Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway.

The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.

Development and validation of an immune-related prognosis signature associated with hypoxia and ferroptosis in hepatocellular carcinoma.

BACKGROUND: Hypoxia and ferroptosis are crucial in the occurrence and development of hepatocellular carcinoma (HCC), and they both affect the immune status of the tumor microenvironment. Previous studies have also shown a link between hypoxia and ferroptosis. PATIENTS AND METHODS: In all, 814 HCC cases from The Cancer Genome Atlas and Gene Expression Omnibus databases were used as the discovery cohort, and 230 HCC cases from the International Cancer Genome Consortium database were used as the validation cohort. Hypoxia subtypes and ferroptosis subtypes were identified by consensus cluster analysis according to 174 hypoxia-related genes and 193 ferroptosis-related genes. The prognostic signature was constructed using the Cox and LASSO regression analyses, and two risk groups were identified. A comprehensive analysis of the clinical and immune characteristics between the two risk groups was further performed. RESULTS: Two hypoxia subtypes and two ferroptosis subtypes were distinguished and verified; subsequently, a five-gene prognostic signature was constructed and the risk score could be acquired by the following formula: risk score = 0.0604*Expression (CA9)-0.0714*Expression (ANXA10) + 0.1501*Expression (CDC20)-0.0853*Expression (CYP7A1) + 0.0530*Expression (SPP1). Compared with the low-risk group, the high-risk group had a worse prognosis. The high-risk group also showed a higher level of immune infiltration than the low-risk group, and immune checkpoints were generally upregulated in the high-risk group. The antigen presentation ability of the low-risk group was poor, which may be related to the immune escape mechanism. Drug sensitivity analysis indicated that the high- and low-risk groups were sensitive to tyrosine kinase inhibitors and chemotherapeutic drugs, respectively. CONCLUSION: The hypoxia-, ferroptosis-, and immune-associated prognostic signature we constructed could stratify patients with HCC and guide precise treatment.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Autophagy Contributes to Liver Regeneration After Portal Vein Ligation in Rats.

BACKGROUND This study investigated the effect of 70% portal vein ligation (PVL), a widely used procedure for inducing rapid liver regeneration, on the expression of autophagy-related proteins in non-ligated liver lobes in rats. MATERIAL AND METHODS Rats were subjected to either sham (n=30, major portal vein branches were exposed but kept intact) or PVL (n=30, major portal vein branches were double-ligated) operations. Liver samples were collected 12, 24, 48, 72, and 168 h after the operation. Liver volume, liver color, non-ligated liver percentage, and the expressions of light chain (LC) 3, beclin 1, and cyclin D1 in the non-ligated liver lobes were determined. RESULTS When compared to sham rats, increased (P<0.001) growth of the non-ligated liver lobes was observed in PVL rats as early as 12 h after surgery; an increased (P≤0.001) LC3 II/I ratio was observed in the non-ligated lobes of PVL rats as early as 24 h after surgery. Increased expressions of beclin 1 (P≤0.001) and cyclin D1 (P<0.001) were observed in the non-ligated lobes of PVL rats from 12 to 72 h after surgery and from 12 to 168 h after surgery, respectively, when compared to sham rats. In the non-ligated lobes, the expressions of beclin 1 and cyclin D1 were linearly and positively correlated with the LC3 II/I ratio. CONCLUSIONS Autophagy is activated in the non-ligated liver after PVL. Both beclin 1 and cyclin D1 are linearly and positively correlated with autophagy activity in the PVL-induced rapid liver regeneration model.

Current status of surgical treatment of colorectal liver metastases.

Liver metastasis (LM) is one of the major causes of death in patients with colorectal cancer (CRC). Approximately 60% of CRC patients develop LM during the course of their illness. About 85% of these patients have unresectable disease at the time of presentation. Surgical resection is currently the only curative treatment for patients with colorectal LM (CRLM). In recent years, with the help of modern multimodality therapy including systemic chemotherapy, radiation therapy, and surgery, the outcomes of CRLM treatment have significantly improved. This article summarizes the current status of surgical treatment of CRLM including evaluation of resectability, treatment for resectable LM, conversion therapy and liver transplantation for unresectable cases, liver resection for recurrent CRLM and elderly patients, and surgery for concomitant hepatic and extra-hepatic metastatic disease (EHMD). We believe that with the help of modern multimodality therapy, an aggressive oncosurgical approach should be implemented as it has the possibility of achieving a cure, even when EHMD is present in patients with CRLM.

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma.

Epithelial-to-mesenchymal transition (EMT) is a complex process involving multiple genes, steps and stages. It refers to the disruption of tight intercellular junctions among epithelial cells under specific conditions, resulting in loss of the original polarity, order and consistency of the cells. Following EMT, the cells show interstitial cell characteristics with the capacity for adhesion and migration, while apoptosis is inhibited. This process is critically involved in embryogenesis, wound-healing, tumor invasion and metastasis. The tumor microenvironment is composed of infiltrating inflammatory cells, stromal cells and the active medium secreted by interstitial cells. Most patients with hepatocellular carcinoma (HCC) have a history of hepatitis virus infection. In such cases, major components of the tumor microenvironment include inflammatory cells, inflammatory factors and virus-encoded protein are major components. Here, we review the relationship between EMT and the inflammatory tumor microenvironment in the context of HCC. We also further elaborate the significant influence of infiltrating inflammatory cells and inflammatory mediators as well as the products expressed by the infecting virus in the tumor microenvironment on the EMT process.

Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial.

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.

Overexpression of δ-catenin is associated with a malignant phenotype and poor prognosis in colorectal cancer.

Little is known regarding the expression or clinical significance of δ-catenin, a member of the catenin family, in colorectal cancer (CRC). The present study examined the expression of δ-catenin using immunohistochemistry in 110 cases of CRC, including 70 cases with complete follow­up records and 40 cases with paired lymph node metastases. In addition, δ­catenin mRNA and protein expression were compared in 30 pairs of matched CRC and normal colorectal tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. δ­Catenin was weakly expressed or absent in the cytoplasm of normal intestinal epithelial cells, whereas positive δ­catenin expression localized to the cytoplasm was observed in CRC cells. The rate of positive δ­catenin expression in CRC (68.18%; 75/110) was significantly higher than that in normal colorectal tissues (36.7%; 11/30; P<0.001). In addition, δ­catenin mRNA and protein expression were significantly increased in CRC tissues compared to those in their matched normal tissues (all P<0.05). The expression of δ­catenin in stage III­IV CRC was higher than that in stage I­II CRC, and the expression of δ­catenin in the tumors of patients with lymph node metastases was higher than that in patients without lymph node metastases. Kaplan­Meier survival curves demonstrated that the survival time of patients with positive δ­catenin expression was shorter than that of patients with negative δ­catenin expression (P=0.005). Furthermore, Cox multivariate analysis indicated that the tumor, nodes and metastasis stage (P=0.02) and positive δ-catenin expression (P=0.033) were independent prognostic factors in CRC. The present study therefore indicated that δ-catenin may be a suitable independent prognostic factor for CRC.

Preconditioning with glutamine protects against ischemia/reperfusion-induced hepatic injury in rats with obstructive jaundice.

OBJECTIVE: To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. METHODS: An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. RESULTS: The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1ß and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. CONCLUSIONS: The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.

Polymyxin B protects against hepatic ischemia/reperfusion injury in a rat model of obstructive jaundice.

This study was conducted in order to investigate the effects of polymyxin B (PMB) against hepatic ischemia/reperfusion (I/R) injury in rats with obstructive jaundice. Thirty-six Wistar rats (eighteen each) with induced hepatic I/R injury by biliary tract ligation and recanalization were assigned to a control group (reperfused with normal saline) and a PMB group (reperfused with PMB). Indicators involving liver function, oxidation resistance, pro-inflammatory state, and anti-apoptosis effect were determined following the instructions. Compared with normal saline, PMB reperfusion resulted in a significant improvement of liver function (increase of glutathione and reduction of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), oxidation resistance (decreased malondialdehyde and myeloperoxidase activity), alleviation of pro-inflammatory state (less tumor necrosis factor (TNF)-α, interleukin-1 beta (IL-1ß), nuclear factor kappa B (NF-κB) mRNA, and intercellular adhesion molecule (ICAM)-1), and anti-apoptosis effect (more Bcl-2 and less Bax). PMB protects the liver from I/R injury mainly through reducing cellular oncosis and apoptosis and regulating the expression of NF-κB, TNF-α, IL-1ß, and ICAM-1.

Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin.

δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases of colorectal cancer (CRC) and 15 normal colon tissues. Co-immunoprecipitation was used to examine whether δ-catenin competed with p120ctn to bind E-cadherin in CRC cells. The effects of δ-catenin overexpression or siRNA-mediated knockdown on the proliferation and invasive ability of CRC cells were investigated using the MTT and Matrigel invasion assays. The results showed that positive δ-catenin expression was significantly more frequent in CRC compared to normal colon tissues and associated with poor differentiation, stage III-IV disease, and lymph node metastasis in CRC (all P < 0.05). In two CRC cell lines, δ-catenin bound to E-cadherin in competition with p120ctn. Overexpression of δ-catenin promoted the proliferation and invasion of CRC cells; knockdown of δ-catenin reduced CRC cell proliferation and invasion. In conclusion, we speculate that overexpression of δ-catenin reduces the expression of E-cadherin and alters the balance between E-cadherin and p120ctn, which in turn affects the formation of intercellular adhesions and promotes invasion and metastasis in CRC.

Attenuation of reperfusion-induced hepatocyte apoptosis is associated with reversed bcl-2/bax ratio in hemi-hepatic artery-preserved portal occlusion.

BACKGROUND: This study aimed to examine the hepatocyte apoptosis in a hepatic blood inflow occlusion rat model without hemi-hepatic arterial control and its association with the expressions of the apoptosis-regulating genes bcl-2 and bax. MATERIALS AND METHODS: Wistar rats were equally and randomly assigned to undergo sham operation (control group, n = 8), Pringle's maneuver (group PR, n = 32), hemi-hepatic occlusion (group HH, n = 32), or hemi-hepatic artery-preserved portal occlusion (group HP, n = 32). The hepatic blood inflow was interrupted for 30 min using a microvascular clip in the three experimental groups. The clips were removed to achieve hepatic reperfusion for up to 24 h. Blood samples and liver specimens were collected following reperfusion to perform pathologic examination, serum transferase assay, apoptosis analysis, and determination of bcl-2 and bax mRNA and protein expressions. RESULTS: The reperfusion-related hepatocytic injuries were more severe in the PR group than in the HH and HP groups, both pathologically and biochemically. More reperfused hepatocytes became apoptotic in the PR group than in the HH and HP groups. However, the values of the HH and HP groups were comparable in cellularity, levels of serum transferases, and apoptosis rate following reperfusion. The ratios of bcl-2/bax were reversed, which was more evident in the HH and HP groups than in the PR group. CONCLUSION: Hemi-hepatic artery-preserved portal occlusion had little effect on hepatocyte apoptosis compared with Pringle's maneuver and caused minor ischemia-reperfusion injury as shown by the reversed bcl-2/bax ratio.

Overwhelming postsplenectomy infection due to Mycoplasma pneumoniae in an asplenic cirrhotic patient: case report.

BACKGROUND: Mycoplasma pneumoniae infection is usually self-limited, but some fulminant cases are fatal, even when occurring in previously healthy individuals. It can also be the cause of overwhelming postsplenectomy infection (OPSI). CASE PRESENTATION: We report a case of OPSI in a 41-year-old woman with hypersplenism associated with hepatitis B cirrhosis. We detected a significant Mycoplasma pneumoniae agglutination titer, but no evidence of infection with Chlamydia pneumoniae, Legionnella spp., or any other bacterial or fungal pathogens. She eventually died despite aggressive therapy. CONCLUSIONS: M. pneumoniae could be an underestimated cause of OPSI, and should be suspected in fulminant infectious cases in asplenic patients.

Hepatic blood inflow occlusion without hemihepatic artery control in treatment of hepatocellular carcinoma.

AIM: To investigate the clinical significance of hepatic blood inflow occlusion without hemihepatic artery control (BIOwHAC) in the treatment of hepatocellular carcinoma (HCC). METHODS: Fifty-nine patients with HCC were divided into 3 groups based on the technique used for achieving hepatic vascular occlusion: group 1, vascular occlusion was achieved by the Pringle maneuver (n = 20); group 2, by hemihepatic vascular occlusion (HVO) (n = 20); and group 3, by BIOwHAC (n = 19). We compared the procedures among the three groups in term of operation time, intraoperative bleeding, postoperative liver function, postoperative complications, and length of hospital stay. RESULTS: There were no statistically significant differences (P > 0.05) in age, sex, pathological diagnosis, preoperative Child's disease grade, hepatic function, and tumor size among the three groups. No intraoperative complications or deaths occurrred, and there were no significant intergroup differences (P > 0.05) in intraoperative bleeding, hepatic function change 3 and 7 d after operation, the incidence of complications, and length of hospital stay. BIOwHAC and Pringle maneuver required a significantly shorter operation time than HVO; the difference in the serum alanine aminotransferase or aspartate aminotransferase levels before and 1 d after operation was more significant in the BIOwHAC and HVO groups than in the Pringle maneuver group (P < 0.05). CONCLUSION: BIOwHAC is convenient and safe; this technique causes slight hepatic ischemia-reperfusion injury similar to HVO.

[Patterns of hepatic cells death during hepatic ischemia/reperfusion injury in cirrhotic rats].

OBJECTIVE: To research on the main pattern of hepatic cells death during hepatic ischemia/ reperfusion (I/R) injury in cirrhotic rat. METHODS: Cirrhotic rat model was established by carbon tetrachloride replication. These rats were randomly divided into sham operation group and I/R group. In the I/R group, 70% i/R injury model was established and then the liver samples were taken 0, 1, 6, 24, and 48 hours after reperfusion. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, Na+ - K+ ATPase, and Ca2+ ATPase were compared. the percentage of apoptotic/oncotic hepatic cells was measured with flow cytometry, and the changes in hepatic cellular structures were observed under transmission electron microscope. RESULTS: Compared with the sham operation group, the levels of serum AST and ALT significantly increased in the I/R group (P < 0.05), reaching their peak levels at the 6th hour. The activities of Na+ - K+ ATPase and Ca2+ ATPase dramatically decreased one hour after reperfusion and then gradually recovered (P < 0.05). Hepatic cells mainly suffered oncosis at the early stage after reperfusion (within 6 hours); at the late stage (around 24 hours after reperfusion), apoptosis became the main death pattern. CONCLUSION: Oncosis is the main pattern of hepatic cells death during I/R injury in cirrhotic rat, and the severity of hepatic injury correlates with the oncosis.

[Resection of centrally located primary liver cancer].

OBJECTIVE: To summarize the experience of hepatectomy for patients with centrally located primary liver cancer. METHODS: The clinical data of patients with centrally and non-centrally located primary liver cancer were retrospectively reviewed. The biochemical indicators, operation duration, hepatic inflow occlusion time, hospital stay, operative blood loss, amount of blood transfusion, complication, and effectiveness of three occlusion methods (semi-hepatic inflow occlusion, Pringle's manoeuvre, and modified Pringle's manoeuvre) were analyzed. RESULTS: Tumor diameter, Child-Pugh score, indocyanine green retention rate, aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, total bilirubin, direct bilirubin, albumin, prealbumin, cholinesterase, hepatic inflow occlusion time, blood transfusion, postoperative complications, and operative blood loss were not significantly different between patients with centrally and non-centrally located primary liver cancer. Patients with centrally located liver cancer had significantly longer operation duration and hospital stay than patients with non-centrally located liver cancer (P < 0.05). The modified Pringle's manoeuvre of hepatic inflow occlusion had the same effectiveness of the Pringle's manoeuvre and could be performed in a simpler way. CONCLUSIONS: Hepatectomy is safe and feasible for patients with centrally located primary liver cancer. Appropriate preoperative evaluation and preparation, sufficient knowledge of liver anatomy, and proper selection of hepatic inflow occlusion method are key factors to guarantee the success of the resection.

Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent gamma-rays.

BACKGROUND: In recent years, interventional tumor therapy, involving implantation of intra-cholangial metal stents through percutaneous trans-hepatic punctures, has provided a new method for treating cholangiocarcinoma. (103)Pd cholangial radioactive stents can concentrate high radioactive dosages into the malignant tumors and kill tumor cells effectively, in order to prevent re-stenosis of the lumen caused by a relapsed tumor. The aim of the present study was to investigate the efficacy of gamma-rays released by the (103)Pd biliary duct radioactive stent in treating cholangiocarcinoma via induction of biliary cholangiocarcinoma cell apoptosis. METHODS: A group of biliary duct cancer cells was collectively treated with a dose of gamma-rays. Cells were then examined by the 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl terazolium-bromide (MTT) technique for determining the inhibition rate of the biliary duct cancer cells, as well as with other methods including electron microscopy, DNA agarose gel electrophoresis, and flow cytometry were applied for the evaluation of their morphological and biochemical characteristics. The growth curve and the growth inhibition rate of the cells were determined, and the changes in the ultrastructure of the cholangiocarcinoma cells and the DNA electrophoresis bands were examined under a UV-lamp. RESULTS: The gamma-ray released by (103)Pd inhibited cholangiocarcinoma cell growth, as demonstrated when the growth rate of the cells was stunned by a gamma-ray with a dosage larger than 197.321 MBq. Typical features of cholangiocarcinoma cell apoptosis were observed in the 197.321 MBq dosage group, while cell necrosis was observed when irradiated by a dosage above 245.865 MBq. DNA agarose gel electrophoresis results were different between the 197.321 MBq irradiation dosage group, the 245.865 MBq irradiation dosage group, and the control group. CONCLUSIONS: (103)Pd radioactive stents which provide a radioactive dosage of 197.321 MBq are effective in the treatment of cholangiocarcinoma; (103)Pd radioactive stents should be useful for the clinical treatment of cholangiocarcinoma.

[Effects of Shenfu injection on prostacyclin, thromboxane A2 and activities of ATPases in rats exposed to hepatic ischemia-reperfusion injury].

OBJECTIVE: To explore the effects of Shenfu Injection on prostacyclin, thromboxane A2 and the activities of ATPases in rats exposed to hepatic ischemia-reperfusion injury. METHODS: Twenty-four male Wistar rats weighing 200-250 g were randomly divided into two groups: Shenfu Injection (SF)-treated group (rats were treated with Shenfu Injection of 10 ml/kg through intraperitoneal injection) and untreated group (rats were administered with normal saline at the same dose and served as a control group). Hepatic ischemia was caused by Pringle's maneuver and lasted for fifteen minutes, and then one-hour or three-hour reperfusion was performed. Venous blood samples for the measurement of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1 alpha)(6-keto-PGF(1 alpha)) were collected three hours after reperfusion. Liver tissue samples were collected one hour or three hours after reperfusion for the measurement of Na(+)-K(+)-ATPase and Ca(+)-Mg(+)-ATPase and for morphological studies. RESULTS: Plasma TXB(2) was lower in the SF-treated group than that in the untreated group after three-hour reperfusion (P>0.05), while 6-keto-PGF(1 alpha) was higher in the SF-treated group than that in the untreated group (P>0.05). The ratio of TXB(2) and 6-keto-PGF(1 alpha) was significantly lower in the SF-treated group than that in the untreated group (P<0.05). The activities of Na(+)-K(+)-ATPase and Ca(+)-Mg(+)-ATPase in the SF-treated group were improved obviously. A three-hour reperfusion after fifteen-minute ischemia caused important hepatic histological alterations. Marked structural abnormalities were observed in the untreated group, such as massive hepatocyte swelling, necrosis, mitochondria edema and vacuolar changes. In the SF-treated group, hepatic tissue injury was reduced significantly. CONCLUSION: Shenfu Injection protects hepatic tissue from ischemia-reperfusion injury, and such protective effects are achieved by decreasing the ratio of thromboxane A(2) and prostacyclin, and increasing the activities of Na(+)-K(+)-ATPase and Ca(+)-Mg(+)- ATPase.