Objective: To construct a novel kind of nonviral gene delivery vector based on polyethylenimine (PEI) conjugated with polypeptides derived from ligand FGF with high transfection efficiency and according to tumor targe...Objective: To construct a novel kind of nonviral gene delivery vector based on polyethylenimine (PEI) conjugated with polypeptides derived from ligand FGF with high transfection efficiency and according to tumor targeting ability. Methods: The synthetic polypeptides CR16 for binding FGF receptors was conjugated to PEI and the characters of the polypeptides in-cluding DNA condensing and particle size were determined. Enhanced efficiency and the targeting specificity of the synthesized vector were investigated in vitro and in vivo. Results: The polypeptides were successfully coupled to PEI. The new vectors PEI-CR16 could efficiently condense pDNA into particles with around 200 nm diameter. The PEI-CR16/pDNA polyplexes showed significantly greater transgene activity than PEI/pDNA in FGF receptors positive tumor cells in vitro and in vivo gene transfer, while no difference was observed in FGF receptors negative tumor cells. The enhanced transfection efficiency of PEI-CR16 could be blocked by excess free polypeptides. Conclusion: The synthesized vector could improve the efficiency of gene transfer and targeting specificity in FGF receptors positive cells. The vector had good prospect for use in cancer gene therapy.展开更多
BACKGROUND Small cell lung cancer(SCLC)accounts for 15%of lung cancers,and it commonly expresses peptide and protein factors that are active as hormones.These secreting factors manifest as paraneoplastic disorders,suc...BACKGROUND Small cell lung cancer(SCLC)accounts for 15%of lung cancers,and it commonly expresses peptide and protein factors that are active as hormones.These secreting factors manifest as paraneoplastic disorders,such as ectopic adrenocorticotropic hormone(ACTH)syndrome(EAS).The clinical features are abnormalities in carbohydrate metabolism,hypokalemia,peripheral edema,proximal myopathy,hypertension,hyperpigmentation,and severe systemic infection.However,it is uncommon that EAS has an influence on hypothalamus-pituitary function.CASE SUMMARY A 62-year-old man presented with complaints of haemoptysis,polyuria,polydipsia,increased appetite,weight loss,and pigmentation.Following a series of laboratory and imaging examinations,he was diagnosed with SCLC,EAS,hypogonadism,hypothyroidism,and central diabetes insipidus.After three rounds of chemotherapy,levels of ACTH,cortisol,thyroid hormone,gonadal hormone,and urine volume had returned to normal levels.In addition,the pulmonary tumor was reduced in size.CONCLUSION We report a rare case of SCLC complicated with panhypopituitarism due to EAS.We hypothesize that EAS induced high levels of serum glucocorticoid and negative feedback for the synthesis and secretion of antidiuretic hormone from the paraventricular nucleus,and trophic hormones from the anterior pituitary.Therefore,patients who present with symptoms of hypopituitarism,or even panhypopituitarism,with SCLC should be evaluated for EAS.展开更多
基金Project (Nos. 2001AA217071 and 2003AA216041) supported by the Hi-Tech Research and Development Program (863) of China
文摘Objective: To construct a novel kind of nonviral gene delivery vector based on polyethylenimine (PEI) conjugated with polypeptides derived from ligand FGF with high transfection efficiency and according to tumor targeting ability. Methods: The synthetic polypeptides CR16 for binding FGF receptors was conjugated to PEI and the characters of the polypeptides in-cluding DNA condensing and particle size were determined. Enhanced efficiency and the targeting specificity of the synthesized vector were investigated in vitro and in vivo. Results: The polypeptides were successfully coupled to PEI. The new vectors PEI-CR16 could efficiently condense pDNA into particles with around 200 nm diameter. The PEI-CR16/pDNA polyplexes showed significantly greater transgene activity than PEI/pDNA in FGF receptors positive tumor cells in vitro and in vivo gene transfer, while no difference was observed in FGF receptors negative tumor cells. The enhanced transfection efficiency of PEI-CR16 could be blocked by excess free polypeptides. Conclusion: The synthesized vector could improve the efficiency of gene transfer and targeting specificity in FGF receptors positive cells. The vector had good prospect for use in cancer gene therapy.
基金Supported by the National Science Foundation for Youth,No.30800533the Public Welfare Project of Science and Technology Department of Zhejiang Province,China,No.2017C33056
文摘BACKGROUND Small cell lung cancer(SCLC)accounts for 15%of lung cancers,and it commonly expresses peptide and protein factors that are active as hormones.These secreting factors manifest as paraneoplastic disorders,such as ectopic adrenocorticotropic hormone(ACTH)syndrome(EAS).The clinical features are abnormalities in carbohydrate metabolism,hypokalemia,peripheral edema,proximal myopathy,hypertension,hyperpigmentation,and severe systemic infection.However,it is uncommon that EAS has an influence on hypothalamus-pituitary function.CASE SUMMARY A 62-year-old man presented with complaints of haemoptysis,polyuria,polydipsia,increased appetite,weight loss,and pigmentation.Following a series of laboratory and imaging examinations,he was diagnosed with SCLC,EAS,hypogonadism,hypothyroidism,and central diabetes insipidus.After three rounds of chemotherapy,levels of ACTH,cortisol,thyroid hormone,gonadal hormone,and urine volume had returned to normal levels.In addition,the pulmonary tumor was reduced in size.CONCLUSION We report a rare case of SCLC complicated with panhypopituitarism due to EAS.We hypothesize that EAS induced high levels of serum glucocorticoid and negative feedback for the synthesis and secretion of antidiuretic hormone from the paraventricular nucleus,and trophic hormones from the anterior pituitary.Therefore,patients who present with symptoms of hypopituitarism,or even panhypopituitarism,with SCLC should be evaluated for EAS.
