The expression of sLea/x which correlates with conventional histopathologic parameters serves as a useful indicator for the prognosis of metastatic disease. The bindings between sLea/x and their common ligand E-selectin initiate hematogenous metastasis of cancer. Certain bioactive conformation is crucial for the interaction between sLea/x and their ligands. Thus, a new class of compounds that mimic the structures of sLea/x can potently inhibit not only their functional bindings to selectins, but also the metastasis of cancer. This review is mainly on the sLea/x molecular structure,biosynthesis,distribution, especially the relationship between sLea/x and hematogenous metastasis of cancer and the design of drugs that mimic the structures of sLea/x.

AIMTo investigate the effects of sulfated polymannuroguluronate (SPMG), a novel candidate anti-AIDS drug in Phase II clinical trial, on Tat-induced release of proinflammatory cytokines (i.e., TNFalpha, IL-1beta and IL-6) and its related mechanism.

METHODSThe effects of SPMG on Tat induced TNFalpha (4 h), IL-1beta and IL-6 (6 h) secretion in THP-1 cells were measured by ELISA. Western blotting analysis was used to study the effects of SPMG on Tat induced PKCzeta, PKCtheta and PKCsigma phosphorylation.

RESULTSSPMG (50 to 100 microg x mL(-1)) markedly suppressed TNFalpha, IL-1beta and IL-6 secretion in Tat activated THP-1 cells. In THP-1 cells the phosphorylation levels of PKCzeta, PKCtheta and PKCsigma significantly increased following Tat stimulation, and only PKCsigma phosphorylation levels was inhibited by SPMG (50 to 100 microg x mL(-1)).

CONCLUSIONSPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCsigma activation.

Cell Line, Tumor ; Gene Products, tat ; pharmacology ; Humans ; Interleukin-1beta ; secretion ; Interleukin-6 ; secretion ; Isoenzymes ; metabolism ; Phosphorylation ; Polysaccharides ; pharmacology ; Protein Kinase C ; metabolism ; Protein Kinase C-delta ; metabolism ; Protein Kinase C-theta ; Tumor Necrosis Factor-alpha ; secretion

Objective To construct a tyrosine kinase B(TrkB) targeted RNA interference (RNAi) lentiviral vector.Methods Four oligonucleotides targeting rat TrkB gene were synthesized and cloned into lentiviral vector pXZRNAi 1.0 to construct recombinant lentiviral vectors pXZRNAi-shTrkB-1,2,3,4.Neural stem cells prepared from rat hippocampus were infected with these high-titer viruses.Real-time PCR was employed to detect the TrkB mRNA expression and western blot was used to assess the gene silencing efficacy of these recombinants.Results Enzyme digestion and DNA sequencing results demonstrated that these shRNAs were correctly inserted into lentiviral vectors and the four recombinants were constructed successfully with the titer of 8.6 × 105cfu/ml.The infection efficiency of the letivirus on neural stem cells reached 80％.Compared with the uninfection group,the expression levels of TrkB mRNA in neural stem cells decreased significantly after transfected with pXZRNAi-shTrkB-3 and 4((66.7 ± 5.5) ％ and(76.8 ± 4.9) ％ respectively,P ＜ 0.05) ; and the protein expression levels were also significantly decreased ((68.5 ± 4.3)％ and (78.2 ± 5.1)％ respectively,P ＜ 0.05).Conclusion The lentiviral vectors for TrkB have been successfully constructed with high yield of lentivirus,which provides versatile method for assessing gene function in neural stem cells.

Objective To evaluate the clinical efficacy and safety of compound polymyxin B ointment combined with desonide cream for the treatment of subacute or chronic eczema. Methods A multicenter, randomized, double?blind, parallel?group, controlled clinical study was conducted. Totally, 144 patients with subacute eczema and 144 patients with chronic eczema were enrolled into this study, and both randomly and equally divided into the test group and control group. The test group and control group firstly topically applied compound polymyxin B ointment and its vehicle respectively, then both topically applied desonide cream 3 hours later. The drugs or vehicle were applied twice a day in all the patients. Patients′ symptoms and signs (including degree of itching, inflammation, erosion/exudation and infiltration/thickening, as well as area of target lesions) were evaluated, and the time to onset and duration of itching?alleviating effect were recorded. The clinical efficacy and safety of treatments were analyzed and compared between the test group and control group. Results The total symptom and sign scores significantly decreased to different extents on days 7 and 14 in the test group(subacute eczema patients:6.09 ± 2.78 and 3.68 ± 3.18 vs. 13.44 ± 1.66; chronic eczema patients: 6.56 ± 2.68 and 4.38 ± 3.27 vs. 12.96 ± 1.16)and control group(subacute eczema patients:8.26 ± 3.17 and 5.28 ± 4.05 vs. 13.60 ± 1.75;chronic eczema patients: 8.84 ± 2.90 and 6.25 ± 3.78 and vs. 12.64 ± 1.18)compared with those at baseline. Moreover, the total symptom and sign score of patients with subacute or chronic eczema was significantly lower in the test group than in the control group on days 7 and 14(all P<0.05). A significant increment was observed in the degree of decrease in scores for itch, infiltration/thickening in patients with subacute eczema in the test group compared with that in the control group(all P<0.01), as well as in scores for itch, infiltration/thickening and area of target lesions in patients with chronic eczema in the test group compared with those in the control group (all P < 0.05). In addition, patients with subacute eczema in the test group showed significantly shorter onset and longer duration of itching?alleviating effect than those in the control group(both P<0.05). The time to onset of itching?alleviating effect was also significantly shorter in patients with chronic eczema in the test group than in those in the control group(P<0.000 1), but there was no significant difference in the duration of it between the two groups of patients with chronic eczema. Clinicians and patients were both more satisfied with therapeutic effects in the test group than in the control group(all P<0.05). Conclusions Topical compound polymyxin B ointment can increase the efficacy of topical desonide cream for the treatment of subacute or chronic eczema, especially subacute eczema. Compound polymyxin B ointment also shows a favorable therapeutic effect on itching and infiltration/thickening in patients with eczema.

Hypoxia-inducible factor-1 (HIF-1), as a transcription factor, plays an important role in the adaptation to hypoxic microenvironment within tumors. It can induce a series of genes transcription that participate in angiogenesis, glucose metabolism, cell proliferation, and cell migration/invasion. Thus HIF-1 not only allows cancer cells to survive in hypoxic microenvironment, but also makes the tumor more aggressive. Moreover, HIF-1 also induces tumors to acquire resistance to chemo-/radio-therapy, and is related to poor prognosis. HIF-1 emerges gradually as a potential target to develop new antitumor drugs. This paper reviews recent progress in this field.
Amphotericin B ; pharmacology ; Animals ; Antineoplastic Agents ; pharmacology ; Echinomycin ; pharmacology ; Humans ; Hypoxia-Inducible Factor 1 ; antagonists & inhibitors ; genetics ; metabolism ; Indazoles ; pharmacology ; Sirolimus ; analogs & derivatives ; pharmacology ; Topotecan ; pharmacology ; Transcription, Genetic

BACKGROUNDTo study the clinical features and more reasonable typing criteria for patients with chronic severe hepatitis and decompensated liver function.

METHODSData of 106 cases of decompensated cirrhosis, 124 cases of chronic liver failure and 100 cases of chronic liver failure (chronic liver failure group I, CLF I) with decompensated cirrhosis (chronic liver failure group II, CLF II) were analyzed retrospectively.

RESULTS(1) The ages were youngest in chronic liver failure group I (about 30 years), and the oldest in decompensated cirrhosis group (about 50 years). (2) There were significant differences in albumin, globulin, ALT, AST, protruding activity, blood glucose, blood lipid and cholinesterase among the three groups. (3) There was no significant difference in upper digestive tract bleeding and hepatorenal syndrome, on the other hand, there was significant difference in ascites and hepatic encephalopathy. (4) The prognosis of the patients in decompensated cirrhosis group was better than that of chronic liver failure group I and chronic liver failure group II.

CONCLUSIONThe clinical feature and prognosis in three groups were different, so, it is suggested that chronic severe liver disease be divided into 2 types: one is chronic severe liver disease type I, which is associated with chronic hepatitis, and the other is chronic severe liver disease type II, which is associated with cirrhosis, and the typing criteria for decompensated cirrhosis remains unchanged.

Adult ; Diagnosis, Differential ; Female ; Hepatitis, Chronic ; classification ; complications ; diagnosis ; Humans ; Liver Cirrhosis ; classification ; complications ; diagnosis ; Liver Failure ; etiology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

Objective To explore the clinical distribution states of human papillomavirus genotypes in tissues of 691 women with vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province and genotyping clinical significance.Methods Polymerase chain reaction(PCR)and gene-chips technology were utilized for the detection of 23 kinds of HPV genotypes in tissue specimens from 619 women of vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province.And related materials of all subjects were analyzed.Results In 691 women of vulva condyloma acuminates,597 women of HPV infecton,total infection rate of HPV was 86.40％(597/691),including single genotype infection rate of HPV was 51.38％(355/691),11、6 and 16 genotypes are the most common in single genotypes,they are successively 51.55％(183/355)、41.97％(149/355)and 3.38％(12/355).multiple genotypes infection rate of HPV was 35.02％(242/691),6+11、11+18、6+16 and 11+16 genotypes are the most common in multiple genotypes,they are successively 9.92％(24/242)、9.09％(22/242)、4.96％(12/242)and 4.13％(10/242).Conclusion The low-risk HPV types are the main factors to cause the female vulva CA,a few high-risk HPV types may cause warts as well in tissues of women with vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province.The vulva examine of HPV types should be held to the vulva CA patients.This precaution will has extremely important meaning to the prevention and treatment of the female vulva CA and cervical lesion in our nation.

OBJECTIVETo investigate the roles of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in dentinogenic ghost cell tumor (DGCT) and ghost cell odontogenic carcinoma (GCOC).

METHODSThe expressions of MMP-2, MMP-9, MMP-14, TIMP-1 and TIMP-2 were examined in 15 DGCT cases and 9 GCOC cases by immunohistochemistry. Their mRNA expression in one DGCT case and one GCOC case were investigated by RT-PCT.MMP-2 and MMP-9 protein activities in the two cases were analyzed by gelatin zymography.

RESULTSMMP-9 and TIMP-1 expressions elevated greatly in GCOC, and there was a significant difference (P < 0.05) in TIMP-1 expression between GCOC and DGCT.Pro-MMP-9, MMP-9 activated form, pro-MMP-2, and MMP-2 activated forms were detected in the GCOC case, while pro-MMP-9 and MMP-9 activated form were very faint in the DGCT case. The mRNA level of MMP-9 elevated obviously in the GCOC case, which was similar to that of TIMP-1.

CONCLUSIONSThe elevated expression of MMP-9 and TIMP-1 may influence the behaviour of GCOC.

Adolescent ; Adult ; Aged ; Child ; Dentin ; Humans ; Mandibular Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinases ; metabolism ; Middle Aged ; Odontogenic Tumors ; metabolism ; pathology ; Tissue Inhibitor of Metalloproteinases ; metabolism ; Young Adult

Objective To explore the clinical distribution and significant of 23 kinds of human papillomavir-us(HPV)genetypes in normal cells and atypical squamous cells(ASC-US),meanwhile analysis result of cervi-cal histological pathology diagnosis in cases of ASC-US.Methods A total of 1 000 women with normal cells specimens were recruited into control group,and 236 women with ASC-US were selected into the ASC-US group.Polymerase chain reaction(PCR)and gene-chips technology were utilized for the detection of 23 kinds of HPV genetypes,all cases of ASC-US diagnosis of cervical pathological histology.Results A total of 106 ca-ses of HPV infection were detected in the control group,as the total HPV infection rate was 10.6%,in which the single genotypes infection rate was 9.3% and the multiple genotypes infection rate was 1.3%.A total of 139 cases of HPV infection were detected in ASC-US group,as the total HPV infection rate was 58.9%,in which the single genotypes infection rate was 38.1%,and the multiple genotypes infection rate was 20.8%. There were significant differences on the total HPV infection rate,the infection rates of type 1 and multiple geontypes between the control group and ASC-US group(P<0.05).The top six of constituent ratio in the control group were type 43,16,58,33,52,18,42,those in the ASC-US group were type 16,18,52,58,33,51,66.Conclusion PCR combined with the gene-chip technology could be used in the HPV genotypes detection in cervical cells,which has important clinical significance on the further distribution management of ASC-US,and should be draw great attention.

Objective: This study aimed to identify proteins related to paclitaxel and carboplatin chemoresistance in cervical cancer. Methods: Quantitative proteomic analysis was performed on normal SiHa cells and those treated with paclitaxel and carboplatin for 14 days, with isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify related processes and differentially expressed proteins. Results: A total of 67 and 96 differentially expressed proteins were identified in the paclitaxel- and carboplatin- treated groups, respectively. GO and KEGG enrichment analyses identified 53 (43 upregulated and 10 downregulated) and 85 differentially expressed proteins (70 upregulated and 15 downregulated) in the paclitaxel- and carboplatin-treated groups, respectively. The cell counting kit-8 results revealed that APOA1 was overexpressed in both the paclitaxel- and carboplatin- resistant SiHa cells compared with the control cells. Immunohistochemistry showed that APOA1 was highly expressed in the paclitaxel- and carboplatin- resistant squamous cell carcinoma of the cervix. Conclusion This study is the first to use iTRAQ to identify paclitaxel- and carboplatin- resistance proteins in cervical cells. We identified several proteins previously unassociated with paclitaxel and carboplatin resistance in cervical cancer, thereby expanding our understanding of paclitaxel and carboplatin resistance mechanisms. Moreover, these findings indicate that the APOA1 protein could serve as a potential marker for monitoring and predicting paclitaxel and carboplatin resistance levels.