Transforming growth factor-1 antisense oligodeoxynucleocurately than glomerular injury [1, 2]. Fibrotic structural tides block interstitial fibrosis in unilateral ureteral obstruction. derangement of the tubulointerstitial compartment oc-Background. Interstitial expression of transforming growth curs in virtually progressive renal diseases. Interstitial factor-1 (TGF-1) is important in tubulointerstitial fibrosis, fibrosis is characterized by the accumulation of matrix a common process in most progressive renal diseases. However, proteins in the renal tubulointerstitial compartment. The no effective therapy for progressive interstitial fibrosis is known. Recently, we developed an artificial viral envelope mechanisms underlying the progression of interstitial fi-(AVE)-type hemagglutinating virus of Japan (HVJ) liposomebrosis are not well understood, but this accumulation of mediated retrograde ureteral gene transfer method, which almatrix is accompanied by infiltrating macrophages and lowed us to introduce the genetic material selectively into renal increased numbers of activated fibroblasts in the interstiinterstitial fibroblasts. tium [3]. Method. We introduced antisense or scrambled oligodeoxynucleotides (ODNs) for TGF-1 into interstitial fibroblasts in Although several cytokines have fibrogenic potential, rats with unilateral ureteral obstruction, a model of interstitial transforming growth factor- (TGF-) remains the fibrosis, to block interstitial fibrosis by retrograde ureteral inprime fibrogenic cytokine in renal interstitial fibrosis. jection of AVE-type HVJ liposomes. Active TGF- evokes a variety of responses relevant to Results. TGF-1 and type I collagen mRNA increased markedly in the interstitium of untreated obstructed kidneys, and renal fibrosis [4]. TGF- stimulates synthesis of individthose were not affected by scrambled ODN transfection. ual matrix components, including proteoglycans, colla-Northern analysis and in situ hybridization revealed that the gens, and glycoproteins [5]. TGF- also inhibits matrix levels of TGF-1 and type I collagen mRNA were dramatically degradation by decreasing synthesis of proteases and decreased in antisense ODN-transfected obstructed kidneys. increasing synthesis of protease inhibitors [6]. TGF- Consequently, the interstitial fibrotic area of the obstructed kidneys treated with antisense ODN was significantly less than modulates the expression of integrin receptors and alters that of the obstructed kidneys untreated or treated with scramtheir relative abundance on the cell surface in a manner bled ODN. capable of facilitating adhesion to the matrix [7]. TGF- Conclusion. The introduction of TGF-1 antisense ODN is also a chemoattractant for fibroblasts [4] and stimuinto interstitial fibroblasts may be a potential therapeutic malates fibroblast proliferation [8]. The net effect of TGF- neuver for interstitial fibrosis. is to shift the balance of matrix synthesis and degradation toward accumulation of matrix proteins. By inhibiting TGF- using a neutralizing...
The ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution was evaluated in order to radiation identify and improve any deficiencies. A questionnaire-based national structure survey was conducted from March 2010 to January 2011 by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study (PCS). The total numbers of new cancer patients and total of cancer patients (new and repeat) treated with radiation in 2009 were estimated at 201,000 and 240,000, respectively. The type and numbers of systems in actual use consisted of Linac (816), telecobalt (9), Gamma Knife (46), 60 Co remote afterloading system (RALS) (29) and 192 Ir RALS systems (130). The Linac systems used dual energy function for 586 (71.8%), 3DCRT for 663 (81.3%) and IMRT for 337 units (41.3%). There were 529 JASTRO-certified radiation oncologists (ROs), 939.4 full-time equivalent (FTE) ROs, 113.1 FTE medical physicists and 1836 FTE radiation therapists. The frequency of interstitial radiation therapy use for prostate and of intensity-modulated radiotherapy increased significantly. PCS stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more radiation therapy tended to be used for cancer patients. In conclusion, the Japanese structure has clearly improved during the past 19 years in terms of equipment and its use, although a shortage of manpower and variations in maturity disclosed by PCS stratification remained problematic in 2009.
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