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Biomedical subjects

C Hu

Publications and source records attributed to C Hu.

At least 91 records · Page 5Linked to original sources
PubMed1999

[The expression in situ of transforming growth factor beta s, their receptors and TGF beta-receptor interacting protein-1 in nasopharygneal carcinoma].

OBJECTIVE: To study the expression of transforming growth factor(TGF) beta s, their receptors and TGF beta-receptor interacting protein-1 (TRIP-1) in nasopharygneal carcinoma. METHODS: Immunohistochemical technology and in situ hybridization methods were adopted to detect the TRIP-1 mRNA and 3 kinds of TGF beta isoforms and 2 kinds of TGF beta receptors protein in the same biopsy specimen. RESULTS: The positive expression of TGF beta 1, TGF beta 2, TGF beta 3, TGF beta R I and TGF beta R II was stronger in the tumor adjacent epithelium than in the tumor itself, which were 65.79%, 66.67%, 55.26%, 48.57% and 63.16% higher than those in the tumor itself respectively(P < 0.01). The level of TRIP-1mRNA measured in the epithelial cells was also higher than that in the tumor cells (19.32 +/- 10.70 versus 11.96 +/- 5.85, P < 0.05). CONCLUSION: The signal transmission of TGF beta family is diminished in the poorly differentiated squamous cell carcinoma of nasopharynx. It may be a factor for the development of nasopharygneal carcinoma.

Carcinoma, Squamous Cell↗
PubMed1998

Th2-specific protein/DNA interactions at the proximal nuclear factor-AT site contribute to the functional activity of the human IL-4 promoter.

IL-4 is a pleiotropic immunoregulatory cytokine secreted by activated Th2, but not Th1, cells. The proximal IL-4 promoter contains MARE, C/EBP, P0, octamer-like, P1, and activating protein-1 elements. The half c-Maf binding site (MARE), P0, and P1 sites were previously shown to be involved in Th2-specific transcriptional activity. Except the MARE and P1 site, the molecular basis for Th2 specificity of the P0 site has not been analyzed. Here, we provide the first detailed analysis of the P0 binding factors and show that in Th2, but not in Th1, cells, NF-AT and proteins of the activating protein-1 family are involved in cooperative binding to the P0 and the adjacent octamer-like site. In the mouse Th2 D10 cells, Oct-1/Oct-2 are also found to participate in formation of the P0-binding complexes. Mutation, deletion, and methylation interference analysis demonstrate that both the P0 and the octamer-like sequence are required for inducible binding. Furthermore, we provide the first report of the functional relevance of each site in the human IL-4 promoter by mutagenesis/transfection analysis and demonstrate that the octamer-like, P0 and P1 sites are important for the biologic function of the IL-4 promoter. The MARE site, although it was shown to be critical for the function of the murine IL-4 promoter, does not appear essential for human IL-4 promoter activity in Jurkat T cells. These findings suggest that besides c-Maf, another Th2-specific factor(s) may be involved in tissue-specific expression of the IL-4 gene.

Animals↗
PubMed1998

Transforming growth factor-alpha and insulin-like growth factor-I, but not epidermal growth factor, elicit autocrine stimulation of mitogenesis in endometrial cancer cell lines.

OBJECTIVES: Endometrial carcinoma cell lines were evaluated for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factor I (IGF-1) production and for autocrine stimulation. METHODS: Conditioned, serum-free media (CM) from cell lines RL95-2, KLE, HEC, and Ishikawa (ISH) were concentrated radioimmunoassayed (RIA). Samples for the IGF-1 assay were extracted with acid-ethanol to remove IGF-1 binding protein. Polymerase chain reaction (PCR) was used to validate the presence of mRNA for growth factors and receptors. Cells were incubated with Ab528, an antibody blocking EGF receptors, and alphaIR3, an antibody blocking IGF-1 receptors. Proliferation was quantified using [3H]thymidine incorporation. RESULTS: TGF-alpha was detected in CM: RL95-2 (0.4 +/- 0.001 ng/ml), KLE (0.7 +/- 0.003 ng/ml), HEC (0.8 +/- 0.01 ng/ml), ISH (1.2 +/- 0.05 ng/ml). No EGF was detected in CM. In extracted samples, IGF-1 was detected in CM: RL95-2 (0.8 +/- 0. 03 ng/ml), KLE (1.25 +/- 0.02 ng/ml), HEC (1.6 +/- 0.01 ng/ml), ISH (1.6 +/- 0.08 ng/ml). Unconditioned media served as the control. EGF, TGF-alpha, and IGF-1 mRNA was identified in all cell lines, as was the mRNA for EGF and IGF-1 receptors. Incubation with Ab528 or alphaIR3 resulted in significant inhibition of DNA synthesis in HEC 1A, KLE, and ISH. No inhibition was detected in the RL95-2 cell line. A control antibody did not inhibit the cell lines. CONCLUSION: Autocrine production and stimulation of endometrial carcinoma cell lines by TGF-alpha and IGF-1 are demonstrated in three of four endometrial cancer cell lines. No measurable EGF was produced by any of the cell lines.

Autocrine Communication↗
PubMed1998

Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis.

OBJECTIVE: To investigate the role of Bcl-xL in resistance to chemotherapy-induced apoptosis in ovarian carcinoma. METHODS: Two human ovarian carcinoma cell lines were used in this study: A2780 and SKOV3. A2780 cells were transfected with human Bcl-xL or control plasmid alone. Expression of Bcl-xL in single cell clones was analyzed by flow cytometry and protein expression was confirmed by Western blot. For in vitro chemotherapy-induced death assays, cisplatin and Taxol were used. The percentage of apoptotic cells was determined by nuclear propidium iodide staining followed by flow cytometric analysis. Human ascites samples were used to make tumor lysates which were then analyzed for expression of Bcl-xL protein by Western blot. RESULTS: A2780 cells express low levels of endogenous Bcl-xL while SKOV3 cells express high amounts as determined by Western blot. In addition, A2780 cells are sensitive to chemotherapy-induced cell death while SKOV3 cells are resistant. To determine if chemoresistance is mediated by expression of Bcl-xL, A2780 cells were transfected with Bcl-xL or control plasmid. Cells were incubated with either cisplatin or Taxol to induce apoptosis. Bcl-xL-expressing cells were highly resistant to cisplatin and Taxol compared with controls (P < 0.05). All samples of malignant ascites analyzed expressed high levels of Bcl-xL on Western blot. CONCLUSIONS: The results of these studies indicate that Bcl-xL is expressed in ovarian carcinoma, and in A2780 cells functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. This may have prognostic significance; previous studies have demonstrated that patients with breast cancer that overexpress Bcl-2 have low-grade, hormonally responsive tumors. In ovarian carcinoma, another Bcl-2 family member, Bcl-xL may be responsible for modulating resistance to chemotherapy-induced apoptosis.

Antineoplastic Agents↗
PubMed1998

[Innominate osteotomy in the treatment of subluxation of hip in adult].

The symptomatic subluxation of hip is not uncommon in adults, and several kinds of surgical options are available. Twenty-six patients (26 hips) suffering from residual symptomatic subluxation of the hip were treated with innominate osteotomy during 1985 to 1991. The patients were followed-up for 4 to 9 years. The ages of the patients ranged from 22 to 38 years with an average of 26 years and 6 months. The duration of symptoms ranged from 3 to 6 years with an average of 3 years and 5 months. The pertinent prior diseases were the congenital dislocation of hip in 12 cases, Perthes disease in 10 cases, and in the remaining 4 cases, the causes were not identified. The indications for operative intervention were that presence of a reasonable articular cartilaginous space, a reasonable range of motion preserved and particularly a reasnable joint congruity must exist. A new method of re-alignment of the acetabulum was used to placing the ipsilateral foot on the contralateral thigh. The result was evaluated by the symptoms, the function of the hip and the radiographic findings. According to these criteria, the excellent results were obtained in 11 cases and the good result in 15 cases. It was suggested that the innominate osteotomy were also suitable for the treatment of residual symptomatic subluxation of hip in carefully selected adults and the new method of re-alignment of acetabulum was simple and effective.

Acetabulum↗
PubMed1998

[Antitumorigenic immunocompetence of alveolar macrophages in patients with lung cancer].

OBJECTIVE: The antitumorigenic immunocompetence of alveolar macrophages(AMs) in patients with lung cancer was investigated. METHODS: Twenty-two patients with lung cancer and 18 control subjects underwent bronchoalveolar lavage (BAL) by fiberoptic bronchoscopy to collect BAL fluid (BALF). AMs in the BALF isolated by adherence on plate surface were incubated for 24 hours at 5% CO2, 37 degrees C in medium with or without granunocyte-macrophage colony stimulating factor (GM-CSF). The cell free supernatants (SP) and AMs were harvested, respectively, the activities of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD), and soluble interleukin 2 receptor in BALF and SP were examined by copper plating cadmium reduction, radioimmunoassay, xanthine-oxidase assay, and ELISA, respectively. mRNA expression of inducible nitric oxide synthase in AMs was detected by reverse transcription-polymerase chain reaction(RT-PCR). RESULTS: (1) The activity of NO was lower in BALF of the tumor-bearing lungs than that of the nontumor-bearing lungs and control groups; the activities of TNF alpha, SOD, and sIL-2R were not statistically significant in BALF between patients with lung cancer and control groups. (2) In supernatants, the activities of NO and TNF alpha were lower in the tumor-bearing lungs than in nontumor-bearing lungs and control groups; sIL-2R concentration of the lung cancers was higher than that of control groups. (3) After AMs were stimulated by GM-CSF, the activities of NO, TNF alpha, and SOD were increased and that of sIL-2R was decreased in SP. (4) mRNA expression of iNOS was demonstrated in AMs of both groups. However, in comparison with beta-actin, the intensity of mRNA expression of iNOS in AMs of lung cancer patients was lower than that of control groups. CONCLUSION: There are some deficiencies in the function of AM at the region of tumors and antitumorigenic immunocompetence in the patients with lung cancer.

Adult↗
PubMed1998

[A study on the activity of nitric oxide in alveolar macrophages from patients with lung cancer].

Nitrite and nitrate (NO2-/NO2-) in the bronchus alveolar lavage fluid (BALF) and the supernatants of incubated alveolar macrophages (AMs) from patients with primary lung cancer were measured by copper-coated cadmium reduction and Griess method. Mrna expression of AM induced nitric oxide synthase (iNOS) were analyzed by RT-PCR. There was NO2-/NO2- in BALF either from lung cancer patients or from control subjects. When compared with control group and the nontumor-bearing lung, the level of NO2-/NO2-was lower in BALF from the tumor-bearing lung [5.18+/-1.1 vs 2.47+/-0.67nmol x mg protein-1 (P< 0.01); 4.65+/- 2.46 vs 2.47+/- 0.67nmol x mg protein-1(P< 0.01)]. We also found a lower level of NO2-/NO2- in the supernatants of incubated AMs from the lung of cancer patients than from control and nontumor-bearing lung [95.03+/- 21.76 vs 63.37+/- 17.58nmol (P< 0.01); 85.61+/- 16.70 vs 63.37+/- 17.58nmol (P< 0.05)]. No significant difference existed between the MRNA expression of AM iNOS in lung cancer patients (69%) and that of control subjects (91%). After the AMs were stimulated with granulocyte-macrophage colony stimulating factor (GM-CSF), the level of NO2-/NO2- in the supernatants was significantly increased (P< 0.01); while the mRNA expression of AM iNOS from patients with lung cancer resulted in an increase of 16.85+/- 7.58% vs 33.38+/- 8.21% of control group (P< 0.05). These observation suggest that some defects of antitumor function occur in the AMs at the tumor region. GM-CSF can stimulate AMs and thus potentiate their NO activity.

Adenocarcinoma↗
PubMed1998

[Human tongue carcinoma model established in nude mice by orthotopic transplantation and studies on its major biological properties].

OBJECTIVE: To establish clinically relevant animal model of human tongue carcinoma. METHODS: Cell suspensions of human tongue squamous cell carcinoma cell line (Tca8113) were inoculated orthotopically into nude mice and the growing tumors were serially passaged by orthotopic transplantation. The oral cavity, mandible and neck of the nude mice were sectioned and examined histologically. The ultrastructure and chromosome of the tumors were also investigated. RESULTS: 1. The success rate of transplant was 90%. 2. The mouse-growing tumors exhibited the same identical properties as the donor tumor. 3. Human tongue cancer cells could grow in the homologous oral cavity site of nude mice, extended and metastasized to adjacent tissues and lymph node of the neck. CONCLUSION: The model can be useful for evaluating biological behavior and new therapeutics for tongue cancer.

Animals↗
PubMed1998

[Evaluation of penicilloyl proteins of allergic impurity in gene engineering drugs].

It is well known that penicillins are necessary for prevention of contamination during cell culture or fermentation in the production of gene engineering drugs. As penicillins are easily combined with proteins forming allergic impurities, the benzyl penicilloyl proteins in aqueous solution, an evaluation system should be established for control of the gene engineering drugs. An enzyme linked immunosorbent assay (ELISA) with high specificity and high sensitivity in vitro, by which the conjugated penicillins of 0.3 ppm in a sample could be detected and a passive cutaneous anaphylaxis (PCA) test, a classical method for evaluation of allergic reaction in vivo are integral parts of this system. Some domestic gene engineering drugs such as erythropoietin (EPO), G-CSF, GM-CSF and 125SerIL-2 are evaluated with this system. No matter whether the expression products was produced in secretion manner or in inclusion body, it was possible that some residues of allergic impurities may remain in the finished products if an unsuitable process of isolation and purification was used. The maximum absolute content of the conjugated penicillins in a sample was up to about one per thousand.

Animals↗
PubMed1998

[Synthesis and anti-influenza virus activities of heteropoly compounds containing rare earth elements].

Tungstoborate and tungstogermanate heteropoly compounds containing rare earth elements with the general formula K15[Ln(BW11O39)2].nH2O and K13[Ln(GeW11O39)2].nH2O, where Ln = La, Ce, Pr, Nd, Sm, have been synthesized and characterized by elemental analysis, IR, 183W NMR spectra. The results of experiments on cytotoxicity and anti-influenza virus activities using cell-cultivation method showed that four compounds among them exhibited good inhibitory effect on influenza virus.

Animals↗
PubMed1998

The multi-channel VEP topographies in patients with late-stage glaucoma.

PURPOSE: To study the clinical application of multi-channel VEP topographies in patients with late-stage glaucoma. METHODS: The multi-channel checkerboard reversal VEP waves of 25 normal persons and 15 patients with late-stage glaucoma were recorded and analyzed, All patients were examined using Humphrey Field Analyzer. The VEP topographies of multi-channel VEP waves were shown by computer processing system. RESULTS: In normal subjects, the topographies showed symmetric distribution to full-field pattern stimulation. In all patients with late-stage glaucoma, even whose visual field was severely damaged, multi-channel VEP could be recorded, All channels showed simple 'NPN' wave form, N1, N2 waves were not conspicuous, even both were lost, all channels showed the reduced amplitudes of P1 waves, and longer latency. The multi-channel VEP topographies showed irregular distribution, Some showed amplitude asymmetry, other limited or widespread, lateralized. CONCLUSIONS: Despite the severely damaged visual field, the patients with late-stage glaucoma showed special multi-channel VEPs topographies, Multi-channel VEP topographies should be useful in following up patients suffering from late-stage glaucoma and studying visual processing in human brain.

Adolescent↗
PubMed1997

Differential ability of T cell subsets to undergo activation-induced cell death.

Human T cell clones were analyzed for their susceptibility to activation-induced cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD. Analysis of a panel of Th0 clones, characterized by their ability to secrete both Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive (type A) and -resistant (type B) clones. Resistance to AICD by Th2 and Th0-type B clones was not due to lack of expression of either Fas receptor or its ligand. Paradoxically, the AICD-resistant clones were susceptible to apoptosis when Fas receptor was directly ligated by anti-Fas antibodies. However, prior activation of the resistant clones by monoclonal antibodies to CD3/TCR complex induced resistance against Fas-mediated apoptosis. Thus, the Fas-FasL pathway is critical for the induction of AICD in T cells, and moreover this pathway can be negatively regulated in the AICD-resistant clones by signals that are generated from ligation of the CD3/TCR complex.

Antigen-Presenting Cells↗
PubMed1997

Characterization of constitutive and inducible transcription factors binding to the P2 NF-AT site in the human interleukin-4 promoter.

Interleukin-4 (IL-4) is a pleiotropic immunomodulatory cytokine secreted by T helper 2 cells. The IL-4 promoter contains multiple sites with DNA sequences homologous to the IL-2 NF-AT binding site. One of these sites--the P2 site--located between -173 and -150 was previously found to be flanked by two octamer-like motifs. NF-ATp/c and octamer proteins were suggested to bind to this region and to cooperatively activate the promoter activity (Chuvpilo et al., 1993). To precisely analyze the P2-binding factors we used antibodies against NF-ATp, NF-ATc, Fos, Jun, Oct-1 and Oct-2 in EMSA. We show here that nuclear extracts from T-cells form two P2-binding complexes--a PMA/ionomycin-inducible and a constitutive one. The PMA/ionomycin-inducible complex contains NF-ATp/c, Fos and Jun. No octamer binding factors could be detected in either of the two complexes. Analysis of the precise DNA contact points of the two complexes showed that both complexes are formed in the center of the NF-AT consensus site. No DNA contact points could be detected in the octamer-like motif site. Furthermore, purified recombinant POU domains of Oct-1 and Oct-2 failed to bind to the P2 site, suggesting that this site is not an independent octamer-binding site. Therefore, the DNA sequence at -173 to -150 of the IL-4 promoter is a binding site for NF-ATp/c and AP-1. Octamer proteins are unlikely to cooperate with NF-ATp/c at this site.

Cells, Cultured↗
PubMed1997

Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets.

The immunomodulatory cytokine IL-4 affects cells of most hemopoietic lineages. IL-4 is secreted by activated Th2 but not Th1 cells and plays a major role in the immune response by modulating the differentiation of naive Th cells toward the Th2 phenotype. We have previously identified an enhancer element, PRE-I, that is essential for the function of the human IL-4 promoter. To investigate the mechanisms responsible for tissue-specific expression of the IL-4 gene, we analyzed nuclear factors binding to the PRE-I site and compared the binding activities of these factors to the IL-4 promoter of Th1 and Th2 cells. We show that PRE-I interacts with PMA- and PMA/ionomycin-inducible, cyclosporin A-sensitive nuclear factors. Using anti-C/EBPbeta (NF-IL6), anti-C/EBPdelta (NF-IL6beta), anti-NF-ATc, anti-NF-ATp, anti-Fos, and anti-Jun Abs we demonstrate that the previously identified PRE-I binding factor POS-1 is composed of different transcription factors in different Th cell subsets. In the IL-4-producing Th0-like human Jurkat and mouse EL-4 cells, POS-1 (designated POS-1a) contains NF-IL6beta and Jun. In the mouse Th2 D10 cells and in the human Th2 clones, POS-1 (designated POS-1b) contains NF-IL6beta, Jun, and NF-ATc/p. In contrast, POS-1 was not found in nuclear extracts of human Th1 clones. These findings suggest that PRE-I may play a role in the differential regulation of IL-4 gene expression levels.

Animals↗
PubMed1997

What controls tissue-specific expression of the IL-4 gene?

Interleukin-4 (IL-4) plays a central role in the pathogenesis of allergic inflammation by inducing Ig class switch to IgE. IL-4 is also the most potent factor that drives naive T helper (Th) cells to differentiate to the Th2 phenotype. Recently, efforts have been made to explore the molecular basis of the Th2-specific IL-4 expression in CD4 T cells. Transcription factors, such as GATA-3, NF-IL6 and c-Maf, were found to be preferentially expressed in Th2 cells and to play an important role in regulation of the IL-4 promoter activity. Yet, other transcription factors may be indirectly involved in Th2-specific expression of IL-4 even though they are present in both Th1 and Th2 cells. In conclusion, Th2-specific expression of the IL-4 gene appears to be controlled by a multi-factor-system.

Animals↗