Clinical applications of TGF-β. John Wiley, Chichester, 1991. No. of pages: 254. Price: £39.50
1
3 52 BOOK REVIEWS placed on the potential role of interleukin 2 and they fail to come together into a cohesive volume. TIL cells as more clinical data is now becoming The question I was left with having reviewed this available. Overall, this book contains a series of book is ‘who is it intended for’?’. very good reviews, but in my opinion the spectrum J. W. SWEETMAN of subjects covered strays from the cancer cell, and MedicuI Oncology Unit is probably a little too broad. Although the Southampton General Hospital SOY 4X Y, U. K. chapters are on the whole individually excellent CLINICAL APPLICATIONS OF TGF-p. John Wiley, Chichester, 1991. No. of pages: 254. Price: f39.50. This volume contains the proceedings of a Sym- posium held at the Ciba Foundation in June 1990. Both the contributed papers and a verbatim report of the extensive discussions are reproduced. The participants included a substantial proportion of the investigators who are most prominent in this field, which has progressed remarkably since the detection in tissue culture supernatantsfrom cancer cells of a transforming growth factor; so-called because it caused fibroblasts to adopt in vitro a growth pattern associated with sarcoma. In mammalian tissues, three isoforms of TGF-P have been identified. In their mature state they are all disulphide linked dimers of 25000 molecular weight and show a high degree of amino acid identity. TGF-Ps are synthesized by many cell types including platelets, lcukocytes and many malignant tumours. There are a number of biologically inac- tive precursors which can be converted into the active mature forms by different chemical or enzy- matic treatments. The genes have been clearly identified and TGF-0s are now available in signifi- cant quantities by recombinant DNA technology. TGF-Ps bind with high affinity to a wide range of cells, both normal and malignant, via a variety of sites on the cell surface and the mechanisms of sig- nal transduction remain to be elucidated. The bio- logical effects produced by the different TGF-Ps are similar, but not identical and range over a wide spectrum. In general, TGF-Ps inhibit the growth of epithelial, endothelial and haemopoietic cells. Probably the most prominent effects are on cell differentiation and the synthesis and re-modelling of the extracellular matrix. Stimulation of synthesis of extracellular macromolecules such as collagen may explain some of the apparently contradictory findings, such that TGF-P promotes the prolifer- ation of fibroblasts when grown in soft agar, but inhibits their growth in monolayers. Also, that TGF-0s promote angiogenesis in vivo, but inhibits the growth ofendothelialcells in vitro. It isclear that the key discoveries concerning the physiological roles of TGF-f3 have yet to be made. The conference and the book are entitled Clinical Applications. This, unfortunately, is misleading since, except for the findings that TGF-P can pro- mote the rate of wound healing and reverse the adverse effects of steroids on wound healing, no other clinically useful applications are documented. What is shown repeatedly is the role of TGF-Ps in thepathogenesis ofarangeofinflammatorydiseases involving fibrogenesis. In glomerulonephritis, TGF-P has been clearly found to be responsible for the pathological production of extracellular matrix macromolecules and an antibody to TGF-P is protective. In other inflammatory diseases an association of synthesis of TGF-P and pathology has been found, such as fibrosis in chronic liver disease, pulmonary fibrosis and destruction and re-modelling of bone. There is also evidencc that TGF-P production can lead to immune suppression and contribute to cardiovascular disease. Reading this volume, one is more impressed with the possibilities of reversing the harmful cffccts of TGF-P rather than the clinical applications of the administration of TGF-P. The opening chapters of this book present a very readable and up-to-date account of the structure and complex biology of TGF-Ps and present a valuable introduction to this important and complex field. PETER ALEXANDER CRC Wessex Regional Medical Oncology Unit, Southampton General Hospital, SO9 4XY, U.K.
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Transcript of Clinical applications of TGF-β. John Wiley, Chichester, 1991. No. of pages: 254. Price: £39.50
3 52 BOOK REVIEWS
placed on the potential role of interleukin 2 and they fail to come together into a cohesive volume. TIL cells as more clinical data is now becoming The question I was left with having reviewed this available. Overall, this book contains a series of book is ‘who is it intended for’?’. very good reviews, but in my opinion the spectrum J. W. SWEETMAN of subjects covered strays from the cancer cell, and MedicuI Oncology Unit is probably a little too broad. Although the Southampton General Hospital SOY 4 X Y , U . K. chapters are on the whole individually excellent
CLINICAL APPLICATIONS OF TGF-p. John Wiley, Chichester, 1991. No. of pages: 254. Price: f39.50.
This volume contains the proceedings of a Sym- posium held at the Ciba Foundation in June 1990. Both the contributed papers and a verbatim report of the extensive discussions are reproduced. The participants included a substantial proportion of the investigators who are most prominent in this field, which has progressed remarkably since the detection in tissue culture supernatants from cancer cells of a transforming growth factor; so-called because it caused fibroblasts to adopt in vitro a growth pattern associated with sarcoma.
In mammalian tissues, three isoforms of TGF-P have been identified. In their mature state they are all disulphide linked dimers of 25000 molecular weight and show a high degree of amino acid identity. TGF-Ps are synthesized by many cell types including platelets, lcukocytes and many malignant tumours. There are a number of biologically inac- tive precursors which can be converted into the active mature forms by different chemical or enzy- matic treatments. The genes have been clearly identified and TGF-0s are now available in signifi- cant quantities by recombinant DNA technology. TGF-Ps bind with high affinity to a wide range of cells, both normal and malignant, via a variety of sites on the cell surface and the mechanisms of sig- nal transduction remain to be elucidated. The bio- logical effects produced by the different TGF-Ps are similar, but not identical and range over a wide spectrum. In general, TGF-Ps inhibit the growth of epithelial, endothelial and haemopoietic cells. Probably the most prominent effects are on cell differentiation and the synthesis and re-modelling of the extracellular matrix. Stimulation of synthesis of extracellular macromolecules such as collagen
may explain some of the apparently contradictory findings, such that TGF-P promotes the prolifer- ation of fibroblasts when grown in soft agar, but inhibits their growth in monolayers. Also, that TGF-0s promote angiogenesis in vivo, but inhibits the growth ofendothelialcells in vitro. It isclear that the key discoveries concerning the physiological roles of TGF-f3 have yet to be made.
The conference and the book are entitled Clinical Applications. This, unfortunately, is misleading since, except for the findings that TGF-P can pro- mote the rate of wound healing and reverse the adverse effects of steroids on wound healing, no other clinically useful applications are documented. What is shown repeatedly is the role of TGF-Ps in thepathogenesis ofarangeofinflammatory diseases involving fibrogenesis. In glomerulonephritis, TGF-P has been clearly found to be responsible for the pathological production of extracellular matrix macromolecules and an antibody to TGF-P is protective. In other inflammatory diseases an association of synthesis of TGF-P and pathology has been found, such as fibrosis in chronic liver disease, pulmonary fibrosis and destruction and re-modelling of bone. There is also evidencc that TGF-P production can lead to immune suppression and contribute to cardiovascular disease.
Reading this volume, one is more impressed with the possibilities of reversing the harmful cffccts of TGF-P rather than the clinical applications of the administration of TGF-P. The opening chapters of this book present a very readable and up-to-date account of the structure and complex biology of TGF-Ps and present a valuable introduction to this important and complex field.
PETER ALEXANDER CRC Wessex Regional Medical Oncology Unit, Southampton General Hospital, SO9 4 X Y , U.K.
