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
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: 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
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
Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunoh...Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results: The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P〈0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. Conclusion: LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.展开更多
The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened ou...The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 (4. 85 %) genes significantly differed between the ESCC with and without lymphatic metastasis (P〈0.05), of which 18(2.03 %)were upregulated and 25 (2.82 %) down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.展开更多
Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma(NPC),but occipital lymph node metastasis in NPC patients has not yet been reported.In this case report,we describe an NPC patient with...Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma(NPC),but occipital lymph node metastasis in NPC patients has not yet been reported.In this case report,we describe an NPC patient with occipital lymph node metastasis.The clinical presentation,diagnostic procedure,treatment,and outcome of this case were presented,with a review of the related literature.展开更多
AIM To study the effect of cell fusion on metastatic ability of mouse hepatocarcinoma cells and the factors involved in the process of metastasis. METHODS By the method of successively increasing the concentrations...AIM To study the effect of cell fusion on metastatic ability of mouse hepatocarcinoma cells and the factors involved in the process of metastasis. METHODS By the method of successively increasing the concentrations, cell fusion and limit dilution, 8 Ag resistant cells were selected, and HGPRT - Hca P cells and eight cloned hybridoma cells were obtained. To observe their metastatic ability, they were inoculated into mice foodtaps and the drainage lymph nodes were examined under microscope. RESULTS The end concentration of 8 Ag which was used to select HGPRT deficient Hca P cells was 30mg/L . All the cells selected died in HAT culture medium in one week. Fused cells appeared approximately 9 days later. They were round, transparent and a little larger than their parental cells. Eight clones of hybridoma cells were obtained and named as PSH1 PSH8. The metastatic rate of HGPRT - Hca P cells and PSH7 cells was 28 6% and 71 4% respectively, the difference being significant ( P <0 05). The metastatic rate of other clones was no more than 20% and there was no significant difference from HGPRT - Hca P cells ( P >0 05). CONCLUSION In normal mice splenic lymphocytes, there are some factors that could inhibit tumor metastasis, however, there are some other factors accelerating tumor cells to metastasize. The establishment of PSH7 provides an experimental model which could be used to study the factors involved in metastasis.展开更多
Objective: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective n...Objective: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.展开更多
This paper introduces an innovative treatment for extrahepatic metastasis of hepatocellular carcinoma. A 71-yearold patient had a stable liver condition following treatment for hepatocellular carcinoma, but later deve...This paper introduces an innovative treatment for extrahepatic metastasis of hepatocellular carcinoma. A 71-yearold patient had a stable liver condition following treatment for hepatocellular carcinoma, but later developed symptomatic mediastinal metastasis. This rapidly growing mediastinal mass induced symptoms including cough and hoarseness. Serial sessions of transarterial embolization (TAE) successfully controlled this mediastinal mass with limited side effects. The patient's survival time since the initial diagnosis of the mediastinal hepatocellular carcinoma was 32 mo, significantly longer than the 12 mo mean survival period of patients with similar diagnoses: metastatic hepatocellular carcinoma and a liver condition with a Child-Pugh class A score. Currently, oral sorafenib is the treatment of choice for metastatic hepatocellular carcinoma. Recentstudies indicate that locoregional treatment of extrahepatic metastasis of hepatocellular carcinomas might also significantly improve the prognosis in patients with their primary hepatic lesions under control. Many effective locoregional therapies for extrahepatic metastasis, including radiation and surgical resection, may provide palliative effects for hepatocellular carcinoma-associated mediastinal metastasis. This case report demonstrates that TAE of metastatic mediastinal hepatocellular carcinoma provided this patient with tumor control and increased survival time. This finding is important as it can potentially provide an alternative treatment option for patients with similar symptoms and diagnoses.展开更多
Objectives To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasi...Objectives To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasis in lingual carcinoma. Methods Thirty patients with lingual carcinoma without lymph metastasis were injected with a dose of about 18.5 MBq of 99m Tc-SC (sulfur colloid), around the tumor tissues before surgery,and lymphoscintigraphy was performed 5,10,30,60 minutes,and 6 hours after injection. In the following day,all patients were injected with isosulfan blue dye around the primary tumor during surgery to trace SLN and underwent standard cervical lymph node dissection after SLN dissection. The pathological results of SLN were compared with standard lymph node dissection for their ability to accurately predict the final pathological status of the cervical lymph nodes.Results SLN was successfully identified in 100% of the patients. Both positive and negative predictive values of SLN were 100%. The accuracy rate was 100%,and there were no false negatives. Conclusions The detection of SLN using combined dye-isotope technique could accurately predict cervical lymph node metastasis in lingual carcinoma.展开更多
Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eig...Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.展开更多
OBJECTIVE To examine the expression of vascular endothelial growth factor C (VEGF-C) in human esophageal squamous cell carcinoma (ESCC), and to clarify its role in lymphatic metastasis in ESCC patients.METHODS Eso...OBJECTIVE To examine the expression of vascular endothelial growth factor C (VEGF-C) in human esophageal squamous cell carcinoma (ESCC), and to clarify its role in lymphatic metastasis in ESCC patients.METHODS Esophageal carcinoma EC9706 cells and samples from 49 patients with primary ESCC were investigated by using S-P immunohistochemistry (IHC), the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC, ISH and RT-PCR. Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in a lymph-node-positive group compared to a node-negative group (χ^2=4.7, P〈0.05). Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group (χ^2=31.3, P〈0.01). The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group. Of 49 ESCC tissues, RT-PCR for VEGF-C mRNA was observed positively in 29 cases. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group (χ^2=23.3, P〈0.01). The expression of VEGF-C was significantly higher in the lymphnode-positive group compared to the node-negative group. Expressions of VEGF-C were not significantly associated with age, gender, and pathological grade. There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH (χ^2=18.5, P〈0.01) in ESCC cases, but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC. There was a close correlation between VEGF-C expression and lymph node metastasis. VEGF-C can serve as a useful prognostic factor for ESCC patients.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 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 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 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.
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 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.
基金supported by the Science and Technology Development Planning of Shandong Provincethe China Postdoctoral Science Fund (Grant No.2012GGE27088 andNo.2011M500531)
文摘Objective: This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results: The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P〈0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors. Conclusion: LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.
基金This project was supported by a grant of 2004 Henan Pro-vincial Science and Technology Key Program Foundation(No .0424410109)
文摘The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 (4. 85 %) genes significantly differed between the ESCC with and without lymphatic metastasis (P〈0.05), of which 18(2.03 %)were upregulated and 25 (2.82 %) down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.
文摘Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma(NPC),but occipital lymph node metastasis in NPC patients has not yet been reported.In this case report,we describe an NPC patient with occipital lymph node metastasis.The clinical presentation,diagnostic procedure,treatment,and outcome of this case were presented,with a review of the related literature.
文摘AIM To study the effect of cell fusion on metastatic ability of mouse hepatocarcinoma cells and the factors involved in the process of metastasis. METHODS By the method of successively increasing the concentrations, cell fusion and limit dilution, 8 Ag resistant cells were selected, and HGPRT - Hca P cells and eight cloned hybridoma cells were obtained. To observe their metastatic ability, they were inoculated into mice foodtaps and the drainage lymph nodes were examined under microscope. RESULTS The end concentration of 8 Ag which was used to select HGPRT deficient Hca P cells was 30mg/L . All the cells selected died in HAT culture medium in one week. Fused cells appeared approximately 9 days later. They were round, transparent and a little larger than their parental cells. Eight clones of hybridoma cells were obtained and named as PSH1 PSH8. The metastatic rate of HGPRT - Hca P cells and PSH7 cells was 28 6% and 71 4% respectively, the difference being significant ( P <0 05). The metastatic rate of other clones was no more than 20% and there was no significant difference from HGPRT - Hca P cells ( P >0 05). CONCLUSION In normal mice splenic lymphocytes, there are some factors that could inhibit tumor metastasis, however, there are some other factors accelerating tumor cells to metastasize. The establishment of PSH7 provides an experimental model which could be used to study the factors involved in metastasis.
基金supported by grants from National Natural Science Foundation of China (No. 81372884 and No. 81672679)5010 Project of Clinical Study, Sun Yat-sen University (No. 2010018)
文摘Objective: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.
文摘This paper introduces an innovative treatment for extrahepatic metastasis of hepatocellular carcinoma. A 71-yearold patient had a stable liver condition following treatment for hepatocellular carcinoma, but later developed symptomatic mediastinal metastasis. This rapidly growing mediastinal mass induced symptoms including cough and hoarseness. Serial sessions of transarterial embolization (TAE) successfully controlled this mediastinal mass with limited side effects. The patient's survival time since the initial diagnosis of the mediastinal hepatocellular carcinoma was 32 mo, significantly longer than the 12 mo mean survival period of patients with similar diagnoses: metastatic hepatocellular carcinoma and a liver condition with a Child-Pugh class A score. Currently, oral sorafenib is the treatment of choice for metastatic hepatocellular carcinoma. Recentstudies indicate that locoregional treatment of extrahepatic metastasis of hepatocellular carcinomas might also significantly improve the prognosis in patients with their primary hepatic lesions under control. Many effective locoregional therapies for extrahepatic metastasis, including radiation and surgical resection, may provide palliative effects for hepatocellular carcinoma-associated mediastinal metastasis. This case report demonstrates that TAE of metastatic mediastinal hepatocellular carcinoma provided this patient with tumor control and increased survival time. This finding is important as it can potentially provide an alternative treatment option for patients with similar symptoms and diagnoses.
文摘Objectives To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasis in lingual carcinoma. Methods Thirty patients with lingual carcinoma without lymph metastasis were injected with a dose of about 18.5 MBq of 99m Tc-SC (sulfur colloid), around the tumor tissues before surgery,and lymphoscintigraphy was performed 5,10,30,60 minutes,and 6 hours after injection. In the following day,all patients were injected with isosulfan blue dye around the primary tumor during surgery to trace SLN and underwent standard cervical lymph node dissection after SLN dissection. The pathological results of SLN were compared with standard lymph node dissection for their ability to accurately predict the final pathological status of the cervical lymph nodes.Results SLN was successfully identified in 100% of the patients. Both positive and negative predictive values of SLN were 100%. The accuracy rate was 100%,and there were no false negatives. Conclusions The detection of SLN using combined dye-isotope technique could accurately predict cervical lymph node metastasis in lingual carcinoma.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)National Natural Science Foundation of China(Grant Nos.81425018,81672868,81802775,and 81602371)+10 种基金Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)Sun Yat-sen University Clinical Research 5010 ProgramSpecial Support Plan of Guangdong Province(Grant No.2014TX01R145)Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)National Science&Technology Pillar Program during the Twelfth FiveYear Plan Period(Grant No.2014BAI09B10)Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)PhD Start-up Fund of Natural Science Foundation of Guangdong Province(Grant No.2016A030310221)。
文摘Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.
基金This work was supported by a grant from theNational Natural Science Foundation of China(No.30470779)the Henan InnovationProject for University Prominent ResearchTalents(No.2006KYCX016)
文摘OBJECTIVE To examine the expression of vascular endothelial growth factor C (VEGF-C) in human esophageal squamous cell carcinoma (ESCC), and to clarify its role in lymphatic metastasis in ESCC patients.METHODS Esophageal carcinoma EC9706 cells and samples from 49 patients with primary ESCC were investigated by using S-P immunohistochemistry (IHC), the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC, ISH and RT-PCR. Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in a lymph-node-positive group compared to a node-negative group (χ^2=4.7, P〈0.05). Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group (χ^2=31.3, P〈0.01). The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group. Of 49 ESCC tissues, RT-PCR for VEGF-C mRNA was observed positively in 29 cases. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group (χ^2=23.3, P〈0.01). The expression of VEGF-C was significantly higher in the lymphnode-positive group compared to the node-negative group. Expressions of VEGF-C were not significantly associated with age, gender, and pathological grade. There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH (χ^2=18.5, P〈0.01) in ESCC cases, but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC. There was a close correlation between VEGF-C expression and lymph node metastasis. VEGF-C can serve as a useful prognostic factor for ESCC patients.