Astrocytes play important roles in normal brain development and the physiological processes. In particular, 30% of the brain volume consists of astrocytes, and they are the primary target cell in the brain for cellular injuries from chemical exposures. The present study attempts to establish an immortalized murine astrocyte cell line to study the mechanisms of chemical-induced carcinogenesis of astrocytes. Primary astrocytes isolated from mice were transfected with plasmid carrying the SV40 T antigen. Clonal cells obtained after G418 selection were continuously subcultured to establish an immortalized astrocyte cell line. The cell line was positive on GFAP expression and was sensitive to exposure to such chemicals as MNNG. Cells were treated with MNNG for 5 days, with doses ranging from 0.001ug/ml to 1ug/ml. Dose-dependent cellular transformations of astrocytes were observed. Treatments at 0.01ug/ml showed the most distinct characteristics of neoplastic transformation. Subsequent treatment with TPA produced higher levels of neoplastic cell transformation than MNNG treatment alone, as evidenced by increases of saturation density, soft-agar colony formation and cell aggregation. Promotional effects of TPA on cell transformation was further demonstrated by the shortening duration of foci appearance. Addition of hydrocortisone to the culture media resulted in further promotion of cell transformation in astrocytes treated with MNNG and TPA, suggesting that glucocortocoid also plays a role in the promotion of chemical-induced astrocyte transformation. The present study demonstrates that astrocytes are susceptible to chemical-induced carcinogenicity and subject to mechanisms of multistage carcinogenesis. Analysis of MNNG-transformed astrocytes showed that, while the expression of TGF-beta was decreased, expression of GFAP, IL-1betaand fibronectin were increased. The results suggest that these factors are associated with mechanisms of MNNG-induced astrocyte transformation and may be used as potential candidates for biomarkers representing astrocyte-related tumors and cell toxicities. The study showed scientific evidence that growth factors, cytokine and the extracellular matrix are involved in processes of chemical-induced transformation of astrocytes. In addition, the present work provided an excellent opportunity to develop an immortalized astrocyte cell line that can be used for studying mechanisms of astrocyte-related diseases.
Animals ; Antigens, Viral, Tumor ; Astrocytes* ; Biomarkers ; Brain ; Carcinogenesis* ; Cell Aggregation ; Cell Line ; Cell Transformation, Neoplastic ; Culture Media ; Extracellular Matrix ; Fibronectins ; Hydrocortisone ; Intercellular Signaling Peptides and Proteins ; Methylnitronitrosoguanidine ; Mice ; Physiological Processes ; Plasmids ; Transforming Growth Factor beta

The emergence of single-cell technology in recent years has made remarkable progress for understanding of biological process in various diseases including cancers. In particular of cancer, single-cell transcriptome analysis provides a powerful tool for comprehensive characterization of cancer cell subpopulations within a heterogeneous bulk populations. Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer and its molecular mechanism is extremely complex associated with a poor prognosis. To date, the molecular mechanisms of hepatocarcinogenesis remain unclear. Here, I review current status of single-cell transcriptome analysis for HCC, focusing on their application for cancer genomics, circulating tumor cells, cancer stem cells and tumor infiltrating cells in HCC.
Biological Processes ; Carcinoma, Hepatocellular ; Gene Expression Profiling ; Genomics ; Neoplastic Cells, Circulating ; Neoplastic Stem Cells ; Prognosis ; Sequence Analysis, RNA ; Transcriptome

OBJECTIVETo investigate the regional spread of micrometastatic nodules in the mesorectum from low rectal cancer, and provide further pathological evidence to optimize radical resection procedure for rectal cancer.

METHODSA total of 62 patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME) was included in this study. Surgical specimens were sliced transversely and serial embedded blocks were made at 2.5 mm interval, and paraffin sections were stained with hematoxylin and eosin. The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic spread were examined microscopically on the sections for the distribution in different mesorectal regions, frequency, types, involvement of lymphatic system and correlation with the primary tumor.

RESULTSMicroscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) involved by microscopic tumor foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involvement was recorded in 6.5% (4/62) with a spread extent within 3 cm of distal border of the main lesions. Most (20/24) of the patients with microscopic spread in mesorectum were in TNM stage III.

CONCLUSIONResults of the present study support that complete excision of mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin should not be less than 4 cm.

Adenocarcinoma ; pathology ; surgery ; Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mesentery ; pathology ; surgery ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual ; Neoplastic Cells, Circulating ; pathology ; Peritoneal Neoplasms ; pathology ; surgery ; Rectal Neoplasms ; pathology ; surgery ; Rectum ; surgery

Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells (CSCs) have the ability to self-renew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBV-associated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A)], cellular microRNAs, and adenosine triphosphate (ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.
Carcinoma ; Cell Transformation, Neoplastic ; China ; Drug Resistance, Neoplasm ; genetics ; Epithelial-Mesenchymal Transition ; Herpesvirus 4, Human ; genetics ; Humans ; MicroRNAs ; Multidrug Resistance-Associated Proteins ; Nasopharyngeal Neoplasms ; Nasopharynx ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplastic Stem Cells ; Signal Transduction ; Viral Matrix Proteins

OBJECTIVETo explore the role of hepatitis C virus core protein on the infiltration and metastasis of cholangiocarcinoma tissues.

METHODSFrom January 2001 to November 2006, 34 patients with cholangiocarcinoma who had intact follow-up data randomly were chosen. The expression of HCVc protein, epithelium markers and mesenchymal markers in cholangiocarcinoma tissues were examined by SP methods of immunohistochemistry, clinical-pathological data were recorded and analyzed.

RESULTSThe positive expression rate was observed in 47.1% for HCVc protein, 50% for N-cadherin, 44.1% for Vimentin, 55.9% for Fibronectin and the decreased expression rate was E-cadherin for 55.9%, alpha-catenin for 70.6%, beta-catenin for 55.9%. The positive expression of HCVc protein was associated with the decreased expression of E-cadherin, alpha-catenin and the positive expression of N-cadherin, Vimentin, Fibronectin (chi(2) = 4.480, 4.163, 4.250, 7.438, 12.260, P < 0.05). A positive-correlation between the expression of HCVc protein and metastasis of lymph nodes and other organs were found (chi(2) = 5.708, 4.163, P < 0.05).

CONCLUSIONHCVc protein might promote cholangiocarcinoma tissues' infiltration and metastasis by inducing it's epithelial-mesenchymal transition.

Adult ; Aged ; Cell Transformation, Neoplastic ; Cholangiocarcinoma ; metabolism ; pathology ; virology ; Epithelium ; metabolism ; pathology ; virology ; Female ; Hepacivirus ; metabolism ; Hepatitis C ; metabolism ; pathology ; virology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Viral Core Proteins ; metabolism ; physiology

OBJECTIVETo explore the correlations of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) with the clinicopathological characteristics, prognostic events, and survival outcomes in esophageal cancer (EC) patients.

METHODSThe PubMed, Web of Science, Embase database and Cochrane database were searched for studies reporting the outcomes of interest. The studies were selected according to established inclusion/exclusion criteria. Meta-analysis of the studies was performed using Review Manager 5.3 and Stata12.0 software with the odds ratio (OR), risk ratio (RR) , hazard ratio (HR) , and 95% confidence interval (95% CI) as the effect indexes.

RESULTSNineteen studies involving a total of 1766 patients were included in the analysis. Significant correlations of CTCs and DTCs were found with the clinicopathological parameters including the tumor stage (OR=1.95), depth of invasion (OR=1.99), lymph node metastasis (OR=2.44), distal metastasis (OR=5.98), histological differentiation (OR=1.67) and lymphovascular invasion (OR=4.48). CTCs and DTCs were also correlated with the prognostic events including relapse (RR=6.86) and metastasis (RR=3.22) and with the survival outcomes including the overall survival (OS) overall analysis (HR=3.46) and disease-free survival/progression-free survival (DFS/PFS) overall analysis (HR=3.00).

CONCLUSIONCTCs and DTCs are significantly associated with an advanced tumor stage, depth of tumor invasion, lymph node metastasis, distant metastasis before therapy, differentiation, lymphovascular invasion, relapse and metastasis in patients with EC. They are also significantly correlated with a poorer survival for OS and DFS/PFS to serve as clinical and prognostic predictors in patients with EC.

Disease-Free Survival ; Esophageal Neoplasms ; diagnosis ; Humans ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Odds Ratio ; Prognosis ; Proportional Hazards Models ; Survival Analysis

Inflammatory myofibroblastic tumor (IMT) is rare mesenchymal solid tumor that consists of proliferating myofibroblasts with an inflammatory infiltrate background. It has a very low prevalence in infants and occurs mainly in children and young adults. IMT are mainly located in the thoracic cavity, but intra-abdominal lesions are rare. IMT can exhibit locally aggressive neoplastic processes and metastases similar to malignancies, so, have clinical importance. Herein, we describe two infantile intra-abdominal IMT cases presenting with incidentally found palpable abdominal mass. A 4-month-old male infant had IMT at the ileal mesentery and a 5-month-old male infant had IMT at liver. Both cases were successfully treated by complete surgical resection without complication or recurrence. Considering the biological behavior of the intermediate type of neoplasm in IMT, we expect good survivals when achieving appropriate surgical resection without adjuvant therapy in infantile intra-abdominal IMT.
Child ; Humans ; Infant ; Liver ; Male ; Mesentery ; Myofibroblasts* ; Neoplasm Metastasis ; Neoplastic Processes ; Prevalence ; Recurrence ; Thoracic Cavity ; Young Adult

OBJECTIVEThe aim of this cohort study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head.

METHODSpatients with pancreatic head cancer undergoing curative resection (R0) between 1997 and 2002 were included in this study. Univariate and multivariate analyses were performed to examine factors affecting clinical outcome and recurrence of the cancer.

RESULTSSurgical procedures consisted of 58 (43.3%) extended pancreaticoduodenectomies (EPD), 47 (35.1%) pancreaticoduodenectomies (PD) and 29 (21.6%) pylorus-preserving pancreaticoduodenectomies (PPPD). The results showed that 81.3% (109/134) of patients had a recurrence during the study period, mainly retroperitoneal combined with distant metastasis (53.7%). The median postoperative survival time was 24.7 months. The 1-, 3- and 5-year overall survival rates for the study population were 67.1%, 38.5% and 17.6%, respectively. Univariate analysis showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion, and CA19-9 level were all significant predictors for poor survival. Multivariate analysis also showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion were all significant predictors for poor survival.

CONCLUSIONOur results suggest that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion are significant predictors for poor survival in patients with pancreatic head cancer.

Adult ; Aged ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Carcinoma, Pancreatic Ductal ; blood ; pathology ; surgery ; Cohort Studies ; Female ; Humans ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Male ; Microvessels ; pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Pancreatic Neoplasms ; blood ; pathology ; surgery ; Pancreaticoduodenectomy ; methods ; Survival Rate ; Tumor Burden

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.
B-Lymphocytes ; Burkitt Lymphoma ; Cell Transformation, Neoplastic ; Cytidine ; Cytidine Deaminase ; DNA ; Genetic Processes ; Germinal Center ; Hand ; Immunity, Humoral ; Immunoglobulins ; Leukemia, B-Cell ; Lymphoma ; Point Mutation ; Protein Processing, Post-Translational ; Recombination, Genetic ; RNA, Messenger ; T-Lymphocytes ; Transcriptional Activation

Activation-induced cytidine deaminase (AID) is an enzyme that is predominantly expressed in germinal center B cells and plays a pivotal role in immunoglobulin class switch recombination and somatic hypermutation for antibody (Ab) maturation. These two genetic processes endow Abs with protective functions against a multitude of antigens (pathogens) during humoral immune responses. In B cells, AID expression is regulated at the level of either transcriptional activation on AID gene loci or post-transcriptional suppression of AID mRNA. Furthermore, AID stabilization and targeting are determined by post-translational modifications and interactions with other cellular/nuclear factors. On the other hand, aberrant expression of AID causes B cell leukemias and lymphomas, including Burkitt's lymphoma caused by c-myc/IgH translocation. AID is also ectopically expressed in T cells and non-immune cells, and triggers point mutations in relevant DNA loci, resulting in tumorigenesis. Here, I review the recent literatures on the function of AID, regulation of AID expression, stability and targeting in B cells, and AID-related tumor formation.
B-Lymphocytes ; Burkitt Lymphoma ; Cell Transformation, Neoplastic ; Cytidine ; Cytidine Deaminase ; DNA ; Genetic Processes ; Germinal Center ; Hand ; Immunity, Humoral ; Immunoglobulins ; Leukemia, B-Cell ; Lymphoma ; Point Mutation ; Protein Processing, Post-Translational ; Recombination, Genetic ; RNA, Messenger ; T-Lymphocytes ; Transcriptional Activation