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HSP90AA1 promotes lymphatic metastasis of hypopharyngeal squamous cell carcinoma by regulating epithelial-mesenchymal transition 被引量:3
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作者 FENGXIANG TANG YANSHI LI +5 位作者 MIN PAN ZHIHAI WANG TAO LU CHUAN LIU XIN ZHOU GUOHUA HU 《Oncology Research》 SCIE 2023年第5期787-803,共17页
Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevan... Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation 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 lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC. 展开更多
关键词 Hypopharyngeal squamous cell carcinoma lymphatic metastasis HSP90AA1 EMT HNSCC
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Extracellular vesicle-mediated heterogeneous communication between cancer and the lymphatic system facilitates lymphatic metastasis
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作者 Changhao Chen Yuming Luo +7 位作者 Hanhao Zheng Dingwen Zhang Yao Kong Jiabin Yang Mingjie An Yan Lin Daowei Lin Rufu Chen 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第3期174-180,共7页
Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system met... Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored. 展开更多
关键词 metastasis lymphatic CANCER
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Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer 被引量:27
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作者 Fusun Ozmen M Mahir Ozmen +5 位作者 Evren Ozdemir Munevver Moran Selda Sekin Dicle Guc Ergun Karaagaoglu Emin Kansu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第27期3220-3228,共9页
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- ... 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 cancer.METHODS: 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. 展开更多
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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Lymphangiogenesis, Lymphatic Endothelial Cells and Lymphatic Metastasis in Head and Neck Cancer—A Review of Mechanisms 被引量:7
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作者 Zhuang Zhang Joseph I. Helman Long-jiang Li 《International Journal of Oral Science》 SCIE CAS CSCD 2010年第1期5-14,共10页
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 commonl... 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. 展开更多
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 被引量:19
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作者 BoSong Jian-WuTang +10 位作者 BoWang Xiao-NanCui LiHou LuSun Li-MinMao Chun-HuiZhou YueDu Li-HuiWang Hua-XinWang Ren-ShuZheng LeiSun 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第10期1463-1472,共10页
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 lymphat... 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 potential.METHODS: 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 bioinformatics.RESULTS: 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 profile.CONCLUSION: 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 investigation.Cyclin 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 experiments.ESTs (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 metastasis, which might be used as the diagnostic markers and the therapeutic targets for lymphatic metastasis. 展开更多
关键词 HEPATOCARCINOMA lymphatic metastasis Cell lines Hca-F and Hca-P Gene chip
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KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo 被引量:3
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作者 Xu Liu Xiao-Zhong Guo +3 位作者 Hong-Yu Li Jiang Chen Li-Nan Ren Chun-Yan Wu 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2014年第1期87-92,共6页
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 can... 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. 展开更多
关键词 KAI1 pancreatic cancer lymphatic metastasis LYMPHANGIOGENESIS
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Risk factors of lymphatic metastasis complement poor radiological detection in gallbladder cancer 被引量:2
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作者 Tu-Nan Yu Bo Shen +2 位作者 Ning Meng Hong Yu Xiu-Jun Cai 《World Journal of Gastroenterology》 SCIE CAS 2014年第1期290-295,共6页
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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Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma 被引量:2
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作者 Ji Li Li Jia +3 位作者 Zhen-Hai Ma Qiu-Hong Ma Xiao-Hong Yang Yong-Fu Zhao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第38期5369-5376,共8页
AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprote... AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy. 展开更多
关键词 Axl Glycosylation Hepatocellular carcinoma lymphatic metastasis
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COMPARATIVE ANALYSIS OF LYMPHATIC METASTASIS——ASSOCIATED GENES IN MOUSE HEPATOCELLULAR CARCINOMA CELL LINES WITH DIFFERENT METASTATIC POTENTIAL
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作者 宋波 王波 +4 位作者 崔晓楠 李晓枫 周春辉 侯力 唐建武 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2006年第1期26-31,共6页
Objective: To investigate the neoplasm lymphatic metastasis-associated genes and its molecular mechanisms. Methods: 22690 mouse genome cDNA microarrays (including 14500 known genes and 4371 ESTs) were used to comp... Objective: To investigate the neoplasm lymphatic metastasis-associated genes and its molecular mechanisms. Methods: 22690 mouse genome cDNA microarrays (including 14500 known genes and 4371 ESTs) were used to compare and analyze the gene expression profiles of mouse hepatocellular carcinoma cell lines Hca-F (highly lymphatic metastasis potential) and Hca-P (low potential). Results: 901 genes and 129 ESTs were up-regulated at least 2-fold in Hca-F cell. 33 genes showing significant alterations in expression were presented, including endoglin (EDG), MCAM, Cdc42ep5, F2r, D7Ertd458e, Serpin hl (HSP47), AXL, Areg and so on. These genes have functions of angiogenesis, cell adhesion, signal transduction, cell motility, chaperone activity, protein kinase activity and receptor binding. Conclusion: cDNA microarray combined with lymphatic metastasis models might contribute new methods and clues to the neoplasm lymphatic metastasis research. Some overexpressed genes might provide novel clues to the molecular mechanisms of neoplasm lymphatic metastasis. 展开更多
关键词 Hepatocellular carcinoma lymphatic metastasis cDNA microarray
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Pattern of Lymphatic Metastasis and Influencing Factors in Thoracic Esophageal Carcinoma
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作者 Jun Wang Chun Han Shuchai Zhu Chao Gao Xiaoning Li 《Clinical oncology and cancer researeh》 CAS CSCD 2009年第5期342-346,共5页
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 esophag... 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 were 14.0%, 9.6%, 4.3% and 18.3%, respectively (X^2 = 19.292, P = 0.000), among which the NMR of the fungoid-type EC was the lowest. The LMRs were 42.5% and 75.0%, respectively in the cases with squamous cell carcinoma (SqCC) and poorly differentiated SqCC (X^2 = 4.852, P = 0.028), and the NMRs were 9.5% and 18.6% correspondingly in the 2 groups (X^2 = 11.323, P = 0.001). LM was commonly seen in the cases with poorly differentiated tumors. CONCLUSION Lymph node metastases of TEC spreads widely and can involve many regions. Metastasis can even be found in early stages of EC. Morphologic type and the degree of tumor differentiation are the main factors affecting the LM. 展开更多
关键词 esophageal carcinoma/thoracic segment lymphatic metastasis surgery.
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Investigation of the relationship between DNA-dependent protein kinase and lymphatic metastasis in colorectal cancer
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作者 Yueyu Chen Zhaohui Liu +2 位作者 Kun Zhu Yuelong Wu Haoran Yin 《The Chinese-German Journal of Clinical Oncology》 CAS 2008年第6期348-351,共4页
Objective: To investigate DNA-dependent protein kinase (DNA-PK) expression,and its relationship with lymphat-ic metastasis in colorectal cancer. Methods: Tumor tissues from 60 patients,divided into two groups accordin... Objective: To investigate DNA-dependent protein kinase (DNA-PK) expression,and its relationship with lymphat-ic metastasis in colorectal cancer. Methods: Tumor tissues from 60 patients,divided into two groups according to lymphatic metastasis,were immunohistochemically stained to detect the DNA-PK expression including Ku70,Ku80 and PKcs proteins. Results: Positivity of both Ku70 and Ku80 in colorectal cancer was negatively correlated with lymphatic metastasis with an r value of -0.57 and -0.38,respectively. Similar correlation was found between Ku expression,especially Ku70,and long-term survival. PKcs,however,displayed no significant correlation. Statistical analysis failed to detect any correlation between DNA-PK expression,and clinical characteristics,such as age,sex,tumor location,tumor thickness and distant metastasis (P>0.05). Conclusion: DNA-PK expression,especially Ku70 expression,is negatively correlated with lymphatic metastasis,and the survival of patients with colorectal cancer. Ku70 expression may be a potential indicator for the preoperative evaluation,and prognosis in colorectal cancer. 展开更多
关键词 colorectal cancer lymphatic metastasis DNA-dependent protein kinase gene (DNA-PK gene)
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Study on the risk factors of lymphatic metastasis and the indications of less invasive operations in early gastric cancer 被引量:15
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作者 Jiang BJ Sun RX +1 位作者 Lin H Gao YF 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第4期553-556,共4页
The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic a... The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic accuracy of early gastric cancer (EGC) without lymphatic metastasis has obviously improved with an improvement in the diagnostic technique and due to the accumulation of knowledge on the biological profiles of EG C[10-17]. The D2 lymph node excision was used as a regular operation to treat the EGC previously. But the concept for the EGC without lymphatic metastasis has gradually changed and the less invasive resections has been applied in some cases[18-20]. This study aimed at investigating the risk factors of lymphatic metastasis in EGC in order to find out the proofs for the suitable indications for less invasive operations such as endoscopic mucosal resectioning (EMR), laparoscopic and laparotomic resectioning. 展开更多
关键词 stomach neoplasms/diagnosis NEOPLASM metastasis PRECANCEROUS conditions risk factors surgery/operative lymphatic metastasis LYMPH node excision
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Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer 被引量:12
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作者 Zhen-Jun Li Xiao-Jiang Ying +6 位作者 Hong-Liang Chen Ping-Jiang Ye Zhi-Liang Chen Gang Li Hua-Feng Jiang Jiang Liu Shu-Zhen Zhou 《World Journal of Gastroenterology》 SCIE CAS 2013年第43期7788-7794,共7页
AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lympha... AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC. 展开更多
关键词 Colorectal cancer INSULIN-LIKE GROWTH factor-1 INSULIN-LIKE GROWTH factor-1 receptor LYMPHANGIOGENESIS lymphatic metastasis
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Matrix metalloproteinase-9-1562C>T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer 被引量:12
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作者 Li-Li Xing Zhen-Ning Wang +5 位作者 Li Jiang Yong Zhang Ying-Ying Xu Juan Li Yang Luo Xue Zhang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第34期4626-4629,共4页
AIM. To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population.METHODS: Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was car... AIM. To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population.METHODS: Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).RESULTS: The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR + RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102, 95% CI = 0.013-0.812; P = 0.012).CONCLUSION: Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer. 展开更多
关键词 Matrix metalloproteinase-9 POLYMORPHISMS Colorectal cancer lymphatic node metastasis
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Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer 被引量:2
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作者 Mingjian GE Mei WANG +5 位作者 Qingchen WU Zhiming QIN Li CHEN Liangbin LI Li LI Xiaolong ZHAO 《中国肺癌杂志》 CAS 2009年第9期945-950,共6页
背景与目的筛选肺鳞癌患者淋巴转移差异表达基因群。方法原发癌组织及区域淋巴结取自10例接受完全性肺癌切除手术的肺鳞癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺鳞癌组织(TxN-,n=5)、伴有淋巴转移的肺鳞癌组织(TxN+,n=5)... 背景与目的筛选肺鳞癌患者淋巴转移差异表达基因群。方法原发癌组织及区域淋巴结取自10例接受完全性肺癌切除手术的肺鳞癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺鳞癌组织(TxN-,n=5)、伴有淋巴转移的肺鳞癌组织(TxN+,n=5)及相应转移淋巴结中的肺鳞癌细胞(N+,n=5)。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果共有37个基因可将TxN+组与TxN-组区分开,其中在TxN+组高表达的基因有8个,主要涉及蛋白合成、信号传导、伴侣蛋白和酶等。有29个基因在TxN-组高表达,这些基因主要编码细胞周期调节子、转导子、信号传导蛋白以及细胞凋亡调节蛋白。比较N+组与TxN+组却没有发现具有显著性的差异表达基因。结论肺鳞癌的淋巴转移表型的获得可能是早期事件。这些差异基因的发现有助于阐明肺鳞癌淋巴转移的分子机制和寻找新的治疗靶点。 展开更多
关键词 肺肿瘤 淋巴转移 基因表达 治疗
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Targeting Annexin A7 in Hepatocarcinoma Lymphatic Metastasis 被引量:1
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作者 Mmgzhong SUN Shuqing LIU Jianwu TANG 《中国肺癌杂志》 CAS 2009年第6期633-634,共2页
Background and objective The rst aim was to measure the expressions of Annexin A7 (Anxa7) at mRNA level and protein level in two mice hepatocarcinoma ascites syngeneic cell
关键词 MRNA 肺癌 临床 治疗 疗效
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SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer 被引量:2
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作者 Xiayao Diao Chao Guo +19 位作者 Hanhao Zheng Ke Zhao Yuming Luo Mingjie An Yan Lin Jiancheng Chen Yuanlong Li Yuting Li Xuehan Gao Jiaqi Zhang Mengxin Zhou Wenliang Bai Lei Liu Guige Wang Lanjun Zhang Xiaotian He Rusi Zhang Zhihua Li Changhao Chen Shanqing Li 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2023年第12期5887-5903,共17页
Lymph node(LN)metastasis is one of the predominant metastatic routes of non-small cell lung cancer(NSCLC)and is considered as a leading cause for the unsatisfactory prognosis of patients.Although lymphangiogenesis is ... Lymph node(LN)metastasis is one of the predominant metastatic routes of non-small cell lung cancer(NSCLC)and is considered as a leading cause for the unsatisfactory prognosis of patients.Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis,the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear.In this study,we employed high-throughput sequencing to identify a novel circular RNA(circRNA),circTLCD4-RWDD3,which was significantly upregulated in extracellular vesicles(EVs)from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort.Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo.Mechanically,circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9.Subsequently,circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif(SIM)of ALIX and activated ALIX to recruit ESCRT-III,thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs.Moreover,EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1,resulting in the lymphangiogenesis and LN metastasis of NSCLC.Importantly,blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo.Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC,suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC. 展开更多
关键词 metastasis inhibited lymphatic
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Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies
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作者 Hanhao Zheng Daiyin Liu +4 位作者 Zhicong Liu Mingjie An Yuming Luo Changhao Chen Tianxin Lin 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第6期445-450,共6页
Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of can... Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system. 展开更多
关键词 metastasis lymphatic LANDSCAPE
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Pathologic features of occult lymphatic metastasis in supraglottic carcinoma 被引量:2
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作者 季文樾 于靖 寰关超 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第1期88-89,共2页
OBJECTIVE: To study the pathologic features of occult lymphatic metastasis in supraglottic carcinoma. METHODS: Serial sections of 153 neck dissection specimens in 100 patients with supraglottic carcinoma were evaluate... OBJECTIVE: To study the pathologic features of occult lymphatic metastasis in supraglottic carcinoma. METHODS: Serial sections of 153 neck dissection specimens in 100 patients with supraglottic carcinoma were evaluated under the microscope. RESULTS: In 100 patients, 38 had occult metastatic lymph nodes. 51 metastatic lymph nodes were found in pathology, and their sizes ranged from 0.5 cm to 2.6 cm (average 1.1 cm). The distribution of 51 lymph nodes was 1 in level I (2%), 37 in level II (73%), 12 in level III (24%), and 1 in level IV (2%). Among the 51 nodes, 21 (41%) were early stage, 18 (35%) were growth stage, 7 (14%) were tull stage, and 5 (10%) were extracapsular stage. The differentiation degree and appearance of supraglottic carcinoma was not directly related with occult metastasis. CONCLUSION: The occult metastatic rate of supraglottic carcinoma is high, and selective neck dissection may be necessary. 展开更多
关键词 GLOTTIS ADULT Aged Female Humans Laryngeal Neoplasms lymphatic metastasis Male Middle Aged Research Support Non-U.S. Gov't
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HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5-WDR5-dependent transcriptional program 被引量:3
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作者 Ming Huang Wen Dong +14 位作者 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 《Cancer Communications》 SCIE 2022年第5期447-470,共24页
Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptom... Background:Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options.Emerging evidence shows that heat shock factor 1(HSF1)drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target.However,the roles of HSF1 in lymphatic metastasis remain largely unknown.Herein,we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential.Methods: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 cohorts.Functional in vitro and in vivo assays were performed in HSF1-silenced and-regained models.We 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 HSF1.The pharmacological inhibitor of HSF1,KRIBB11,was evaluated in popliteal lymph node metastasis models and patientderived xenograft models of bladder cancer.Results:HSF1 expression was positively associated with lymphatic metastasis status,tumor stage,advanced grade,and poor prognosis of bladder cancer.Importantly,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 metastasis.Mechanistically,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 metallopeptidase 9(MMP9),C-C motif chemokine ligand 20(CCL20),and E2F transcription factor 2(E2F2).Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity.Conclusion:Our findings reveal a novel transcriptional program directed by the HSF1-PRMT5-WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer.Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis. 展开更多
关键词 HSF1 PRMT5 KRIBB11 transcriptional program bladder cancer lymphatic metastasis prognostic factor targeted therapy
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