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Lee, Youngjoo,Lee, Ki Hyeong,Lee, Geon Kook,Lee, Soo-Hyun,Lim, Kun Young,Joo, Jungnam,Go, Yun Jung,Lee, Jin Soo,Han, Ji-Youn Korean Cancer Association 2017 Cancer Research and Treatment Vol.49 No.4
<P><B>Purpose</B></P><P>This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).</P><P><B>Materials and Methods</B></P><P>Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).</P><P><B>Results</B></P><P>Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (<I>EGFR</I>) mutation (p=0.122), <I>EGFR</I> fluorescence <I>in situ</I> hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).</P><P><B>Conclusion</B></P><P>There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.</P>
Body mass index and mortality in patients with gastric cancer: A large cohort study.
Lee, Jung Hwan,Park, Boram,Joo, Jungnam,Kim, Young-Il,Kim, Chan Gyoo,Lee, Jong Yeul,Choi, Il Ju,Yoon, Hong Man,Eom, Bang Wool,Ryu, Keun Won,Kim, Young Woo,Cho, Soo-Jeong Grune & Stratton 2018 Journal of clinical oncology Vol.36 No._suppl4
<P> 16 </P><P> Background: Although excess body weight has been known to be an important risk factor for mortality from many cancers including colorectal, endometrial and breast cancers, the prognosis of gastric cancer (GC) in obese patients seems controversial. Methods: We aimed to evaluate the association between body mass index (BMI) and mortality in GC in a large cohort. A single institute cohort of 7,765 GC patients undergoing curative gastrectomy between October 2000 and June 2016 were categorized into 6 groups; underweight (< 18.5 kg/m2), normal (18.5 to < 23 kg/m2), overweight (23 to < 25 kg/m2), obese I (25 to < 28 kg/m2), obese II (28 to < 30 kg/m2), and severely obese (≥30 kg/m2). The hazard ratios (HRs) for overall survival and disease-specific survival were calculated using Cox proportional hazard model. Results: We identified 1,279 all-cause and 763 disease-specific deaths among 7,765 patients, and the median follow-up period was 83.05 months (range, 1.02-186.97 months). In multivariable analyses adjusted by age, sex, tumor stage, comorbidity and operation methods, preoperative BMI was associated with all-cause mortality in a nonlinear pattern. As compared with patients who were normal weight, underweight BMI showed increasing mortality risk (hazard ratio (HR), 1.42, 95% confidence interval (CI), 1.15-1.77). In contrast, patients who were overweight (HR, 0.84; 95% CI, 0.73-0.97), obese I (HR, 0.77; 95% CI, 0.66-0.90) and obese II (HR, 0.77; 95% CI, 0.59-1.01) had lower risk of mortality. disease-specific mortality also had a similar pattern to overall survival showing the lowest mortality in obese II group (HR, 0.59; 95% CI, 0.40-0.88). There was no significant difference in severely obese patients in both all-cause and disease-specific mortalities. In spline analyses illustrated by a bell-shaped curve, risk for all-cause mortality was the lowest in patients with 26.67 kg/m<SUP>2</SUP>. Conclusions: Preoperative overweight and obese patients (23 to < 30 kg/m2) had lower all-cause and disease-specific mortalities compared to those with normal weight in GC patients who underwent curative surgical resection. </P>
Lee Kyung Eun,Mun Seyoung,Kim Song-mi,Shin Wonseok,Jung Won,Paek Joon,Lee Jungnam,Hudson Erin,Reeves Wesley H.,Han Kyudong,Cha Seunghee 한국유전학회 2022 Genes & Genomics Vol.44 No.10
Background: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Objective: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. Methods: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. Results: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. Conclusions: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.
Body mass index and mortality in patients with gastric cancer: a large cohort study
Lee, Jung Hwan,Park, Boram,Joo, Jungnam,Kook, Myeong-Cherl,Kim, Young-Il,Lee, Jong Yeul,Kim, Chan Gyoo,Choi, Il Ju,Eom, Bang Wool,Yoon, Hong Man,Ryu, Keun Won,Kim, Young-Woo,Cho, Soo-Jeong Springer-Verlag 2018 GASTRIC CANCER Vol.21 No.6
Jungnam Lee,Young-Joo Jin,Seung Kak Shin,Jung Hyun Kwon,Sang Gyune Kim,Young Ju Suh,Yujin Jeong,Jung Hwan Yu,Jin-Woo Lee,Oh Sang Kwon,Soon Woo Nahm,Young Seok Kim 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.2
Background/Aims: We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). Methods: We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. Results: The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396– 1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively. Conclusions: SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.
Robust Association Tests for the Replication of Genome-Wide Association Studies
Joo, Jungnam,Park, Ju-Hyun,Lee, Bora,Park, Boram,Kim, Sohee,Yoon, Kyong-Ah,Lee, Jin Soo,Geller, Nancy L. Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-
<P>In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum <I>p</I> value of Pearson's Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by <I>p</I> values of the discovery and replication studies.</P>