Specific gene knockdown facilitated by short interfering RNA (siRNA) is a potential approach for suppressing the expression of ion channels and transporter proteins to kill breast cancer cells. The overexpression of calcium ion channels and transporter genes is seen in the MCF-7 breast cancer cell line. Since naked siRNA is anionic and prone to nuclease-mediated degradation, it has limited permeability across the cationic cell membrane and short systemic half-life, respectively. Carbonate apatite (CA) nanoparticles were formulated, characterized, loaded with a series of siRNAs, and delivered into MCF-7 and 4T1 breast cancer cells to selectively knockdown the respective calcium and magnesium ion channels and transporters. Individual knockdown of TRPC6, TRPM7, TRPM8, SLC41A1, SLC41A2, ORAI1, ORAI3, and ATP2C1 genes showed significant reduction (p < 0.001) in cell viability depending on the cancer cell type. From a variety of combinations of siRNAs, the combination of TRPC6, TRPM8, SLC41A2, and MAGT1 siRNAs delivered via CA produced the greatest cell viability reduction, resulting in a cytotoxicity effect of 57.06 ± 3.72% (p < 0.05) and 59.83 ± 2.309% (p = 0.09) in 4T1 and MCF-7 cell lines, respectively. Some of the combinations were shown to suppress the Akt pathway in Western Blot analysis when compared to the controls. Therefore, CA-siRNA-facilitated gene knockdown in vitro holds a high prospect for deregulating cell proliferation and survival pathways through the modulation of Ca2+ signaling in breast cancer cells.
Metastatic abdominal carcinomas have been reported in the literature to cause bowel ischaemia. However, these are often associated with diffuse disease or direct invasion of adjacent bowel secondary to high-grade malignancies. There are no reported cases of extensive small bowel wall nor arterial occlusion as a result of metastasis from treated early-stage urothelial carcinoma. We present an octogenarian male patient who was diagnosed with small bowel ischaemia secondary to extensive metastatic urothelial carcinomatous to the small bowel. Thorough consideration of the patient’s clinical presentation and high index of suspicion was required to differentiate this from other causes of ischaemic bowel. The pathophysiology of the disease differentiated the end treatment most suitable for the patient.
Immediate trauma splenectomy following video-assisted thoracoscopic surgeryAbdominal complications following video-assisted thoracoscopic surgery (VATS) are exceedingly rare. A case is described of a patient undergoing left-sided VATS pleurodesis that was complicated by splenic injury requiring an immediate trauma splenectomy.
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