ABSTRACT
Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue. We examined the route of administration as a potential modifier of both trafficking and antitumor efficacy. Femoral artery cannulation and tail vein injection for the intra-arterial (IA) and IV delivery, respectively, were utilized in the B16-OVA/OT-I mouse model system. Both IV and IA infusions showed decreased tumor growth and prolonged survival. However, although significantly increased T-cell tumor infiltration was observed in IA mice, tumor growth and survival were not improved as compared with IV mice. These studies suggest that IA administration produces increased early lymphocyte trafficking, but a discernable survival benefit was not seen in the murine model examined.
Subject(s)
Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/therapy , T-Lymphocytes/immunology , Administration, Intravenous , Adoptive Transfer , Animals , Cell Movement , Disease Models, Animal , Femoral Artery/surgery , Humans , Immunotherapy, Adoptive , Injections, Intra-Arterial , Melanoma/immunology , Melanoma, Experimental , Mice , Mice, Inbred C57BL , Neoplasms, Experimental , Tumor Burden , Tumor MicroenvironmentABSTRACT
PURPOSE: Quinacrine is a relatively non-toxic drug, once given almost exclusively for malaria. However, recent studies show that quinacrine can suppress nuclear factor-κB (NF-κB), and activate p53 signaling. We investigated the anti-cancer effect of quinacrine, using a novel mouse model of isolated limb perfusion (ILP) for extremity melanoma. METHOD: Female C57BL/6 mice (22-25 g) were injected with B16 melanoma cells (1 × 10(5)) subcutaneously in the distal thigh. After 7 days of tumor establishment, mice were perfused with either PBS, melphalan (90 µg), or quinacrine (3.5 and 4.5 mg) through the superficial femoral artery for 30 min at either 37 or 42 °C in a non-oxygenated circuit. We analyzed morbidity, toxicity, tumor apoptosis, and responses. RESULTS: Melanoma cell death following in vitro exposure to quinacrine was dose and time dependent. A significant decrease in mean tumor volume was observed after perfusion with low-dose and high-dose quinacrine (both P = 0.002) at 37 °C as well as after perfusion with low-dose quinacrine (P = 0.0008) at 42 °C. CONCLUSION: Quinacrine has demonstrable efficacy against melanoma cells in vitro and in a clinically relevant model of ILP. Further studies to evaluate the optimal conditions for quinacrine usage are warranted.
Subject(s)
Antineoplastic Agents , Extremities , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Perfusion/methods , Quinacrine/pharmacology , Quinacrine/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Animals , Disease Models, Animal , Female , Melanoma, Experimental/genetics , Mice, Inbred C57BL , NF-kappa B/metabolism , Neoplasm Transplantation , Skin Neoplasms/genetics , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolismABSTRACT
Gynecomastia-like hyperplasia of orthotopic female breast tissue is a rare entity. We present the singularly unique case of a 22-year-old female who presented with a small axillary mass subsequently discovered to be a discrete deposit of ectopic breast tissue with gynecomastia-like hyperplasia. This case highlights the etiology, variable presentation, and evaluation of ectopic breast tissue.
