The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption

Metastasis accounts for most deaths from breast cancer, driving the need for new therapeutics that can impede disease progression. Rationally designed peptides that take advantage of cancer-specific differences in cellular physiology are an emerging technology that offer promise as a treatment for metastatic breast cancer. We developed CT20p, a hydrophobic peptide based on the C terminus of Bax that exhibits similarities with antimicrobial peptides, and previously reported that CT20p has unique cytotoxic actions independent of full-length Bax. In this study, we identified the intracellular actions of CT20p which precede cancer cell-specific detachment and death. Previously, we found that CT20p migrated in the heavy membrane fractions of cancer cell lysates. Here, using MDA-MB-231 breast cancer cells, we demonstrated that CT20p localizes to the mitochondria, leading to fusion-like aggregation and mitochondrial membrane hyperpolarization. As a result, the distribution and movement of mitochondria in CT20p-treated MDA-MB-231 cells was markedly impaired, particularly in cell protrusions. In contrast, CT20p did not associate with the mitochondria of normal breast epithelial MCF-10A cells, causing little change in the mitochondrial membrane potential, morphology or localization. In MDA-MB-231 cells, CT20p triggered cell detachment that was preceded by decreased levels of alpha 5 beta 1 integrins and reduced F-actin polymerization. Using folate-targeted nanoparticles to encapsulate and deliver CT20p to murine tumors, we achieved significant tumor regression within days of peptide treatment. These results suggest that CT20p has application in the treatment of metastatic disease as a cancer-specific therapeutic peptide that perturbs mitochondrial morphology and movement ultimately culminating in disruption of the actin cytoskeleton, cell detachment, and loss of cell viability

Primary recovery factor as a function of production rate: implications for conventional reservoirs with different drive mechanisms

This study evaluates the dependency of production rate on the recovery of hydrocarbon from conventional reservoirs using MBAL simulator. The results indicated that the recoveries are sensitive to the production rate in almost all hydrocarbon reservoirs. It was also found that the recovery of volumetric gas drive reservoirs is not impacted by the production rate. In fact, any increase in the production rate improves gas recovery in weak and strong water drive reservoirs. Moreover, increasing the production rate in oil reservoirs decreases the recovery with a significant effect observed in the weak water drive reservoirs. The results of this study demonstrate the need for implementing an effective reservoir management in order to obtain a maximum recovery

Giant cervicothoracic extradural arachnoid cyst: case report

The pathogenesis, etiology, and treatment of the spinal arachnoid cyst have not been well established because of its rarity. A 57-year-old male was presented with spastic quadriparesis predominantly on the left side. His radiological examination showed widening of the cervical spinal canal and left neural foramina due to a cerebrospinal fluid - filled extradural cyst that extended from C2 to T2 level. The cyst was located left anterolaterally, compressing the spinal cord. Through a C4–T2 laminotomy, the cyst was excised totally and the dural defect was repaired. Several features of the reported case, such as cyst size, location, and clinical features make it extremely unusual. The case is discussed in light of the relevant literature

Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor

<p>Abstract</p> <p>Background</p> <p>In the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic stellate cell (HSC) differentiation and a novel subpopulation of HSCs which express CD133 and exhibit properties of progenitor cells has been described in rats. The carbon tetrachloride (CCl₄)-induced mouse model has been historically relied upon to study liver injury and regeneration. We exposed mice to CCl₄to assess whether EGF and CD133+ HSCs are up-regulated in chronically injured liver.</p> <p>Methods</p> <p>CCl₄in olive oil was administered to strain A/J mice three times per week by oral gavage.</p> <p>Results</p> <p>Multiple well-differentiated HCCs were found in all livers after 15 weeks of CCl₄treatment. Notably, HCCs developed within the setting of fibrosis and not cirrhosis. CD133 was dramatically up-regulated after CCl₄treatment, and increased expression of desmin and glial fibrillary acidic protein, representative markers of HSCs, was also observed. EGF expression significantly decreased, contrary to observations in humans, whereas the expression of amphiregulin, another EGFR ligand, was significantly increased.</p> <p>Conclusions</p> <p>Species-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease. CCl₄-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC.</p