Biomedical subjects

Hui Wang

Publications and source records attributed to Hui Wang.

At least 217 records · Page 12Linked to original sources

PubMed2005

Oncogenes as novel targets for cancer therapy (part IV): regulators of the cell cycle and apoptosis.

This is the final part of a four-part serial review on oncogenes and their potential use as targets for cancer therapy. Previous sections discussed various categories of oncogenes (growth factors, tyrosine kinases, intermediate signaling molecules, and transcription factors) and the advances made in various strategies being used to alter their actions. This part describes four oncogenes, MDM2, BCL2, XIAP, and Survivin, that are involved in regulation of the cell cycle and apoptosis.

Animals↗

PubMed2005

Synthetic oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine dinucleotides (CpG ODNs) and modified analogs as novel anticancer therapeutics.

Oligodeoxynucleotides containing deoxycytidyl-deoxyguanosine dinucleotides (CpG ODNs) activate the host immune system, leading to innate and acquired immune responses. The immune stimulatory effects of CpG ODNs are being exploited as a novel therapeutic approach to treatment of human diseases, and some CpG ODNs are being evaluated in clinical trials. The cellular recognition of CpG motifs requires the presence of the Toll-like receptor (TLR) 9, which triggers cell signaling and immune responses. There are three main types of first-generation CpG ODNs, which mimic the immunostimulatory activity of bacterial DNA and are recognized by TLR9, A-, B- and C-Class ODNs. Although all three CpG ODN classes stimulate TLR9-dependent signaling, there are striking differences in the cell types they activate and their dose-dependent immunostimulatory efficacy. Second-generation CpG ODNs, with advanced nucleic acid chemistry and unique modifications to their sequences and structures are being developed. Medicinal chemistry studies suggest that the immunomodulatory activity of CpG ODNs can be altered by site-specific incorporation of modifications in order to develop disease-specific drugs. Both first- and second-generation CpG ODNs have potential for treatment of various human diseases, such as infections, immunodeficiencies, and cancers. This article will focus on the recent advances in developing CpG ODNs as novel anti-cancer therapeutic agents.

Animals↗

PubMed2005

MDM2 and human malignancies: expression, clinical pathology, prognostic markers, and implications for chemotherapy.

The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed in more than forty different types of malignancies, including solid tumors, sarcomas and leukemias. Because of its prevalent expression and its interactions with p53 and other signaling molecules, MDM2 plays a central role in cancer development and progression. The expression of this oncoprotein is being studied by researchers world-wide, and the amount of data published about it is increasing exponentially. Although there are some conflicting data about the effects of MDM2 expression in individual cancers, the overall evidence is convincing, indicating that increased MDM2 expression is related to a worse clinical prognosis. There is an increased likelihood of distant metastases, as well as a decreased response to therapeutic intervention in MDM2-positive cancers. MDM2 may also serve as a diagnostic marker, not only for cancer stage, but to differentiate between similar cancers. MDM2 may also be associated with drug resistance in cancer chemotherapy. These findings make studying the oncoprotein necessary to aid in our understanding of cancer development, to identify novel cancer drug targets, and to increase the efficacy of cancer therapy.

Animals↗

PubMed2005

Novel antisense anti-MDM2 mixed-backbone oligonucleotides: proof of principle, in vitro and in vivo activities, and mechanisms.

The MDM2 oncogene has been suggested as a novel target for cancer therapy, based on the following observations: 1) MDM2 is overexpressed in many human cancers, including breast, colon, and prostate cancer; 2) high MDM2 levels are associated with poor prognosis in patients with cancer; 3) MDM2 overexpression is associated with advanced cancer phenotypes such as metastatic tumors and hormone-independent tumors; 4) MDM2 overexpression is associated with tumor resistance to chemotherapy and radiation therapy; and 5) inhibiting MDM2 expression or function results in tumor growth inhibition and regression. There are many options for inhibiting MDM2 function, including the use of gene silencing technologies, antibodies, peptides and small molecules. Considering the complexity of MDM2 functions, we have chosen to use gene silencing technologies including antisense oligonucleotides and RNA interference. In this article, we summarize the investigation of the antisense technology for inhibiting MDM2 expression. Antisense mixed-backbone oligonucleotides (MBO) specifically inhibit MDM2 expression in a dose- and time-dependent manner, resulting in significant anti-tumor activity in vitro and in vivo. The MBO also potentiates the therapeutic effects of chemotherapeutic agents and radiation therapy in various tumors, through both p53-dependent and p53-independent mechanisms, indicating that MDM2 inhibitors have a broad spectrum of anti-tumor activity in human cancers, regardless of p53 status. These results provide a basis for clinical evaluation of antisense anti-MDM2 oligonucleotides as chemosensitizers and radiosensitizers. In addition, the MBO has been successfully used to identify novel functions of MDM2.

Animals↗

PubMed2005

[The histological changes and the revascularization process in the grafted dermal substitutes].

OBJECTIVE: To observe the revascularization process and histological changes in the dermal substitutes after grafting. METHODS: Twenty-one SD rats were enrolled in the study and were randomly divided into swine acellular dermal matrix (sADM), human acellular dermal matrix (hADM), and artificial dermal equivalent (Integra) groups according to different dermal substitutes grafted underneath the skin of SD rats. The gross appearance of the grafts was observed, and the tissue biopsies were harvested at 2, 3, 4, 7, 10, 14, 21, 30, 60, 90, 120, 150, 180 post grafting day (PGD) for the observation of the revascularization process and their histological changes. RESULTS: Gross observation: The incision in each group healed well without local swelling and inflammatory response after grafting. The grafts had a compact contact with the wounds. The texture of the grafted dermis in each group was soft and could not be felt from the surface of the body on 90 PGD. The presence of the grafts could be discerned on 180 PGD in all the groups, but some of them became smaller in size and thinner, even hard to identify in a few. Fibroblasts, neutrophils and lymphocytes migrated into the grafts from 2PGD on. New capillary sprouts from the receiving beds could be observed after 3PGD. Affluent capillary nets formed in the grafts during 30 to 60 PGD. The structure of the grafts became nearly unidentifiable from the native dermis after 150 PGDs. Absorption and degradation to various degrees occurred in some of the grafts after 180 PGD. CONCLUSION: The revascularization of the three dermal substitutes could begin shortly after grafting. The sponge-like structure of the substitutes was advantageous for the migration of the host fibroblast into the substitute and for the secretion of the new extra-cellular matrix. The dermal substitutes could last in the wound for a long time with partial absorption and degeneration.

Animals↗

PubMed2005

[Preventive effects of montelukast on the collagen expression of pulmonary arterioles in rats with chronic hypoxia].

OBJECTIVE: To evaluate the preventive effects of montelukast on the collagen expression of pulmonary arterioles in chronic hypoxic rats. METHODS: Thirty male Wistar rats were randomly divided into three groups: control group, hypoxic group and montelukast preventive group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions 8 hours q.d. for 3 weeks. The expression levels of collagen I and III in arterioles were observed by immunohistochemistry. RESULTS: The positive degree of collagen I in pulmonary arterioles of hypoxic group was higher than that of control group (1.51+/-0.09 vs 1.15+/-0.05, P<0.01), and the positive degree of collagen I in pulmonary arterioles of preventive group (1.19+/-0.06) was lower than that of hypoxic group (P<0.01). The differences of positive degree of collagen III in pulmonary arterioles were not significant among the three groups (P>0.05). CONCLUSION: Montelukast can reduce the hypoxia-induced deposition of collagen I in the pulmonary arterioles wall.

Acetates↗

PubMed2005

[Study on AHL-like quorum signals in Mesorhizobium huakuii].

Quorum sensing is a mechanism used by single-cell bacteria to monitor their population density and control a variety of physiological functions in a cell-density-dependent manner. An ultrasensitive quorum signal acyl-homoserine lactone (AHL) detecting Agrobacterium tumefaciens strain, which strongly overproduces quorum-sensing regulator TraR and was proved to be able to detect AHLs at nano-molar concentration, was used to detect the production of AHLs in three Mesorhizobium huakuii strains. We showed that AHLs were produced in these strains with some variations. We also found that elevating of medium pH during cell growth greatly affected the stability of AHL signals. This study paved the way of further studying the relationship between quorum sensing and symbiotic nitrogen fixation of the M. huakuii strains.

4-Butyrolactone↗

PubMed2005

[Wave-type time series variation of the correlation between NDVI and climatic factors].

Based on the 1992-1996 data of 1 km monthly NDVI and those of the monthly precipitation and mean temperature collected by 400 standard meteorological stations in China, this paper analyzed the temporal and spatial dynamic changes of the correlation between NDVI and climatic factors in different climate districts of this country. The results showed that there was a significant correlation between monthly precipitations and NDVI. The wave-type time series model could simulate well the temporal dynamic changes of the correlation between NDVI and climatic factors, and the simulated results of the correlation between NDVI and precipitation was better than that between NDVI and temperature. The correlation coefficients (R2) were 0.91 and 0.86, respectively for the whole country.

Climate↗

PubMed2005

Cloning and characterization of a novel intronless lactate dehydrogenase gene in human testis.

Using cDNA microarray hybridization from a human testicular cDNA library, one gene named lactate dehydrogenase A-like gene (LDHL, also known as LDHL6B) was cloned. LDHL exhibited 3.8-fold difference at expression level between adult and fetal human testes. The full cDNA length of LDHL is 1680 bp and had a 1145 bp open reading frame, which encoded a 41.9 kDa protein of 381 amino acids. Sequence analysis showed that LDHL harbors all the domains (one lactate/malate dehydrogenase, NAD binding domain and one lactate/malate dehydrogenase, alpha/beta C-terminal domain) in lactate dehydrogenase gene family. Blasting human genome database localized LDHL to human chromosome 15q22.2 and it was an intronless gene. Results of multiple-tissue PCR and real-time PCR showed that LDHL expressed mainly in testis and its mRNA abundance was testis development-related. In summary, LDHL is believed to be involved in testis development and spermatogenesis.

Amino Acid Sequence↗

PubMed2005

[Immunogenicity of bovine jugular vein conduits treated with different cross-linking methods].

OBJECTIVE: To evaluate the immunogenicity of bovine jugular vein conduits (BJVCs) treated with different cross-linking methods. METHODS: The BJVCs were treated with glutaradehyde (GA), dye-mediated photooxidation (DMP) and polyepoxy compound (PC) (n = 10). The tissue homogenates obtained from BJVCs treated with PC, GA, DMP, and fresh BJVCs, were mixed with the complete Freand adjavant to form the emulsive antigen, which were used to immunize rabbits correspondently. The antibody concentrations to BJVCs in those rabbits' serum were measured by counter double immuno diffusion. The immunologic responses to the BJVCs in different groups were measured with Western blotting. RESULTS: The positive bands appeared when the sera of rabbits were immunized by fresh BJVCs reacted with antigens of fresh BJVCs, but no bands appeared when the sera of rabbits were immunized by fresh BJVCs reacted with those antigens of the BJVCs treated with GA, DMP, and PC in Western blotting. CONCLUSION: The immunogenicity of BJVCs treated with PC, DMP, and GA can be reduced significantly and meet the clinical standard.

Animals↗

PubMed2005

[Myocardial protective effects of pretreatment with captopril on ischemia-reperfusion myocardium in rabbits].

OBJECTIVE: To investigate the effect of pretreatment with captopril on myocardium ischemia-reperfusion injury in atherosclerotic rabbits. METHODS: Thirty-two New Zealand white rabbits were assigned randomly to the normally feed group, cholesterol-feed (CF) group, and cholesterol food plus captopril group (cap-feed group), which were fed for 10 weeks. We examined the changes in the size of the infarct and changes in the myocardium ultrastructure resulting from coronary ischemia/reperfusion. Levels of endothelin (ET) and nitic oxide (NO) were measured in the different experiment stages. RESULTS: The ET levels significantly increased and the content of NO significantly decreased in the CF group compared with those of the cap-feed group. The ultrastructure of myocardium cell was slightly destroyed and the infarct size was significantly smaller in the cap-feed group than the normally feed rabbits and CF rabbits. CONCLUSION: The long-term captopril treatment can lighten the severity of myocardial injury produced by coronary ischemia/reperfusion.

Animals↗

PubMed2005

[Monitoring bcr/abl mRNA levels in imatinib mesylate treated chronic myeloid leukemia patients by real-time quantitative RT-PCR].

OBJECTIVE: To quantify bone marrow bcr/abl mRNA levels in imatinib mesylate treated Ph chromosome positive chronic myeloid leukemia (CML) patients. METHODS: Serial monitoring of bcr/abl mRNA levels by real-time quantitative RT-PCR technique (RQ-PCR) was performed in 34 cases (120 samples) of CML treated with imatinib mesylate. All the patients were IFNalpha based treatment failure before enrolled in this study and the percentage of Ph(+) bone marrow cells were over 95%. RESULTS: The sensitivity of RQ-PCR was 10 pg RNA, with both coefficients of interassay and intraassay variation below 5% for standard samples. The median bcr/abl mRNA level of 10 patients' samples pre imatinib treatment was 5.79% with marked variation (0.24%-60.90%). In 72 samples post imatinib treatment, which the rates of Ph(+) cells [Ph(+)%] were between 0 and 94%, the mRNA level well correlated with Ph(+)% (r = 0.82, P < 0.001). The mRNA levels of 7 patients who achieved complete cytogenetic response (CCyR) within 12 months decreased markedly, the levels of 6 analysable patients decreased by 65.9% - 98.8% after 3 months'treatment accordingly. The level further decreased to 0 after achieving CCyR. For 4 patients who achieved major cytogenetic response (Ph(+) cells < 35%) later than 12 months, the mRNA levels decreased slowly. The levels of 3 analysable patients on 3 month therapy decreased by 2.5%, 18.5% and 61.6% compared with that before treatment. Out of 5 patients in chronic phase without cytogenetic response, 1 decreased, 2 increased gradually and 2 had no change. In 4 disease progression patients, the levels increased stepwise. CONCLUSIONS: Serial quantifications of bcr/abl mRNA levels are necessary for imatinib treated patients, and are more informative than a single detection. A sharp decline of bcr/abl mRNA levels after the treatment implies a promise of CCyR.

Adolescent↗

PubMed2005

[Ectogenous fragile histidine triad gene inhibits the malignant phenotype of human lung cancer cell line A549 in vitro and in vivo].

OBJECTIVE: To investigate the inhibition effects of fragile histidine triad (FHIT) gene on the malignant growth of A549 cell line. METHODS: A mammalian expression vector PEGFP-FHIT was constructed and transfected into the A549 cell line by lipofectamine. Then the transfected cell line was screened by G418. Individual G418-resistant colonies were isolated by limited dilution. The monoclonal transfected cell line was screened by RT-PCR and immunochemical staining. The inhibition growth efficacy of extraneous FHIT was evaluated by clonogenic survival assay, flow cytometry and heteroplastic transplant on nude mice. RESULTS: Presence of extraneous FHIT gene in FHIT-A549 cell was proved by RT-PCR. Immunochemical stain demonstrated that the expression of extraneous FHIT protein was positive in FHIT-A549 cell and negative in PEGFP-A549 cell and A549 cell. The clonal formation rate of FHIT-A549 (2.6%) was significantly lower than that of A549 cell (50.1%) and PEGFP-A549 cell (53.6%, P < 0.01). FHIT-A549 cell (95.8%) was blocked in G(2) phage. Tumorigenicity of A549 cells in nude mice was greatly inhibited by expression of ectogenous FHIT gene. The weight of tumor was significantly lower in FHIT-A549 cell (0.04 +/- 0.03) than in A549 cell (0.24 +/- 0.11) and PEGFP-A549 cell (0.25 +/- 0.07, P < 0.01). CONCLUSIONS: Reintroduction of the expression of ectogeneous FHIT gene can obviously suppress the proliferation and tumorigenicity in human lung cancer cell line A549 and induce apoptosis. The data demonstrate oncosuppressive properties of FHIT gene.

Acid Anhydride Hydrolases↗

PubMed2005

[Activation of Kupffer cell TLR2 signaling pathway during hepatic ischemia/reperfusion injury process in mice and it's significance].

OBJECTIVE: To study changes of TLR2 signaling pathway expression in Kupffer cells during the process of hepatic ischemia/reperfusion in a mice model and the mechanism of TLR2 signaling pathway participating in hepatic ischemia/reperfusion injury. METHODS: BALB/c mice were divided into 3 groups: sham operation (SH), ischemia/reperfusion (I/R) and GdCl3 treatment (Gd) groups. After 4 h of reperfusion, the expression of TLR2 mRNA and membrane TLR2 protein were analyzed in ischemic lobes of the livers, and in Kupffer cells isolated from ischemic lobes. The expression of NF-kappaB in ischemic lobes was also examined. Levels of endotoxin, ALT and TNFalpha were measured at the same time point. RESULTS: The expressions of TLR2 mRNA and protein in both ischemic hepatic lobes and Kupffer cells isolated from ischemic lobes were increased in the I/R group compared to those in the SH group, as well as the expression of NF-kappaB in ischemic lobes, which was down regulated by intravenous GdCl3 treatment. Levels of ALT and TNFalpha in the portal vein were higher in the I/R group than in the SH group, which also were decreased with treatment of GdCl3. The level of endotoxin in the three groups remained constant. CONCLUSION: TLR2 signaling pathway in Kupffer cells is activated during the process of hepatic ischemic/reperfusion injury. The activation of TLR2 signaling pathway in Kupffer cells may play a role in this process.

Animals↗

PubMed2005

[Recombinant design and expression of human three-domain antibody against BoNTa].

VH and Vkappa genes were amplified from human ScFv B17 specific against botulinum neurotoxin serotype A (BoNTa). Gene sequence encoding 5'-terminal 12 amino acid of heavy chain constant region CH1, as a linker, linked VH and Vkappa to construct a new three-domain antibody molecule VH/Vkappa. VH/Vkappa was expressed at high level over 34% of total host cell proteins in E. coli. Recombinant protein were purified up to 95% by affinity column. As a result, recombinant VH/Vkappa could recognize and bind specific to BoNTa in ELISA. However, comparing with its parent ScFv, VH/Vkappa has higher relative affinity and stability.

Antibodies, Monoclonal↗

PubMed2005

[Dermatomyositis/polymyositis associated with head and neck malignancy].

OBJECTIVE: To observe the relation between dermatomyositis/polymyositis and head-neck malignancy. METHOD: All 136 cases of dermatomyositis/polymyositis admitted to PUMCH during 10 years (1994-2003) were studied. The clinical features of 6 patients with an associated head-neck malignancy were analyzed. RESULT: There were 17 cases of malignancy in 136 patients with dermatomyositis/polymyositis, of which, 6 cases (6/17, 35.29%) were found to have head-neck malignancy: 4 cases of nasopharyngeal carcinoma, 1 case of non-Hodgkin lymphoma and 1 case of hypopharynx carcinoma. CONCLUSION: Nasopharyngeal carcinoma represents the first neoplasm among head-neck malignancy associated with dermatomyositis/polymyositis. Nasal endoscopic and/or fibrolaryngoscopic search for potential head-neck malignancy should be performed in every patient with dermatomyositis/polymyositis.

Adult↗

PubMed2005

[The clinical significance of detecting minimal residual disease in acute childhood B-cell lymphoblastic leukemia with flow cytometry].

OBJECTIVE: Flow cytometry may be used to detect minimal residual disease (MRD) in acute lymphoblastic leukemia because leukemic cells often display aberrant phenotypes when compared to normal cells. The present study was designed to establish a flow cytometric method for detecting MRD in children with B-ALL and evaluate its clinical prognostic value. The investigators also aimed to study the value of the detection of MRD by flow cytometry in childhood B-ALL without effective antibody combinations. METHODS: Thirty-six cases of childhood B-ALL with effective antibody combinations were performed MRD analysis after induction therapy. The authors detected MRD in 6 cases without effective antibody combinations by the four-color antibody combinations consisting of CD(45)/CD(19)/CD(10)/CD(34) and CD(45)/CD(19)/CD(20)/CD(22) and detected the aberrance of the minor subsets of CD(19)(+) cells. RESULTS: (1) Forty-two cases of childhood B-ALL were screened for antibody combinations of interest and were identified in 86% (36/42) of the cases. The sensitivity of this method was 0.01%. (2) Patients with MRD levels > or = 0.01% at 9 and 12 months of therapy had significantly low disease-free survival compared with patients with MRD levels < 0.01%. (3) Six out of seven patients with recurrence in the BM had MRD levels > or = 0.1% prior to recurrence. Patients with MRD levels > or = 0.1% during chemotherapy had significantly low disease-free survival as compared with patients with MRD values < 0.1%. (4) Two out of seven patients with recurrence had positive results of the qualitative PCR prior to recurrence. (5) Five patients with recurrence had no shift of antigen expression at relapse except that a patient missed CD(13). (6) Detectable MRD was not found in six patients without effective antibody combinations. CONCLUSION: (1) Flow cytometry is a sensitive and specific method for detecting MRD of childhood ALL, and could predict the coming relapse. (2) Patients with MRD levels > 10(-3) had poor prognosis. (3) The levels of MRD at month 9 and 12 had prognostic value. (4) The value of antibody combinations consisting of CD(45)/CD(19)/CD(10)/CD(34) and CD(45)/CD(19)/CD(20)/CD(22) should be further investigated in patients without effective antibody combinations.

Adolescent↗

PubMed2005

Variability for the presence of pyrrolizidine alkaloids in Crotolaria juncea L.

Sunn hemp (Crotalaria juncea L.) is the most widely grown legume used as green manure in the tropics where it is also grown as a fiber and animal fodder crop. It has been reported that sunn hemp seeds contain several pyrrolizidine alkaloids that when ingested in sufficient amount can be toxic to animals and birds. No information is available regarding variability for the presences of the different types of pyrrolizidine alkaloids in the seeds. The objective of this research was to analyze sunn hemp seeds of nine populations that originated in different parts of the world for several pyrrolizidine alkaloids to determine their level of variability for the presence of these compounds and to quantify the total amount of pyrrolizidine alkaloids in the seeds. Of the nine pyrrolizidine alkaloids tested, the sunn hemp populations only had junceine and trichodesmine. PI 207657 had very low levels of both alkaloids and PI 314239, PI 322377, PI 346297, and the US cultivar Tropic Sun had very low levels of trichodesmine. Although juncein was present in higher amounts than trichodesmine in the seeds of most accessions, its value was deemed to be small. The amount of pyrrolizidine alkaloids present in the sunn hemp populations studied was low.

Chromatography, High Pressure Liquid↗