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Tao Lu

Publications and source records attributed to Tao Lu.

32 records · Page 2Linked to original sources
PubMed2004

Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells.

The basis of constitutive activation of NF-kappaB, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor beta2 (TGFbeta2), predominantly in its latent form, is secreted by several different types of tumor cell lines that exhibit constitutively active NF-kappaB and that TGFbeta2 potently stimulates the activation of NF-kappaB in reporter cells. Suppression of TGFbeta2 expression by small interfering RNA kills prostate cancer PC3 cells, indicating that the TGFbeta2-NF-kappaB pathway is important for their viability. These findings identify TGFbeta2 as a potential target for therapeutic strategies to inhibit the growth of tumor cells that depend on constitutively active NF-kappaB, or to sensitize them to treatment with cytotoxic drugs.

Apoptosis↗
PubMed2004

Secretion of cytokines and growth factors as a general cause of constitutive NFkappaB activation in cancer.

The constitutive activation of nuclear factor kappaB (NFkappaB) helps a variety of tumors to resist apoptosis and desensitizes them to chemotherapy, but the causes are still largely unknown. We have analysed this phenomenon in eight mutant cell lines derived from human 293 cells, selected for NFkappaB-dependent expression of a marker gene, and also in seven tumor-derived cell lines. Conditioned media from all of these cells stimulated the activation of NFkappaB (up to 30-fold) in indicator cells carrying an NFkappaB-responsive reporter. Therefore, secretion of extracellular factors as the cause of constitutive activation seems to be general. The mRNAs encoding several different cytokines and growth factors were greatly overexpressed in the tumor and mutant cells. The pattern of overexpression was distinct in each cell line, indicating that the phenomenon is complex. Two secreted factors whose roles in the constitutive activation of NFkappaB are not well defined were investigated further as pure proteins: transforming growth factor beta2 (TGFbeta2) and fibroblast growth factor 5 (FGF5) were both highly expressed in some mutant clones and tumor cell lines, each activated NFkappaB alone, and the combination was synergistic. Our data indicate that a group of different factors, expressed at abnormally high levels, can contribute singly and synergistically to the constitutive activation of NFkappaB in all of the mutant and tumor cell lines we studied. Since several NFkappaB target genes encode secreted proteins that induce NFkappaB, autocrine loops are likely to be ubiquitously important in the constitutive activation of NFkappaB in cancer. We provide the first evidence of the general, complex, and synergistic activation of NFkappaB in tumor and mutant cell lines through the action of secreted factors and suggest that the same explanation is likely for the constitutive activation of NFkappaB in cancers.

Cell Line, Tumor↗
PubMed2004

Role of mitochondria in neuron apoptosis during ischemia-reperfusion injury.

To investigate the role of mitochondria in neuronal apoptosis, ischemia-reperfusion mediated neuronal cell injury model was established by depriving of glucose, serum and oxygen in media. DNA fragmentation, cell viability, cytochrome C releasing, caspase3 activity and mitochondrial transmembrane potential were observed after N2a cells suffered the insults. The results showed that N2a cells in ischemic territory exhibited survival damage, classical cell apoptosis change, DNA ladder and activation of caspase3. Apoptosis-related alterations in mitochondrial functions, including release of cytochrome C and depression of mitochondrial transmembrane potential (deltapsim) were testified in N2a cells after mimic ischemia-reperfusion. Moreover, activation of caspase3 occurred following the release of cytochrome C. However, the inhibitor of caspase3, Ac-DEVD-CHO, couldn't completely rescue N2a cells from apoptosis. Administration of cyclosporine A, an inhibitor of mitochondria permeability transition pore only partly inhibited caspase3 activity and reduced DNA damage. Interestingly, treatment of Z-IETD-FMK, an inhibitor of caspase8 could completely reverse DNA fragmentation, but can't completely inhibit caspase3 activity. It was concluded that there were caspase3 dependent and independent cellular apoptosis pathways in N2a cells suffering ischemia-reperfusion insults. Mitochondria dysfunction may early trigger apoptosis and amplify apoptosis signal.

Animals↗
PubMed2004

Application of mechanical dilatation of the pyloric sphincter in esophagectomy for esophageal carcinoma.

The objective of this study was to investigate the effectiveness of additional intraoperative mechanical dilatation of the pyloric sphincter in order to prevent early postoperative gastric retention after esophagectomy using the stomach as substitute for esophageal carcinoma patients. Between October 2001 and May 2002, 32 consecutive esophageal carcinoma patients were treated with esophagectomy combined with additional intraoperative mechanical dilatation of pyloric sphincter (trial group). Another 30 patients underwent esophagectomy without additional intraoperative mechanical dilatation of the pyloric sphincter (control group). Both groups were compared in the following aspects: amount of postoperative GI drainage, time of flatus, intrathoracic gastric fluid retention and other surgical related complications. The amount of GI drainage in the trial group was significantly less than that in the control group (p < 0.05), and time of anal exsufflation was 1 to 2 days. X-ray demonstrated only 0 to 25% of intrathoracic gastric fluid retention and no related complications such as anastomotic leakage, so the patients in the trial group suffered less gastric reflux. Additional intraoperative mechanical dilatation of the pyloric sphincter in radical esophagectomy can accelerate gastric emptying, the recovery of gastric-intestinal function and obviously decrease the occurrence of early postoperative gastric retention and related complications. This method does have the advantages of ease of performance, confirmed effectiveness and safety. It can be utilized in radical esophagectomy through any approach of thoracotomy.

Aged↗
PubMed2004

[Comparison studies on epidermis cell culture efficiency between big graft method and small strip method].

OBJECTIVE: To compare the efficiency of epidermis cell culture between big graft method and small strip method. METHODS: The big graft method was to cut the skin tissue reticularly from dermis layer while the epidermis were not cut off. After it was digested fully in trypsin, the epidermis was separated from skin and was used to culture epidermal cells. The small strip method was routine. The time to cut the skin and to separate the epidermis was recorded, and the number and quality of cells were compared between two methods. RESULTS: It took 8-10 minutes to cut an area of 5 cm2 skin into small strips and 1-2 minutes into big grafts. It took 10-15 minutes to separate the epidermis from the same area skin by small strip method and 2 minutes by big graft method. The cells showed better vigor and its number was more by big grafts than by small strips. The chance of fibroblast contamination was reduced obviously. CONCLUSION: The big graft method is simpler than the small strip method and can culture more epidermis cells with less chance of fibroblast contamination.

Animals↗
PubMed2003

In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with anti-tuberculosis agents.

OBJECTIVES: To examine the effect of first-line and second-line anti-tuberculosis agents on the ability of fluoroquinolones to kill mycobacteria. METHODS: A clinical isolate of Mycobacterium tuberculosis and a laboratory strain of Mycobacterium smegmatis were grown in liquid medium and treated with a fluoroquinolone in the presence or absence of anti-tuberculosis agents. Bacterial survival was determined by viable colony counts on agar medium. RESULTS: When moxifloxacin activity was examined in two-drug combinations containing traditional anti-tuberculosis agents, activity was greater than either compound alone with isoniazid, capreomycin and low, but not high, concentrations of rifampicin. Cycloserine contributed no additional activity, and ethambutol interfered with the lethal action of moxifloxacin and gatifloxacin. Experiments with M. smegmatis confirmed that both rifampicin and ethambutol reduce fluoroquinolone lethality. Moreover, ethambutol increased the recovery of fluoroquinolone-resistant mutants newly created by ethyl methanesulphonate treatment. CONCLUSIONS: The intrinsic bactericidal activity of C-8-methoxy fluoroquinolones can be adversely affected by some agents currently used for treatment of tuberculosis.

Anti-Bacterial Agents↗
PubMed2003

Effect of chloramphenicol, erythromycin, moxifloxacin, penicillin and tetracycline concentration on the recovery of resistant mutants of Mycobacterium smegmatis and Staphylococcus aureus.

The effect of antimicrobial concentration on colony-forming ability of resistant mutant subpopulations of Mycobacterium smegmatis and Staphylococcus aureus was measured for chloramphenicol, erythromycin, moxifloxacin, penicillin and tetracycline. The relationship between drug concentration and the recovery of mutant colonies was distinct for each bacterium-antimicrobial combination; however, in each case application of large numbers of cells to drug-containing agar plates revealed a progressive reduction in mutant recovery as antimicrobial concentration increased. The minimal concentration that allowed no mutant recovery from more than 10(10) input cells was measured to estimate the minimum inhibitory concentration (MIC) of the least susceptible, single-step mutant subpopulation, a parameter also called the mutant prevention concentration (MPC). These data expand the number of antimicrobial-bacterial combinations for which a mutant selection window can be measured.

Anti-Bacterial Agents↗
PubMed2003

Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability.

p53-binding protein-1 (53BP1) is phosphorylated in response to DNA damage and rapidly relocalizes to presumptive sites of DNA damage along with Mre11 and the phosphorylated histone 2A variant, gamma-H2AX. 53BP1 associates with the BRCA1 tumor suppressor, and knock-down experiments with small interfering RNA have revealed a role for the protein in the checkpoint response to DNA damage. By generating mice defective in m53BP1 (m53BP1(tr/tr)), we have created an animal model to further explore its biochemical and genetic roles in vivo. We find that m53BP1(tr/tr) animals are growth-retarded and show various immune deficiencies including a specific reduction in thymus size and T cell count. Consistent with a role in responding to DNA damage, we find that m53BP1(tr/tr) mice are sensitive to ionizing radiation (gamma-IR), and cells from these animals exhibit chromosomal abnormalities consistent with defects in DNA repair. Thus, 53BP1 is a critical element in the DNA damage response and plays an integral role in maintaining genomic stability.

Active Transport, Cell Nucleus↗
PubMed2002

Participation of the conventional calpains in apoptosis.

The conventional calpains, m- and micro-calpain, are suggested to be involved in apoptosis triggered by many different mechanisms. However, it has not been possible to definitively associate calpain function with apoptosis, largely because of the incomplete selectivity of the cell permeable calpain inhibitors used in previous studies. In the present study, Chinese hamster ovary (CHO) cell lines overexpressing micro-calpain or the highly specific calpain inhibitor protein, calpastatin, have been utilized to explore apoptosis signals that are influenced by calpain content. This approach allows unambiguous alteration of calpain activity in cells. Serum depletion, treatment with the endoplasmic reticulum (ER) calcium ATPase inhibitor thapsigargin, and treatment with calcium ionophore A23187 produced apoptosis in CHO cells, which was increased in calpain overexpressing cells and decreased by induced expression of calpastatin. Inhibition of calpain activity protected beta-spectrin, but not alpha-spectrin, from proteolysis. The calpains seemed not to be involved in apoptosis triggered by a number of other treatments. Calpain protected against TNF-alpha induced apoptosis. In contrast to previous studies, we found no evidence that calpains proteolyze I kappa B-alpha in TNF-alpha-stimulated cells. These studies indicate that the conventional calpains participate in some, but not all, apoptotic signaling mechanisms. In most cases, they contributed to apoptosis, but in at least one case, they were protective.

Animals↗
PubMed2002

hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage.

snm1 mutants of Saccharomyces cerevisiae have been shown to be specifically sensitive to DNA interstrand crosslinking agents but not sensitive to monofunctional alkylating agents, UV, or ionizing radiation. Five homologs of SNM1 have been identified in the mammalian genome and are termed SNM1, SNM1B, Artemis, ELAC2, and CPSF73. To explore the functional role of human Snm1 in response to DNA damage, we characterized the cellular distribution and dynamics of human Snm1 before and after exposure to DNA-damaging agents. Human Snm1 was found to localize to the cell nucleus in three distinct patterns. A particular cell showed diffuse nuclear staining, multiple nuclear foci, or one or two larger bodies confined to the nucleus. Upon exposure to ionizing radiation or an interstrand crosslinking agent, the number of cells exhibiting Snm1 bodies was reduced, while the population of cells with foci increased dramatically. Indirect immunofluorescence studies also indicated that the human Snm1 protein colocalized with 53BP1 before and after exposure to ionizing radiation, and a physical interaction was confirmed by coimmunoprecipitation assays. Furthermore, human Snm1 foci formed after ionizing radiation were largely coincident with foci formed by human Mre11 and to a lesser extent with those formed by BRCA1, but not with those formed by human Rad51. Finally, we mapped a region of human Snm1 of approximately 220 amino acids that was sufficient for focus formation when attached to a nuclear localization signal. Our results indicate a novel function for human Snm1 in the cellular response to double-strand breaks formed by ionizing radiation.

BRCA1 Protein↗
PubMed2002

Boundary element analysis of dielectric waveguides.

We apply the boundary element method to the analysis of optical waveguides. After summarizing constant and linear element algorithms for both two- and three-dimensional simulations, we introduce a new recursive series procedure for constructing the diagonal matrix elements. We then demonstrate that our method can be employed to minimize the reflectivity of optical waveguide antireflection coatings with both straight and angled facets.

Journal Article↗
PubMed2002

Phase II clinical trial of N-(4-Hydroxyphenyl)retinamide and tamoxifen administration before definitive surgery for breast neoplasia.

PURPOSE: Surrogate end point biomarkers (SEBs) that can be measured in ductal carcinoma in situ or early-stage invasive cancer are needed to improve the efficiency and reduce the cost of chemoprevention trials. EXPERIMENTAL DESIGN: We conducted a prospective study to develop SEBs for tamoxifen and N-[4-hydroxyphenyl]retinamide by administering either a placebo or both drugs for 2-4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery. The major statistical end point of the study was pre- versus posttreatment change in cell proliferation, as measured by changes in Ki67 labeling indices. In addition, estrogen receptor (ER), HER2/neu, p53, retinoid receptors, and DNA index were measured. RESULTS: Between February 1997 and April 200, 52 patients were registered on the study, and 36 (20 in the placebo arm and 16 in the treatment arm) were available for analysis. No statistically significant pre- versus posttreatment differences in Ki67 labeling index or in the other markers were observed in the treatment arm compared with the placebo arm. There was a trend toward increased treatment response in ER-positive versus ER-negative patients, but this could not be rigorously analyzed because of the low sample size and the unequal distribution of ER-positive patients in the two study arms. CONCLUSION: Future SEB trials for breast carcinoma must (a) incorporate information about patient hormonal status into the study design and (b) resolve problems in patient accrual.

Adult↗
PubMed1997

The Nucleotide Sequence of gltD Gene Encoding the Small Subunit of Rhodobacter sphaeroides Glutamate Synthase.

We have determined the complete nucleotide sequence of a 2 387 bp chromosomal SalI-EcoRI fragment, which contains the structural gene (gltD) for the small subunit of Rhodobacter sphaeroides glutamate synthase, as well as the 5'- and 3'-flanking regions. An open reading frame of 1 242 base pairs was identified as the R. sphaeroides gltD gene. The MW of the small subunit, as deduced from the nucleotide sequence, was estimated to be 44 kD. A comparison of the nucleotide sequence revealed a high similarity among gltD genes of R. sphaeroides, Azospirillum brasilense and Escherichia coli. The deduced amino acid sequence of R. sphaeroides GltD showed a high similarity with that of A. brasilense GltD. The analysis of the binding domains of R. sphaeroides GltD was also carried out. The gltD-lacZ fusion was observed in the presence of 15 mM leucine.

Journal Article↗