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Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression
Liang, Zhongxing,Cho, Heidi T.,Williams, Larry,Zhu, Aizhi,Liang, Ke,Huang, Ke,Wu, Hui,Jiang, Chunsu,Hong, Samuel,Crowe, Ronald,Goodman, Mark M.,Shim, Hyun-Suk The Korea Society of Nuclear Medicine 2011 핵의학 분자영상 Vol.45 No.2
Purpose L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. Methods LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[$^{18}F$]fluorocyclobutane-1-carboxylic acid (anti-[$^{18}F$]FACBC) PET was assessed for its diagnostic biomarker potential. Results Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-aminobicyclo[ 2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[$^{18}F$]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. Conclusions The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[$^{18}F$]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.
Liang-ke Zhang,Shi-xiang Hou,Jing-qin Zhang,Wen-jing Hu,Cheng-yuan Wang 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8
Folic acid was covalently conjugated to bovine serum albumin nanoparticles (BSANP) to target the nanoparticles to SKOV3 cells expressing folate receptors. Mitoxantrone was incorporated into the folate-conjugated albumin nanoparticles, and the final nanoparticle size was 68 nm, as measured by a laser light scattering particle analyzer. The cytotoxic activity of mitoxantrone-loaded, folate-conjugated albumin nanoparticles (MTO-BSANP-folate), which was quantitated by 3H-thymidine incorporation, was higher than mitoxantrone-loaded BSANP (MTO-BSANP) and MTO solution, and could be inhibited by free folic acid. MTO-BSANPfolate may be endocytosed via the folate receptor on the surface of SKOV3 cells. MTO-BSANPfolate also inhibited tumor growth better than the MTO-BSANP and MTO solution in vivo. These results indicate that folate-conjugated BSANP may have therapeutic potential as a vector for anticancer drugs in cancer chemotherapy.
Liang, Yong,Bu, Jun-Guo,Cheng, Jin-ling,Gao, Wei-Wei,Xu, Yao-Can,Feng, Jian,Chen, Bo-Yu,Liang, Wei-Chao,Chen, Ke-Quan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14
Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.
Shi-Ke Liang,Zi-Qiang Liang,Xiao-Sui Zhou,Jia-Lin Chen,Guang-Hong Li,Fang-Hai Wang 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.3
Sogatella furcifera is amajor rice pest that exhibits wing dimorphism. The methylation-sensitive representational difference analysis (MS-RDA) is widely used in plants and some animals to identify methylation differences in genomic DNA regions. However the method has been applied to insects very less. The objective of the current research was tomonitor differential cytosine methylations at CCGG sequences inmacropterous and brachypterous adults of female S. furcifera to determine the association between gene methylation and wing phenotypes using MS-RDA. After the second subtractive hybridization, two differentially methylated DNA fragments were obtained. These DNA fragments were then cloned into the pGEM-T vector and sequenced. One fragment fromthe positive hybridization was 464 bp, and highly similar to the 18S ribosomal RNA (rRNA) genes from some animals. Another fragment from the reverse hybridization was 453 bp, and homologous to the 28S rRNA gene of S. furcifera with a similarity rate as high as 99%. These results provide potential evidence that DNA methylation of rRNA genes may be related to wing phenotype variations in S. furcifera, and will facilitate future studies on the epigenetic mechanisms of insect wing polymorphism.
Prognostic Value of C-Reactive Protein in Esophageal Cancer: a Meta-analysis
Zheng, Tian-Liang,Cao, Ke,Liang, Cui,Zhang, Kai,Guo, Hai-Zhou,Li, De-Ping,Zhao, Song Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19
Background: The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. Materials and Methods: We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. Results: The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by "country", "cut-off value", "treatment" and "number of patients", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. Conclusions: Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction.
Liang, Meng,Hu, Ke Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.11
Ultraviolet light (UV)-induced cellular response has been studied by numerous investigators for many years. Long noncoding RNAs (lncRNAs) are emerging as new regulators of diverse cellular process; however, little is known about the role of lncRNAs in the cellular response to UV treatment. Here, we demonstrate that levels of lncRNA-HOTTIP significantly increases after UV stimulation and regulates the UV-mediated cellular response to UV through the coordinate activation of its neighboring gene Hoxa13 in GC-1 cells (spermatogonia germ cell line). UV-induced, G2/M-phase arrest and early apoptosis can be regulated by lncRNA-HOTTIP and Hoxa13. Furthermore, lncRNA-HOTTIP can up-regulate ${\gamma}-H_2AX$ and p53 expression via Hoxa13 in UV-irradiated GC-1 cells. In addition, p53 has the ability to regulate the expression of both lncRNA-HOTTIP and Hoxa13 in vitro and in vivo. Our results provide new data regarding the role lncRNAs play in the UV response in spermatogenic cells.