Publications by authors named "Dong-Mei Fan"

36 Publications

Low-Coverage Sequencing of Urine Sediment DNA for Detection of Copy Number Aberrations in Bladder Cancer.

Cancer Manag Res 2021 26;13:1943-1953. Epub 2021 Feb 26.

Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, 518110, People's Republic of China.

Purpose: Chromosomal copy number aberrations (CNAs) are a hallmark of bladder cancer and a useful target for diagnostic explorations. Here we constructed a low-coverage whole-genome sequencing method for the detection of CNAs in urine sediment DNA from patients with bladder cancer.

Patients And Methods: We conducted a prospective study using urine sediment samples from 65 patients with bladder tumors, including 54 patients with bladder cancer and 11 patients with benign bladder tumors. Forty-three healthy individuals were included as normal controls. DNA was extracted from urine sediments and analyzed by low-coverage whole-genome sequencing to compare differences in CNAs among these three groups. CNAs are defined by arbitrary R values (normal range ± 2). When these values exceed ± 0.2 of normal range, gain/duplication or loss/deletion are suspected.

Results: With this method, CNAs were detected in 39 of 51 patients with bladder cancer, 2 of 10 patients with benign bladder tumors, and 8 of 39 normal controls. The lengths of DNA deletion and duplication were significantly larger in patients with bladder cancer than in patients with benign tumors or normal controls (P < 0.05). Bladder cancer duplicate CNAs mainly occurred on chromosomes 1q, 5p, 6p, 7p, 8q, and 13q, while deletions mainly occurred on 2q, 8p, 9q, 9p, and 11p. Those regions contained bladder cancer tumor-related genes, such as STK3, COX6C, SPAG1, CDKAL1, C9orf53, CDKN2A, CDKN2B, MIR31, and IFNA1. The number of CNAs detected in urine sediment DNA during the follow-up period was significantly reduced.

Conclusion: Our sequencing method is highly sensitive and can detect a minimal chromosome repeat/microdeletion change of 0.15 Mb. The use of 0.1~0.3× low-coverage whole-genome sequencing can be used to detect bladder cancer CNAs in urine sediment DNA. This method provides a promising method for noninvasive diagnosis of bladder cancer, but still needs further verification in a larger sample size.
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http://dx.doi.org/10.2147/CMAR.S295675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924115PMC
February 2021

Discovery of isopenicin A, a meroterpenoid as a novel inhibitor of tubulin polymerization.

Biochem Biophys Res Commun 2020 04 20;525(2):303-307. Epub 2020 Feb 20.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. Electronic address:

Microtubules are involved in celluar processes of movement, intracellular trafficking and mitosis, thus microtubule-targeting agents have been widely used in cancer therapy. Herein, we report isopenicin A, a novel meroterpenoid isolated from the plant endophytic fungus of Penicillium sp. sh18, as a novel microtubule binding molecule that efficiently depolymerizes microtubule polymerization to evoke G2/M cell cycle arrest and subsequent cell apoptosis, contributing to proliferation inhibition of human tumor cell lines. The discovery of isopenicin A provides a new chemotype for discovery and development of promising microtubule inhibitors.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.026DOI Listing
April 2020

Musashi 1-positive cells derived from mouse embryonic stem cells treated with LY294002 are prone to differentiate into intestinal epithelial-like tissues.

Int J Mol Med 2019 Jun 26;43(6):2471-2480. Epub 2019 Mar 26.

Department of Gastroenterology, The Second Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China.

The majority of Musashi 1 (Msi1)‑positive cells derived from mouse embryonic stem cells (mESCs) are prone to differentiate into neural epithelial‑like cells, and only a small proportion of Msi1‑positive cells differentiate into intestinal epithelial‑like cells. Whether inhibiting the phosphatidylinositol 3‑kinase (PI3K) signaling of mESCs can promote the differentiation of Msi1‑positive cells into intestinal epithelial‑like cells remains to be fully elucidated. In the present study, to inhibit PI3K signaling, mESCs were treated with LY294002. A pMsi1‑green fluorescence protein reporter plasmid was used to sort the Msi1‑positive cells from mESCs treated and untreated with LY294002 (5 µmol/l). The Msi1‑positive cells were hypodermically engrafted into the backs of non‑obese diabetic/severe combined immunodeficient mice. The presence of neural and intestinal epithelial‑like cells in the grafts was detected by reverse transcription‑quantitative polymerase chain reaction analysis and immunohistochemistry. Compared with the Msi1‑positive cells derived from mESCs without LY294002 treatment, Msi1‑positive cells derived from mESCs treated with LY294002 expressed higher levels of leucine‑rich repeat‑containing G‑protein coupled receptor, a marker of intestinal epithelial stem cells, and lower levels of Nestin, a marker of neural epithelial stem cells. The grafts from Msi1‑positive cells treated with LY294002 contained more intestinal epithelial‑like tissues and fewer neural epithelial‑like tissues, compared with those from untreated Msi1‑positive cells. LY294002 had the ability to promote the differentiation of mESCs into intestinal epithelial‑like tissues. The Msi1‑positive cells selected from the cell population derived from mESCs treated with LY294002 exhibited more characteristics of intestinal epithelial stem cells than those from the untreated group.
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http://dx.doi.org/10.3892/ijmm.2019.4145DOI Listing
June 2019

Simultaneous detection of target CNVs and SNVs of thalassemia by multiplex PCR and next‑generation sequencing.

Mol Med Rep 2019 Apr 24;19(4):2837-2848. Epub 2019 Jan 24.

Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Thalassemia is caused by complex mechanisms, including copy number variants (CNVs) and single nucleotide variants (SNVs). The CNV types of α‑thalassemia are typically detected by gap‑polymerase chain reaction (PCR). The SNV types are detected by Sanger sequencing. In the present study, a novel method was developed that simultaneously detects CNVs and SNVs by multiplex PCR and next‑generation sequencing (NGS). To detect CNVs, 33 normal samples were used as a cluster of control values to build a baseline, and the A, B, C, and D ratios were developed to evaluate‑SEA, ‑α4.2, ‑α3.7, and compound or homozygous CNVs, respectively. To detect other SNVs, sequencing data were analyzed using the system's software and annotated using Annovar software. In a test of performance, 128 patients with thalassemia were detected using the method developed and were confirmed by Sanger sequencing and gap‑PCR. Four different CNV types were clearly distinguished by the developed algorithm, with ‑SEA, ‑α3.7, ‑α4.2, and compound or homozygous deletions. The sensitivities for each CNV type were 96.72% (59/61), 97.37% (37/38), 83.33% (10/12) and 95% (19/20), and the specificities were 93.94% (32/33), 93.94% (32/33), 100% (33/33) and 100% (33/33), respectively. The SNVs detected were consistent with those of the Sanger sequencing.
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http://dx.doi.org/10.3892/mmr.2019.9896DOI Listing
April 2019

Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

Int J Cancer 2017 10 7;141(7):1445-1457. Epub 2017 Jul 7.

State Key Laboratory of Experimental Hematology, Department of Pharmacy, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy.
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http://dx.doi.org/10.1002/ijc.30846DOI Listing
October 2017

The Levels of Serum Irisin as a Predictor of Insulin Resistance in Han Chinese Adults with Metabolically Healthy Obesity.

Clin Lab 2017 May;63(5):881-886

Background: The aim of this study was to evaluate serum irisin levels and analyze its related factors in Han adults with metabolically healthy obesity.

Methods: This cross-sectional study included 75 metabolically healthy, non-obese adults and 51 metabolically healthy, obese adults. Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and serum irisin were measured.

Results: The levels of serum irisin (5.40 ± 1.69 vs. 6.46 ± 1.37 µg/mL) were significantly lower in the metabolically healthy obese group (p < 0.05). Irisin correlated positively with high density lipoprotein cholesterol (HDL-C) (r = 0.303) and correlated negatively with body mass index (BMI) (r = -0.389), WC (r = -0.324), fasting plasma glucose (FPG) (r = -0.441), HOMA-IR (r = -0.429), triglycerides (TG) (r = -0.185), total cholesterol (TC) (r = -0.209), low density lipoprotein cholesterol (LDL-C) (r = -0.157) (p < 0.05). Multiple regression analysis revealed that FPG (β = -1.720, p = 0.001) and HOMA-IR (β = -0.399, p = 0.006) were still significantly associated with irisin. Serum irisin (β = -0.246, p = 0.005) and BMI (β = 0.078, p = 0.043) were significant independent predictors for HOMAIR.

Conclusions: Serum irisin levels were reduced in metabolically healthy, obese Han adults. Irisin reduction appears to be associated with elevated FPG and insulin resistance but not obesity. In additional, falling irisin may increase the occurrence of insulin resistance in metabolically healthy Han adults and should be examined in future studies.
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http://dx.doi.org/10.7754/Clin.Lab.2016.160805DOI Listing
May 2017

Effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain.

Mol Pain 2017 Jan-Dec;13:1744806917706582

5 Department of Anesthesia, the First Affiliated Hospital of Zhengzhou University, Luoyang, China.

Objective To investigate the effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain. Methods Our study selected 100 clean grade healthy Sprague-Dawley adult male rats weighing 200 to 250 g. After establishment of a rat model of chronic constriction injury, these rats were divided into 10 groups (10 rats in each group): the normal control, sham operation, chronic constriction injury, normal saline, morphine, miR-223, NLRP3, miR-223 + morphine, NLRP3 + morphine, and miR-223 + NLRP3 + morphine groups. The real-time quantitative polymerase chain reaction assay, Western blotting, and enzyme-linked immunosorbent assay were used for detecting the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, Interleukin (IL)-1β, and IL-18 in sections of lumbar spinal cord. Immunohistochemistry was applied for detecting the positive rates of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18. Results The paw withdrawal threshold and percentage maximum possible effect (%MPE) were higher in chronic constriction injury group when compared with the normal control and sham operation groups. Behavioral tests showed that compared with the chronic constriction injury and normal saline groups, the morphine and miR-223 + morphine groups showed obvious analgesic effects. Expressions of miR-223 in the miR-223, miR-223 + morphine, and miR-223 + NLRP3 + morphine were significantly higher than those in the chronic constriction injury, normal saline, and morphine groups. Compared with chronic constriction injury, normal saline and morphine groups, the mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18 were significantly decreased in the miR-223 and miR-223 + morphine groups, while mRNA and protein expressions of NLRP3, apoptosis-associated speck-like protein, Caspase-1, IL-1β, and IL-18 were significantly increased in the NLRP3 and NLRP3 + morphine group. Conclusion Our study provides strong evidence that miR-223 could suppress the activities of NLRP3 inflammasomes ( NLRP3, apoptosis-associated speck-like protein, and Caspase-1) to relieve morphine analgesic tolerance in rats by down-regulating NLRP3.
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http://dx.doi.org/10.1177/1744806917706582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464520PMC
April 2018

Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia.

Biosci Rep 2017 Jun 27;37(3). Epub 2017 Jun 27.

Department of Anesthesiology, The First Affiliated Hospital of Henan University of Science and Technology (New District Hospital), Luoyang 471300, P.R. China.

The study aims to explore the effects of on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. negatively targetted JAK2. Inhibition of can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.
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http://dx.doi.org/10.1042/BSR20170186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434087PMC
June 2017

Tea polyphenols dominate the short-term tea (Camellia sinensis) leaf litter decomposition.

J Zhejiang Univ Sci B 2017 Feb.;18(2):99-108

Institute of Tea Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China.

Polyphenols are one of the most important secondary metabolites, and affect the decomposition of litter and soil organic matter. This study aims to monitor the mass loss rate of tea leaf litter and nutrient release pattern, and investigate the role of tea polyphenols played in this process. High-performance liquid chromatography (HPLC) and classical litter bag method were used to simulate the decomposition process of tea leaf litter and track the changes occurring in major polyphenols over eight months. The release patterns of nitrogen, potassium, calcium, and magnesium were also determined. The decomposition pattern of tea leaf litter could be described by a two-phase decomposition model, and the polyphenol/N ratio effectively regulated the degradation process. Most of the catechins decreased dramatically within two months; gallic acid (GA), catechin gallate (CG), and gallocatechin (GC) were faintly detected, while others were outside the detection limits by the end of the experiment. These results demonstrated that tea polyphenols transformed quickly and catechins had an effect on the individual conversion rate. The nutrient release pattern was different from other plants which might be due to the existence of tea polyphenols.
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http://dx.doi.org/10.1631/jzus.B1600044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296227PMC
July 2017

Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis.

Oncotarget 2017 Feb;8(6):9660-9671

Department of Obstetrics and Gynecology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.

Urine HE4 has been reported as the potential novel diagnostic biomarker for ovarian cancer in several studies, but their results were inconsistent. Therefore, we conducted a systematic analysis to evaluate the diagnostic value of urine HE4 in detecting ovarian cancer. A comprehensive electronic and manual search was conducted for relevant literatures through several databases up to May 5, 2016. The quality of the studies included in the systematic review was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were conducted using Meta-DiSc 1.4 and STATA 12.0 software. A total of seven publications were included in this study, and these studies included 413 ovarian cancer patients and 573 controls. The summary estimates were: sensitivity 0.76 (95% confidence interval [CI]: 0.72-0.80), specificity 0.92 (95% CI: 0.89-0.94), positive likelihood ratio 8.39 (95%CI: 4.81-14.63), negative likelihood ratio 0.23 (95% CI: 0.13-0.39), diagnostic odds ratio 37.90 (95% CI: 18.69-76.83), and area under the curve 0.93. According to our results, urine HE4 has greater diagnostic value in detecting ovarian cancer. In addition, considering the high heterogeneity, further research studies with more well-designed and large sample sizes are needed in the future.
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http://dx.doi.org/10.18632/oncotarget.14173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354761PMC
February 2017

Forkhead factor FOXQ1 promotes TGF-β1 expression and induces epithelial-mesenchymal transition.

Mol Cell Biochem 2014 Dec 7;397(1-2):179-86. Epub 2014 Oct 7.

Department of Gynecology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, Henan, People's Republic of China.

Epithelial-mesenchymal transition (EMT) promotes tumor invasion and metastasis, but the coordination and integration mechanisms of these processes are still not fully understood. In this study, we used a cross-species expression profiling strategy of Hela cells to determine an important genetic program transfers. In particular, we have discovered a new transfer function, which is not previously known about transcription factor forkhead box Q1 (FOXQ1). The shRNA anti-FOXQ1 gene was synthesized and transfected into the Hela and EpRas cells. RT-PCR assay was performed to detect the mRNA levels in cells. Cell adhesion and separation assay were used to examine the cell-cell adhesion and separation among cells. Wound healing assay was utilized to examine cell migration and invasion ability. Chromatin immunoprecipitation assay was used to investigate the interaction between E-cadherin and N-cadherin and FOXQ1 promoter region. The results indicated that ectopic expression of FOXQ1 increased cell migration and invasion in vitro, enhanced mammary epithelial cells in vivo lung metastasis, and triggered significant EMT. In contrast, the opposite effects in vitro and in vivo of FOXQ1 knockdown phenotypes were caused by these mechanisms. Notably, FOXQ1 repressed core EMT regulation of the expression of TGF-β1. FOXQ1 protein directly interacts with E-cadherin and N-cadherin promoter region. And surveys show that FOXQ1 expression regulation by TGF-β1 and blockade induced EMT both morphological and molecular levels. Our findings emphasize the feasibility of cross-species expression profiles, as a strategy to identify metastasis-related genes. The induction of EMT by FOXQ1 defines a new transfer function in promoting cancer behind possible mechanisms.
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http://dx.doi.org/10.1007/s11010-014-2185-1DOI Listing
December 2014

TGF-β1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition in some tumor lines.

Tumour Biol 2014 Nov 13;35(11):11277-82. Epub 2014 Aug 13.

Department of Gynecology, The 1st Affiliated Hospital of He'nan University of Science and Technology, LuoYang, 471003, People's Republic of China.

More and more studies have reported that epithelial-mesenchymal transition (EMT) involved in the process of cancer development and progression occurs. The EMT also plays an important role in the movement and transfer of the tumors. Transforming growth factor-β (TGF-β) could induce the EMT in some cancer cell types. However, the mechanism underlying this transition process has also not been entirely clarified. In this study, the results indicated that TGF-β1-mediated EMT in the tumor was associated with the estrogen receptor (ER). The decreased expression of vimentin and snail resulted in the decrease of the ER expression by small interfering RNA-mediated silencing and preventing the TGF-β-induced EMT. In conclusion, our results indicated that TGF-β1 is an estrogen receptor signaling and essential novel downstream targets and could act as an important factor in the TGF-β-induced EMT.
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http://dx.doi.org/10.1007/s13277-014-2166-8DOI Listing
November 2014

The prognosis significance of TGF-β1 and ER protein in cervical adenocarcinoma patients with stage Ib~IIa.

Tumour Biol 2014 Nov 12;35(11):11237-42. Epub 2014 Aug 12.

The Department of Gynecology, The First Affiliated Hospital of Henan University of Science and Technology, 471023, Luoyang, China.

The incidence of stage Ib~IIa of cervical adenocarcinoma accounts about 60 to 70% of all patients. This study aims to investigate the prognostic significance of protein estrogen receptor alpha (ERα) and transforming growth factor beta 1 (TGF-β1) level in different glandular epithelia of the cervix. In this study, immunohistochemistry was used to detect ERα and TGF-β1 in carcinomas and incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was applied to evaluate the prognostic significance of TGF-β1 and ERα in carcinomas. The results indicated that the positive expression of TGF-β1 in carcinomas was 71.21%, significantly higher compared to that in the normal cervix (35%) and chronic cervicitis (55%) (χ(2) = 8.901, P = 0.012). Similarly, the positive expression of ERα in the carcinomas was 68.18%, significantly higher compared to the normal cervix (35%) and chronic cervicitis (50%) (χ(2) = 7.693, P = 0.021). Both TGF-β1 and ERα in the carcinomas were associated with the vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic metastasis (P < 0.05). The conjugation of TGF-β1 and ERα was an independent prognostic factor for cervical adenocarcinoma. Survival curve showed that the positive TGF-β1 and ERα indicated a short lifetime of patient with cervical adenocarcinoma. In conclusion, the expression of TGF-β1 and ERα protein in the carcinomas had a significant prognostic value in a patient of stage Ib~IIa in cervical adenocarcinoma.
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http://dx.doi.org/10.1007/s13277-014-2110-yDOI Listing
November 2014

Pilot study: alteration of deleted in liver cancer1 and phosphorylated focal adhesion kinase Y397 cytoplasmic expression and the prognostic value in advanced epithelial ovarian carcinoma.

Int J Mol Sci 2011 29;12(12):8489-501. Epub 2011 Nov 29.

Department of Obstetrics and Gynecology, First Affiliated Hospital, Zhengzhou University, No.1 Jianshe Road, Zhengzhou 450052, China.

Background: Deletion in liver cancer gene (DLC1) and phosphorylated focal adhesion kinase (p-FAK) have recently been reported as metastasis-related genes. However, the roles and prognostic values of their expression in epithelial ovarian carcinomas (EOCs) remain unclear.

Methods: The expression and prognostic value of DLC1 and p-FAK Y397 in EOC were evaluated by immunohistochemistry and multivariate analysis.

Results: Low expression of DLC1 and high expression of p-FAK Y397 were found in the 76 cases of EOC. The expression of DLC1 and p-FAK Y397 were negatively correlated. Multivariate analysis showed that the combination of them was an independent prognostic marker of EOC (P = 0.0319).

Conclusions: DLC1 and pFAK Y397 had an association with the clinicopathologic characteristics of EOC. Expression of neither of these genes was a prognostic factor alone, but the combination revealed a significant prognostic value in the 60 cases of advanced stage EOC.
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http://dx.doi.org/10.3390/ijms12128489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257083PMC
January 2015

1-Benzyl-6-chloro-indoline-2,3-dione.

Acta Crystallogr Sect E Struct Rep Online 2011 Dec 25;67(Pt 12):o3427. Epub 2011 Nov 25.

Sate Key Laboratory of Materials-Oriented Chemcial Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China.

In the title compound, C(15)H(10)ClNO(2),the dihedral angle between the mean planes of the benzene and 6-chloro-indoline-2,3-dione ring systems, linked through a methyl-ene group, is 81.68 (10)°. In the crystal, mol-ecules are connected by C-H⋯O hydrogen bonds, generating C(6) chains propagating in [010].
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http://dx.doi.org/10.1107/S1600536811048665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239061PMC
December 2011

High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma.

Mol Biol Rep 2012 Apr 20;39(4):3925-31. Epub 2011 Jul 20.

The Department of Gynecology, The First Affiliated Hospital of Henan University of Science and Technology, Jinghua Road, Luoyang, 471003, Henan, China.

This study evaluated the relationship between altered cytoplasmic expression of TGF-β1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-β1 expression at these locations. We found that TGF-β1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.
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http://dx.doi.org/10.1007/s11033-011-1171-xDOI Listing
April 2012

[Interferon-alpha-2b induces molecular responses of patients with polycythemia vera and its post-polycythemic myelofibrosis].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2011 Apr;19(2):444-9

Chinese Academy of Medical Sciences, Tianjin 300020, China.

To evaluate the efficacy and safety of interferon-alpha-2b (IFN-α-2b) in polycythemia vera patients(PV patient) with or without post-polycythemic myelofibrosis (post-PV MF), 30 patients with mutated JAK2V617F were enrolled in this study, from which 29 patients were evaluable. The percentage of mutated JAK2V617F allele (V617F%) was evaluated by real-time polymerase chain reaction (RT-PCR) before and after treatment with IFN-α-2b. The correlation of V617F allele burden with the major clinical outcomes was studied. Adverse effects appeared in patients was observed. The results showed that the median follow-up was 24 (12 - 42) months for 29 evaluable patients. Complete hematologic response was achieved in 10%, 48%, 72% and 78% of patients after treatment for 6, 12, 24 and 36 months respectively. The detection of V617F allele burden revealed that the molecular remission of patients (V617F%) was achieved in 41%, 76%, 89% and 89% after treatment for 6, 12, 24 and 36 months respectively. Molecular complete remission (JAK2V617F undetectable) was achieved in 4 patients, lasted from 6 to 12 months after IFN-α-2b discontinuation. The decrease of V617F% in patients with post-PV MF was significantly higher than that in patients without post-PV MF (53 ± 18% vs 32 ± 22%, respectively; p = 0.031) after treatment for 12 months. PV patients had a good tolerance to IFN-α-2b. It is concluded that IFN-α-2b can decrease the mutated V617F allele burden. Patients with PV, especially with post-PV MF, can achieve molecular remission after treatment with IFN-α-2b.
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April 2011

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

Nat Genet 2010 Sep 22;42(9):759-63. Epub 2010 Aug 22.

Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, China.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
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http://dx.doi.org/10.1038/ng.648DOI Listing
September 2010

[Expression of TGF-beta1 and E-cadherin in primary and metastatic ovarian carcinoma].

Nan Fang Yi Ke Da Xue Xue Bao 2010 Jun;30(6):1355-8

Department of Gynecology and Obstetrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Objective: To detect the expression of the protein of TGF-beta1 and E-cadherin in the primary and metastatic lesions of ovarian carcinoma and explore the mechanism of the metastasis of ovarian carcinoma.

Methods: Immunohistochemistry (IHC) was performed to detect the expression of TGF-beta1 and E-cadherin proteins in primary and metastatic ovarian carcinoma, benign epithelial ovarian tumor and normal ovarian tissue.

Results: The expression of TGF-beta1 was significantly higher in ovarian carcinoma (67.2%) than in benign tumors (28.6%) and normal ovarian tissue (18.9%) (Chi2=26.94, P<0.001), but E-cadherin expression showed a reverse pattern. TGF-beta1 expression in the primary ovarian carcinoma carcinoma was associated with the FIGO stage, lymph metastasis and ascites of the tumor (P=0.01, P=0.01, and P=0.04, respectively). E-cadherin expression in the tumor was associated with the differentiation (P=0.02) and lymph metastasis of ovarian carcinoma (P=0.04). The expressions of TGF-beta1 and E-cadherin were all significantly lower in the primary tumors than in the metastatic tumor (Chi2=4.70, P=0.03; Chi2=5.91, P=0.015). A significant correlation was found between the expressions of the TGF-beta1 and E-cadherin in the primary carcinoma (Kappa value of -0.32, P=0.01).

Conclusion: TGF-beta1 and E-cadherin are closely associated with the metastasis of ovarian carcinoma and might be potential targets for controlling the metastasis of ovarian carcinoma.
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June 2010

[The influence of Ara-C on anti-CD3/anti-Pgp mediating T-lymphocytes activities against multi-drug resistant leukemia cells.].

Zhonghua Xue Ye Xue Za Zhi 2009 Dec;30(12):812-5

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.

Objective: To investigate the role of Ara-C in regulating anti-CD3/anti-Pgp mediating T-lymphocytes activities against multi-drug resistant leukemia cells.

Methods: The diabody of anti-CD3/anti-Pgp was purified by E-tag affinity chromatography. K562 and K562/A02 cells were treated with Ara-C. The expressions of B7-1 and B7-2 on K562 and K562/AO2 cells were detected by FACS. The cytotoxicity of T-lymphocytes combined with anti-CD3/anU-Pgp plus Ara-C was analyzed by CytoTox 96 nonradioactive method.

Results: The expressions of B7-1 and B7-2 on K562 and K562/A02 cells treated by Ara-C was significantly higher than those untreated. The effect/target ratio was from 0.39:1 to 25:1, and the killing rate of activated T cells to anti-drug-resistant leukemia cells was from (16.44 +/- 1.20)% to (60.49 +/- 2.90)%. The killing rates were increased gradually, with both the effect/target ratio and the antibody concentration increasing (P < 0.05).

Conclusion: Ara-C may be an important adjuvant for improving anti-CD3/anti-Pgp mediating T-lymphocytes activities against multi-drug resistant leukemia cells.
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December 2009

3-Chloro-azepan-2-one.

Acta Crystallogr Sect E Struct Rep Online 2010 Jan 23;66(Pt 2):o438. Epub 2010 Jan 23.

State Key Laboratory of Materials-Oriented Chemcial Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China.

In the title compound, C(6)H(10)ClNO, an inter-mediate for the production of lysine, there are intra-molecular C-H⋯Cl hydrogen bonds.
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http://dx.doi.org/10.1107/S1600536810002060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2979924PMC
January 2010

[Effect of calmodulin antagonist O-4-ethoxyl- butyl-berbamine on the proliferation of human breast cancer cell line MCF-7 and its relevant mechanism].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2009 Jun;31(3):326-9

State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.

Objective: To investigate the effect of calmodulin antagonist O-(4-ethoxyl-butyl)-berbamine (EBB) on proliferation of human breast cancer cell MCF-7 and its possible mechanism.

Methods: MTT assay was used to analyze the effect of EBB on tumor cells growth. Flow cytometry was used to detect its impact on the cell cycle of MCF-7 cells. Immunofluoresce labeling technique and laser scanning confocal microscope were used to reveal the changes of the microtubule, microfilament, mitochondrion, and endoplasmic reticulum in the cells.

Results: The IC50 value of EBB in MCF-7 cells was (13.0 +/- 3.7) micromol/L. MCF-7 cells were arrested at S phase after EBB treatment. Meanwhile, depolymerization of the microtubule and microfilament, impairment of the mitochondrion and swelling of endoplasmic reticulum were observed.

Conclusion: EBB arrests MCF-7 cells at S phase by inhibiting the growth of MCF-7 cells, which may be related to the changes of structures and functions of the microtubule, microfilament, mitochondrion, and endoplasmic reticulum.
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June 2009

[Mechanism of synergistic anti-tumor effect of PH II -7 with doxorubicin on multi-drug resistant HL-60/ADR cells].

Zhonghua Xue Ye Xue Za Zhi 2008 Sep;29(9):599-602

State Key Laboratory of Experiment Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.

Objective: To study the synergistic mechanism between PH II -7 and doxorubicin against multi-drug resistant HL-60/ADR cells and its parent HL-60 cells.

Methods: The anti-tumor activity of doxorubicin alone and combined with PH II -7 were measured by MTT assay. RNA was extracted from the cells treated with PH II -7 for different times or doses then the expression of MRP gene was measured by RT-PCR. Confocal laser scanning microscopy and FACS were used to detect the intracellular cumulation of doxorubicin in PH II -7 treated HL-60 and HL-60/ADR cells.

Results: PH II -7 has anti-tumor effect with IC50 of (0.83 +/- 0.08) micromol/L and (1.74 +/- 0.56) micromol/L for HL-60 and HL-60/ADR, respectively. It could potentiate the anti-tumor effect of doxorubicin with CDI of 0.7 and 0.43 for HL-60 and HL-60/ADR, respectively. PH II -7 and doxorubicin act synergistically in inhibiting the proliferation of HL-60 and HL-60/ADR cells and down-regulating the expression of MRP gene in a dose and time dependent manner. PH II -7 restored the intracellular cumulation of doxorubicin in HL-60/ADR cells to 55% of that in HL-60 cells.

Conclusion: PH II -7 can significantly hasten the cytotoxicity of doxorubicin to HL-60 and HL-60/ADR cells through down-regulating the expression of MRP. The synergistic effect was more obvious in HL-60/ADR cells.
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September 2008

1-Benzoyl-3-chloro-azepan-2-one.

Acta Crystallogr Sect E Struct Rep Online 2009 Sep 9;65(Pt 10):o2383. Epub 2009 Sep 9.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China.

In the crystal structure of the title compound, C(13)H(14)ClNO(2), inter-molecular C-H⋯O inter-actions link the mol-ecules into a two-dimensional network.
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http://dx.doi.org/10.1107/S1600536809033510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2970295PMC
September 2009

[Three-step purification of preparative-scale antiCD20 (Fab')2].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2008 Oct;30(5):622-5

State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.

Objective: To establish a three-step purification method of preparative-scale antiCD20 (Fab')2 using AKTA prime.

Methods: AntiCD20 (Fab')2 was extracted by hyperosmotic solution and then purified by CM sepharose FF, phenyl sepharose FF, and protein G sepharose FF.

Results: Around 8 mg anti-CD20 (Fab')2, whose purification was 96.678%, was purified. The antigen-binding activity of antiCD20 (Fab')2 was similar to that of antiCD20 (Fab')2 purified by protein G sepharose FF and S-100.

Conclusion: The three-step purification method can obtain high-purity preparative-scale antiCD20 (Fab')2 in a simple way.
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October 2008

[Preparation and activity detection of monoclonal antibody against anti-CD3 ScFv].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2008 Jun;30(3):354-9

State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China.

Objective: To prepare monoclonal antibody (McAb) against anti-CD3 ScFv for purifying and detecting serum anti-CD3 antibody concentration.

Methods: McAb against anti-CD3 ScFv was prepared by hybridoma technique and used to prepare affinity chromatography column, which was used to purify anti-CD3 ScFv and Diabody [CD3 x Pgp] without E-tag. The binding activities of anti-CD3 ScFv, Diabody [CD3 x Pgp] without E-tag, and Diabody [CD3 x Pgp] purified by anti-CD3 affinity chromatography column or anti-E-tag affinity chromatography column against K562/A02 cell and Jurket cells were detected by fluorescence activated cell sorting (FACS) method. ELISA was used to identify the specificity of the McAb.

Results: McAb against anti-CD3 ScFv specifically detected serum anti-CD3 ScFv without reacting with sera. The anti-CD3 ScFv purified by anti-CD3 affinity chromatography column and purified by anti-E-tag affinity chromatography column had the same specific binding activity with Jurkat cells. The positive binding rates of Diabody [CD3 x Pgp] without E-tag to K562/A02 and Jurkat cells were 89.87% and 83.95%, respectively. In the competitive binding experiments with K562/A02 and Jurkat cells, the binding rates of Diabody [CD3 x Pgp] without E-tag decreased to 56.30% and 43.78%, respectively.

Conclusion: The McAb against anti-CD3 ScFv prepared in our lab can be used to purify and detect serum anti-CD3 antibody concentration.
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June 2008

[Up-regulation of CD86 and cytokine expression in acute leukemia cells by Ara-C].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008 Jun;24(6):550-2

Institute of Hematology & Hospital of Blood Diseases, Chinese Academic of Medical Sciences & Peking Union Medical College, Tianjin, China.

Aim: To observe the effects of Ara-c on the expression of CD86 molecule on acute leukemia cells and explore the possible mechanisms.

Methods: The expression of CD86 on U937, HL-60 and NB4 cell lines treated with or without Ara-C wa assayed by flow cytometry. The mRNA expression of CD86, NF-kappaB, IFN-gamma was examined by semiquantitative RT-PCR.

Results: UP-regulation of CD86 was observed on those cells treated by Ara-c. The level of CD86 and NF-kappaB mRNA in Ara-c treated cells was significantly enhanced. IFN-gamma was detectable 72 hours after T cell activation.

Conclusion: Ara-C can enhance CD86 and NF-kappaB expression on acute leukemia cells, which may play critical role in T cell activation and differentiation.
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June 2008

[Construction and expression of human 4-1BBL/anti-CD20 fusion protein].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008 Jun;24(6):543-5

Institute of Hematology & Hospital of Blood Disease, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.

Aim: To construct and express human 4-1BBL/anti-CD20 bispecific fusion protein and identify its biological activity.

Methods: PCR and overlapping PCR were used to construct human 4-1BBL/anti-CD20 bispecific fusion protein. DNA sequencing was performed by the terminus of the fusion protein nucleotide.The product was purified by affinity chromatography and analyzed by Western blot and its antigen-binding activity was examined by FACS.

Results: The data of DNA sequence showed that human 4-1BBL/anti-CD20 bispecific fusion protein was correct. The fusion protein was recovered in high yield (up to 4 mg/L) after E-tag purification and predominantly(90%) as a dimer. The fusion protein could bind to Raji cells(CD20(+)) and A549 cells(4-1BB(+)), respectively.

Conclusion: The human 4-1BBL/anti-CD20 bispecific fusion protein with high level expression was successfully obtained and could bind to Raji ceIls and A549 cells.
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June 2008

[The role of extracellular domain of human 4-1BBL in regulating activities of human peripheral blood lymphocytes in vitro].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2008 May;24(5):431-3

State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

Aim: To investigate the role of the extracellular domain of human 4-1BBL (ex4-1BBL) in regulating the in vitro activities of peripheral blood lymphocytes (PBL).

Methods: Viable cells were quantified with Trypan-blue exclusion assay. CytoTox 96 Nonradioactive Cytotoxicity Assay Kit was used for measuring LDH levels of supernatant. ELISA kit was used for measuring IL-2 level. In vitro cytotoxity of PBL combined with anti-CD3/anti-Pgp bispecific diabody plus ex4-1BBL was analyzed with CytoTox 96 nonradioactive method.

Results: Ex4-1BBL can increase the proliferation of PBL, reduce cell death, promote IL-2 secretion, and the experimental group with ex4-1BBL showed obviously enhanced cytotoxic effect toward K562/A02 cells.

Conclusion: Ex4-1BBL may be an important adjuvant for improving activities of PBL.
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May 2008

[Construction and expression of diabody [CD3 x Pgp] without Etag].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2007 Oct;23(10):946-9

State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academic of Medical Sciences and Peking Union Medical College, Tianjin, China.

Aim: To construct and express a diabody [CD3 x Pgp] without Etag and analyse its biological activity.

Methods: In this study, the diabody [CD3 x Pgp] was obtained by PCR and restriction cleavage, and expressed in E.coli 16C9. The product was purified by anti-anti-CD3 scFv affinity chromatography and verified through SDS-PAGE electrophoresis. Flow cytometry(FCM) was used to analyse the bingding properties and competitive bingding capacity.

Results: The sequence of diabody [CD3 x Pgp] without Etag was correct. It migrated as two bands with the expected molecular weight(25 kD and 26 kD) in SDS-PAGE. The binding rate to CD3 and Pgp antigen was 83.95% and 89.87% respectively. The competitive bingding rate to CD3 and Pgp was 43.78% and 50.25% respectively.

Conclusion: The diabody [CD3 x Pgp] without Etag has been successfully constructed, expressed and purified. The product can bind to CD3 and Pgp antigen specifically, and its biological activity doesn't decrease.
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October 2007