Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT.

Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.

Rare postoperative hemorrhage after robotic-assisted pancreatoduodenectomy for pancreatic head cancer: a case report.

Post-pancreaticoduodenectomy hemorrhage is a life-threatening complication that occurs in 2-10% of patients. The most common location for post-pancreaticoduodenectomy hemorrhage is the gastroduodenal artery stump. Nonetheless, unusual sources of hemorrhage, which are hard to locate, exist. Here, we report a rare postoperative hemorrhage after robotic-assisted pancreatoduodenectomy for pancreatic head cancer. A 67-year-old man presenting with appetite loss, general fatigue and painless jaundice was admitted to our ward. The patient had an elevated level of carbohydrate antigen 19-9 (50 U/mL). Computed tomography scan revealed a 17-mm wide low-density area in the uncinate process of the pancreas. Magnetic resonance cholangiopancreatography showed the dilation of bile and pancreatic ducts. Robotic-assisted pancreaticoduodenectomy was performed on the patient by using the da Vinci Model S Surgical System. On postoperative days 5 and 6, the patient vomited blood, and bloody fluid was observed in the drainage. Emergent gastroscopic examination was performed and revealed a large amount of hematocele in the stomach. On postoperative day 6, emergency operation was undertaken, and the output jejunal loop was found to have intussuscepted in the stomach. This is the first case report of output jejunal loop intussusception in the stomach that consequently caused hemorrhage after robotic-assisted pancreaticoduodenectomy for pancreatic head cancer.

Comparison of FIB-4 Index and Child-Pugh Score in Predicting the Outcome of Hepatic Resection for Hepatocellular Carcinoma.

BACKGROUND AND AIMS: The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy. METHODS: A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score. RESULTS: Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively). CONCLUSION: The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score.

End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's sixth most common malignant tumor and the third cause of cancer death. Although great progress has been made in hepatectomy, it is still associated with a certain degree of risk of post-hepatectomy liver failure (PHLF), which extends the length of hospital stay and remains the leading cause of postoperative death. Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF. AIM: To assess the value of model for end-stage liver disease (MELD) score combined with standardized future liver remnant (sFLR) volume in predicting PHLF in patients undergoing hepatectomy for HCC. METHODS: This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018. Discrimination of sFLR volume, MELD score, and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve. RESULTS: The patients were divided into two groups according to whether PHLF occurred after hepatectomy. The incidence of PHLF was 8.4% in our research. The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score. Both sFLR volume and MELD score were considered independent predictive factors for PHLF. Moreover, the cut-off value of the sFLR/MELD score to predict PHLF was 0.078 (P < 0.001). This suggests that an sFLR/MELD ≥ 0.078 indicates a higher incidence of PHLF than an sFLR/MELD < 0.078. CONCLUSION: MELD combined with sFLR is a reliable and effective PHLF predictor, which is superior to MELD score or sFLR volume alone.

ALBI/ST ratio versus FIB-4 and APRI as a predictor of posthepatectomy liver failure in hepatocellular carcinoma patients.

A precise and noninvasive method to predict posthepatectomy liver failure (PHLF) in clinical practice is still lacking. Liver fibrosis or cirrhosis accompanied with varying degrees of portal hypertension plays an important role in the occurrence of PHLF in hepatocellular carcinoma (HCC) patients. This study aims to compare the predictive ability of the albumin-bilirubin score to spleen thickness ratio (ALBI/ST) versus fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet count ratio index (ARPI) for the occurrence of PHLF. We retrospectively enrolled 932 patients who underwent liver resection for HCC between 2010 and 2017. The predictive accuracy of ALBI/ST ratio, FIB-4, and APRI for occurrence of PHLF was evaluated by receiver operating characteristic curve analysis. PHLF was diagnosed in 69 (7.4%) patients. The ALBI/ST ratio was found to be a significant predictor of PHLF. The AUC of ALBI/ST (AUC = 0.774; 95% CI, 0.731-0.817; P <.001) was larger than that of FIB-4 (AUC = 0.696; 95% CI, 0.634-0.759; P <.001) and APRI (AUC = 0.697; 95% CI, 0.629-0.764; P <.001). Multivariate analysis demonstrated that ALBI/ST ratio was a strong risk factor of PHLF in all hepatectomy subgroups. In conclusion, the ALBI/ST ratio has a superior predictive ability for PHLF compared with APRI and FIB-4.

Photodynamic therapy for middle-advanced stage upper gastrointestinal carcinomas: A systematic review and meta-analysis.

AIM: To determine the therapeutic effect of photodynamic therapy (PDT) for middle-advanced stage upper gastrointestinal carcinomas. METHODS: We searched PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database from inception to April 2018 for randomized controlled studies. These studies compared PDT with other palliative therapies (radiotherapy, chemotherapy, or Nd:YAG laser) and compared PDT, radiotherapy, or chemotherapy alone with PDT combined with chemotherapy/radiotherapy. In our meta-analysis, both fixed and random effects models were used to estimate the risk ratio (RR) for dichotomous outcomes (the response rate and one-year survival rate). RESULTS: Ten random controlled clinical studies with 953 patients were included in the analysis. The effective rate for PDT was better than that of radiotherapy or Nd:YAG laser for the treatment of middle-advanced upper gastrointestinal carcinomas [RR = 1.36; 95% confidence interval (CI): 1.13-1.65; P = 0.001]. In addition, PDT combined with chemotherapy had significantly better efficacy and a higher one-year survival rate than PDT or chemotherapy alone (significant remission rate, RR = 1.62; 95%CI: 1.34-1.97; P < 0.00001; one-year survival rate, RR = 1.81; 95%CI: 1.13-2.89; P = 0.01). CONCLUSION: PDT is a useful method for the treatment of middle-advanced stage upper gastrointestinal carcinomas. PDT combined with chemotherapy or radiotherapy can enhance its efficacy and prolong survival time.

Ability of the ALBI grade to predict posthepatectomy liver failure and long-term survival after liver resection for different BCLC stages of HCC.

BACKGROUND: Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. METHODS: Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. RESULTS: A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P = 0.222). CONCLUSION: The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients.

Combining albumin-bilirubin score with future liver remnant predicts post-hepatectomy liver failure in HBV-associated HCC patients.

BACKGROUND AND AIMS: Accurate assessment of liver functional reserve pre-operatively is vital for safe hepatic resection. The ALBI score is a new model for assessing liver function. This study aimed to evaluate the value of combining ALBI score with sFLR in predicting post-operative morbidity and PHLF in HCC patients who underwent hepatectomy. METHODS: Patients undergoing three-dimensional CT reconstruction prior to hepatectomy for HCC between January 2015 and January 2017 were enrolled. The values of the CP score, ALBI score and sFLR in predicting post-operative outcomes were evaluated. RESULTS: A total of 229 HCC patients were enrolled; 24 (10.5%) experienced major complications and 21 (9.2%) developed PHLF. The incidence of major complications and PHLF increased with increasing ALBI grade. The ALBI grade classified patients with CP grade A into two subgroups with different incidences of PHLF (P=.029). sFLR and ALBI scores were identified as independent predictors of PHLF. The AUC values for the CP score, ALBI score, sFLR and sFLR×ALBI for predicting major complications were 0.600, 0.756, 0.660 and 0.790 respectively. The AUC values of the CP score, ALBI score, sFLR and sFLR×ALBI for predicting PHLF were 0.646, 0.738, 0.758 and 0.884 respectively. CONCLUSIONS: The ALBI score showed superior predictive value of post-operative outcomes over CP score, and the combination of sFLR and ALBI score was identified as a stronger predictor of post-operative outcomes than the sFLR or ALBI score alone.

Predictive power of splenic thickness for post-hepatectomy liver failure in HBV-associated hepatocellular carcinoma patients.

BACKGROUND: The purpose of this case series is to investigate the relationship between splenic thickness (ST) and postoperative outcomes after hepatic resection in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. METHODS: The clinical data of 320 patients with HBV-associated HCC who had undergone liver resection were retrospectively analyzed. The value of ST in predicting postoperative outcomes was evaluated. RESULTS: A total of 320 patients were enrolled in the study. An increase in ST was significantly associated with an increase in portal vein diameter (PVD), indocyanine green retention rate 15 min (ICG R15), and total bilirubin (TBIL); however, it was negatively correlated with platelet count (PLT). Post-hepatectomy liver failure (PHLF) occurred in 35 (10.9%) patients. Multivariate logistic regression analysis showed that ST was an independent predictor of morbidity and mortality after hepatectomy. Meanwhile, ST was associated with an almost sixfold increased risk for developing perioperative complications (OR 5.678; 95% CI 2.873 to 11.224; P < 0.001) and almost 13-fold increased risk for mortality after hepatectomy (OR 13.007; 95% CI 1.238 to 136.627; P = 0.033).The area under the receiver operating characteristic (ROC) curve (AUC) of ST for predicting the incidence of PHLF was 0.754 (95% confidence interval (CI) 0.667 to 0.841; P < 0.001), with a sensitivity of 57.1% and a specificity of 82.5%, which were significantly greater than those of the ICG R15 level (AUC 0.670; 95% CI 0.560 to 0.779; P < 0.001). The critical value of ST was 43.5 mm. CONCLUSIONS: ST, which is an easy, inexpensive, and routinely available perioperative marker, showed a favorable predictive value for postoperative outcomes in HBV-associated HCC patients.

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.

Fisetin (3,3',4',7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein­coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF­ß1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

Comparative study of ROR2 and WNT5a expression in squamous/adenosquamous carcinoma and adenocarcinoma of the gallbladder.

AIM: To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS: EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS: Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION: SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.

Jagged1 and DLL4 expressions in benign and malignant pancreatic lesions and their clinicopathological significance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.

Overexpression of Thy1 and ITGA6 is associated with invasion, metastasis and poor prognosis in human gallbladder carcinoma.

Gallbladder cancer (GBC) is a rare but highly aggressive cancer for which no well-accepted prognostic biomarkers have been identified. Thymus cell antigen 1 (Thy1), also known as cluster of differentiation (CD)90, and integrin α6 (ITGA6), also known as CD49f, are important molecules in cancer and putative markers of various stem cell types. However, their role in GBC remains to be elucidated. In the present study, Thy1 and ITGA6 expression status in clinical GBC samples, which comprised squamous cell/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC) subtypes, was investigated. The associations between Thy1 and ITGA6 expression and clinical parameters and survival rate were analyzed separately. The THY1 and ITGA6 messenger RNA levels were significantly higher in both SC/ASC and AC tissues than in adjacent non-tumor tissues (all P<0.001). These results were subsequently confirmed by immunohistochemical analyses. Overexpression of Thy1 and ITGA6 was correlated with poor differentiation, large tumor size, lymph node metastasis and great invasiveness in SC/ASC (Thy1, P=0.045, P=0.005, P=0.003 and P=0.009, respectively, and ITGA6, P=0.029, P=0.011, P=0.009 and P=0.004, respectively) and AC (Thy1, P=0.027, P<0.001, P=0.003 and P 0.004, respectively, and ITGA6, P=0.002, P=0.003, P=0.006 and P=0.006, respectively). Both Thy1 and ITGA6 were expressed at higher levels in AC with advanced tumor-node-metastasis stage (TNM) than in AC with low TNM stage (P=0.001 and P=0.018, respectively). In addition, patients with elevated Thy1 or ITGA6 expression had shorter overall survival than those with negative Thy1 or ITGA6 expression. Multivariate Cox regression analysis demonstrated that Thy1 (SC/ASC, P=0.001 and AC, P=0.005) and ITGA6 (both P=0.003) were independent predictors of poor prognosis in both SC/ASC and AC patients. In conclusion, Thy1 and ITGA6 could be clinical prognostic markers for GBC.

Splenic artery trunk embolization reduces the surgical risk of liver transplantation.

BACKGROUND: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation. METHODS: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients. RESULTS: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications. CONCLUSION: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer.

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II (p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

EphB1 and Ephrin-B, new potential biomarkers for squamous cell/adenosquamous carcinomas and adenocarcinomas of the gallbladder.

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC (P SC/ASC =0.000) or AC (P AC =0.000 or P AC =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

Expression of DNA-repair proteins and their significance in pancreatic cancer and non-cancerous pancreatic tissues of Sprague-Dawley rats.

BACKGROUND: To establish a model of pancreatic cancer induced by 7,12-dimethylbenzantracene (DMBA) in Sprague-Dawley (SD) rats, and detect the expression of DNA-repair proteins (MGMT, ERCC1, hMSH2, and hMLH1) and their significance in pancreatic cancer and non-cancerous pancreatic tissues of SD rats. METHODS: DMBA was directly implanted into the parenchyma of rat pancreas (group A and group B), and group B rats were then treated with trichostatin A (TSA). The rats in both groups were executed within 3 to 5 months, and their pancreatic tissues were observed by macrography and under microscopy. Meanwhile, the rats in the control group (group C) were executed at 5 months. Immunohistochemistry was used to assay the expression of MGMT, ERCC1, hMSH2, and hMLH1. RESULTS: The incidence of pancreatic cancer in group A within 3 to 5 months was 48.7% (18/37), including 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3% (12/36), including 1 case of fibrosarcoma. The mean of maximal diameters of tumors in group A was higher than that in group B (P <0.05). No pathological changes were found in pancreas of group C and other main organs (except pancreas) of group A and group B. No statistical differences were found among the positive rates of MGMT, ERCC1, hMSH2, and hMLH1 in ductal adenocarcinoma and non-cancerous pancreatic tissues of group A (P >0.05). The positive rates of MGMT, ERCC1, hMSH2, and hMLH1 were significantly lower in ductal adenocarcinoma than those in non-cancerous tissues of group B (P ≤0.05). All pancreas of group C had positive expression of MGMT, ERCC1, hMSH2, and hMLH1 and two cases of fibrosarcoma showed a negative expression. CONCLUSIONS: DMBA, directly implanted into the parenchyma of pancreas, creates an ideal pancreatic cancer model within a short time. TSA might restrain DNA damage related to the genesis and growth of pancreatic cancer in rats. The DNA-repair proteins, including MGMT, ERCC1, hMSH2, and hMLH1, might play an important role in the genesis of pancreatic cancer induced by DMBA in rats.

Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope.

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.

Clinicopathological significance of DNA fragmentation factor 45 and thyroid transcription factor 1 expression in benign and malignant lesions of the gallbladder.

Gallbladder cancer (GBC) is one of the most aggressive tumors; we examined the expression level of DNA fragmentation factor 45 (DFF45) and thyroid transcription factor 1 (TTF-1) in benign and malignant lesions of the gallbladder by immunohistochemistry. The results were correlated with clinicopathological features and prognosis. DNA fragmentation factor 45 and TTF-1 expression was significantly higher in gallbladder adenocarcinomas than in the corresponding peritumoral tissues (χ²DFF45 = 6.92, χ²TTF-1 = 8.68, ps < 0.01), polyps (χ²DFF45 = 4.49, χ²TTF-1 = 5.35, ps < 0.05), and chronic cholecystitis (χ²DFF45 = 12.98, χ²TTF-1 = 17.74, ps < 0.01). Negative expression of DFF45 and TTF-1 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinomas (p < 0.05). Univariate Kaplan-Meier analysis showed that elevated expression levels of DFF45 and TTF-1 (p < 0.05) were closely associated with increased overall survival. In addition, the average survival time of patients with DFF45(+) TTF-1(+) tumors was significantly higher than those with DFF45(-) TTF-1(-) tumors (p < 0.05). Finally, multivariate Cox regression analysis showed that negative expression of DFF45 and TTF-1 was an independent prognostic predictor in gallbladder adenocarcinoma (p < 0.05). The expression of DFF45 and/or TTF-1 is closely related to the carcinogenesis, progression, clinical behavior and prognosis of gallbladder adenocarcinomas. DNA fragmentation factor 45 and TTF-1 could be progression-associated genes correlating with good prognosis in GBC.