To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

500 pmol/L were greater than those in any group.Conclusion Serum MMP-2 can be involved in left ventricular remodeling of HF,and measuring its concentration is helpful to judge the severity and prognosis of HF.

OBJECTIVETo study the content of phytoestrogen in dissimilarity herbs.

METHODThe activity of phytoestrogen in heat-clearing drugs, drugs for relieving exterior syndrome, diuretic, anastaltics, tonics and astringents were detected based on the recombinant yeast cell (W303-1A/hER-ERE-Lac Z). The estrogenic activity in traditional Chinese materia medica were assayed quantitatively by determining the expression of beta-galactosidase.

RESULTThe phytoestrogen concentration (6.35 x 10(-3) nmol x g(-1) E2 equivalent) in heat-clearing drugs was the highest while that in anastaltic and tonic drugs was the lowest, which was less than the detected limit.

CONCLUSIONCompared with the other traditional Chinese materia medica, the content of phytoestrogen, which can bind to estrogen receptor, in giant knotweed rhizome, forsythia suspense, ash bark, baical skullcap root and ophiopogonis tuber were higher.

Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Phytoestrogens ; analysis ; metabolism ; Plants, Medicinal ; chemistry ; Receptors, Estrogen ; metabolism ; Recombination, Genetic ; Saccharomyces cerevisiae ; chemistry ; cytology ; drug effects ; genetics ; beta-Galactosidase ; analysis

Not Abstract.

OBJECTIVETo investigate the effect of arctiin on advanced oxidation protein product (AOPP)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells and explore the mechanisms underlying this effect.

METHODSHuman proximal tubular cells (HK-2 cells) were treated with bovine serum albumin (BSA) or AOPPs in the presence or absence of arctiin. The expressions of E-cadherin, vimentin, and GRP78 at the protein and mRNA levels in the cells were examined using Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry with DCFH-DA as the fluorescent probe.

RESULTSCompared with BSA-treated cells, the cells treated with AOPPs showed decreased expression of epithelial cell marker E-cadherin and overexpression of mesenchymal marker vimentin and endoplasmic reticulum stress marker GRP78 with an increased ROS level. These changes induced by AOPPs were partly inhibited by arctiin.

CONCLUSIONArctiin can ameliorate AOPP-induced EMT in tubular cells by inhibiting endoplasmic reticulum stress, and oxidative stress response may participate in this process.

Advanced Oxidation Protein Products ; adverse effects ; Cadherins ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; Epithelial Cells ; cytology ; drug effects ; Epithelial-Mesenchymal Transition ; Furans ; pharmacology ; Glucosides ; pharmacology ; Heat-Shock Proteins ; metabolism ; Humans ; Kidney Tubules ; cytology ; drug effects ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Vimentin ; metabolism

OBJECTIVETo investigate whether the p38 mitogen-activated protein kinase (MAPK) signaling pathway mediates advanced oxidation protein products (AOPPs)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells.

METHODSHuman proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA) were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using Western blotting. Western blotting and quantitative RT-PCR were used to examine the protein and mRNA expressions of EMT markers E-cadherin and vimentin and endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to AOPP exposure. The cells treated with AOPPs following pretreatment with salubrinal (an inhibitor of endoplasmic reticulum stress) were also examined for expressions of p38 MAPK and phosphorylated p38 MAPK.

RESULTSAOPP treatment induced the phosphorylation of p38 MAPK in HK-2 cells. AOPP-induced decrease in E-cadherin expression and overexpression of vimentin and GRP78 were partly inhibited by pretreatment of the cells with SB203580. Salubrina partly suppressed AOPP-induced phosphorylation of p38 MAPK in the cells.

CONCLUSIONp38 MAPK signaling pathway, which is regulated by endoplasmic reticulum stress, might mediate AOPP-induced EMT in HK-2 cells.

Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Microbubbles ; Oligoribonucleotides, Antisense ; genetics ; Transfection ; methods ; Ultrasonics

OBJECTIVETo investigate the effect of adiponectin on hepatocyte steatosis.

METHODSL02 cells were transfected with pEGFP-N1-AdipoQ, a plasmid encoding pEGFP-adiponectin fusion protein, or pEGFP-N1. Lipid droplets in the hepatocytes were observed by oil red staining at 72 h. The contents of TG, FFA and glycerol in hepatocytes were measured.

RESULTSCompared to cells transfected with pEGFP-N1-AdipoQ plasmid, much more lipid droplets were observed in cells transfected with pEGFP-N1 plasmid. TG, FFA and glycerol contents in L02 cells and L02/pEGFP-N1 cells were significantly higher than those in L02/pEGFP-N1-AdipoQ cells.

CONCLUSIONSOverexpression of adiponectin prevent hepatocyte steatosis.

Adiponectin ; genetics ; Cell Line ; Fatty Acids, Nonesterified ; analysis ; Fatty Liver ; metabolism ; Genetic Vectors ; Glycerol ; analysis ; Hepatocytes ; cytology ; metabolism ; Humans ; Plasmids ; Recombinant Fusion Proteins ; genetics ; Transfection ; Triglycerides ; analysis

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes, including aberrant promoter methylation and histone modification, plays a critical role in human breast carcinogenesis. Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression, thus directly contributing to breast tumorigenesis. Usually, aberrant promoter methylation of TSGs, which can be reversed by pharmacological reagents, occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer. In this review, we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; diagnosis ; drug therapy ; genetics ; metabolism ; CpG Islands ; genetics ; DNA (Cytosine-5-)-Methyltransferases ; antagonists & inhibitors ; therapeutic use ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Silencing ; Humans ; Promoter Regions, Genetic ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the prognostic factors and to analyze the efficacy of chemotherapy and/or radiotherapy for Barrett's esophageal adenocarcinoma after radical surgical resection.

METHODSThe clinical data of 108 patients with adenocarcinoma Barrett's esophagus picking out from 783 esophageal adenocarcinoma patients surgically treated between June 1978 to June 2001 in the Shandong Provincial Hospital and Shandong Qianfoshan Hospital were analyzed retrospectively. 60Co gamma-irradiation or 6MVX-ray with conventional fraction were used for radiotherapy with a total volume dosage of 55-70 Gy. The chemotherapy was either FAM (iv infusion of 5-Fu 500 mg, d1-d5; ADM 50 mg d1; MMC 12 mg, d1) or CMF regimen (iv infusion of CTX 800 mg d1, d8; MTX 30 mg d1; 5-Fu 500 mg, d1-d5) for 4-6 cycles. The Kaplan-Meier amalysis was used to estimate the survival rate. Log rank test was used for comparison of the survival difference among different groups.

RESULTSIn this series, 76 of 92 patients who underwent radical surgical resection received postoperative radiotherapy alone, and 16 received radiotherapy plus chemotherapy. Twelve of the other 16 patients who underwent palliative surgical resection received chemotherapy plus radiotherapy, the remaining 4 patients died of operative complications during surgery. The overall 1-, 3- and 5-year survival rate of this series was 81.5%, 51.9% and 22.2%, respectively. In the radical resection group, it was 15.8% for the patients received radiotherapy alone versus 75.0% for those treated by chemotherapy plus radiotherapy. The 5-year survival rate was 33.3% for the patients without extra-esophageal infiltration and 33.3% for the patients without lymph node metastasis, respectively. However, it was only 9.1% for the patients with extra-esophageal infiltration and 14.3% for those with lymph node metastasis, respectively. For the patients who had palliative surgical resection, though they received chemotherapy plus radiotherapy postoperatively, none of them survived longer than 5-year. Statistically significant difference among these groups was demonstrated by Log rank test (P < 0.05).

CONCLUSIONChemotherapy plus radiotherapy after radical surgical resection may improve the survival of patients with adenocarcinoma in Barrett's esophagus adenocarcinoma patient. The pathological stage, extra-esophageal infiltration, lymph node metastasis and postoperative chemotherapy plus radiotherapy are important prognostic factors.

Adenocarcinoma ; pathology ; surgery ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Barrett Esophagus ; pathology ; surgery ; therapy ; Combined Modality Therapy ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Esophageal Neoplasms ; pathology ; surgery ; therapy ; Esophagectomy ; methods ; Female ; Fluorouracil ; therapeutic use ; Humans ; Lymphatic Metastasis ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Staging ; Postoperative Period ; Prognosis ; Radiotherapy, High-Energy ; methods ; Retrospective Studies ; Survival Analysis ; Treatment Outcome