In China, the incidence of prostate cancer has been increasing in recent years. Hormonal therapy has been the mainstay of the therapeutic options for metastatic diseases for many years. But many metastatic tumors progress at a median of two to five years and become hormonal refractory prostate cancer (HRPC). This article summarizes in the advances of diagnostic criteria, molecular biological features, prediction markers, new therapeutic agents and further researches to be undertaken concerning HRPC.
Aged ; Androgen Antagonists ; pharmacology ; Biomarkers, Tumor ; analysis ; Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; drug therapy ; pathology

Prostate cancer is a most common malignant neoplasm in males. In recent years, its incidence has been rising dramatically in China. Patients with recurrent prostate cancer may be treated with androgen deprivation strategies, but most cases will eventually develop into androgen-independent prostate cancer (AIPC). Until recently, chemotherapy has been shown to be effective in palliating the symptoms of the disease but not in improving survival. Current strategies for the treatment of AIPC have shown significant palliation, but no definitive increase in survival. Molecular mechanisms underlying the development of androgen-independent prostate cancer (AIPC) are poorly understood. However, there is growing evidence that different molecular profiles may result in the development of AIPC. In this paper, we not only review the molecular mechanism of AIPC, but also present some of the promising management principles and systemic chemotherapy options against AIPC.
Androgens ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Genetic Therapy ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; therapy

OBJECTIVETo investigate the effect of Helicobacter Pylori lipopolysaccharide (Hp-LPS) on expression of Gli and Ptch-1 proteins in sonic hedgehog (Shh) signaling pathway of gastric mucosa GES-1 cells.

METHODSThe LPS was extracted from Hp by hot phenol water method, and then the concentration of LPS was detected by the kinetic turbidimetric assay. GES-1 cells were stimulated by different concentrations of Hp-LPS (0, 1, 10, 20, 30 and 40 μg/ml). The inhibition rates of cell growth were measured by MTT assay after treated with Hp-LPS for 24 h. The expression of Gli and Ptch-1 proteins were determined by Western Blot.

RESULTSMTT assay showed that the inhibition rates of GES-1 cell growth after treatment by different concentrations of Hp-LPS (1, 10, 20, 30 and 40μg/ml) were 25.8% ± 2.7%, 34.2% ± 3.1 %, 46.3% 3.4%, 60.8% ± 2.1% and 82.9% ± 2.8% respectively (r=0.985, P<0.001). Western blot showed that the expressions of Gli and Ptch-1 proteins were decreased after Hp-LPS treatment (0, 1, 10, 20, 30 and 40 μg/ml): the relative expression values of Gli were 1.286 ± 0.180, 0.963 ± 0.067, 0.850 ± 0.085, 0.566 ± 0.058, 0.549 ± 0.056 and 0.377 ± 0.047, respectively (r=-0.945, P<0.001); those of Ptch-1 were 1.688 ± 0.088, 1.466 ± 0.061, 1.170 ± 0.065, 1.042 ± 0.064, 0.648 ± 0.057 and 0.482 ± 0.074, respectively (r=-0.985, P<0.001).

CONCLUSIONHp-LPS can decrease the related protein expression of Shh signaling pathway, which indicates that Hp may interfere with the function of Shh signaling pathway in gastric mucosa via the effect of its LPS.

Cells, Cultured ; Epithelial Cells ; drug effects ; Gastric Mucosa ; cytology ; Hedgehog Proteins ; metabolism ; Humans ; Lipopolysaccharides ; administration & dosage ; pharmacology ; Patched Receptors ; Patched-1 Receptor ; Receptors, Cell Surface ; metabolism ; Signal Transduction ; Transcription Factors ; metabolism ; Zinc Finger Protein GLI1

OBJECTIVETo summarize early diagnosis and treatment methods of 20 patients with compartment syndrome caused by landslides during coal mine accidents in order to improve the level of diagnosis and treatment of compartment syndrome and reduce disability.

METHODSFrom September 2006 to April 2010,20 patients with compartment syndrome were treated with the methods of early decompression, systemic support. All the patients were male with an average age of 42 years (ranged, 23 to 54). All the patients with high tension limb swelling, pain, referred pain passive positive; 5 extremities feeling diminish or disappear and the distal blood vessel beat were normal or weakened or disappeared; myoglobinuria, hyperkalemia, serum urea nitrogen and creatinine increased in 5 cases and oliguria in occurred 1 case. The function of affected limbs was observed according to disability ratings.

RESULTSThree cases complicated with infection of affected limb and 6 cases occurred with renal function insufficiency. Total recovery was in 16 cases, basically recovery in 3, amputation in 1 case. All patients were followed up for 6-15 months with an average of 12 months. The ability to work according to national standard identification--Employee work-related injuries and occupational disability rating classification (GB/T16180-2006) to assess, grade 5 was in 1 case, grade 8 in 2 cases, grade 10 in 1 case, no grade in 16 cases.

CONCLUSIONArteriopalmus of dorsalis pedis weaken and vanished can not be regard as an evidence in early diagnosis of compartment syndrome. Early diagnosis and decompression, systemic support and treatment is the key in reducing disability.

Adult ; Compartment Syndromes ; diagnosis ; surgery ; Decompression, Surgical ; methods ; Early Diagnosis ; Humans ; Landslides ; Male ; Middle Aged ; Water-Electrolyte Imbalance ; therapy

AIMTo evaluate the effects of molecular weight of dextran on drug-release of conjugate in vitro by screening colon-specific conjugates.

METHODSThe conjugates, synthesized with different molecular-weight dextran and dexamethasone, were incubated in the contents of different parts of rat gastrointestinal tract at 37 degrees C. The release of dexamethasone(Dex) and dexamethasonehemisuccinate was determined by HPLC. The mobile phase consisted of 35% acetonitrile and 65% trisodium citrate (50 mmol.L-1, adjusted to pH 4.1 with phosphoric acid).

RESULTSThere was no release of dexamethasone or dexamethasonehemisuccinate from conjugates in the stomach contents. The amount of Dex (including dexamethasonehemisuccinate) released from DexD26 in the contents of colon and cecum was shown to be 4.0 times higher than that released in the contents of proximal and distal small intestine while the amount of Dex (including dexamethasonehemisuccinate) released from DexD50 was shown to be 3.6 times higher. The amount of Dex (including dexamethasonehemisuccinate) released from DexD2 in the contents of colon and cecum and from DexD7.6 were 2.0 times and 1.9 times higher, respectively, than that released in contents of proximal and distal small intestine.

CONCLUSIONThe molecular weight of dextran showed marked effect on drug-release of the conjugate in vitro, and the conjugates with larger molecular-weight dextran have great potential in colon-specific delivery of dexamethasone.

Animals ; Colon ; metabolism ; Dexamethasone ; administration & dosage ; metabolism ; Dextrans ; chemistry ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Female ; In Vitro Techniques ; Intestine, Small ; metabolism ; Male ; Molecular Weight ; Rats ; Rats, Sprague-Dawley ; Stomach ; metabolism

BACKGROUNDCathespin-B (cath-B) is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice.

METHODSThirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region. Besides volume, weight of subcutaneous tumor, and change in body weight, cath-B expression in each group was measured by immunohistochemical staining, PCR and Western blotting. Its relationship to microvessel density (MVD), CD44v6, and placenta growth factor (PLGF) was also examined. CA-074Me, a specific inhibitor of cath-B, was injected intraperitoneally (i.p.) at different stages of tumor growth in group B and C. Gemcitabine (GEM), was also injected (i.p.) in group D to compare anti-tumor efficacy with CA-074Me.

RESULTSExpression of cath-B at different levels was related to tumor growth, MVD, and PLGF expression. In group A (control group), cath-B expression was enhanced more than that seen in other groups. CA-074Me clearly inhibited cath-B expression and tumor growth in group B. There was no difference between group C and D with respect to anti-tumor effect.

CONCLUSIONSCath-B correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6. CA-074Me clearly inhibited cath-B expression and demonstrated an anti-neoplastic and anti-angiogenesis effect.

Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Body Weight ; Cathepsin B ; antagonists & inhibitors ; genetics ; metabolism ; physiology ; Cell Line, Tumor ; Dipeptides ; therapeutic use ; Female ; Humans ; In Vitro Techniques ; Mice ; Mice, Nude ; Pancreatic Neoplasms ; drug therapy ; metabolism ; Placenta Growth Factor ; Pregnancy Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous

Prostate cancer is one of the most common type of cancer among men after middle age. Androgen withdrawal can delay its progression in the initial stage, but it finally becomes independent of androgens in almost all the cases. The combination of docetaxel with prednisone is currently a standard first-line treatment for patients with hormone-refractory prostate cancer (HRPC), but hitherto there is no established second-line therapy. In view of the molecular pathogenesis of HRPC, this article presents an overview on several promising drugs that target specific pathways, involving angiogenesis, cell signaling, apoptosis and proliferation, and immune modulation, either as single agents or in combination with cytotoxic chemotherapy.
Drug Resistance, Neoplasm ; Hormones ; pharmacology ; Humans ; Male ; Prostatic Neoplasms ; drug therapy

OBJECTIVETo analyze the molecular characteristics of the newly isolated two Japanese encephalitis virus strains (JEV) in Wuhan.

METHODSThe mosquitoes were collected in Wuhan from April to October in 2009. The envelope (E) protein gene of JEV was detected using RT-PCR and sequenced. Sequence comparisons and phylogenetic analysis were conducted using DNAstar and MegAlign.

RESULTSTwo Japanese encephalitis virus (JEV) strains (WHJX09-9, WHJX09-10) were isolated from Culex tritaeniorhynchus among 16 mosquito pools and identified as genotype I. The result showed that the homology of the two strains was 98. 9% in nucleotides and 100% in deduced amines. The comparison between the new genotype 1 JEV strains and live attenuated vaccine strain SA14-14-2 in E gene showed that the homology of nucleotide sequence was 87.4% and 87.9%, the homology of amino acid was 96.9% (total 15 amino acid were different) in E gene. The mutation sites of amino acid distributed among three different coding domain, but no antigen binding site and neurotoxin-involved site of amino acid were changed.

CONCLUSIONWuhan had appeared a new genotype of JEV which was different from the former strain isolated in Wuhan, the new JEV strains still had neurotoxicity but had high homology with the vaccine strains adopted in Wuhan. The vaccine could still be adopted to prevent Japanese encephalitis if steps were take to eradicate mosquitos at the same time. laboratory surveillance were also an important task to build an early-warning mechanism against JEV.

Amino Acid Sequence ; Animals ; Cell Line ; China ; Culicidae ; virology ; Encephalitis Virus, Japanese ; chemistry ; classification ; genetics ; isolation & purification ; Genotype ; Insect Vectors ; virology ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Viral Envelope Proteins ; chemistry ; genetics

RASSF1A gene cloned from 3p21.3 region is a novel candidate tumor suppressor gene. The aberrant methylation of CpG lands in the promoter region is the major inactivation mechanism of RASSF1A, and is significantly involved in the genesis and development of multiple solid tumors including prostate cancer. The methylation status examination of RASSF1A could serve as an important technique for the early diagnosis of prostate cancer, while methylation inhibitor is likely to become a novel therapeutic agent.
DNA Methylation ; Early Diagnosis ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; genetics ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo investigate the autophagy in human bone marrow mesenchymal stem cells (hBMMSC) exposed to irradiation.

METHODSThe apoptosis and necrosis rate were assessed by Annexin V and propidium (PI) staining in hBMMSC at 4h after irradiated with X-ray at 0, 2, 4, 8 and 10 Gy. The autophagy was observed by transmission electron microscopy. The mRNA expression of Beclin1 and microtubule-associated protein 1 light chain 3 (MAPLC3 or LC3) was analyzed by RT-PCR in hBMMSC at 4h after X-ray irradiation at 0, 8 and 10 Gy.

RESULTSThe apoptosis rate of hBMMSC was markedly decreased while the necrosis and death rate were slowly increased with the increase of irradiation dose when under 8 Gy. The apoptosis rate was significantly increased and reached a peak while the necrosis and whole death rate were obviously increased when irradiated with 10 Gy X-rays. In addition, the change of apoptosis rate was more significant than that of necrosis rate. By electron microscopy, a mass of autophagic vacuoles (autophagosome and autolysosome) were observed in irradiation and positive control groups, but were only occasionally seen in normal control group. The proportion of hBMMSC with autophagic vacuoles in 8 Gy irradiation group was higher than that in 10 Gy one. The mRNA expression of Beclin1 and LC3 in irradiation groups and positive control group was significantly higher than in normal control group, and so did in 8 Gy irradiation group than that in 10 Gy group.

CONCLUSIONIrradiation may induce the autophagy in hBMMSC, and autophagy could protect hBMMSC from irradiation injury in a certain dose range.

Apoptosis ; radiation effects ; Autophagy ; radiation effects ; Bone Marrow Cells ; radiation effects ; Cell Line ; Humans ; Mesenchymal Stromal Cells ; radiation effects ; X-Rays