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- Kharaziha, Pedram, et al.
(författare)
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Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection : a phase I-II clinical trial
- 2009
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Ingår i: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 21:10, s. 1199-1205
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage liver disease is a medical problem with high morbidity and mortality. We have investigated the feasibility, safety, and efficacy of using autologous mesenchymal stem cells (MSCs) as a treatment. METHODS: Eight patients (four hepatitis B, one hepatitis C, one alcoholic, and two cryptogenic) with end-stage liver disease having Model for End-Stage Liver Disease score > or =10 were included. Autologous MSCs were taken from iliac crest. Approximately, 30-50 million MSCs were proliferated and injected into peripheral or the portal vein. Liver function and clinical features were evaluated at baseline and 1, 2, 4, 8, and 24 weeks after injection. RESULTS: Treatment was well tolerated by all patients. Liver function improved as verified by the Model for End-Stage Liver Disease score, which decreased from 17.9±5.6 to 10.7±6.3 (P<0.05) and prothrombin complex from international normalized ratio 1.9±0.4 to 1.4±0.5 (P<0.05). Serum creatinine decreased from 114±35 to 80±18 µmol/l (P<0.05). Serum albumin changed from 30±5 to 33±5 g/l and bilirubin from 46±29 to 41±31 µmol/l. No adverse effects were noted. CONCLUSION: Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.
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| 2. |
- Akhoondi, Shahab, et al.
(författare)
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FBXW7/hCDC4 is a general tumor suppressor in human cancer
- 2007
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:19, s. 9006-9012
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Tidskriftsartikel (refereegranskat)abstract
- The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skpl-Cdc53/ Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin El, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of ∼ 6%. The highest mutation frequencies were found in tumors of the bile duct (cholangio-carcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational "hotspots," which alter Arg residues (Arg465 and Arg479) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.
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