ABSTRACT
The mevalonate pathway plays an important role in cancer biology and has been targeted with farnesyl transferase inhibitors, although their efficacy is limited due to significant adverse effects. Statins and bisphosphonates inhibit the mevalonate pathway at different steps, thus having negative effects at various levels on cancer cells. A combination of these drugs may result in an amplified cytotoxic effect and allow for use of significantly lower doses of the drugs involved. Statins inhibit the mevalonate pathway at 3-hydroxy-3-methylglutaryl coenzyme A reductase and bisphosphonates at farnesyl pyrophosphate synthase. Our results show that low-dose combinations of simvastatin and alendronate have a synergistic cytotoxic effect on androgen-independent prostate cancer PC-3 cells, but not on androgen-dependent LNCaP or DU 145 prostate cancer cells. These two drugs cause a sequential blockade of the mevalonate pathway and significantly affect survival and apoptotic pathways by down-regulating phospho-AKT and activating c-JUN and ERK.
Subject(s)
Alendronate/administration & dosage , Drug Synergism , Prostatic Neoplasms/drug therapy , Simvastatin/administration & dosage , Apoptosis/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic/drug effects , Humans , JNK Mitogen-Activated Protein Kinases/biosynthesis , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/biosynthesisABSTRACT
CONTEXT: Pseudocysts are a common complication of acute and chronic pancreatitis. These are usually located within the pancreas but they can occur at other sites as well, including the mediastinum, neck, pelvis and rarely in the liver as in our case. The diagnosis of intrahepatic pancreatic pseudocyst relies on the demonstration of a high amylase level in the sampled cystic fluid in the absence of infection or neoplasm. CASE REPORT: A 60-year-old man with a history of chronic pancreatitis presents with a clinical and laboratory picture suggestive of acute exacerbation of his pancreatitis. A computed tomogram (CT) scan of the abdomen revealed a pancreatic pseudocyst and a cystic lesion involving both lobes of the liver. CT diagnostic aspiration of the intrahepatic cyst revealed high amylase level (greater than 20,000 U/L). The cyst was treated with percutaneous drainage with complete resolution of the cyst. CONCLUSION: In the setting of pancreatitis, intrahepatic pancreatic pseudocyst should be considered in the differential diagnosis of cystic lesion of the liver.
Subject(s)
Cysts/complications , Liver Diseases/complications , Pancreatic Pseudocyst/complications , Cysts/diagnosis , Cysts/therapy , Diagnosis, Differential , Drainage/methods , Humans , Liver Diseases/diagnosis , Liver Diseases/therapy , Male , Middle Aged , Pancreatic Pseudocyst/diagnosis , Pancreatic Pseudocyst/therapy , Pancreatitis, Chronic/complications , Treatment OutcomeABSTRACT
Neuropathic pain is common in the palliative care population; unless adequately treated, the pain can lead to chronic anxiety, depression, and social impairment. Many treatments have been proposed for neuropathic pain; however, it remains underdiagnosed, under-treated, and often requires long-term therapy with risk of adverse effects. Memantine (Namenda), an N-Methyl, D-aspartate receptor inhibitor currently marketed for the treatment of dementia, has been proposed as a medication for the treatment of neuropathic pain for its mechanism, safety, lack of serious adverse effects, and relatively rapid onset of action. However, clinical trials have not been promising so far and its routine use in neuropathic pain is not currently recommended.
