Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer.

BACKGROUND: Individualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed. METHODS: Ninety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated. RESULTS: The expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at -211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or -3156 of UGT1A1 tended to have a local invasion. CONCLUSIONS: The UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance.

Hand-assisted laparoscopic versus laparoscopy-assisted D2 radical gastrectomy: a prospective study.

BACKGROUD: The feasibility and safety of Hand-assisted laparoscopic D2 radical gastrectomy (HALG) have been seldom reported, also, benefits and outcomes are not defined. METHODS: We performed a comprehensive and in-depth comparative analysis of the general information, the intraoperative data and postoperative data in the Group HALG and the Group laparoscopy-assisted D2 radical gastrectomy (LAG). RESULTS: The general data of HALG and LAG were no differences (P > 0.05); the blood loss and unexpected injury were similar(P > 0.05); the operative time, the incision length, the number of lymph nodes recovered, the rate of procedure conversion, the amount of postoperative complications, and the length of postoperative hospital stay of Group HALG were prior to that of Group LAG(P < 0.05); there were no differences for the pain score after day 2, the recovery time of intestinal function, the rate of reoperation, the 30-day hospital and readmission rate(P > 0.05); and there were significant linear correlations between the length of postoperative hospital stay and the operative time for both groups(P = 0.00). CONCLUSION: Compared with LAG, HALG had similar features of being minimally invasive and radical in treating gastric cancers, and HALG was safer than LAG.

The naïve effector cells of collagen type I during acute experimental pancreatitis are acinar cells and not pancreatic stellate cells.

OBJECTIVE: The purpose of this study was to investigate the expression of collagen type I and the mRNA level of its regulatory factor, TGF-ß1, in tissue samples of acute pancreatitis and to determine the significance of collagen type I in predisposition to pancreatic fibrosis during acute pancreatitis. METHODS: Sprague-Dawley rats were divided into an experimental group (30 rats) and a control group (12 rats). The rats in the experimental group were intraperitoneally injected with cerulein to induce acute pancreatitis. The distribution and expression of collagen type I in the pancreatic tissues were examined by immunohistochemical staining. The mRNA level of TGF-ß1 was determined by real-time polymerase chain reaction (PCR). RESULTS: (1) Collagen type I was localized in the cytoplasm of pancreatic acinar cells. With pancreatitis progressed, strong positive staining for collagen type I covered whole pancreatic lobules, whereas, the islet tissue, interlobular area, and pancreatic necrotic area were negative for collagen type I. (2) The level of TGF-ß1 mRNA in rats from the experimental group increased gradually the establishment of acute pancreatitis, and was significantly higher than that in the control group at every time point. CONCLUSIONS: (1) During acute pancreatitis, pancreatic acinar cells, not pancreatic stellate cells as traditionally believed, were the naïve effector cells of collagen type I. (2) TGF-ß1 played a key role in regulating collagen I expression during acute pancreatitis.

Uncut interposed jejunum pouch versus esophago-gastrostomy and double anastomoses of jejunum to the esophagus and residual stomach: An innovative method of digestive tract reconstruction following proximal gastrectomy.

AIM: An innovative method of digestive tract reconstruction following proximal gastrectomy, the uncut interposed jejunum pouch, esophagus and residual stomach double anastomosis(Uncut-D), was established in recent years. In order to fully clarify the superiority of the procedure, this study has conducted a systematic analysis and thorough discussion. METHODS: 118 patients with adenocarcinoma of the esophagogastric junction who underwent proximal gastrectomy were enrolled in this study. According to the methods of digestive tract reconstruction, these patients were divided into three groups: Uncut-D(n = 43), esophagogastrostomy (EG, n = 36), jejunal interposition (JI, n = 39).The preoperative indicators, surgical complications and related indicators of postoperative quality of life were analyzed. RESULTS: There were no significant differences in preoperative data among all groups (P > 0.05); The digestive tract reconstruction time in Uncut-D group was more than that in EG group, and less than that in JI group (P < 0.05). The incidence of esophageal anastomotic stenosis in Uncut-D group was significantly lower than that in EG group (P < 0.05); In Uncut-D group, the incidence of reflux esophagitis, postoperative nutrition index(PNI), weight recovery and Visick classification were significantly better than those in EG group (P < 0.05), furthermore, the incidence of delayed gastric emptying,PNI and weight recovery were better than those in JI group (P < 0.05). CONCLUSIONS: The Uncut-D procedure gave full play to jejunal continuity and the advantages of pouch, and played a valuable role in gastric and cardiac replacement, which significantly reduced long-term complications, improved postoperative nutritional status of patients and long-term quality of life.

Continuous Jejunal Pouch and Residual Stomach Anastomosis Combined with Jejunal Lateral Anastomosis: An Improved Method of Gastrointestinal Reconstruction following Distal Gastrectomy.

AIM: Currently, there is no optimal digestive tract reconstruction technique well recognized by scholars after distal gastrectomy. A new reconstruction method, which was modified from the classic Roux-en-Y procedure, the continuous jejunal pouch and residual stomach anastomosis combined with jejunal lateral anastomosis (Contin-L), was established. In order to fully clarify the superiority of this procedure, this study has conducted a systematic analysis and prepared a summary of the clinical data of patients who underwent distal gastrectomy for gastric cancer. METHODS: From June 2013 to March 2016, we enrolled 198 patients with gastric cancer who underwent radical D2 distal gastrectomy. According to the reconstruction methods, these patients were divided into three groups: Contin-L (n = 74), Billroth II (n = 59), and Roux-en-Y (n = 65) groups. The operation time for reconstruction, complications, prognostic nutritional index (PNI), and the Visick grading were analyzed. RESULTS: Regarding long-term complications, such as reflux gastritis, the Contin-L procedure showed significantly better results than Billroth II (p < 0.0001). Regarding the long-term postoperative nutritional status, such as the PNI and body weight recovery, the Contin-L procedure displayed significantly better results than Billroth II and Roux-en-Y (p < 0.05). Postoperative subjective feelings evaluated by Visick grading were significantly more improved in the Contin-L than in the Billroth II and Roux-en-Y groups (p ≤ 0.01). CONCLUSIONS: The Contin-L procedure gave full play to the advantages of jejunal continuity, and pouch and lateral anastomoses, which significantly reduced short- and long-term complications, and improved the long-term patient quality of life following the surgical procedure.

Hand-assisted laparoscopic versus laparoscopic-assisted radical gastrectomy in the treatment of advanced distal gastric cancer: final results of a single-center randomized study.

OBJECTIVE: To compare the results and 5- and 8-year overall survival (OS) and disease-free survival (DFS) of hand-assisted laparoscopic surgery (HALS) and laparoscopic-assisted surgery (LAS) in radical gastrectomy for advanced distal gastric cancer. METHODS: A total of 124 patients admitted to our institution from May 2009 to April 2013 were randomly divided into a HALS group (n = 62) and a LAS group (n = 62). Postoperatively, 110 patients were followed for 5 and 8 years, and 14 patients were lost to follow-up. The 5- and 8-year OS and DFS rates of the groups were compared and analyzed. RESULTS: The 5- and 8-year OS rates, respectively, were 38.8% and 19.4% in the HALS group and 38.3% and 15.3% in the LAS group (log-rank test, χ2 = 0.250). The 5- and 8-year DFS rates, respectively, were 23.1% and 10.6% in the HALS group and 19.3% and 11.6% in the LAS group (log-rank test, χ2 = 0.109). No significant differences were found. CONCLUSION: Compared with LAS, HALS radical gastrectomy for advanced distal gastric cancer had a lower conversion rate to open surgery, shorter surgical duration, and more thorough dissection of lymph nodes; 5- and 8-year OS and DFS rates were similar to those with LAS.

Hand-assisted laparoscopic versus open surgery for radical gastrectomy in the treatment of advanced distal gastric cancer: long-term overall and disease-free survival (final results of a single-center study).

OBJECTIVE: To compare the surgical effects and long-term efficacy of hand-assisted laparoscopic surgery (HALS) and open surgery (OS) in radical gastrectomy for advanced distal gastric cancer. METHODS: One hundred twenty-four patients who were admitted to the Department of Gastrointestinal Surgery of the West War Zone General Hospital from May 2008 to April 2012 were randomly divided into a HALS group (n = 62) and an OS group (n = 62). After surgery, 113 patients were followed up for 5 and 8 years, and 11 patients were lost to follow-up. The 5- and 8-year overall survival and disease-free survival rates of the two groups were compared and analyzed. RESULTS: The 5- and 8-year overall survival rates were 31.90% and 18.40% in the HALS group and 32.50% and 18.60% in the OS group, respectively. The 5- and 8-year disease-free survival rates were 21.50% and 13.00% in the HALS group and 21.90% and 13.10% in the OS group, respectively. No significant differences were found. CONCLUSION: Hand-assisted laparoscopic radical gastrectomy for advanced distal gastric cancer has the advantages of less severe trauma, less intraoperative blood loss, more rapid postoperative recovery, and equivalent long-term efficacy compared with OS.

Experimental evidence supporting the lack of primary stem cells in adult pancreatic tissue.

PURPOSE: To investigate the origin and localization of pancreatic stem cells in adult pancreatic tissues and to determine the primary mechanism underlying the participation of these cells in repairing pancreatic injuries. METHODS: Sprague-Dawley rats were divided into experimental and control groups. The experimental group was given intraperitoneal injections of cerulein to induce acute pancreatitis. At 6 h, 1, 2, 3, 5 and 7 days, 5 rats from the experimental group and 2 rats from the control group were sacrificed; all sacrificed animals were intraperitoneally injected with 5-bromo-2'-deoxyuracil nucleotides (BrdU) 6 and 3 h prior to sacrifice. The pathological changes of pancreatic tissue were observed. The stem cell marker nestin and the cell proliferation marker BrdU were detected with immunohistochemistry. Pancreatic duodenal homeobox-1 (PDX-1) was determined by real-time PCR. RESULTS: (1) The pathological changes of acute pancreatitis can be divided into three phases: the edema and apoptosis phase, the hemorrhagic necrosis phase, and the reconstruction phase. (2) Nestin-positive cells mainly appeared in the interlobular vascular lumen after cerulein injection, and they peaked at day 3 when the positive cells spread all over the pancreatic tissues. (3) BrdU-positive cells began to appear in the area surrounding the interlobular region, and the number of positive cells peaked on day 7. (4) The expression of PDX-1 mRNA initially increased, then decreased and gradually got close to a normal level. CONCLUSION: Primary pancreatic stem cells may not exist in the adult pancreatic tissues. The so-called pancreatic stem cells may actually originate from bone marrow stem cells. When pancreatic tissue is injured, bone marrow stem cells may participate in the repair.

[Safety and efficacy of hand-assisted laparoscopic versus open distal gastrectomy for gastric cancer: A systematic review and meta-analysis].

OBJECTIVE: To systematically assess the safety and efficacy of hand-assisted laparoscopic distal gastrectomy (HALG) versus open distal gastrectomy (ODG) for gastric cancer. METHODS: Chinese or English literature regarding comparison of HALG and ODG were collected by searching in databases (such as PubMed, Cochrane Library, CNKI, Wanfang database) between January 1996 and September 2016. The data of operative time, incision length, blood loss, number of harvested lymph nodes, time to flatus, hospital stay, postoperative complication morbidity and long-term outcomes were compared between the two procedures. Then funnel plot was used to evaluate publication bias and sensitivity analysis was used to evaluate the stability of the results. All these data analyses were performed using the Meta for or Meta package of R version 3.3.1. RESULTS: A total of 7 studies with 835 patients (323 cases in HALG group and 512 cases in ODG group) were included. Compared with ODG, HALG had a longer operative time (WMD=28.93 minutes, 95%CI=9.59 to 48.28, Z=2.93, P=0.000), a shorter incision length (WMD=-10.31 cm, 95%CI=-14.01 to -6.62, Z=-5.47, P=0.000), less blood loss (WMD=-140.08 ml, 95%CI=-215.07 to -65.09, Z=-3.66, P=0.000), faster gastrointestinal recovery (WMD=-1.23 days, 95%CI=-1.89 to -0.56, Z=-3.62, P=0.000), shorter postoperative hospital stay (WMD=-3.24 days, 95%CI=-5.47 to -1.02, Z=-2.85, P=0.000). In subgroup analysis, 3 studies published before 2013 vs. 4 studies published afterwards, the number of harvested lymph nodes (WMD=-0.78, 95%CI=-2.05 to 0.50, Z=-1.19, P=0.235) and postoperative complication morbidity (RR=1.02, 95%CI=0.43 to 2.44, Z=0.05, P=0.961) did not differ significantly between two groups. Compared with ODG, the RR(95%CI) of ileus of HALG was 0.43 (0.07 to 2.82), but the difference was not statistically significant (P=0.383). One study reported the 5-year overall survival rates of HALG and ODG were 81.0% vs 67.5%, and the tumor recurrence rates were 7.1% vs 22%, respectively, but the differences were not statistically significant(all P>0.05). Sensitivity analysis showed that the above results were stable. The funnel plots of the lymph nodes and postoperative complication morbidity did not present significant publication bias. CONCLUSIONS: HALG has the advantages of minimal invasiveness such as shorter incision length and quicker recovery. Furthermore, the short-term efficacy of HALG is similar to conventional open surgery. However, the long-term efficacy is lack of support from multicenter long-term follow-up results.

[Efficacy comparison of lymph node dissection patterns of the reverse and the cabbage in hand-assisted laparoscopic D2 radical gastrectomy].

OBJECTIVE: To compare the clinical efficacy of the lymph node dissection patterns of the reverse and the traditional cabbage in hand-assisted laparoscopic D2 radical gastrectomy (HALG). METHODS: From December 2010 to October 2013, 194 patients with HALG in Chengdu Military General Hospital were enrolled in this study. According to the pattern of lymph node dissection, 108 patients were performed with the reverse procedure which took spleen as starting point, from left to right, and 86 patients were performed with the traditional cabbage procedure which took the abdominal cavity as the center, from both sides to middle. A retrospective comparative analysis was made on the intra- and post-operative data between the two groups. RESULTS: All the patients were successfully performed with HALG, and no peri-operative death occurred. There were no significant differences in the incision length [(7.0 ± 0.2) cm vs. (6.9 ± 0.3) cm], the operative time [(170.9 ± 33.8) minute vs. (174.6 ± 22.4) minute], dissected lymph node number (17.6 ± 7.5 vs. 17.1 ± 5.8) and post-operative complications [(6.5%(7/108) vs. 8.1%(7/86)] between the reverse group and cabbage group (all P>0.05). However, less blood loss [(204.6 ± 98.2) ml vs. (259.1 ± 122.6) ml, P<0.01] and shorter postoperative hospital stay [(9.0 ± 1.7) day vs. (10.5 ± 4.0) day, P<0.01] were observed in reverse group as compared to cabbage group. During 1 to 6 months follow-up, no death case was found in reverse group, while 1 case died due to upper gastrointestinal bleeding 48 days after operation in cabbage group. CONCLUSION: Efficacy is similar between the two HALG procedures in lymph node dissection, while reverse procedure has certain advantages, such as less blood loss and faster recovery.

Three-step hand-assisted laparoscopic d2 radical gastrectomy for chinese obese patients: a highly efficient and feasible surgical approach.

Three-step hand-assisted laparoscopic D2 radical gastrectomy (HALG) is a modified surgical procedure that has achieved satisfactory results for obese patients in our surgical center. To fully elucidate the advantages of this procedure, in this study, comprehensive and in-depth comparative analyses were performed to assess clinical data from obese gastric cancer patients who underwent HALG, laparoscopic-assisted D2 radical gastrectomy (LAG), and open D2 radical gastrectomy (OG) in our surgical center during a specific time period. For the 3 groups, incision length was 1.25 cm longer for the HALG group than for the LAG group but was significantly shorter for the HALG group than for the OG group (P =0.00). The rate of conversion to laparotomy , the pneumoperitoneum time and the number of recovered lymph nodes were significantly better for the HALG group than for the LAG group (P <0.05). The pain score at day 2 after surgery, intestinal function recovery time, and duration of postoperative hospital stay were not significantly different for the HALG and LAG groups ( P >0.05) but were significantly better for the HALG group than for the OG group (P <0.05). There were significantly fewer postoperative complications for the HALG group than for the LAG and OG groups (P =0.049). According to the results, the "three-step HALG method" incorporates both the thoroughness of the radical OG approach and the minimal invasiveness of the LAG approach for obese patients. Thus, the HALG approach is a relatively safe and extremely feasible surgical procedure for the treatment of these patients.

Gastric-jejunum pouch side-to-end anastomosis: a novel and safe operation of gastrojejunostomy for preventing reflux gastritis.

PURPOSE: This study aims to introduce a simple operation method of gastrojejunostomy for preventing reflux esophagitis --gastric-jejunum pouch side-to-end anastomosis. METHODS: Based on Billroth II anastomosis (Billroth II) method, we designed a new technique of anastomosis between stomach wall and jejunal pouch. The technique was named gastric-jejunum pouch side-end anastomosis. We retrospectively analyzed the clinical data which was collected from March 2012 to February 2014. Among all the recruited 66 patients, 51 gastric cancer patients and 7 pyloric obstruction patients were implemented with hand-assisted laparoscopic distal gastrectomy plus D2 lymph node dissection. The remaining 8 patients were malignant pyloric obstruction; they were treated with small exploratory incision on the upper abdomen and distal gastric partial transection. All the patients were treated with gastric-jejunum pouch side-to-end anastomosis. RESULTS: The surgical incision was small, the operative time was short, their bleeding volume was little, the recovery time of the bowel function and hospitalization time was relatively short. Postoperatively, there was neither mortality and gastroparesis, nor anastomotic leakage and jejunal pouch leakage. Minor postoperative complications were detected followed up for 12 months, no acid reflux and reflux esophagitis symptoms was reported. CONCLUSIONS: Gastric -jejunum pouch side-to-end anastomosis is a simple operation technique with highly surgical safety.

Hand-assisted laparoscopic versus open radical resection of gastric remnant cancer: a clinical comparison.

OBJECTIVE: To compare the perioperative clinical data between hand-assisted laparoscopic and open radical resection of gastric remnant cancer, and analyze the feasibility and advantages of hand-assisted laparoscopic resection of gastric remnant cancer. METHODS: The clinical data of 18 patients with gastric remnant cancer who underwent hand-assisted laparoscopic (n=9) or open surgery (n=9) were retrospectively analyzed to compare the perioperative outcomes and recovery between December 2007 and October 2014. RESULTS: All 18 patients underwent surgery without post-operative complications. In the hand-assisted laparoscopy group, none required conversion to open surgery, and no intraoperative auxiliary injury occurred. The incision length was (8.78±0.62) cm in the hand-assisted laparoscopy group, and (14.06±0.81) cm in the open surgery group (t=15.565, P=0.000). The duration of the operation averaged (221.11±19.48) min in the hand-assisted laparoscopy group, and (212.89±14.30) min in the open surgery group (t=-1.021, P=0.323). The intraoperative blood loss was (105.56±35.04) ml in the hand-assisted laparoscopy group, and (147.78±41.92) ml in the open surgery group (t=2.319, P=0.034). The number of lymph nodes scavenged was (16.22±2.99) and 16.67±3.28 in the hand-assisted laparoscopy group and in the open surgery group, respectively (t=-.300, P=0.768). The postoperative time to passage of gas by anus was (68.67±10.00) hr in the hand-assisted laparoscopy group, and (79.78±9.16) hr in the open surgery group (t=2.458, P=0.026). Mild postoperative hemorrhage occurred at the anastomotic site in one patient in each surgery group. These complications resolved after treatment. And no serious perioperative complications, such as anastomotic site fistula, massive hemorrhage in the peritoneal cavity or digestive tract or death occurred in either group. CONCLUSIONS: Hand-assisted laparoscopic radical resection of gastric remnant cancer is feasible, is of comparable efficacy to open surgery, and offers several advantages including small incisions, mild intraoperative hemorrhage, rapid postoperative recovery, and few postoperative complications.

Learning curve for hand-assisted laparoscopic D2 radical gastrectomy.

AIM: To describe the learning curves of hand-assisted laparoscopic D2 radical gastrectomy (HALG) for the treatment of gastric cancer. METHODS: The HALG surgical procedure consists of three stages: surgery under direct vision via the port for hand assistance, hand-assisted laparoscopic surgery, and gastrointestinal tract reconstruction. According to the order of the date of surgery, patients were divided into 6 groups (A-F) with 20 cases in each group. All surgeries were performed by the same group of surgeons. We performed a comprehensive and in-depth retrospective comparative analysis of the clinical data of all patients, with the clinical data including general patient information and intraoperative and postoperative observation indicators. RESULTS: There were no differences in the basic information among the patient groups (P > 0.05). The operative time of the hand-assisted surgery stage in group A was 8-10 min longer than the other groups, with the difference being statistically significant (P = 0.01). There were no differences in total operative time between the groups (P = 0.30). Postoperative intestinal function recovery time in group A was longer than that of other groups (P = 0.02). Lengths of hospital stay and surgical quality indicators (such as intraoperative blood loss, numbers of detected lymph nodes, intraoperative side injury, postoperative complications, reoperation rate, and readmission rate 30 d after surgery) were not significantly different among the groups. CONCLUSION: HALG is a surgical procedure that can be easily mastered, with a learning curve closely related to the operative time of the hand-assisted laparoscopic surgery stage.

Function of oval cells in hepatocellular carcinoma in rats.

AIM: To study oval cells' pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression. METHODS: One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villus-like apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of c-myc mRNA increased with the progression of HCC. However, in the intervention group, UTI could retard its increase. CONCLUSION: Oval cells work throughout the development of HCC, and might play important roles in this process. c-myc gene may be a kind of promoter gene of HCC, and play a key role in hepatic injury and development of HCC. UTI could retard the occurrence of HCC.

The expression of c-kit and proliferating cell nuclear antigen in oval cells of rats with hepatocellular carcinoma.

OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and the expression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellular carcinoma. METHODS: A hundred and twenty clean SD rats were divided into three groups: normal group, cancer-induction group and intervention group. The normal group was fed with standard forage while the rest two groups were fed with 3'-methyl-2-methylamino-azobenzene (DAB) to induce carcinoma for 14 weeks and then fed with standard forage and water. Uscharidin was injected abdominally to the intervention group from the first week to the 14th week. All rats were killed and biopsy specimens were taken from the left and right liver lobes for immunohistochemical staining of c-kit and PCNA on the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week. RESULTS: From the 2nd to 14th week after liver infection, c-kit positive cells, mainly oval cells were found in the portal area in the carcinoma-induction group and dotted positive pigmentations in liver lobules. In the 22nd week, a large number of cancerous nodes occurred and nuclei heteromorphism was apparent; the number of positive cell decreased but positive cells could be sparsely observed in cancerous nodes. In the 2nd week of the carcinoma-induction process, PCNA positive cells were oval cells in the portal area. In the 4th week, a lot of hepatic cells were positively stained, especially in the central vein area. In the 6th week, PCNA positive cells could be seen in the lobules of the liver. In the 8th week, the number of PCNA cells decreased comparatively. From the 10th to 14th week, oval cells in the portal area were still over-expressed. From the 16th to 24th week, a large number of cancerous nodes occurred and PCNA was over-expressed in some of them. In necrotic cancerous nodes, the para-cancerous PCNA positive cells were sparsely distributed and their number was less than that of PCNA positive cells of cancerous tissues. CONCLUSIONS: Hepatic stem cells originating from the terminal biliary plexus of the portal area are involved in the development of hepatocarcinoma because c-kit positive cells expressed in cancerous nodes, accompany the whole process of the development. In the middle inflammatory period of carcinoma-induction, the expression of PCNA in hepatic cells peaked, but the index decreased in the late inflammatory period and in the proliferated fibrosis stage. The expression of PCNA is a tortuous process, going up, down, then up again from normal tissues to cancerous tissues. Combined with pathological findings, PCNA can be considered as a warning index for carcinomatous cells.

Distribution of oval cells and c-myc mRNA expression in mouse hepatocarcinogenesis.

BACKGROUND: This study was designed to assess the roles of oval cells and c-myc mRNA in the process of hepatocarcinogenesis and to clarify the function of carcinogene c-myc in the development of hepatocellular carcinoma (HCC) and the mechanism of inhibitory function of uscharidin on HCC in mouse hepatocarcinogenesis. METHODS: A total of 120 clean SD mice were divided into normal group, cancer induction group, and intervention group. The normal group was fed with standard forage while the rest two groups were given p-dimethylaminoazobenzene (DAB) to induce cancer. Thirteen weeks after induction of cancer, the two groups were fed with standard forage and water. Once the pattern was set up, the intervention group was given uscharidin injection into the abdominal cavity from the first week to the 14th week. On the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week, all mice were killed and biopsied from the liver lobe for pathological analysis. At the same time, the number of tumor nodes was counted and the expression of c-myc mRNA was tested by RT-PCR. RESULTS: Since the 2nd week after cancer induction, proliferated oval cells could be seen in the portal area. Initially, the oval cells appeared in the cortical layer of the portal area, then proliferated gradually and immigrated into the liver parenchyma. In the period of fibrosis after liver proliferation, proliferated heaps of oval cells were noted in both portal and peripheral areas. In the period of carcinomatous change, oval cells could be seen both outside and inside of cancer nodes, but most of them were distributed outside. The c-myc gene was expressed negatively in the liver tissue of mice. The quantity of the expression began to increase at the time of infection of the liver and tended to increase with the degree of hepatic injury. In the period of canceration, the expression level of c-myc mRNA increased gradually. The intervention of uscharidin could not inhibit but delay the increase of the expression of c-myc mRNA. CONCLUSION: Oval cells are closely related to hepatocarcinoma cells, which play an important role in the occurrence and development of hepatocarcinogenesis. Uscharidin can inhibit the occurrence of hepatocarcinogenesis or local spreading at the early stage of cancer induction by DAB, but it cannot inhibit the expression of c-myc.