Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases.

Human Wnt family comprises 19 proteins which are critical to embryo development and tissue homeostasis. Binding to different frizzled (FZD) receptor, Wnt7a initiates both ß-catenin dependent pathway, and ß-catenin independent pathways such as PI3K/Akt, RAC/JNK, and extracellular signal-regulated kinase 5/peroxisome proliferator-activated receptor-γ. In the embryo, Wnt7a plays a crucial role in cerebral cortex development, synapse formation, and central nervous system vasculature formation and maintenance. Wnt7a is also involved in the development of limb and female reproductive system. Wnt7a mutation leads to human limb malformations and animal female reproductive system defects. Wnt7a is implicated in homeostasis maintenance of skeletal muscle, cartilage, cornea and hair follicle, and Wnt7a treatment may be potentially applied in skeletal muscle dystrophy, corneal damage, wound repair, and hair follicle regeneration. Wnt7a plays dual roles in human tumors. Wnt7a is downregulated in lung cancers, functioning as a tumor suppressor, however, it is upregulated in several other malignancies such as ovarian cancer, breast cancer, and glioma, acting as a tumor promoter. Moreover, Wnt7a overexpression is associated with inflammation and fibrosis, but its roles need to be further investigated.

High serum microRNA-122 level is independently associated with higher overall survival rate in hepatocellular carcinoma patients.

Previous studies have shown that some microRNAs (miRs) are intensively involved in the development of hepatocellular carcinoma. We analyzed the prognostic role of serum microRNA (miR-122) levels in hepatocellular carcinoma patients using a retrospective design. MiR-122 levels in 122 hepatocellular carcinoma patients were measured, and Cox regression analysis was performed to analyze the prognostic role of miR-122 in hepatocellular carcinoma, and the hazard ratio (HR) with 95 % confidence interval (95 %CI) was used to evaluate its prognostic role. Patients with large tumor size had lower levels of serum miR-122 (P = 0.04). However, there was no significant association of serum miR-122 levels with other clinical characteristics. Kaplan-Meier method showed that there was higher overall survival rate in hepatocellular carcinoma patients with high serum miR-122 levels compared with those with low miR-122 level (P < 0.01). When using Cox regression analysis, high serum miR-122 level was independently associated with better overall survival in hepatocellular carcinoma patients (HR = 0.26; 95 %CI 0.14-0.47, P < 0.01). Subgroup analysis by gender showed that high serum miR-122 level was independently associated with better overall survival in male patients (HR = 0.08; 95 %CI 0.03-0.22, P < 0.01), but not in female patients (HR = 0.48; 95 %CI 0.18-1.32, P = 0.16). Thus, the outcomes in the analysis suggest that high serum miR-122 level is independently associated with higher overall survival rate in hepatocellular carcinoma patients, and it is a good biomarker of better prognosis in patients with hepatocellular carcinoma.

Idiopathic desmoid-type fibromatosis of the pancreatic head: case report and literature review.

Desmoid-type fibromatosis (DTF) is an uncommon nonmetastatic fibrous neoplasm. Sporadic intraperitoneal DTF is rarely described in current literature. We herein report a case of DTF of unknown cause involving the pancreatic head. A 41-year-old man presented with recurrent epigastric pain and weight loss. An abdominal computed tomography scan showed a well-delineated solid cystic mass inside the pancreatic head. Pylorus-preserving pancreaticoduodenectomy was performed due to the patient's debilitating symptoms and suspected malignancy. The pathological examination revealed massive fibroblastic proliferation arising from the musculoaponeurotic tissues, consistent with a diagnosis of DTF. Immunohistochemical phenotyping determined positive immunoreactivity to vimentin and ß-catenin, but negative immunoreactivity to smooth muscle actin, CD117, CD34, or S-100, confirming the diagnosis of DTF. No local recurrence or distant metastasis was found during a 24-month follow-up. Radical resection is recommended as first-line treatment for pancreatic DTF. Long-term follow-up studies are required to establish the prognosis of pancreatic DTF.

SFRP5 inhibits gastric epithelial cell migration induced by macrophage-derived Wnt5a.

Secreted frizzled-related protein 5 (SFRP5) is frequently found downregulated in gastric cancer due to SFRP5 gene hypermethylation, and there is a great necessity to elucidate the role of its downregulation in gastric cancer. By binding Wnt molecules, SFRP5 is generally supposed to exert negative effects on Wnt signal pathways widely linked to human cancers. This study found that macrophages over-produced Wnt5a under the stimulation of Lipopolysaccharide (LPS) or Helicobacter pylori, the most common infectious agent in human stomach. Wnt5a-conditioned medium from macrophages enhanced cell migration and CXCR4 expression in either SFRP5-negative gastric epithelial cells (GEC) harboring SFRP5 methylation or SFRP5-positive cells treated with SFRP5 small interfering RNA (siRNA). However, such induced effect was remarkably eliminated by either Wnt5a siRNA in macrophages or treatment with recombinant SFRP5. We also found that Wnt5a-conditioned medium stimulated phosphorylation of c-jun N-terminal kinase (JNK) and c-Jun, and JNK inhibitor SP600125 blocked Wnt5a-induced CXCR4 expression and cell migration in SFRP5-negative cells. Taken together, these findings suggest that epithelium-derived SFRP5 may play a probable defensive role in impeding gastric cancer progression, characteristically by inhibiting GEC migration induced by macrophage-derived Wnt5a via JNK signaling activation.

The association between cyclooxygenase-2 1195 G/A polymorphism and hepatocellular carcinoma: evidence from a meta-analysis.

Cyclooxygenase-2 (COX-2) is proven to influence the carcinogenesis through immune response suppression, apoptosis inhibition, angiogenesis regulation, and tumor cell invasion. Previous studies assessing the association between COX-2 1195 G/A polymorphism and susceptibility to hepatocellular carcinoma (HCC) reported conflicting results. The objective of the study was to investigate the association between COX-2 1195 G/A polymorphism and HCC by a meta-analysis. PubMed, Embase, Web of Science, and Wangfang databases were searched for studies investigating the association between COX-2 1195 G/A polymorphism and HCC risk. The pooled odds ratio (OR) and its 95 % confidence interval (CI) were used to assess the strength of the association. Five studies with a total of 1,690 HCC cases and 1,961 controls were identified. Meta-analyses of total included studies showed that there was an obvious association between COX-2 1195 G/A polymorphism and HCC risk under two main genetic models (for AA versus GG, fixed-effects OR=1.45, 95 % CI 1.15-1.81, P=0.001, I (2) =0.0 %; for AA/GA versus GG, fixed-effects OR=1.26, 95 % CI 1.05-1.51, P=0.011, I (2) =0.0 %). Subgroup analysis by ethnicity showed that association was still obvious in Asians under two genetic models (for AA versus GG, fixed-effects OR=1.45, 95 % CI 1.16-1.82, P=0.001, I (2) =21.7 %; for AA/GA versus GG, fixed-effects OR=1.27, 95 % CI 1.05-1.54, P=0.013, I (2) =0.4 %). The evidence from the meta-analysis supports an association between COX-2 1195 G/A polymorphism and HCC risk in Asians. Further studies with large sample and careful design are needed to identify the possible association in Caucasians.

Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer.

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk for pancreatic cancer, but those studies have yielded contradictory findings on the association. We performed a comprehensive search in the PubMed, EMBASE, and the Chinese National Knowledge Infrastructure databases to identify relevant studies. A meta-analysis was performed to examine the association between GSTT1 polymorphism and susceptibility to pancreatic cancer by calculating the pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs). Eight studies involving a total of 4,437 individuals were included. Overall, significantly increased pancreatic cancer risk was associated with GSTT1 null genotype when all studies were pooled into the meta-analysis (random effects OR = 1.61, 95 % CI 1.06-2.44; P = 0.025). Significantly increased risk of pancreatic cancer was also found for GSTT1 null genotype in Asians when stratified by ethnicity (fixed effects OR = 2.67, 95 % CI 1.74-4.09; P < 0.001). The findings demonstrate that GSTT1 null genotype have a modest effect on the genetic susceptibility to pancreatic cancer, and GSTT1 null genotype is associated with increased risk of pancreatic cancer.

Continuous irrigation around pancreatic remnant decreases pancreatic fistula-related intraabdominal complications after distal pancreatectomy.

PURPOSE: To evaluate whether the technique of irrigation around pancreatic remnant after distal pancreatectomy (DP) can reduce the incidence of postoperative pancreatic fistula (PF) and its related intraabdominal complications. METHODS: In the retrospective clinical trial, the technique of irrigation around pancreatic remnant after DP was introduced. The clinical data of 60 patients who underwent the irrigation technique (irrigation group) and the other 65 patients who did not undergo the technique (non-irrigation group) were recorded, respectively. Preoperative clinicopathological features, intraoperative parameters, postoperative morbidity, clinically significant PF, and its related intraabdominal complications were compared between the two groups. RESULTS: The patency of irrigation tubes and drains was maintained in 59 patients. The overall incidence of PF was 31.2 %. There was no significant difference in the rate of PF between the two groups (P = 0.781), but the rate of PF-related intraabdominal complications was significantly lower in the irrigation group than that in the non-irrigation group (5 vs. 18, P = 0.005). The overall incidence of intraabdominal complications was significantly lower in the irrigation group than that in the non-irrigation group (23 vs. 39, P = 0.025). CONCLUSION: The technique of irrigation around pancreatic remnant after DP is a simple method for prevention of clinically significant PF and its related intraabdominal complications.

Undifferentiated embryonal sarcoma of the liver in a middle-aged adult with systemic lupus erythematosus.

Adult primary undifferentiated embryonal sarcoma of the liver (UESL) is a rare disease. While the etiology of UESL remains largely unknown, association with systemic inflammatory disorders has been observed. Here, we report a case of UESL in a 46-year-old woman with systemic lupus erythematosus (SLE) and without chronic hepatitis or liver cirrhosis. Systematic review of the publicly available English language medical literature identified only 27 cases of UESL in patients aged >45 years and none with SLE. Our patient presented with abdominal pain and had a 2-year history of SLE. Abdominal ultrasonography and enhanced computed tomography revealed a solid mass in the right lobe of the liver. Presumptive diagnosis of atypical hepatocellular carcinoma was made and the patient was treated with segmentectomy of S5 and S4a and cholecystectomy. The final diagnosis of UESL was made according to the pathology results. Since SLE patients may be at increased risk of malignancy, it is possible that the SLE pathogenesis may have contributed to the development of UESL in our patient. According to this case, UESL should be considered when SLE patients present with hepatic space-occupying lesions.

Resection of a malignant paraganglioma located behind the retrohepatic segment of the inferior vena cava.

BACKGROUND: Resection of a retrocaval paraganglioma is technically challenging due to limited tumor accessibility and proximity to the vena cava. CASE PRESENTATION: A large, malignant paraganglioma was found behind the retrohepatic segment of the inferior vena cava of a 60-year-old male. During resection of this rare paraganglioma, the left lateral lobe of the liver, a portion of the caudate lobe of the liver, and the gallbladder were also removed. Unfortunately, the patient died six months after surgery due to hepatic metastasis. CONCLUSION: This case demonstrates that a partial hepatectomy may be necessary to improve tumor accessibility during resection of a retrocaval paraganglioma, particularly if the tumor is proximal to the vena cava. Furthermore, palliative treatments may help prevent tumor recurrence and metastasis of malignant paragangliomas.

Effects of 1-stage revascularization and temporary external fixation combined with 2-stage Ilizarov technique in the treatment of bone defects in lower limb destruction injury: A case report.

RATIONALE: To evaluate the clinical effects of 1-stage revascularization, vacuum sealing drainage covering the wound, temporary external fixation and 2-stage Ilizarov bone transport for the treatment limb destruction injury. PATIENT CONCERNS AND DIAGNOSIS: Nine patients with limb destruction injury between September 2014 and June 2019 at our institute were evaluated retrospectively. The age of patient was 21 to 51 years with an average of 33 years. The injuries were caused by vehicle accidents in 4 patients, gunshot in 1 patient, and crushing injuries in 4 patients. All of them had vascular injury. The average length of bone defect was 9.5 (8.3-10) cm. Regular follow-up was performed on wound healing, bone transport time, bone healing time, external fixation index, and limb function. INTERVENTIONS: All patients underwent 1-stage revascularization and temporary external fixation during emergency surgery, and then gradual bone transport by Ilizarov fixator was performed until the broken fracture site was reunited. OUTCOMES: Nine patients were followed up for 12 to 48 months (average 30 months). Six patients were treated with autogenous cancellous bone graft for the second time, and 2 patients healed spontaneously. The mean wound healing time was 86 (73-90) days. The bone transport time was 97 (88.3-105.3) days, and the bone mineralization time was 164.5 (156.8-181.3) days, and the healing time of the docking sites was 6.8 (6.1-8.3) months. The external fixator time was 14.5 (12.5-17) months with the external fixation index was 1.5 (1.4-1.8) m/cm. At the last follow-up, according to the Association for the Study of the Method of Ilizarov functional scores, excellent functional outcomes were obtained in 5 patients, good in 1 patients, moderate in 2 patients. According to the Association for the Study of the Method of Ilizarov Radiological System, excellent functional outcomes were obtained in 6 cases and good in 2 cases. LESSONS: One-stage revascularization and temporary external fixation combined with 2-stage Ilizarov bone transport technique for the treatment of bone defects in limb destruction injury have satisfactory clinical effects and few complications, and can be applied under the condition of strict understanding of surgical indications.

Open total dislocation of ankle joint without fractures: A case report.

RATIONALE: Open total dislocation of ankle joint is rare and often caused by high-energy injury. The present study describes a patient with open total lateral dislocation of ankle joint without fractures and obtained a satisfactory clinical result following early debridement and irrigation, one-stage repairment of ligaments, and plaster external fixation. PATIENT CONCERNS: The patient, a 45-year-old male, complained of right foot pain with bleeding and limited motion. Physical examination showed a 15-cm open wound at the medial ankle region, with soft tissues impaired and ankle bones exposed. The 3 dimensional reconstruction computed tomography (CT) examination showed an open total dislocation of ankle joint without concomitant fractures. DIAGNOSES: open total lateral dislocation of ankle joint without fractures. INTERVENTIONS: Early modern wound care including thorough debridement and irrigation on the wound was performed to remove contaminated soft tissues. Subsequently, the dislocated ankle joint was reduced by hand and the medial and lateral collateral ligaments were repaired using wire anchors. OUTCOMES: The medial wound healed at 2 weeks after surgery, and several common complications such as infection and skin necrosis did not occur. The last follow-up showed a good range of metatarsal flexion and extension of the injured foot, and obvious signs of traumatic arthritis were not observed. According to Kaikkonen ankle function score, the patient was assessed with 90 points. LESSONS: For open total dislocation of ankle joint, early treatment should focus on debridement and irrigation, reduction and fixation of the dislocated ankle, protection of the weak soft tissues, and stable external fixation to promote wound healing and reduce the incidence of related complications.

Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori.

BACKGROUND: H. pylori, whose infection increases tumor invasiveness and metastasis, is generally labelled as the strongest risk factor for the development of gastric cancer. It appears not to be a coincidence that there is also an overexpression of CXCR4 and an obvious involvement in gastric cancer metastasis. The aim of this study attempts to investigate and further to establish a link between them. With H. pylori being a potent inducer of TNF-alpha, whether TNF-alpha, a tumor promoter, is involved in the induction of CXCR4 expression by H. pylori was also under research in this study. METHODS: Expression of CXCR4, TNF-alpha, IL-6 and IL-1 beta mRNA was determined by real-time PCR. CXCR4 protein expression was detected by Western blotting. Concentrations of TNF-alpha, IL-6 and IL-1 beta in cell culture supernatants were measured using the Quantikine Elisa kit. To abrogate TNF-alpha expression in HGC27 cells, TNF-alpha RNAi plasmid was used to transfect them. RESULTS: Levels of CXCR4 and TNF-alpha mRNA were significantly higher in H. pylori-positive gastric cancers (n = 19) compared to H. pylori-negative ones (n = 15). A subsequently Spearman's rank correlation test showed there was a positive correlation between the level of CXCR4 mRNA and that of TNF-alpha in 34 primary gastric cancers. Other results followed: Expression of CXCR4 and TNF-alpha was upregulated in gastric cancer cell MKN45 and HGC27 after infection with H. pylori 26695 (cag PAI+ ) or Tx30a (cag PAI- ); The induction of CXCR4 expression by H. pylori was inhibited significantly by a neutralizing TNF-alpha antibody, infliximab; CXCR4 expression was upregulated in MKN45 cells after treatment with exogenous TNF-alpha or co-culture with macrophage, and was downregulated in HGC27 cells after transfection with TNF-alpha RNAi plasmid. There was a significant increase in the migration of MKN45 cells treated with H. pylori 26695, and a strong inhibition when AMD 3100, a CXCR4 antagonist, or infliximab, was added. CONCLUSIONS: Our findings demonstrated that H. pylori upregulates CXCR4 expression in gastric cancer through TNF-alpha.

Pancreaticojejunal bridge-anastomosis: a novel option for surgeon to preserve pancreatic body and tail in urgent reoperation for intra-abdominal massive hemorrhage after pancreaticoduodenectomy.

BACKGROUND: Postoperative intra-abdominal massive bleeding is a rare and life-threatening complication associated with pancreaticoduodenectomy. Completion pancreatectomy (CP) was usually performed during reexploration for the complication. The management could decrease the complications, such as the pancreatic leakage or intraluminal infection after reexploration, but could increase mortality during the perioperative period. It also could result in loss of pancreatic function forever. This study evaluated an alternative surgical management for intra-abdominal massive hemorrhage to prevent pancreas function, simplify the surgical processes, and decrease the mortality of relaparotomy. METHODS: Outcome after pancreaticojejunal bridge-anastomosis (PJBA) performed between January 2006 and June 2009 was compared with that after CP performed between February 1984 and December 2005. RESULTS: Between February 1984 and June 2009, 963 patients underwent the Whipple procedure (PD) or pylorus-preserving pancreaticoduodectomy (PPPD). Pancreatic leakage occurred in 103 patients (10.7%); 22 cases (21.4%) developed into intra-abdominal massive bleeding. Nonsurgical procedures of transarterial embolization (TAE) were performed in ten (45.45%) patients, of whom one died (10%). Twelve (54.55%) underwent reoperation. Five had CP with one death (20%). Pancreatic remnant was preserved by pancreaticojejunal bridge-anastomosis (PJBA) in seven patients with no deaths. The reexploration time was 340 +/- 48.2 min vs. 247.9 +/- 40.8 min (P < 0.01) for CP and PJBA group and the blood loss was 2,180 +/- 526.3 ml vs. 1,628.6 +/- 325.1 ml (P < 0.05). In-hospital time for CP was less than that for PJBA (P < 0.05). All patients with CP still developed endocrine insufficiency ("brittle" diabetes) and diarrhea (exocrine insufficiency). There were no evidences of exocrine and endocrine insufficiency in patients with PJBA. CONCLUSIONS: Pancreaticojejunal bridge-anastomosis is an easy, simple, and safe procedure for intra-abdominal massive hemorrhage associated with pancreaticoduodenectomy. It could decrease the mortality of reoperation and preserve the pancreatic function.

A novel technique for the management of pancreaticojejunal anastomosis dehiscence following pancreaticoduodenectomy.

BACKGROUND: To report a novel technique for management of pancreaticojejunal anastomosis dehiscence after pancreaticoduodenectomy. MATERIAL AND METHODS: The anastomosis is disconnected and the blind jejunal limb is shortened and closed. A silicon tube in the pancreatic duct introduced in the first operation is fixed at the pancreatic stump. If no tube was placed during pancreaticoduodenectomy, it is placed at reoperation. The transected edge of the pancreas is stitched, and the distal part of the silicon tube is inserted into the jejunal loop and fixed in the jejunal wall. Drains and a catheter for continuous irrigation are placed. RESULTS: All patients tolerated reoperation and experienced unremarkable postoperative courses. Follow-up ranged from 5 to 27 months, and all patients exhibited normal pancreatic function and no pseudocyst formation. CONCLUSION: This technique is an effective method for management of pancreaticojejunal anastomosis dehiscence that avoids complications associated with completion pancreatectomy and preserves pancreatic function.

Downregulation of SFRP5 expression and its inverse correlation with those of MMP-7 and MT1-MMP in gastric cancer.

BACKGROUND: As negative regulators in Wnt signaling, Secreted Frizzled-Related Proteins (SFRPs) are downregulated in a series of human cancers; and specifically, some matrix metalloproteinases (MMPs), including MMP-2, MMP-7, MMP-9 and MT1-MMP, are frequently overexpressed in gastric cancer. The aim of this study is to determine the expression status of SFRP5 in gastric cancer and explore the correlation between both the expression of SFRP5 and that of these MMPs in this cancer. METHODS: Expression of SFRP5, MMP-2, MMP-7, MMP-9 and MT1-MMP was determined by real-time PCR, RT-PCR or Western blotting. The methylation status of SFRP5 was detected by Methylation-specific PCR (MSP). Cell lines with SFRP5 methylation were demethylated by a DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (DAC). KatoIII cells were transfected with pcDNA3.1 SFRP5 vector to strengthen SFRP5 expression. To abrogate SFRP5 expression in MKN1 cells, SFRP5 RNAi plamid was used to transfect them. RESULTS: SFRP5 expression was remarkably downregulated in 24 of 32 primary gastric cancer specimens, and even was not detectable in 5 of 8 gastric cancer cell lines. MMP-7 and MT1-MMP mRNA showed a stronger expression in these 24 specimens compared to the other 8 specimens. They also showed higher levels in gastric cancer cell lines AGS and NCI-N87 which had no SFRP5 expression, compared to MKN1 with strong SFRP5 expression. However, they were significantly downregulated, with SFRP5 expression restored in AGS and NCI-N87; and were considerably upregulated with it abrogated in MKN1. CONCLUSION: The results indicate there are frequent occurrences of downregualtion of SFRP5 expression in gastric cancer, primarily due to SFRP5 methylation. It seems to be responsible for the upregulation of MMP-7 expression and MT1-MMP expression on the ground that they are inversely correlated with SFRP5 expression.

WNT7A Overexpression Inhibits Growth and Migration of Hepatocellular Carcinoma via the ß-Catenin Independent Pathway.

Background/Aims. Hepatocellular carcinoma (HCC) is the lethal digestive cancer and the second leading cause of cancer death in men worldwide. Wnt7a, a 39Kd secreted glycoprotein composed of 349 amino acids, was reported to be related to various diseases. However, its role in HCC has not been studied yet. In this study, using gene expression data and clinical information obtained from the Oncomine and KMplot database, we acknowledged that WNT7A was underexpressed in HCC cancer tissue compared with normal tissue, and WNT7A underexpression was correlated with the decreased survival rate of HCC patients. The function of Wnt7a in cell viability, apoptosis, and migration was evaluated by biological behavior assay and molecular analysis. The findings revealed that WNT7A overexpression significantly restrained cell viability and migration while enhancing apoptosis. In addition, WNT7A overexpression promoted cell apoptosis by strengthening Caspase-3 activity and inhibited migration by downregulating EMT transcriptional factor Snail. Furthermore, the expression level of SKP2 was significantly downregulating in the WNT7A overexpression group. In conclusion, this study illustrated that overexpression of WNT7A inhibited cell viability and migration, which was likely attributed to the regulation of SKP2/P21.

Hypermethylation and aberrant expression of secreted frizzled-related protein genes in pancreatic cancer.

AIM: To determine the methylation status and aberrant expression of some secreted frizzled-related protein (SFRP) genes in pancreatic cancer and explore their role in pancreatic carcinogenesis. METHODS: Methylation status and expression of SFRP genes were detected by methylation-specific PCR (MSPCR) and reverse-transcription PCR (RT-PCR) respectively. RESULTS: The frequencies of methylation for SFRP genes 1, 2, 4, 5 were 70%, 48.3%, 60% and 76.7% in pancreatic cancer samples, and 21.7%, 20%, 10% and 36.7% in matched cancer adjacent normal tissue samples, respectively (c2 = 28.23, P < 0.0001 for SFRP gene 1; c2 = 10.71, P = 0.001 for SFRP gene 2; c2 = 32.97, P < 0.0001 for SFRP gene 4; c2 = 19.55, P < 0.0001 for SFRP gene 5). Expression loss of SFRP genes 1, 2, 4 and 5 was found in 65%, 40%, 55% and 71.7% of 60 pancreatic cancer samples, and 25%, 15%, 18.3% and 31.7% of matched cancer adjacent normal tissue samples, respectively (c2 = 19.39, P < 0.0001 for SFRP gene 1; c2 = 9.40, P = 0.002 for SFRP gene 2; c2 = 17.37, P < 0.0001 for SFRP gene 4; c2 = 19.22, P < 0.0001 for SFRP gene 5). SFRP gene 1 was methylated but not expressed in PC-3 and PANC-1, SFRP gene 2 was methylated but not expressed in PANC-1 and CFPAC-1, SFRP gene 4 was methylated but not expressed in PC-3, and SFRP gene 5 was methylated but not expressed in CFPAC-1. CONCLUSION: Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer, which may be involved in pancreatic carcino-genesis.

Hypermethylation and aberrant expression of Wnt antagonist secreted frizzled-related protein 1 in gastric cancer.

AIM: To identify the methylation of secreted frizzled-related protein 1 (SFRP1) in gastric cancer and to investigate the aberrant expression of SFRP1 and its correlation with the clinical pathological features of patients. METHODS: We determined SFRP1 methylation and SFRP1 mRNA expression in 3 gastric cancer cell lines SGC-7901, BGC-823, HGC-27, from 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens by methylation-specific (MSP) PCR and RT-PCR respectively. Fisher's exact test was used to analyze the statistical association between clinical pathological data and aberrant expression of SFRP1. RESULTS: In 3 cancer cell lines, BGC-823 and HGC-27 had methylated SFRP1 and lost SFRP1 mRNA expression. After treatment of BGC-823 and HGC-27 with the demethylating agent, 5-aza-2'-deoxycytidine, SFRP1 was re-expressed. In 52 primary gastric cancer specimens and matched tumor adjacent tissue specimens, hypermethylation of SFRP1 was detected in 23 (44%) and 8 (15%) specimens respectively (chi(2) = 10.34, P < 0.01). Loss of SFRP1 expression was detected in 17(33%) and 6 (12%) specimens respectively (chi(2) = 6.75, P < 0.01). There was a significant correlation between SFRP1 hypermethylation and SFRP1 expression loss. SFRP1 expression was also correlated significantly with tumor stage and lymph node status, but not with patient sex, age and histological type. CONCLUSION: SFRP1 inactivation is a common and early event caused mainly by hypermethylation in gastric cancer. SFRP1 expression loss may be correlated with tumor metastasis in primary gastric cancer.

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells.

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.