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Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

Asian Journal of Andrology 2022年第4期24卷 380-385页

作者： Xian-Zi Zeng Zhan-Sen Huang Hong-Peng Fang Jie-Ying Wu Qun-Xiong Huang Chu-Bin Zhuang Jing Zhou Jin-Ming Di Department of Urology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Infertility and Sexual Medicine The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Pathology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Prostate cancer(PCa)is one of the most frequent cancers in men,and its biomolecular targets have been extensively *** study aimed to analyze the expression of toll-like receptor 9(TLR9)and vascular endothelial growth factor C(VEGF-C)and the clinical value of the coexpression of TLR9 and VEGF-C in *** retrospectively evaluated 55 patients with clinically localized,intermediate-risk,or high-risk PCa who underwent laparoscopic radical prostatectomy(LRP)and extended pelvic lymph node dissection(ePLND)without neoadjuvant hormonal therapy at a single institution from June 2013 to December *** all 55 patients,the median number of lymph nodes(LNs)resected was 23(range:18-31),and a total of 1269 LNs were removed,of which 78 LNs were *** patients had positive LNs,with a positive rate of 30.9%.In addition,the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score(GS)(P=0.049),increased LN metastasis(P=0.004),and more perineural invasion(PNI)(P=0.033).Moreover,VEGF-C expression was associated with GS(P=0.040),pathological stage(pT stage)(P=0.022),LN metastasis(P=0.003),and PNI(P=0.001).Furthermore,a significant positive correlation between TLR9 and VEGF-C was found(Pmetastasis(P=0.047).Collectively,we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression,thereby affecting the prognosis of PCa ***,these markers may serve as valuable targets for the treatment of PCa.

关键词： biochemical progression-free survival coexpression lymphatic metastasis prostate cancer toll-like receptor 9 vascular endothelial growth factor C

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HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program

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Cancer Communications 2022年第5期42卷 447-470页

作者： Ming Huang Wen Dong Ruihui Xie Jilin Wu Qiao Su Wuguo Li Kai Yao Yuelong Chen Qianghua Zhou Qiang Zhang Wenwen Li Liang Cheng Shengmeng Peng Siting Chen Jian Huang Xu Chen Tianxin Lin Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China Guangdong Provincial Clinical Research Center for Urological Diseases GuangzhouGuangdong 510120P.R.China Animal Experiment Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Department of Urology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China

Background:lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic *** evidence shows that heat shock factor 1(HSF1)drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic ***,the roles of HSF1 in lymphatic metastasis remain largely ***,we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic ***:We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors(HSFs)and heat shock proteins(HSPs),and analyzed its clinical relevance in three *** in vitro and in vivo assays were performed in HSF1-silenced and-regained *** also used Coimmunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual-luciferase reporter assays to investigate the transcriptional program directed by *** pharmacological inhibitor of HSF1,KRIBB11,was evaluated in popliteal lymph node metastasis models and patientderived xenograft models of bladder ***:HSF1 expression was positively associated with lymphatic metastasis status,tumor stage,advanced grade,and poor prognosis of bladder ***,HSF1 enhanced the epithelial-mesenchymal transition(EMT)of cancer cells in primary tumor to initiate metastasis,proliferation of cancer cells in lymph nodes,and macrophages infiltration to facilitate multistep lymphatic ***,HSF1 interacted with protein arginine methyltransferase 5(PRMT5)and jointly induced the monomethylation of histone H3 at arginine 2(H3R2me1)and symmetric dimethylation of histone H3 at arginine 2(H3R2me2s).This recruited the WD repeat domain 5(WDR5)/mixed-lineage leukemia(MLL)complex to increase the trimethylation of histone H3 at lysine 4(H3K4me3);resulting in upregulation of lymphoid enhancer-binding factor 1(LEF1),matrix me

关键词： HSF1 PRMT5 KRIBB11 transcriptional program bladder cancer lymphatic metastasis prognostic factor targeted therapy

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Risk factors of lymphatic metastasis complement poor radiological detection in gallbladder cancer

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World Journal of Gastroenterology 2014年第1期20卷 290-295页

作者： Tu-Nan Yu Bo Shen Ning Meng Hong Yu Xiu-Jun Cai The Second Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang University

AIM: To explore risk factors of lymphatic metastasis (LM) in gallbladder cancer, and their potential to complement unsatisfactory radiological detection.

关键词： Gallbladder cancer Multidetector computed tomography lymphatic metastasis Lymph node excision Carbohydrate antigen 19-9 Age

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HSP90AA1 promotes lymphatic metastasis of hypopharyngeal squamous cell carcinoma by regulating epithelial-mesenchymal transition

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Oncology Research 2023年第5期31卷 787-803页

作者： FENGXIANG TANG YANSHI LI MIN PAN ZHIHAI WANG TAO LU CHUAN LIU XIN ZHOU GUOHUA HU Department of Otolaryngology The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment *** study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in ***:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of *** of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell ***:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk *** down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and *** in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by ***:HSP90AA1,by controlling EMT,can foster LM in *** finding sets the foundation for delving into new therapeutic targets for HPSCC.

关键词： Hypopharyngeal squamous cell carcinoma lymphatic metastasis HSP90AA1 EMT HNSCC

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KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 87-92页

作者： Xu Liu Xiao-Zhong Guo Hong-Yu Li Jiang Chen Li-Nan Ren Chun-Yan Wu Department of Gastroenterology General Hospital of Shenyang Military Area

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

关键词： KAI1 pancreatic cancer lymphatic metastasis lymphangiogenesis

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Pattern of lymphatic metastasis and Influencing Factors in Thoracic Esophageal Carcinoma

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Clinical oncology and cancer researeh 2009年第5期6卷 342-346页

作者： Jun Wang Chun Han Shuchai Zhu Chao Gao Xiaoning Li Department of Radiation Therapy the Fourth Hospital of Hebei Medical University Shijiazhuang 050011 Hebei Province China.

OBJECTIVE To explore the regular patterns of lymphatic metastasis in thoracic esophageal carcinoma （TEC） and the factors influencing these patterns. METHODS Data of 229 TEC patients who underwent radical esophagectomy and thoracoabdominal 2-field lymphadenectomy were reviewed. Within this patient population, a total of 2458 lymph nodes were dissected during surgery. The distribution of the nodular metastasis rates （NMR） in various diseased regions in the esophageal carcinoma （EC） patients as well as factors influencing metastases such as the depth of tumor infiltration, tumor size, tumor morphology, and degree of tumor differentiation were analyzed. RESULTS i） lymphatic metastasis （LM） occurred in 102 EC cases, and the lymphatic metastasis rate （LMR） was 44.5% （102/229）. The NMR was 9.5% （258/2458）. ii） The NMRs were 19.0%, 6.7%, 9.8% and 12.2% in the superior, middle and inferior mediastinum, and abdominal cavity, respectively, in patients with EC in the superior thoracic segment; 26.1%, 7.4%, 11.8% and 11.9% in the same sites of the mediastinum, respectively, in those with middle thoracic-segment EC; and 0%, 1.6%, 5.3%, and 10.0%, respectively, in the same sites in those with inferior thoracic EC. iii） The LMRs of the EC patients in stage-T1, T2, T3 and T4 were 28.6%, 43.8%, 47.6% and 31.3%, respectively, and the NMRs of the patients were 7.9%, 10.8%, 10.7% and 10.8%, respectively. There were no significant differences between the LMR and the NMR of the EC patients in stage T1 to T4 （X^2 = 2.733, P = 0.435 and X2 = 0.686, P = 0.876）. iv） The LMR of the patients with the length of tumor 〈 3 cm, 〉 3 cm and 〈 5 cm, and 〉 5 cm were 45.2%, 43.4% and 46.2%, respectively, and the NMR according to the same range of the tumor size above were 9.1%, 11.6% and 11.7%, respectively. There were no significant differences between the groups （X2 --- 0.094, P = 0.954 and X2 = 3.933, P = 0.140）. v） The NMRs of the medullary, ulcerative, fungoid and sclerotic-type EC

关键词： esophageal carcinoma/thoracic segment lymphatic metastasis surgery.

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Lymphangiogenesis, lymphatic Endothelial Cells and lymphatic metastasis in Head and Neck Cancer—A Review of Mechanisms

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International Journal of Oral Science 2010年第1期2卷 5-14页

作者： Zhuang Zhang Joseph I. Helman Long-jiang Li State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University Chengdu China Department of Oral and Maxillofacial Surgery the Medical School Hospital of Qingdao University Qingdao China Section of Oral and Maxillofacial Surgery University of Michigan Ann Arbor USA

lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels, Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.

关键词： lymphangiogenesis lymphatic endothelial cell lymphatic metastasis head and neck cancer

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Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip

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World Journal of Gastroenterology 2005年第10期11卷 1463-1472页

作者： BoSong Jian-WuTang BoWang Xiao-NanCui LiHou LuSun Li-MinMao Chun-HuiZhou YueDu Li-HuiWang Hua-XinWang Ren-ShuZheng LeiSun DepartmentofPathology DalianMedicalUniversityDalian116027LiaoningProvinceChina ShanghaiJingtaiBiotechnologyCorporationLtd Shanghai200000China

AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis ***: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by ***: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function ***: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further *** D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later *** (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic m

关键词： Hepatocarcinoma lymphatic metastasis Cell lines Hca-F and Hca-P Gene chip

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Clinical features related to lymphatic metastasis in grade 3 endometroid endometrial cancer:a retrospective cross-sectional study

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Chinese Medical Journal 2021年第17期134卷 2102-2109页

作者： Bo Wang Qian Wang Yue Shi Wen-Yu Shao Jiong-Bo Liao Xue-Zhen Luo Xiao-Jun Chen Chao Wang Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Department of Gynecology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesObstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Background Endometrial cancer(EC)has been one of the most general cancers with respect to gynecological malignancies;however,there are debates on clinical strategies concerning treatments especially for patients with grade 3(G3)endometroid endometrial cancer(EEC).Present study aimed to evaluate the lymphatic metastasis(LM)related factors and figure out the necessity of lymphadenectomy for G3 EEC *** From January 2009 to April 2019,3751 EC patients were admitted to Obstetrics and Gynecology Hospital of Fudan *** characteristics include age,grade,stage,and clinical pathological features.A total of 1235 EEC patients were involved in the multivariable *** hundred and eighty-one patients were involved in the survival analysis and the data attributed to sufficient follow-up ***-Meier curve and log-rank test were utilized to analyze the survival *** Among the 1235 EEC patients,181(14.7%)were categorized as G3 and 1054(85.3%)were grade 1 to grade 2(G1-2).Multivariate analysis demonstrated that lymphovascular space invasion,adnexal involvement,and cervical stroma involvement were independent risk factors of LM in G3 cohort with odds ratio 3.4,5.8,and 8.9;95%confidence interval 1.1–10.6,1.5–22.4,and 2.8–28.0,*** rates increased from 3.3%(3/92)to 75%(9/12)for G3 EEC cohort as related factor numbers increased from one to *** were no differences between G3 and G1-2 EEC in overall survival and progression free ***,no survival advantage was observed for G3 EEC patients at early stage with different plans of adjuvant *** For G3 EEC patients without other pathological positive factor,theLMrate is lower than those with other pathological positive *** analysis showed no difference between G3 cohort and G1-2 ***,different adjuvant treatments had no impact on the overall survival for G3 EEC patients.

关键词： Endometrial cancer lymphatic metastasis Multivariate analysis Survival

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Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

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World Journal of Gastroenterology 2011年第27期17卷 3220-3228页

作者： Fusun Ozmen M Mahir Ozmen Evren Ozdemir Munevver Moran Selda Sekin Dicle Guc Ergun Karaagaoglu Emin Kansu Department of Basic Oncology Hacettepe University Institute of Oncology06100 Ankara Turkey Department of General Surgery Ankara Numune Teaching and Research Hospital06100 Ankara Turkey Department of Emergency Medicine Hacettepe University Medical School06100 Ankara Turkey Department of Medical Oncology Hacettepe University Institute of Oncology06100 Ankara Turkey Department of Pathology Ankara Numune Teaching and Research Hospital06100 Ankara Turkey Department of Biostatistics and Medical Informatics Hacettepe University Faculty of Medicine06100 AnkaraTurkey

AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric ***: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

关键词： CD44 Gastric cancer lymphatic metastasis lymphatic vessel endothelial hyaluronan receptor-1 metastasis Vascular endothelial growth factor receptor-3

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