• Radiation Oncology Journal
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• 제24권1호
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• pp.1-10
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• 2006

목적: 비인강암 환자를 대상으로 시행한 동시차등조사가속치료(simultaneous modulated accelerated radiation therapy, SMART)를 이용한 세기조절방사선치료(Intensity modulated radiation therapy, IMRT)의 예비적 임상결과를 보고하고자 하였다. 대상 및 방법: 2001년 9월부터 2003년 12월까지 서울아산병원에서 근치적 목적의 동시차등조사가속치료를 시행 받은 20명의 비전이성 비인강암 환자를 대상으로 전향적 분석을 시행하였다. IMRT는 "step and shoot" SMART를 사용하여 시행되었으며, 각각 육안적종양체적(gross tumor volume, GTV)에 72 Gy (2.4 Gy/day), 비인강과 전이성 림프절부위(metastatic nodal station) 등을 포함하는 임상표적체적 1 (Clinical target volume 1, CTV1)에 60 Gy (2.0Gy/day), 그리고 임상적으로 전이가 없는 경부 부위림프절을 포함하는 임상표적체적 2 (clinical target volume 2, CTV2)에 46 Gy (2 Gy/day)를 조사하였다. 18명의 환자는 주당 1회의 isplatin 화학요법을 시행받았다. 결과: 연구대상에 포함된 환자의 추적관찰 기간의 중앙값은 27개월이었다. 19명의 환자는 치료 중단 없이 계획된 치료를 성공적으로 수행하였으나, 1명은 고도의 인두염과 영양불량으로 2주간 치료가 중단되었다. 치료 기간 중급성 독성은 RTOG 3도의 점막염과 인두염이 각각 5명(25%)과 9명(45%)에서 관찰되었다. 7명(35%)은 10% 이상의 체중 감소를 보였으며 11명(55%)은 정맥수액요법 혹은 경관영양요법을 필요로 하였다. 만성 독성에서 3급 이상의 구강건조증은 관찰되지 않았다 치료 반응은 모든 환자에서 완전관해를 보였고, 원격전이와 국소재발이 각각 2명과 1명에서 관찰되었다. 결론: SMART를 사용한 IMRT를 도입하여 임상적으로나 선량측정상 이하선의 기능 보존이 가능하였으며, 또한 생물학적으로 더욱 효과적일 것으로 생각되었다 향후 정확한 종양억제 효과와 만기 독성을 알기 위해서는 추가적인 연구대상과 추적관찰이 필요하다고 생각한다.

• Toxicological Research
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• 제8권2호
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• pp.343-357
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• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.