Search PubMed⌕ Search

Biomedical subjects

Gang Li

Publications and source records attributed to Gang Li.

At least 235 records · Page 13Linked to original sources

A sample size adjustment procedure for clinical trials based on conditional power.

When designing clinical trials, researchers often encounter the uncertainty in the treatment effect or variability assumptions. Hence the sample size calculation at the planning stage of a clinical trial may also be questionable. Adjustment of the sample size during the mid-course of a clinical trial has become a popular strategy lately. In this paper we propose a procedure for calculating additional sample size needed based on conditional power, and adjusting the final-stage critical value to protect the overall type-I error rate. Compared to other previous procedures, the proposed procedure uses the definition of the conditional type-I error directly without appealing to an extra special function for it. It has better flexibility in setting up interim decision rules and the final-stage test is a likelihood ratio test.

Journal Article↗

Regulation of the Mdr1 isoforms in a p53-deficient mouse model.

Both p53 and multidrug transporters play important roles in chemoresistance. A transcriptional dependence of the Mdr1 gene promoter by p53 was first established a decade ago, and despite intense study, the p53-Mdr1 relationship still remains vague in vivo. The general model proposes that wild-type p53 down regulates, while mutant p53 up regulates, the Mdr1 promoter. Given that many studies have utilized cancer cell lines, minimal promoters and non-specific cDNA expression for in vitro experiments, we first sought to confirm the model using dermal fibroblasts isolated from the p53-knockout mice. We show that the gene products of the mouse Mdr1 homologue (Mdr1a and Mdr1b), namely P-glycoprotein (P-gp), appear upregulated at both the protein and mRNA levels in p53(-/-) mFbs compared with p53(+/+) cells. We demonstrate that transient transfection of a mouse p53(WT) expression plasmid into short-term primary p53(-/-) fibroblasts can revert P-gp overexpression. The difference in P-gp levels has functional significance in that p53(-/-) fibroblasts are more resistant to doxorubicin and vincristine treatment and this resistance can be attenuated in the presence of the P-gp inhibitor, verapamil. Furthermore, we demonstrate that in kidney, spleen and testis, P-gp expression is elevated in the absence of p53. In contrast, other organs such as heart, liver, lung, brain, thymus and skeletal muscle, show no difference in expression between p53(+/+) and p53(-/-) mice. Thus, our data shows a tissue-specific regulation of P-gp isoforms by p53 in the context of a p53-null mouse model.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland.

PTEN tumor suppressor is frequently mutated in human cancers, including breast cancers. Female patients with inherited PTEN mutations suffer from virginal hypertrophy of the breast with high risk of malignant transformation. However, the exact mechanisms of PTEN in controlling mammary gland development and tumorigenesis are unclear. In this study, we generated mice with a mammary-specific deletion of the Pten gene. Mutant mammary tissue displayed precocious lobulo-alveolar development, excessive ductal branching, delayed involution and severely reduced apoptosis. Pten null mammary epithelial cells were disregulated and hyperproliferative. Mutant females developed mammary tumors early in life. Similar phenotypes were observed in Pten-null mammary epithelia that had been transplanted into wild-type stroma, suggesting that PTEN plays an essential and cell-autonomous role in controlling the proliferation, differentiation and apoptosis of mammary epithelial cells.

Animals↗

Cell proliferation and apoptosis during fracture healing.

This study investigated the relation between cell proliferation and apoptosis during fracture healing in a mouse femoral fracture model. Left femoral osteotomies were performed in 30 mature male CFLP mice immobilized with uniplanar external fixators. Six animals were killed on days 2, 4, 8, 16, and 24 postfracture for examination. Localization of cell proliferation was examined using immunohistochemistry with proliferating cell nuclear antigen (PCNA) monoclonal antibody. Apoptotic cells were visualized with the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL) method. Images of each time-specific specimen were captured. The total callus area, the positively labeled cells by PCNA, and TUNEL per high-power field were quantified. Cell proliferation and apoptosis were found coexisting during the entire period of study. In the early phases of fracture healing (days 2-8), PCNA-positive labeling was predominant and peaked at day 8 and the TUNEL-positive labeling was minimal. In later stages of fracture healing (days 16-24), PCNA expression declined at day 16 as callus ossification and remodeling spread within the fracture site and apoptosis was the dominant cell activity with the TUNEL-positive labeling peaking at day 16 and declining sharply at day 24. These cell activities were reflected by the change of fracture callus, where there was a continuous increase in total callus area to day 16 and subsequent decrease at day 24. This study indicated that cell proliferation and apoptosis are coupled events during fracture repair, cell proliferation is active at the early stages, and apoptosis is active during the phase of callus remodeling.

Animals↗

The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line.

AIM: The goal of this study was to characterize the AFP receptor, its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402. METHODS: Cell proliferation enhanced by AFP was detected by MTT assay, 3H-thymidine incorporation and S-stage percentage of cell cycle analysis. With radioactive labeled 125I-AFP for receptor binding assay; cAMP accumulation, protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium (Ca2+i) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncogenes N- ras, p 53, and p21( ras ) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively. RESULTS: It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay, (3)H-thymidine incorporation and S-phase percentage up to 2-fold. Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9 x10(-8)mol. (-1)L respectively. Pretreatment of cells with AFP resulted in a significant increase (625%) in cAMP accumulation. The activity of protein kinase A activity were increased up to 37.5, 122.6, 73.7 and 61.2% at treatment time point 2, 6, 12 and 24 hours. The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204% at 4 min. The results also showed that AFP(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells. In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control. CONCLUSION: These results demonstrate that AFP is a potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells. Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium to regulate the expression of oncogenes.

Calcium↗

Prevalence of hepatitis G virus infection and homology of different viral strains in Southern China.

AIM: To investigate the prevalence of hepatitis G virus (HGV) infection and to analyse the homology of different HGV strains in Southern China. METHODS: A total of 1993 sera from different groups in Guangdong, Hong Kong, and Yunnan were detected by reverse transcription polymerase chain reaction (RT-PCR). The nucleotide sequences of 5'untranslated region (5'UTR) derived from 20 strains and NS5 region from 3 strains were determined. RESULTS: The positive rate of HGV RNA was 0.89 % in community population, 2.57 % in blood donors, 17.86 % in intravenous drug abusers, 14.13 % in patients with hemodialysis, 13.66 % in those with hepatocellular carcinoma, 25.30 % in non A-E hepatitis, 7.22 % in hepatitis B, 12.73 % in hepatitis C, 41.67 % in patients received bone marrow transplantation, respectively. The homology was 90.40-100 % in 5'UTR among different strains, while that of NS5 region was 93.3-94 % in nucleotide sequence, and 97-99.2 % in amino acid sequence. CONCLUSION: These results showed that there was a high incidence of HGV infection in patients from Southern China, being treated for bone marrow transplantation, hepatocellular carcinoma and those on haemodialysis. Furthermore, there was also a high frequency of co-infection of HGV with HBV, HCV, non A-E viral hepatitis and that among intravenous drug abusers. The study also showed that sequence variation in different strains was associated with geographical factors but there was no significant difference in 5'UTR in circulating viruses between different patient groups. Finally, by sequential analysis of viral species present in individual patients over a three months period there was no evidence of sequence variation in the 5' UTR.

5' Untranslated Regions↗

Insulin-like growth factor-I-induced migration of melanoma cells is mediated by interleukin-8 induction.

Successive events of growth factor-induced autocrine and paracrine activation promote tumor growth and metastasis. Insulin-like growth factor-I (IGF-I) stimulates melanoma cells to grow, survive, and migrate. Interleukin-8 (IL-8) is produced by melanoma cells and has been correlated with melanoma metastasis, but the biological functions of this cytokine have not been elucidated. We show here that IGF-I-induced migration of melanoma cells could be inhibited by neutralizing antibody against IL-8. IGF-I overexpression induced IL-8 production in melanoma cells, especially in biologically early melanomas by accelerating its transcription rate via activation of mitogen-activated protein kinase pathway. IGF-I treatment phosphorylated c-Jun and stimulated the binding of AP-1 but not NF-kappaB to the IL-8 promoter. These data identify IL-8 as a new target of IGF-I in melanoma and suggest that some of the biological functions of IGF-I are mediated by IL-8.

Antibodies, Monoclonal↗

Analysis of DNA and hemoglobin adducts and sister chromatid exchanges in a human population occupationally exposed to propylene oxide: a pilot study.

Propylene oxide (PO), a simple alkylating agent used in the chemical industry, is weakly genotoxic and induces nasal cavity tumors in rodents on inhalation at high air concentrations. DNA adducts, hemoglobin adducts, and sister chromatid exchanges (SCE) were analyzed as biomarkers of exposure in a group of eight PO-exposed workers and eight nonexposed subjects. 1-2-Hydroxypropyladenine (1-HP-adenine) in DNA of WBCs was analyzed using a hypersensitive (32)P-postlabeling assay. HP-valine in hemoglobin was measured using gas chromatography/tandem mass spectrometry. Air measurements indicated PO levels in the range of 1-7 ppm. All three biomarkers showed significantly increased levels in the exposed workers. 1-HP-adenine was recorded in seven of the exposed workers (mean 0.66 mol/10(9) mol nucleotides) but was not detected in any of the control subjects. HP-valine was found in all subjects (means of 2.7 and 0.006 pmol/mg globin in exposed workers and controls, respectively). The average frequencies of SCE were 3.7/cell in exposed workers and 2.0/cell in controls, respectively. DNA and hemoglobin adducts were correlated (r = 0.887), as well as DNA adducts and SCE (r = 0.792) and hemoglobin adducts and SCE (r = 0.762). The present study is the first demonstrating PO-DNA adducts in human individuals. It is also the first study indicating cytogenetic effects in humans from PO exposure, although confounding effects from other sources cannot be excluded.

Adult↗

The tumour suppressor p33ING1 does not enhance camptothecin-induced cell death in melanoma cells.

The tumour suppressor ING1 shares many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. Previous findings indicate that the isoform p24ING1 is capable of enhancing chemosensitivity in human fibroblasts. To investigate if the p33ING1 isoform is also involved in chemosensitivity, we overexpressed p33ING1 in melanoma cells and assessed for cell death after treatment with camptothecin. Results from the sulforhodamine B cell survival assay and flow cytometry analysis show no significant difference among cells transfected with vector, p33ING1, and antisense p33ING1. Furthermore, co-transfection of the p33ING1 and p53 constructs had no effect on the frequency of cell death, indicating that there is no synergistic effect between the two tumour suppressors in camptothecin-induced cell death in melanoma cells. This is in contrast to previously observed collaboration between p33ING1 and p53 in DNA repair and apoptosis. Taken together, we demonstrate that p33ING1 does not enhance camptothecin-induced cell death in melanoma cells.

Antineoplastic Agents, Phytogenic↗

Tissue-specific regulation of Fas/APO-1/CD95 expression by p53.

The regulation of Fas/APO-1(CD95), an important member of the tumor necrosis factor (TNF) superfamily involved in membrane-mediated apoptosis, has been a subject of recent research. Ligation of Fas by Fas ligand or an anti-Fas cross-linking antibody triggers receptor trimerization followed by recruitment of FADD to the cytoplasmic domain of the receptor and the activation of the caspase cascade. The tumor suppressor p53 has been shown to upregulate Fas expression under numerous pro-apoptotic stimuli in vitro. Using the p53 knockout mouse model, we demonstrate by Western blot analysis, immunohistochemistry, and semi-quantitative RT-PCR that Fas expression is reduced in spleen and liver from p53-/- mice compared to p53+/+ controls, while similar expression levels were observed in brain, heart, kidney, lung, skin, testis, and thymus between the two groups. While Fas protein was abundant in brain, heart, liver, and spleen, low levels of endogenous expression was observed in other tissues from the p53+/+ and p53-/- mice. These data indicate that p53 regulates Fas expression in a tissue-specific manner.

Animals↗

[Clinical characteristics of chronic subdural hematoma evolving from traumatic subdural effusion].

OBJECTIVE: To probe into the incidence, mechanism and clinical characteristics of chronic subdural hematoma (CSDH) evolving from traumatic subdural effusion (TSE). METHODS: The clinical materials of 32 patients with CSDH evolving from TSH were analyzed retrospectively and the correlative literature was reviewed. RESULTS: 16.7% of the patients with TSH evolved into CSDH. The time of evolution was 22 - 100 days after head injury. All patients were cured with hematoma drainage. CONCLUSIONS: TSE is one of the origins of CSDH. The clinical characteristics of TSE evolving into CSDH include polarization of patient age, and chronic small effusion. The patients are usually injured deceleratedly and accompanied with mild cerebral damage.

Adolescent↗

[CT-guided stereotactic evacuation of cerebral hemorrhage in hypertensive patients: report of 32 cases].

OBJECTIVE: To evaluate the application of CT-guided stereotactic evacuation in the treatment of cerebral hemorrhage in hypertensive patients. METHODS: A retrospective analysis was conducted of 32 hypertensive patients with cerebral hemorrhage who underwent CT-guided stereotactic evacuation. RESULTS: The hematomas were effectively removed after the surgical procedure. Follow-up visit of the patients lasting for 6 to 10 months found that 31 patients survived, among whom 12 had total recovery and could live independently, 4 lived with tolerable independence while 15 were bedridden and required assistance. Death occurred in 1 case due to neurogenic pulmonary edema. CONCLUSION: CT-guided stereotactic evacuation is effective to reduce mortality and disability rate of patients with cerebral hemorrhage, improving their quality of life. Due to the merit of minimal invasion and high precision, this technique is most applicable in the treatment of deep cerebral hematoma.

Aged↗

Enhancement of proliferation of HeLa cells by the alpha-fetoprotein.

A lot of investigations showed that alpha-fetoprotein(AFP) could regulate the proliferation of tumors or neoplastic cells. In order to study the enhancement of this function, AFP was extracted from human cord blood serum and was allowed to act on HeLa cell in vitro. The cellular proliferation was investigated by using the MTT assay and the [(3)H]-incorporation, and the cell cycle was analysed with flow cytometry. Radioactive immunosorbent assay was utilized to detect cAMP accumulation, protein kinase A activity and confocal microscopy was used f or scanning intracellular calcium. The expression of mutant p53 and p21(ras) protein were analyzed by Western blotting. Our results showed that AFP (>10 mg/L ) had strong effect of enhancement on the proliferation of HeLa cells; AFP (20 mg /L) could significantly increase the concentration of cAMP (300%), Ca(2+) (154.9%) and protein kinase A activity (100%). It was also shown that the expression of mutant p53 and p21(ras) protein of HeLa cells were enhanced after t he treatment with AFP (20 mg/L) for 24 hours. Compared with control, the expression of mutant p53 protein was increased by 81.1% (24 h), p21(ras) protein was increased by 96.2% (24 h) respectively; but the monoclonal antibody to AFP blocked these functions of AFP. In conclusion, AFP enhanced the proliferation of HeLa cells; AFP may regulate the growth of the cells by influencing the transmembrane signal pathway and enhancing the expression of the oncogenes.

Calcium↗

The tumour suppressor p33ING1 does not regulate migration and angiogenesis in melanoma cells.

The tumour suppressor ING1 shares many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. Since p53 inhibits invasion and angiogenesis of melanoma cells, we sought to investigate if p33ING1 (one of ING1 isoforms) is also involved in these biological processes. We first overexpressed p33ING1 in melanoma cells and assessed the protein levels in MMP-1, MMP-2, and MMP-9. Results from Western blot analysis showed no significant difference in these matrix metalloproteinase levels between cells transfected with vector, p33ING1, and antisense p33ING1. Wound healing assay was performed to examine if p33ING1 plays a role in migration and invasion. Results showed that there was no difference between vector, p33ING1, and antisense p33ING1 groups in melanoma cell migration across the wound. Western blot analysis also indicated that there is no difference in the levels of proteins which are directly involved in angiogenesis, such as VEGF, Flt-1, and Flk-1, between cells transfected with vector, p33ING1, and antisense p33ING1. Furthermore, functional studies indicated that cultured medium derived from p33ING1-transfected melanoma cells did not stimulate the growth of HUVEC cells, compared to controls, providing support to the lack of functional role of p33ING1 in angiogenesis. In conclusion, we demonstrate in vitro that p33ING1, unlike p53, does not play a role in angiogenesis and migration in melanoma cells.

Blotting, Western↗

[The in vitro study of the effects of 11 kinds of traditional Chinese medicine on the growth and acid production of Actinomyces viscosus].

OBJECTIVE: To assess the effects of different natural medicines on the growth and acid production of Actinomyces viscosus, thus making preparations for screening an effective agent to mediate the balance of oral microflora. METHODS: Actinomyces viscosus ATCC 19246 was chosen as the experimental bacteria. 11 kinds of traditional Chinese medicine, such as Rhizoma Ligustici Chuanxiong, Sargentodoxa Cuneata and Galla Chinensis were extracted by means of maceration, percolation and reflux extraction. First, the values of MIC of various extracts were measured. Second, the experimental medium containing various extracts was prepared. The concentration of the extracts was lower than the MIC of the medicine, and the initial pH of the medium was 7.4. Then Actinomyces viscosus was cultured in the medium for 48 h, and finally the rest pH was measured. RESULTS: When the concentration of the medicines was lower than or equal to 8.000 mg/ml, it was found that all kinds of medicine except Radix Notoginseng can inhibit the growth of Actinomyces viscosus effectively, especially Polistes mandarinus and Semen Arecae. Tea polyphenols, Radix Notoginseng, Radix et Rhizoma Rhei, Polistes mandarinus and Sargentodoxa cuneata can inhibit the acid production of Actinomyces viscosus effectively, but Radix Scutellariae, Rhizoma Ligustici Chuanxiong, Semen Arecae, Radix Angelicae Dahuricae, Galla Chinensis and Catechu have no preliminary effect on it. CONCLUSION: Tea polyphenols, Radix et Rhizoma Rhei, Polistes mandarinus and Sargentodoxa cuneata can inhibit the growth and the acid production of Actinomyces viscosus effectively.

Acids↗

[The advances on the research of the body surface mapping].

Body surface mapping is introduced in this paper. The research of body surface mapping involves two main aspects: data acquiring system and data processing methods. The recommended design utilizes the virtual instruments concept and high-speed open bus standard. The data processing methods involve qualitative and quantitative methods. Dynamic and static mapping techniques are introduced here as the qualitative methods while statistical methods, inverse calculation and principle component analysis are introduced as the quantitative methods.

Algorithms↗