Publications by authors named "Jinfang Jiang"

43 Publications

Long non-coding RNA MIR31HG as a prognostic predictor for malignant cancers: A meta- and bioinformatics analysis.

J Clin Lab Anal 2022 Jan 27;36(1):e24082. Epub 2021 Nov 27.

NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases (First Affiliated Hospital, School of Medicine, Shihezi University), Shihezi, China.

Background: The possible regulatory mechanism of MIR31HG in human cancers remains unclear, and reported results of the prognostic significance of MIR31HG expression are inconsistent.

Methods: The meta-analysis and related bioinformatics analysis were conducted to evaluate the role of MIR31HG in tumor progression.

Results: The result showed that high MIR31HG expression was not related to prognosis. However, in the stratified analysis, we found that the overexpression of MIR31HG resulted in worse OS, advanced TNM stage, and tumor differentiation in respiratory system cancers. Moreover, our results also found that MIR31HG overexpression was related to shorter OS in cervical cancer patients and head and neck tumors. In contrast, the MIR31HG was lower in digestive system tumors which contributed to shorter overall survival, advanced TNM stage, and distant metastasis. Furthermore, the bioinformatics analysis showed that MIR31HG was highly expressed in normal urinary bladder, small intestine, esophagus, stomach, and duodenum and low in colon, lung, and ovary. The results obtained from FireBrowse indicated that MIR31HG was highly expressed in LUSC, CESC, HNSC, and LUAD and low in STAD and BLCA. Gene Ontology analysis showed that the co-expressed genes of MIR31HG were most enriched in the biological processes of peptide metabolism and KEGG pathways were most enriched in Ras, Rap1, and PI3K-Akt signaling pathway.

Conclusion: MIR31HG may serve as a potential biomarker in human cancers.
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http://dx.doi.org/10.1002/jcla.24082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761471PMC
January 2022

A simple and fast LC-MS/MS method for the simultaneous determination of tenofovir alafenamide and tenofovir in human plasma.

Biomed Chromatogr 2021 Nov 1:e5273. Epub 2021 Nov 1.

Suzhou Haike Medical Technology Co. Ltd., Suzhou, China.

A simple and fast liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of tenofovir alafenamide (TAF) and tenofovir (TNF) in human plasma. A simple protein precipitation procedure was employed to extract analytes from plasma. Chromatographic separation was performed on an Eclipse Plus C column utilizing a fast gradient elution starting with 2% of 2 mM ammonium acetate-formic acid (100/0.1, v/v) followed by increasing the percentage of acetonitrile. Detection was performed on a tandem mass spectrometer equipped with an electrospray ionization source operated in the positive ionization mode, using the transitions m/z 477.2 → m/z 346.1 for TAF and m/z 288.1 → m/z 176.1 for TNF. TAF-d and TNF-d were used as the internal standard of TAF and TNF, respectively. The method was validated in the concentration ranges 1.25-500 ng/mlfor TAF and 0.300-15.0 ng/ml for TNF with acceptable accuracy and precision.
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http://dx.doi.org/10.1002/bmc.5273DOI Listing
November 2021

Risk factors and nursing countermeasures of postoperative pulmonary infection in patients with breast cancer: A retrospective analysis.

Medicine (Baltimore) 2021 Sep;100(37):e26952

Department of Oncology, Guangxi Tumor Hospital, China.

Abstract: It is necessary to elucidate the potential risk factors of pulmonary infection to provide references for the management of breast cancer.Our study was a retrospective design, patients who underwent modified radical mastectomy for breast cancer in our department of breast surgery from January 2019 to November 2020 were included. The personal and clinical data of included patients with and without pulmonary infection were compared.A total of 234 patients with radical mastectomy were included, the incidence of pulmonary infection was 15.38% with 95%confidence interval (CI) 11.42% to 18.98%. There were significant differences in the age, body mass index, diabetes, duration of surgery, combined radiotherapy and chemotherapy, and duration of drainage between patients with and without pulmonary infections (all P < .05). Logistic regression analysis indicated that age ≥55 years (odds ratio [OR] 2.128, 95%CI 1.105-3.426), body mass index ≥ 24 kg/m2(OR 2.344, 95%CI 1.031-3.299), diabetes (OR 2.835, 95%CI 1.132-4.552), duration of surgery ≥120 minutes (OR 1.394, 95%CI 1.012-1.044), combined radiotherapy and chemotherapy (OR 3.122, 95%CI 1.124-5.273), duration of drainage ≥5 days (OR 1.851, 95%CI 1.112-2.045) might be the independent risk factors of pulmonary infection in patients after radical mastectomy(all P < .05). Pseudomonas aeruginosa and Klebsiella pneumoniae are the most commonly seen bacteria.The incidence of postoperative pulmonary infections in breast cancer patients is high, and there are many associated risk factors. The perioperative management of patients should be strengthened targeted on those risk factors in clinical practice.
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http://dx.doi.org/10.1097/MD.0000000000026952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448041PMC
September 2021

[Correlation Study on Expression of PD-1 and PD-L1 in Non-small Cell Lung Cancer and Epidermal Growth Factor Receptor Mutations].

Zhongguo Fei Ai Za Zhi 2021 Sep 30;24(9):623-631. Epub 2021 Aug 30.

First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832002, China.

Background: The treatment mode of lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for patients with EGFR mutant in non-small cell lung cancer (NSCLC). At the same time programmed death receptor 1 (PD-1) and its programmed death receptor ligand 1 (PD-L1) inhibitors therapy as the representative immune checkpoint inhibitors (ICIs) has a significant effect in the treatment of lung cancer. The aim of this study was to investigate the correlation between the expression of PD-1 and PD-L1 in NSCLC and clinicopathologic feature, EGFR gene mutation.

Methods: The protein expression of PD-1 and PD-L1 was detected by immunohistochemistry from 127 patients with NSCLC and EGFR gene mutation was detected by quantitative polymerase chain reaction (qPCR) to analyze its relation with clinicopathologic feature. Also, the correlation between protein expression of PD-1 and PD-L1 and EGFR mutation.

Results: The PD-1 positive expression in NSCLC tumor cells and tumor infiltrating immune cells is 53.5% (68/127), PD-L1 is 57.5% (73/127). The PD-1 and PD-L1 expression significantly higher in well-differentiated and moderately-differentiated carcinoma than poorly differentiated carcinoma, I+II than III+IV in clinical staging (P<0.05). The EGFR mutation rate was 46.5% (59/127), correlate with female, without smoking history, adenocarcinoma and well-differentiated and moderately-differentiated patients respectively higher than male, smoking history, squamous carcinoma and poorly differentiated patients (P<0.05). The protein expression of PD-L1 and PD-1 had the consistency in NSCLC patients (kappa=0.107,5, P=0.487). There was a negative correlation between the EGFR mutation and PD-1 and PD-L1 expression (Φ=-0.209, Φ=-0.221, P<0.05). Follow-up of NSCLC patients, the median total survival in under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, with PD-L1 expression patients respectively higher than over the age of 65, squamous carcinoma, poorly differentiated, without PD-L1 expression patients (P<0.05). The median survival of hypo expression patients of PD-L1 significantly higher than hyper expression patient (P=0.04).

Conclusions: According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503982PMC
September 2021

Phase 2a, open-label, dose-escalating, multi-center pharmacokinetic study of favipiravir (T-705) in combination with oseltamivir in patients with severe influenza.

EBioMedicine 2020 Dec 22;62:103125. Epub 2020 Nov 22.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Department of Respiratory Medicine, Capital Medical University, Beijing, China.

Background: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19.

Methods: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (C) ≥20 mg/L at all measured time points after the second dose.

Results: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir C decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved C ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza.

Conclusion: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.
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http://dx.doi.org/10.1016/j.ebiom.2020.103125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689521PMC
December 2020

Direct quantification of anorethidrani disuccinate and determination of sterol metabolites by chemical derivatization combined with LC-MS/MS: Application to a Phase I pharmacokinetic study in humans.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Nov 1;1157:122290. Epub 2020 Aug 1.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201210, China. Electronic address:

Anorethidrani disuccinate (ACP) is a domestically designed A-decarbonized steroid that is currently being investigated in Phase I clinical trials for the treatment of solid tumors. Only the parent drug exhibited antitumor activity; its sterol metabolite M2 showed obvious antiestrogenic effects. We have developed a rapid, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the direct quantification of ACP and a chemical derivatization method that can be used to quantify M2 derivatized with glycidyl trimethyl ammonium chloride (GTMA). A simple protein precipitation procedure was performed to quantify ACP. Injections were obtained within 3.5 min on an Eclipse Plus Phenyl-Hexyl column (50 mm × 2.1 mm i.d., 1.8 μm) with gradient elution; the calibration curve was linear over the range of 2.00-8000 ng/mL. For quantification of M2 in plasma, analytes were extracted by protein precipitation and converted to their GTMA derivatives at 60 °C for 2 h at pH 12; the analytes and coelutants were separated on a Luna C8(2) column (50 mm × 2.0 mm i.d., 5.0 μm). The precision (RSD) and accuracy (RE) of the intra- and interday determinations were within 10%. The derivatization procedure is a novel method for sterol determination by LC-MS/MS. The results confirmed the usefulness of this method for characterizing the pharmacokinetic profiles of ACP and its major metabolite M2 in a Phase I pharmacokinetic study.
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http://dx.doi.org/10.1016/j.jchromb.2020.122290DOI Listing
November 2020

The Expression of Perilipin Family Proteins can be used as Diagnostic Markers of Liposarcoma and to Differentiate Subtypes.

J Cancer 2020 7;11(14):4081-4090. Epub 2020 Apr 7.

Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, China.

: Liposarcoma is a mesenchymal malignant tumor characterized by adipocyte differentiation which is divided into four subtypes with different prognosis. Accurate histopathological diagnosis is essential for precise treatment. Perilipins, including PLIN1, PLIN2, PLIN3, PLIN4, PLIN5, is a family of lipid droplet-associated proteins that participate in lipid metabolism regulation. The role that perilipins play in sarcomas is not clear. This study aims to assess perilipins expression in subtypes of liposarcoma and various non-lipomatous sarcomas. : A large set of 245 soft tissue sarcoma paraffin-embedded samples including 66 liposarcomas and 179 non-lipomatous sarcomas were collected for tissue microarray and immunohistochemistry to assess perilipins expression. : PLIN1 expression was shown in most liposarcomas (41/66) and was absent in non-lipomatous sarcomas (0/179). PLIN4 expression was shown in some liposarcomas (21/66) and was almost negative in non-lipomatous sarcomas (2/179). PLIN1 and PLIN4 expressions in liposarcoma were higher (both P<0.001) than those in non-lipomatous sarcoma. Both PLIN1 and PLIN4 also had a significant difference in liposarcoma subtypes (both P<0.001). PLIN2, PLIN3 and PLIN5 were widely expressed in liposarcomas, rhabdomyosarcomas, leiomyosarcomas, dermatofibrosarcoma protuberans, undifferentiated sarcomas, fibrosarcomas, Ewing's sarcomas and epithelioid sarcomas. PLIN2, PLIN3 and PLIN5 expressions were significantly different among non-lipomatous sarcoma (all P<0.01). Except for PLIN3, the expression of the other four perilipin members in liposarcoma was pairwise related. : PLIN1 and PLIN4 can be used as diagnostic markers of liposarcoma and to differentiate liposarcoma subtypes. The combined application of whole perilipin family immunohistochemistry may help to distinguish differently differentiated sarcomas.
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http://dx.doi.org/10.7150/jca.41736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196260PMC
April 2020

Prognostic value of cripto-1 expression in non-small-cell lung cancer patients: a systematic review and meta-analysis.

Biomark Med 2020 03 5;14(4):317-329. Epub 2020 Mar 5.

Department of Pathology, The First Affiliated Hospital to Shihezi University School of Medicine, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.

This systematic review and meta-analysis aimed to analyze the association between cripto-1 expression and prognosis as well as clinicopathological features of non-small-cell lung cancer (NSCLC) patients. The electronic databases for all articles about NSCLC and cripto-1 expression were searched. Twelve articles were enrolled in this meta-analysis (3130 samples). In NSCLC patients, cripto-1 was expressed higher than in normal tissues. Cripto-1 expression was closely correlated with lymph node metastasis, histological differentiation and advanced clinical stage of NSCLC patients, but not related to smoking, age and gender. Pooled hazard ratios found that high cripto-1 expression had poor overall survival and progression-free survival. Cripto-1 could serve as a novel biomarker for predicting poor prognosis in NSCLC patients.
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http://dx.doi.org/10.2217/bmm-2019-0159DOI Listing
March 2020

Ewing's sarcoma/peripheral primitive neuroectodermal tumor with extraskeletal myxoid chondrosarcoma-like areas: a case report.

Int J Clin Exp Pathol 2019 1;12(10):3940-3943. Epub 2019 Oct 1.

Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi 832002, Xinjiang, China.

Introduction: Ewing's sarcoma (EWS)/peripheral primitive neuroectodermal tumor (pPNET) (EWS/pPNET) is a group of highly aggressive small round cell tumors of the bone or soft tissue with high metastatic potential and an aggressive course in children and young adults. EWS/pPNET microscopically does not often have a myxoid background.

Case Description: We report an EWS/pPNET, which exhibited an unusual morphology with cells having an acidophilic cytoplasm set in a myxoid background, raising the possibility of extraskeletal myxoid chondrosarcoma (EMC). A reverse transcription-polymerase chain reaction analysis confirmed the presence of an EWS-FLI1 fusion transcript.

Conclusions: Morphology, immunohistochemistry, and molecular assays may be necessary to avoid a potential diagnostic pitfall as EWS/pPNET with a myxoid background may histologically resemble an EMC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949751PMC
October 2019

CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis.

BMC Med Genomics 2019 12 23;12(1):198. Epub 2019 Dec 23.

Department of Pathology, Shihezi University School of Medicine and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Chinese Ministry of Education, Shihezi, Xinjiang, 832002, China.

Background: Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance.

Methods: The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs. The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan-Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC).

Results: A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient's onset.

Conclusions: These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.
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http://dx.doi.org/10.1186/s12920-019-0645-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929508PMC
December 2019

Ewing's sarcoma of the cervix: A case report and review of literature.

Histol Histopathol 2020 May 5;35(5):475-480. Epub 2019 Nov 5.

Department of Pathology, Shihezi University School of Medicine and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Chinese Ministry of Education, Shihezi, Xinjiang, China.

Ewing's sarcoma (ES) is a small cell malignant tumor that occurs in the bone of children or adolescents. ES can also occur in extraskeletal organs, such as the pancreas, thyroid, liver, proximal phalanx, and, rarely, cervix. Only 15 published case reports have discussed ES arising in the cervix. We report a 76-year-old woman who had groin mass. ES was diagnosed in accordance with morphological and immunohistochemical maps. Fluorescence in situ hybridization and RT-PCR (reverse transcription PCR) revealed ESWR1 gene rearrangement and fusion gene formation (EWS-FLI-1), both of which confirmed the diagnosis of ES. Although the patient underwent surgical resection, the patient died without chemotherapy and radiotherapy. This case is the first one to involve a patient aged over 70 years and the fifth one to show metastasis occurrence.
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http://dx.doi.org/10.14670/HH-18-181DOI Listing
May 2020

Enantioselective determination of ketamine in dog plasma by chiral liquid chromatography-tandem mass spectrometry.

Biomed Chromatogr 2019 Sep 2;33(9):e4578. Epub 2019 Jun 2.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Ketamine is an N-methyl-d-aspartate receptor antagonist that is usually used clinically as a racemic mixture. Its two enantiomers exhibit different pharmacological activities. To determine whether the enantiomers have different pharmacokinetic profiles, a chiral liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of ketamine enantiomers in dog plasma. The enantiomers of ketamine were extracted from 50 μL of plasma by methyl tert-butyl ether. Adequate chromatographic retention and baseline resolution of the enantiomers were achieved within a runtime of 5 min on a chiral column coated with polysaccharide derivatives, using a gradient mobile phase of acetonitrile and 10 mm ammonium bicarbonate aqueous solution. Ketamine enantiomers were detected by mass spectrometry with multiple reaction monitoring mode using the transitions of m/z 238.3 → 125.9 for the analytes and m/z 237.1 → 194.1 for carbamazepine (internal standard). The method was linear over the concentration range from 0.5 to 500 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was 0.5 ng/mL. The intra- and inter-day precision was <7.3% and 8.5% for R- and S-ketamine, respectively. The accuracy was 92.9-110.4% for R-ketamine and 99.8-102.4% for S-ketamine. The method was successfully applied to characterize the stereoselective pharmacokinetic profiles of ketamine in beagle dogs.
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http://dx.doi.org/10.1002/bmc.4578DOI Listing
September 2019

Matrix metalloproteinase-14 induces epithelial-to-mesenchymal transition in synovial sarcoma.

Hum Pathol 2018 10 20;80:201-209. Epub 2018 Jun 20.

Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China; Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. Electronic address:

Synovial sarcoma (SS) is a highly aggressive malignant soft tissue sarcoma with typical characteristics of both epithelial and mesenchymal differentiation. Matrix metalloproteinase-14 (MMP-14) is reported to play an important role in some of these tumors. It induces epithelial-to-mesenchymal transition (EMT) in some carcinomas, such as breast and prostate cancers. However, the role of MMP-14 in the pathogenesis of SS remains unclear. Therefore, we investigated the role of MMP-14 and EMT/mesenchymal-to-epithelial transition in SS. The expression of MMP-14 and EMT-related proteins was determined in 37 SS cases and transfected cells by immunohistochemistry staining and Western blotting. The invasion ability of transfected cells was determined by transwell invasion assay. The expression rates of MMP-14, E-cadherin, N-cadherin, and vimentin were 75.7%, 54.1%, 75.7%, and 100%, respectively, in the cases of SS. The expression of MMP-14 correlated negatively with E-cadherin and positively with N-cadherin in monophasic fibrous SS. The MMP-14 protein expression was higher in stage III/IV than in stage I/II. After MMP-14 was transfected into SW982 cells, MMP-14, N-cadherin, and vimentin expression was up-regulated, and E-cadherin expression was down-regulated. High expression of MMP-14 enhanced the invasive ability of SW982 cells. Our findings suggest that MMP-14 enhances the invasive ability of SW982 cells by inducing EMT. By this action, it may play an important role in the occurrence and development of SS.
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http://dx.doi.org/10.1016/j.humpath.2017.12.031DOI Listing
October 2018

Overexpression of Polo-like kinase1 (PLK1) in chondrosarcoma and its implications for cancer progression.

Int J Clin Exp Pathol 2018 1;11(3):1707-1711. Epub 2018 Mar 1.

Department of Pathology, First Affiliated Hospital, Shihezi University Shihezi, China.

Polo-like kinase1 (PLK1) is a new therapeutic target for osteosarcoma with good application prospects. Whether PLK1 is highly expressed in chondrosarcoma and whether PLK1 can be a potential therapeutic target for chondrosarcoma are worth exploring. However, PLK1 expression in chondrosarcoma is scarcely investigated. Therefore, we collected 11 cases of chondrosarcoma and 26 cases of osteochondroma with complete clinical pathological data and used immunohistochemical staining to detect the expression of PLK1 in chondrosarcoma and osteochondroma and then studied its significance and relationship with clinical pathological parameters. Our results showed that the positive expression rate of PLK1 in chondrosarcoma tissue (90.91%, 10/11) was significantly higher than the rate of osteochondroma tissues (53.85%, 14/26) (P<0.05). The expression of PLK1 enhanced gradually with the increase in histological grade (P<0.05). PLK1 was highly expressed in chondrosarcoma, and the high expression of PLK1 might be involved in cartilage tumor malignant progression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958127PMC
March 2018

Primary Cervical Malignant Melanoma: 2 Cases and a Literature Review.

Int J Gynecol Pathol 2019 Mar;38(2):196-203

Department of Pathology, Shihezi University School of Medicine, Xinjiang (C.Y., Y.Z., L.T., H.Z., Y.R., W.L., J.J., J.Z., W.Z., W.J., F.L.) Department of Pathology, Wuxi Maternity and Child Health Hospital, Nanjing Medical University, Jiangsu (A.Y.) Department of Pathology, Beijing Chao-Yang Hospital, Beijing (F.L.), China.

Primary cervical malignant melanoma (MM) is an extremely rare tumor, and we are only aware of 44 reported cases. Further information is needed with regard to this disease's clinicopathologic features. Two patients (55 and 81 yr old) with postmenopausal vaginal bleeding were diagnosed with primary cervical MM on the basis of hematoxylin-eosin staining and immunohistochemistry findings. Our literature review revealed that the average age in cases of primary cervical MM was 59 yr (range, 34-81 yr); 93% of patients presented with vaginal bleeding, and 82% of patients were diagnosed at an early clinical stage (International Federation of Gynecology and Obstetrics stages I-II). Primary cervical MM is an extremely rare cervical tumor and is associated with a poor prognosis. Histologic morphology and immunohistochemistry are very important considerations for diagnosing this disease, which must be differentiated from cervical undifferentiated carcinoma, leiomyosarcoma, and malignant peripheral schwannoma.
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http://dx.doi.org/10.1097/PGP.0000000000000480DOI Listing
March 2019

Ovarian microcystic stromal tumor with undetermined potential: case study with molecular analysis and literature review.

Hum Pathol 2018 08 17;78:171-176. Epub 2018 Feb 17.

Department of Pathology, Shihezi University School of Medicine, Xinjiang 832002, China; Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:

Ovarian microcystic stromal tumor is a relatively rare tumor type. This tumor is characterized by a unique microcyst structure, and essentially all tumors show benign biological behavior. Here, we report a case with a primary ovarian microcystic stromal tumor that experienced recurrence. Pathological findings showed that the original tumor, relapsed tumor in the ovary, and the recurrent tumor in the iliac fossa presented similar histologic features. The tumor mainly consisted of microcysts, solid cellular regions, and a fibrous stroma. Immunohistochemically, the tumor cells were positive for β-catenin, CD10, vimentin, and WT-1. Mutational analysis revealed a missense mutation (c.1590C>T; pG530E) in exon 15 of the APC gene and another missense mutation (c.740G>A; pA247V) in exon 1 of the KRAS gene. We also reviewed other published cases to evaluate the prognosis and treatment. This is the first report to describe a microcystic stromal tumor of the ovary presenting with undetermined biological potential.
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http://dx.doi.org/10.1016/j.humpath.2018.02.012DOI Listing
August 2018

Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9.

J Exp Clin Cancer Res 2017 Dec 13;36(1):182. Epub 2017 Dec 13.

Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.

Background: Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and their therapeutic relevance in ESCC.

Methods: Linc-ROR and SOX9 expression were examined in ESCC specimens, cell lines, and cultured tumorspheres. We investigated the effects of linc-ROR on SOX9 expression and malignant phenotypes by CCK8, colony formation, Transwell, and sphere-forming assay. The linc-ROR/SOX9 interaction mediated by multiple microRNAs (miRNAs) was confirmed by bioinformatic analysis, luciferase assay, and RNA-binding protein immunoprecipitation, transient overexpression or antagonizing endogenous candidate miRNAs. The effect of linc-ROR depletion on tumor growth was assessed by xenograft assay.

Results: A positive correlation between linc-ROR and SOX9 expression was found in clinical ESCC specimens (r = 0.562, P = 0.036), cell lines, and tumorspheres. Silencing of linc-ROR significantly inhibited cell proliferation, motility, chemoresistance, and self-renewal capacity. Mechanistically, linc-ROR modulating the derepression of SOX9 by directly sponging multiple miRNAs including miR-15b, miR-33a, miR-129, miR-145, and miR-206. Antagonizing these miRNAs counteracted with linc-ROR silencing, whereas the repression of SOX9 abrogated malignant phenotypes induced by the cocktail of miRNA inhibitors. Moreover, linc-ROR disruption was sufficient to attenuate tumor growth and cancer stem cell marker expression in vivo.

Conclusions: Our results demonstrate that the linc-ROR-miRNA-SOX9 regulatory network may represent a novel therapeutic target for ESCC.
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http://dx.doi.org/10.1186/s13046-017-0658-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727696PMC
December 2017

Arylacetamide Deacetylase Is Involved in Vicagrel Bioactivation in Humans.

Front Pharmacol 2017 20;8:846. Epub 2017 Nov 20.

State Key Laboratory of Drug Research, Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Vicagrel, a structural analog of clopidogrel, is now being developed as a thienopyridine antiplatelet agent in a phase II clinical trial in China. Some studies have shown that vicagrel undergoes complete first-pass metabolism in human intestine, generating the hydrolytic metabolite 2-oxo-clopidogrel via carboxylesterase-2 (CES2) and subsequently the active metabolite H4 via CYP450s. This study aimed to identify hydrolases other than CES2 that are involved in the bioactivation of vicagrel in human intestine. This study is the first to determine that human arylacetamide deacetylase (AADAC) is involved in 2-oxo-clopidogrel production from vicagrel in human intestine. hydrolytic kinetics were determined in human intestine microsomes and recombinant human CES and AADAC. The calculated contribution of CES2 and AADAC to vicagrel hydrolysis was 44.2 and 53.1% in human intestine, respectively. The AADAC-selective inhibitors vinblastine and eserine effectively inhibited vicagrel hydrolysis . In addition to CES2, human intestine AADAC was involved in vicagrel hydrolytic activation before it entered systemic circulation. In addition, simvastatin efficiently inhibited the production of both 2-oxo-clopidogrel and active H4; further clinical trials are needed to determine whether the hydrolytic activation of vicagrel is influenced by coadministration with simvastatin. This study deepens the understanding of the bioactivation and metabolism properties of vicagrel in humans, which can help further understand the bioactivation mechanism of vicagrel and the variations in the treatment responses to vicagrel and clopidogrel.
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http://dx.doi.org/10.3389/fphar.2017.00846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701912PMC
November 2017

Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal squamous cell carcinoma in the Kazakh population but is not associated with HPV infection.

PLoS One 2017 26;12(10):e0186319. Epub 2017 Oct 26.

Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.

The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186319PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657974PMC
November 2017

Exploring the Histogenesis and Diagnostic Strategy Using Immunoassay and RT-PCR in Alveolar Soft Part Sarcoma.

Pathol Oncol Res 2018 Jul 1;24(3):593-600. Epub 2017 Aug 1.

Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma, but it's easily misdiagnosed in rare locations. The derivation of ASPS is still uncertain, therefore we conducted this study to explore the histogenesis of ASPS by analyzing stem cell markers (ALDH1, CD29, CD133 and Nestin). Protein TFE3 and fusion gene ASPS-TFE3 were tested in paraffin to explore diagnostic strategy and molecular pathological features. In this study, nine cases of ASPS were immunostained with stem cell surface markers (ALDH1, CD29, CD133 and Nestin) and protein TFE3. Seven cases of ASPS mRNA were successfully extracted from nine paraffin-embedded tissues. The expression of fusion gene ASPL-TFE3 was examined by reverse transcriptase-polymerase chain reaction. The immunohistochemical staining of nine patients showed that CD29 and Nestin were negative in all nine cases (0/9). CD133 was weakly positive in one cases (1/9) and ALDH1 was weakly positive in one cases (1/9). TFE3 was positive in nine cases (9/9). Seven paraffin tissues could be successfully extracted with mRNA in nine cases. The results of Reverse Transcription Polymerase Chain Reaction (RT-PCR) showed that ASPL-TFE3 fusion transcripts could be tested in the seven cases (four cases being type 2 and three cases being type 1). The positive rate of CD133 and ALDH1 were less than 1% and the expression of CD29 and Nestin were negative in ASPS. Immunohistochemistry results indicated that the histogenesis of ASPS maybe not derive from mesenchymal stem cells. Immunohistochemistry staining showed that TFE3 protein expression was highly sensitive in ASPS. Furthermore, RT-PCR results showed that fusion gene ASPL-TFE3 (ASPL-TFE3 type 1 and ASPL-TFE3 type 2) was expressed in ASPS, which could provide information for clinical molecular pathological diagnosis and improve the diagnosis rate of rare atypical ASPS.
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http://dx.doi.org/10.1007/s12253-017-0280-9DOI Listing
July 2018

Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans.

Xenobiotica 2018 May 7;48(5):533-540. Epub 2017 Jun 7.

a State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.

1. Anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate) is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans. 2. Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance was 684 ± 83 μL/min/mg protein, which was considerably higher than the value of intestine microsomes (94.6 ± 13.3 μL/min/mg protein). Carboxylesterase (CES) 1 has more contribution than CES2 in human liver. 3. Inhibition studies were performed using representative esterase inhibitors to confirm esterase isoforms involved in anordrin hydrolysis. Simvastatin strongly inhibited hydrolytic process of anordrin in liver and intestine microsomes, with IC values of 10.9 ± 0.1 and 6.94 ± 0.03 μM, respectively. 4. The present study investigated for the first time hydrolytic enzyme phenotypes of anordrin. Anordrin is predominantly catalyzed by CES1 and CES2 to generate the main active metabolite, anordiol. Moreover, anordrin and its metabolite anordiol can be altered by esterase inhibitors, such as simvastatin, upon exposure in vivo.
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http://dx.doi.org/10.1080/00498254.2017.1333658DOI Listing
May 2018

Evaluation of expression of cancer stem cell markers and fusion gene in synovial sarcoma: Insights into histogenesis and pathogenesis.

Oncol Rep 2017 Jun 2;37(6):3351-3360. Epub 2017 May 2.

Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.

Synovial sarcoma (SS) is an aggressive soft tissue tumor, with uncertain histological and cellular origin. SYT-SSX is considered to be responsible for sarcoma initiation and progression. The histogenesis and pathogenesis of this tumor are poorly understood, and prognosis of patients of SS is unsatisfactory. Recent studies have shown an association of cancer stem cells with the initiation and development of tumors. We explored immunohistochemical expression level of stem cell associated markers to determine the possible histogenesis and pathogenesis of SS. Fusion gene SYT-SSX was tested to assess diagnostic value and the molecular pathological features. We obtained the clinicopathological data of 20 SS patients, immunohistochemical staining were used to evaluate stem cell-associated markers included CD133, CD29, CD44, nestin, and ALDH1. Fusion gene SYT-SSX was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Twenty SS cases were observed and the positive immuno-expression results showed CD133 (17/20), CD29 (11/20), CD44 (11/20), nestin (6/20), and ALDH1 (5/20). Fusion gene SYT-SSX was successfully detected by RT-PCR from 18 available samples. The expression of stem cell-associated markers (CD133, CD29, CD44, Nestin, and ALDH1) and clinical data (age, gender, sites, tumor size, histological type, tumor stage, and distant metastases) did not show statistically significant relationship (P>0.05), whereas, statistically significance between ALDH1 and metastases was observed (P<0.01). The ALDH1 positive synovial sarcoma (ALDH1+ SS) cases had significantly poor prognosis compared to ALDH1 negative synovial sarcoma (ALDH1- SS) cases (P<0.05). Immunohistochemical results indicated different expression levels of the five cancer stem cell markers in SS suggesting that SS may arise from cancer stem cells. Fusion gene SYT-SSX may play a critical role in the molecular pathological of SS.
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http://dx.doi.org/10.3892/or.2017.5617DOI Listing
June 2017

Probabilistic Neighborhood-Based Data Collection Algorithms for 3D Underwater Acoustic Sensor Networks.

Sensors (Basel) 2017 Feb 8;17(2). Epub 2017 Feb 8.

School of Information Science and Engineering, Shenyang Ligong University, China.

Marine environmental monitoring provides crucial information and support for the exploitation, utilization, and protection of marine resources. With the rapid development of information technology, the development of three-dimensional underwater acoustic sensor networks (3D UASNs) provides a novel strategy to acquire marine environment information conveniently, efficiently and accurately. However, the specific propagation effects of acoustic communication channel lead to decreased successful information delivery probability with increased distance. Therefore, we investigate two probabilistic neighborhood-based data collection algorithms for 3D UASNs which are based on a probabilistic acoustic communication model instead of the traditional deterministic acoustic communication model. An autonomous underwater vehicle (AUV) is employed to traverse along the designed path to collect data from neighborhoods. For 3D UASNs without prior deployment knowledge, partitioning the network into grids can allow the AUV to visit the central location of each grid for data collection. For 3D UASNs in which the deployment knowledge is known in advance, the AUV only needs to visit several selected locations by constructing a minimum probabilistic neighborhood covering set to reduce data latency. Otherwise, by increasing the transmission rounds, our proposed algorithms can provide a tradeoff between data collection latency and information gain. These algorithms are compared with basic Nearest-neighbor Heuristic algorithm via simulations. Simulation analyses show that our proposed algorithms can efficiently reduce the average data collection completion time, corresponding to a decrease of data latency.
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http://dx.doi.org/10.3390/s17020316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336108PMC
February 2017

A Greedy Scanning Data Collection Strategy for Large-Scale Wireless Sensor Networks with a Mobile Sink.

Sensors (Basel) 2016 Sep 6;16(9). Epub 2016 Sep 6.

National Institute of Telecommunications (Inatel), Minas Gerais 30000-000, Brazil.

Mobile sink is widely used for data collection in wireless sensor networks. It can avoid 'hot spot' problems but energy consumption caused by multihop transmission is still inefficient in real-time application scenarios. In this paper, a greedy scanning data collection strategy (GSDCS) is proposed, and we focus on how to reduce routing energy consumption by shortening total length of routing paths. We propose that the mobile sink adjusts its trajectory dynamically according to the changes of network, instead of predetermined trajectory or random walk. Next, the mobile sink determines which area has more source nodes, then it moves toward this area. The benefit of GSDCS is that most source nodes are no longer needed to upload sensory data for long distances. Especially in event-driven application scenarios, when event area changes, the mobile sink could arrive at the new event area where most source nodes are located currently. Hence energy can be saved. Analytical and simulation results show that compared with existing work, our GSDCS has a better performance in specific application scenarios.
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http://dx.doi.org/10.3390/s16091432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038710PMC
September 2016

Effect of N-methyl deuteration on metabolism and pharmacokinetics of enzalutamide.

Drug Des Devel Ther 2016 7;10:2181-91. Epub 2016 Jul 7.

University of Chinese Academy of Sciences, Beijing; Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences; Hinova Pharmaceuticals Inc, Chengdu, People's Republic of China.

Background: The replacement of hydrogen with deuterium invokes a kinetic isotope effect. Thus, this method is an attractive way to slow down the metabolic rate and modulate pharmacokinetics.

Purpose: Enzalutamide (ENT) acts as a competitive inhibitor of the androgen receptor and has been approved for the treatment of metastatic castration-resistant prostate cancer by the US Food and Drug Administration in 2012. To attenuate the N-demethylation pathway, hydrogen atoms of the N-CH3 moiety were replaced by the relatively stable isotope deuterium, which showed similar pharmacological activities but exhibited favorable pharmacokinetic properties.

Methods: We estimated in vitro and in vivo pharmacokinetic parameters for ENT and its deuterated analog (d3-ENT). For in vitro studies, intrinsic primary isotope effects (K H/K D) were determined by the ratio of intrinsic clearance (CLint) obtained for ENT and d3-ENT. The CLint values were obtained by the substrate depletion method. For in vivo studies, ENT and d3-ENT were orally given to male Sprague Dawley rats separately and simultaneously to assess the disposition and metabolism of them. We also investigated the main metabolic pathway of ENT by comparing the rate of oxidation and hydrolysis in vitro.

Results: The in vitro CLint (maximum velocity/Michaelis constant [V max/K m]) of d3-ENT in rat and human liver microsomes were 49.7% and 72.9% lower than those of the non-deuterated compound, corresponding to the K H/K D value of ~2. The maximum observed plasma concentration, C max, and area under the plasma concentration -time curve from time zero to the last measurable sampling time point (AUC0-t) were 35% and 102% higher than those of ENT when orally administered to rats (10 mg/kg). The exposure of the N-demethyl metabolite M2 was eightfold lower, whereas that of the amide hydrolysis metabolite M1 and other minor metabolites was unchanged. The observed hydrolysis rate of M2 was at least ten times higher than that of ENT and d3-ENT in rat plasma.

Conclusion: ENT was mainly metabolized through the "parent→M2→M1" pathway based on in vitro and in vivo elimination behavior. The observed in vitro deuterium isotope effect translated into increased exposure of the deuterated analog in rats. Once the carbon-hydrogen was replaced with carbon-deuterium (C-D) bonds, the major metabolic pathway was retarded because of the relatively stable C-D bonds. The systemic exposure to d3-ENT can increase in humans, so the dose requirements can be reduced appropriately.
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http://dx.doi.org/10.2147/DDDT.S111352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939996PMC
May 2017

p53 expression but not p16(INK4A) correlates with human papillomavirus-associated esophageal squamous cell carcinoma in Kazakh population.

Infect Agent Cancer 2016 13;11:19. Epub 2016 Apr 13.

Department of Pathology and Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang China.

Background: p16(INK4A) expression has been used as a surrogate marker for human papillomavirus (HPV) infection in cervical cancer and head and neck cancer. p53 has also been reported as a feasible marker to identify HPV-positive oropharyngeal carcinoma and penile lesions. This study aimed to investigate p16(INK4A) and p53 expression levels and their correlation with HPV status and clinical parameters in Kazakh patients with esophageal squamous cell carcinoma.

Methods: Immunohistochemical expression of p16 (INK4A) and p53 were evaluated in 163 cases of esophageal squamous cell carcinoma in Kazakh patients. The presence of HPV DNA was detected by polymerase chain reaction.

Results: p16 (INK4A) -positive expression was detected in 19.0 % of patients, and its expression was significantly correlated with a lower frequency of lymph node metastasis (p = 0.038). By contrast no significant association was found between p16 (INK4A) -positive expression and HPV status (correlation coefficient = -0.062, p = 0.499). p16 (INK4A) -positive expression did not affect the odds of tumors being HPV positive (odds ratio [OR] = 0.727 with 95 % confidence interval [CI] = 0.288-1.836). The sensitivity of p16 (INK4A) -positive expression as an HPV marker was 0.164, with a specificity of 0.788 and a positive predictive value of 0.391. p53-positive expression was present in 88.3 % of all cases. Although no significant correlation with available clinical parameters was found, a significantly inverse correlation was observed between p53 expression and HPV status (correlation coefficient = -0.186, p = 0.039). Moreover, p53-positive expression decreased the odds of tumors being HPV positive (OR = 0.292 with 95 % CI = 0.086-0.990). The sensitivity of p53-negative expression as an HPV marker was 0.179, with a specificity of 0.940 and a positive predictive value of 0.714. The overall HPV prevalence was high (45.5 %) in Kazakh patients, with no significant association between HPV positivity and available clinical parameters or combined p16 (INK4A) /p53 expression.

Conclusions: p16 (INK4A) -positive expression was associated with lymph node metastasis. Results indicate that p53-negative expression and not p16 (INK4A) -positive expression may be used as a marker for HPV status in ESCC; however, this finding requires further studies for validation.
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http://dx.doi.org/10.1186/s13027-016-0065-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830030PMC
April 2016

MAP3K3 overexpression is associated with poor survival in ovarian carcinoma.

Hum Pathol 2016 Apr 30;50:162-9. Epub 2015 Dec 30.

Tongji Hospital Cancer Center, Tongji Medical College, Huazhong University of Science and Technology, Hubei, 430000, China; Department of Pathology, Shihezi University School of Medicine, Xinjiang, 832002, China; Department of Pathology, Beijing ChaoYang Hospital, Beijing, 100020, China. Electronic address:

Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is ubiquitously expressed in numerous tissues and is activated by various extracellular stimuli to regulate processes, such as cell proliferation and differentiation. Recent studies have identified potentially pathologic conditions of MAP3K3 as an oncogene that promotes tumor progression and metastasis in a number of malignancies. However, the clinical significance of MAP3K3 expression in ovarian carcinoma (OC) remains unclear. In this study, the correlation between MAP3K3 expression and OC prognosis was assessed by immunohistochemistry. MAP3K3 overexpression was observed in 59.1% (55/93) of OCs and was significantly associated with histological type and grade, chemotherapy response, and challenge model (P < .05, respectively). MAP3K3 overexpression was also used as an independent prognostic marker for decreased disease-free survival and overall survival. In OC cell lines, MAP3K3 expression was evaluated by Western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence. High MAP3K3 expression is significantly detected in SKOV3, C13*, and A2780 cells. All these findings suggested that MAP3K3 overexpression is an independent poor prognostic indicator of OC and can be a clinically effective biomarker of OC.
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http://dx.doi.org/10.1016/j.humpath.2015.12.011DOI Listing
April 2016

A Collaborative Secure Localization Algorithm Based on Trust Model in Underwater Wireless Sensor Networks.

Sensors (Basel) 2016 Feb 16;16(2):229. Epub 2016 Feb 16.

Instituto de Telecomunicações, University of Beira Interior, Portugal and University of Fortaleza (UNIFOR), Ceará 60811-905, Brazil.

Localization is one of the hottest research topics in Underwater Wireless Sensor Networks (UWSNs), since many important applications of UWSNs, e.g., event sensing, target tracking and monitoring, require location information of sensor nodes. Nowadays, a large number of localization algorithms have been proposed for UWSNs. How to improve location accuracy are well studied. However, few of them take location reliability or security into consideration. In this paper, we propose a Collaborative Secure Localization algorithm based on Trust model (CSLT) for UWSNs to ensure location security. Based on the trust model, the secure localization process can be divided into the following five sub-processes: trust evaluation of anchor nodes, initial localization of unknown nodes, trust evaluation of reference nodes, selection of reference node, and secondary localization of unknown node. Simulation results demonstrate that the proposed CSLT algorithm performs better than the compared related works in terms of location security, average localization accuracy and localization ratio.
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http://dx.doi.org/10.3390/s16020229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801605PMC
February 2016

Effect of TGF-β1 on the Migration and Recruitment of Mesenchymal Stem Cells after Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14.

Sci Rep 2016 Feb 16;6:21176. Epub 2016 Feb 16.

Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, 59 North 2nd Road, Shihezi, Xinjiang 832002, China.

Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-β1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury, and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-β1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-β1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-β1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29, and Sca1(+)CD29(+)CD11b/c(-)CD45(-). Intimal hyperplasia was reduced in SB- and rhTGF-β1-treated rats. The expression of TGF-β1, TGF-β1RI, and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF-β1 administration decreased the expression of TGF-β1/Smad pathway proteins, except for TGF-β1RI. Nestin and CD29 expression and the number of Sca1(+)CD29(+)CD11b(-)CD45(-) cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-β1 administration. These results suggest that TGF-β1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling.
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http://dx.doi.org/10.1038/srep21176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754777PMC
February 2016

Expression of CD44 and CD29 by PEComa cells suggests their possible origin of mesenchymal stem cells.

Int J Clin Exp Pathol 2015 1;8(10):13023-33. Epub 2015 Oct 1.

Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine 59 North 2nd Road, Shihezi 832002, Xinjiang, China.

Background: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell (PEC) co-expresses melanocytic and muscle markers. Since no normal counterpart to the PEC has ever been identified in any normal tissue, the cell origin of these tumors is still uncertain. Although, several hypotheses have recently been advanced to explain the histogenesis of PEComa, it remains unclear.

Methods: The aim of this study was to discuss whether differential expression of stem cell-associated proteins could be used to aid in determining the histogenesis of PEComa. For this purpose, we detected the immunoexpression of 5 kinds of stem cell markers on PEComas, including CD29, CD44, CD133, ALDH1, and nestin. In addition to observed histopathologic morphology, we also performed PEComa relevant clinical diagnostic markers (HMB-45, SMA, melan-A, Desmin, Ki-67, S-100 and TFE3) to identify whether they belonged to PEComas.

Results: Our study included 13 PEComa samples, and we obtained positive immunoexpression results as follows: CD29 (13/13), CD44 (8/13), ALDH1 (10/13), nestin (1/13), and CD133 (0/13).

Conclusions: Since CD44 and CD29 are surface proteins associated with MSCs, these results suggest that PEComa might arise from MSCs. However, whether MSCs are the origin of PEComa needs to be further explored in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680442PMC
October 2016
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