Radiosensitivity of β-elemene on rabbit VX2 renal transplant carcinoma model

Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.

Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.

Establishment of VX2 breast carcinoma model in rabbit by injecting tumor mass suspension

Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way. Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.

Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model

AIM:To investigate the possible role of chitinase3-like-1(CHI3L1)in the progression of colitis-associated carcinoma(CAC).METHODS:Thirty-four Balb/c mice were randomly assigned to five groups,including the control,CAC control,CAC+caffeine,colitis control and colitis+caffeine.Three animals were sacrificed every two weeks for blinded macroscopic inspection,histological analysis,and total RNA extraction.An immunofluorescent assay was performed using specimens from the colitis control and colitis+caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage.In vitro,HT29 cells prestimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFHDA fluorescent probe to determine the effect of CHI3L1on intracellular reactive oxygen species production.RESULTS:CHI3L1 mRNA was increased during the progression of colon carcinogenesis.Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon.Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice.CHI3L1protein increased reactive oxygen species in HT29 cells when exposed to H2O2.CONCLUSION:Caffeine reduces tumor incidence by decreasing oxidative DNA damage.CHI3L1 may contribute to CAC by increasing reactive oxygen species production.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

A modified rat model for hepatocellular carcinoma

BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

Chronic hepatitis B virus(HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma(HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B(CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-na?ve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM(Individual Prediction Model), CU-HCC(Chinese University-HCC), GAG-HCC(Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC(NomogramHCC), REACH-B(Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM(Liver Stiffness Measurement)-based model, LSM-HCC, and mR EACH-B(modified REACH-B).

Hepatocellular carcinoma mouse models:Hepatitis B virusassociatedhepatocarcinogenesis and haploinsufficienttumor suppressor genes

The multifactorial and multistage pathogenesis of hepatocellular carcinoma(HCC)has fascinated a wide spectrum of scientists for decades.While a number of major risk factors have been identified,their mechanistic roles in hepatocarcinogenesis still need to be elucidated.Many tumor suppressor genes(TSGs)have been identified as being involved in HCC.These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors:the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele.Hepatitis B virus(HBV)is one of the most important risk factors associated with HCC.Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor,one advantage of mouse models for HBV/HCC research is the numerous and powerfulgenetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs.Here,we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner.Discoveries obtained using mouse models will have a great impact on HCC translational medicine.

Zebrafish as a disease model for studying human hepatocellular carcinoma

Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma(HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel smallmolecule inhibitors. This review will focus on illustrativeexamples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts,drug discovery, and drug-induced toxic liver injury.

Construction of a risk score prognosis model based on hepatocellular carcinoma microenvironment

BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.

Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.

Establishment of NOD/SCID mouse models of human hepatocellular carcinoma via subcutaneous transplantation of histologically intact tumor tissue

Hepatocellular carcinoma （HCC） is one of the most deadly human cancers, but it is very difficult to establish an animal model by using surgical specimens. In the present experiment, histologically intact fresh surgical specimens of HCC were subcutaneously transplanted in non-obese diabetic/severe combined immunodeficienccy （NOD/SCID） mice. The biological characteristics of the original and the corresponding transplanted tumors and cell lines were investigated. The results showed that 5 new animal models and 2 primary cell lines were successfully established f^om surgical specimens. Hematoxylin-eosin staining showed that xenografts retained major histological features of the original surgical specimens. The two new cell lines had been cultivated for 3 years and successively passaged for more than 100 passages in vitro. The morphological characteristics and biologic features of the two cell lines were genetically similar to the original tumor. The subcutaneous transplant animal models with histologically intact tumor tissue and primary cell lines could be useful for in vivo and in vitro testing of anti-cancer drugs and be ideal models to study various biologic features of HCC.

Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice

AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

Anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of humanhepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inoculated to formsubcutaneous tumors in nude mice by subcutaneous injection. Then the subcutaneous tumors were implanted into the liver ofnude mice, and the orthotopic transplantation tumor models of human hepatocellular carcinoma were established. Seventy-fivemodels were randomized into 5 groups ( n = 15). Bufalin was injected intraperitoneally into the 3 groups at dose of 1.5,1 and0.5 mg/kg for day 15 - 24, respectively. NS group were injected equal volume saline as above and adriamycin were injectedintraperitoneally into ADM group at dose of 8.0 mg/kg for day 15. Ten mice in each group were killed at day 25 and detectedon morphological and ultrastructural changes in myocardium, brain, liver, kidney and tumor tissues by pathology and electronmicroscope. The survival time in each group were observed. Results: The tumor volumes in each group of bufalin were re-duced significantly compared with NS group ( P＜0.01), the survival time were prolonged in group Bu 1 and Bu 2 comparedwith NS group (P＜0.05), and tumor tissues were mainly necrosis in severe or moderate degree in Bu 1, Bu 2 groups, andmild degree or moderate degree in Bu 3 group. No morphological changes were detected in myocardium, brain, liver and kid-ney tissues, respectively. Apoptotic characteristics could be seen in tumor tissues of group Bu 1 and group Bu 2. Conclusion:Bufalin has significant anti-tumor effects on the orthotopic transplantation tumor model of human hepatocellular carcinoma innude mice without marked toxicity. To guide cell apoptosis may be one of its anti-tumor mechanism of bufalin.

Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma

BACKGROUND The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma(GBC)after curative resection remain unclear.AIM To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy.METHODS Patients with curatively resected advanced gallbladder adenocarcinoma(T3 and T4)were selected from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.A survival prediction model based on Bayesian network(BN)was constructed using the tree-augmented na?ve Bayes algorithm,and composite importance measures were applied to rank the influence of factors on survival.The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3.The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy.RESULTS A total of 818 patients met the inclusion criteria.The median survival time was 9.0 mo.The accuracy of BN model was 69.67%,and the area under the curve value for the testing dataset was 77.72%.Adjuvant radiation,adjuvant chemotherapy(CTx),T stage,scope of regional lymph node surgery,and radiation sequence were ranked as the top five prognostic factors.A survival prediction table was established based on T stage,N stage,adjuvant radiotherapy(XRT),and CTx.The distribution of the survival time(>9.0 mo)was affected by different treatments with the order of adjuvant chemoradiotherapy(cXRT)>adjuvant radiation>adjuvant chemotherapy>surgery alone.For patients with node-positive disease,the larger benefit predicted by the model is adjuvant chemoradiotherapy.The survival analysis showed that there was a significant difference among the different adjuvant therapy groups(log rank,surgery alone vs CTx,P<0.001;surgery alone vs XRT,P=0.014;surgery alone vs cXRT,P<0.001).CONCLUSION The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients.Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

Research Progress in Animal Models of Hepatocellular Carcinoma

[Objective] To establish good animal models of hepatocellular carcinoma （HCC） and serve treatment of HCC in humans. [Method] Several common animal models of HCC were introduced briefly. [Result] The commonly used animal models include C57BL/6J mouse model of or- thotopic HCC induced with Hepa1-6 cells, nude mouse model of HCC constructed with Hep_G2 cell lines, rat HCC model constructed through direct transplantation or direct injection, HU-PBL-SCID mice modal, and other transplanted HCC models or genetic HCC models. [ Conclusion] Animal model is an important means and platform for experimental studies. To establish animal models of HCC is of important significance for studies on pathogenesis, diagnosis and treatment of HCC.

Risk prediction models for hepatocellular carcinoma in different populations

Hepatocellular carcinoma （HCC） is a malignant disease with limited therapeutic options due to its aggressive progression. It places heaW burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well.

Validated model for prediction of recurrent hepatocellular carcinoma after liver transplantation in Asian population

BACKGROUND Liver transplantation(LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma(HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive agents.AIM To develop a scoring system to predict HCC recurrence after LT in an Asian population.METHODS Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic curve.RESULTS In total, 330 patients were eligible for analysis(183 in training and 147 invalidation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio(HR) 2.92], sum of maximum tumor size and number(P = 0.013, HR 1.15), and salvage LT(P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power(c-stat 0.748 and 0.85, respectively,in the training and validation sets). With the derived scores, patients were classified into low-(0–9), moderate-(> 9–14), and high-risk groups(> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54%(cstat 0.67) and 4%, 22%, 62%(c-stat 0.811), accordingly. The risk stratification model was validated with chi-squared goodness-of-fit test(P = 0.425).CONCLUSION A validated predictive model featuring alpha-fetoprotein, salvage LT, and the sum of largest tumor diameter and total number of tumor nodule provides simple and reliable guidance for individualizing postoperative surveillance strategy.

Analysis of Prognostic Factors of Esophageal and Gastric Cardiac Carcinoma Patients after Radical Surgery Using Cox Proportional Hazard Model-A Random Sampling Study from the Fourth Hospital of Hebei Medical University during the Period of 1996-2004

OBJECTIVE To retrospectively analyze clinical data of patientsfrom our hospital who underwent radical surgery for esophagealcarcinoma and for adenocarcinoma of the gastric cardia,as well asto investigate prognostic factors affecting the long-term survival ofthe patients.METHODS Data from the patients eligible for our study,admitted to the 4th Hospital of Hebei Medical University fromJanuary 1996 to December 2004,were randomized,and 12distinctive clinicopathologic factors influencing the survival rateof those who underwent radical surgery for esophageal carcinomaor carcinoma of the gastric cardia were collected.Univariate andmultivariate analysis of these individual variables were performedusing the Cox proportional hazard model.RESULTS It was shown by univariate analysis that age,tumorsize,pathologic type,lymph node status,TNM staging,depthof infiltration and encroachment into local organs,etc.,were thefactors that markedly influenced the prognosis of patients(P<0.01).Multivariate analysis showed that pathologic type,numberof the lymph node metastases,involvement of local organs,andTNM staging were independent prognostic factors(P<0.05).CONCLUSION The independent factors influencing theprognosis of patients with esophageal cancer and carcinoma ofthe gastric cardia include pathologic type,number of lymph nodemetastases,involvement of local organs and TNM staging.Themain prognostic factors affecting the patient's survival are patientage,tumor size and depth of infiltration.In addition,patients withinvolvement of the local organs have a worse prognosis,and theyshould be closely followed up.

Establishment of various biliary tract carcinoma cell lines and xenograft models for appropriate preclinical studies

We recently reported several driver genes of biliary tract carcinoma(BTC) that are known to play important roles in oncogenesis and disease progression. Although the need for developing novel therapeutic strategies is increasing, there are very few BTC cell lines and xenograft models currently available for conducting preclinical studies. Using a total of 88 surgical BTC specimens and 536 immunodeficient mice, 28 xenograft models and 13 new BTC cell lines, including subtypes, were established. Some of our cell lines were found to be resistant to gemcitabine, which is currently the first choice of treatment, thereby allowing highly practical preclinical studies to be conducted. Using the aforementioned cell lines and xenograft models and a clinical pathological database of patients undergoing BTC resection, we can establish a preclinical study system and appropriate parameters for drug efficacy studies to explore new biomarkers for practical applications in the future studies.