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Direct delivery of a cytotoxic anticancer agent into the metastatic lymph node using nano/microbubbles and ultrasound.

ABSTRACT: Direct injection of an anticancer agent into a metastatic lymph node (LN) has not been used as a standard treatment because evidence concerning the efficacy of local administration of a drug into a metastatic LN has not been established. Here we show that the combination of intralymphatic drug delivery with nano/microbubbles (NMBs) and ultrasound has the potential to improve the chemotherapeutic effect. We delivered cis-diamminedichloroplatinum (II) (CDDP) into breast carcinoma cells in vitro and found that apoptotic processes were involved in the antitumor action. Next, we investigated the antitumor effect of intralymphatic chemotherapy with NMBs and ultrasound in an experimental model of LN metastasis using MXH10/Mo-lpr/lpr mice exhibiting lymphadenopathy. The combination of intralymphatic chemotherapy with NMBs and ultrasound has the potential to improve the delivery of CDDP into target LNs without damage to the surrounding normal tissues. The present study indicates that intralymphatic drug delivery with NMBs and ultrasound will potentially be of great benefit in the clinical setting.

SUBMITTER: Sato T

PROVIDER: S-EPMC4405545 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Direct delivery of a cytotoxic anticancer agent into the metastatic lymph node using nano/microbubbles and ultrasound.

Sato Takuma T Mori Shiro S Sakamoto Maya M Arai Yoichi Y Kodama Tetsuya T

PloS one 20150421 4

Direct injection of an anticancer agent into a metastatic lymph node (LN) has not been used as a standard treatment because evidence concerning the efficacy of local administration of a drug into a metastatic LN has not been established. Here we show that the combination of intralymphatic drug delivery with nano/microbubbles (NMBs) and ultrasound has the potential to improve the chemotherapeutic effect. We delivered cis-diamminedichloroplatinum (II) (CDDP) into breast carcinoma cells in vitro an ...[more]

PMID: 25897663

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Project description:Lessons learnedRemoval of sonographically abnormal (up to 3) metastatic clipped nodes, without sentinel lymph node biopsy, could accurately predict axillary status in breast cancer patients receiving neoadjuvant chemotherapy. ypT and the first clipped node status were statistically significant factors for nodal pathologic complete response. This novel approach requires validation in larger studies.BackgroundIn patients who have node-positive breast cancer, neoadjuvant chemotherapy could result in nodal pathologic complete response (pCR) and avoid an axillary lymph node dissection (ALND). Axillary staging, in such cases, can be performed using targeted axillary dissection (TAD) with a low false negative rate. However, identification of sentinel lymph nodes (SLNs) after chemotherapy can be difficult, and currently, it is the standard to remove only one clipped node in TAD. We aimed to determine if removal of all sonographically abnormal metastatic clipped nodes, without SLN biopsy, could accurately predict the axillary status post neoadjuvant chemotherapy.MethodsPatients with breast cancer with one to three sonographically abnormal metastatic axillary nodes were prospectively recruited. Each abnormal node had histology and clip insertion before neoadjuvant chemotherapy. After chemotherapy, the patients underwent removal of clipped nodes using the Skin Mark clipped Axillary nodes Removal Technique (SMART) and ALND.ResultsFourteen patients were recruited, having a total of 21 sonographically abnormal metastatic nodes, with nine, three, and two patients having 1, 2, and 3 malignant nodes clipped, respectively. Mean age was 55.5 years; 92.9% and 57.1% of patients had invasive ductal carcinoma and grade III tumors, respectively; and 35.7% patients achieved nodal pCR. The first clipped node predicted the axillary status with a false negative rate of 7.1%. Adding to this another second clipped node, the false negative rate was 0%. Pathologic tumor staging after neoadjuvant chemotherapy (ypT) (p = .0390) and the first clipped node pathological response status (p = .0030) were statistically significant predictors for nodal pCR.ConclusionRemoval of sonographically abnormal metastatic clipped nodes using SMART, without sentinel lymph node biopsy, could accurately predict axillary status. This finding needs validation in larger studies.

Dataset Information

Direct delivery of a cytotoxic anticancer agent into the metastatic lymph node using nano/microbubbles and ultrasound.

Publications

Direct delivery of a cytotoxic anticancer agent into the metastatic lymph node using nano/microbubbles and ultrasound.

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