Tumor lymph node(LN)metastasis seriously affects the treatment prognosis.Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration.Here,we ...Tumor lymph node(LN)metastasis seriously affects the treatment prognosis.Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration.Here,we speculate through introducing targeting capacity,the nanoparticle accumulation in LN metastases would be further enhanced for improved local treatment such as photothermal therapy.Trastuzumabtargeted micelles(<50 nm)were formulated using a unique surfactantstripping approach that yielded concentrated phthalocyanines with strong near-infrared absorption.Targeted micellar phthalocyanine(T-MP)was an effective photothermal transducer and ablated HT-29 cells in vitro.A HER2-expressing colorectal cancer cell line(HT-29)was used to establish an orthotopic mouse model that developed metastatic disease in mesenteric sentinel LN.T-MP accumulated more in the LN metastases compared to the micelles conjugated with control IgG.Following surgical resection of the primary tumor,minimally invasive photothermal treatment of the metastatic LN with T-MP,but not the control micelles,extended mouse survival.Our findings demonstrate for the first time that targeted small-sized nanoparticles have potential to enable superior paradigms for dealing with LN metastases.展开更多
Objective:To investigate the activity of anti-malarial dihydroartemisinin (DHA) on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma (LLC). Methods: The model...Objective:To investigate the activity of anti-malarial dihydroartemisinin (DHA) on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma (LLC). Methods: The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups: control group, DHA group, DHA+ferrous sulfate (FS) group and FS group, with 25 mice in each group. Tumor volumes and weights, nodal and lung metastasis, and survival were monitored. Tumor lymphatic microvessel density (LMVD) was determined by lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) immnohistochemistry. After LLC cells were treated with DHA or DHA+FS, protein and mRNA levels of vascular endothelial growth factor (VEGF) -C were evaluated by Western blotting and real time quantitative RT-PCR, respectively. Results: Oral administration of DHA or DHA+FS inhibited lymph node and lung metastasis, and prolonged survival. However, no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions, but not in the intratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion: DHA effectively inhibits LLC transplantation tumor lymphangiogenesis, nodal and lung metastasis, and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.展开更多
Objective.To identify a subset of breast cancer patients in whom metastatic disease is confined on-ly to the sentinel lymph node(SLN).Methods.Sentinel lymph node biopsy is performed with the injecetion of Tc99m-SC,and...Objective.To identify a subset of breast cancer patients in whom metastatic disease is confined on-ly to the sentinel lymph node(SLN).Methods.Sentinel lymph node biopsy is performed with the injecetion of Tc99m-SC,and a gamma probe.Sentinel node biopsy was compared with standard axillary dissection for its ability to reflect the fi-nal pathological status of the axillary nodes.The factors associated with non-SLN metastases were as-sessed in the univariate and multivariate analysis.Result.We successfully identified91out of95patients for SLN(95.8%).The accuracy of sentinel lymph node to predict the axillary lymph node status was93.4%.Clinical tumor size and tumor grade were proved to be the independent predictive factors for non-SLN metastases by logistic regression model.Conclusion.In most cases,the gamma probe guided method is technically feasible for detecting sentinel nodes,accurately predicting the axillary lymph node status.A subset of the patients identified who have a low risk of non-SLN metastases may not require axillary lymph node dissection.展开更多
Objective: To investigate the potential of superparamagnetic iron oxide particles (SPIO) in MR imaging for the differentiation between hyperplastic and metastatic lymph node. Methods: Animal models of malignant lymph ...Objective: To investigate the potential of superparamagnetic iron oxide particles (SPIO) in MR imaging for the differentiation between hyperplastic and metastatic lymph node. Methods: Animal models of malignant lymph node metastasis were established in 6 New-Zealand rabbits by a unilateral intra-muscular injection of VX2 carcinoma cells, and models of hyperplastic lymph nodes were induced in another 6 rabbits by a unilateral intra-muscular injection of egg yolk emulsion. MR images of the lymph nodes were obtained before and 12 h after interstitial injection of SPIO. Image results were analyzed and compared with pathological findings. Results: On unenhanced images, the signal intensity of hyperplastic and metastatic lymph nodes did not differ significantly. After administration of SPIO, the signal intensity of both hyperplastic and metastatic lymph nodes remained unchanged on T1-weighted SE images. On T2-weighted SE images, the signal intensity of hyperplastic lymph nodes decreased heterogeneously, while that of all metastatic ones remained unchanged. On T2-weighted GRE images, the signal intensity of hyperplastic lymph nodes decreased significantly and homogeneously, while that of 4 metastatic ones remained unchanged and that of the rest 2 decreased heterogeneously. Conclusion: SPIO-enhanced MR imaging may enable the differentiation between the hyperplastic and metastatic lymph nodes.展开更多
基金Hai-Yi Feng and Yihang Yuan contributed equally to this work.We thank Prof.Gang Zheng(University of Toronto)for valuable discussion.We also thank the Core Facility of Basic Medical Sciences(SJTU-SM)for frozen section making and scanningThis work was supported by National Natural Science Foundation of China(81572998,81773274,82073379)+1 种基金Shanghai Municipal Science and Technology Commission(20ZR1451700,16520710700)Shanghai Collaborative Innovation Center for Translational Medicine(TM201731).
文摘Tumor lymph node(LN)metastasis seriously affects the treatment prognosis.Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration.Here,we speculate through introducing targeting capacity,the nanoparticle accumulation in LN metastases would be further enhanced for improved local treatment such as photothermal therapy.Trastuzumabtargeted micelles(<50 nm)were formulated using a unique surfactantstripping approach that yielded concentrated phthalocyanines with strong near-infrared absorption.Targeted micellar phthalocyanine(T-MP)was an effective photothermal transducer and ablated HT-29 cells in vitro.A HER2-expressing colorectal cancer cell line(HT-29)was used to establish an orthotopic mouse model that developed metastatic disease in mesenteric sentinel LN.T-MP accumulated more in the LN metastases compared to the micelles conjugated with control IgG.Following surgical resection of the primary tumor,minimally invasive photothermal treatment of the metastatic LN with T-MP,but not the control micelles,extended mouse survival.Our findings demonstrate for the first time that targeted small-sized nanoparticles have potential to enable superior paradigms for dealing with LN metastases.
文摘Objective:To investigate the activity of anti-malarial dihydroartemisinin (DHA) on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma (LLC). Methods: The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups: control group, DHA group, DHA+ferrous sulfate (FS) group and FS group, with 25 mice in each group. Tumor volumes and weights, nodal and lung metastasis, and survival were monitored. Tumor lymphatic microvessel density (LMVD) was determined by lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) immnohistochemistry. After LLC cells were treated with DHA or DHA+FS, protein and mRNA levels of vascular endothelial growth factor (VEGF) -C were evaluated by Western blotting and real time quantitative RT-PCR, respectively. Results: Oral administration of DHA or DHA+FS inhibited lymph node and lung metastasis, and prolonged survival. However, no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions, but not in the intratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion: DHA effectively inhibits LLC transplantation tumor lymphangiogenesis, nodal and lung metastasis, and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.
文摘Objective.To identify a subset of breast cancer patients in whom metastatic disease is confined on-ly to the sentinel lymph node(SLN).Methods.Sentinel lymph node biopsy is performed with the injecetion of Tc99m-SC,and a gamma probe.Sentinel node biopsy was compared with standard axillary dissection for its ability to reflect the fi-nal pathological status of the axillary nodes.The factors associated with non-SLN metastases were as-sessed in the univariate and multivariate analysis.Result.We successfully identified91out of95patients for SLN(95.8%).The accuracy of sentinel lymph node to predict the axillary lymph node status was93.4%.Clinical tumor size and tumor grade were proved to be the independent predictive factors for non-SLN metastases by logistic regression model.Conclusion.In most cases,the gamma probe guided method is technically feasible for detecting sentinel nodes,accurately predicting the axillary lymph node status.A subset of the patients identified who have a low risk of non-SLN metastases may not require axillary lymph node dissection.
文摘Objective: To investigate the potential of superparamagnetic iron oxide particles (SPIO) in MR imaging for the differentiation between hyperplastic and metastatic lymph node. Methods: Animal models of malignant lymph node metastasis were established in 6 New-Zealand rabbits by a unilateral intra-muscular injection of VX2 carcinoma cells, and models of hyperplastic lymph nodes were induced in another 6 rabbits by a unilateral intra-muscular injection of egg yolk emulsion. MR images of the lymph nodes were obtained before and 12 h after interstitial injection of SPIO. Image results were analyzed and compared with pathological findings. Results: On unenhanced images, the signal intensity of hyperplastic and metastatic lymph nodes did not differ significantly. After administration of SPIO, the signal intensity of both hyperplastic and metastatic lymph nodes remained unchanged on T1-weighted SE images. On T2-weighted SE images, the signal intensity of hyperplastic lymph nodes decreased heterogeneously, while that of all metastatic ones remained unchanged. On T2-weighted GRE images, the signal intensity of hyperplastic lymph nodes decreased significantly and homogeneously, while that of 4 metastatic ones remained unchanged and that of the rest 2 decreased heterogeneously. Conclusion: SPIO-enhanced MR imaging may enable the differentiation between the hyperplastic and metastatic lymph nodes.
