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Chae, Heejung,Kim, Deokhoon,Yoo, Changhoon,Kim, Kyu-pyo,Jeong, Jae Ho,Chang, Heung-Moon,Lee, Sang Soo,Park, Do Hyun,Song, Tae Jun,Hwang, Shin,Kim, Ki-Hun,Song, Gi-Won,Ahn, Chul Soo,Lee, Jae Hoon,Hwang Elsevier 2019 European journal of cancer Vol.120 No.-
<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers.</P> <P><B>Methods</B></P> <P>Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease.</P> <P><B>Results</B></P> <P>Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were <I>TP53</I> (44.4%), <I>KRAS</I> (29.0%), <I>ARID1A</I> (12.1%) and <I>IDH1</I> (9.7%). <I>IDH1/2</I> mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while <I>ERBB2</I>/<I>3</I> mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring <I>TP53</I> mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, <I>P</I> = 0.018), while <I>IDH1</I> mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, <I>P</I> = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, <I>P</I> = 0.013) and OS (21.0 vs. 13.3 months, <I>P</I> = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88).</P> <P><B>Conclusions</B></P> <P>A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We examined genetic landscape of biliary tract cancer with targeted sequencing. </LI> <LI> Certain genetic mutations were associated with clinical outcomes. </LI> <LI> More than half of patients harboured at least one potentially actionable alteration. </LI> <LI> DNA damage repair gene alterations were associated with a better response to platinum-based treatment. </LI> </UL> </P>
Chae, Han-Jung,Lee, Jun-Gi,Kang, Jang-Sook,Park, Young-Chul,Park, Joo-Bae,Kim, Hyung-Ryong 원광대학교 생체재료·매식연구소 2000 원광생체재료·매식 Vol.9 No.1
The gas radical, nitric oxide(NO), is a major autacoid regulating cell behavior in the cardioviscular, immune and central nervous systems. Recently, it was shown that it is produced by both the osteoblast and osteoclast and that NO appears to be an important regulatory molecule in the processes of bone remodeling. By measurements of nitrite production, Northen blot analysis, and Western blot analysis, we studied the effects of a membrane-permeable cAMP derivative, DBcAMP and 8-bromo-cAMP, on the expression of inducible nitric oxide synthase (iNOS) mRNA and protein and the synthesis of nitrite in ROS 17/2.8 cells. DBcAMP and 8-bromo-cAMP stimulated NO production and iNOS mRNA and protein expression in IFN-γ-treated ROS 17/2.8 cells in a dose-dependent manner. Compounds that increase intracellular cAMP levels(forskolin, theohylline, PGE_2), all stimulated No production and iNOS mRNA and protein expression in IFN-γ-treated ROS 17/2.8 cells. Sp-cAMPS(a selective activator of cAMP-dependent protein kinase I and II) also increased NO production and iNOS mRNA and protein expression in IFN-γ-treated ROS 17/2.8 cells. N^G - monomethyl-L-arginine, a NOS inhibitor, completely blocked the cAMP-elevating agents-induced NO production IFN-γ-treated ROS 17/2.8 cells. These observations indicate that cAMP is important in considering experiments involving the production of nitric oxide with IFN-γ.
Jun Sang Ham,Ji Hye Shin,Young Bae Noh,Seok Geun Jeong,Gi Sung Han,Hyun Seok Chae,Young Mo Yoo,Jong Nam Ahn,Wan Kyu Lee,Cheorun Jo 한국식품과학회 2008 Food Science and Biotechnology Vol.17 No.1
To see the possibility of irradiation as an alternative to ultra high temperature (UHT) sterilization, the quality characteristics of milk were analyzed. Milk treated by UHT (135℃ for 4 sec) and irradiation at higher than 3 kGy showed no viable counts after 7 days of storage at 4℃. The contents of certain amino acids of milk, such as Arg, Asp, Glu, Ile, Leu, Lys, Pro, Ser, Thr, and Tyr, were lower in irradiated groups at 10 kGy than in UHT-treated one, but no difference was observed between irradiated milks at less than 5 kGy and UHT. The capillary electrophoresis (CE) patterns of the milk irradiated at 10 kGy showed a similar trend to the raw milk, low temperature long time (LTLT, 63℃ for 30 min), and high temperature short time (HTST, 72℃ for 15 sec) treated. However, the CE pattern of UHT-treated milk was different. Rennet coagulation test agreed with the CE results, showing that all milk samples were coagulated by rennet addition except for UHT-treated milk after 1 hr. These results suggest that irradiation of milk reduce the content of individual amino acids but it may not induce severe conformational change at a protein level when compared with UHT treatment.