ABSTRACT
Development of new radiopharmaceuticals is crucial for the advance of nuclear medicine and molecular imaging. In recent years, significant progress has been made in the development of radiopharmaceuticals based on radioactive metal nuclides such as 64Cu. Copper is a transition metal element necessary for human physiology. Disorders of copper metabolism not only cause hereditary Wilson disease and Menkes disease, but also play an important role in the development of malignant tumors. In addition to radiolabeling for probes, 64Cu can be used for PET diagnostic imaging of copper metabolism disorders. 64CuCl2 is a useful radiotracer that can be used to track the dynamic flow of copper ions in human body copper metabolism by PET imaging. In recent years, many preclinical and clinical studies of 64CuCl2 radiotracer have achieved good results, and have attracted a lot of attention in the field of nuclear medicine and molecular imaging. In this article, the progress in the development of 64CuCl2 as a radiotracer for PET diagnostic imaging of hereditary copper metabolism disorders and copper hypermetabolic tumors is reviewed, and further research studies and potential clinical application of 64CuCl2 PET/CT imaging is prospected.
ABSTRACT
Development of new radiopharmaceuticals is crucial for the advance of nuclear medicine and molecular imaging.In recent years,significant progress has been made in the development of radiopharmaceuticals based on radioactive metal nuclides such as 64Cu.Copper is a transition metal element necessary for human physiology.Disorders of copper metabolism not only cause hereditary Wilson disease and Menkes disease,but also play an important role in the development of malignant tumors.In addition to radiolabeling for probes,64Cu can be used for PET diagnostic imaging of copper metabolism disorders.64CuCl2 is a useful radiotracer that can be used to track the dynamic flow of copper ions in human body copper metabolism by PET imaging.In recent years,many preclinical and clinical studies of 64CuCl2 radiotracer have achieved good results,and have attracted a lot of attention in the field of nuclear medicine and molecular imaging.In this article,the progress in the development of 64CuCl2 as a radiotracer for PET diagnostic imaging of hereditary copper metabolism disorders and copper hypermetabolic tumors is reviewed,and further research studies and potential clinical application of 64CuCl2 PET/CT imaging is prospected.
ABSTRACT
As an important branch of systematic biology, metabonomics is an emerging discipline following genomics, proteomics and transcriptomics. It focuses on the quality and quantity changes of the small molecular metabolites in appointed physiological or pathological state, and provides important informa?tion for studies of diseases mechanism, clinical early diagnosis and prognosis prediction. Compared with tra?ditional clinical diagnostic method ( single index) , metabonomics method can more comprehensively analyze metabolites changes in the body. This review introduces the metabonomics and summarizes its application in thyroid diseases.
ABSTRACT
The radioactive iodine-refractory differentiated thyroid carcinoma (RIR-DTC) is a complex process that involves multiple genetic changes and multiple signaling pathways.Radionuclide imaging, genomics and proteomics are effective to clarify the mechanism and helpful in clinical diagnosis and therapy.The treatment of RIR-DTC includes the removal of distant metastases, drug therapy, external radiotherapy and radiofrequency ablation.This review mainly focuses on the pathogenesis, diagnosis and treatment of RIR-DTC.
ABSTRACT
Objective Some drugs can effectively improve the uptake of 131 I in dedifferentiated thyroid cancer .This study was to investigate the effect of all-trans retinoic acid (ATRA) combined with interferon-α2a (IFN-α2a) on the iodine uptake and re-tention rate of FTC-133 follicular thyroid carcinoma cells . Methods FTC-133 cells were cultured in the presence of 2 μmol/L AT-RA and/or 1500 IU/mL IFN-α2a for 72 hours.The the cells were collected for measurement of the uptake and retention rate of Na 125 I. Results The Na125 I uptake of the FTC-133 cells was significantly increased after 72-hour incubation with 2μmol/L ATRA and 1500 IU/mL IFN-α2a (2423.1 ±237.5) as compared with those of the control (1279.5 ±102.8), ATRA (1438.2 ±149.6), and IFN-α2a groups (1355.3 ±198.4) (P<0.05).Statistically significant differences were observed in the retention rate of Na 125I in the FTC-133 cells at different time points in the each of the blank control , 2μmol/L ATRA, 1500 IU/mL IFN-α2a, and combination groups (P<0.01), but not in that of Na125I among these groups (P<0.05). Conclusion ATRA in combination with IFN-α2a can promote the Na125 I uptake but cannot improve the Na 125 I retention rate in FTC-133 cells.
ABSTRACT
Cancer development is a complex process that involves multiple genetic changes and multiple signaling pathways . Recent findings show that the GRIM-19 is a novel apoptosis regulation gene , and its gene mutations and loss of protein expression have been observed in many tumor types such as urinarysystem tumor , digestive system neoplasm , which are closely related to cancer devel-opment.Thus, GRIM-19 may be a potential target for gene therapy .Pro-apoptotic mechanisms of GRIM-19 and its related proteins such as STAT3,GW112,p16INK4aare overviewed in this article.
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Due to their lower risk for induction of resistance, membrane-active antimicrobial peptides with anticancer effect are attractive in cancer therapy. Because cell binding contributes to the cytotoxicity of peptide, it is possible to enhance the cytotoxicity of antimicrobial peptide in tumor cells by conjugation to a cell-penetrating peptide (CPP). In this paper, a fusion peptide MPGA by conjugation of antimicrobial peptide MP to CPP Antp at its N-terminus was constructed. After compared the cytotoxicity of unconjugated MP with that of the fusion peptide, it was found that MPGA showed higher cytotoxicity than that of unconjugated MP. And the fusion peptide MPGA induced cell death in tumor cells by membrane disruption. These results demonstrated that the cytotoxicity of antimicrobial peptide can be significantly enhanced by conjugation to CPP, which might be an effective way to develop novel anticancer drugs.
Subject(s)
Humans , Antimicrobial Cationic Peptides , Pharmacokinetics , Pharmacology , Antineoplastic Agents , Pharmacokinetics , Pharmacology , Cell Line, Tumor , Cell Membrane PermeabilityABSTRACT
TNF-related apoptosis-inducing ligand (TRAIL) is a member of factor TNF family, which could be potentially developed as novel antitumor agent due to its selective and efficient induction of apoptosis in tumor cells. Gene recombinant expression is an important tool for production of pharmaceutical protein. In this paper, the gene encoding human soluble TRAIL (114-281aa fragment) was cloned by PCR and then inserted into the Pichia Pastoris expression vector pPIC9K. The transformants were double-screened on plates containing neomycin G418 and many clones with high levels of G418-resistance were selected for further studies on protein expression. The recombinant human soluble TRAIL was secreted into the BMMY media under the condition of 3% methanol. And the recombinant protein was purified to homogeneity (-80% purity) by using Ni-agarose affinity chromatography. The yield of this protein is about 1-2 mg per liter culture. Cell viability assays demonstrated that human soluble TRAIL was cytotoxic in both leukemia cells Jurkat and lung cancer cells A549. After treatment with 0.05 microg/ml TRAIL, the survival rate of Jurkat cells was about 10%. The expressed TRAIL showed dose-dependent cytotoxicity in A549 cells within the range of 0.1-1 microg/ml. When the protein concentration reached 1 microg/ml, the survival rates of A549 cells were about 30%. However, the recombinant human soluble TRAIL did not show obvious cytotoxicity in human skin fibroblast cells (HSF) at concentrations tested. There results demonstrate that human soluble TRAIL is selectively cytotoxic in tumor cells. The expression system constructed in this experiment might contribute to further production of soluble TRAIL and TRAIL-based novel fusion proteins in large quantities.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cloning, Molecular , Cytotoxicity Tests, Immunologic , Methods , Genetic Vectors , Genetics , Pichia , Genetics , Metabolism , Recombinant Proteins , Genetics , Pharmacology , TNF-Related Apoptosis-Inducing Ligand , GeneticsABSTRACT
Cytochrome C plays important roles in electron transferring, oxidative stress and apoptosis. In this study, soluble cytochrome C was accumulated in cytoplasm of E. coli by utilizing the co-expression of human cytochrome c and yeast heme lyase from a single plasmid. After ultrasonic disruption of the bacteria, a lot of contaminated proteins were discarded by addition of 350 g/L ammonium sulfate into the supernatant. Then the recombinant human cytochrome C was purified to 80% homogeneity after two times cation exchange chromatography on SP-Sepharose Fast Flow. Yields of cytochrome C greater than 10 mg per liter culture were attained. This efficient system for producing human cytochrome C is helpful for us to understand the roles of this protein in biological processes and therapy of human diseases relevant to apoptosis and oxidative stress.