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
Nyiragongo volcanic eruptions of 1977 and 2002 emitted silica-undersaturated lavas named melilite-nephelinites with microlithic to sub-porphyritic textures, and consisted of olivine, clinopyroxene (augite), phlogopite...Nyiragongo volcanic eruptions of 1977 and 2002 emitted silica-undersaturated lavas named melilite-nephelinites with microlithic to sub-porphyritic textures, and consisted of olivine, clinopyroxene (augite), phlogopite, melilite, magnetite, and rare plagioclases. This melilite-nephelinite as an evolved rock, shows low SiO<sub>2</sub> (38.40 - 39.52 wt%) and MgO (3.10 - 4.01 wt%), and relatively high FeOt (13.76 - 14.10 wt%), Al<sub>2</sub>O<sub>3</sub> (15.01 - 16.48 wt%), CaO (11.00 - 12.29 wt%) and Na<sub>2</sub>O + K<sub>2</sub>O (10.34 - 11.85 wt%). Unlike LA-ICP-MS on silicate melt inclusions (SMIs) hosted in augite show a pristine melt of picrobasaltic (low Ti-picrite) rock poor in SiO<sub>2</sub> (31.14 - 32.26 wt%), FeOt (2.19 - 2.79 wt%), Al<sub>2</sub>O<sub>3</sub> (8.01 - 9.57 wt%), and Na<sub>2</sub>O + K<sub>2</sub>O (2.34 - 3.05 wt%), while enriched in MgO (20.27 - 28.63 wt%), and CaO (24.95 - 33.17 wt%). The sums (∑REEs) for lavas and SMIs are ranging 712 - 799 and 43 - 119 ppm respectively. REE contracted multi-element patterns showed a W-feature for most lavas except for SMIs. High Rb/Sr, and low Ba/Rb, Zr/Nb, and Sm/Hf ratios of lavas suggest a phlogopite-rich source of materials. .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Nyiragongo volcanic eruptions of 1977 and 2002 emitted silica-undersaturated lavas named melilite-nephelinites with microlithic to sub-porphyritic textures, and consisted of olivine, clinopyroxene (augite), phlogopite, melilite, magnetite, and rare plagioclases. This melilite-nephelinite as an evolved rock, shows low SiO<sub>2</sub> (38.40 - 39.52 wt%) and MgO (3.10 - 4.01 wt%), and relatively high FeOt (13.76 - 14.10 wt%), Al<sub>2</sub>O<sub>3</sub> (15.01 - 16.48 wt%), CaO (11.00 - 12.29 wt%) and Na<sub>2</sub>O + K<sub>2</sub>O (10.34 - 11.85 wt%). Unlike LA-ICP-MS on silicate melt inclusions (SMIs) hosted in augite show a pristine melt of picrobasaltic (low Ti-picrite) rock poor in SiO<sub>2</sub> (31.14 - 32.26 wt%), FeOt (2.19 - 2.79 wt%), Al<sub>2</sub>O<sub>3</sub> (8.01 - 9.57 wt%), and Na<sub>2</sub>O + K<sub>2</sub>O (2.34 - 3.05 wt%), while enriched in MgO (20.27 - 28.63 wt%), and CaO (24.95 - 33.17 wt%). The sums (∑REEs) for lavas and SMIs are ranging 712 - 799 and 43 - 119 ppm respectively. REE contracted multi-element patterns showed a W-feature for most lavas except for SMIs. High Rb/Sr, and low Ba/Rb, Zr/Nb, and Sm/Hf ratios of lavas suggest a phlogopite-rich source of materials. .
