached by pancreatic carcinoma, the MSCTA result has a b consistency to the surgical result. It has a value of clinical application in evaluation of peripancreatic vessel encroached by pancreatic carcinoma.
Objective To investigate the effects of cediranib on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway and proliferation, migration and invasion of liver cancer cells. Methods The hypoxia microenvironment was simulated in vitro, and different doses of cediranib were used to intervene the human hepatoma cell HepG2, MTT assay was used to detect the proliferation of human hepatoma cell HepG2, Transwell chamber assay was used to detect the invasion and migration of human hepatoma cell HepG2, tumor formation in nude mice was used to detect the growth of human hepatoma cell HepG2 in vivo, the angiogenesis of tumor tissue and expression level of HIF-1α/VEGF pathway protein were detected by immunohistochemistry. Results Compared with the control group, the proliferation rate, invasion and migration abilities, and the expression of HIF-1α/VEGF pathway proteins of human hepatoma cell HepG2 were significantly decreased in the different concentration of cediranib treatment group (P<0.05), the tumor volume and microvessel formation of tumor tissues in nude mice were significantly reduced (P<0.05). Conclusion Cediranib may inhibit the proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF signaling pathway.
Objective To investigate effect of hepatocyte growth factor (HGF) after lentivirus-mediated RNA interference (RNAi) targeting c-Met on invasion of colonic carcinoma cell line SW480. Methods The experiment was assigned into 3 groups: NC group, the normal cells were infected by the shRNA negative control virus (the NC-20 andNC-40 represented the negative group which were added 20 ng/mL and 40 ng/mL respectively HGF after being infected); KD group, the normal cells were infected by the shRNA-c-Met target virus (the KD-20 and KD-40 represented the interfered group which were added 20 ng/mL and 40 ng/mL HGF respectively after being infected; KD1, KD2, KD3, and KD4 represented the different RNAi targets for the purpose gene); CON group, the normal cells were not infected by any virus. The lentiviral vector shRNA-c-Met was constructed and verified by polymerase chain reaction (PCR) and DNA sequencing. The SW480 cells were infected with the shRNA-c-Met after packed with lentivirus plasmid. Fourty-eight hours transfection later, the c-Met mRNA of the transfected SW480 cell was detected by real time PCR and the c-Met protein was examined by Western blot. Seventy-two hours after transfection, the cell apoptosis was detected by flow cytometry and the invasions in the different cells with stable transfection were detected by Transwell test. Results The RNAi sequence targeting c-Met gene was successfully inserted into the lentiviral vector. The shRNA-c-Met transfection resulted in an obviously reduced expression of c-Met mRNA in the SW480 cells. The efficency of gene knock down of the KD4 (the cells with No.4 target spot knocked down) was 81.4%. The shRNA-c-Met tansfection resulted in an obviously reduced expression of c-Met protein in the SW480 cells. After transfection, the apoptosis rate of the KD group was significantly higher than that in the NC group (P<0.001) or the CON group (P<0.001). The invasion ratios in the NC group, NC-20 group, and NC-40 group were significantly higher than those in the KD group (P<0.001), KD-20 group (P=0.015), and KD-40 group (P=0.017), respectively; which in the NC-20 group and NC-40 group were increased as compared with the NC group (P<0.001,P<0.001), and in the NC-40 group was increased as compared with the NC-20 group (P=0.005). The invasion ratios in the KD-20 group and KD-40 group were increased as compared with the KD group (P<0.001,P<0.001), and in the KD-40 group was increased as compared with the KD-20 group (P=0.014). Conclusion Lentivirus-mediated RNAi targeting c-Met could effectively suppress expression of c-Met in SW480 cells and could reduce invasion of HGF on SW480 cells with knocked down c-Met.