Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 145 records · Page 8Linked to original sources

PubMed2000

Laminin inhibits estrogen action in human breast cancer cells.

Breast tumors that lack estrogen responsiveness have a poor prognosis. Despite the critical importance to breast cancer treatment, little is known about the loss of estrogen responsiveness and the development of antiestrogen resistance. We have examined the regulation of estrogen-induced proliferation, estrogen regulation of progesterone receptor (PR) expression, and estrogen signaling pathways in estrogen receptor (ER) positive (MCF-7 and T47D) breast cancer cell lines by specific extracellular matrix proteins (ECM) under serum-free conditions. Estrogen, supplemented with submaximal concentrations of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF), stimulated DNA synthesis of MCF-7 cells 7- to 10-fold and T47D cells 2-fold on collagen I or fibronectin. However, estrogen-induced proliferation was greatly reduced on laminin. In contrast, IGF-I or EGF, alone, stimulated proliferation of MCF-7 and T47D cells on all ECM. Thus, ER+ breast cancer cells were not refractory to mitogens when cultured on laminin. Similarly, estrogen induction of PR occurred on fibronectin or collagen I, but not on laminin. While ER content was similar on all ECM, estrogen stimulation of estrogen response element (ERE)-luciferase activity was significantly lower in MCF-7 cells cultured on laminin. Therefore, changes in ECM composition that occur in breast cancer may alter estrogen-responsiveness and the effectiveness of antiestrogen therapies in ER+ breast cancer cells.

Breast Neoplasms↗

PubMed2000

Potentiation of BCNU anticancer activity by O6-benzylguanine: a study in vitro and in vivo.

O6-Alkylguanine-DNA alkyltransferase (O6-AGT), a constitutively expressed DNA repair protein, removes alkyl groups from the O6-position of guanine in DNA. Tumor cells with high O6-AGT activity are resistant to nitrosoureas and other agents that form toxic O6-alkyl adducts. We evaluated O6-benzylguanine (O6-BG) for its activity to inhibit O6-AGT and potentiate 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in O6-AGT-positive human gastric adenocarcinoma cell line, BGC-823 and its tumor xenograft. The sensitivity of BGC-823 cells to BCNU was increased by pretreatment for 2 hours with 1.5 to 6.0 microg/mL O6-benzylguanine. O6-benzylguanine (0.75-6.0 microg/mL) completely and rapidly suppressed the O6-AGT activity of cells for up to 12 hours. When given i.p. 2 hours before BCNU (25 mg/kg) to animals bearing s.c. tumors, O6-BG (90 mg/kg) produced a growth delay of 38.6 days in human gastric adenocarcinoma xenograft. Furthermore, O6-BG significantly inhibited the O6-AGT activity of tumor tissue and induced evident apoptosis. These results suggest that combination of O6-BG with BCNU may have a significant therapeutic effect in the treatment of mer + tumor.

Alkyl and Aryl Transferases↗

PubMed2000

LFA-1 (CD11a/CD18) triggers hydrogen peroxide production by canine neutrophils.

The respiratory burst of neutrophils stimulated by chemotactic factors is markedly augmented by Mac-1-dependent adhesion such as the interaction of Mac-1 (CD11b/CD18) with intercellular adhesion molecule-1 (ICAM-1; CD54) expressed on the surface of parenchymal cells (e.g., cardiac myocytes). In the current study, we evaluate the hypothesis that lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) can also trigger the respiratory burst in neutrophils. To isolate LFA-1/ICAM-1 interactions from Mac-1/ ICAM-1 interactions, full-length chimeric ICAM-1 was developed and expressed in L cells with domains 1 and 2 from canine ICAM-1 and domains 3-5 from human ICAM-1 (C1,2;H3-5). We have shown that canine neutrophils do not bind to human ICAM-1. We demonstrated that chimeric ICAM-1 C1,2;H3-5 supported only LFA-1-dependent adhesion of canine neutrophils and that such adhesion triggered rapid onset of H2O2 production from canine neutrophils. The following seven experimental conditions distinguished LFA-1-dependent H2O2 production from Mac-1-dependent production: It did not require exogenous chemotactic stimulation; H2O2 release was more rapid, but the amount released was <40% of that mediated by Mac-1 adhesion; it was inhibited by anti-CD11a and anti-ICAM-1 antibodies; in contrast to that mediated by Mac-1, it was not inhibited by anti-CD11b antibody, neutrophil inhibitory factor (NIF), or cytochalasin B or H7. Thus, canine neutrophils seem to be able to utilize two members of the beta2 integrin family to interact with ICAM-1 and signal H2O2 production, with LFA-1 at an early stage without prior chemotactic stimulation and Mac-1 at a later stage requiring chemotactic stimulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Grafting of stomach tissue into the duodenum in F344 rats results in chimeric crypts and tumor development.

Gastric tissue was transplanted from the fundic and pyloric mucosa of 8-week old female F344 rats into the duodenum of males. Autopsy, 12 months after the operation, revealed grafts associated with persistent stones in the duodenum and/or calcification in the tissue. Pepsinogen positive chimeric glands with goblet cells also appeared in the grafts which gave rise to tumors in 18 out of 45 animals (40%). In conclusion, stomach grafts re-differentiate into intestine with goblet cells in the duodenum and this process predisposes to tumor development.

Animals↗

PubMed2000

Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages of MoPn infection. This further confirmed that IL-18 was not essential for host defense against chlamydia infection. CONCLUSIONS: These results suggest that IL-12, rather than IL-18, plays the dominant role in the development of protective immunity against chlamydia lung infection, although both cytokines are involved in the in vivo regulation of IFN-gamma production.

Animals↗

PubMed2000

Effect of ATP-potassium channel opener nicorandil on long-term cardiac preservation.

BACKGROUND: ATP-sensitive potassium channels have been shown to be one of the important protective mechanisms for the ischemic myocardium. The purpose of this study was to evaluate the protective effect of nicorandil, an ATP-sensitive potassium channel opener, on myocardium during 6 hours hypothermic preservation. METHODS: Preserved rat hearts were randomly divided into 4 groups according to cardioplegia and preservation protocols as follows: (1) histidine-tryptophan-ketoglutarate solution (HTK) for both cardioplegic and immersing solutions (group A); (2) nicorandil-added HTK for cardioplegic solution and nicorandil-free HTK for immersing solution (group B); (3) nicorandil-free HTK for cardioplegic solution and nicorandil-added HTK for immersing solution (group C); and (4) nicorandil-added HTK for both cardioplegic and immersing solutions (group D). RESULTS: The recovery of postischemic cardiac function, including left ventricular developed pressure and end-diastolic pressure, was significantly improved in group B and group C as compared with the other groups (p<0.05). Postischemic intracellular calcium concentration was significantly lower in group B and group C than in group A (p<0.05). CONCLUSIONS: We concluded that nicorandil-induced hyperpolarizing arrest could reduce ischemia-derived myocyte injury and inhibit the influx of calcium into the myocytes in long-term cardiac preservation.

Animals↗

PubMed2000

Effects of angiotensin II receptor blockade on hepatic fibrosis in rats.

OBJECTIVE: To investigate the effects of angiotensin II type 1 receptor blockade, losartan, on serum levels of components of extracellular matrix in experimental fibrotic rats. METHODS: Fifty male Spague-Dawley rats were separated into five groups (control, model, and 3 treatment groups). Excepting rats in control group, all rats were given subcutaneous injection of 40% carbon tetrachloride (once every 3 days for 6 weeks). Rats in 3 treatment groups were also given losartan of 10mg/kg, 5mg/kg, 2.5mg/kg daily for 6 weeks via gastrogavage, respectively. At the end of sixth week, all rats were sacrificed. Radioimmunoassay was performed to determine the serum levels of hyaluronic acid (HA), Laminin (LN), procollagen type III (PCIII) and collagen type IV. Van Giesion collagen staining was used to evaluate the extracellular matrix of the liver tissue. RESULTS: Compared with model group, losartan significantly reduced the serum levels of HA [from (911.66 +/- 345.49)microg/L to (425.05 +/- 115.80)microg/L], LN [from (209.87 +/- 91.57)microg/L to (83.56 +/- 22.12)microg/L, PCIII [from (31.82 +/- 6.90)microg/L to (22.78 +/- 8.38)microg/L] and collagen IV [from (54.09 +/- 19.81)microg/L to (30.51 +/- 12.39)microg/L] (P<0.05) and greatly attenuated the degree of liver fibrosis (P<0.05). CONCLUSION: Losartan can markedly reduce the serum levels of LN, HA, PCIII and collagen type IV of fibrotic rats induced by CCl(4) and greatly attenuate the degree of liver fibrosis.

Angiotensin Receptor Antagonists↗

PubMed2000

Detection of interleukin-8 in exudates from normal and inflamed human dental pulp tissues.

OBJECTIVE: The purpose of this study was to investigate the level of IL-8 in exudates clinically obtained from normal and inflamed human dental pulp tissues so as to reveal the possible relationship between IL-8 and pulpitis. METHODS: Samples of 2 microliters of pulpal exudate from each normal or clinically diagnosed as acute or chronic pulpitis teeth was obtained by filter paper strips and IL-8 level was measured by ELISA method. RESULTS: No IL-8 was detected in the samples from normal pulp, but significant amount of IL-8 appeared in inflamed pulp tissues, and the level of IL-8 in exudates of acute stage of pulpitis was higher than that of chronic stage (P < 0.01). CONCLUSIONS: This study demonstrates that IL-8 is produced and accumulated in pulp inflammation and may play a role in the occurrence and development of human pulpitis.

Acute Disease↗

PubMed2000

[Vascular endothelial growth factor expression in placenta from intrauterine growth retardation fetus with abnormal umbilical artery flow velocity waveforms].

OBJECTIVE: To study the relationship between placental vascular endothelial growth factor (VEGF) expression and intrauterine growth retardation (IUGR) with abnormal Umbilical artery flow velocity waveforms (UmA FVWS), and deduce the oxygen content in placental terminal villi. METHODS: The VEGF expression levels in syncytiotrophoblast and stroma cells were determined by sp immunohistochemistry, and were compared between the following 4 groups: abnormal UmA FVWS and IUGR (AVAW), abnormal UmA FVWS and normal birth-weight (AVNW), normal UmA FVWS and IUGR (NVAW), normal UmA FVWS and normal birth-weight (NVNW). Each group included 10 cases. RESULTS: In all the placentae, VEGF was mainly expressed in syncytiotrophoblasts with less immunostaining in stroma cells. The intensity of VEGF immunostaining in stroma cells was similar in the groups studied so far. The VEGF expression in syncytiotrophoblasts was significantly reduced in group AVAW (VEGF positive rate in syncytiotrophoblasts is 13.0%), compared with NVAW (VEGF positive rate in syncytiotrophoblasts is 38.50%; P < 0.01) and NVNW (VEGF positive rate in syncytiotrophoblasts is 39.6%; P < 0.01). There was a negative linear correlation between VEGF positive rate in syncytiotrophoblasts and the values of UmA PI (r = -0.52, P < 0.001), RI (r = -0.43, P < 0.01), S/D (r = -0.40, P < 0.01). CONCLUSIONS: The reduction of VEGF expression levels in syncytiotrophoblasts correlates with abnormal UmA FVWS and IUGR. The reduced expression of VEGF in syncycciotrophoblasts may be responsible for the impaired development of all classes of vessels and villi of the placentas from IUGR with abnormal UmA FVWS. The oxygen content is increased within terminal villi of IUGR with abnormal UmA FVWS.

Adult↗

PubMed2000

[A special software for area and volume measurement and 3D image of skin expander].

OBJECTIVE: A special software for measuring expanded skin area and volume and creating a 3D image of skin expander protrusion has been introduced. METHODS: The 3D coordinates of all the points on the surface were obtained by means of interpolation in computer, according to its base, central horizontal and vertical sections that should be adopted in advance. This software was programmed with C language and performed in Microsoft Windows. RESULTS: The area, volume, and 3D image were acquired according to 3D coordinates. The deviation of the software measurement was less than 4% of actual sizes at most in our reliability demonstration. CONCLUSION: This software, combined with our protocol of conversion from tridimensional surface to a plane reported previously, makes up a preferable scheme in this field.

Adult↗

PubMed2000

Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis.

OBJECTIVES: To study mitogen-activated protein kinase (MAPKs) activation in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL-1 beta, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs. METHODS: Primary cultures of RA FLS were used. Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL-1 beta at various doses, and over different periods. Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL-1 beta. RESULTS: IL-1 beta transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK2, JNK2 and P38) in RA FLS. There was no obvious difference in MAPKs activation among different doses of IL-1 beta (1 IU/ml, 10 IU/ml, 100 IU/ml), but the peak activation of ERK2, JNK2 and P38 took place at 5 min, 15 min and 1 min, respectively, after stimulation with IL-1 beta. The activation of ERK2 was inhibited by genistein, but the inhibitory role on that of JNK and P38 was relatively weak. CONCLUSIONS: During signal transduction of IL-1 beta in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members. PTK had a role in the activation of ERK, but had weak effects on that of JNK and P38.

Arthritis, Rheumatoid↗

PubMed2000

Emodin on hepatic fibrosis in rats.

OBJECTIVE: To investigate effect of emodin on hepatic fibrosis in rats. METHODS: The rat hepatic fibrosis model was induced by the subcutaneous injection of 40% CCl4 (twice a week for 6 weeks) dissolved in olive oil. The emodin-treated rats were treated with low-dose, mediate-dose and high-dose emodin (20, 40 and 80 mg/kg body weight, once a day for 42 days) dissolved in 0.5% sodium carboxymethylcellulose (CMC), except receiving CCl4. Control group received only olive oil and 0.5% CMC. Liver functions were determined by standard procedure. Serum hyaluronic acid and laminin were determined by radioimmunoassay. Liver hydroxyprolines were determined. Histopathological changes were examined by optical microscopy. RESULTS: Compared with model group, the emodin-treated rats showed (1) liver functions were improved, alanine transaminase (ALT) and alkaline phosphatase (AKP) were obviously reduced, and total protein (TP) and albumin (ALB) were significantly increased; (2) serum hyaluronic acid and laminin were markedly reduced; (3) liver hydroxyproline was significantly decreased; (4) the degrees of fibrosis were reduced. The changes of parameters mentioned above were significant (P < 0.05 or P < 0.01). CONCLUSION: Emodin has effect on hepatic fibrosis in rats. The hepatoprotective of emodin may be one of mechanisms for liver fibrosis.

Animals↗

PubMed2000

Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients.

OBJECTIVE: To investigate the role of hepatitis C virus (HCV) in the malignant transformation of bile duct cells. Tissues from 6 Chinese patients and 6 American patients with cholangiocarcinoma were studied. METHODS: RNA was extracted from the selected tumor areas of formalin-fixed, paraffin embedded sections, followed by reverse transcription double polymerase chain reaction (RT-PCR) and Southern blotting. RESULTS: Positive and negative strand HCV RNA sequences were detected in seven out of twelve patients with cholangiocarcinoma. A high positive rate was found in Chinese patients (83%) as compared to US patients (33%). CONCLUSION: Our finding suggests HCV may play a role in the malignant transformation of bile duct cells.

Adult↗

PubMed2000

[Down regulation of HER2/neu expression by adenovirus E1A and its anti-tumor activity].

OBJECTIVE: To study the growth inhibitory and chemo-sensitizing effects of adenovirus E1A gene on HER2/neu-overexpressing tumor cell lines. METHODS: E1A was transfected in vitro and in vivo by adenovirus vector into HER2/neu overexpressing human mammary cancer cell lines MDA-MB-453 and SKBR3 and their growth was monitored. The chemo-sensitizing effect was examined by MTT assay. RESULTS: E1A greatly inhibited growth of HER2/neu-overexpressing tumor and prolonged the survival time of tumor-bearing mice. Western blot and immunohistochemical analysis both showed suppression of p185 protein expression in E1A-transfected HER2/neu overexpressing cancer cell lines. E1A could sensitize HER2/neu-overexpressing human breast cancer cells to Taxotere by repressing HER2/neu expression. CONCLUSION: Adenovirus E1A inhibits tumor growth and sensitizes tumor cells to chemotherapeutic agent via down regulation of HER2/neu expression.

Adenoviridae↗

PubMed2000

[Low-molecular-weight heparin for preventing deep-vein thrombosis after total joint arthroplasty].

OBJECTIVE: To evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) in preventing deep-vein thrombosis (DVT) after total hip and knee replacement (THR, TKR). METHODS: From November 1997 to March 1999, we performed total joint replacement for 47 control patients (34 knees, 28 hips) and for 31 patients (19 knees, 17 hips) who had been given low-molecular-weight heparin for preventing deep-vein thrombosis. All patients received venography of the operated limbs after operation. RESULTS: DVT occurred in 19.4% of the LMWH patients (26.3% in TKR, 11.8% in THR) and the reduction was significant (P < 0.05) compared to the control group (48.4%, 55.9%, 39.3% respectively). The incidence of proximal DVT was also reduced significantly (P < 0.05) from 19.4% of the control group to 2.8% of the LMWH group. CONCLUSION: Low-molecular-weight heparin can significantly reduce the incidence of deep-vein thrombosis after total joint replacement.

Arthroplasty, Replacement, Hip↗

PubMed2000

[Long-term therapeutic effects of extended radical resection and radical resection of cancer of cardia and stomach fundus].

OBJECTIVE: To study the best range of radical resection in the treatment of cancer of the cardia and fundus of stomach. METHODS: 418 patients with cancer of the cardia and fundus of stomach underwent radical resection. Of them 192 were treated by extended radical resection (extended group), and 226 by radical resection (radical group). The 5-year and 10-year survival rates were followed up and compared in the two groups. RESULTS: Analysis failed to demonstrate significant difference between the two operations for TNM stage I and II (P > 0.05). For stage III, however, the 5-year and 10-year survival rates in the extended group increased by 14.2% and 15.9% as compared with those in the radical group (P < 0.05). The two groups survival rates were similar for stage IV (P > 0.05). CONCLUSIONS: To completely clean the lymph nodes of splenic hilus and artery and improve long-term survival rate, extended radical resection including spleen and body and tail of the pancreas should be recommended for stage III patients with cancer of the cardia and fundus of stomach when their serosa was involved or lymph node metastasis took place.

Cardia↗

PubMed2000

[Long-term effect on preoperative ulnaris arterial intubation chemotherapy in treatment of stage III breast cancer].

OBJECTIVE: To evaluate preoperative ulnaris arterial intubation chemotherapy as a step of multidisciplinary treatment of stage III breast cancer. METHODS: 109 patients with stage III breast cancer were studied. 64 patients (group A) were treated by preoperative ulnaris arterial intubation chemotherapy and others (group B) were not. The 5 and 10-year survival rates and disease-free survival rates were analyzed. RESULTS: In patients with stage III breast cancer, the overall response rate of group A was 76.6%, and the response rate to histological study was 89.1%. The 5-year and 10-year survival rates of group A were 64.0% and 47.9% respectively. The disease-free survival rate of group A was 59.4% at 5 years and 43.3% at 10 years. All were higher than the 5-year and 10-year survival rates (31.1%, 21.9%) and the 5-year and 10-year disease-free survival rates (22.2%, 12.5%) of group B (P < 0.05). CONCLUSION: Preoperative ulnaris arterial intubation chemotherapy is an effective measure for the treatment of stage III breast cancer. It can improve the long-term effects on stage III breast cancer and reduce local relapse and distant metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[Reconstruction of hip, knee, and ankle bony fused in non-functional position of ankylosing spondylitis patients].

OBJECTIVE: To evaluate the reconstruction of hip, knee and ankle joints with bony fusion at non-functional positions for patients with severe late-stage ankylosing spondylitis (AS). METHODS: From January 1996 to May 1997, simultaneous ipsilateral total hip, knee and ankle replacement was performed under single anesthesia on 2 patients (3 sides) with multiple joint deformity including bony fusion at non-functional positions. They were followed for 29 months on average. RESULTS: Satisfactory range of motion and function were observed. HSS knee score on average was improved by 45 points and Harris hip score by 37.7 points. There were no wound healing problems or late infection. No aseptic loosening was found. CONCLUSIONS: Simultaneous ipsilateral total hip, knee and ankle replacement not only reduced cost for hospitalization, but also facilitated early rehabilitation. To our knowledge, this is the first report on this type of surgery, named ipsilateral tri-arthroplasty.

Adult↗