Publications by authors named "Jing-Yan Tian"

9 Publications

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PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells.

Colloids Surf B Biointerfaces 2021 Jul 26;203:111723. Epub 2021 Mar 26.

Department of Urology, Second Division of The First Hospital of Jilin University, 3302 Jilin Rd, Changchun, 130031, Jilin, People's Republic of China. Electronic address:

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111723DOI Listing
July 2021

A novel GPCR target in correlation with androgen deprivation therapy for prostate cancer drug discovery.

Basic Clin Pharmacol Toxicol 2021 Feb 1;128(2):195-203. Epub 2020 Dec 1.

Department of Urology, Second Division of The First Hospital of Jilin University, Changchun, People's Republic of China.

Most prostate carcinomas require androgen stimulation to grow, and for nearly 70 years, androgen ablation therapy has been one of the central therapeutic strategies against advanced prostate cancer. Although most tumours initially respond to this therapy, some will be acquired resistant and progress to metastatic castration-resistant (mCRPC) disease which clinically tends to progress more rapidly than earlier disease manifestations. The underlying molecular biology of mCRPC is highly complex, and numerous mechanisms have been proposed that promote and retain androgen independence. In various clinical and preclinical data explored, the nature of intracellular signalling pathways mediating mitogenic acquired resistant effects of GPCRs in prostate cancer is poorly defined. G-protein-coupled receptor kinase 2 (GRK2) contributes to the modulation of basic cellular functions-such as cell proliferation, survival or motility-and is involved in metabolic homeostasis, inflammation or angiogenic processes. Moreover, altered GRK2 levels are starting to be reported in different tumoural contexts and shown to promote breast tumourigenesis or to trigger the tumoural angiogenic switch. Thus, we are exploring recent findings that present unexpected opportunities to interfere with major tumourigenic signals by manipulating GPCR-mediated pathways.
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http://dx.doi.org/10.1111/bcpt.13499DOI Listing
February 2021

Prostate cancer: updates on current strategies for screening, diagnosis and clinical implications of treatment modalities.

Carcinogenesis 2018 03;39(3):307-317

Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

Prostate cancer is the most common cancer in men by way of diagnosis and a leading cause of cancer-related deaths. Early detection and intervention remains key to its optimum clinical management. This review provides the most updated information on the recent methods of prostate cancer screening, imaging and treatment modalities. Wherever possible, clinical trial data has been supplemented to provide a comprehensive overview of current prostate cancer research and development. Considering the recent success of immunotherapy in prostate cancer, we discuss cell, DNA and viruses based, as well as combinatorial immunotherapeutic strategies in detail. Furthermore, the potential of nanotechnology is increasingly being realized, especially in prostate cancer research, and we provide an overview of nanotechnology-based strategies, with special emphasis on nanotheranostics and multifunctional nanoconstructs. Understanding these recent developments is critical to the design of future therapeutic strategies to counter prostate cancer.
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http://dx.doi.org/10.1093/carcin/bgx141DOI Listing
March 2018

Effects of cyclooxygenase-2 gene silencing on the biological behavior of SKOV3 ovarian cancer cells.

Mol Med Rep 2015 Jan 21;11(1):59-66. Epub 2014 Oct 21.

Department of Obstetrics and Gynaecology, The Second Hospital, Jilin University, Changchun 130041, P.R. China.

The aim of the present study was to investigate the effects of plasmid-mediated RNA interference targeting of cyclooxygenase-2 (COX-2) on the biological behaviors of SKOV3 human ovarian cancer cells and to analyze the function of COX-2 in carcinogenesis and development of ovarian cancer. A COX-2 small hairpin (sh)RNA sequence was designed and synthesized and pGPU6-COX-2-shRNA plasmids were constructed. The recombinant vector plasmids were stably transfected into SKOV3 cells. The mRNA and protein expression of COX-2 was subsequently analyzed by quantitative polymerase chain reaction and western blot analysis, respectively. MTT and colony formation assays were used to detect the cellular proliferation ability and flow cytometry was performed to detect phase changes in the cell cycle. Finally, a Transwell assay was used to detect cell invasion. The SKOV3 cells, transfected with recombinant vector plasmids, and control cells, were injected into nude mice and the tumor emergence time, volume and weight were measured. The impact of COX-2 gene silencing on the growth of xenograft tumors in nude mice was analyzed. Following transfection of the pGPU6-COX-2-shRNA plasmid, in vitro analyses indicated that the shRNA efficiently suppressed the mRNA and protein expression of COX-2. COX-2 gene silencing significantly inhibited the proliferation and invasion ability of SKOV3 cells, leading to cell cycle arrest in G1. The tumor formation time in the interference group was significantly prolonged, and the tumor volume and weight were significantly decreased, as compared with the control group. Plasmid-mediated shRNA was shown to effectively silence COX-2 expression in SKOV3 ovarian cancer cells. It was identified that COX-2 functioned in regulating proliferation, cell cycle and invasion of ovarian cancer cells. These findings provided a theoretical basis for determining the function of COX-2 in the development of ovarian cancer and suggested that COX-2 may be an effective target for gene therapy and clinical applications.
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http://dx.doi.org/10.3892/mmr.2014.2732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237092PMC
January 2015

Association of WBC count and glucose metabolism among Chinese population aged 40 years and over.

Diabetes Res Clin Pract 2008 Oct 8;82(1):132-8. Epub 2008 Aug 8.

Ruijin Hospital affiliated to Shanghai JiaoTong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, 197 Ruijin Er Lu, Shanghai 200025, China.

Chronic subclinical inflammation may be involved in the pathogenesis of Type 2 diabetes. We examined whether elevated WBC count, a marker of inflammation, was associated with worsening of glucose tolerance among Chinese population aged 40 years and over. Based on the 75g OGTT, 1016 subjects aged from 40 to 88 years were classified into four groups: NFG/NGT (n=299), isolated IFG (n=213), IGT (n=213) and Type 2 diabetes (n=291). We compared the WBC count among the four groups and investigated relevant variables associated significantly with the WBC count. The IGT and Type 2 diabetes groups had a significantly higher WBC count than the NFG/NGT and isolated IFG groups. By stepwise regression analyses, we found that waist circumference, DBP, total cholesterol, HDL cholesterol and 2-h PG showed an independent association with the WBC count. In the analysis stratified by sex and smoking status, WBC count was independently associated with age and triglycerides in males, whereas it was associated with BMI, SBP, triglycerides and 2-h PG in females. BMI, SBP, triglycerides and 2-h PG showed an independent association with WBC count in subjects who never smoked. We concluded that an increase in WBC count was associated with the deterioration of glucose tolerance. WBC count was associated with lipid metabolism in males and with various components of the metabolic syndrome in females and subjects who never smoked.
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http://dx.doi.org/10.1016/j.diabres.2008.05.014DOI Listing
October 2008

[The metabolic characteristics of isolated impaired fasting glucose and fasting hyperglycemia].

Zhonghua Nei Ke Za Zhi 2007 Jul;46(7):555-8

Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Objective: To evaluate the metabolic characteristics of insulin secretion and insulin sensitivity in isolated impaired fasting glucose (iIFG) and isolated fasting hyperglycemia (IFH) and to clarify the factors responsible for the development of IFH.

Methods: Receiver operating characteristic curve (ROC) analysis was conducted in 1852 subjects. Three groups were classified according to a 75 g oral glucose tolerance test (OGTT): (1) normal glucose tolerance (NGT), n = 557; (2) iIFG, n = 221; (3) IFH, n = 81. The three groups were compared with insulin secretion (insulinogenic index) and insulin sensitivity (insulin sensitivity index).

Results: Using ROC analysis, the optimal cut point of fasting plasma glucose (FPG) related to diabetes diagnosis with OGTT was 6.695 mmol/L and the optimal cut point of FPG related to impaired glucose to lerance (IGT) diagnosis with OGTT was 5.590 mmol/L. From NGT to iIFG and IFH in these subjects, the insulinogenic index and insulin sensitivity index showed gradual decrease.

Conclusion: Subjects with iIFG and IFH exhibit distinctly impaired early-phase insulin secretion and insulin sensitivity, indicating that both reduced insulin secretion and insulin resistance are the determinants of deterioration from NGT to iIFG and IFH.
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July 2007

Birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults.

Eur J Endocrinol 2006 Oct;155(4):601-7

Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Ruijin Er Lu, Shanghai 20025, China.

Objective: To investigate the association between birth weight and risk of type 2 diabetes, abdominal obesity and hypertension among Chinese adults.

Research Methods And Procedures: Nine hundred and seventy-three individuals from a population-based cross-sectional survey for the prevalence of type 2 diabetes conducted in Shanghai in 2002 were enrolled and followed up to 2004 with yearly examination. Birth weight was classified into four categories: <2500, 2500-2999, 3000-3499 and >or=3500 g.

Results: In this study, there were 373 males and 600 females, with a mean age of 46.2+/-9.9 years. Fasting plasma glucose was higher in subjects with the lowest birth weight (<2500 g) compared with those with the highest birth weight. Waist circumference and systolic blood pressure showed U-shaped relationships with birth weight. Birth weight was found to be an independent risk factor for type 2 diabetes, abdominal obesity and hypertension. For type 2 diabetes, the crude odds ratio (95% confidence interval) was 3.17 (1.48-6.78) in the lowest birth weight category when compared with that in the highest birth weight category (>or=3500 g) and the ratio increased to 3.97 (1.71-9.22) after adjustment for related variables. The highest prevalence of type 2 diabetes (34.5%) was observed among those with the lowest birth weight and abdominal obesity.

Conclusions: Birth weight is inversely associated with the risk of type 2 diabetes. Subjects with the lowest or the highest birth weight were associated with a high risk of developing abdominal obesity and hypertension. Low birth weight coupled with abdominal obesity is a strong predictor of type 2 diabetes.
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http://dx.doi.org/10.1530/eje.1.02265DOI Listing
October 2006

Role and mechanism of rosiglitazone on the impairment of insulin secretion induced by free fatty acids on isolated rat islets.

Chin Med J (Engl) 2006 Apr;119(7):574-80

Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.

Background: Prolonged exposure of pancreatic beta-cells to fatty acids increases basal insulin secretion but inhibits glucose-stimulated insulin secretion. Rosiglitazone is a new antidiabetic agent of the thiazolidinediones. However, the relationship between thiazolidinediones and insulin secretion is highly controversial. The aim of this study is to explore the effect and mechanism of rosiglitazone on insulin secretion of islets under chronic exposure to free fatty acids (FFA).

Methods: Pancreatic islets were isolated from the pancreata of male Sprague-Dawley rats by the collagenase digestion and by the dextran gradient centrifugation method. The purified islets were cultured in the presence or absence of rosiglitazone and palmitate for 48 hours. The insulin secretion was measured by radioimmunoassay. The mRNA level of peroxisome proliferator-activated receptor gamma, uncoupling protein 2 (UCP-2) and insulin were determined by real-time polymerase chain reaction (PCR). The cell cytotoxicity assay was measured by cell counting kit-8.

Results: Islets exposed to elevated palmitate for 48 hours showed an increased basal and a decreased glucose-stimulated insulin secretion (P < 0.01). The mRNA level of UCP-2 was increased by 3.7 fold in the 0.5 mmol/L concentration of palmitate. When islets were cultured with palmitate (0.5 mmol/L) in the presence of rosiglitazone (1.0 micromol/L), both basal and glucose-stimulated insulin secretion reversed to a pattern of control islets (P < 0.05, P < 0.01). The addition of rosiglitazone in the culture medium decreased the mRNA level of UCP-2 by 2.2 fold, having a statistically significant difference (P < 0.05) as compared with islets cultured with palmitate alone. The cell viability was not affected.

Conclusion: The protective effects of rosiglitazone on insulin secretion of isolated pancreatic islets under chronic exposure to palmitate might be mediated through the downregulation of UCP-2 expression.
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April 2006

Cloning and sequence analysis of tumor-associated gene hMMTAG2 from human multiple myeloma cell line ARH-77.

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 2003 Feb;35(2):143-8

Molecular Biology Research Center, Xiangya Medical College, Central South University, Changsha 410078, China.

In order to look for the tumor-associated genes from human multiple myeloma (MM), a cDNA library of human multiple myeloma cell line ARH-77 was constructed with eukaryote expression vector pcDNA3.1(+). The length of inserted fragments in library was 1.2 kb in average. All clones in cDNA library were transferred in situ to nylon membrane, which was divided into eight equal parts (A-H) and cultured in LB medium to set up gene pools. The plasmids in cDNA library and in gene pools were extracted and NIH/3T3 cells were transfected respectively. By G418 screening and colonies counting, gene pool A was chosen for the second cycle transfection. After several cycles, a clone, A62-17, was obtained, which had significant transforming ability. The length of this clone was 993 bp. The RACE technique was used for rapid amplification of A62-17 5'-end. The full length of this sequence has 1300 bp and was named as hMMTAG2 gene. hMMTAG2 consists of 8 exons and codes for a polypeptide of 263 amino acids (the accession number in GenBank: AY137773). It was located at chromosome 1q42.13. hMMTAG2 had same transforming activities in NIH/3T3 cells as the clone A62-17, and the number of transformant foci was 6 folds more than the blank vector pcDNA3.1(+). The analysis of bioinformatics revealed that hMMTAG2 had many phosphorylation sites for several protein kinases, N-myristoylation sites and nuclear localization signals, so it may be a signal molecule in the nucleus.
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February 2003