1. Effect of intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC
Luqing CHEN ; Min WANG ; Wanli ZHOU ; Fajun XIANG ; Dejuan HAN ; Zhenyou SUN ; Guowei LIU ; Hongsheng GAO
Chinese Journal of Primary Medicine and Pharmacy 2020;27(3):322-325
Objective:
To investigate the effect and safety of intensive hyperthermia combined with low-dose cisplatin plus radiotherapy in the treatment of patients with locally advanced NSCLC.
Methods:
From January 2012 to December 2015, 104 patients with locally advanced NSCLC were chosen in the Second People's Hospital of Weifang and randomly divided into two groups according to the digital table, with 52 patients in each group.The control group was given low-dose cisplatin plus radiotherapy, and the observation group was given intensive hyperthermia on the basis of control group.The ORR, DCR, median OS, median PFS, KPS score, the levels of coagulation function index and tumor markers before and after treatment and incidence of side effects in the two groups were compared.
Results:
The DCR of the observation group was significantly higher than that of the control group(86.54% vs.69.23%, χ2=8.24,
2.Arf6 as a therapeutic target: Structure, mechanism, and inhibitors.
Dejuan SUN ; Yuanyuan GUO ; Piyu TANG ; Hua LI ; Lixia CHEN
Acta Pharmaceutica Sinica B 2023;13(10):4089-4104
ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.
3.Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer.
Wenwen ZHONG ; Dejuan WANG ; Bing YAO ; Xiaoxia CHEN ; Zhongyang WANG ; Hu QU ; Bo MA ; Lei YE ; Jianguang QIU
Journal of Zhejiang University. Science. B 2021;22(8):664-681
Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely
4.PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids.
Yanli WU ; Yueying YANG ; Wang WANG ; Dejuan SUN ; Jing LIANG ; Man ZHU ; Hua LI ; Lixia CHEN
Acta Pharmaceutica Sinica B 2022;12(11):4262-4265
5.The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer.
Yang LIU ; Wei XU ; Mingxue LI ; Yueying YANG ; Dejuan SUN ; Lidian CHEN ; Hua LI ; Lixia CHEN
Acta Pharmaceutica Sinica B 2023;13(4):1438-1466
Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.
6.Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly(ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy
Xiaosa CHANG ; Dejuan SUN ; Danfeng SHI ; Guan WANG ; Yanmei CHEN ; Kai ZHANG ; Huidan TAN ; Jie LIU ; Bo LIU ; Liang OUYANG
Acta Pharmaceutica Sinica B 2021;11(1):156-180
This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.