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
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
INTRODUCTIONThe principle of surgical treatment for gastric cancer is theradical resectioning although the suitable resetting range fordifferent cases of gastric cancer is still being arguedupon.However,the diagnostic...INTRODUCTIONThe principle of surgical treatment for gastric cancer is theradical resectioning although the suitable resetting range fordifferent cases of gastric cancer is still being arguedupon.However,the diagnostic accuracy of展开更多
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
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
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
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
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
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 MMP-9 -1562C>T and 279R>Q polymorphisms was ca...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 MMP-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 MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph 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
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
Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapie...Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)展开更多
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
AIM:To explore risk factors of lymphatic metastasis(LM)in gallbladder cancer,and their potential to complement unsatisfactory radiological detection.METHODS:Radiological detection of LM by computed tomography(CT)was r...AIM:To explore risk factors of lymphatic metastasis(LM)in gallbladder cancer,and their potential to complement unsatisfactory radiological detection.METHODS:Radiological detection of LM by computed tomography(CT)was reported to fail in more than60%of patients with pathological LM.In order to find risk factors highly suggestive of LM other than radiological manifestations,the documents of 63 patients were analyzed statistically.Except for 4 patients having T1a disease,in whom cholecystectomy is enough for radical resection,59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected.Fifty point eight percent(32/63)of patients were found to have LM during pathological examination.The median number of dissected lymph nodes was 6(range 3-20).RESULTS:Only 31.3%(10/32)of patients with LM were detected by CT.Through multivariate analysis,two risk factors of LM were discovered as age<60years(OR=6.24;P<0.01)and carbohydrate antigen(CA)19-9 elevation(OR=5.70;P<0.05).By analysis of patients with pathological LM but failed to be detected by CT,81.8%(18/22)of patients had at least one risk factor,including 31.3%(10/32)who had the risk factor of age<60 years,and 37.5%(12/32)who had the risk factor of CA 19-9 elevation.Besides,among patients with LM(n=32),those whose age were younger than 60 years(OR=3.41;P<0.05)were more likely to have 3 or more positive lymph nodes.CONCLUSION:Age<60 years and CA 19-9 elevation could complement radiological detection of LM.Patients aged<60 years are at higher risk of multiple positive nodes.展开更多
Objective:Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported,the risk factors for skip lymphatic metastasis are still controversy and debatable.This study inve...Objective:Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported,the risk factors for skip lymphatic metastasis are still controversy and debatable.This study investigated,by multivariate logistic regression analysis,the clinical features of skip metastasis to mediastinal lymph nodes(N2) in non-small cell lung cancer(NSCLC) patients.Methods:We collected the clinicopathological data of 256 pN2-NSCLC patients who underwent lobectomy plus systemic lymph node dissection in Fujian Medical University Union Hospital.The cases in the present study were divided into two groups:skip metastasis(N2 skip+) and non-skip metastasis(N2 skip-).A retrospective analysis of clinical pathological features of two groups was performed.To determine an independent factor,multivariate logistic regression analysis was used to identify possible risk factors.Results:A total of 256 pN2-NSCLC patients were recruited.The analysis results showed that gender,pathologic types,surgery,pleural involvement,smoking history,age,tumor stages,and differentiation were not statistical significant factors impacting on skip metastasis in pN2-NSCLC(P>0.05),whereas tumor size was an independent factor for skip metastasis(P=0.02).Conclusions:The rate of skip lymphatic metastasis increases in pN2-NSCLC patients,in accompany with an increased tumor size.展开更多
AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high pote...AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed.RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes.CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.展开更多
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 ...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 h1 (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
OBJECTIVE To explore the regular patterns of lymphaticmetastasis in thoracic esophageal carcinoma (TEC) and the factorsinfluencing these patterns.METHODS Data of 229 TEC patients who underwent radicalesophagectomy and...OBJECTIVE To explore the regular patterns of lymphaticmetastasis in thoracic esophageal carcinoma (TEC) and the factorsinfluencing these patterns.METHODS Data of 229 TEC patients who underwent radicalesophagectomy and thoracoabdominal 2-field lymphadenectomywere reviewed.Within this patient population,a total of 2458lymph nodes were dissected during surgery.The distributionof the nodular metastasis rates (NMR) in various diseasedregions in the esophageal carcinoma (EC) patients as wellas factors influencing metastases such as the depth of tumorinfiltration,tumor size,tumor morphology,and degree of tumordifferentiation were analyzed.RESULTS i) Lymphatic metastasis (LM) occurred in 102 ECcases,and the lymphatic metastasis rate (LMR) was 44.5%(102/229).The NMR was 9.5% (258/2458).ii) The NMRs were19.0%,6.7%,9.8% and 12.2% in the superior,middle and inferiormediastinum,and abdominal cavity,respectively,in patientswith EC in the superior thoracic segment;26.1%,7.4%,11.8% and11.9% in the same sites of the mediastinum,respectively,in thosewith 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 were28.6%,43.8%,47.6% and 31.3%,respectively,and the NMRs of thepatients were 7.9%,10.8%,10.7% and 10.8%,respectively.Therewere no significant differences between the LMR and the NMR ofthe EC patients in stage T1 to T4 (X^2=2.733,P=0.435 and X^2=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 crn were 45.2%,43.4% and 46.2%,respectively,and the NMR according to the same range of thetumor size above were 9.1%,11.6% and 11.7%,respectively.Therewere no significant differences between the groups (X^2=0.094,P=0.954 and X^2=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 theNMR of the fungoid-type EC was the lowest.The LMRs were42.5% and 75.0%,respectively in the cases with squamous cellcarcinoma (SqCC) and poorly differentiated SqCC (X^2=4.852,P=0.028),and the NMRs were 9.5% and 18.6% correspondingly inthe 2 groups (X^2=11.323,P=0.001).LM was commonly seen in thecases with poorly differentiated tumors.CONCLUSION Lymph node metastases of TEC spreads widelyand can involve many regions.Metastasis can even be found inearly stages of EC.Morphologic type and the degree of tumordifferentiation are the main factors affecting the LM.展开更多
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
Objective: To identify new markers for prediction of lymph node metastasis. Methods: cDNA probeswere prepared by labeling mRNA from samples of four pancreatic carcinoma tissues with Cy5-dUTP andmRNA from adjacent norm...Objective: To identify new markers for prediction of lymph node metastasis. Methods: cDNA probeswere prepared by labeling mRNA from samples of four pancreatic carcinoma tissues with Cy5-dUTP andmRNA from adjacent normal tissues with Cy3-dUTP respectively through reverse transcription. The mixedprobes of each sample were then hybridized with 4,096 cDNA arrays (4,000 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values ofCy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Genes that differentially expresses in eachcancerous tissue were sought out according to thestandard that the absolute value of natural logarithm of the ratio of Cy5 to Cy3 is greater than 0.69, i. e., more than 2 times change of gene expression, and the signal value of either Cy3 and Cy5 need to be greater than600. Then, the genes differently expressed in cancerwith and without lymphatic metastasis were screenedout for further analysis. Results: Among 2 samples with lymphatic metastasis and 2 samples without metastasis, 56 genes, which accounted for 1.40% of genes on the microarray slides, exhibited differentially expression in cancerous tissues with lymphatic metastasis. There were 32 over-expressed genes including 11 having beenregistered in Genebank, and 24 under-expressed genes including 3 in Genebank. Conclusion: Microarray analysis may provide invaluable information to identify specific gene expression profile of lymphatic metastasis in pancreatic cancer.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82173303)Natural Science Foundation of Chongqing,China(Grant No.cstc2021ycjh-bgzxm0149).
文摘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.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2022YFA1305500)the National Natural Science Foundation of China(Grant Nos.82173272,82103536,81871945,and 81902589)+1 种基金the Guangdong Science and Technology Department(Grant Nos.2022B1515120086,and 2021B1515020091)the Science and Technology Program of Guangzhou(Grant Nos.202002030388,2022A1515012288,and 2021A1515010355)。
文摘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.
基金Scientific Research Foundation for Returned Overseas Chinese Scholars,Slate Education Commission(1997-832)
文摘INTRODUCTIONThe principle of surgical treatment for gastric cancer is theradical resectioning although the suitable resetting range fordifferent cases of gastric cancer is still being arguedupon.However,the diagnostic accuracy of
基金Supported by Technological Research Project for Public Welfare from Science and Technology Department of Zhejiang Province,No.2010C33099
文摘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.
基金supported by a grant from the National Nature Science Foundation of China(81071982)
文摘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.
基金Supported by TUBTAK-SBAG (Project Number 104S581)the Turkish Academy of Sciences (TUBA)
文摘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.
基金Supported by the National Natural Science Foundation of China,No. 30371583
文摘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.
文摘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.
基金Program for New Century Excellent Talents in University, NCET-06-0296
文摘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 MMP-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 MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph 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.
基金Supported by Creating Team Item of Liaoning Province, No.2008T033the Technological Natural Fund Item of Liaoning Province, China, No. 20092164
文摘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.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81802296)Natural Science Foundation of Tianjin(Grant No.18JCQNJC82500)Tianjin Municipality Science and Technology Commission Projects(Grant No.12ZCDZSY15600).
文摘Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)
基金supported by grant from the scientif ic fund of the Ministry of Personnel for returned overseas expert (2006)Natural Science Foundation Project of CQ CSTC (to Mingjian GE)(CSTC, No.2008BB5210)
文摘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
文摘AIM:To explore risk factors of lymphatic metastasis(LM)in gallbladder cancer,and their potential to complement unsatisfactory radiological detection.METHODS:Radiological detection of LM by computed tomography(CT)was reported to fail in more than60%of patients with pathological LM.In order to find risk factors highly suggestive of LM other than radiological manifestations,the documents of 63 patients were analyzed statistically.Except for 4 patients having T1a disease,in whom cholecystectomy is enough for radical resection,59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected.Fifty point eight percent(32/63)of patients were found to have LM during pathological examination.The median number of dissected lymph nodes was 6(range 3-20).RESULTS:Only 31.3%(10/32)of patients with LM were detected by CT.Through multivariate analysis,two risk factors of LM were discovered as age<60years(OR=6.24;P<0.01)and carbohydrate antigen(CA)19-9 elevation(OR=5.70;P<0.05).By analysis of patients with pathological LM but failed to be detected by CT,81.8%(18/22)of patients had at least one risk factor,including 31.3%(10/32)who had the risk factor of age<60 years,and 37.5%(12/32)who had the risk factor of CA 19-9 elevation.Besides,among patients with LM(n=32),those whose age were younger than 60 years(OR=3.41;P<0.05)were more likely to have 3 or more positive lymph nodes.CONCLUSION:Age<60 years and CA 19-9 elevation could complement radiological detection of LM.Patients aged<60 years are at higher risk of multiple positive nodes.
文摘Objective:Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported,the risk factors for skip lymphatic metastasis are still controversy and debatable.This study investigated,by multivariate logistic regression analysis,the clinical features of skip metastasis to mediastinal lymph nodes(N2) in non-small cell lung cancer(NSCLC) patients.Methods:We collected the clinicopathological data of 256 pN2-NSCLC patients who underwent lobectomy plus systemic lymph node dissection in Fujian Medical University Union Hospital.The cases in the present study were divided into two groups:skip metastasis(N2 skip+) and non-skip metastasis(N2 skip-).A retrospective analysis of clinical pathological features of two groups was performed.To determine an independent factor,multivariate logistic regression analysis was used to identify possible risk factors.Results:A total of 256 pN2-NSCLC patients were recruited.The analysis results showed that gender,pathologic types,surgery,pleural involvement,smoking history,age,tumor stages,and differentiation were not statistical significant factors impacting on skip metastasis in pN2-NSCLC(P>0.05),whereas tumor size was an independent factor for skip metastasis(P=0.02).Conclusions:The rate of skip lymphatic metastasis increases in pN2-NSCLC patients,in accompany with an increased tumor size.
基金Supported by National Natural Science Foundation of China, No.30371583
文摘AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed.RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes.CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.
基金This work was supported by the National Natural Science Foundation of China (No.30371583).
文摘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 h1 (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.
基金supported by a grant from the Hebei Provincial Foundation for the Subjects with High Scholarship and Creative Research Potential in Ordinary Colleges and Universities,China (No.52,2005)
文摘OBJECTIVE To explore the regular patterns of lymphaticmetastasis in thoracic esophageal carcinoma (TEC) and the factorsinfluencing these patterns.METHODS Data of 229 TEC patients who underwent radicalesophagectomy and thoracoabdominal 2-field lymphadenectomywere reviewed.Within this patient population,a total of 2458lymph nodes were dissected during surgery.The distributionof the nodular metastasis rates (NMR) in various diseasedregions in the esophageal carcinoma (EC) patients as wellas factors influencing metastases such as the depth of tumorinfiltration,tumor size,tumor morphology,and degree of tumordifferentiation were analyzed.RESULTS i) Lymphatic metastasis (LM) occurred in 102 ECcases,and the lymphatic metastasis rate (LMR) was 44.5%(102/229).The NMR was 9.5% (258/2458).ii) The NMRs were19.0%,6.7%,9.8% and 12.2% in the superior,middle and inferiormediastinum,and abdominal cavity,respectively,in patientswith EC in the superior thoracic segment;26.1%,7.4%,11.8% and11.9% in the same sites of the mediastinum,respectively,in thosewith 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 were28.6%,43.8%,47.6% and 31.3%,respectively,and the NMRs of thepatients were 7.9%,10.8%,10.7% and 10.8%,respectively.Therewere no significant differences between the LMR and the NMR ofthe EC patients in stage T1 to T4 (X^2=2.733,P=0.435 and X^2=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 crn were 45.2%,43.4% and 46.2%,respectively,and the NMR according to the same range of thetumor size above were 9.1%,11.6% and 11.7%,respectively.Therewere no significant differences between the groups (X^2=0.094,P=0.954 and X^2=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 theNMR of the fungoid-type EC was the lowest.The LMRs were42.5% and 75.0%,respectively in the cases with squamous cellcarcinoma (SqCC) and poorly differentiated SqCC (X^2=4.852,P=0.028),and the NMRs were 9.5% and 18.6% correspondingly inthe 2 groups (X^2=11.323,P=0.001).LM was commonly seen in thecases with poorly differentiated tumors.CONCLUSION Lymph node metastases of TEC spreads widelyand can involve many regions.Metastasis can even be found inearly stages of EC.Morphologic type and the degree of tumordifferentiation are the main factors affecting the LM.
基金a grant from the Scientific Research Project of the Bureau of Health of Jiading in Shanghai (No KYXM-2004-11-07)
文摘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.
文摘Objective: To identify new markers for prediction of lymph node metastasis. Methods: cDNA probeswere prepared by labeling mRNA from samples of four pancreatic carcinoma tissues with Cy5-dUTP andmRNA from adjacent normal tissues with Cy3-dUTP respectively through reverse transcription. The mixedprobes of each sample were then hybridized with 4,096 cDNA arrays (4,000 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values ofCy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Genes that differentially expresses in eachcancerous tissue were sought out according to thestandard that the absolute value of natural logarithm of the ratio of Cy5 to Cy3 is greater than 0.69, i. e., more than 2 times change of gene expression, and the signal value of either Cy3 and Cy5 need to be greater than600. Then, the genes differently expressed in cancerwith and without lymphatic metastasis were screenedout for further analysis. Results: Among 2 samples with lymphatic metastasis and 2 samples without metastasis, 56 genes, which accounted for 1.40% of genes on the microarray slides, exhibited differentially expression in cancerous tissues with lymphatic metastasis. There were 32 over-expressed genes including 11 having beenregistered in Genebank, and 24 under-expressed genes including 3 in Genebank. Conclusion: Microarray analysis may provide invaluable information to identify specific gene expression profile of lymphatic metastasis in pancreatic cancer.
