STRATEGI PROMOSI DALAM MENINGKATKAN VOLUME PENJUALAN PADA MEBEL RIMBA SENTOSA DI SUKOHARJO

2015-2016 > Academic research: refereed > Publication in refereed journalVersion of RecordRGC531213 and 15206915Publishe

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The number of resected lymph nodes is associated with the long-term survival outcome in patients with T2 N0 non-small cell lung cancer

Ying-Sheng Wen,1,2,* Ke-Xing Xi,3,* Ke-Xiang Xi,4 Ru-Si Zhang,1,2 Gong-Ming Wang,1,2 Zi-Rui Huang,1,2 Lan-Jun Zhang1,5 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, People’s Republic of China; 4Department of Obstetrics, Jieyang People’s Hospital (Jieyang Affiliated Hospital, Sun Yat-sen University), Jieyang 522000, People’s Republic of China; 5Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, People’s Republic of China *These authors have contributed equally to this work Objective: For the patients with pathologic T2 N0 non-small cell lung cancer (NSCLC), the extent of lymph node (LN) removal required for survival is controversial. We aimed to explore the prognostic significance of examined LNs and to identify how many nodes should be examined.Methods: We reviewed 549 patients who underwent pulmonary or pneumonectomy surgery or plus lymphadenectomy who were confirmed as T2 stage and LN negative by postoperative pathological diagnosis. According to Martingale residuals of the Cox model, the patients were classified into four groups by the number of examined LNs (1–2 LNs, 3–7 LNs, 8–11 LNs, and ≥12 LNs). Kaplan–Meier analysis and Cox regression analysis were used to evaluate the association between survival and the number of examined LNs.Result: Compared with the 1–2 LNs, 3–7 LNs, and 8–11 LNs groups, the survival was significantly better in the ≥12 LNs group. The 5-year cancer-specific survival rate was 60.5% for patients with 1–2 negative LNs, compared with 68.7%, 72.6%, and 78.4% for those with 3–7, 8–11, and >11 LNs examined, respectively. The 7-year cancer-specific survival rate was 52.9% for patients with 1–2 negative LNs, compared with 63.7%, 63.8%, and 70.8% for those with 3–7, 8–11, and >11 LNs examined, respectively (P=0.045). There was a significant drop in mortality risk with the examination of more LNs. The lowest mortality risk occurred in those with 32 or more LNs examined. Multivariate analysis showed that age and the number of examined LNs were strong independent predictors of survival.Conclusion: The number of examined LNs is a strong independent prognostic factor. Our study demonstrates that patients with T2 N0 NSCLC should have at least 12 LNs examined and that the results of this study may provide information for the optimal number of resected LNs in surgery. Keywords: number of resected lymph nodes, non-small cell lung cancer, survival outcom

Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

Dan Shi,1,* Yan Liu,1,* Ronggang Xi,1 Wei Zou,2 Lijun Wu,3 Zhiran Zhang,1 Zhongyang Liu,1 Chao Qu,1 Baoli Xu,1 Xiaobo Wang1 1Department of Pharmacy, The 210th Hospital of People’s Liberation Army, 2College of Life Science, Liaoning Normal University, Dalian, Liaoning, 3Department of Pharmaceutics, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Chronic myelogenous leukemia (CML) is characterized by the t(9;22) (q34;q11)-associated Bcr-Abl fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs) have been prepared with an average particle size of <100 nm in a previous work. Compared with coarse realgar, the realgar NPs have higher bioavailability. As a principal constituent protein of caveolae, caveolin-1 (Cav-1) participates in regulating various cellular physiological and pathological processes including tumorigenesis and tumor development. In previous studies, it was found that realgar NPs can inhibit several types of tumor cell proliferation. However, the therapeutic effect of realgar NPs on CML has not been fully elucidated. In the present paper, it was demonstrated that realgar NPs can inhibit the proliferation of K562 cells and degrade Bcr-Abl fusion protein effectively. Both apoptosis and autophagy were activated in a dose-dependent manner in realgar NPs treated cells, and the induction of autophagy was associated with class I phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Morphological analysis indicated that realgar NPs induced differentiation effectively in CML cells. Furthermore, it was identified that Cav-1 might play a crucial role in realgar NP therapy. In order to study the effects of Cav-1 on K562 cells during realgar NP treatment, a Cav-1 overexpression cell model was established by using transient transfection. The results indicated that Cav-1 overexpression inhibited K562 cell proliferation, promoted endogenic autophagy, and increased the sensitivity of K562 cells to realgar NPs. Therefore, the results demonstrated that realgar NPs degraded Bcr-Abl oncoprotein, while the underlying mechanism might be related to apoptosis and autophagy, and Cav-1 might be considered as a potential target for clinical comprehensive therapy of CML. Keywords: realgar nanoparticles, Bcr-Abl fusion protein, apoptosis, autophagy, caveolin-