This splinted lymphedema model closely simulates the volume response, histopathology, and lymphography characteristics of human acquired lymphedema. Given these similarities to human lymphedema, this refinement of a mouse hindlimb model of acquired lymphedema represents a promising platform for the study of lymphatic vascular insufficiency and for the evaluation of new therapeutic modalities.

Lymphatic flow was rerouted after lymph node resection. A transplanted lymph node can be made viable with normal lymph flow by reconnecting the transplanted lymph node to a lymphatic vessel.

Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.

NIR fluorescence imaging with ICG can be a useful additional monitor for percutaneous sclerotherapy of venous malformations, especially in the face and hands, enabling noninvasive assessment of real-time spread of sclerosant.

DE-310 is a macromolecular carrier conjugate containing an anti-tumor camptothecin derivative, DX-8951, which is conjugated to a water-soluble polymer via a peptide spacer. Assay methods have been developed for the determination of a polymer-bonded DX-8951 conjugate, DX-8951, and Glycyl-DX-8951 concentrations in murine Meth A tumor tissue. Free DX-8951 and Glycyl-DX-8951 were extracted from tumor tissue homogenates by protein precipitation and analyzed by LC/MS/MS (method I). Conjugated DX-8951 was isolated by solid-phase extraction after digestion with a thermolysin. The productive phenylalanyl-glycyl-DX-8951 was analyzed by LC/MS/MS (method II). The lower limits of quantitation of DX-8951, Glycyl-DX-8951, and conjugated DX-8951 were 1.36, 1.34 and 73.7 ng/g (as DX-8951 equivalent). These two methods showed satisfactory sensitivity, precision and accuracy. To study the pharmacokinetics of DE-310, it would be of great help to assay the polymer-bonded DX-8951 and its released drugs in tumor tissue.