Dec 2010, Volume 4 Issue 4
    

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  • Research articles
    Translational medicine promising personalized therapy in oncology
    Yi-Xin ZENG, Xiao-Shi ZHANG, Qiang LIU,
    2010, 4(4): 351-355. https://doi.org/10.1007/s11684-010-0320-2
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  • Research articles
    Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives
    Felicitas THOL, Arnold GANSER
    2010, 4(4): 356-362. https://doi.org/10.1007/s11684-010-0220-5
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    Acute myeloid leukemia (AML) is a very heterogeneous neoplasm of the hematopoietic stem cell. Despite important achievements in the treatment of AML, the long term survival of patients with the disease remains poor. Understanding the pathogenesis of AML better is crucial for finding new treatment approaches. During AML development hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene mutations. Over recent years, novel gene mutations have been found in patients with AML. These mutations can be divided into two important categories, class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid differentiation. Screening for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML patients. Information about the mutation status of specific genes is useful for risk-stratification, minimal residual disease (MRD) monitoring and increasingly also for targeted therapy, especially for patients with cytogenetically normal AML (CN-AML). Besides chromosomal rearrangements and gene mutations, epigenetic regulation of genes – meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence – also represents an important mechanism of leukemogenesis. This article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.
  • Research articles
    Molecular mechanisms of leukemia-associated protein degradation
    Ying-Li WU, Guo-Qiang CHEN, Hu-Chen ZHOU,
    2010, 4(4): 363-370. https://doi.org/10.1007/s11684-010-0210-7
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    Chemical biology, using small molecules as probes to study the cellular signaling network, has developed rapidly in recent years. The interaction between chemistry and biology not only provides new insight into the understanding of cellular activities, but also generates new lead compounds for the treatment of diseases. Transcription factors and kinases such as retinoic acid receptor-alpha (RARα), acute myeloid leukemia 1 (AML1), CAAT/enhancer-binding protein α (C/EBPα), c-myc, and c-abl play important roles in the differentiation of hematopoietic stem/progenitor cells. Abnormalities in these proteins may cause the dysregulation of hematopoiesis and even the occurrence of leukemia. Ubiquitin-mediated protein degradation represents a critical mechanism in regulating the cellular levels and functions of these proteins. Thus, targeting protein degradation has been emerging as an important strategy to conquer malignant diseases. In this review, we will summarize the recent advances in the understanding of the roles of protein degradation in leukemia, with an emphasis on the mechanisms revealed by small molecules.
  • Research articles
    Hilar cholangiocarcinoma: Pathology and tumor biology
    Dong KUANG, Guo-Ping WANG,
    2010, 4(4): 371-377. https://doi.org/10.1007/s11684-010-0130-6
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    Hilar cholangiocarcinoma, first described by Klatskin in 1965, is a relatively rare tumor arising from the bile ducts. The histomorphological features of hilar cholangiocarcinoma are identical with other extra- and intra-hepatic bile duct carcinomas. The most common disease associated with cholangiocarcinoma is primary sclerosing cholangitis. The development of cholangiocarcinoma is a multistep process associated with several mutations in oncogenes and tumor-suppressor genes. Based on macroscopic appearance, three distinct subtypes have been described: sclerosing, nodular, and papillary. Microscopically, more than 95% of tumors are adenocarcinomas. Hilar cholangiocarcinoma is a slowly growing tumor and tends to spread longitudinally along the bile ducts with neural, perineural, and subepithelial extension. Lymph node invasion can be found in 30%–50% patients at the time of diagnosis, but blood-born metastases are rare and usually occur at late stages.
  • Research articles
    The value of epigenetic markers in esophageal cancer
    Xiao-Mei ZHANG, Ming-Zhou GUO,
    2010, 4(4): 378-384. https://doi.org/10.1007/s11684-010-0230-3
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    Developing esophageal cancer is a multi-step process that begins with the accumulation of genetic and epigenetic alterations, and leads to the activation of oncogenes and the inactivation or loss of tumor suppressor genes (TSG). In addition to genetic alteration, epigenetic modifications, and in particular DNA methylation, are recognized as a common molecular alteration in human tumors. In esophageal cancer, aberrant methylation of promoter regions occurs not only in advanced cancer, but also in premalignant lesions. DNA methylation is related to survival time and sensitivity of chemoradiotherapy. This review is mainly focused on epigenetic changes in esophageal cancer and the value of early detection for patient prognosis, treatment choices, and potential targeting therapy.
  • Research articles
    Toll-like receptors in innate immunity and infectious diseases
    Min-Hao WU, Ping ZHANG, Xi HUANG,
    2010, 4(4): 385-393. https://doi.org/10.1007/s11684-010-0600-x
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    The protective ability of host defense system is largely dependent on germ-line encoded pattern-recognition receptors (PRRs). These PRRs respond to a variety of exogenous pathogens or endogenous danger signals, by recognizing some highly conserved structures such as pathogen-associated molecular patterns (PAMPs) and danger/damage associated molecular patterns (DAMPs). The most studied PRRs are Toll-like receptors (TLRs). Activation of TLRs triggers production of inflammatory cytokines and type I interferons (IFNs) via myeloid differentiation primary response gene 88 (MyD88)-dependent or-independent signaling respectively, thereby modulating innate and adaptive immunity, as well as inflammatory responses. This review introduces the classification, structure, and specific ligands of TLRs, and focuses on their signal pathways and biological activities, as well as clinical relevance. These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including tuberculosis (TB), microbial keratitis, and hepatitis B and C.
  • Research articles
    Diagnosis and management against the complications of human cystic echinococcosis
    Hao WEN, Tuerganaili AJI, Ying-Mei SHAO,
    2010, 4(4): 394-398. https://doi.org/10.1007/s11684-010-0180-9
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    Cystic echinococcosis (CE) (hydatidosis, hydatid disease) is a zoonosis caused by the larval stage of Echinococcus granulosus, typically affecting the liver. Hepatic cystic echinococcosis (HCE) is often asymptomatic, and symptoms occur largely when complications develop. Up to one-third of HCE can be shown their complications such as rupture of the cyst, secondary infection, and anaphylactic reaction. Clinically, patients present with pain, obstructive jaundice, cholangitis, anaphylactic reaction, and shock. Early diagnosis and treatment of complications of CE must be very important, since mortality is high when obstruction of the biliary ducts occurs, leading to ascending cholangitis and septicemia, anaphylactic shock, or even life-threatening conditions.
  • Research articles
    Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas
    Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,
    2010, 4(4): 399-411. https://doi.org/10.1007/s11684-010-0170-y
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    β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway. In our study, we found that, in the development of hepatocellular carcinoma (HCC), β-catenin was correlated with hepatitis B virus (HBV) X gene encoded protein, which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis. The expression levels of wild-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs versus 19.2% of non-HBV-related tumors. Our data suggest that the expression of HBx contributed to the development of HCC, in part, by repressing the wild-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.
  • Research articles
    p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines
    Junfang JI, Kun WU, Min WU, Qimin ZHAN,
    2010, 4(4): 412-418. https://doi.org/10.1007/s11684-010-0260-x
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    p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type p53 or the functional activation of mutant-type p53 might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150 with wild-type p53, p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the p53 genotype.
  • Research articles
    Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma
    Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,
    2010, 4(4): 419-429. https://doi.org/10.1007/s11684-010-0160-0
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    The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (P<0.001), whereas a haplotypic carriage with a single mutation and another three wild-types were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.
  • Research articles
    Influence of the adjuvant therapy on the survival of patients with stage II pancreatic carcinoma
    Xi-Yan WANG, Hai-Jun LI, Dong YAN, Hao WEN, Shu-Yong PENG,
    2010, 4(4): 430-435. https://doi.org/10.1007/s11684-010-0700-7
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    This study aimed to investigate the effect of adjuvant therapy on the treatment of stage II pancreatic carcinomas. The clinical data of 139 cases of stage II pancreatic carcinoma were analyzed retrospectively. The overall 1-, 3-, and 5-year cumulative survival rates of 139 patients were 40%, 6%, and 3%, respectively, and the median survival time (MST) was 279 days. The MST was 399 days for those with adjuvant therapy, 210 days for those without adjuvant therapy, 390 days for the radical resection group, 270 days for the bypass operation and laparotomy group, and 132 days for the nonsurgical group. The adjuvant therapy could not prolong the survival time and decrease the liver metastasis rate of the patients with stage II carcinoma significantly in radical resection group (P>0.05). In the bypass operation and laparotomy group and nonsurgical group, the adjuvant therapy could improve the survival of the patients significantly (P<0.05); however, the survival rate was not significantly different among systemic venous chemotherapy, radiation therapy, interventional therapy, and combination therapy (P>0.05); or between gemcitabine (GEM) regimen and 5-fluorouracil regimen (P>0.05); or between GEM monotherapy and GEM combined with platinum/capecitabine (P>0.05). The proper adjuvant therapy can be suggested according to the general condition of the patients after radical resection for stage II pancreatic carcinoma. Chemotherapy combined with radiation should be applied actively for the patients whose cancerous tissues were not radically resected. The clinical efficacy of GEM combined with platinum/capecitabine is relatively better than GEM.
  • Research articles
    The first year follow-up after colorectal adenoma polypectomy is important: A multiple-center study in symptomatic hospital-based individuals in China
    Qin-Yan GAO, Hui-Min CHEN, Jing-Yuan FANG, Jian-Qiu SHENG, Ping ZHENG, Cheng-Gong YU, Bo JIANG,
    2010, 4(4): 436-442. https://doi.org/10.1007/s11684-010-0200-9
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    The recurrence of colorectal adenoma (CRA) is high. Although there are guidelines for colonoscopy surveillance after polypectomy in other countries, little is known about its recurrence rate and recurrence peak, especially in China. The aim of the present research is to investigate how long after polypectomy follow-up should take and to analyze risk factors of recurrence. 1208 patients who received polypectomies from five clinical research centers in four regions of China (Shanghai, Guangzhou, Nanjing and Beijing) were included. They were divided into 4 groups: group A (follow-up≤1 year after polypectomy), group B (follow-up 2–3 years after polypectomy), group C (follow-up 4–5 years after polypectomy), and group D (follow-up>5 years after polypectomy). The sex, age, adenoma location, size, number, and pathological characteristics were compared. On the whole, the recurrence rate was 59.46% in group A, 61.09% in group B, 78.07% in group C, and 87.12% in group D, which indicated an increased tendency with a prolonged follow-up duration. There was a significant difference between group A and C or D, and between group B and C or D (P<0.01), but there was no statistical difference between group A and B. Additionally, the recurrent patients in the first year had a recurrence rate of 97.33% in the first three years (59.46/61.09), which means that the peak of recurrence was almost entirely concentrated in the first year. The recurrence rate was higher in males and the elder. The risk factors included multiple numbers, villous feature, high-grade dysplasia of medium or smaller size and location in the distal colon. In conclusion, the peak of recurrence was almost totally concentrated in the first year; meanwhile, the first year follow-up is of critical importance in China. It may not be necessary to do the follow-up examination during the second and third years, but after three years, another colonoscopy should be undertaken.
  • Research articles
    The liver tissue bank and clinical database in China
    Yuan YANG, Yi-Min LIU, Ming-Yue WEI, Wei-Ping ZHOU, Hong-Yang WANG, Meng-Chao WU, Yi-Fei WU, Jun-Hui GAO, Lei LIU,
    2010, 4(4): 443-447. https://doi.org/10.1007/s11684-010-0190-7
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    To develop a standardized and well-rounded material available for hepatology research, the National Liver Tissue Bank (NLTB) Project began in 2008 in China to make well-characterized and optimally preserved liver tumor tissue and clinical database. From Dec 2008 to Jun 2010, over 3000 individuals have been enrolled as liver tumor donors to the NLTB, including 2317 cases of newly diagnosed hepatocellular carcinoma (HCC) and about 1000 cases of diagnosed benign or malignant liver tumors. The clinical database and sample store can be managed easily and correctly with the data management platform used. We believe that the high-quality samples with detailed information database will become the cornerstone of hepatology research especially in studies exploring the diagnosis and new treatments for HCC and other liver diseases.
  • Research articles
    Alcohol and tea consumption in relation to the risk of nasopharyngeal carcinoma in Guangdong, China
    Hong-Lian RUAN, Feng-Hua XU, Wen-Sheng LIU, Qi-Sheng FENG, Li-Zhen CHEN, Yi-Xin ZENG, Wei-Hua JIA,
    2010, 4(4): 448-456. https://doi.org/10.1007/s11684-010-0280-6
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    To investigate whether alcohol and tea consumption has an etiological association with nasopharyngeal carcinoma (NPC) in a high-incident population, a large scale case-control study was conducted. The study included 2846 individuals in Guangdong Province, China, with 1387 newly diagnosed cases of NPC and 1459 frequency-matched controls. Exposure histories of alcohol and tea consumption were obtained via personal interviews. Information regarding socio-demographic characteristics (age, sex, education, dialect and household type), family history of NPC, Epstein-Barr virus (EBV) infection, dietary habits and other potential confounding factors was also studied. An analysis was performed using unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The risk of NPC was found to be associated with habitual alcohol consumption and tea consumption. Tea consumption has been associated with a decreased occurrence of NPC (OR= 0.62), while consumption of alcohol was associated with a complex effect. Specifically, moderate consumption of alcohol was associated with decreased risk of NPC, while overuse, especially strong distillate spirits, appeared to be a risk factor.
  • Research articles
    Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis
    Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,
    2010, 4(4): 457-462. https://doi.org/10.1007/s11684-010-0240-1
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    This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1st, 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval= 1.10–1.46), and the Z-score for overall effect was 13.83 (P<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval= 0.411–5.264) and Z-score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.
  • Research articles
    Comparing the effects of Bassini versus tension-free hernioplasty: 3 years’ follow-up
    Yulong SHI, Zhongxue SU, Leping LI, Hongjun LIU, Changqing JING,
    2010, 4(4): 463-468. https://doi.org/10.1007/s11684-010-0050-5
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    In order to compare the effects of Bassini and tension-free mesh hernioplasty, a total of 552 patients with inguinal hernia who were subjected to surgical treatment in our hospital were randomly divided into the following two groups: the Bassini group (n=269) and the tension-free mesh group (n=283). The recurrence rates, pain, discomfort, and other complications were recorded, and the causes of the complications were explored. The recurrence rate in the Bassini group was 8.9% (24/269), significantly higher than that in the tension-free repair group (2.8%, 8/283). In addition, the recurrence rates in the Bassini and tension-free groups before 2004 were 12.6% and 5.6%, respectively, which were markedly higher than the rates after 2004 (5.3% and 0.7%, respectively). The rate of post-operative discomfort and pain within the first three months was higher in the Bassini group compared to the tension-free group (25.7% vs 18.5%, respectively). However, there was no difference after three months in the rate of post-operative discomfort and pain, incidence of infection, or scrotal edema between the two groups. The average hospital stay in the Bassini group was longer than that in the tension-free repair group (7.6€±€1.2 vs 4.5€±€2.2 days, respectively), but the cost was lower (4518.0€±€510 vs 6221.3€±€578 yuan, respectively). Thus, tension-free mesh hernioplasty is indicated for most inguinal hernia patients due to the low recurrence rate, rapid recovery time, and treatment success, but the traditional Bassini procedure has lower cost and other beneficial effects and is still suitable for some patients.
  • Research articles
    Graft versus host disease after liver transplantation: A case report
    Peng-Ji GAO, Xi-Sheng LENG, Dong WANG, Guang-Ming LI, Lei HUANG, Jie GAO, JI-Ye ZHU,
    2010, 4(4): 469-472. https://doi.org/10.1007/s11684-010-0120-8
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    In documenting clinical experience in the diagnosis and treatment of graft versus host disease (GVHD), we retrospectively analyzed data of one case that has developed GVHD after liver transplantation. This patient exhibited fever, skin rash, and diarrhea on day 9 after liver transplantation. His liver function was normal. Skin biopsy showed scattered keratinocytes accompanied by satellite-like lymphocyte infiltration and basal cell liquefaction degeneration. After carefully analyzing the complications, we took the strategy of decreasing the dose of tacrolimus. Thereafter, the patient’s temperature decreased to normal, his skin rashes subsided, and his diarrhea was relieved. This case suggests that reducing the dosage of immunosuppressive agents can be an effective strategy for GVHD after liver transplantation.
  • Research articles
    Effectively cultivate the next generation of competent Chinese physicians: a perspective from a physician trained in both Chinese and US medical institutions
    Zongyu John CHEN,
    2010, 4(4): 473-476. https://doi.org/10.1007/s11684-010-0290-4
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  • Research articles
    Polycystic ovary syndrome
    Zi-Jiang CHEN, Yuhua SHI,
    2010, 4(4): 477-477. https://doi.org/10.1007/s11684-010-0330-0
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