Transforming growth factor-β?(TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β,...Transforming growth factor-β?(TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost three decades ago, there have been tremendous advances in our understanding of its complex biology. TGF-β?misregulation has been implicated in the pathogenesis of a variety of diseases, including cancer with a direct role in facilitating metastasis, fibrosis and inflammation. Consequently, TGF-β?is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis;and it offers an attractive target for cancer therapy. Several anti-TGF-β?approaches, such as TGF-β?antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-β?type 1 receptor kinase, have shown great promise in the preclinical studies. Here, we consider why the TGF-βsignaling pathway is a drug target, the potential clinical applications of TGF-β?inhibition, the issues arising with anti-TGF-β?therapy and how these might be adopted using personalized approaches with a special care for patient selection and timing of therapy so that we may bring forward all the potentials of targeting this pathway for therapeutic uses in both cancer, preferentially in combination therapy, and non-neoplastic diseases.展开更多
Bone marrow specimens from 100 cases of acute leukemia (AL) diagnosed by MIC were detected with fluorescence microscopy for their mdr-1 expression using monoclonal antibody JSW-1 against P-glycoprotein (Pgp).The resu...Bone marrow specimens from 100 cases of acute leukemia (AL) diagnosed by MIC were detected with fluorescence microscopy for their mdr-1 expression using monoclonal antibody JSW-1 against P-glycoprotein (Pgp).The results showed that almost all subtypes of AL had Pgp expression and M5 of ANLL had a significantly higher expression rate in the newly diagnosed group.The MDR expression highly correlatetl with the cliuical drug resistance and prognosis. The positive rate of Pgp (20.8%±14.9%) and MDR expression (78.g%) in refractory group were significantly higher than those in the newly diagnosed group (7.5%±9.8% and 18.2%), respectively.Cases with MDR+ expression had poor response to chemotherapy and had prognosis.展开更多
文摘Transforming growth factor-β?(TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost three decades ago, there have been tremendous advances in our understanding of its complex biology. TGF-β?misregulation has been implicated in the pathogenesis of a variety of diseases, including cancer with a direct role in facilitating metastasis, fibrosis and inflammation. Consequently, TGF-β?is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis;and it offers an attractive target for cancer therapy. Several anti-TGF-β?approaches, such as TGF-β?antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-β?type 1 receptor kinase, have shown great promise in the preclinical studies. Here, we consider why the TGF-βsignaling pathway is a drug target, the potential clinical applications of TGF-β?inhibition, the issues arising with anti-TGF-β?therapy and how these might be adopted using personalized approaches with a special care for patient selection and timing of therapy so that we may bring forward all the potentials of targeting this pathway for therapeutic uses in both cancer, preferentially in combination therapy, and non-neoplastic diseases.
文摘Bone marrow specimens from 100 cases of acute leukemia (AL) diagnosed by MIC were detected with fluorescence microscopy for their mdr-1 expression using monoclonal antibody JSW-1 against P-glycoprotein (Pgp).The results showed that almost all subtypes of AL had Pgp expression and M5 of ANLL had a significantly higher expression rate in the newly diagnosed group.The MDR expression highly correlatetl with the cliuical drug resistance and prognosis. The positive rate of Pgp (20.8%±14.9%) and MDR expression (78.g%) in refractory group were significantly higher than those in the newly diagnosed group (7.5%±9.8% and 18.2%), respectively.Cases with MDR+ expression had poor response to chemotherapy and had prognosis.