Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going

Chen Liang,Si Shi,Qingcai Meng,Dingkong Liang,Shunrong Ji,Bo Zhang,Yi Qin,Jin Xu,Quanxing Ni,Xianjun Yu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

Synthesis, Application, and Recovery of Alkali-Clearable Disperse Dyes Containing Azo Pyridone Structure

Liang Jin,Tao Qian,Ren-Liang Wang,Tao Zhu,Wei-Guo Chen,Hua Jiang,Zhi-Hua Cui 한국섬유공학회 2022 Fibers and polymers Vol.23 No.4

Carboxylic acid ester disperse dyes containing an azo pyridone structure have a high molar extinction coefficient,excellent washing color fastness, and simple synthetic methods. Dyes were readily synthesized through a conventional diazocoupling reaction between the reactant ethyl p-aminobenzoate and a coupling component containing an azo pyridonestructure. Subsequently, the molecular structures of the target products were characterized by FTIR, mass spectrometry,1H NMR, 13C NMR, UV-vis absorption spectroscopy, and elemental analysis. The synthesized dyes were used to dyepoly(ethylene terephthalate) fabric, and their washing and rubbing color fastness properties were tested and compared underdifferent post-treatment methods. Moreover, under the condition of alkali clearing, the relationships among different alkaliconcentrations and clearing effects were studied to determine the optimal alkali clearing process conditions for dyed fabrics,and the minimum alkali consumption required to obtain the best results was determined. It was found that carboxylic esterdisperse dyes containing an azo pyridone structure showed good dyeing performance and alkali-clearable properties onpolyester fibers. In addition, in hydrolyzate recovery, BaCl2 (salting out) can be used instead of acidification to recover thedye hydrolyzate, which has good environmental benefits.

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.

Rehmannioside D mitigates disease progression in rats with experimental-induced diminished ovarian reserve via Forkhead Box O1/KLOTHO axis

Yan Liang,Huimin Wang,Jin Chen,Lingyan Chen,Xiaoyong Chen 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.2

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E2 expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis

Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells

Fan Liang-Liang,Du Ran,Liu Ji-Shi,Jin Jie-Yuan,Wang Chen-Yu,Dong Yi,He Wan-Xia,Yan Ri-Qiang,Xiang Rong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play roles in neurodegenerative diseases, but little is known about its function in the kidneys. The aim of the present study was to clarify the roles of RTN3 in chronic kidney disease (CKD) and kidney fibrosis. In this study, RTN3 levels were measured in kidney tissues from healthy controls and CKD or kidney fibrosis patients. An RTN3-null mouse model was generated to explore the pathophysiological roles of RTN3 in the kidneys. The underlying mechanisms were studied in primary proximal tubular epithelial cells and HEK293 cells in vitro. The results showed that (1) a reduction in RTN3 in mice induces CKD and kidney fibrosis; (2) decreased RTN3 expression is found in patients with CKD; (3) RTN3 plays critical roles in regulating collagen biosynthesis and mitochondrial function; and (4) mechanistically, RTN3 regulates these phenotypes by interacting with GC-Rich Promoter Binding Protein 1 (GPBP1), which activates the IGF2-JAK2-STAT3 pathway. Our study indicates that RTN3 might play crucial roles in CKD and kidney fibrosis and that a reduction in RTN3 in the kidneys might be a risk factor for CKD and kidney fibrosis.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Song-Wu Liang,Gang Chen,Yi-Ge Luo,Peng Chen,Jin-Han Gu,Qiong-Qian Xu,Yi-Wu Dang,Li-Ting Qin,Hui-Ping Lu,Wen-Ting Huang,Zhi-Guang Huang,Li Gao,Jia-Bo Chen 대한외과학회 2020 Annals of Surgical Treatment and Research(ASRT) Vol.99 No.2

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

( Rui Dong Li ),( Zhong Liang Deng ),( Ning Hu ),( Xi Liang ),( Bo Liu ),( Jin Yong Luo ),( Liang Chen ),( Liang Jun Yin ),( Xiao Ji Luo ),( Wei Shui ),( Tong Chuan He ),( Wei Huang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.9

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with TGFβ1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFβ1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of TGFβ1 inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of TGFβ1 potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGFβ1 decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that TGFβ1 inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in G0/G1 phase. Our findings strongly suggest that TGFβ1 may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells. [BMB Reports 2012; 45(9): 509-514]

Piperonyl butoxide synergizes the larvicidal activity of Origanum vulgare essential oil and its major constituents against the larvae of Aedes albopictus and Culex pipiens quinquefasciatus

Chen Junhui,Liu Yangqing,Ma Guangqiang,Yang Feiying,Zhan Zhigao,Guan Limei,Kuang Wendong,Wang Jinchang,Li Jianghuai,Han Fei,Jin Liang 한국응용곤충학회 2023 Journal of Asia-Pacific Entomology Vol.26 No.1

Mosquitoes bite human beings and transmit many diseases, such as malaria, dengue fever, and Zika virus. Vector control of mosquitoes is an effective strategy for reducing the spread of disease. However, extensive use of in secticides (e.g. pyrethroids and organophosphorus) has caused resistance in mosquitoes, which weakens the effectiveness of mosquito control. Phytochemicals have been considered an alternative approach to mosquito control. Essential oil (EO) was obtained from the leaves and flowers of Origanum vulgare, and its synergistic activity with piperonyl butoxide (PBO) was tested against Aedes albopictus and Culex pipiens quinquefasciatus larvae. Thirty-seven compounds were identified, among which carvacrol and thymol were two major constitu ents (30.73 % and 18.81 %, respectively). O. vulgare EO had a significant toxic effect against fourth-stage larvae of Cx. p. quinquefasciatus and Ae. albopictus, with LC 50 values of 17.51 and 75.90 mg/L. Carvacrol and thymol also each appeared to be more effective against Cx. p. quinquefasciatus (LC 50 = 19.30 and 11.56 mg/L, respectively) than Ae. albopictus (LC 50 = 26.62 and 26.66 mg/L, respectively). PBO interacted synergistically with O. vulgare EO, carvacrol and thymol with 2.60–6.26 times as much of the active compound needed without PBO as against Cx. p. quinquefasciatus and Ae. albopictus larvae. Overall, our results contribute to the development of new natural mosquito insecticides.

Growth and Optical Properties of Nanocrystalline/Microcrystalline DiamondMultilayer Films

Jin-Long Luo,Xuan-Tong Ying,Liang-Yao Chen,Pei-Nan Wang 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.46 No.2

Nanocrystalline/microcrystalline diamond (NCD/MCD) multilayer film with high sp3 bonded carbon concentration and smooth surface has been successfully deposited on silicon substrate. Optimized deposition parameters based on substrate temperature modulation were adopted to grow the NCD/MCD film. The nanocrystallinity, purity and the multilayer structure were characterized by Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The smoothness of the film surface was shown by surface profile measurements and further verified by its high optical transmittance from visible to infrared band. Therefore, this newly proposed NCD/MCD multilayer film would have a variety of optical applications.

Lectin from Agrocybe aegerita as a Glycophenotype Probe for Evaluation of Progression and Survival in Colorectal Cancer

Liang, Yi,Chen, Hua,Zhang, Han-Bin,Jin, Yan-Xia,Guo, Hong-Qiang,Chen, Xing-Gui,Sun, Hui Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Background: Agrocybe aegerita Lectin (AAL) has been identified to have high affinity for sulfated and ${\alpha}2$-3-linked sialic acid glycoconjugates, especially the sulfated and sialyl TF (Thomsen-Friedenreich) disaccharide. This study was conducted to investigate the clinicopathological and prognostic value of AAL in identifying aberrant glycosylation in colorectal cancer (CRC). Materials and Methods: Glycoconjugate expression in 59 CRC tissues were detected using AAL-histochemistry. Clinicopathological associates of expression were analyzed with chisquare test or Fisher's exact test. Relationships between expression and the various clinicopathological parameters was estimated using Kaplan-Meier analysis and Cox regression models. Results: AAL specific glycoconjugate expression was significantly higher in tumor than corresponding normal tissues (66.1% and 46.1%, respectively, p=0.037), correlating with depth of invasion (p=0.015) and TNM stage (p=0.024). Patients with lower expression levels had a significantly higher survival rate than those with higher expression (p=0.046 by log rank test and p=0.047 by Breslow test for overall survival; p=0.054 by log rank test and P=0.038 by Breslow test for progress free survival). A marginally significant association was found between AAL specific glycoconjugate expression and overall survival by univariate Cox regression analysis (p=0.059). Conclusions: Lower AAL specific glycoconjugate expression is a significant favorable prognostic factor for overall and progress free survival in CRC. This is the first report about the employment of AAL for histochemical analysis of cancer tissues. The binding characteristics of AAL means it has potential to become a powerful tool for the glycan investigation and clinical application.