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      • KCI등재

        Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation

        Yuchun Wei,Chuqing Wei,Liang Chen,Ning Liu,Qiuxiang Ou,Jiani C. Yin,Jiaohui Pang,Zhenhao Fang,Xue Wu,Xiaonan Wang,Dianbin Mu,Yang Shao,Jinming Yu,Shuanghu Yuan 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4

        Purpose Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence. PurposeNeoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer.Materials and MethodsA total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits.ResultsGenetic alterations of <i>PIK3CA</i> were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including <i>TERT, POLD1, NOS2</i>, and <i>FGFR3</i> was significantly higher in Chinese patients whereas <i>RPTOR, EGFR</i>, and <i>TP53</i> were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including <i>BRCA1/2, TP53</i> and <i>PALB2</i>. Importantly, high tumor mutation burden, <i>TP53</i> polymorphism (rs1042522), and <i>KEAP1</i> mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. <i>KEAP1</i> mutations, <i>PIK3CA-SOX2</i> co-amplification, <i>TERC</i> copy number gain, and <i>TYMS</i> polymorphism correlated with an increased risk of disease relapse.ConclusionWe report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

      • KCI등재

        Effect of Sc Content on the Microstructure and Properties of Al–Mg–Sc Alloys Deposited by Wire Arc Additive Manufacturing

        Lingling Ren,Huimin Gu,Wei Wang,Shuai Wang,Chengde Li,Zhenbiao Wang,Yuchun Zhai,Peihua Ma 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.1

        Despite showing considerable potential, wire arc additive manufacturing (WAAM) has been limited to producing Al–Mgalloys. As the addition of Sc can improve the mechanical properties of Al–Mg alloys, in this study, Al–Mg–Sc alloy depositswith different Sc contents were prepared by a WAAM process. The porosity, microstructure, and mechanical properties ofthe deposits were studied. At Sc contents less than 0.15%, Sc was completely dissolved in the Al matrix without grain refinement,and the mechanical properties were slightly improved. At a Sc content of 0.3%, the primary Al3Scphase precipitatedout of the as-deposited body, resulting in an abrupt change in the microstructure, significant grain refinement, significantlyincreased tensile strength and yield strength, with a tensile strength, yield strength, and elongation of 372 MPa, 270 MPa,and 22.5%, respectively. Following heat treatment at 350 °C for 1 h, the grain boundaries were refined and the secondaryAl3Scphase was precipitated. Furthermore, the tensile strength and yield strength were significantly increased to 415 MPaand 279 MPa, respectively, and elongation decreased to 18.5%. At a Sc content of 0.45%, due to the aggregated precipitatedphase, the coarsened grain boundaries and the limited solid solution amount of Sc in the α(Al) matrix (~ 0.25%), themechanical properties were not further improved compared with the deposit with Sc content of 0.3%. Thus, based on economicconsiderations, the optimal Sc content was 0.3%. Owing to their enhanced mechanical properties, WAAM-producedAl–Mg–Sc alloys are expected to have a wide range of applications in aviation, aerospace.

      • KCI등재

        Two Indolocarbazole Alkaloids with Apoptosis Activity from a Marine-derived Actinomycete Z2039-2

        Rui Liu,Tianjiao Zhu,Dehai Li,Jingyan Gu,Wei Xia,Yuchun Fang,HongbingLiu,Weiming Zhu,Qianqun Gu 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.3

        Bioassay-guided fractionation of the EtOAc extract from the fermentation broth of a marinederived actinomycete Z2039-2 led to the isolation of two known indolocarbazole alkaloids, K252c (1) and arcyriaflavin A (2). 1 and 2 exhibited moderate cytotoxic activities against the K562 cell line, and induced apoptotic activities at 10 and 100 µM, respectively. This is the first report on the significant apoptosis inducing effect of indolocarbazole alkaloids against K562 cancer cells.

      • SCIESCOPUSKCI등재

        Two Indolocarbazole Alkaloids with Apoptosis Activity from a Marine-derived Actinomycete Z$_2$039-2

        Liu, Rui,Zhu, Tianjiao,Li, Dehai,Gu, Jingyan,Xia, Wei,Fang, Yuchun,Zhu, Weiming 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.3

        Bioassay-guided fractionation of the EtOAc extract from the fermentation broth of a marine-derived actinomycete Z$_2$039-2 led to the isolation of two known indolocarbazole alkaloids, K252c (1) and arcyriaflavin A (2). 1 and 2 exhibited moderate cytotoxic activities against the K562 cell line, and induced apoptotic activities at 10 and 100 ${\mu}$M, respectively. This is the first report on the significant apoptosis inducing effect of indolocarbazole alkaloids against K562cancer cells.

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