Frontiers of medicine in China最新文献

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 1(st), 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.

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.

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.

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.

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 wildtypes 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.

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 workup 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.

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.

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.