Recurring Extracorporeal Circuit Clotting During Continuous Renal Replacement Therapy in a Patient With Scedosporium Prolificans-Induced Fungal Sepsis: Successful Treatment With Argatroban.

Recurring Extracorporeal Circuit Clotting During Continuous Renal Replacement Therapy in a Patient With Scedosporium prolificans-Induced Fungal Sepsis: Successful Treatment With Argatroban.

Filed under: Drug and Alcohol Rehabilitation

Am J Med Sci. 2012 Dec 21;
Ferguson LM, Dreisbach AW, Csongrádi E, Juncos LA, Fulop T

ABSTRACT:: The relative effectiveness of anticoagulation strategies during continuous renal replacement therapy (CRRT) may vary according to the clinical circumstances. In this study, the case of a 46-year-old man who developed fungal mediastinitis with the pathogen Scedosporium prolificans after coronary bypass surgery is reported. Numerous debridements and multiple antifungal agents were not effective in this patient. Miltefosine, a non-Food and Drug Administration-approved agent, was started after institutional review board request and approval. CRRT was initiated with regional citrate anticoagulation (RCA) for clinical sepsis with acute kidney injury. Subsequently, crescendo clotting of the extracorporeal circuit (ECC) occurred. Multiple interventions, including escalating RCA, adding increasing heparin to RCA and exchanging the dialysis catheter, were not effective. Argatroban anticoagulation was started without further ECC clotting, and the patient recovered from both acute kidney injury and septic shock, despite continued miltefosine administration. Sepsis may contribute to recurrent ECC clotting. Argatroban, a direct thrombin inhibitor, had a disproportionate effectiveness to maintain ECC patency in this patient.
HubMed – drug


The Nanoparticulate Quillaja Saponin BBE Is Selectively Active Towards Renal Cell Carcinoma.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2013 Jan; 33(1): 143-51
Hassan SB, Gullbo J, Hu K, Berenjian S, Morein B, Nygren P

Aim: To characterize the cytotoxic effect of BBE, the particulate of desacyl-saponin, in model systems of solid tumours.Cytotoxic activity of BBE was investigated in solid human tumour cell lines, in tumour cells from patients with renal cell carcinoma, in normal human renal cells and in peripheral blood mononuclear cells. The BBE mode of cell death was assessed in vitro. In vivo effect of BBE was evaluated in xenograft-bearing mice.BBE was selectively active against renal cell carcinoma, with no or little effect on normal cells. BBE induced caspase activity and apoptosis. An inhibitory activity of BBE on xenograft tumour growth, with no apparent signs of haematological toxicity was shown. In the non-proliferative model of patient tumour cells, BBE was active on only 1/5 patient samples, suggesting association of BBE effect with cell proliferation.BBE has interesting activities against renal cell carcinoma and should be further explored as a drug against this resistant tumour type.
HubMed – drug


Subcellular real-time imaging of the efficacy of temozolomide on cancer cells in the brain of live mice.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2013 Jan; 33(1): 103-6
Momiyama M, Suetsugu A, Chishima T, Bouvet M, Endo I, Hoffman RM

Novel subcellular imaging technology has been developed in order to visualize drug efficacy on single cancer cells in the brain of mice in real time. The efficacy of temozolomide on cancer cells in the brain was determined by observation of subcellular cancer-cell dynamics over time through a craniotomy open window. Dual-color U87 human glioma and Lewis lung carcinoma (LLC) cells, expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, were imaged through the craniotomy open window 10 days after treatment with temozolomide (100 mg/kg i.p. for five consecutive days). After treatment, dual-color cancer cells with fragmented nuclei were visualized, indicating apoptosis. GFP-expressing apoptotic bodies and the destruction of RFP-expressing cytoplasm were also visualized. In addition, the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay was used to confirm apoptosis visualized by imaging of the behavior of GFP-labeled cancer-cell nuclei. Tumor volume in the treated group was significantly smaller than in the control group (at day 19, p<0.001). The present study demonstrates technology capable of subcellular real-time imaging in the brain that reports induction of cancer-cell apoptosis by therapeutic treatment. More effective drugs for brain cancer and brain metastasis can be screened and can be identified with this technology. HubMed – drug


Anticancer Activity of ?-Elemene and its Synthetic Analogs in Human Malignant Brain Tumor Cells.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2013 Jan; 33(1): 65-76
Li QQ, Lee RX, Liang H, Zhong Y

Malignant brain tumors are aggressive in both children and adults. Despite recent improvements in diagnostic techniques, therapeutic approaches remain disappointing and unsuccessful. There is an urgent need for promising anticancer agents to improve overall survival of patients with brain cancer. ?-Elemene has been shown to have antiproliferative effects on many types of carcinomas. In this study, we compared the cytotoxic efficacy of ?-elemene and its synthetic analogs in the brain tumor cell lines A172, CCF-STTG1, and U-87MG. ?-Elemene exhibited cytotoxicity towards the tumor lines, effectively suppressing tumor cell survival. The inhibitory effect of ?-elemene was mediated by the induction of apoptosis, as demonstrated by three assays. The annexin V assay showed that ?-elemene increased the percentage of early- and late-apoptotic cells. Apoptotic nuclei were detected in cancer cells in situ by the terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end labeling (TUNEL) staining, and the number of TUNEL-positive cells was significantly increased at 24-72 h following drug treatment of the cell lines. Cell death enzyme-linked immunosorbent assay (ELISA) gave similar results. Furthermore, ?-elemene increased caspase-3/7/10 activity, up-regulated protein expression of BAX, and down-regulated the one of BCL-2, BCL-XL, and of X-linked inhibitor of apoptosis (XIAP) in the cells, suggesting that apoptotic signaling pathways are involved in the responses triggered by ?-elemene. Compared with ?-elemene, only three of the 10 synthetic ?-elemene analogs studied here, exerted comparable cytotoxic efficacy towards the three brain tumor lines: the analogs Lr-1 and Lr-2 had the same antitumor efficacy, while Lr-3 was less potent than ?-elemene. Thus, some synthetic analogs of ?-elemene may inhibit brain cancer cell growth and proliferation, and the synthetic analogs Lr-1 and Lr-2 may have great potential as alternatives to ?-elemene for anticancer therapy. Overall, this study provides, to our knowledge, the first evidence showing that synthetic analogs of ?-elemene hold promise for patients with brain tumors.
HubMed – drug


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