Once tumors reached the endpoint volume of 3000 mm3, the mice were sacrificed. Upon sacrifice, whole blood and tumor tissue were harvested. Mice were weighed on day one of their treatment and at necropsy. no notable changes were seen in any cohorts. Two mice were excluded from the http://www.selleckchem.com/products/dorsomorphin-2hcl.html analyses. One mouse assigned to the rapamycin 8 mg kg daily IP group was euthanized due to weight loss and dehydration prior to starting any drug treatments. Another mouse assigned to rapamycin 8 mg kg plus sorafenib 60 mg kg daily treat ment was removed from study due to an extremely slow growing tumor that did not reach treatment threshold vol umes. Both mice that were excluded did not start any treatments prior to euthanasia so their conditions were unrelated to study treatments.

Inhibitors,Modulators,Libraries All drug doses were calcu lated based on an average weight of 30 g per mouse. Treatment of subcutaneous Inhibitors,Modulators,Libraries tumors with atorvastatin, doxycycline, and rapamycin To determine if atorvastatin or doxycycline are useful ther apeutic drugs for TSC, the efficacy of atorvastatin and dox ycycline as single agents and in combination with rapamycin were tested in the subcutaneous tumor model for TSC related tumors. A cohort of 48 CD 1 nude mice was injected with NTC T2null cells. The cohort was then divided into Inhibitors,Modulators,Libraries 6 randomly assigned groups untreated control group, single Inhibitors,Modulators,Libraries agent rapamycin, atorvas tatin, combination atorvastatin plus Inhibitors,Modulators,Libraries rapamycin, single agent doxycycline, and combination doxycycline plus rapamycin. All drug treatments started when tumors reached a vol ume of 50 mm3, regardless of treat ment schedule, and animals were euthanized when tumors reached a volume of 3000 mm3.

If a volume of 40 mm3 was reached on Thursday or Friday, treatment began that day. Otherwise, treatment was started on the day tumor volume was 50 mm3. Untreated mice did not receive any treatment even after tumors reach a volume 50 mm3. Please note that Cabozantinib this is a minor difference in study design from the sorafenib study. We have previously shown that differences in tumor volume at the start of treatment are not likely to have any major impact on effi cacy. Rapamycin treated groups received 200l of a 1. 2 mg ml solution of rapamycin three times per week by IP injection. Mice being treated with doxycycline were treated daily Monday through Friday with 200l of a 1. 5 mg ml IP injection. Atorvastatin groups received 200l daily of a 3 mg ml solution by IP injection Monday through Friday. All drug doses were calculated based on an average weight of 30 g per mouse. Atorvastatin powder was obtained from LKT Laboratories, Inc. and was diluted in 1% ethanol in sterile PBS. This dose of atorvastatin was based on a study in which this dose was effective in reducing atherosclerotic lesions in a mouse model.