ABSTRACT
RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies.
ABSTRACT
The control of severe cancer pain may be problematic despite advances in pain management. Patients with severe intractable pain and/or intractable side effects may require aggressive interventional pain management strategies including the administration of medications by the continuous intrathecal route and/or neurosurgical procedures. Various medications, including opioids, local anesthetics, and alpha-2 agonists may be used intrathecally for the control of cancer pain. Failure of the intrathecal route may require the additional use of neurosurgical procedures such as cordotomy for pain control. We describe a case of severe cancer pain refractory to conventional intrathecal medications and cordotomy that was successfully managed by the addition of meperidine to the intrathecal regimen.
