Growth and progression of malignant brain tumours occurs in a micromilieu consisting of both tumour and normal cells. Several proteins have been identified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continuous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therapeutic importance. In this study we have investigated the growth characteristics of cells encapsulated in alginate, which represents a potential delivery system for recombinant proteins that may have antitumour effects. Three different cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, which is an immuno-isolating substance extracted from brown seaweed. The encapsulated cells were observed at specific intervals during a 4-month period after in vitro propagation and as transplants into the cortex of BD-IX rats. Morphological studies showed that encapsulated cells proliferated and formed spheroids within the alginate in the in vitro cultures and after implantation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltration of mononuclear cells was observed in the brain bordering the alginate beads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation. The majority of inflammatory cells were reactive microglia and invading monocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N2 and will retain their viability and proliferative capacity.
Summary:Garment-like giant congenital melanocytic nevi are very rare, and those being treated are most often offered excision and split-thickness skin transplantation. Due to the risk of restricted mobility secondary to shrinkage and hypertrophic scarring of the transplant, we treated to date the largest reported giant congenital melanocytic nevus (16% total body surface area) with Integra dermal regeneration template (Integra Life Sciences, Plainsboro, N.J.), giving a more functional skin reconstruction. In addition, the dermal regeneration template had to be covered with split-thickness skin transplant including multiple smaller nevi due to lack of larger area with normal skin.
We report the case of a newborn boy with multinodular NRAS and BRAF mutation-negative congenital melanocytic nevi and cerebral lesions compatible with congenital intraparenchymal melanosis. Histopathology from skin lesions showed atypical nodular melanocytic proliferation with marked melanocytic atypia and a large number of mitoses and apoptosis, indicating aggressive proliferation. The child developed several new subcutaneous tumors and multiple internal lesions, which were confirmed to be metastases, and died at 5 months of age. This case may represent an infantile melanoma developing from a giant congenital melanocytic nevus or a congenital melanoma.
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