Biomedical subjects

Ping Jiang

Publications and source records attributed to Ping Jiang.

85 records · Page 5Linked to original sources

PubMed2002

Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model.

We report here whole-body optical imaging, in real time, of genetically fluorescent pancreatic tumors growing and metastasizing to multiple sites in live mice. The whole-body optical imaging system is external and noninvasive. Human pancreatic tumor cell lines, BxPC-3 and MiaPaCa-2, were engineered to stably express high-levels of the Aequorea victoria green fluorescent protein (GFP). The GFP-expressing pancreatic tumor cell lines were surgically orthotopically implanted as tissue fragments in the body of the pancreas of nude mice. Whole-body optical images visualized real-time primary tumor growth and formation of metastatic lesions that developed in the spleen, bowel, portal lymph nodes, omentum, and liver. Intravital images in the opened animal confirmed the identity of whole-body images. The whole-body images were used for real-time, quantitative measurement of tumor growth in each of these organs. Intravital imaging was used for quantification of growth of micrometastasis on the liver and stomach. Whole-body imaging was carried out with either a trans-illuminated epi-fluorescence microscope or a fluorescence light box, both with a thermoelectrically cooled color CCD camera. The simple, noninvasive, and highly selective imaging made possible by the strong GFP fluorescence allowed detailed simultaneous quantitative imaging of tumor growth and multiple metastasis formation of pancreatic cancer. The GFP imaging affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals without the need for anesthesia, substrate injection, contrast agents, or restraint of animals required by other imaging methods. The GFP imaging technology presented in this report will facilitate studies of modulators of pancreatic cancer growth, including inhibition by potential chemotherapeutic agents.

Animals↗

PubMed2002

Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity.

Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate chains of proteoglycan, a component of blood vessel walls and the extracellular matrix. Recent studies demonstrated that HPR1 expression is increased in a variety of malignancies and may play a critical role in tumor metastases. The HPR1 gene and its genomic structure have been recently cloned and characterized. To understand the mechanisms of HPR1 gene expression and regulation, we first mapped the transcription start site of the HPR1 gene and found that HPR1 mRNA was transcribed from the nucleotide position 101 bp upstream of the ATG codon. A 3.5-kb promoter region of the HPR1 gene was cloned. Sequence analysis revealed that the TATA-less, GC-rich promoter of the HPR1 gene belongs to the family of housekeeping genes. This 3.5-kb promoter region exhibited strong promoter activity in two thyroid tumor cell lines. Truncation analysis of the HPR1 promoter identified a minimal 0.3-kb region that had strong basal promoter activity. Truncation and mutational analysis of the HPR1 promoter revealed three Sp1 sites and four Ets-relevant elements (ERE) significantly contributing to basal HPR1 promoter activity. Binding to the Sp1 sites by Sp1 and to the ERE sites by GA-binding protein (GABP) was confirmed by electrophoretic mobility shift assay and competition and supershift electrophoretic mobility shift assays. Cotransfection of Sp- and GABP-deficient Drosophila SL-2 cells with the HPR1 promoter-driven luciferase construct plus the expression vector encoding the Sp1, Sp3, or GABP gene induced luciferase gene expression. Mutation or truncation of the Sp1 or ERE sites reduced luciferase expression in both SL-2 cells and thyroid tumor cell lines. Coexpression of GABPalpha/beta and Sp1 or Sp3 further increased luciferase reporter gene expression. Our results collectively suggest that Sp1 cooperates with GABP to regulate HPR1 promoter activity.

Base Sequence↗

PubMed2002

Optically imageable metastatic model of human breast cancer.

We report an optically imageable orthotopic metastatic nude mouse model of the human breast cancer MDA-MB-435 expressing green fluorescent protein (GFP). We demonstrate fluorescent imaging of primary and metastatic growth in live tissue and in intact animals. Fragments of tumor tissue expressing GFP were sutured into the pocket in the right second mammary gland. Tumor tissue was strongly fluorescent, enabling whole-body imaging of tumor growth by week 5. Neovascularization of the primary tumor was also visualized by whole-body imaging by contrast of the vessels to the fluorescent tumor. At autopsy, the MDA-MB-435-GFP was found to have metastasized to various organs, including the lung in 55% of the animals, the lymph nodes in 15% of the animals including axillary nodes, and the liver in 10% of the animals. These metastases could be visualized in fresh tissue by fluorescent imaging. Detailed fluorescence analysis visualized extensive metastasis in the thoracic cavity and the lymphatic system. Large metastatic nodules in the lung involved most of the pulmonary parenchyma in all lobes. Lymph node metastasis was found mainly in the axillary area. In the liver, fluorescent macroscopic metastatic nodules were found under the capsule. The metastatic pattern in the model thus reflected clinical metastatic breast cancer and provides a powerful model for drug discovery for this disease.

Adult↗

PubMed2002

Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia.

Depending on the degree of underlying resistance present, optimization of the pharmacokinetics of protease inhibitors may result in improved virologic suppression. Thirty-seven human immunodeficiency virus (HIV)-infected subjects who had chronic detectable viremia and who were receiving 800 mg of indinavir three times a day (TID) were switched to 400 mg of indinavir BID with 400 mg of ritonavir two times a day (BID) for 48 weeks. Full pharmacokinetic evaluations were obtained for 12 subjects before the switch and 3 weeks after the switch. Combination therapy increased the indinavir predose concentrations in plasma by 6.47-fold, increased the minimum concentration in serum by 3.41-fold, and reduced the maximum concentration in serum by 57% without significantly changing the area under the plasma concentration-time curve at 24 h. At week 3, 58% (21 of 36) of the subjects for whom postbaseline measurements were available achieved a viral load in plasma of <50 copies/ml or a reduction from the baseline load of > or =0.5 log(10) copies/ml. Of these subjects, 82% (14 of 17) whose viruses had three or fewer protease inhibitor mutations and 88% (14 of 16) whose viruses had an indinavir virtual phenotypic susceptibility test of more than sixfold less than that for the baseline isolate were considered virologic responders. The indinavir virtual inhibitory quotient, which is a function of baseline indinavir phenotypic resistance (estimated by virtual phenotype) and the indinavir predose concentration in plasma achieved with indinavir-ritonavir combination therapy, was the best predictor of a viral load reduction. Sixteen subjects discontinued the study by week 48 due to adverse events, predominantly related to hyperlipidemia. Pharmacokinetic intensification of indinavir-based therapy with ritonavir reduced the viral loads in subjects but added toxicity. The virtual inhibitory quotient, which incorporates both baseline viral resistance and the level of drug exposure in plasma, was superior to either baseline resistance or drug exposure alone in predicting the virologic response.

Adult↗

PubMed2002

RXR receptor agonist suppression of thyroid function: central effects in the absence of thyroid hormone receptor.

High-affinity agonists for the retinoic acid X receptors (RXR) have pleotropic effects when administered to humans. These include induction of hypertriglyceridemia and hypothyroidism. We determined the effect of a novel high-affinity RXR agonist with potent antihyperglycemic effects on thyroid function of female Zucker diabetic rats and nondiabetic littermates and in db/db mice. In both nondiabetic and ZFF rats, AGN194204 causes a 70-80% decrease in thyrotropin (TSH), 3,3',5-triiodothyronine, and thyroxine (T(4)) concentrations. In the db/db mouse, AGN194204 causes a time-dependent decrease in thyroid hormone levels with the fall in TSH that was significant after 1 day of treatment preceding the fall in T(4) levels that was significant at 3 days of treatment. Treatment with AGN194204 caused an initial increase in hepatic 5'-deiodinase mRNA levels which then fell to undetectable levels by 3 days of treatment and continued to be low at 7 days of treatment. After treatment for 5 days with AGN194204, both wild-type and thyroid hormone receptor beta (TR beta(-/-))-deficient mice demonstrated a nearly 50% decrease in serum TSH and T(4) concentrations. The results suggest that a high-affinity RXR agonist with antihyperglycemic activity can cause central hypothyroidism independently of TR beta, the main mediator of hormone-induced TSH suppression.

Animals↗

PubMed2002

[Changes of antioxidative capacity and endothelial function before and after treatment among patients with high altitude pulmonary edema].

OBJECTIVE: To investigate the changes of antioxidative capacity and endothelial function among patients with high altitude pulmonary edema (HAPE). METHODS: The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were measured before and after treatment among 34 cases of patients with HAPE, and 20 local healthy volunteers served as control. RESULTS: The serum levels of SOD, GSH, NO and NOS were lower in patient-group before treatment than after treatment and those in control-group significantly (P < 0.01), while the concentration of MDA and ET-1 were higher in patient-group before treatment than after treatment and those in the control-group significantly (P < 0.01). The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were not different between patient-group after treatment and the control-group (P > 0.05). CONCLUSION: The results indicated that changes of SOD, MDA, GSH, NO, NOS and ET-1 may participate in the course of HAPE.

Adolescent↗

PubMed2002

[Study on intervention and comparison of rational use of antibiotics on perioperative period of clean incision and clean-defiled incision].

OBJECTIVE: To explore a set of scientific evaluation and intervention methods on perioperatur period which fits for China's situation, and to promote the development of rational drug use. METHODS: Two would tertiary general hospitals were selected and separated in to intervention group and control group. Intervention was carried out and compared at the same period on inpatient surgical cases of thryroidectomy, mastectomy, cholescystectomy, and hysteromyomectomy plus appendix. RESULTS: The average drug costs was decreased from 1 601.27 yuan to 1 489.59 yuan and the average antibiotics use from 740.20 yuan to 352.03 yuan (P < 0.01) in the intervention group pre and post intervention. There was a remarkable improvement on the rationality of antibiotics use in intervention group, from 31.35% to 91.81% (P < 0.01) pre and post intervention, implemented in the hospital. CONCLUSION: It is practicable and effective to implement rational drug use where intervention was carried out, since it plays an active role on promoting safely, effectively and economic antibiotic use in China.

Anti-Bacterial Agents↗

PubMed2002

[Preimplantation genetic diagnosis].

OBJECTIVE: To evaluate the clinical effectiveness of preimplantation genetic diagnosis (PGD) for the couples having a higher risk of genetic diseases with fluorescence in situ hybridization (FISH). METHODS: Ovarian hyperstimulation, oocyte retrieval and in vitro fertilization were performed in 4 cases. Blastomere biopsy were performed from the embryos at the 6 - 8 cell stage. Genetic diagnosis was identified by single blastomere FISH. The female embryos or normal embryos were transferred into uterus. RESULTS: Twelve embryos were available for embryo biopsy. Twenty cells were collected. Seventeen nuclei were found after fixation. Hybridization signals of 11 embryos were clear and 8 embryos were transferred into uterus. One clinical pregnancy was achieved, and 1 normal female infant was delivered on september 14, 2001. CONCLUSION: PGD is very valuable for avoiding selective abortion and birth of affected child of the couples having a higher risk of genetic diseases by detecting embryo sex and chromosome number using FISH.

Adult↗

PubMed2002

[Immunohistochemical study of the epithelial hyperproliferation in middle ear cholesteatoma].

OBJECTIVE: To elucidate the role of epidermal growth factor (EGF) in the growth of cholesteatoma, and to investigate the biological behaviour of cholesteatoma. METHODS: The expression of EGF receptor (EGFR), proliferating cell nuclear antigen Ki-67, collagen IV protein and laminin in 18 specimens of cholesteatoma was stained immunohistochemically and compared with that in epidermis of 8 specimens of normal external auditory meatus skin. RESULTS: The immunostaining for EGFR showed two patterns: strong linear or granular cell surface staining and granular cytoplasmic staining. In epidermis of normal skin, EGFR appear to be highly expressed on the basal layer. Cholesteatoma epithelium showed increased positive reactions in the super basal layers. The Ki67 was expressed in nuclei, and a dot-like as well as a diffuse nuclear staining pattern was detected. The Ki67 expression was restricted in the basal layer of normal epithelium, and the positive of Ki67 in nuclei was rare. The expression of Ki67 in cholesteatoma extended to the suprabasal and upper layers of the epithelium with an increasing frequency of positive cells. Collagen IV and Laminin were similary localized in the basement membrane of normal epithelium with a continuously staining pattern and a similar staining pattern was also found in the cholesteatoma, and the vas is abundant under basement membrane in some cholesteatoma samples. CONCLUSION: The overexpression of EGFR suggest a hyperproliferative state in cholesteatoma and there is a close relationship between the EGF and hyperproliferation of cholesteatoma. The increased expression of Ki67 confirms the hyperproliferative nature of cholesteatoma. The results of expression of Collagen IV and Laminin in cholesteatoma indicate it is a benign disease.

Adolescent↗

PubMed2002

[Study on drug-resistance of Mycobacterium tuberculosis isolated from coal workers with silico-tuberculosis].

OBJECTIVE: To study the gene mutation and streptomycin, isoniazid or rifampicin resistance of Mycobacterium isolated from silico-tuberculosis patient's sputum so as to find a more effective therapy for this disease. METHODS: Mycobacteria tuberculosis were separated from 96 coal worker with silico-tuberculosis firstly. Then rpsL, KatG and rpoB fragments of genome were copied with PCR and compared their SSCP profiles with standard strains. RESULTS: 67 strains of streptomycin, isoniazid or rifampicin resistant Mycobacteria tuberculosis were found in routine drug resistance test, with the percentages of 80.5% (54/67), 58.2% (39/67) respectively. PCR-SSCP showed that out of 67 drug-resistant strains, 66(98.5%) of rpsL, 47(70.1%) of rpoB and 42(62.7%) of KatG appeared abnormal. CONCLUSION: Most of the resistant strains appeared gene mutation. The mution rates were higher than the results from routine drug resistance test.

Coal↗

PubMedDate not supplied

Efficacy of DNA vaccines against infectious bursal disease virus in chickens enhanced by coadministration with CpG oligodeoxynucleotide.

The objective of the present study was to investigate the feasibility of a DNA vaccine and CpG oligodeoxynucleotide (ODN) to protect chickens against infectious bursal disease virus (IBDV) infection. Two plasmids DNA carrying VP2 genes of the very virulent (vv) strain of IBDV were constructed with reverse transcription-polymerase chain reaction and designated as pcDNA3.1-VP2 and pCI-VP2. The VP2 protein expressed in COS-7 cells transfected with the plasmid was confirmed by indirect immunofluorescence assay. Seven-day-old chickens were intramuscularly injected with the plasmids alone or plus commercial attenuated infectious bursal disease (IBD) vaccine or synthetic CpG ODN twice at weekly intervals. Chickens at 5 wk old were orally inoculated with vvIBDV strain 99J1 and observed for 7 days after challenge. Immunization with plasmid plus commercial attenuated IBD vaccine or CpG ODN conferred protection for 70%-80% of chickens, as evidenced by the absence of dinical signs, mortality, and atrophy in the cloacal bursa. About 25%-45% of chickens vaccinated with commercial attenuated IBD vaccine or pcDNA3.1-VP2 or pCI-VP2 plasmid alone had dinical signs and died after challenge. Furthermore, there were significantly different histopathologic lesion scores in the clocal bursae between the pcDNA3.1-VP2 or pCI-VP2 plus CpG or live vaccine and pcDNA3.1-VP2, pCI-VP2, or live vaccine vaccinated group. Enzyme-linked immunosorbent assay antibody titers in chickens vaccinated the constructs DNA plus live vaccine or CpG ODN were significantly higher than in those inoculated with the constructs or the live vaccine alone. These results suggest that coadministration of the constructed plasmid pcDNA3.1-VP2 or pCI-VP2 with CpG ODN or commercial attenuated IBD vaccine could protect chickens efficiently from direct vvIBDV challenge.

Animals↗

PubMedDate not supplied

Global genechip profiling to identify genes responsive to p53-induced growth arrest and apoptosis in human lung carcinoma cells.

To identify critical genes that mediate p53-induced growth arrest and apoptosis at a global level, we profiled a human lung carcinoma cell model in which cells undergo growth arrest and apoptosis in a p53 and DNA damage-dependent manner. Profiling of the Affymetrix human HG-U1333 GeneChip, covering the entire human transcriptome, revealed about 3, 000 unique genes either induced or repressed during p53-induced growth arrest or apoptosis, respectively. A total of 1, 057 genes, including many well-known p53 targets, responded to both conditions. A mini apoptotic protein database was generated from 3, 033 unique apoptosis responsive genes. Analysis of this database yielded 23 proteins with a pro-apoptotic BH3 domain and three with anti-apoptotic BIR2/BIR3 domains, including well-known p53 targets: Bax, Puma, Noxa and survivin. In addition, 14 mitochondrial proteins were identified that contain a pro-apoptotic AVPI-like motif, and 15 proteins were identified that contain a DAVPI-like domain with the potential of being cleaved by caspases during apoptosis to release the AVPI motif. Many of the genes we identified with these domains do contain p53-binding sites either in the promoter or in the first three introns, suggesting a high probability of being direct p53 targets. Pathway analysis revealed that p53 might control the Wnt pathway through transcriptional regulation of some of its components. Thus, global chip profiling coupled with bioinformatics analysis is a powerful tool in identification of genes critical for p53-induced apoptosis. Further characterization of these genes will lead to a better understanding of the mechanism of p53 action and p53 regulation of other signaling pathways. It will also provide novel cancer drug targets for further validation.

Apoptosis↗

PubMedDate not supplied

Color coding cancer cells with fluorescent proteins to visualize in vivo cellular interaction in metastatic colonies.

We report here in vivo visualization of cancer cell interaction using stable sublines of green fluorescent protein (GFP)- and red fluorescent protein (RFP)-expressing HT-1080 human fibrosarcoma cells. These color-coded fibrosarcoma cell lines show similar cell proliferation and lung metastasis potential. The color-coded cells were mixed at a ratio of 1:1 and were injected into the tail vein of severe combined immunodeficient (SCID) mice. The resulting experimental lung metastases were simultaneously imaged and their ratio was determined by color-pixel analysis. Fluorescence color coding of cancer cells enables visualization of the interaction of cancer cells and can be used to distinguish cancer cells of any genotype or phenotype.

Animals↗