ITGB6 may promote proliferation and invasion in pancreatic cancer.

Introduction: The ITGB6 gene encoding a protein that can regulate the integrin αvß6 heterodimer protein expression in different status was shown to play an important role in multiple human cancers, such as brain cancer, colon cancer and oral cancer, and is related to clinical progression. This study aims to explore the function and the mechanism of the ITGB6 gene or protein in pancreatic cancer. Material and methods: We examined the expression of ITGB6 in pancreatic cancer using immunohistochemistry and analyzed the relationship between the expression of ITGB6 and the clinicopathologic features in pancreatic cancer patients. In addition, a bioinformatic method was used to analyze the ITGB6 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the correlation between high KIF23 expression and prognosis in pancreatic cancer patients. Moreover, colony formation assay, MTT assay, cell scratch, cell invasion and western blot assays in vitro and a xenograft mouse model in vivo were performed to analyze the effect of KIF23 on proliferation and invasion of pancreatic cancer cells. Results: Increased expression of ITGB6 was significantly correlated with poor clinical outcome in both our clinical data and TCGA data of pancreatic cancer. Furthermore, functional assays revealed that ITGB6 knockdown in vivo and in vitro might inhibit cancer cell proliferation and the ability of invasion or migration. Conclusions: Our data suggest that ITGB6 is associated with pancreatic cancer malignant progression. Hence, ITGB6 may serve as a potential target of pancreatic cancer for future research, and further study is needed.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.

Renal venous sampling assisted the diagnosis of juxtaglomerular cell tumor: a case report and literature review.

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancers, with more than a million cases per year by 2025. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes (CRGs) in HCC remain largely unknown. Methods: In the present study, we constructed and validated a four CRGs signature for predicting the overall survival (OS) of HCC patients in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Results: Patients with high CRGs risk score showed shorter OS than those with low CRGs risk score. Functional analysis suggested that the CRGs-based prognostic signature was associated with metabolism remodeling which facilitated liver cancer progression. In addition, reduced infiltration of CD8+ T cells and increased macrophages were found in HCCs from patients with high CRGs risk score. As one of the four CRGs, higher expression of dihydrolipoamide S-acetyltransferase (DLAT) was accompanied by higher expression of program death ligand 1 (PD-L1) in HCC. Further, we confirmed that DLAT was up-regulated and correlated with poor prognosis in a clinical HCC cohort. Conclusion: In conclusion, our study constructed a four CRGs signature prognostic model and identified DLAT as an independent prognostic factor for HCC, thus providing new clues for understanding the association between cuproptosis and HCC.

Effect of dexmedetomidine on intraoperative Surgical Pleth Index in patients undergoing video-assisted thoracoscopic lung lobectomy.

BACKGROUND: The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery. METHODS: We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 µg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated. RESULTS: SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit. CONCLUSIONS: Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450 , Registered 16 October, 2016.

The association of hepatitis B virus screening and antiviral prophylaxis with adverse liver outcomes in Chinese cancer patients undergoing chemotherapy: A retrospective study.

Currently, the association of the initiation time of hepatitis B virus (HBV) screening and antiviral prophylaxis with adverse liver outcomes in cancer patients undergoing chemotherapy remains conflicting.This retrospective study was designed to determine the association of HBV screening and antiviral prophylaxis with adverse liver outcomes, and then proposed optimal management strategies on HBV screening and antiviral prophylaxis.We analyzed the medical data of Chinese cancer patients undergoing chemotherapy between 2000 and 2015. Descriptive statistics and Chi square tests were performed to analyze the basic characteristics of patients. Time-to-event analysis was used to determine incidence, and competing risk analysis was used to determine the hazard ratios (HRs) for outcomes.A total of 12,158 patients (81.1% with solid tumors) were analyzed. Among solid tumors patients, late screening and late antiviral therapy of chronic HBV were associated with higher incidence of hepatitis flare (HR 3.29, 95% confidence interval [CI] 2.26-4.79; HR 6.79, 95% CI 4.42-10.41), hepatic impairment (HR 2.96, 95% CI 2.03-4.32; HR 8.03, 95% CI 4.78-13.48), liver failure (HR 2.19, 95% CI 1.41-3.40; HR 14.81, 95% CI 6.57-33.42), and HBV-related death (HR 3.29, 95% CI 2.26-4.79; HR 8.30, 95% CI 4.95-13.91) in comparison with early screening and early therapy.Early HBV screening and antiviral therapy could reduce the risk of adverse liver outcomes among chronic HBV patients receiving chemotherapy. Hepatitis B surface antibody-positivity was associated with a decreased risk of liver failure and chronic HBV, late screening or late antiviral therapy were predictors of liver failure for patients with anti-tumor therapy. However, it should be applied cautiously into each types of solid tumors and hematologic malignancies because subgroup analysis according to type of cancer was not designed.

H2S attenuates injury after ischemic stroke by diminishing the assembly of CaMKII with ASK1-MKK3-p38 signaling module.

Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H2S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H2S agonist, and NaHS, an H2S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.

The potential role of HO-1 in regulating the MLK3-MKK7-JNK3 module scaffolded by JIP1 during cerebral ischemia/reperfusion in rats.

Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1. Prior to the ischemia-reperfusion experiment, CoPPIX was injected through the lateral ventricle for 5 consecutive days or Ros was administered via intraperitoneal administration in the week prior to transient ischemia. Our results demonstrated that HO-1 could inhibit the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and could ultimately diminish the phosphorylation of JNK3. Furthermore, the inhibition of JNK3 phosphorylation downregulated the level of p-c-Jun and elevated neuronal cell death in the CA1 of the hippocampus. Taken together, these findings suggested that HO-1 could ameliorate brain injury by regulating the MLK3-MKK7-JNK3 signaling module, which was scaffolded by JIP1 and JNK signaling during cerebral ischemia/reperfusion.

High expression of TGR5 predicts a poor prognosis in patients with pancreatic cancer.

Previous studies have showed that bile acids (BAs) play essential roles in the progression of various human cancers, and the G-protein coupled bile acid receptor-1 (Gpbar-1, or TGR5), a receptor of BAs, has been reported to connect BAs with cancers. However, little is known about the prognostic role of TGR5 in pancreatic cancer. In this study, we found that the expression of TGR5 was significantly higher in the cancerous tissues than the adjacent normal tissues by immunohistochemical staining (81.6% vs. 36.8%). Meanwhile, TGR5 was positively correlated with lymph node metastasis (P=0.021) and advanced stage (P=0.011). Finally, univariate analysis showed that patients with high TGR5 expression (P<0.001), lymph node metastasis (P=0.002) and advanced tumor stage (P=0.008) had decreased overall survival, and Cox proportional hazards regression analysis confirmed that TGR5 expression was an independent predictor of the overall survival of patients with pancreatic cancer (P=0.019). Our findings suggested that TGR5 might serve as an important predictor of poor survival in pancreatic cancer.

siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo.

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.

Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro.

The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis among the experimental groups was statistically significant (P<0.05). The Transwell assay showed that the number of cells permeating the septum in the control group was 82.7±2.3/high power lens (HP), while the average number of cells permeating septum in groups S1-4 following treatment with sorafenib for 24 h was 58.2±2.5, 41.3±1.3, 22.6±2.1 and 14.7±1.1/HP, which was significantly lower compared with the control group. The number of cells permeating the septum in each experimental group decreased with the enhancement of the concentration gradient. The differences were statistically significant (P<0.05). In conclusion, sorafenib inhibits the proliferation of A549/DDP cisplatin­resistant lung adenocarcinoma cells in a time­ and concentration­dependent manner. In addition, sorafenib induces apoptosis in A549/DDP cisplatin­resistant lung adenocarcinoma cells, thus reducing their invasiveness.

[Expression of glypican-3, hepatocyte antigen, alpha-fetoprotein, CD34 and CD10 in hepatocellular carcinoma: a clinicopathologic analysis of 375 cases].

OBJECTIVE: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value. METHODS: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated. RESULTS: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis. CONCLUSIONS: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.

Combined SVM-based and docking-based virtual screening for retrieving novel inhibitors of c-Met.

Aberrant c-Met activation has been demonstrated to be implicated in tumorigenesis and anti-cancer drug resistance. Discovery of c-Met inhibitors has attracted much attention in recent years. In this study, a support vector machine (SVM) classification model that discriminates c-Met inhibitors and non-inhibitors was first developed. Evaluation through screening a test set indicates that combined SVM-based and docking-based virtual screening (SB/DB-VS) considerably increases hit rate and enrichment factor compared with the individual methods. Thus the combined SB/DB-VS approach was adopted to screen PubChem, Specs, and Enamine for c-Met inhibitors. 75 compounds were selected for in vitro assays. Eight compounds display a good inhibitory potency against c-Met. Five of them are found to have novel scaffolds, implying a good potential for further chemical modification.

Coexpression of PDGFR-alpha, PDGFR-beta and VEGF as a prognostic factor in patients with hepatocellular carcinoma.

AIMS: To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-a) and beta (PDGFR-ß) expression in patients with hepatocellular carcinoma (HCC).? METHODS: The expression of PDGFR-a, PDGFR-ß and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model.? RESULTS: Univariate survival analysis showed that PDGFR-a or PDGFR-ß overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-a/PDGFR-ß/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (p<0.05). More importantly, PDGFR-a/PDGFR-ß/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000).? CONCLUSIONS: Coexpression of PDGFR-a, PDGFR-ß and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

Effects of propofol anesthesia and sevoflurane anesthesia on the differentiation of human T-helper cells during surgery.

BACKGROUND: Surgical stress causes a helper T-cell type 2 (Th2)-dominant status and disturbs the Th1/Th2 cytokine balance. Anesthesia can suppress the stress response to surgery, therefore it may inhibit the imbalance in the Th1/Th2 ratio. In this study, we assessed if propofol anesthesia and sevoflurane anesthesia influence the Th1/Th2 cytokine balance, and which anesthesia method better attenuates this ratio. METHODS: Twenty-eight patients with an American Society of Anesthesiologists (ASA) physical status of I undergoing laparoscopic cholecystectomy were selected. They were randomly allocated into two groups of 14. Group 1 received propofol anesthesia by a target-controlled-infusion (TCI) pump and group 2 received sevoflurane anesthesia. Non-invasive blood pressure, heart rate, and end-expiration CO2 partial pressure were monitored during anesthesia. The depth of anesthesia was measured using the bispectral index (BIS), and maintained between 50 and 60. During surgery we adjusted the doses of propofol and sevoflurane according to the BIS. Samples of peripheral blood were taken before the induction of anesthesia (T1), after the induction of anesthesia (T2), at the beginning of surgery (T3), at the end of surgery (T4) and on the first day after surgery (D1). Blood samples were analyzed to give the Th1/Th2 ratio and plasma level of cortisol. RESULTS: Non-invasive blood pressure, heart rate and end-expiration CO2 partial pressure were not notably different in the two groups. At T4, the percentage of T1 cells was higher in group 1 and had statistical significance (P < 0.05). The percentage of T2 cells was not significantly different in the two groups. At T4, the difference in the Th1/Th2 ratio was significantly different. At T3, T4, and D1, the plasma level of cortisol was lower in group 1 (P < 0.05). CONCLUSION: Compared with sevoflurane, propofol can preferably promote Th cells to differentiate into Th1 cells and inhibit surgical stress. Propofol may therefore be immunoprotective for such patients.

[Expression and clinicopathologic significance of GPC3 and other antibodies in well-differentiated hepatocellular carcinoma].

OBJECTIVE: To study the expression and significance of GPC3, CD10 and CD34 in hepatocellular carcinoma (HCC), dysplastic nodules (DN), cirrhotic regenerative nodules (CRN), focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA). METHODS: Immunohistochemical study for GPC3, CD10, CD34 and AFP was performed on 80 cases of HCC (30 cases of well-differentiated HCC and 50 cases of advanced HCC), 30 cases of DN (18 cases of high-grade DN and 12 cases of low-grade DN), 36 cases of CRN, 20 cases of FNH and 20 cases of HA. RESULTS: (1) The positive expression rate of GPC3 was 92% (46/50) in advanced HCC, 66.7% (20/30) in well-differentiated HCC, 2/18 in high-grade DN, and 0 in low-grade DN, CRN, FNH and HA. The expression rate of GPC3 in well-differentiated HCC was lower than that in advanced HCC and higher than that in high-grade DN (P < 0.05). (2) The negative expression rate of CD10 was 78% (39/50) in advanced HCC, 43.3% (13/30) in well-differentiated HCC, 20% (4/20 and 4/20) in both FNH and HA, 2.8% (1/36) in CRN and 0 in both high-grade DN and low-grade DN. The occurrence of CD10-strongly positive cells was 2% (1/50) in advanced HCC, 16.7% (5/30) in well-differentiated HCC, 15/18 in high-grade DN, 11/12 in low-grade DN, 80.6% (29/36) in CRN and 60% (12/20 and 12/20) in both FNH and HA. The positive expression rate of CD10 in well-differentiated HCC was higher than that in advanced HCC and lower than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (3) The positive expression rates of CD34 in advanced HCC and well-differentiated HCC ranged from 25% to 100% [and strongly positive in 76% (38/50) and 70% (21/30), respectively]. The rates in high-grade DN and low-grade DN ranged from 5% to 25% (and weakly positive in 16/18 and 10/12, respectively). In CRN, the rate ranged from 0 to 5% [and weakly positive in 27.8% (10/36)]. In FNH and HA, the positive rates ranged from 25% to 50%. The positive expression rate of CD34 in well-differentiated HCC was significantly higher than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (4) The positive expression rate of AFP was 44% (22/50) in advanced HCC, 20% (6/30) in well-differentiated HCC, no expression in DN, LCN, LCN, FNH and HA. The positive expression rate of AFP in well-differentiated HCC was lower than that in advanced HCC and higher than that in LCN, FNH and HA. The different expression had statistical significance (P < 0.05). CONCLUSIONS: GPC3 is a relatively sensitive and specific marker in pathologic diagnosis of HCC. When coupled with immunohistochemical results of CD34, CD10 and AFP, GPC3 is useful in differentiating HCC from DN, LCN, FNH and HA.

Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma.

BACKGROUND: Recently, there is evidence that the number of mast cells in various solid cancers increases with tumor progression. The role of mast cells in promoting tumor progression, however, has not been well studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the prognostic value of mast cell counts in different zones of the neoplasm in patients with PDAC after curative resection. METHODS: Numbers of mast cells and microvessels were assessed by immunohistochemistry in tissues from 103 patients with PDAC and 10 patients with normal pancreas. All patients with PDAC underwent partial pancreatic resection. The investigators paid particular attention to the distribution of mast cells in each specimen. RESULTS: High mast cell counts in the intratumoral border zone correlated with the presence of lymphatic and microvascular invasion, lymph node metastasis, and TNM stage, and were an independent prognostic factor for overall survival (P < .001). In contrast, neither in the intratumoral center zone nor in the peritumoral zones was mast cell count associated with OS. Mast cell counts in the intratumoral border zone, but not in the peritumoral or in the intratumoral center zone, were correlated with microvessel counts. CONCLUSION: The present study shows a zone-specific distribution of mast cells in PDAC and highlights the importance of invasive front in the prognosis of patients with PDAC after curative resection. Zone-specific evaluation of mast cell and microvessel counts may be helpful for prognostic assessment and therapeutic decision making in PDAC.

[Clinicopathologic features of hepatocellular carcinoma: an analysis of 185 cases].

OBJECTIVE: To analyze the clinicopathologic features and prognostic factors of hepatocellular carcinoma. METHODS: Clinicopathological data of 185 cases of hepatocellular carcinoma treated in our hospital between 2000 and 2005 were collected and their follow up information was obtained. The clinicopathological features and prognostic factors were analyzed by Kaplan-Meier and multivariate Cox regression analysis. RESULTS: The 185 patients had a median age of 51.0 ± 11.0 (range, 19 - 72) years. The apparent peak incidence age was 40 to 60 years old, and the ratio of male to female was 10.6:1; the 3- and 5-year postoperational survival rates were 52.0% and 38.0%; respectively. The tumour numbers (P = 0.000), tumor size (P = 0.025), histological pattern (P = 0.000), nuclear features (P = 0.000), differentiation (P = 0.001) and vascular invasion (P = 0.000) were significantly correlated with prognosis. The postoperational survival times of patients with thin trabeculae pattern, compact pattern and pseudoglandular pattern were significantly longer than that of thick trabeculae, scirrhous pattern, and solid pattern (P ≤ 0.009). The postoperational survival time of patients with nuclear features grade 1 and 2 was significantly longer than that of grade 3 and 4 (P = 0.000). Multivariate Cox regression analysis showed that the tumor number (P = 0.001), tumor size (P = 0.042), nuclear features (P = 0.023) and vascular invasion (P = 0.000) were independent prognostic factors. CONCLUSION: The postoperational survival rate of HCC patients is low. The tumor size, tumor number, differentiation and vascular invasion are major prognostic factors of hepatocellular carcinoma, The higher is the tumor number, tumor size, degree of differentiation and presence of vascular invasion, the higher risk of mortality is.

Risk factors for intrahepatic cholangiocarcinoma: a case-control study in China.

AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China. METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertension, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. RESULTS: Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%, P<0.000), and hepatolithiasis (5.4% vs 1.1%, P=0.001). By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity (adjusted OR, 8.876, 95% CI, 5.973-13.192), and hepatolithiasis (adjusted OR, 5.765, 95% CI, 1.972-16.851). The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertension, cigarette smoking, and alcohol consumption were not significantly different between cases and controls. CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.