Publications by authors named "Hongxue Meng"

46 Publications

Interactive regulation of laryngeal cancer and neuroscience.

Biochim Biophys Acta Rev Cancer 2021 Jun 12;1876(1):188580. Epub 2021 Jun 12.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150081, China. Electronic address:

Nerve fibres are distributed throughout the body along with blood and lymphatic vessels. The intrinsic morphological characteristics of nerves and the general characteristics of secretions in the tumour microenvironment provide a solid theoretical basis for exploring how neuronal tissue can influence the progression of laryngeal cancer (LC). The central nervous system (CNS) and the peripheral nervous system (PNS) jointly control many aspects of cancer and have attracted widespread attention in the study of the progression, invasion and metastasis of tumour tissue banks. Stress activates the neuroendocrine response of the human hypothalamus-pituitary-adrenal (HPA) axis. LC cells induce nerve growth in the microenvironment by releasing neurotrophic factors (NTFs), and they can also stimulate neurite formation by secreting axons and axon guides. Conversely, nerve endings secrete factors that attract LC cells; this is known as perineural invasion (PNI) and promotes the progression of the associated cancer. In this paper, we summarize the systematic understanding of the role of neuroregulation in the LC tumour microenvironment (TME) and ways in which the TME accelerates nerve growth, which is closely related to the occurrence of LC.
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http://dx.doi.org/10.1016/j.bbcan.2021.188580DOI Listing
June 2021

A Novel Ferroptosis Related Gene Signature for Prognosis Prediction in Patients With Colon Cancer.

Front Oncol 2021 11;11:654076. Epub 2021 May 11.

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Purpose: Colon cancer (CC) is a serious disease burden. The prognosis of patients with CC is different, so looking for effective biomarkers to predict prognosis is vitally important. Ferroptosis is a promising therapeutic and diagnosis strategy in CC. However, the role of ferroptosis in prognosis of CC has not been studied. The aim of the study is to build a prognosis model related ferroptosis, and provide clues for further therapy of CC.

Methods: The RNA-seq data were from TCGA (training group) and GEO (testing group). The R language and Perl language were used to process and analyze data. LASSO regression analysis was used to build the prognosis model. ssGSEA was used to compare the immune status between two groups. Immunohistochemistry was used to detect expression of AKR1C1 and CARS1 in colon cancer tissues and adjacent tissues.

Results: The prognosis model consisted of five ferroptosis related genes (AKR1C1, ALOX12, FDFT1, ATP5MC3, and CARS1). The area under curve (AUC) at 1-, 2-, and 3-year were 0.668, 0.678, and 0.686, respectively. The high- and low-risk patients had significant survival probability and could be clearly distinguished by the PCA and t-SNE analysis. The multivariate cox regression analysis also showed the riskscore is an independent prognosis factor. Importantly, we found that the immune status between high- and low-risk patients were different obviously, such as CD8T cells. And STING, a new promising immune target, was also correlated to our signature genes statistically significantly.

Conclusion: Our ferroptosis prognosis signature could predict survival of CC patients to a certain degree. And the crosstalk between ferroptosis and immune, especially STING need further studies.
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http://dx.doi.org/10.3389/fonc.2021.654076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144717PMC
May 2021

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Biomaterials 2021 05 25;272:120777. Epub 2021 Mar 25.

Harbin Medical University Cancer Hospital, Harbin, 150080, China. Electronic address:

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4 and CD8 T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120777DOI Listing
May 2021

IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.

Mol Ther Oncolytics 2021 Mar 19;20:187-198. Epub 2020 Dec 19.

Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both and . We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.
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http://dx.doi.org/10.1016/j.omto.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889451PMC
March 2021

Prognostic value of platelet distribution width and mean platelet volume in patients with laryngeal cancer.

Future Oncol 2021 Mar 5;17(9):1025-1037. Epub 2021 Feb 5.

Department of Head & Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.

To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.
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http://dx.doi.org/10.2217/fon-2020-0658DOI Listing
March 2021

Correction: Tumor-associated macrophages promote tumor metastasis via the TGF-β/SOX9 axis in non-small cell lung cancer.

Oncotarget 2020 Dec 29;11(52):4845-4846. Epub 2020 Dec 29.

The Sixth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

[This corrects the article DOI: 10.18632/oncotarget.21068.].
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http://dx.doi.org/10.18632/oncotarget.27740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779255PMC
December 2020

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma.

Cancer Control 2020 Jan-Dec;27(1):1073274820978795

Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.
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http://dx.doi.org/10.1177/1073274820978795DOI Listing
December 2020

Ciliated Muconodular Papillary Tumors of the Lung: Distinct Molecular Features of an Insidious Tumor.

Front Genet 2020 29;11:579737. Epub 2020 Sep 29.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

Introduction: Ciliated muconodular papillary tumors (CMPTs) are rare special peripheral pulmonary nodule composed of different cell proportions, characterized by papillary structures and significant alveolar mucus. Because of their rarity, underrecognized processes, the full range clinical course and histogenesis of CMPTs remains uncertain.

Methods: Molecular features of 5 CMPTs cases (one case with mucinous adenocarcinoma simultaneously) were observed by whole exon gene detection. The histological features of CMPTs and the development trends of three major constituent cells were studied by immunohistochemistry and PCR.

Results: NGS revealed 77 gene mutations in the patient's tumor tissue and 31 mutations in the border tissue. TMB of CMPT tends to TMB of cancer tissues, and both are higher than normal tissues, CMPT share the same phylogenetic tree with cancer tissues. Moreover, PDL1, B7H3, and B7H4 were overexpressed in high columnar cells and eosinophilic ciliated cells of CMPT, tends to cancer tissues, while LAG3 and siglec15 were not found in CMPT.

Conclusion: The high prevalence of driver gene mutations in CMPTs, similar TMB and phylogenetic tree with cancer tissues indicate their malignant potential. Distinct molecular and immune check point features of each component support the notion that ciliated columnar cells in CMPT are insidious with immune escape.
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http://dx.doi.org/10.3389/fgene.2020.579737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550676PMC
September 2020

Hypoxia contributes to galectin-3 expression in renal carcinoma cells.

Eur J Pharmacol 2021 Jan 13;890:173637. Epub 2020 Oct 13.

Department of Urology Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China. Electronic address:

Galectin-3 is supposed as a prognostic factor and therapeutic target for many cancers. In a previous study, we have reported that galectin-3 was related to the development of renal cell cancer and served a therapeutic target for renal cell carcinoma (RCC). However, the mechanisms underlying the regulation of galectin-3 in RCC are still not known. In this study, we detected the expression of galectin-3 and hypoxia-inducible factor 1 (HIF-1) α in RCC using immunohistochemistry, and then conducted in vitro experiments to verify the regulation of galectin-3 by hypoxia in RCC. Our results showed that the expression of galectin-3 and HIF-1α were remarkably high in RCC tissues compared with those in the paracancerous tissues. Interestingly, hypoxia significantly promoted cytoplasmic and nuclear HIF-1α and galectin-3 expression in renal carcinoma cell lines, but not in renal tubular epithelial cell (HK-2). Renal carcinoma cell line (Caki-1), but not HK-2 showed significant increase of luciferase reporter activity of galectin-3 encoding the fragment from the site of -845 to +50 upon hypoxic insult. Moreover, HIF-1α overexpression vector promoted, while HIF-1α silencing vector reduced luciferase reporter activity of galectin-3 in Caki-1 and HK-2 cells in both normal and hypoxia conditions. A direct interaction of HIF-1α with Gal-3 promoter was also verified by electrophoretic mobility shift assay and chromatin immunoprecipitation. Together, our data indicated that hypoxia was critical for galectin-3 expression in RCC in a HIF-1α-dependent manner.
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http://dx.doi.org/10.1016/j.ejphar.2020.173637DOI Listing
January 2021

Evaluation of p16 in Epithelial Ovarian Cancer for a 10-Year Study in Northeast China: Significance of HPV in Correlation with PD-L1 Expression.

Cancer Manag Res 2020 3;12:6747-6753. Epub 2020 Aug 3.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China.

Background: Human papillomavirus (HPV) is a high-risk etiological factor for cervical and ovarian carcinomas. p16 protein can be used as a surrogate biomarker for HPV infection in high-risk tumors. A strong correlation between HPV infection and programmed death ligand 1 (PD-L1) protein expression has consistently been reported.

Objective: Given this background, this study investigates the prevalence, prognostic and clinicopathologic features of HPV-related epithelial ovarian cancer (EOC) for the last 10 years in Northeast China to elucidate the involvement of p16 in the PD-L1 protein expression, tumorigenesis, and progression of EOC.

Methods: Specimens from 310 patients diagnosed with EOC collected from 2006 to 2016 were analyzed by polymerase chain reaction (PCR) for HPV DNA, and overexpression of p16 by immunohistochemistry was also evaluated. Statistical analysis was performed to estimate the significant difference between HPV positive and negative patients, the correlation among HPV state, p16 and PD-L1 expression, and clinical presentation.

Results: Overexpression of p16 protein and HPV DNA were present in 100 (32.3%) of the 310 cases, and correlated with high PD-L1 expression. There was a good concordance between HPV positivity, p16 protein overexpression and PD-L1 expression. The etiological fraction of HPV in EOC is substantially higher in Northeast China than other cohorts previously reported.

Conclusion: Our study demonstrates that HPV infection and p16 overexpression is significantly associated with PD-LI expression in EOC, through the cooperative roles of dendritic cells (DCs) and IFN-γ, which may represent a promising strategy for therapeutic intervention in EOC.
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http://dx.doi.org/10.2147/CMAR.S262678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425106PMC
August 2020

Analysis of microbial changes in the tonsillar formalin-fixed paraffin-embedded tissue of Chinese patients with IgA nephropathy.

Pathol Res Pract 2020 Nov 15;216(11):153174. Epub 2020 Aug 15.

Department of pathology, Harbin Medical University, Heilongjiang, Harbin, 150081, PR China; Department of pathology, Harbin Medical University Cancer Hospital, Harbin Medical University, Heilongjiang, Harbin, 150081, PR China. Electronic address:

Background: Immunoglobulin A nephropathy (IgAN) is a prevalent chronic glomerular disease contribution to end-stage renal failure (ESRD). The tonsillar microbiota is closely associated with IgAN diseases based on the mucosal immune response. However, the composition and function of in tonsillar microbiota in participant patients with IgAN remains unknown. In this study, we detected the tonsillar microbiota changes of IgAN patients in Heilongjiang province located in northeast China.

Material And Methods: We collected from 21 patients with IgAN and 16 patients with chronic tonsillitis (CT) who had undergone tonsillectomy previously. Histological review of all samples from formalin-fixed paraffin-embedded (FFPE) tissue were performed. Extracted DNA from FFPE tissue blocks, after that V4 regions of 16S ribosomal RNA (rRNA) sequencing and comparative analyses of tonsillar flora between two groups were performed. The statistical analysis used the SPSS version of 21.

Results: Visualization of microorganisms by Gram and Warthin-Starry (WS) silver stains, preliminarily observed the morphological characteristics of microbiome in FFPE tissue cases, such as bacteria or fungi. Tonsillar FFPE samples from the IgAN patients and CT controls showed significant differences in tonsillar microbial certain compositions and functions. We found that there were eight dominant genera that can be available to distinguish IgAN patients from CT controls. Compared with CT controls, at genus level, the relative abundances of Methylocaldum and unclassified_f_Prevotellaceae were significantly higher, while the abundances of Anaerosphaera, Halomonas, Trichococcus, Peptostreptococcus, norank_f_Synergistaceae and unclassified_k_norank_d_Bacteria were significantly lower in IgAN patients. Principal co-ordinates analysis (PCOA) distinguished IgAN patients from CT controls, and receiver operating characteristic (ROC) curves analysis confirmed that the diagnosis of disease has certain diagnostic significance. In addition, Functional analysis revealed that partly Enzymes and KOs were increased in the IgAN patients.

Conclusions: Histological screening results were very helpful for further gene sequencing, not only to supplement the observation of bacterial morphology and structure, but also to prepare for subsequent gene sequencing and bioinformatics analysis. We elucidated subtle relevance between changes in tonsillar microbiota and IgAN patients, which can be utilized to predict the incidence of IgAN disease. In addition, we predicted that some enzymes, and KOs were closely related to IgAN.
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http://dx.doi.org/10.1016/j.prp.2020.153174DOI Listing
November 2020

Glucocorticoid receptor modulates dendritic cell function in ulcerative colitis.

Histol Histopathol 2020 Dec 24;35(12):1379-1389. Epub 2020 Jul 24.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

Ulcerative colitis (UC) is a serious form of inflammatory bowel disease (IBD) occurring worldwide. Although anti-TNF therapy is found to be effective in over 70% of patients with UC, nearly one-third are still deprived of effective treatment. Because glucocorticoids (GC) can effectively inhibit granulocyte-recruitment into the mucosa, cytokine secretion and T cell activation, they are used widely in the treatment of UC. However, remission is observed in only 55% of the patients after one year of steroid use due to a condition known as steroid response. Additionally, it has been noted that 20%-40% of the patients with UC do not respond to GC treatment. Researchers have revealed that the number of dendritic cells (DCs) in patients with UC tends to increase in the colonic mucosa. Many studies have determined that the removal of peripheral DCs through the adsorption and separation of granulocytes and monocytes could improve tolerance of the intestine to its symbiotic flora. Based on these results, further insights regarding the beneficial effects of Adacolumn apheresis in patients subjected to this treatment could be revealed. GC can effectively inhibit the activation of DCs by reducing the levels of major histocompatibility complex class II (MHC II) molecules, which is critical for controlling the recruitment of granulocytes. Therefore, alternative biological and new individualized therapies based on these approaches need to be evaluated to counter UC. In this review, progress in research associated with the regulatory effect of glucocorticoid receptors on DCs under conditions of UC is discussed, thus providing insights and identifying potential targets which could be employed in the treatment strategies against UC.
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http://dx.doi.org/10.14670/HH-18-241DOI Listing
December 2020

Tonsillar immunology in IgA nephropathy.

Pathol Res Pract 2020 Jul 16;216(7):153007. Epub 2020 May 16.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China. Electronic address:

As one of the most common types of primary glomerulonephritis, IgA nephropathy (IgAN) is often characterized by the immunoprecipitation of IgA1 in mesangial area. In clinical terms, IgA nephropathy can be treated with tonsillectomy or conservative treatment, basing on modern immunology knowledge in which the mucosa immune system (MIS), especially the widely distributed mucosa-associated lymphoid tissue (MALT) is focused accordingly In terms of basic research, IgAN has been shown correlated with multiple factors, including serum Gd-IgA1 level, IgA-IgG immunity, tonsil-associated bacteria,GADD34, CX3CR1, FOXP3 and the expression of other related intrinsic immune antibody. Therefore, it is reasonable there could be mutual correlation among IgAN-associated factors. The purpose of this study is to review the new progress on the treatment and prevention of IgAN diseases and related mechanisms of IgAN tonsils, which will be of great significance for the therapy of IgAN patients.
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http://dx.doi.org/10.1016/j.prp.2020.153007DOI Listing
July 2020

CircRNA 001418 Promoted Cell Growth and Metastasis of Bladder Carcinoma via EphA2 by miR-1297.

Curr Mol Pharmacol 2021 ;14(1):68-78

Department of Urology, Harbin Medical University Cancer Hospital, Harbin, 150086, China.

Background: Cancer is one of the major causes of human deaths at present. It is the leading cause of deaths in developed countries. Moreover, Circular RNAs (circRNAs) have been discovered to play important roles in tumor genesis and development and are abnormally expressed in bladder cancer .

Objective: The present study aims to investigate the anti-cancer effects of circ 001418 on bladder carcinoma and its possible mechanism.

Methods: Quantitative PCR (qPCR) and gene chip were used to measure the circ 001418 expression. Cell proliferation and transfer, apoptosis and caspase-8 and caspase-3 activity levels were measured using MTT, Transwell assay, Flow cytometry. Caspase-3 and 9 activity levels, EphA2, cytochrome c and FADD protein expression, were detected using Western blotting.

Results: The expression of circ 001418 was increased in patients with bladder carcinoma. Over-expression of circ 001418 promoted cell proliferation and transfer, and reduced apoptosis in vitro model of bladder carcinoma. Down-regulation of Circ 001418 inhibited cell proliferation and transfer, and induced apoptosis in vitro model of bladder carcinoma. Meanwhile, over-expression of circ 001418 induced EphA2 and cytochrome c protein expression, and suppressed FADD protein expression in vitro model of bladder carcinoma by the suppression of miR-1297. MiR-1297 reduced the pro-cancer effect of circ 001418 on apoptosis of bladder carcinoma.

Conclusion: Results showed that circRNA 001418 promoted cell growth and metastasis of bladder carcinoma via EphA2 by miR-1297.
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http://dx.doi.org/10.2174/1874467213666200505093815DOI Listing
January 2021

Cell-cargo mediated ZrN nanoparticle for the synergetic phototherapy on both of mice and rabbits.

Eur J Pharm Biopharm 2020 Apr 19;149:163-169. Epub 2020 Feb 19.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150080, China. Electronic address:

Realization of phototherapy on the big animal modal with orthotopic tumor is of considerable significance in view of its great clinical relevance to the human deep tumor treatment. Herein, near infrared (NIR)-active ZrN nanoparticles were chosen for both of photothermal and photodynamic purposes to achieve the synergetic phototherapy on mice with subcutaneous tumor and even rabbits bearing with orthotopic tumor. Broad and strong photoabsorption, photosensitive ROS generation and photothermal effect of ZrN nanoparticles together made it to be ideal candidate for the effective tumor photoablation. Meanwhile, cell-cargo of macrophage enables targeted delivery of ZrN nanoparticles without influence on its photophysical properties. Resultantly, macrophage loaded ZrN could efficiently mediate synergetic phototherapeutic outcome as proved by complete removal of solid tumor from mice and rabbits. In this work, we also introduced B-mode ultrasonography and contrast-enhanced ultrasound technique for monitoring the evolution process of deep orthotopic tumor on rabbits post-treatment and confirmed the pathological changes of vascular degeneration and liquefaction necrosis post phototherapy.
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http://dx.doi.org/10.1016/j.ejpb.2020.02.006DOI Listing
April 2020

High expression levels of TLR9 and PD-L1 indicates a poor prognosis in patients with angioimmunoblastic T-cell lymphoma: a retrospective study of 88 cases in a single center.

J Cancer 2020 1;11(1):57-68. Epub 2020 Jan 1.

Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P. R. China.

The role of TLR9 expressed by tumor cells in evading immune surveillance was confirmed. PD-L1 expression in tumor cells plays a key role in tumor immune escape, which is associated with poor prognosis. However, the clinical relevance of TLR9 and PD-L1 expression in angioimmunoblastic T-cell lymphoma (AITL) has not been evaluated. In this study, we identified differentially expressed genes in AITL samples by bioinformatic analysis, and we first examined TLR9 and PD-L1 expression by immunohistochemical staining in patients with AITL and compared these data with clinical features and survival time. It was found that the expression of PD-L1 and multiple TLRs was higher in AITL than normal T-cell samples, and TLR9 and PD-L1 expression displayed complex interactions by bioinformatic analysis. The rates of TLR9 and PD-L1 high expression were 69% and 50%, respectively. High expression of either TLR9 or PD-L1 indicated a poor survival rate for patients with AITL. Multivariate analysis further confirmed that high expression levels of TLR9 and PD-L1 were unfavorable prognostic factors for AITL. We further found inferior overall survival in AITL with clinical features of ECOG status ≥ 2, advanced-stage, elevated serum LDH levels, elevated serum β-MG levels, and high IPI score. : TLR9 and PD-L1 expression may be a novel predictor of prognosis for patients with AITL and may serve as potential therapeutic strategy.
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http://dx.doi.org/10.7150/jca.37033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930404PMC
January 2020

TLR9 expression is associated with PD-L1 expression and indicates a poor prognosis in patients with peripheral T-cell lymphomas.

Pathol Res Pract 2020 Mar 25;216(3):152703. Epub 2019 Oct 25.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, PR China. Electronic address:

Toll-like receptor9 (TLR9), a member of pattern recognition receptors, play an important role in tumor immunologic surveillance. However, the clinical impact of TLR9 and programmed cell death-ligand 1 (PD-L1) in peripheral T-cell lymphomas (PTCL) remains unclear. In this study, we examined the expression of TLR9 and PD-L1 by immunohistochemical staining in patients with PTCL, and evaluated the clinical significance between expression and clinicopathological features. We found that the rates of high expression of TLR9 and PD-L1 on tumor cells were 65.3% and 45.8% in PTCL, respectively. TLR9 expression was associated with PD-L1 expression in PTCL. Moreover, TLR9 expression was associated with gender, ECOG score, Ki-67 expression, while PD-L1 expression was associated with the number of extranodal involvement and platelet count. High expression of either TLR9 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analysis confirmed that high expression of TLR9 and PD-L1 were unfavorable prognostic factors for patients with PTCL. Thus, TLR9 and PD-L1 expression might be important on the point of prognostic markers in PTCL.
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http://dx.doi.org/10.1016/j.prp.2019.152703DOI Listing
March 2020

Triptolide inhibits tonsillar IgA production by upregulating FDC-SP in IgA nephropathy.

Histol Histopathol 2020 Jun 9;35(6):599-608. Epub 2019 Dec 9.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

IgA nephropathy (IgAN) is primarily resulted of qualitative abnormality of IgA. The occurrence of IgAN is associated with affected tonsils which enhances the IgA production via IgA class switching and immuno-activation. Follicular dendritic cell-secreted protein (FDC-SP) was found to be a negative effect for IgA production in tonsil. The previous studies suggested that Triptolide might reduce IgA production by its immunosuppression role. Given this background, this study investigated the mechanisms underlying the role of Triptolide and FDC-SP in the generation of IgA and IgA class switching in tonsil of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction revealed that the expression of FDC-SP was increased in the tonsils of IgAN patients with Triptolide treatment compared with those without treatment. Meanwhile, the expression of FDC-SP was negatively correlated with IgA inducing cytokines in the tonsils of IgAN patients treated with Triptolide, due to the significant decreased IgA-bearing cells. The expression of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. Importantly, Triptolide promoted FDC-SP secretion, and correlated negatively with decreased IgA production in isolated FDC-associated clusters, which had been isolated from patients without TW treatment previously. Our study demonstrated that Triptolide might have an impact on FDC-SP production and downregulation of IgA synthesis in the tonsils of IgAN patients, which could be a promising strategy for therapeutic intervention in IgAN patients.
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http://dx.doi.org/10.14670/HH-18-190DOI Listing
June 2020

Genomic Profiling of Driver Gene Mutations in Chinese Patients With Non-Small Cell Lung Cancer.

Front Genet 2019 18;10:1008. Epub 2019 Oct 18.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

Worldwide, especially in China, lung cancer accounts to a major cause of mortality related to cancer. Treatment decisions mainly depend on oncogenic driver mutations, which offer novel therapeutic targets for anticancer therapy. However, studies of genomic profiling of driver gene mutations in mainland China are rare. Hence, this is an extensive study of these mutations in Non-small-cell lung cancer (NSCLC) Chinese patients. Comparison of driver gene mutations of lung adenocarcinoma with other races showed that the mutational frequencies were similar within the different East Asian populations, while there were differences between East Asian and non-Asian populations. Further, four promising candidates for druggable mutations of epidermal growth factor receptor () were revealed that open up avenues to develop and design personal therapeutic approaches for patients harboring mutations. These results will help to develop personalized therapy targeting NSCLC.
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http://dx.doi.org/10.3389/fgene.2019.01008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842958PMC
October 2019

Metadherin Promotes Malignant Phenotypes And Induces Beta-Catenin Nuclear Translocation And Epithelial-Mesenchymal Transition In Gastric Cancer.

Cancer Manag Res 2019 11;11:8911-8921. Epub 2019 Oct 11.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, People's Republic of China.

Purpose: Metadherin (MTDH), as an oncogene, is associated with metastasis and poor prognosis. This study investigated MTDH expressions and development of gastric cancer (GC) cell phenotypes and the contribution of MTDH to epithelial-mesenchymal transition (EMT).

Patients And Methods: MTDH expression was assayed in human GC cell lines and tumor tissue from 92 GC patients. Functional experiments were performed to characterize MTDH activity. Expressions of EMT-related proteins (vimentin and E-cadherin), phosphorylated β-catenin and β-catenin were assayed by immunohistochemistry, Western blotting, immunofluorescence, and co-immunoprecipitation, respectively.

Results: MTDH expressions were higher in GC tissue than that in gastric mucosa from the same patient. MTDH overexpression was correlated with metastasis and enhanced malignant GC phenotypes, i.e., proliferation, migration, invasiveness, and chemoresistance. MTDH overexpression was associated with expressions of vimentin, E-cadherin and cancer stem-cell biomarkers including CD44, CD133, and Oct4. MTDH complexed with β-catenin and decreased phosphorylated β-catenin levels to facilitate β-catenin translocation into the nucleus and expressions of downstream genes.

Conclusion: MTDH overexpression in GC cells is associated with EMT and development of cancer stem cell malignant phenotypes and affects the subcellular translocation of β-catenin. The results warrant investigation of the prognostic value of MTDH in GC and as a therapeutic target.
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http://dx.doi.org/10.2147/CMAR.S221422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792945PMC
October 2019

Targeted photothermal therapy of mice and rabbits realized by macrophage-loaded tungsten carbide.

Biomater Sci 2019 Dec 16;7(12):5350-5358. Epub 2019 Oct 16.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.

Although great advances have been made in photothermal therapy, the efforts hitherto have mainly achieved antitumor effects in mice with a subcutaneous tumor model, which is less clinically relevant. Therefore, it is very urgent to make further progress in investigating the possibility of larger animal models with orthotopically xenografted tumors for further clinical trials. Herein, macrophage-loaded tungsten carbide has been employed for the photothermal ablation of orthotopic breast tumors in rabbits in a targetable way. Tungsten carbide as an excellent photoactive material can induce on-site hyperthermia and even reactive oxygen species for tumor destruction; meanwhile, the macrophage is a biocarrier that behaves as a "Trojan horse" for tumor targeting. Both experimental results and theoretical simulations verified the broadband photoabsorption of WC. The WC loaded in the macrophages readily maintains the photothermal and photodynamic effects of the bare WC, while its accumulation at the tumor site is nearly 10 times that of bare WC. As such, the complete removal of solid tumors in rabbits was confirmed with the aid of B-mode ultrasound and contrast-enhanced ultrasound surveillance. Apparently, this work advances photothermal therapy one step further to large animal models with orthotopic tumors.
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http://dx.doi.org/10.1039/c9bm00911fDOI Listing
December 2019

miR-211 facilitates platinum chemosensitivity by blocking the DNA damage response (DDR) in ovarian cancer.

Cell Death Dis 2019 06 24;10(7):495. Epub 2019 Jun 24.

Department of Pathology, Harbin Medical University, Harbin, 150081, China.

The DNA damage response (DDR) is one of the most important mechanisms of platinum resistance in ovarian cancer. Some miRNAs have been identified to be involved in the regulatory network of DDR, thus the abnormal expression of miRNAs might affect platinum chemosensitivity in ovarian cancer. In this study, by assessing miRNAs simultaneously targeting a set of DDR genes that exhibited response to platinum, we found that miR-211 inhibited most of those genes, and proposed that miR-211 might affect the sensitivity of ovarian cancer cells to platinum by targeting multiple DDR genes and thereby determine the prognosis of ovarian cancer. To verify the hypothesis, we analyzed the association between miR-211 level and clinical prognosis, assessed the effect of miR-211 on DDR and platinum chemosensitivity, and explored the possible molecular mechanism. We revealed that miR-211 enhanced platinum chemosensitivity and was positively correlated with favorable outcomes in ovarian cancer patients. Many DDR genes including TDP1 were identified as targets of miR-211. In contrast, TDP1 suppressed DNA damage and platinum chemosensitivity. Moreover, the miR-211 level in tissues was shown to be associated with the good outcome of neoadjuvant chemotherapy and negatively correlated with the expression of TDP1. Conclusively, we demonstrated that miR-211 improves the prognosis of ovarian cancer patients by enhancing the chemosensitivity of cancer cells to platinum via inhibiting DDR gene expression, which provides an essential basis to identify novel treatment targets to block DDR effectively and improve chemosensitivity in ovarian cancer.
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http://dx.doi.org/10.1038/s41419-019-1715-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591289PMC
June 2019

TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas.

Cancer Manag Res 2019 23;11:4743-4756. Epub 2019 May 23.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People's Republic of China.

Toll-like receptor 4 (TLR4), a member of the pattern recognition receptors, has been reported to be involved in carcinogenesis. However, the clinical impact of TLR4 in peripheral T-cell lymphomas (PTCL) remains unclear. The current study, using immunohistochemical staining, first examined TLR4 and programmed cell death-ligand 1 (PD-L1) expression in patients with PTCL, to correlate TLR4 and PD-L1 expression with clinicopathological parameters. It was found that the rates of high expression of TLR4 and PD-L1 were 41.7% and 45.8%, respectively. TLR4 expression was closely associated with PD-L1 expression. The expression of TLR4 was closely related to primary extranodal site involvement, increased Ann Arbor stage, and low hemoglobin expression, while the expression of PD-L1 was closely related to a low platelet count and multiple extranodal organ involvements (>1). High expression of either TLR4 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analyses further confirmed that increased expression levels of TLR4 and PD-L1 are unfavorable prognostic factors for PTCL. This study demonstrates that the expressions of TLR4 and PD-L1 are independent predictors of survival time for patients with PTCL. Thus, TLR4 and PD-L1 may serve as potential therapeutic targets in PTCL patients.
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http://dx.doi.org/10.2147/CMAR.S203156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536125PMC
May 2019

The prognostic value of toll-like receptor5 and programmed cell death-ligand1 in patients with peripheral T-cell non-Hodgkin lymphoma.

Leuk Lymphoma 2019 11 24;60(11):2646-2657. Epub 2019 Apr 24.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P. R. China.

TLR5 is expressed in a variety of tumors. However, the clinical impact of TLR5 in Peripheral T-cell non-Hodgkin lymphomas (PTCLs) remains unclear. We analyzed differentially expressed genes in PTCLs samples from Gene Expression Omnibus database. We examined TLR5 and programed cell death-ligand1 (PD-L1) expression by immunohistochemistry in PTCLs tissues. Gene expression profiling shown PD-L1 and TLR5 expression was higher in PTCLs than in normal samples. The rates of high TLR5 and PD-L1 expression were 12.5% and 45.8%. We found association between TLR5 and PD-L1 expression. Low TLR5 expression or high PD-L1 expression was correlated with shorter overall survival and inferior disease-free survival. Multivariate Cox regression analysis shown low TLR5 expression, high PD-L1 expression, gender, and high IPI score were prognostic factors ( < .05). PTCLs patients with low TLR5 expression and high PD-L1 expression had worse prognosis. TLR5 and PD-L1 may serve as potential therapeutic targets in PTCLs patients.
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http://dx.doi.org/10.1080/10428194.2019.1602266DOI Listing
November 2019

Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China.

Cell Physiol Biochem 2018 25;50(4):1496-1509. Epub 2018 Oct 25.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin,

Background/aims: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status.

Methods: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples.

Results: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States.

Conclusion: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC.
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http://dx.doi.org/10.1159/000494649DOI Listing
November 2018

Expression of TRPM8 in human reactive lymphoid tissues and mature B-cell neoplasms.

Oncol Lett 2018 Nov 3;16(5):5930-5938. Epub 2018 Sep 3.

Department of Pathological Diagnostics, Yamagata University Faculty of Medicine, Yamagata, Yamagata 990-9585, Japan.

Transient receptor potential melastatin 8 (TRPM8) is a member of the transient receptor potential superfamily of Ca channels. The aim of the present study was to clarify TRPM8 expression in reactive lymphoid tissues and mature B-cell neoplasms. Reactive and neoplastic lymphoid tissues were used to evaluate TRPM8 expression by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TRPM8 cells were frequently detected in the follicular light zone and marginal zone of reactive lymphoid tissues. Double immunostaining revealed that TRPM8 cells co-expressed cluster of differentiation (CD) 38, CD79a, CD138, interferon regulatory factor 4/melanoma associated antigen (mutated) 1, B cell CLL/lymphoma 6 and transmembrane activator and CAML interactor. TRPM8 neoplastic cells were frequently detected in plasma cell myeloma. The positive band of TRPM8 mRNA was confirmed by RT-PCR in cases of myeloma. The present study is, to the best of our knowledge, the first to demonstrate the expression of TRPM8 in reactive lymphoid tissues and mature B-cell neoplasms, revealing that TRPM8 is frequently expressed in pre-plasmablasts, plasmablasts, plasma cells and mature B-cell lymphomas that are likely to differentiate into plasma cells.
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http://dx.doi.org/10.3892/ol.2018.9386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176370PMC
November 2018

The prognostic value of programmed cell death ligand 1 expression in non-Hodgkin lymphoma: a meta-analysis.

Cancer Biol Med 2018 Aug;15(3):290-298

Department of Medical Oncology.

Objective: Although the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a meta-analysis.

Methods: The PubMed, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio (HR), 95% confidence interval (CI), and odds ratios (OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival (OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this meta-analysis.

Results: A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis (HR=2.04, 95% CI: 1.18-3.54, =0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma (HR=1.92, 95% CI: 1.06-3.48, =0.03) but not for natural killer/T-cell lymphoma (HR=2.41, 95% CI: 0.47-12.22, =0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of ≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like lymphoma.

Conclusions: High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size, high-quality studies with larger sample sizes are needed to validate our results.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121049PMC
August 2018

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China.

Cell Physiol Biochem 2018 22;49(1):206-216. Epub 2018 Aug 22.

Department of Microbiology, Harbin Medical University, Harbin, China.

Background/aims: Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. Here, we sought to evaluate the prevalence and genotype distribution of HPV in patients with laryngeal squamous cell carcinoma (LSCC) in northeast China.

Methods: HPV DNA in specimens from 211 patients diagnosed with LSCC was analyzed by the polymerase chain reaction and in situ hybridization, and p16 overexpression was evaluated by immunohistochemistry. p16 expression was scored positive if strong and diffuse nuclear and cytoplasmic staining was present in > 75% of tumor cells.

Results: In this study, infection with HPV and p16 expression were not absolutely consistent. Among all patients, 132 (62.6%) were positive for HPV DNA (HPV+), while 23 (10.9%) were inconsistent for HPV and p16. Multivariate analysis indicated that HPV, but not p16, is an independent prognostic factor for overall survival in LSCC. Overall survival was significantly improved in HPV+ LSCC patients compared with the HPV-negative group (hazard ratio, 0.395; 95% confidence interval, 0.185-0.843; p = 0.016). Among the 132 HPV+ patients, 28 (21.2%) were HPV-16 single infection.

Conclusion: This study indicates that HPV DNA is a more reliable surrogate marker than p16 for the prediction of survival in patients with LSCC.
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http://dx.doi.org/10.1159/000492858DOI Listing
September 2018

MicroRNA-650 targets inhibitor of growth 4 to promote colorectal cancer progression via mitogen activated protein kinase signaling.

Oncol Lett 2018 Aug 6;16(2):2326-2334. Epub 2018 Jun 6.

Department of Pathology, Basic Research College, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

Colorectal cancer (CRC) is the third most common malignant disease globally and causes numerous cancer-associated mortalities; however, the underlying molecular mechanisms remain unresolved. MicroRNAs (miRs) are endogenous noncoding RNAs that regulate post-transcriptional gene silencing by annealing to partially complementary sequences in the 3'-untranslated regions of target mRNAs. In the present study, expression of the tumor suppressor gene inhibitor of growth protein 4 () in cell lines was investigated using reverse transcription-quantitative polymerase chain reaction and western blotting. miR-650 overexpression promoted CRC cell proliferation and migration by targeting ING4 when the cells were transfected with the miR-650 mimics. Additionally, overexpression of miR-650 increased the epithelial-mesenchymal transition and activation of the Ras homolog gene family member A/Ras-related C3 botulinum toxin GTPase. Extracellular signal-regulated kinases and p38 mitogen-activated protein kinase signaling were markedly activated when miR-650 was increased in CRC cells. Combined, the results indicate the mechanism underlying the miR-650 promotion of CRC progression, and provide promising potential biomarkers for the prognosis and treatment of CRC.
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http://dx.doi.org/10.3892/ol.2018.8910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036455PMC
August 2018

AEG-1 Contributes to Metastasis in Hypoxia-Related Ovarian Cancer by Modulating the HIF-1alpha/NF-kappaB/VEGF Pathway.

Biomed Res Int 2018 25;2018:3145689. Epub 2018 Mar 25.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.

Objective: Ovarian carcinoma represents one of the deadliest malignancies among female cancer patients. Astrocyte-elevated gene-1 (AEG-1) participates in the ontogenesis of multiple human malignant diseases. Here we evaluated AEG-1, hypoxia-inducible factor- (HIF-) 1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), and vascular endothelial growth factor (VEGF) amounts in hypoxia induced ovarian carcinoma cells. This study aimed to explore the mechanism by which AEG-1 regulates metastasis in hypoxia induced ovarian carcinoma.

Patients And Methods: AEG-1, HIF-1, and VEGF protein amounts were evaluated by immunohistochemistry in 40 and 170 normal ovary and ovarian cancer tissue specimens, respectively. In addition, AEG-1, HIF-1, NF-B, and VEGF mRNA and protein levels were determined by reverse quantified RT-PCR and WB, respectively, at different time periods (0-24 h) in epithelial ovarian cancer (EOC) SKOV3 cells treated in a hypoxia incubator. Furthermore, NF-B and VEGF gene and protein expression levels in AEG-1 knockdown EOC cells were quantitated by RT-PCR and WB, respectively.

Results: AEG-1, HIF-1, and VEGF amounts were significantly elevated in EOC tissue samples compared with normal ovary specimens ( < 0.001). Positive expression of HIF-1 and AEG-1 was associated with higher metastatic rate ( < 0.01), lower FIGO stage ( < 0.001), and degree of differentiation ( < 0.001). Meanwhile, EOC SKOV3 cells grew upon exposure to hypoxia for 8 h ( < 0.001); at this time point, AEG-1, HIF-1, NF-B, and VEGF amounts peaked ( < 0.001), at both the gene and the protein levels. After AEG-1 knockdown, HIF-1, NF-B, and VEGF amounts were significantly decreased in EOC SKOV3 cells, also under hypoxic conditions ( < 0.01).

Conclusions: As an independent prognostic factor, AEG-1 was found to be significantly associated with hypoxia in ovarian cancer by regulating the HIF-1alpha/NF-kappaB/VEGF pathway. Therefore, AEG-1 may be useful in determining disease stage and prognosis in ovarian cancer.
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http://dx.doi.org/10.1155/2018/3145689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889902PMC
September 2018
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