ABSTRACT
Background: Breast cancer is one of the most common malignancies worldwide and remains incurable after metastasis, with a 3-year overall survival rate of <40%. Case presentation: A 40-year-old, Caucasian patient with a grade-3 estrogen receptor-, progesterone receptor-, Her2-positive breast tumor and two lung nodules was treated with intramuscular targeted immunotherapy with trastuzumab and oral tamoxifen hormone therapy, together with customized intra-tumoral oncolytic virotherapy (IT-OV) over a 17-month period. PET/CT imaging at 3 and 6 months showed increased primary tumor size and metabolic glucose uptake in the primary tumor, axillary lymph nodes and lung nodules, which were paralleled by a hyperimmune reaction in the bones, liver, and spleen. Thereafter, there was a steady decline in both tumor size and metabolic activity until no radiographic evidence of disease was observed. The treatment regimen was well tolerated and good quality of life was maintained throughout. Conclusion: Integration of IT-OV immunotherapy in standard treatment protocols presents an attractive modality for late-stage primary tumors with an abscopal effect on metastases.
ABSTRACT
Kindled seizures are widely used as a model for epileptogenesis. Although the achievement of kindling criterion is known to require time to develop, the precise developmental period has not been identified. We now report that optimal achievement of the kindling criterion in the Sprague-Dawley rat is associated with a critical inter-stimulus interval of 24 to 26 days. We show that highly efficient kindling can be achieved with only two subconvulsive doses of pentylenetetrazole so long as they are given 25 days apart. Using Northern blot hybridization we show that the increased seizure susceptibility at 25 days coincides with an increased expression of the plasticity-associated proteins, growth-associated protein-43 (GAP-43), microtubule-associated protein 1B (MAP1B), and tissue plasminogen activator (tPA) mRNAs in the hippocampus. By in situ hybridization and immunocytochemistry on tissue sections, we also show an increased expression for GAP-43 in the polymorphic layer of the dentate gyrus, mossy fibers, and pyramidal cells in the CA3 region of the hippocampus. The demonstration of a long, defined developmental interval for inducing the kindling criterion should enable a dissection of the cellular and genetic events underlying this phenomenon in the rat.