Alterations in cellular metabolism and bioenergetics are vital for cancer cell growth and motility. Here, the role of the mitochondrial protein voltage-dependent anion channel (VDAC1), a master gatekeeper regulating the flux of metabolites and ions between mitochondria and the cytoplasm, in regulating the growth of several cancer cell lines was investigated by silencing VDAC1 expression using small interfering RNA (siRNA). A single siRNA specific to the human VDAC1 sequence at nanomolar concentrations led to some 90% decrease in VDAC1 levels in the lung A549 and H358, prostate PC-3, colon HCT116, glioblastoma U87, liver HepG2, and pancreas Panc-1 cancer cell lines. VDAC1 silencing persisted 144 hours post-transfection and resulted in profound inhibition of cell growth in cancer but not in noncancerous cells, with up to 90% inhibition being observed over 5 days that was prolonged by a second transfection. Cells expressing low VDAC1 levels showed decreased mitochondrial membrane potential and adenoside triphosphate (ATP) levels, suggesting limited metabolite exchange between mitochondria and cytosol. Moreover, cells silenced for VDAC1 expression showed decreased migration, even in the presence of the wound healing accelerator basic fibroblast growth factor (bFGF). VDAC1-siRNA inhibited cancer cell growth in a Matrigel-based assay in host nude mice. Finally, in a xenograft lung cancer mouse model, chemically modified VDAC1-siRNA not only inhibited tumor growth but also resulted in tumor regression. This study thus shows that VDAC1 silencing by means of RNA interference (RNAi) dramatically inhibits cancer cell growth and tumor development by disabling the abnormal metabolic behavior of cancer cells, potentially paving the way for a more effective pipeline of anticancer drugs.

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BackgroundPatients who undergo surgical procedures that impair the integrity of the chest wall frequently experience extremely severe postoperative pain. Opiates and weaker analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are not sufficiently effective in achieving control of severe pain and might cause respiratory and gastrointestinal complications. In the past decade, there has been an increased interest in the use of regional nerve blocks for post-thoracoscopy and post-thoracotomy analgesia.MethodsThis is a prospective, randomized, double-blind and single-center study. We recruited 104 patients who underwent elective thoracoscopy. Prior to surgery, the participating patients were randomized into one of two study groups: Group 1- the “standard control group” that received standard postoperative pain control with intravenous opioids, NSAIDs and acetaminophen (paracetamol) and Group 2- the “block group” that was treated by ultrasound-guided serratus anterior plane (SAP) block (a single injection of 0.25% bupivacaine hydrochloride 2 mg/kg plus dexamethasone 8 mg) with standard postoperative pain control regimen. We compared the clinical, laboratory, and postoperative pain assessment data of both groups.ResultsPatients in the SAP block Group 2 reported significantly lower levels of pain after thoracic surgery as assessed by their visual analog scale scores, as compared to the patients in the standard pain control Group 1 (P<0.001). The total dosage of morphine and tramadol required for pain relief during the first hours after surgery was significantly lower in the patients who received SAP block. Also, the incidence of vomiting after surgery was significantly lower among the patients who received SAP block than among the patients who received standard pain control.ConclusionThe results of the present study suggest that SAP block is an effective adjuvant treatment option for post-thoracic surgery analgesia. Compared to the current methods used for post-thoracic surgery pain relief, SAP block has some significant merits, particularly its ease of use and its low potential for side effects.

BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

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