The diagnosis and treatment of prostate cancer are being improved due to the popularized screening of prostate specific antigen. Advanced prostate cancer, in spite of its response to androgen deprivation therapy, may finally develop into castration-resistant prostate cancer (CRPC) and shorten the overall survival of the patients. Many efforts have been made by worldwide researchers for new approaches to the management of CRPC, including new hormonal therapy, cytotoxic chemotherapy, immunotherapy, and bone metastasis-targeted therapy. This paper reviews the emerging agents undergoing clinical evaluation and drugs that have received approval for the treatment of CRPC in order to provide doctors and patients with more treatment options for CRPC and improve the overall survival rate and quality of life of the patients.
Androgen Antagonists ; Bone Neoplasms ; prevention & control ; Humans ; Immunotherapy ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; therapy ; Quality of Life

Objective To evaluate myocardial apoptosis with 99Tcm-C2A-GST myocardial imaging using the recombined C2A domain of Synaptotagmin Ⅰ by gene engineering. Methods ( 1 ) The C2A gene was inserted into the prokaryotic glutathione S-transferate (GST) fusion protein expression plasmid pGEX-6P-1. The recombinant plasmid was transformed into E. coli BL21. C2A-GST fusion protein was purified after BL21 was induced with isopropyl-β-D-1-thiogalactopyranoside (IPTG). (2)The activity of fusion protein was identified by cell binding test with fluorescein-5-isothiocyanate (FITC)-C2A-GST. (3) The C2A-GST fusion protein was labeled with 99Tcm using 2-iminothiophene hydrocoride method. Radiochemical purity was determined with thin layer chromatography. (4)99Tcm-C2A-GST (7.4 MBq) was injected to ischemia-reperfusion rat models through tail vein. The image was acquired with SPECT at 1 h after injection, and then hearts were removed, rinsed with saline and dyed with triphenyl tetrazolium coride (TTC). The ischemic myocardium was separated from the viable myocardium and was weighted. Its radioactivity was measured by gamma counting. The difference of uptake of radiotracer between ischemic myocardium and normal myocardium was compared using percentage activity of injected dose per gram of tissue ( % ID/g) with standard deviation. SPSS 12.0 and t-test were used for data analysis. Results ( 1 ) C2A-GST fusion protein wassuccessfully expressed and its relative molecular weight was 3.8 × 104. (2) FITC-C2A-GST binding to apoptotic cells could be observed by fluorescent microscopy. (3) The radiochemical purity of 99Tcm-C2A-GST was (98.90 ±0.43)%. (4)The imaging studies showed that there was focal uptake of radioactivity in the ischemic myocardium. In vitro uptake of 99Tcm-C2A-GST was (2.41 ±0.32) % ID/g by the ischemic myocardium, however 99Tcm-C2A-GST-N-hydroxysuccinimide (C2A-GST-NHS) was (0. 82 ± 0. 24) % ID/g. There was statistically significant difference between those two groups (t = 10. 6, P ＜0.01 ). Conclusion The C2A domain of Synaptotagmin Ⅰ expressed by gene engineering can be used as the tracer for noninvasive detection of ischemic myocardium in the ischemia-reperfusion rat model.

Objective To explore the relationship of methylenetetrahydrofolate reductase (MTHFR)gene C677T,factor V(FV)gene G1691A and prothrombin(PT)gene G20210A polymorphisms to unexplained recurrent early spontaneous abortion(URESA).Methods One hundred and twelve patients with URESA and 100 women with at least 1 normal pregnancy and without any miscarriage were analyzed for MTHFR,FV and PT gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results MTHFR gene T/T genotype and T allele frequencies were increased in URESA patients[38.4%(43/112)and 59.8%(134/224)]versus controls[18.0%(18/100)and 43%(43/100),P

OBJECTIVETo investigate the expression of suppressor of cytokine signaling(SOCS)-3 and caspase-3 and their correlative significance in endometriosis.

METHODSImmunohistochemical EnVision method was used to detect the SOCS-3 and caspase-3 protein expression in ectopic and eutopic endometrium (n = 32) of patients with endometriosis, as well as normal endometrium (n = 30) of women without endometriosis.

RESULTSSOCS-3 and caspase-3 proteins were expressed in all three groups and not affected by the menstrual cycles. The expression of SOCS-3 in ectopic endometrium (5.54 ± 2.12) was significantly lower than that in eutopic (7.39 ± 1.09, P = 0.001) and control group (7.48 ± 1.26, P < 0.01), but without difference between the eutopic and control group (P = 0.756). SOCS-3 expression in ectopic and eutopic endometrium was significantly lower in III/IV stages than that in I/II stages of endometriosis (P < 0.05). Significantly lower expression of caspase-3 protein was found in ectopic (3.20 ± 1.24) and eutopic endometrium (3.88 ± 1.93) as compared with the control group (6.49 ± 1.85, P < 0.01), however ectopic and eutopic endometrium showed no significant difference (t = 1.66, P = 0.10). There was no significant difference of the expression of caspase-3 in ectopic and eutopic endometrium at different disease stages (P > 0.05). Positive correlation was found between the expression of SOCS-3 and caspase-3 proteins in ectopic endometrium (r = 0.655, P < 0.01).

CONCLUSIONSOCS-3 may be involved in the development of endometriosis through inhibition of apoptosis of ectopic endometrial cells.

Adult ; Caspase 3 ; metabolism ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Menstrual Cycle ; Middle Aged ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Uterine Diseases ; metabolism ; pathology ; Young Adult

AIM:To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) activation by 18α-gly-cyrrhetinic acid (18α-GA) on the proliferation and self-renewal of adult neural stem cells (aNSCs), and to explore an ef-fective way of maintaining the viability of aNSCs .METHODS:NSCs were dissociated from subventricular zone of the mice at postnatal days 0, 60, and 300.The expression levels of Nrf2 in the NSCs at various ages were compared .After treatment with 18α-GA, the expression of Nrf2 was examined by real-time PCR and Western blot.shRNA lentiviral vector (LV) car-rying green fluorescent protein (GFP) gene was constructed to knock down Nrf2 expression.The knockdown efficiency in the aNSCs was detected by real-time PCR and Western blot .Subsequently , the aNSCs were divided into DMSO group , 18α-GA group, LV-GFP group and LV-Nrf2-shRNA group.BrdU incorporation assay , Tuj1 staining, CCK-8 assay, Hoechst 33342/PI staining and detection of reactive oxygen species ( ROS) were performed to analyze the proliferation , dif-ferentiation, viability, apoptosis and oxidative stress levels of the NSCs .RESULTS:The mRNA expression level of Nrf2 in adult and aged NSCs was significantly lower than that in newborn NSCs (P<0.01), while the ROS level of aNSCs was significantly higher (P<0.05).After treatment with 18α-GA, the expression level of Nrf2 in the aNSCs was significantly up-regulated as compared with DMSO group ( P<0.01).Increased number of BrdU +and Tuj1 +cells was observed in 18α-GA group, indicating that 18α-GA-treated cells had higher viability (P<0.05).Meanwhile, there were fewer apop-totic cells and lower ROS level in 18α-GA group than those in DMSO group (P<0.05).After knockdown of Nrf2 in aNSCs and then treated with 18α-GA, there were less BrdU +and Tuj1 +cells, as well as the aNSCs with lower viability in LV-Nrf2-shRNA group (P<0.05).Moreover, the ROS level was increased in LV-Nrf2-shRNA group as compared with LV-GFP group (P<0.05).CONCLUSION:Activation of Nrf2 by 18α-GA elevates the antioxidant capacity of aNSCs , thus ameliorating the cell proliferation and differentiation potentials .

OBJECTIVETo investigate the clinical efficacy of Shenqi Fuzheng Injection (SFI) combined with chemotherapy in treatment of patients with acute leukemia and its effect on the levels of T-lymphocyte subsets (CD4, CD8, CD4/CD8) and serum interferon-gamma(IFN-gamma), interleukin-10 (IL-10) and IL-2.

METHODSSixty-five patients with initial treating acute leukemia were randomly divided into 2 groups, the SFI group (n = 32) treated with SFI plus chemotherapy (CT), the control group (n = 33) treated with CT only. The remission rate, changes of peripheral mature neutrophilic granulocyte (PMNG) count, T-lymphocyte subsets, serum IL-10 and IL-2 before and after treatment were determined.

RESULTSThe remission rate in the two groups showed no obvious difference (P > 0.05). After CT for the 1st, 2nd and 3rd weeks, the PMNG count decreased in both groups, showing significant difference as compared with that before CT (P < 0.01 or P < 0.05). The PMNG count at the end of the 3rd and 4th week of CT remounted to higher than that at 1st and 2nd week, and the increment in the SFI group was significantly higher than that in the control group (P < 0.05). The levels of CD4, CD4 /CD8, IFN-gamma and IL-2 all increased in the two groups after treatment (P < 0.05, P < 0.01), however, that of IL-10 was significantly decreased (P < 0.01). The difference between the two groups in these criteria after treatment was also significant (P < 0.05).

CONCLUSIONSFI can improve and regulate the immune function of the patients with acute leukemia undergoing CT, it could promote bone marrow cells proliferation and enhance the efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; Male ; Middle Aged ; Phytotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo establish discriminant functions of diarrhea-predominant irritable bowel syndrome (IBS-D) by studying it from quantitative diagnosis angle, hoping to reduce interference of subjective factors in diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D.

METHODSA Chinese medical clinical epidemiological survey was carried out in 439 IBS-D patients using Clinical Information Collection Table of IBS. Initial syndromes were obtained by cluster analysis. They were analyzed using step-by-step discrimination by taking information of four Chinese medical diagnostic methods and serum brain-gut peptides (BGP) as variables.

RESULTSClustering results were Gan stagnation Pi deficiency syndrome (GSPDS), Pi-Wei weakness syndrome (PWWS), Gan stagnation qi stasis syndrome (GSQSS), Pi-Shen yang deficiency syndrome (PSYDS), Pi-Wei damp-heat syndrome (PWDHS), cold-damp disturbing Pi syndrome (CDDPS). Of them, GSPDS was mostly often seen with effective percentage of 34. 2%, while CDDPS was the least often seen with effective percentage of 5.5%. A total of 5 discriminant functions for GSPDS, PWWS, GSQSS, PSYDS, and PWDHS were obtained by step-by-step dis- crimination method. The retrospective misjudgment rate was 4.1% (16/390), while the cross-validation misjudgment rate was 15.4% (60/390).

CONCLUSIONThe establishment of discriminant functions is of value in objectively diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D.

Alarmins ; Brain ; Cluster Analysis ; Diarrhea ; classification ; diagnosis ; Hot Temperature ; Humans ; Irritable Bowel Syndrome ; classification ; diagnosis ; Medicine, Chinese Traditional ; Qi ; Retrospective Studies ; Surveys and Questionnaires ; Yang Deficiency

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

OBJECTIVETo observe the efficacy of treatment of acute leukemia by Shengfu Injection (SFI) in combination with chemotherapy and the effect of treatment on T-lymphocyte subsets (CD4, CD8, CD4/CD8), serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).

METHODSSixty-one patients with acute leukemia of initiatory treating were randomly divided into two groups, the 31 patients in the treated group were treated with SFI plus chemotherapy and the 30 patients in the control group treated with chemotherapy alone. The remission rate, changes of absolute number of peripheral mature neutrophils, T-lymphocyte subsets, serum levels of IL-6 and TNF-alpha before and after treatment were observed.

RESULTSThe remission rate was higher in the treated group than that in the control group but the difference was insignificant (P > 0.05). The restoring of peripheral mature neutrophils in the treated group was higher than that in the control group, from the 3rd week of treatment, the difference was significant (all P < 0.05). CD4 and CD4/CD8 ratio after treatment increased in both groups, the increment was more obvious in the treated group than that in the control group significantly (P < 0.05). Serum levels of IL-6 and TNF-alpha lowered in both groups after treatment significantly(all P < 0.01), but the decrement was greater in the treated group with significant difference to the control group (P < 0.05).

CONCLUSIONSFI could improve and regulate the immune function in acute leukemia patients undergoing chemotherapy and enhance the therapeutic effect.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-6 ; blood ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; Male ; Middle Aged ; Phytotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

It was estimated that about 428 species of genus Corydalis are distributed all worldwide, with about 298, especially 10 groups and 219 species being uniquely spread in China. The genus Corydalis have been widely employed as folk medicines in China, especially as traditional Tibetan medicines, for treatment of fever, hepatitis, edema, gastritis, cholecystitis, hypertension and other diseases. The phytochemical studies revealed that isoquinoline alkaloids are its major bioactive ingredients. The extensive biological researches suggested its pharmacological activities and clinic applications against cardiovascular diseases and central nervous system, antibacterial activities, analgesic effects, anti-inflammatory, anti-oxidation and anti-injury for hepatocyte, and so on. As an effort in promoting the research of pharmacodynamic ingredients, this article presents an overview focusing on the distribution, phytochemical and pharmacological results of Corydalis species that have been applied in traditional Tibetan medicinal, hopefully to provide a reference for the new Tibetan medicine development from Corydalis plant resource.
Alkaloids ; chemistry ; pharmacology ; Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Corydalis ; chemistry ; classification ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Mice ; Molecular Structure ; Phytotherapy