Dept . of Pathology , Hiroshima University School of Medicine , Japan .
Gan To Kagaku Ryoho 21 : 2371-7 ( 1994)
Abstract
Genetic characteristics of scirrhous gastric carcinomas are overviewed .
Scirrhous carcinomas of the stomach frequently show amplification of c-met and K-sam oncogenes as well as overexpression of 6.0 kb c-met abnormal transcript .
For the formation of productive fibrosis and the diffuse infiltrative growth pattern of this malignancy , the essential factors would be not only the loss of cell adhesion molecule function through depressed expression or loss of cadherin or catenin , but also the synchronous overexpression of growth factors from the cancer cells including TGF-beta , PDGF , IGF-II and basic FGF with intimate cancer-stromal interaction through paracrine loop of IL-1 alpha/HGF system .
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Ludwig Institute for Cancer Research , Melbourne , Australia .
Bioessays 16 : 489-96 ( 1994)
Abstract
The mitogenic action of cytokines such as epidermal growth factor ( EGF ) or platelet derived growth factor ( PDGF ) involves the stimulation of a signal cascade controlled by a small G protein called Ras .
Mutations of Ras can cause its constitutive activation and , as a consequence , bypass the regulation of cell growth by cytokines .
Both growth factor-induced and oncogenic activation of Ras involve the conversion of Ras from the GDP-bound ( D-Ras ) to the GTP-bound ( T-Ras ) forms .
T-Ras activates a network of protein kinases including c-Mos , c-Raf-1 and MAP kinase .
Eventually the activation of MAP kinase leads to the activation of the elongation factor 4E and several transcription factors such as c-Jun , c-Myc and c-Fos .
There are several modulators of Ras activity , such as the GTPase activating proteins ( GAP1 and NF1 ) , which stimulate the conversion of T-Ras to D-Ras .
A series of small NF1 fragments , which bind T-Ras , as well as truncated forms of derivatives of c-Raf-1 , c-Jun and c-Myc , are capable of blocking the T-Ras-activated mitogenesis in a competitive manner .
These agents offer a unique opportunity to control the proliferation of T-Ras-associated tumors , which represent more than % of total human carcinomas .
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Department of Medicine , Jewish Hospital at Washington University Medical Center , St. Louis , MO 63110 .
Biochem Biophys Res Commun 203 : 1815-20 ( 1994)
Abstract
Platelet-derived growth factor ( PDGF ) and serum both stimulate the transcription of the mouse early response gene , JE .
JE and its human homolog , macrophage chemotactic protein-1 ( MCP-1 ) , encode potent monocyte chemotactic factors .
JE/MCP-1 is a member of the chemokine superfamily of small inducible genes whose products are multifaceted mediators of inflammatory and immune responses .
We now report evidence that the serine/threonine kinase inhibitors H7 and H8 but not HA1004 , W-7 , and ML-7 inhibit the transcriptional induction of the JE gene by serum whereas the phosphatase inhibitor , okadaic acid , increases JE expression .
Downregulation of protein kinase C by prior exposure to TPA does not inhibit the induction of JE by serum , nor does it affect the inhibition of JE induction by H7 .
These results suggest that one or more serine/threonine kinases may be important in the signal transduction mechanism that leads to the induction of the JE gene .
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Institut fur Zoologie , Technische Hochschule Darmstadt , Fed . Rep . of Germany .
Arzneimittelforschung 44 : 872-6 ( 1994)
Abstract
Blood or its constituents , respectively , contain a.o .
substances such as TGF-beta ( transforming growth factor-beta ) , PDGF ( platelet-derived growth factor ) and other factors , which beneficially influence wound healing .
Patients with perivascular disturbances and consequently with inadequate supply of the affected tissue cells often suffer from poor healing of dermal wounds .
Here , various cellular functions in situations of poor supply and related to wound healing , such as proliferation , colony formation , and migration of fibroblasts , and of monolayer formation by keratinocytes were emulated in vitro by supplementing cultures with reduced amounts of serum .
Computer-aided image analysis allowed to quantify the cellular reactions under normal and serum-deprived medium conditions and under the influence of a low molecular weight fraction manufactured by dialysis of hemolyzed calf blood ( HD , Solcoseryl ) and of TGF-beta .
Both preparations are in use for the treatment of poorly healing wounds .
While HD preferentially normalized the reduced viability of fibroblasts , the keratinocyte activity was enhanced by TGF-beta .
Restoration of fibroblast and keratinocyte functions proved most effective when combining HD with TGF-beta .