Search PubMed⌕ Search

Biomedical subjects

X Cao

Publications and source records attributed to X Cao.

At least 199 records · Page 11Linked to original sources
PubMed1998

Adenovirus-mediated combined suicide gene and interleukin-2 gene therapy for the treatment of established tumor and induction of antitumor immunity.

The antitumor effect of the combined transfer of a suicide gene and a cytokine gene was evaluated in the present study. Adenoviruses expressing Escherichia coli cytosine deaminase (AdCD) and adenoviruses expressing murine interleukin-2 (AdIL-2) were utilized for the treatment of established tumors. The mice were inoculated s.c. with FBL-3 erythroleukemia cells and 3 days later received an intratumoral injection of AdCD in the presence or absence of AdIL-2 followed by intraperitoneal 5-fluorocytosine (5-FC) administration. The results demonstrated that tumor-bearing mice treated with AdCD/5-FC in combination with AdIL-2 showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdCD/5-FC, AdIL-2, adenovirus expressing beta-galactosidase/5-FC or phosphate-buffered saline. The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD4+ and CD8+ T cells infiltrating the tumor after combined therapy. The splenic natural killer and cytotoxic T lymphocyte activities increased significantly in the mice after combined therapy with AdCD/5-FC/AdIL-2. Our results demonstrate that therapy combining a suicide gene and IL-2 gene can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.

Adenoviridae↗
PubMed1998

NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas.

The NM23-H1 gene product has been recently identified as a potential metastasis suppressor. Studies on breast carcinomas have shown an inverse correlation between NM23-H1 status and stage of carcinogenesis and overall survival. However, in colorectal cancer, conflicting data have been reported. This study aimed to investigate whether NM23-H1 immunostaining is correlated with tumour stage, overall survival, disease recurrence, tumour differentiation, age and sex in colorectal carcinomas for the Singapore population using chi-square analysis. The staining was performed on 141 paraffin-embedded surgical specimens collected between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of patients was until time of death or for 5 years. There was a very significant inverse association between tumour staging and NM23-H1 status (P = 0.0004). However, NM23-H1 expression was not significantly correlated to overall 5-year survival, disease recurrence, tumour differentiation, age or sex. Thus, although NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry has no prognostic value in colorectal cancer. This is the first report of a significant inverse association of NM23-H1 status with tumour staging in colorectal cancer which showed no correlation with overall survival or disease recurrence. Our result thus cautions against the practice of equating an inverse relation of genetic markers with tumour staging to survival or disease recurrence.

Adult↗
PubMed1998

B cells inhibit induction of T cell-dependent tumor immunity.

Cytotoxic T lymphocyte (CTL) mediated tumor immunity against major histocompatibility antigen (MHC) class I-positive but class II-negative tumors often requires help from CD4+ T cells. These CD4 cells are activated by MHC class II-positive cells that present tumor derived antigens. Considering that different antigen presenting cells, such as B cells, macrophages and dendritic cells compete for antigen and influence the outcome of an immune response, we analyzed tumor immunity in B cell-deficient mice. These mice appear normal with regard to T cell immunity and tolerance to some pure foreign antigens. We show here that the low immunogenicity of tumors is caused by B cells whose presence in the priming phase results in disabled CD4+ T cell help for CTL mediated tumor immunity. Instead, in the presence of B cells, a non-protective humoral immune response is induced. Our results may explain the enigmatic observation that tumor-reactive antibodies occur frequently in cancer patients.

Adenocarcinoma↗
PubMed1998

Adenovirus-mediated GM-CSF gene and cytosine deaminase gene transfer followed by 5-fluorocytosine administration elicit more potent antitumor response in tumor-bearing mice.

Antitumor effects of combined transfer of suicide and cytokine genes were investigated in this study. Adenovirus harboring E. coli cytosine deaminase gene (AdCD) and adenovirus harboring murine granulocyte-macrophage colony-stimulating factor gene (AdGMCSF) were used simultaneously for in vivo gene transfer in melanoma-bearing mice. Growth inhibition of established tumors and prolongation of survival period were observed more significantly in tumor-bearing mice after transfection with AdGMCSF and AdCD followed by continuous injection of prodrug 5-fluorocytosine (5FC) when compared with mice treated with control adenovirus AdlacZ/5FC, AdCD/5FC or AdGMCSF alone (P < 0.01). After combined therapy the expression of MHC-I (H-2Db) and B7-1 molecules on freshly isolated tumor cells increased greatly and more dendritic cells and CD8+ T cells infiltrated into the tumor mass. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy. Further experiments showed that apoptosis of tumor cells and induction of antitumor immune response might be involved in the mechanisms of the tumor cell killing by the combined therapy. Our results demonstrated that combined transfer of the GM-CSF and CD suicide genes, being able to inhibit the growth of melanoma synergistically and induce specific antitumor immune response efficiently, thus addressing the drawbacks of suicide gene therapy or cytokine gene therapy which were proved to be not satisfactory when used alone, might be of therapeutic potential for gene therapy of cancer.

Adenoviridae↗
PubMed1998

Flow injection on-line photochemical reaction coupled to spectrofluorimetry for the determination of thiamine in pharmaceuticals and serum.

The photochemical reaction of thiamine was studied with a photochemical reactor made by coiling a knotted PTFE reactor around a low-pressure mercury lamp. Acetone, which was previously reported to be a sensitizer for the photochemical reaction that took place in situ in a flow-through cell, severely depressed the fluorescence signal of the photochemical reaction that took place on-line in the knotted PTFE reactor when sodium sulfite was involved in the photochemical reaction. Experiments revealed that the effect of acetone on the photochemical reaction was dependent on the intensity of the irradiation that was used to induce the photochemical reaction, and that acetone might impair the photochemically induced fluorescence if strong UV irradiation was applied to induce the photochemical reaction and sodium sulfite was used to enhance the fluorescence signal. Based on these observations, a flow injection on-line photochemical-spectrofluorimetric method for the determination of thiamine was developed without using acetone. With the proposed method, a detection limit of 0.11 micrograms l-1 thiamine, a relative standard deviation of 0.36% for 11 determinations of 1 mg l-1 thiamine and a sampling frequency of 100 h-1 were achieved. The developed method was successfully applied to the determination of the thiamine content in various pharmaceutical preparations and serum.

Flow Injection Analysis↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor induces the differentiation of murine erythroleukaemia cells into dendritic cells.

Dendritic cells (DC) are professional antigen-presenting cells (APC) within the immune system and antigen-pulsed DC can be used as an effective vaccine for active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the generation of DC. We previously showed that GM-CSF can induce murine erythroleukaemia cells (FBL-3) to differentiate into monocyte-like cells. To develop a new vaccinating method to stimulate the host immune response to leukaemia, we further investigate whether FBL-3 cells induced by GM-CSF can differentiate into DC in the present study. After being treated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC-145, which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and vascular cell adhesion molecule-1 (VCAM-1) was up-regulated markedly; the typical morphology of DC were also observed by electron microscopy. Functionally, the GM-CSF-induced FBL-3 cells could apparently stimulate the proliferation of naive allogeneic and autologous T lymphocytes and induce the generation of specific CTL more efficiently than the wild-type FBL-3 cells. Mice immunized with GM-CSF-induced FBL-3 cells could resist the subsequent challenge with the wild-type FBL-3 cells. Collectively, these data indicate that GM-CSF differentiates murine erythroleukaemia cells into DC phenotypically, morphologically and functionally. FBL-3-derived DC can be used as a new type of vaccine. Our results may have important implications for the immunotherapy of leukaemia.

Adoptive Transfer↗
PubMed1998

Semi-preparative separation and purification of taxol analogs by high-speed countercurrent chromatography.

High-speed countercurrent chromatography (HSCCC) was applied to the semi-preparative separation of taxol and its analogs, such as cephalomannine and 7-epi-10-deacetyltaxol from the extract of the bark of Taxus yunnannesis. The experiments were performed with a quaternary two-phase solvent system composed of n-hexane-thyl acetate-ethanol-water through two steps. In the first step, the four components were separated into two groups at a volume ratio of 1:1:1:1 and, in the second step, two components in each group were separated at different volume ratios of 3:3:2:3 or 4:4:3:4. The present method also allows consecutive injections with reproducible results. HPLC analysis showed that the purity of the four components obtained from a partially purified sample, containing taxol at 10%, ranged from 85 to 99%. The results indicated that HSCCC can be effectively used for the semi-preparative separation and purification of taxol and its analogs.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Augmentation of hematopoiesis by fibroblast-mediated interleukin-6 gene therapy in mice with chemotherapy.

Murine fibroblast NIH3T3 cells engineered to secrete interleukin-6 (NIH3T3-IL-6) were implanted intraperitoneally into mice and observed for their hematopoietic effects with or without 5-fluorouracil (5-FU) administration. In normal mice, the platelet and neutrophil counts in peripheral blood increased significantly after implantation of NIH3T3-IL-6 cells, but the total white blood cell numbers showed no obvious elevation. The granulocyte-macrophage colony-forming unit (CFU-GM) and megakaryocyte colony-forming unit (CFU-MK) numbers formed by stem cells in bone marrow and spleen were also found to be significantly increased after implantation of NIH3T3-IL-6 cells when compared with those in mice after implantation of NIH3T3 cells transduced with neomycin gene (NIH3T3-Neo). To observe the protective effects of NIH3T3-IL-6 cells on hematopoietic depression in chemotherapy-treated mice, the mice were preinjected with 5-FU at a dosage of 150 mg/kg before implantation of NIH3T3-IL-6 cells. The platelet and neutrophil counts showed accelerated recovery after implantation of NIH3T3-IL-6 cells. The numbers of CFU-GM and CFU-MK in bone marrow and spleen were also found to be markedly increased in hematopoietic-depressed mice when compared with those in mice implanted with NIH3T3-Neo cells. These data suggest that fibroblast-mediated IL-6 gene therapy, which can augment hematopoiesis in mice with or without chemotherapy, will be of great help in the recovery from hematopoietic depression after chemotherapy.

3T3 Cells↗
PubMed1998

Intrinsic neural regulation of the heart in the chronic, conscious dog.

The present experiments were performed to examine the capability of the intrinsic cardiac nerves (ICN) to modify cardiac performance in the resting chronic, conscious dog. Control and cardiac-denervated dogs were instrumented for recording of left atrial (LA) and ventricular (LV) contractility, heart rate, and atrioventricular (AV) conduction time. Acetylcholine (ACh) and nicotine (Nic) were administered via an indwelling coronary artery catheter. Limited distribution from the injection site only allowed access to the LA, LV, and AV node. Both beta-blockade with timolol and cardiac denervation were used to separate direct effects of ICN stimulation from indirect (e.g., reflex) effects. ACh produced the expected negative inotropic and dromotropic changes. ICN stimulation with Nic caused large decreases in LA on but only trivial effects on the LV. We concluded that the ICN has limited effects on cardiac performance in the resting animal under minimal sympathetic drive. It is likely, however, that the ICN is capable of significantly depressing cardiac function under conditions of elevated sympathetic tone as would be encountered in exercise.

Acetylcholine↗
PubMed1998

Esculentoside A inhibits tumor necrosis factor, interleukin-1, and interleukin-6 production induced by lipopolysaccharide in mice.

Esculentoside A, a kind of saponin isolated from the root of the Chinese herb Phytolaca esculenta, is reported to possess potent anti-inflammatory effects in acute and chronic experimental models. In the present study, we investigated the effects of esculentoside A on the production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in mice. In vitro experiments demonstrated that esculentoside A (0.1-10 mumol/l) significantly reduced the release of TNF from the peritoneal macrophages derived from mice pretreated with thioglycolate. IL-1 and IL-6 secretion was also obviously inhibited in a concentration-dependent manner by esculentoside A from 0.01 to 10 mumol/l. In vivo experiments demonstrated that detectable TNF was observed 0.25 h after injection, was maximal at 0.5 h, and returned to baseline at 4 h. Maximal production of IL-1 and IL-6 were observed to be 1 and 2 h, respectively, after injection of LPS. Pretreatment of mice with 5, 10, or 20 mg/kg esculentoside A once a day for 7 consecutive days dose-dependently decreased the TNF, IL-1 and IL-6 levels in the sera of mice following LPS challenge. TNF, IL-1, and IL-6 are important cytokines involved in the pathogenesis of inflammatory lesions. Inhibition of inflammatory cytokine production may contribute to the anti-inflammatory effects of esculentoside A.

Animals↗
PubMed1998

Experimental model of renovascular hypertension.

OBJECTIVE: To establish a model of renovascular hypertension. METHODS: A 4/0 resorbable chromic catgut ligature was used to ligate subtotally the renal arteries of 18 dogs, forming experimental renovascular hypertension steadily. Blood pressure, plasma renin activity, the ultrastructural changes of juxtaglomerular apparatus and renal artery wall were studied after the constriction. RESULTS: It was reasonable that renal blood flow measured with an electromagnetic flowmeter was reduced by 30% after the constriction. The pathological changes of the induced renal artery stenosis were similar to those of fibromuscular dysphasia. CONCLUSION: The findings provide valuable evidence for the treatment of renovascular hypertension.

Animals↗
PubMed1998

[Changes of carbohydrate metabolism in normal pregnancy and its relationship with placental lactogen concentrations].

OBJECTIVE: To observe the changes of glucose metabolism and its relationship with human placental lactogen (HPL) in normal pregnant women. METHOD: 94 normal pregnant women had their serum HPL concentration tested and had undergone a 75 g oral glucose tolerance tests (OGTT). Both serum insulin and glucose levels at different time intervals were determined, and the areas under curve (IAUC, GAUC) were caculated, also insulin resistance (IAI) was evaluated. RESULTS: GAUC, IAUC, IAI and HPL are all significantly increased with advance of gestation (P < 0.05). Multiple correlation coefficient study demonstrated that HPL is significantly positively correlated with GAUC, IAUC and IAI(P < 0.001). But when IAUC and IAI were controlled, the relationship between HPL and GAUC was not found. CONCLUSION: There are hyperinsulinemia and insulin resistance during pregnancy, and they are related to HPL. HPL is one of the factors that contributing to carbohydrate metabolism changes during pregnancy.

Adult↗
PubMed1998

[Antitumor effect of combined therapy with adenovirus-mediated CD suicide gene and interleukin 2 gene transfer and its immunological mechanism].

OBJECTIVE: Adenovirus harboring E. coli cytosine deaminase gene(AdCD) and adenovirus harboring interleukin 2 gene (AdIL-2) were used for the combined treatment of established tumors in vivo. METHODS: C57BL/6 mice were inoculated with B16F10 melanoma cells and 3 days later received at the tumor site injections of AdCD and/or AdIL-2 followed by i.p. injection of 5-fluorocytosine (5-Fc) 300 mg/kg per day for 10 days. RESULTS: Mice received combined therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5-Fc, AdIL-2, control adenovirus AdlacZ/5-FC, or PBS. To investigate the immunological mechanism of the antitumor effects of the combined treatment it was found to induce enhanced natural killer cell activity and specific cytotoxic T cell activity. FACS analysis demonstrated that AdIL-2/AdCD/5-Fc therapy increased the expression of H-2Kb and B7-1 on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly. CONCLUSION: Transfer of CD suicide gene plus 5-Fc combined with transfer of IL-2 gene synergistically inhibits the growth of melanoma in mice. Besides the cytotoxic effect of 5-Fc, specific and non-specific antitumor immunity might be responsible for the therapeutic effect. The combined therapy might have therapeutic potentials for human cancer.

Adenoviridae↗
PubMed1998

[Short-and long-term therapeutic effects of brachytherapy on intracavitary residual tumor in 563 nasopharyngeal carcinoma (NPC) patients].

OBJECTIVE: To evaluates the effect of brachytherapy on intracavitary residual tumor in patients with NPC after external radiation therapy. METHODS: Five hundred fifty three NPC patients with residual tumor in the nasopharynx were treated with large dose brachytherapy (20-25 Gy). The treatment results were retrospectively evaluated. RESULTS: Within 3 months after brachytherapy, the overall regression rate of the residual tumor was 90.4%. Upon long-term follow-up, the 1-, 3-, and 5-year survival rate was 89.6%, 67.0% and 55.4%, respectively. The major complications of the after-loading treatment were nasal obstruction (16.2%), necrosis of the naso-pharynx (0.9%) and perforation of soft palate in 2 patients. CONCLUSION: Brachytherapy is effective in the treatment of residual NPC especially in patients in early stage. It may not be helpful for stage IV patients.

Adolescent↗
PubMed1998

[Enhanced antitumor effect of suicide gene therapy by SCF, GM-CSF gene transfer in vivo and its immunological mechanism].

OBJECTIVE: To explore an efficient approach to enhance antitumor effect of suicide gene therapy by improving in vivo antigen presenting function and their immunological mechanisms. METHODS: The CT26 colon adenocarcinoma was treated with CD/5FC system combined with the mGM-CSF or/and mSCF gene transfection, and the antitumor effects were evaluated by the tumor growth, tumor-free mouse rate, splenic CTL activity and cytokine expression of tumor milieu. RESULTS: The tumor burden was reduced significantly and higher survival rate was obtained after the combined treatment. It was found that some cytokines(including mIL-4, mIL-2, mIFN-gamma and mTNF-alpha) were expressed in the tumor milieu after mGM-CSF or/and mSCF gene transfection following CD/5FC treatment but not in the control groups. The cytotoxic activity against CT26 cells of spleen cells of the treated mice was significantly incressed. CONCLUSION: The combination of mSCF or/and mGM-CSF gene transfection enhances the antitumor effect of the suicide gene therapy. Such an enhancement is associated with the induction of specific antitumor immune response and secretion of cytokines in tumor milieu.

Adenocarcinoma↗
PubMed1998

[Antitumor effect of M-CSF and/or IFN-gamma gene cotransfected-macrophages by intratumoral injection].

OBJECTIVE: To investigate the in vivo antitumor effects of M-CSF and/or IFN-gamma gene transfected-macrophages and their related immunological mechanisms. METHODS: Survival time and antitumor effects in vivo of tumor-bearing mice treated with gene-transfected macrophages were observed. NK cell and CTL activity was detected with 4 hr 51Cr release assay, cytotoxicity of macrophages was detected with indirect MTT methods, activity of IL-2, TNF, IFN-gamma were detected by routine methods. RESULTS: 25% of the tumor-bearing mice after treatment with IFN-gamma gene-transfected, M-CSF and IFN-gamma gene co-transfected macrophages survived more than 3 month. The CTL and macrophage activity of the tumor-bearing mice was enhanced. Levels of TNF, IL-2, IFN-gamma in the supernatants of splenocytes induced in vitro were also increased. Histologic analyses of the tumor tissue after treatment with M-CSF and/or IFN-gamma gene-transfected macrophages showed a large amount of lymphocyte infiltration. CONCLUSION: IFN-gamma and M-CSF gene co-transfection into macrophages are proved to enhance their antitumor potential efficiently through direct augmentation of their tumoricidal cytotoxicity and induction of host antitumor immunity.

Animals↗
PubMed1998

[Binding activity of retinoids with recombinant human retinoic acid receptor RAR alpha].

OBJECTIVE: To establish a model for the rapid screening of differentiation-inducing agents. METHODS: Human RAR alpha cDNA was cloned into the PT7-7 plasmids and the human recombinant RAR alpha protein was expressed in Escherichia coli. The ligand-binding activity of the receptor with all-trans retinoic acid was studied by competitive binding assay. For comparison of the binding activity, five retinoids, with different activities and chemical structures, were chosen. The binding of these retinoids to RAR alpha was investigated and compared with the NBT reduction and acid phosphatase activity of HL-60 cells induced by these compounds. RESULTS: The binding activity of these retinoids was well correlated to their ability to induce differentiation of HL-60 cell line. CONCLUSION: This model could be used to screen differentiation-inducing agents.

Acid Phosphatase↗