Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features.

BACKGROUND: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. CASE PRESENTATION: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. CONCLUSION: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

Infection of epithelioma papulosum cyprini (EPC) cells with spring viremia of carp virus (SVCV) induces autophagy and apoptosis through endoplasmic reticulum stress.

Spring viremia of carp virus (SVCV) is a lethal freshwater pathogen of cyprinid fish that has caused significant economic losses to aquaculture. To reduce the economic losses caused by SVCV, its pathogenic mechanism needs to be studied more thoroughly. Here, we report for the first time that SVCV infection of Epithelioma papulosum cyprini (EPC) cells can induce cellular autophagy and apoptosis through endoplasmic reticulum stress. The presence of autophagic vesicles in infected EPC cells was shown by transmission electron microscopy. Quantitative fluorescence PCR and Western blot results showed that p62 mRNA expression was decreased, and the expression of Beclin1 and LC3 mRNA was increased. The p62 protein was decreased, and the Beclin1 protein and LC3 were increased in the endoplasmic reticulum stress activation state. To further clarify the mode of death of SVCV-infected EPC cells, we examined caspase3, caspase9, BCL-2, and Bax mRNA, which showed that they were all increased. Apoptosis of SVCV-infected cells increased upon activation of endoplasmic reticulum stress. Our results suggest that endoplasmic reticulum stress can regulate SVCV infection-induced autophagy and apoptosis. The results of this study provide theoretical data for the pathogenesis of SVCV and lay the foundation for future drug development and vaccine construction.

[Analysis of Predictive Value of Laboratory Indexes for Malignant Lymphoma Patients with Bone Marrow Involvement].

OBJECTIVE: To analyze the influence of bone marrow involvement (BMI) in patients with malignant lymphoma (ML) on laboratory indexes, and evaluate the laboratory markers that can be used to predict/diagnose BMI. METHODS: The clinical characteristics and laboratory indexes of 137 ML patients were analyzed retrospectively, from which the indexes of BMI in ML patients was studied. The logistic regression analysis and receiver operating curve (ROC) were used to evaluate independent risk factors and predictors of BMI diagnosis in ML patients. RESULTS: Compared with non-BMI group, the red blood cell distribution width, C-reactive protein, erythrocyte sedimentation rate, D-dimer, lactate dehydrogenase, alkaline phosphatase, ß2-microglobulin, transferrin, CA153, CA125, and soluble interleukin-2 receptor (sIL-2R) levels were increased while platelet (PLT) count was decreased in BMI group, and the difference was statistically significant (P<0.05). The blood indexes related to BMI and the statistically significant indexes in the univariate regression analysis were corrected by multivariate logistic regression analysis. The corrected results showed that T cell-related non-Hodgkin lymphoma (adjusted OR=2.18, 95%CI: 1.48-4.90, P＜0.001), clinical stage Ⅲ-Ⅳ (adjusted OR=3.32, 95%CI: 2.16-5.83, P＜0.001), sIL-2R (adjusted OR=4.26, 95%CI: 2.95-12.85, P＜0.001) were the risk factors for ML patients with BMI, while PLT (adjusted OR=0.89, 95%CI: 0.55-0.96, P= 0.003) was a protective factor. ROC analysis showed that the areas under the ROC curve of PLT and sIL-2R predicting BMI in ML patients was 0.712 (95%CI: 0.646-0.776, P<0.001) and 0.796 (95%CI: 0.739-0.853, P<0.001), respectively. The best cut-off point of PLT and sIL-2R was 160×109/L and 2 568 U/ml, respectively. The diagnostic specificities of the two indexes here were both greater than 80%. CONCLUSION: PLT and sIL2R show good diagnostic value for ML patients with BMI.

A New Triangular Rotation and Advancement Pulp Flap for Lateral Oblique Fingertip Defect.

The fingertip is one of the most common sites of traumatic injuries faced by hand surgeons. In cases of lateral oblique amputation, only limited alternatives are available for reconstruction. This study introduced a new method involving rotation and use of an advancement pulp flap for covering lateral oblique defect and evaluated its outcome. METHOD: A series of 12 patients with 14 lateral oblique fingertip defects were recruited in this study. All fingertips were unreplantable and were injured distal to the proximal one-third of nail bed, with phalanx exposed. All cases received surgical reconstruction using a triangular rotation and advancement pulp flap. Static 2-point discrimination, cold intolerance, pain, hypersensitivity, range of motion, and aesthetic satisfaction were evaluated 6 months to 12 months postoperation. RESULT: Bone defect was noted in 7 cases. The area of defect was 10×7-20×12 mm2, and the angle of defect was 30-60 degrees. Mean follow-up was 14.3 months. No hook nail deformity, cold intolerance, and hypersensitivity were observed. One patient complained about pain postoperation, demanding a second operation. Static 2-point discrimination was between 5 and 8 mm in all cases. Range of motion of distal interphalangeal joint recovered to 20-45 degrees at the last follow-up. No stiffness was observed in the interphalangeal or metacarpophalangeal joints. All patients were satisfied with the appearance of the flap. CONCLUSION: The triangular rotation and advancement pulp flap is simple, safe, and reliable for treating lateral oblique defect of fingertip, providing scope for anatomical reconstruction and fair sensation and aesthetic recovery.

Transcriptome Analysis of Epithelioma Papulosum Cyprini Cells Infected by Reovirus Isolated from Allogynogenetic Silver Crucian Carp.

The present study aimed to identify differentially expressed genes (DEGs) and major signal transduction pathways that were related to the immune response of epithelioma papulosum cyprinid (EPC) cells to reoviruses isolated from allogynogenetic silver crucian carp. The study also lays a theoretical foundation for the pathogenesis and immunity of the reovirus, which is helpful to the breeding of cyprinids fish. Reovirus infected and uninfected EPC cells were analyzed by using a new-generation high-throughput sequencing technology. DEGs were identified, annotated, and classified, and the signal pathways involved in the response to reovirus infection were identified by using bioinformatics tool. The data were assembled into 92,101 contigs with an average length of 835.24 bp and an N50 value of 1432 nt. Differential expression analysis of all the genes identified 3316 DEGs at a false discovery rate (FDR) of <0.01 and a fold-change of ≥3, of which 1691 were upregulated genes, 1625 were downregulated, and about 305 were immune-related genes. Gene Ontology (GO) enrichment analysis resulted in the annotation of 3941 GO terms, including 2719 biological processes (37,810 unigenes), 376 cell components (7943 unigenes), and 846 molecular functions (11,750 unigenes). KEGG metabolic pathway analysis matched the DEGs from pre-and post-infection EPC cells to 193 pathways, of which 35 were immune-related, including the Toll-like receptor, cytokine-cytokine receptor interaction, and the JAK-STAT signaling pathways.

MicroRNA­146a/NAPDH oxidase4 decreases reactive oxygen species generation and inflammation in a diabetic nephropathy model.

The present study investigated the role of microRNA (miR)­146a in a diabetic nephropathy (DN) model, and its molecular mechanism. DN mice were given intraperitoneal injections of streptozotocin (55 mg/kg/day) for 5 consecutive days as an in vivo DN model. The HK­2 human kidney cell line were exposed to 45% D­glucose as an in vitro DN model. Firstly, it was demonstrated that miR­146a expression was inhibited and NAPDH oxidase 4 (Nox4) was increased in DN mice. In HK­2 cells, overexpression of miR­146a inhibited Nox4 protein expression and decreased reactive oxygen species (ROS) generation, oxidative stress and inflammation, and suppressed vascular cell adhesion molecule­1 (VCAM­1) and intracellular adhesion molecule­1 (ICAM­1) protein expression. Nacetylcysteine, a Nox4 inhibitor, was demonstrated to inhibit ROS generation, suppress VCAM­1 and ICAM­1 protein expression, and decrease oxidative stress and inflammation in HK­2 cells following overexpression of miR­146a. In conclusion, these results indicated that miR­146a/Nox4 decreases ROS generation and inflammation and prevents DN. Therefore, miR­146a may represent a novel anti­inflammatory and ­oxidative modulator of DN.

Effects of Artesunate prevent nephritis via the Toll­like receptor 4/nuclear factor­κB signaling pathway in rats.

The active ingredient in Artemisia carvifolia, artemisinin, may alleviate inflammation and toxicity. Artemisinin and its derivatives are first­line anti­malarial drugs currently, which have rapid effects on fever caused by malaria parasites with fewer side effects. The present study investigated the effects of Artesunate in a mouse nephritis model. Mice were injected intraperitoneally with 500 µl pristine to induce nephritis, and were treated with 28.8 mg/kg Artesunate. Subsequently, proteinuria, renal function, and tumor necrosis factor (TNF)­α and interleukin (IL)­6 levels were assessed to evaluate the effects of Artesunate on nephritis. Western blot analysis was used to measure the protein expression levels of α­smooth muscle actin (SMA), TLR4, myeloid differentiation primary response gene 88 (MyD88), NF­κB p65 and transforming growth factor (TGF)­ß1 to investigate the underlying mechanisms of Artesunate on nephritis. The results demonstrated that Artesunate reduced proteinuria and preserved renal function in nephritis mice. Artesunate attenuated TNF­α and IL­6 levels, suppressed α­SMA, TLR4, MyD88, NF­κB p65 and TGF­ß1 protein expression, and decreased caspase­3 activity in nephritis mice. These results indicated that the effects of Artesunate may prevent nephritis and inhibit inflammation via the TLR4/NF­κB signaling pathway in mice. Therefore, Artesunate may be a potential therapeutic agent to prevent nephritis.

Expression of PH Domain Leucine-rich Repeat Protein Phosphatase, Forkhead Homeobox Type O 3a and RAD51, and their Relationships with Clinicopathologic Features and Prognosis in Ovarian Serous Adenocarcinoma.

BACKGROUND: Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. METHODS: The PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. RESULTS: In high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P< 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P< 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. CONCLUSIONS: Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting common molecular pathways. Decreased PHLPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.

New and highly efficient column chromatographic extraction and simple purification of camptothecin from Camptotheca acuminata and Nothapodytes pittosporoides.

INTRODUCTION: Camptothecin, a widely used natural anti-cancer drug, is difficult to extract and purify effectively from plants. OBJECTIVE: To develop new and highly efficient extraction and purification methods for analysis and production of camptothecin from leaves and fruits of Camptotheca acuminata and Nothapodytes pittosporoides roots. METHODS: Dried materials were loaded in empty columns with fivefold 60% ethanol for leaves or 70% ethanol for fruits of C. acumnata, and sixfold 70% ethanol for N. pittosporoides roots. The columns were eluted with the same solvents at room temperature. Eluent was collected as extraction solution. Extraction solution from leaves and fruits of C. acuminata was vacuum-evaporated to remove ethanol, precipitated at pH 8.0 to remove alkaline insolubles and fractionated with chloroform at pH 3.0, which yields a crude product with 70% purity. Extraction solution from N. pittosporoides roots was concentrated to 1/10 volume and precipitated at pH 3.0, which yields a crude product with 60% purity. All crude products were purified by crystallisation. All steps were monitored by HPLC. RESULTS: Camptothecin was extracted from the three plant materials at a 98% rate with 15- or 18-fold solvent for content analysis, or at a 97% rate with five- or sixfold solvent for production. All crude products were purified to 98%. The overall recovery rates of camptothecin from plant materials to purified products reached 92% or higher. CONCLUSION: The new procedures are simple and highly efficient, and have multiple advantages for quantitative analysis and large production of camptothecin from plants.

The paradox of IL-10-mediated modulation in cervical cancer.

Interleukin-10 (IL-10) has opposing effects as an anti-inflammatory (potentially cancer-promoting) and antiangiogenic (potentially cancer-inhibiting) agent. The role of IL-10 in cervical cancer is also dual. Here, we review the IL-10-mediated tumor-promoting effect and tumor-inhibiting effects in cervical cancer, among which, human papilloma virus (HPV), human leukocyte antigen-G (HLA-G) and IL-10 polymorphisms are associated with the development of cervical cancer. IL-10 is also used for the therapy of cervical cancer through enhancing proliferation, expression of immunologically important surface molecules and increasing Th1 cytokine production and cytotoxic potential in HPV-specific CD8 (+) cytotoxic T lymphocytes.

Involvement of MAPK and PI3K signaling pathway in sterigmatocystin-induced G2 phase arrest in human gastric epithelium cells.

SCOPE: Sterigmatocystin (ST), a mycotoxin commonly found in foodstuff and feedstuff, has been shown to be a carcinogenic mycotoxin in animal models. Many studies showed that the high level of ST contamination in grains might be related to the high incidence of gastric carcinoma in rural areas of China. However, up to now, the potential effects of ST on human gastric epithelium cells remain largely unknown. In this study, we explored the effects of ST on cell-cycle distribution and the regulatory mechanism in immortalized human gastric epithelium cells (GES-1). METHODS AND RESULTS: The effects of ST on the cell cycle distribution of GES-1 cells were determined with flow cytometric (FCM) analysis, Giemsa staining and immunofluorescence staining, while that on the expression of related gene-Cdc25C, Cdc2, CyclinB1 and the complex of CyclinB1-Cdc2 were studied with Western blot, reverse transcription polymerase chain reaction (RT-PCR) and immunoprecipitation assay respectively. We found that ST induced GES-1 cells arrested at G2 phase by regulating the expression of Cdc25C, Cdc2, CyclinB1 and the formation of CyclinB1-Cdc2 complex. Further study suggested JNK, ERK and PI3K/AKT/mTOR pathways to be involved in the process of G2 arrest induced by ST. The specific inhibitors of JNK and ERK reversed the role of ST, whereas that of PI3K/AKT/mTOR reinforced the effect of ST on cell-cycle distribution. CONCLUSION: This study demonstrates that JNK, ERK and PI3K/AKT/mTOR pathways participated in the G2 arrest induced by ST through the deregulation of CyclinB1, Cdc2 and Cdc25C. It may play some roles in the gastric carcinogenesis in ST exposure populations.

[Correlation between PPARgamma and VEGF-C expression in extrahepatic cholangioadenocarcinoma (EHCAC) and their prognostic significance].

OBJECTIVE: To evaluate the expression of vascular endothelial growth factor C (VEGF-C) and peroxisome proliferators-activated receptors (PPARgamma) in extrahepatic cholangioadenocarcinoma (EHCAC) and to elucidate its correlation with clinicopathological factors and their significance in prognosis. METHODS: The expressions of PPARgamma and VEGF-C were detected by immunohistochemistry in 69 cases of EHCAC, 12 cases of non-tumor bile duct epithelium, and their relationship to clinicopathological parameters and follow-up were analyzed. RESULTS: The positive rate of PPARgamma expression in 69 cases of EHCAC was 59.4%, significantly higher than that in 12 cases of non-tumor bile duct epithelium (0%), (P < 0.01). The positive rate of VEGF-C in 69 cases of EHCAC was 84.1%, also significantly higher than 16.7% in 12 cases of benign bile duct epithelium (P < 0.05). PPARgamma expression was associated with clinical TNM stage and lymph node metastasis. VEGF-C expression was associated with lymph node metastasis. Cox analysis results showed that portal vein and/or hepatic artery invasion, lymph node metastasis and VEGF-C expression were independent prognostic factors of EHCAC (P < 0.05). CONCLUSION: PPARgamma expression may play an important role during tumorigenesis of extrahepatic cholangioadenocarcinoma. The expressions of PPARgamma and VEGF-C are significantly correlated with the clinicopathological characteristics and biological behavior of EHCAC. Expression of VEGF-C is an independent prognosis factors in EHCAC. The detection of PPARgamma and VEGF-C is valuable for evaluation of prognosis of EHCAC.

[Relationship of ezrin protein expression to the carcinogenesis and prognosis of infitrating breast ductal carcinoma].

OBJECTIVE: To investigate the relationship of ezrin protein expression to the carcinogenesis and prognosis of infiltrating breast ductal carcinoma. METHODS: S-P immunohistochemical staining was used to detect the ezrin protein expression in 88 patients with infiltrating ductal carcinoma, and in 54 patients with intraductal hyperplastic lesions of the breast. The clinicopathological data and follow-up information of these patients were all obtained. The relationship of ezrin protein expression to the clinicopathological parameters and the prognostic significance in the infiltrating breast ductal carcinoma was analyzed using Chi-square test (chi2), Kaplan-Meier and Cox models. RESULTS: The immunohistochemical staining results showed that the strong positive expression rate of ezrin protein in the normal ductal epithelium, simple ductal hyperplasia, atypical hyperplasia and infiltrating ductal carcinoma of the breast was 9.1%, 16.7%, 43.3% and 64.8%, respectively, which was significantly higher in atypical hyperplasia and infiltrating ductal carcinoma than that in the normal ductal epithelium and simple ductal hyperplasia (P < 0.05). The strong ezrin protein expression in the infiltrating ductal carcinoma was positively correlated with axillary lymph node metastasis, histological differentiation grade, TNM stage and CD44v6 expression, but negatively correlated with the expression of E-cadherin (P < 0.05). It was also found that the survival of the patient with strong positive expression of ezrin protein was significantly shorter than that of the control (P < 0.05). CONCLUSION: Ezrin protein may play an important role in the carcinogenesis of infiltrating breast ductal carcinoma. The strong expression of ezrin protein may be used as a biomarker for predicting poor prognosis in the patients with infiltrating breast ductal carcinoma.

[Expression and clinical relevance of ARHI, STAT3 and E2F1 in ovarian serous carcinoma].

OBJECTIVE: To investigate the variation in expression of ARHI, STAT3 and E2F1 and the correlation among them during carcinogenesis of ovarian serous carcinoma. METHODS: Immunohistochemical staining was used to detect the expression of ARHI, STAT3 and E2F1 in samples of 25 normal ovaries, 35 ovarian serous cystadenomas, 18 borderline serous cystadenomas and 56 ovarian serous carcinomas. The variation in expression of the three genes and relationship among them were analyzed. RESULTS: ARHI expression was detected in 22 of 25 (88.0%) normal ovaries and 30 of 35 (85.7%) cystadenomas, but only in 10 of 18 (55.6%) borderline serous cystadenomas and 22 of 56 (39.3%) ovarian serous carcinomas, significantly lower than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). STAT3 expression was found in 14 of 18 (77.8%) borderline serous cystadenomas and 49 of 56 (87.5%) ovarian serous carcinomas, significantly higher than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). To compare with E2F1 expression in the normal ovaries, serous cystadenomas and borderline serous cystadenomas, E2F1 expression in 46 of 56 (82.1%) ovarian serous carcinomas was significantly higher (P < 0.05). It was found that the expression of ARHI was inversely correlated with that of STAT3 and E2F1. CONCLUSION: Our findings indicate that ARHI expression is down-regulated, but STAT3 and E2F1 expressions are up-regulated, with an inverse correlation between ARHI and STAT3 in the carcinogenesis of ovarian serous carcinoma.

[Correlations of polymorphisms in matrix metalloproteinase-3 and -7 promoters to susceptibility to brain astrocytoma].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs) are key enzymes involved in tumor development, invasion and metastasis. The single nucleotide polymorphisms (SNPs) in the promoter regions of MMP genes may influence tumor development and progression via modulating mRNA transcription and protein expression. This study was to explore the correlations of the promoter SNPs in MMP-3 and MMP-7 genes to susceptibility to brain astrocytoma. METHODS: The genotype of MMP-3 -1171 5A/6A and MMP-7 -181A/G polymorphisms in 236 patients with brain astrocytoma and 366 healthy controls was detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). RESULTS: The allelotype and overall genotype distribution of MMP-3 SNP among the astrocytoma patients and healthy controls were similar (P>0.05). Stratified by sex, age, and histological grade, the susceptibility to brain astrocytoma among the subjects with 5A/5A and 5A/6A genotypes and the subjects with 6A/6A genotype were similar(P>0.05). The overall genotype distribution of MMP-7 SNP among the astrocytoma patients and healthy controls were significantly different (P = 0.001). Compared with the A/A genotype, both the G/G and the A/G genotypes significantly increased the susceptibility to astrocytoma [sex-and age-adjusted odds ratio (OR) = 2.77 and 1.69, 95% confidence interval (CI)=1.27-6.02 and 1.01-2.84, respectively]. Stratification analysis showed that the G/G genotype significantly increased the susceptibility to astrocytoma in men (adjusted OR = 3.24, 95% CI = 1.12-9.41) and in the individuals younger than 45 years (adjusted OR = 3.16, 95% CI = 1.09-9.16). When stratified by histological grade, the A/G genotype increased the susceptibility to grade II astrocytoma by about 2 folds (adjusted OR = 2.06, 95% CI = 1.05 - 4.05), while the G/G genotype increased the susceptibility to grade II-IV astrocytoma by about 3 folds. CONCLUSION: MMP-7 -181A/G polymorphism may influence the susceptibility to astrocytoma, while MMP-3-1171 5A/6A polymorphism has no correlation to the susceptibility.

[Correlation of serum pepsinogen level and gastric mucosal changes of residents in the high incidence area of gastric cancer].

OBJECTIVE: To study the correlation between serum pepsinogen (PG) level and gastric mucosal changes of the residents who live in the high incidence area of gastric cancer, and investigate the value of serum PG level in screening for chronic atrophic gastritis (CAG) and gastric cancer (GC). METHODS: Serum PG level was detected with time resolved fluorescence immunoassay (TRFIA). The correlation between serum PG level and gastric mucosal changes was analyzed through endoscopic biopsy and pathological examination in 720 adult residents. RESULTS: The median serum PG I, PG II level and PG I / PG II ratio in 30 healthy residents with normal gastric mucosa was 172.0 microg/L, 9.6 microg/L and 17.5, respectively. The median serum PG I level of GC patients was significantly lower than that of chronic gastritis patients, gastric ulcer (GU) patients and local healthy residents (P < 0.05). The median PG I level of GU patients was significantly higher than that of the healthy resident group and the other groups (P <0.05). Serum PG II level in CAG, GC and GU groups were all significantly higher than that in CSG and healthy resident group (P <0.05). The PG I/PG II ratio in CAG or GC patients was significantly lower than that in the other groups (P < 0.05). The sensitivity and specificity of serum PG I < or = 60 microg/L for screening CAG or GC was 19.7% and 95.5% respectively, which were 34.7%, 89.3% for PG I/PG II < or =6, and 14.1%, 97.3% for PG I < or =60 microg/L + PG I /PG II < or =6. None in GU group was found to have serum PG I < or =60 microg/L. The median serum PG I level and PG I /PG II ratio in chronic gastritis (including CSG and CAG) with intestinal metaplasia were significantly lower than that of healthy resident group (P < 0.05). The sensitivity and specificity for screening of intestinal metaplasia were 16.6% and 92.9% by PG I < or =60 microg/L; 25.6% and 80.4% by PG I/PG II < or =6; 11.9% and 93.9% by PG I < or =60 microg/L + PG I/ PG II < or = 6. CONCLUSION: Serum pepsinogen level of the residents in the high incidence area of gastric cancer is closely correlated with the pathological changes of gastric mucosa. Though the sensitivity of serum pepsinogen level is relatively lower in the screening for chronic gastritis, gastric cancer and intestinal metaplasia, the specificity was quite high. PG I < or = 60 microg/L may be usful in differential diagnosis of gastric cancer from gastric ulcer.

[Studies on the cut-off value of serum pepsinogen abnormality for screening chronic atrophic gastritis and gastric carcinoma].

OBJECTIVE: To evaluate the fast serum pepsinogen level of the healthy adults among local population in areas with high incidence of gastric cancer and to study the suitable cut-off values of serum pepsinogen abnormality for the screen of chronic atrophic gastritis (CAG) and gastric carcinoma (GC) in China. METHODS: Serum PG I and PG II levels were detected with time resolved fluorescence immunoassay (TRFIA). The fast serum PG I and PG I level as well as PG I/PG II ratio of 606 healthy adult residents among local population in Zanhuang county, Hebei province were detected and the normal distribution ranges determined. The relationship between different cut-off values of serum PG I level, PG I/PG II ratio and corresponding pathological changes in gastric mucosae were comparatively analyzed with serum PG detection, endoscopic biopsy and pathological observation in 720 cases of local residents receiving endoscopic examination in the high incidence area of gastric cancer. The efficacy, sensitivity and specificity of different PG I, PG II abnormality cut-off values in the screen p rogram of CAG and GC were statistically analyzed. RESULTS: The serum PG I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. The median level of PG I, PG II and PG I/PG II were 161 microg/L, 14.8 microg/L and 10.5 respectively. Data from comparative studies on serum PG level and pathological changes of gastric mucosae showed that within the serum PG I range from 40 microg/L to 80 microg/L and PG I/PG II ratio range from 3 to 8, sensitivity of the screening program for CAG and GC increased while the specificity decreased along with the increase of cutoff values of serum PG I and PG I/PG II ratio. Results from statistical receiver operator characteristic curve (ROC) analysis suggested that the best cut-off value of PG I and PG I/PG II abnormality for the screening of CAG and GC being PG I < or =60 microg/L,PG I/PG II < or =6 respectively. CONCLUSION: The serum PC I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. Serum PG I < or =60 microg/L and PG I/PG II ratio < or =6 as abnormal cut-off value for the screen of CAG and GC could result relatively good sensitivity and specificity.

[Histogenesis of lung adenocarcinoma induced by oral adminstration of mycotoxins in mice].

OBJECTIVE: To study the histogenesis and the putative mechanisms of adenocarcinoma induced by AFG1 and ST in NIH mice. METHODS: Thirty-four cases of lung adenocarcinomas induced by AFG1 and ST in NIH mice were included in this study and 12 cases of normal lung tissues were used as control. The phenotype of the lung adenocarcinomas was determined by immunohistochemical expression of SP-C and CC-10 at protein level. The expression of P53, Ras P21 and PCNA was studied with immunohistochemical staining. RESULT: The positive expression of SP-C was found in all the lung adenocarcinomas, while no expression of CC-10 could be seen. The labelling index of PCNA in the adenocarcinomas were significantly higher than that of control (P < 0.01). No positive expression of mutant P53 and Ras at protein level could be found. CONCLUSION: The lung adenocarcinomas induced by the two mycotoxins in NIH mice arise from alveolar type II cells and no expression of mutant P53 and Ras at protein level was found in the lung adenocarcinomas.