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Further experiments demonstrate that the toxicity of oxazaphosphorine cytostatics may be drastically reduced if the formation of the pharmacologically active metabolite ALDO bypasses the formation of OHCP. Toxicity experiments in mice with S-ethanol-cyclophosphamide (SECP) that hydrolyzes to OHCP show that SECP is as toxic as OHCP, whereas the thiazolidine of ALDO, which hydrolyzes to ALDO bypassing OHCP is 7-9 times less toxic without loss of antitumor activity.Patients with advanced or metastatic castration-resistant prostate cancer have a dismal prognosis and are therefore in urgent need for therapeutic innovations. Spleen tyrosine kinase has emerged as a new molecular target for castration-resistant prostate cancer. This study was done to test the cytotoxicity of the lead nanoformulation of a potent spleen tyrosine kinase inhibitor, C61-LNP, against the human prostatic carcinoma cell line, PC-3. PC-3 cells were treated with various concentrations of C61-LNP either alone or in combination with cisplatin (CDDP) for 24, 48 and 72 hours. The cell viability was evaluated by MTS assay. Cellular expression levels of various regulatory proteins in treated PC-3 cells were evaluated by Western blot analyses. C61-LNP exhibited dose-dependent cytotoxicity against PC-3 cells. C61-LNP, as well as C61-LNP + CDDP treatments, caused pro-apoptotic proteomic changes including an increase in cleaved fragments of caspases-3 and -9 consistent with caspase activation as well as an improvement in the anti-apoptotic Bcl2 and Bax levels. The combination of C61-LNP and CDDP changed in alterations of the cell cycle regulatory proteins p53, p21, p27, cyclin D1 and cyclin E levels. C61-LNP exhibited cytotoxicity against the castration-resistant prostate cancer cell line PC3. It also caused alterations in expression levels of regulatory proteins involved in apoptosis and cell cycle regulation and these effects were not abrogated by the standard chemotherapy drug CDDP. We are planning to further develop C61-LNP as a selective spleen tyrosine kinase inhibitor as part of a multi-modality treatment strategy for advanced/metastatic castration-resistant prostate cancer.This study aims to investigate the effects of albendazole on pancreatic cancer cells and to explore the possible mechanisms involved. MTT, colony formation, wound healing and Transwell assays and immunocytochemistry analyses of proliferation antigen Ki-67 were employed to evaluate the role of albendazole in pancreatic cancer cell line proliferation and migration. Moreover, flow cytometry cell apoptosis evaluation was used for mechanism analysis. Finally, the in-vivo effects of albendazole were examined in an in-vivo nude mouse xenograft model. Compared to the control treatment, albendazole significantly decreased the growth of the pancreatic cancer cell lines SW1990 and PANC-1 in a time- and dose-dependent manner, as evidenced by decreased MTT absorbance, colony number and Ki-67 levels. Furthermore, albendazole decreased cell migration in 2- and 3-dimensional models in a dose-dependent manner. In addition, albendazole increased the apoptotic cell ratio in a dose-dependent manner. Finally, the in-vivo results confirmed that albendazole could decrease tumor growth. We demonstrated the inhibitory effects of albendazole on pancreatic cell proliferation and migration in vitro and in vivo, which indicate that albendazole might serve as a novel treatment modality for pancreatic cancer.CASE A 14-year-old girl sustained a posterior elbow dislocation and presented with a proximal radioulnar translocation (PRUT) and a displaced fracture of the radial head. Reduction of the elbow dislocation and the proximal radioulnar translocation were achieved by external manipulation in the operating room. The radial head was not amenable to closed reduction and remained entrapped in the anteromedial compartment of the elbow. So open reduction and internal stabilization was carried out. CONCLUSIONS In PRUT, closed reduction should be attempted. The radial head should be preserved even if it is fully dislocated from metaphysis. see more Retrograde intramedullary radial nailing provides enough stability of the fracture to promote early mobilization and facilitate union.CASE We report a 27-year-old man who presented with thigh swelling and inability to bear weight after blunt trauma 24 hours before. Based on the clinical assessment, the patient was diagnosed with anterior compartment syndrome of the thigh and underwent fasciotomy. Postoperatively, 1.5 L of blood were drained from his wound in the first 30 minutes after the operation. Angiography was performed demonstrating bleeding from the lateral femoral circumflex which was successfully embolized. CONCLUSIONS Our case represents the underlying arterial injury that was initially undiagnosed as a cause for thigh compartment syndrome. Physicians should consider associated injuries (beyond muscle crush) when making a diagnosis of compartment syndrome.CASE A 52-year-old man known for a recent cardiac transplantation presented with 6 weeks of incapacitating left shoulder pain with normal x-rays and CT scans. MRI revealed bone edema of the coracoid and glenoid neck with a supraspinatus abscess. Biopsy of the coracoid demonstrated Aspergillus osteomyelitis of the scapula. CONCLUSION Aspergillus osteomyelitis is a rare manifestation of invasive aspergillosis and mostly manifests as spondylodiscitis. In this report, we describe a case of Aspergillus osteomyelitis of the scapula treated with combined antifungal therapy and surgery.CASE We present a case of acute disseminated intravascular coagulation (DIC) after prophylactic femoral intramedullary stabilization in a patient with metastatic prostate cancer. Preoperative international normalized ratio of 1.4 was attributed to malnutrition, and the patient was not medically optimized. DIC developed 1 hour postoperatively and was managed with blood product resuscitation. At the 4-month follow-up, the patient presented with bilateral pulmonary emboli and was transitioned to palliative care. CONCLUSIONS DIC after intramedullary stabilization in patients with metastatic bone disease is a rare condition with high mortality rate. Early recognition, blood product resuscitation, and involvement of appropriate subspecialty services are imperative in DIC management.
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