Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

Zhang, Ling-Qiang,Zhang, Xiu-De,Xu, Jia,Wan, Yong,Qu, Kai,Zhang, Jing-Yao,Wang, Zhi-Xin,Wei, Ji-Chao,Meng, Fan-Di,Tai, Ming-Hui,Zhou, Lei,Liu, Chang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

Editorial

정기준,Chao-Ling Yao,Phang Lai Yee 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Evaluation of reference genes for miRNA expression analysis in Galeruca daurica (Coleoptera: Chrysomelidae) using qRT‐PCR

Hai-Chao WANG,Ling LI,Yan-Yan LI,Yao TAN,Bao-Ping PANG 한국곤충학회 2021 Entomological Research Vol.51 No.8

The selection of suitable reference genes (RGs) for data normalization is a crucial step for obtaining reliable results from gene expression analysis using the quantitative real-time polymerase chain reaction (qRT-PCR). Expression stability of eleven putative RGs (miR-100-5p, miR-92a-3p, miR-998-3p, miR-279d-3p, miR-305-5p, miR-276a-3p, miR-275-3p, miR-9a-5p, miR-2a-3p, U6 snRNA and 5S rRNA) was assessed by using a web-based tool: RefFinder, which integrates four algorithms (Delta Ct, geNorm, NormFinder, and BestKeeper), and the best combination number of RGs was calculated by geNorm. Validation of selected RGs was performed by an expression analysis of let-7-5p under different experimental conditions. The best combinations of RGs were shown as follows: miR-100-5p + miR-275-3p for temperature treatment, miR-100-5p + miR-305-5p for adult tissues, miR- 276a-3p + miR-9a-5p for genders, miR-2a-3p + miR-276a-3p for days after eclosion, U6 snRNA + miR-9a-5p + miR-2a-3p for developmental stages, and U6 snRNA + miR-279d-3p for all above conditions, and there was no one RG suitable for all experimental conditions. Incorrect RG selection affected the evaluation of let-7-5p abundance. Our findings demonstrate that an integrated approach of multiple algorithms is necessary to identify reliable, stable RGs for miRNA evaluation, and provide a basis for further studies on expression and function analysis of miRNAs and their target genes in Galeruca daurica, a new pest with great outbreaks in Inner Mongolia since 2009.

Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

Jia-Piao Lin,Chao-Qin Chen,Ling-Er Huang,Na-na Li,Yan Yang,Sheng-Mei Zhu,Yong-Xing Yao 한국뇌신경과학회 2018 Experimental Neurobiology Vol.27 No.4

α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves’ tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 μg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.

Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer

Lin Fang,Fei-Hu Yan,Chao Liu,Jing Chen,Dan Wang,Chun-Hui Zhang,Chang-Jie Lou,Jie Lian,Yang Yao,Bo-Jun Wang,Rui-Yang Li,Shu-Ling Han,Yi-Bing Bai,Jia-Ni Yang,Zhi-Wei Li,Yan-Qiao Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

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.

Mechanical Stretch Promotes Invasion of Lung Cancer Cells via Activation of Tumor Necrosis Factor-alpha

Liang-Kun Chen,Ching-Chi Hsieh,Yi-Chao Huang,Yuan-Jung Huang,Chun-Fan Lung,Wei-En Hsu,Chao-Ling Yao,Tsung-Yu Tseng,Chi-Chung Wang,Yi-Chiung Hsu 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Most of the gas exchange in the human body is carried out by the lungs, and the physiological activities of the lungs are uninterrupted. Due to the deterioration of the external environment, pulmonary cell lesions are common clinical lung diseases. Mechanical cyclic stretching is one kind of bionic technology to observe lung cancer cells. The A549 cell line is the human lung adenocarcinoma cell line derived from a primary lung tumor. This study investigated the effects of mechanical cyclic stretching on A549 cell activity and gene expression profile. Whereas mechanical cyclic stretching had no significant difference in colony formation and cell migration of A549 cells, the cell invasion increased significantly in A549 cells after stretching. In addition, the microarray data showed that mechanical cyclic stretching altered gene expression, induced inflammation of cells, and activation of Wnt/β- catenin and tumor necrosis factor pathways. More importantly, mechanical cyclic stretching activated the expression of tumor necrosis factor-alpha (TNF-α) protein. Therefore, the increase of cell invasion induced by mechanical cyclic stretching might be associated with the activation of TNF-α in human lung adenocarcinoma cells.

Hyaluronic Acid Stimulated Enterocytic Differentiation of Intestinal Stem Cells and Enhanced Enteroid Grafting on Scaffolds

Siu Chung Ha,Ya-Hui Tsai,Shinn-Gwo Hong,Yun Chen,Chao-Ling Yao 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Hyaluronic acid (HA) is one of the main components of the extracellular matrix, and functions as a stabilizing molecule for cell-niche interactions. Although the mechanism of HA in supporting cell attachment is debatable, HA-based scaffolds are increasingly being applied in tissue engineering owing to their excellent mechanical properties and biocompatibility. HA reportedly enhances the intestinal growth in postnatal mice. In the present study, we aimed to investigate the effects of HA on intestinal stem cells (ISCs) using an in vitro enteroid culture system. A high-concentration of HA (0.5 mg/mL) significantly lowered the proliferative activity of ISCs with decreased enteroid-forming efficiency compared to the control ISCs. In contrast, a low-concentration of HA (0.1 mg/mL) did not affect the enteroid-forming efficiency of ISCs, but up regulated markers of enterocytic differentiation, villin, and HA receptor, CD44 and TLR4, in the enteroid cells. When enteroid fragments were seeded on an intestinal submucosa bioscaffold, HA treatment enhanced the growth and differentiation of enteroid cells on the material with a high villin expression level in the cell grafts. These results suggest that HA treatment is effective in promoting enterocytic differentiation of ISCs and enteroid grafting on scaffolds.

Decellularized Human Umbilical Artery Exhibits Adequate Endothelialization in Xenogenic Transplantation

Kai Hsia,Tien-Shiang Wang,Chin-Su Liu,Chih-Kuan Su,Chien-Chin Chen,Chang-Ching Yeh,Hsinyu Lee,Chao-Ling Yao,Tsung-Yu Tseng,Shih-Hwa Chiou,Hsu Ma,Chih-Hsun Lin,Jen-Her Lu 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Decellularized human umbilical arteries (dHUA) is an off-the-shelf graft that can potentially serve as vascular scaffolds in tissue engineering of small-diameter vascular grafts. This research aimed to investigate that dHUA could exhibit adequate endothelialization for a long term in xenogenic transplantation. 13 dHUAs were implanted in rat abdominal aortas up to 90 days. Rats were divided into three groups in terms of survival period: Group 1, one to seven days (n = 6); Group 2, 14 to 30 days (n = 4) and Group 3, 90 days (n = 3). The explants were analyzed by histological, immunohistochemistry and magnetic resonance angiography (MRA) examination. Allograft implantation of 12 decellularized rat abdominal aortas` were processed the same way as the rat in order to make a comparison for survival rates (Group 1, n = 5; Group 2, n = 4; Group 3, n = 3). The results demonstrated that the survival rates of xenograft and allograft implantation were estimated to be 59.2% vs. 58.3% in Group 1, 50.7% vs. 58.3% in Group 2 and 3. Grafts harvested from Group 2 were showed CD31, endothelial nitric oxide synthase expression at intima, and α-smooth muscle actin, CD45, CD68 and CD168 expression at the tunica externa. A layer structure with obvious endothelialization and fiber regeneration/orientation could be inspected from the explants of Group 3. MRA demonstrated the patency of dHUA on day 30 and 90. In conclusion, more than 50% dHUA maintained patency in the xenogenic model till 90 days after surgery. A mature vessel-like functional structure with intact endothelial layer was observed then. This warrants further study in the reinforcement of decellularized vascular scaffolds.

Distinctions Between Clinicopathological Factors and Prognosis of Alpha-fetoprotein Negative and Positive Hepatocelluar Carcinoma Patients

Xu, Jia,Liu, Chang,Zhou, Lei,Tian, Feng,Tai, Ming-Hui,Wei, Ji-Chao,Qu, Kai,Meng, Fan-Di,Zhang, Ling-Qiang,Wang, Zhi-Xin,Zhang, Jing-Yao,Chang, Hu-Lin,Liu, Si-Nan,Xu, Xin-Shen,Song, Yan-Zhou,Liu, Jun,Z Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ${\leq}$20ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.