Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

<P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Park, J‐,C.,So, S‐,S.,Jung, I‐,H.,Yun, J‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

<P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</P>

Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration

Song, D‐,S.,Park, J‐,C.,Jung, I‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,K.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.2

<P> <I>Song D‐S, Park J‐C, Jung I‐H, Choi S‐H, Cho K‐S, Kim C‐K, Kim C‐S. Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration. J Periodont Res 2011; 46: 193–203. © 2010 John Wiley & Sons A/S</I> </P><P><B>Background and Objective: </B> Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP‐2 on the <I>in vitro</I> and <I>in vivo</I> biologic activity of well‐characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP‐2.</P><P><B>Material and Methods: </B> hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP‐2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8‐wk healing period. The effects of rhBMP‐2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP‐2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed.</P><P><B>Results: </B> In the present study, rhBMP‐2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs <I>in vitro</I>, and the <I>in vivo</I> potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down‐regulated following treatment with rhBMP‐2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles.</P><P><B>Conclusion: </B> In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP‐2 on cementum and PDL tissue regeneration by hPDLSCs.</P>

200 GeV/핵자 유황이온과 핵건판핵의 충돌에 의해 생성된 헬륨 파쇄핵의 극한파쇄 연구

김동철,송진섭,윤천실,정성헌,박인곤,김종오,김철수,김태연,이승희,조재희,천병구,김재률,김준원,김태익,박명렬,장한일,임인택 慶尙大學校 기초과학연구소 1992 基礎科學硏究所報 Vol.8 No.-

고에너지 중이온 원자핵과 핵건판의 충돌에서, 200GeV/핵자 유황이온에 의해 생성된 파쇄 헬륨핵(Z=2)의 실험실계의 방출각 분포는 표적핵에 무관한 회귀공식. dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)]로 잘 표현된다. 여기에서 의사신속도 η=-ln[tan(θ/2)]이고, y_b는 실험실계의 입사입자(^32S)의 신속도이다. 이 공식에 의한 적합에서 k=-0.057±0.008로 얻어진다. 즉, 핵건판과 고에너지 중이온의 충돌에서 파쇄 헬륨핵의 exp(η-y_b)의 분포는 "극한파쇄" 현상을 잘 설명하고 있다. The angular distribution of emission angle θ of helium (Z=2) produced in the collisions of incident particles of 200 GeV/nucleon ^32S in nuclear emulsion is well expressed by dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)] where the pseudorapidity is η=-ln[tan(θ/2)], the laboratory system primary rapidity is y_b, and k=-0.057+0.008. The shape of this frequency of occurrence distributions in terms of exp(η-y_b) attests to the validity of the concept of "limiting fragmentation" for helium projectile fragments produced in the projectile fragmentation regions of heavy ion collisions in nuclear emulsion.

Trypsin inhibitor 결여 大豆品種의 탐색 및 그의 遺傳育種學的 硏究 : I. Trypsin inhibitors의 전기영동 감정방법에 의한 대두 품종별 비교 및 DEAE-cellulose에 의한 분리 I. Soybean trypsin inhibitors: electrophoretic differences among varieties and their fractionation on DEAE-cellulose

金秀一,李錫河,李弘石,文亢植,羅志英 서울大學校 農科大學 1985 서울대농학연구지 Vol.10 No.1

대두의 단백추출액을 polyacrylamide gel 전기영동에 의하여 분류하고 trypsin inhibitor (T.I) band를 동정하였다. T.I. band는 전기영동한 gel을 trypsin으로 가수분해하거나 추출액에 trypsin을 처리한 후 전기영동하거나 발색기질을 이용하여 gel을 착색시키거나 또는 gel slice의 T.I.activity를 측정하는 등 네 가지 방법을 사용하여 검정하였다. 이중 추출액을 trypsin으로 처리한 후 전기영동하는 방법과 gel slice의 T.I.activity를 측정하는 방법이 가장 적합하였으며 두 방법의 결과를 비교하여 T.I.band를 검정하는 것이 보다 확실하였다. Sephadex G-75 Chromatography 에서 물로 추출한 대두 단백질은 3 fraction으로 분리하였고 T.I.activity는 제 2 fraction 에만 나타났다. Kunitz 및 Bowman-Birk형 inhibitor는 DEAE-cellulose column chromatography로 분리하였다. Kunitz형은 5개의 fraction으로, Bowman-birk형은 4개의 fraction으로 분리되었다. 단백질 추출액과 DEAE-cellulose chormatography에서 분리된 Kuniz 및 Bowman-Birk T.I.의 polyacryamide gel 전기영동 pattern을 비교하여 본 결과, 확실하게 동정된 T.I.band는 band3과 band4로서 각각 Orf등이 발표한 Ti¹과 Ti2에 해당하였으며, 그 외에 band 6과 band 10이 T.I.로 추정되었고 band 1,2,5,7,8,9는 T.I.가 아닌 것으로 판명되었다. trypsin inhibitor 함유량은 총 trypsin units inhibited 값(T.U.I)으로 볼 때 42품종에서 25에서 76까지 품종 간에 차이가 현저하였으며 시비 및 파종기의 영향은 나타나지 않았다. Ti¹ inhibitor 를 보유하고 있는 것은 37품종이었고, Ti²를 보유하는 것은 7품종이었으며, Ti¹과 Ti²를 같이 가지고 있는 품종은 발견되지 않았다. 이러한 품종의 Ti¹,Ti² 보유 pattern은 재배조건에 의해 변화되지 않았다. 2조합의 pattern은 재배조건에 의해 변화되지 않았다. 2조합의 정역교배에서 얻은 F₁ 종자의 전기영동 pattern을 비교해 본 결과, Ti¹품종끼리의 교배종자에서는 정역교배에 상관없이 Ti¹ inhibitor 만 나타났고 Ti¹품종과 Ti²품종의 교배종자에서는 Ti²를 모본으로 한 종자에서는 Ti¹과 Ti² 두 inhibitor가 검출되었으나 여교배에서는 모본의 Ti¹ inhibitor만 검출되었다. 여교배에서 Ti¹만 나타난 것은 분석시료 종자가 적었고 교배의 여부를 확인할 수 없어 모본의 세포질적 영향에 의한 것인지 또는 자가수정에 의한 것인지 분명치 않았다. The protein extracts from soybean seeds were examined by polyacrylamide gel electrophoresis and the trypsin inhibitor (T.I) bands were detected. The water-extractable protein was fractionated into three fractions by Sephadex G-75 gel filtration. The T.I activity was found only in the second fraction. Kunitz and Bowman-Birk inhibitors were fractionated by DEAE-cellulose chromatography into seven and six fractions, respectively. In kunitz inhibitor, 5 fractions were found to have T.I activity and 4 fractions in Bowman-Birk inhibitor. From the and patterns of the protein extracts and those of DEAE-cellulose chromatographic fractions, it was found that band 3 and 4 were T.I. band, corresponding to Ti¹ and Ti² band, respectively. In addition, band 6 and 10 were presumed to be T.I. band. Of the 42 varieties sampled, 35 revealed only Ti¹ band and 7 only Ti² band. The T.I. band patterns were not changed by the culture condition. The T.I. content, when expressed as the number of trypsin units inhibited (T.U.I), showed remarkable differences from 25 to 76 between varieties. The seedtime and fertilization condition had no effect on the T.I. content. Judged from the results of F ₁seeds analysis, we assumed that Ti¹ and Ti²band were controlled by codominant allele at a single locus.

Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells

Lee, K.H.,Choi, E.Y.,Hyun, M.S.,Jang, B.I.,Kim, T.N.,Kim, S.W.,Song, S.K.,Kim, J.H.,Kim, J.-R. S. Karger AG 2007 European surgical research Vol.39 No.4

<P><I>Background:</I> Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells. <I>Methods:</I> The effects of HGF on the expression of E-cadherin/β-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid. <I>Results:</I> Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of β-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with β-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion. <I>Conclusions:</I> These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.</P><P>Copyright © 2007 S. Karger AG, Basel</P>

5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced by <i>Bacteroides fragilis</i> enterotoxin via dissociating the complex of heat shock protein 90 and I&kgr;B&agr; and I&kgr;B kinase-&ggr; in intestinal epithelial cell cultu

Kim, J. M.,Lee, D. H.,Kim, J. S.,Lee, J. Y.,Park, H.-G.,Kim, Y.-J.,Oh, Y.-K.,Jung, H. C.,Kim, S. I. Blackwell Publishing Ltd 2009 Clinical and experimental immunology Vol.155 No.3

<P>Summary</P><P>Enterotoxin produced by enterotoxigenic <I>Bacteroides fragilis</I> (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti-inflammatory molecular mechanism of 5,7-dihydroxy-3,4,6-trimethoxyflavone (eupatilin) was characterized in an HT-29 intestinal epithelial cell line stimulated with BFT. Pre-treatment of HT-29 cells with eupatilin decreased the production significantly of both interleukin (IL)-8 and prostaglandin E<SUB>2</SUB> induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-&kgr;B) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-&kgr;B activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both I&kgr;B&agr; and I&kgr;B kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-&agr; and IKK-&bgr; decreased the production of IL-8 and prostaglandin E<SUB>2</SUB>; however, the transfection of IKK-&bgr; siRNA showed a more significant reduction of BFT-induced I&kgr;B&agr; phosphorylation compared with that of IKK-&agr; siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-&kgr;B, suggesting that Hsp90 is associated with a pathway of IKK-NF-&kgr;B-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-&ggr; in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-&kgr;B signalling pathway by targeting the Hsp90-IKK-&ggr; complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.</P>

Differentiation of Recurrent Tumor and Posttreatment Changes in Head and Neck Squamous Cell Carcinoma: Application of High b-Value Diffusion-Weighted Imaging

Hwang, I.,Choi, S.H.,Kim, Y.-J.,Kim, K.G.,Lee, A.L.,Yun, T.J.,Kim, J.-h.,Sohn, C.-H. American Society of Neuroradiology 2013 AJNR, American journal of neuroradiology Vol.34 No.12

<P><B>BACKGROUND AND PURPOSE:</B></P><P>High b-value DWI has been expected to have an additional diagnostic role and demonstrated some promising results in head and neck cancer. The aim of this study was to evaluate the diagnostic performance of DWI at a high b-value (<I>b</I>=2000 s/mm<SUP>2</SUP>) compared with a standard b-value (<I>b</I>=1000 s/mm<SUP>2</SUP>) and the ratio of ADC values of high and standard b-values for their ability to differentiate between recurrent tumor and posttreatment changes after the treatment of head and neck squamous cell carcinoma.</P><P><B>MATERIALS AND METHODS:</B></P><P>A total of 33 patients diagnosed with head and neck squamous cell carcinoma were enrolled in the present study; all had contrast-enhancing lesions on follow-up MR imaging. All patients underwent single-shot echo-planar DWI at <I>b</I>=1000 s/mm<SUP>2</SUP> and <I>b</I>=2000 s/mm<SUP>2</SUP>, and corresponding ADC maps were generated (ADC<SUB>1000</SUB> and ADC<SUB>2000</SUB>, respectively). The mean ADC<SUB>1000</SUB>, ADC<SUB>2000</SUB>, and ADC<SUB>ratio</SUB> (ADC<SUB>ratio</SUB> = ADC<SUB>2000</SUB>/ADC<SUB>1000</SUB> × 100) values were evaluated within a manually placed ROI with contrast-enhanced T1-weighted images as references. For the statistical analysis, we performed a Student <I>t</I> test and multivariate logistic regression.</P><P><B>RESULTS:</B></P><P>The mean ADC<SUB>1000</SUB> in recurrent tumor was significantly lower than that in posttreatment changes (<I>P</I> < .001), whereas the mean ADC<SUB>2000</SUB> resulted in no significant difference (<I>P</I> = .365). The mean ADC<SUB>ratio</SUB> was significantly higher in recurrent tumor than that in posttreatment changes (73.5 ± 7.2% vs 56.9 ± 8.8%, respectively; <I>P</I> < .001). Multivariate logistic regression analysis revealed that the ADC<SUB>ratio</SUB> was the only independently differentiating variable (<I>P</I> = .024). The sensitivity, specificity, and accuracy of ADC<SUB>ratio</SUB> were 95.0%, 69.2%, and 84.8%, respectively, by use of the optimal cutoff value of 62.6%.</P><P><B>CONCLUSIONS:</B></P><P>We suggest that the ADC<SUB>ratio</SUB> calculated from the ADC<SUB>1000</SUB> and ADC<SUB>2000</SUB> is a promising value for the differentiation of recurrent tumor and posttreatment changes in head and neck squamous cell carcinoma.</P>

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

Park, S R,Kim, H K,Kim, C G,Choi, I J,Lee, J S,Lee, J H,Ryu, K W,Kim, Y-W,Bae, J-M,Kim, N K Cancer Research UK 2008 The British journal of cancer Vol.98 No.8

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m<SUP>−2</SUP> b.i.d.) and docetaxel (25–40 mg m<SUP>−2</SUP>); MTD was 45 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel and RD was 40 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.British Journal of Cancer (2008) 98, 1305–1311. doi:10.1038/sj.bjc.6604312 www.bjcancer.com Published online 25 March 2008