FOXA1: a Promising Prognostic Marker in Breast Cancer

Hu, Qing,Luo, Zhou,Xu, Tao,Zhang, Jun-Ying,Zhu, Ying,Chen, Wei-Xian,Zhong, Shan-Liang,Zhao, Jian-Hua,Tang, Jin-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Accurate diagnosis and proper monitoring of cancer patients remain important obstacles for successful cancer treatment. The search for cancer biomarkers can aid in more accurate prediction of clinical outcome and may also reveal novel predictive factors and therapeutic targets. One such prognostic marker seems to be FOXA1. Many studies have shown that FOXA1 is strongly expressed in a vast majority of cancers, including breast cancer, in which high expression is associated with a good prognosis. In this review, we summarize the role of this transcription factor in the development and prognosis of breast cancer in the hope of providing insights into utility of FOXA1 as a novel biomarker.

Suppression of Ku80 Correlates with Radiosensitivity and Telomere Shortening in the U2OS Telomerase-negative Osteosarcoma Cell Line

Hu, Liu,Wu, Qin-Qin,Wang, Wen-Bo,Jiang, Huan-Gang,Yang, Lei,Liu, Yu,Yu, Hai-Jun,Xie, Cong-Hua,Zhou, Yun-Feng,Zhou, Fu-Xiang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening.

Down-regulation of miRNA-452 is Associated with Adriamycin-resistance in Breast Cancer Cells

Hu, Qing,Gong, Jian-Ping,Li, Jian,Zhong, Shan-Liang,Chen, Wei-Xian,Zhang, Jun-Ying,Ma, Teng-Fei,Ji, Hao,Lv, Meng-Meng,Zhao, Jian-Hua,Tang, Jin-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

The effect of Panax notoginseng saponins on oxidative stress induced by PCV2 infection in immune cells: in vitro and in vivo studies

Qiu-Hua Wang,Na Kuang,Wen-yue Hu,Dan Yin,Ying-Yi Wei,Ting-Jun Hu 대한수의학회 2020 Journal of Veterinary Science Vol.21 No.4

Background: Panax notoginseng saponins (PNS) are bioactive substances extracted from P. notoginseng that are widely used to treat cardiovascular and cerebrovascular diseases and interstitial diseases. PNS have the functions of scavenging free radicals, anti-inflammation, improving blood supply for tissue and so on. Objectives: The aim of this study was to investigate the effects of PNS on the oxidative stress of immune cells induced by porcine circovirus 2 (PCV2) infection in vitro and in vivo. Methods: Using an oxidative stress model of PCV2 infection in a porcine lung cell line (3D4/2 cells) and mice, the levels of nitric oxide (NO), reactive oxygen species (ROS), total glutathione (T-GSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) and the activities of xanthine oxidase (XOD), myeloperoxidase (MPO) and inducible nitric oxide synthetase (iNOS) were determined to evaluate the regulatory effects of PNS on oxidative stress. Results: PNS treatment significantly reduced the levels of NO and ROS, the content of GSSG and the activities of XOD, MPO, and iNOS (p < 0.05), while significantly increasing GSH and the ratio of GSH/GSSG in infected 3D4/2 cells (p < 0.05).Similarly, in the in vivo study, PNS treatment significantly decreased the level of ROS in spleen lymphocytes of infected mice (p < 0.05), increased the levels of GSH and T-GSH (p < 0.05), significantly decreased the GSSG level (p < 0.05), and decreased the activities of XOD, MPO, and iNOS. Conclusions: PNS could regulate the oxidative stress of immune cells induced by PCV2 infection in vitro and in vivo.

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

Li-jun Liang,Chen-xi Hu,Yi-xuan Wen,Xiao-wei Geng,Ting Chen,Guo-qing Gu,Lei Wang,You-you Xia,Yong Liu,Jia-yan Fei,Jie Dong,Feng-hua Zhao,Yiliyar Ahongjiang,Kai-yuan Hui,Xiao-dong Jiang 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Construction and Characterization of a Full-length cDNA Library and Identification of Genes Involved in Salinity Stress in Wild Eggplant (Solanum torvum Swartz)

Gang Chen,Hua Wang,Jun-Yi Gai,Yue-Lin Zhu,Li-Fei Yang,Qian-Qian Liu,Gong-Chen Zhang,Guo-Hu Chen 한국원예학회 2012 Horticulture, Environment, and Biotechnology Vol.53 No.2

The objectives of this paper were to construct a full-length cDNA library and to isolate genes that confer salt tolerance from the leaves of salinity-tolerant wild eggplant variety, ‘Torvum Vigor’ (Solanum torvum Swartz). A full-length cDNA library from the leaves was successfully constructed by a switching mechanism at 5’-end of RNA transcript (SMART) approach and a long-distance PCR (LD-PCR) technique. The titer of the primary cDNA library was 3.6 ×106 cfu・mL-1 and that of the amplified library was 1.2 × 1010 cfu・mL-1. Gel electrophoresis results showed that most of the cDNA inserts ranged from 0.40 to 2.5 kb, with a recombination rate of 99%. A total of 427 randomly selected positive clones were sequenced. After removing the unsuccessful reads, 364 datasets were obtained and have been submitted to the NCBI Nucleotide Sequence Database under GenBank accession numbers JK265131-JK265494. Among the 364 submitted sequences, 74.45% of them contained full-length coding regions. BLASTX analysis revealed that 62.36% of the ‘Torvum Vigor’ expressed sequence tags (ESTs) possessed homology to known or putative proteins of other organisms. Seven genes that might be responsible for the encoding of known proteins in other organisms were identified to confer salt tolerance. This evidence demonstrated that the cDNA library constructed was a full-length library of high quality. It could be a useful resource for further research in the cloning of stress-related genes, which could be utilized in the genetic improvement of vegetable crops using transgenic technology.

Association of Rs11615 (C>T) in the Excision Repair Cross-complementing Group 1 Gene with Ovarian but not Gynecological Cancer Susceptibility: a Meta-analysis

Ma, Yong-Jun,Feng, Sheng-Chun,Hu, Shao-Long,Zhuang, Shun-Hong,Fu, Guan-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Evidence suggests that the rs11615 (C>T) polymorphism in the ERCC1 gene may be a risk factor for gynecological tumors. However, results have not been consistent. Therefore we performed this meta-analysis. Methods: Eligible studies were identified by search of PubMed, MEDLINE and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess associations between rs11615 (C>T) and gynecological tumor risk. Heterogeneity among studies was tested and sensitivity analysis was applied. Results: A total of 6 studies were identified, with 1,766 cases and 2,073 controls. No significant association was found overall between rs11615 (C>T) polymorphism and gynecological tumors susceptibility in any genetic model. In further analysis stratified by cancer type, significantly elevated ovarian cancer risk was observed in the homozygote and recessive model comparison (TT vs. CC: OR=1.69, 95% CI=1.03-2.77, heterogeneity=0.876; TT vs. CT/CC: OR=1.72, 95% CI=1.07-2.77, heterogeneity=0.995). Conclusion: The results of the present meta-analysis suggest that there is no significant association between the rs11615 (C>T) polymorphism and gynecological tumor risk, but it had a increased risk in ovarian cancer.

Tanshinone II-A Inhibits Angiogenesis through Down Regulation of COX-2 in Human Colorectal Cancer

Zhou, Li-Hong,Hu, Qiang,Sui, Hua,Ci, Shu-Jun,Wang, Yan,Liu, Xuan,Liu, Ning-Ning,Yin, Pei-Hao,Qin, Jian-Min,Li, Qi Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

Zhong, Shan-Liang,Zhang, Jun,Hu, Qing,Chen, Wei-Xian,Ma, Teng-Fei,Zhao, Jian-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838, 95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysis was performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverse association was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for the PB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.

Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

Wang, Di,Xiao, Pei-Ling,Duan, Hua-Xin,Zhou, Ming,Liu, Jin,Li, Wei,Luo, Ke-Lin,Chen, Jian-Jun,Hu, Jin-Yue Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.