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Biomedical subjects

F Luo

Publications and source records attributed to F Luo.

At least 19 recordsLinked to original sources
PubMed2006

Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma.

MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors.

Animals↗
PubMed2006

K-ras 4A and 4B are co-expressed widely in human tissues, and their ratio is altered in sporadic colorectal cancer.

Ras activating mutations result in constitutive activation of Ras signalling pathways and occur in 30% of human malignancies. K-ras encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in lung, pancreatic and colorectal cancers. Using RT-PCR we examined their expression in normal adult human tissues and addressed whether K-ras splicing is altered in sporadic colorectal cancer by comparing normal colon with colon carcinoma cell lines, and 'matched' tumour and tumour-free colon tissues from the same patient. K-ras 4B was expressed ubiquitously and was the predominant splice variant. K-ras 4A was expressed differentially, with detection in colorectal tumours and cell lines, and normal colon, pancreas and lung--sites where tumours with K-ras activating mutations arise. Both K-ras splice variants were co-expressed by single colon carcinoma cells. The K-ras 4A/4B ratio was significantly reduced in all 6 cell lines examined, including two that lacked K-ras activating mutations, and in 4/9 primary adenocarcinomas. We conclude that K-ras activating mutations do not affect K-ras splicing per se, both isoforms may play a role in neoplastic progression, and altered splicing of either the K-ras proto-oncogene or oncogene, in favour of K-ras 4B, may modulate tumour development.

Adenocarcinoma↗
PubMed2005

Dose and behavioral context dependent inhibition of movement and basal ganglia neural activity by Delta-9-tetrahydrocannabinol during spontaneous and treadmill locomotion tasks in rats.

The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor activities and related basal ganglia neural responses were investigated in rats. A multiple-channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0 mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered walking patterns in treadmill locomotion in that stance time was increased and step number was decreased. In parallel with the behavioral effects, Delta-9-THC treatment inhibited neural activity across all four basal ganglia areas recorded during both motor tests. Further, this inhibition of basal ganglia neural activity was behavioral context-dependent. Greater inhibition was found during resting than during walking periods in the treadmill locomotion test. Delta-9-THC treatment also changed firing patterns in the striatum and globus pallidus. More neurons in these regions discharged in an oscillatory pattern during treadmill walking with Delta-9-THC, and the oscillatory frequency was similar to that of the step cycle. Synchronized firing patterns were found in few basal ganglia neurons in the control condition (approximately 1%). Synchronized firing patterns increased during the treadmill resting phase after Delta-9-THC treatment, but still represented a very small proportion of the total neural population (1.9%). The drug treatment did not change neural responses to the tone cue proceeding treadmill locomotion. This study demonstrates dose-dependent inhibitory effects of cannabinoid injection on motor activity. This effect may be related to the behavioral context-dependent inhibition observed in the basal ganglia system where CB1 receptors are densely distributed.

Action Potentials↗
PubMed2004

Neural responses in multiple basal ganglia regions during spontaneous and treadmill locomotion tasks in rats.

To investigate the role of basal ganglia in locomotion, a multiple-channel, single-unit recording technique was used to record neural activity simultaneously in the dorsal lateral striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) during spontaneous and treadmill locomotion tasks in freely moving rats. Active and quiescent phases appeared alternately in a spontaneous movement session that lasted 60 min. Principal component analysis of the ensemble neural activity from each region revealed a close correlation with spontaneous motor activity. Most of the neurons in these four basal ganglia areas increased their firing rates during the active phase. In the treadmill locomotion task, the firing rates of neurons in all recording areas, especially in the STN, increased significantly during locomotion. In addition, neural responses related to tone cue, initiation and termination of treadmill were observed in a subset of neurons in each basal ganglia region. Detailed video analysis revealed a limb movement related neural firing, predominantly in the STR and the GP, during treadmill walking. However, the proportion of neurons exhibiting limb movement related firing was significantly greater only in the STR. A few neurons in the STR (4.8%) and the GP (3.4%) discharged in an oscillatory pattern during treadmill walking, and the oscillatory frequency was similar to the frequency of the step cycle. This study demonstrates a variety of neural responses in the major basal ganglia regions during spontaneous and forced locomotion. General activation of all major basal ganglia regions during locomotion is more likely to provide a dynamic background for cortical signal processing rather than to directly control precise movements. Implications of these findings in the model of basal ganglia organization are discussed.

Action Potentials↗
PubMed2002

Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand.

PURPOSE: Cantharidin, a natural toxin, is the active substance of mylabris and has antitumor effects in man. Norcantharidin, the demethylated analogue of cantharidin, has been used in the treatment of patients with primary hepatoma and those with leukopenia in China. The present study was designed to investigate whether norcantharidin exerts cytotoxic activity against colorectal cancer cells by inducing apoptosis and to examine the possible mechanism in the phenomenon. METHODS: Inhibition of proliferation of norcantharidin on Colo205, HT-29, and SW480 colorectal cancer cells was determined by the trypan blue dye exclusion test. Apoptosis of norcantharidin-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis, and quantitated by flow cytometry after staining with propidium iodide. Cell cycle and the cell surface expression of the CD95/CD95 ligand were evaluated by flow cytometry. Caspase 8-like protease and protein phosphatase 1 and 2A activities were also analyzed. RESULTS: Treatment with norcantharidin of colorectal cancer cells not only inhibited cell proliferation, but also induced apoptosis. Norcantharidin induced apoptosis mainly in two phases: rapid apoptosis in S-phase cells and delayed apoptosis in G2/M arrested cells. Treatment with norcantharidin resulted in an upregulation of the CD95 receptor and CD95 ligand on the cell surface. Furthermore, stimulation with anti-CD95 monoclonal antibody (mAb) resulted in further induction of apoptosis after treatment with norcantharidin. In addition, the apoptosis-inducing effect of norcantharidin was almost completely inhibited by anti-CD95 ligand mAb. Norcantharidin-treated cells showed the activation of caspase 8. Both zVAD-FMK (a broad range caspase inhibitor) and IETD-FMK (a caspase-8 inhibitor) showed apparent inhibition of the apoptosis-inducing effect. Norcantharidin did not show an inhibitory effect on protein phosphatase. CONCLUSIONS: These results suggest that norcantharidin triggers apoptosis in colorectal cancer cell lines via the activation of the CD95 receptor/ligand system, and that this agent may be useful for developing new therapeutic regimens for the treatment of colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed2001

Neuronal responses in the frontal cortico-basal ganglia system during delayed matching-to-sample task: ensemble recording in freely moving rats.

Electrophysiological recording of single neuron activity has been conducted in rats to investigate the patterns of distributed neuronal responses in the frontal cortico-basal ganglia system that code information during a spatial-delayed matching-to-sample task (DMTSt). Rats were trained to press one of the two retractable levers presented randomly as a sample response. The first valid nose-poke after a delay resulted in the presentation of both levers. Pressing the same lever as the sample lever led to a water reward (match to sample), whereas pressing the lever opposite the sample lever resulted in a time-out (house light turned off). One hundred seventy-one neurons in the medial prefrontal cortex (mPFC), 51 in the dorsal striatum (STR), and 93 in the nucleus accumbens (NAc) were recorded during DMTSt. Different patterns of neuronal responses were observed during different behavioral episodes (sample, delay, and match phases) in all three recording areas. Space-related neuronal responses specific to the side of the lever pressed were more often found in the sample phase than in the match phase in all three areas studied. Neuronal responses specific to either correct or error trials were observed with similar percentages in the mPFC and the NAc, while the incidence of correct/error-coded activity in the STR was lower. Ensemble neuronal activity that coded sample versus match lever presses was observed in three out of five rats in sets of trials with similar speed and trajectory of lever press. The results reveal specific patterns of neural responses in the frontal cortico-basal ganglia system in rats during the DMTSt and suggest the existence of specific neuronal coding for different behavioral events associated with a learned short-term memory process.

Action Potentials↗
PubMed2001

Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen.

Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGF-mediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4(+) T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.

Animals↗
PubMed2001

Role of actin filaments in endothelial cell-cell adhesion and membrane stability under fluid shear stress.

Clostridium botulinum C2 toxin (C2 toxin) and purified ADP-ribosylated-alpha-actin (ADP-r-alpha-actin) cause specific actin depolymerisation in living cells. This effect was used to investigate the actin microfilament system with particular emphasis on cell-cell adhesion and plasma membrane integrity in endothelial cells. C2 toxin caused time- and dose-dependent (15-100 ng/ml) changes in endothelial surface morphology (investigated by atomic force microscopy), intercellular gap formation and cell detachment under shear stress. Low concentrations of C2 toxin (1.5 ng/ml), however, did not induce cell detachment but inhibited shear stress-dependent cell alignment. Gap formation as well as cell loss under shear stress was also observed in cells microinjected with purified ADP-r-alpha-actin. Intercellular gap formation was mediated by increased alpha-catenin solubility (40%) due to actin filament depolymerisation. Disintegration of plasma membranes (measured by LDH release) and cell fragmentation during simultaneous exposure to shear stress and C2 toxin were due to a loss of more than 50% of membrane-associated actin. These data show that small disturbances in actin dynamics inhibit shear stress-dependent cell alignment; that depolymerisation of actin filaments increases the solubility of alpha-catenin, thus resulting in cell dissociation and that actin filaments of the membrane cytoskeleton are required to protect the cells from haemodynamic injury such as shear stress. Together, the study shows a heterogeneous regulation of actin filament dynamics at subcellular locations. Junction-associated actin filaments displayed the highest sensitivity whereas stress fibres were far more stable.

Actin Cytoskeleton↗
PubMed2001

Molecular cloning and characterization of four scorpion K(+)-toxin-like peptides: a new subfamily of venom peptides (alpha-KTx14) and genomic analysis of a member.

Four full-length cDNAs encoding the precursors of four K(+)-toxin-like peptides (named BmKK(1), BmKK(2), BmKK(3) and BmmKK(4), respectively) were first isolated from a venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch. The deduced precursors of BmKK(1), BmKK(2) and BmKK(3) are all made of 54 amino acid residues including a signal peptide of 23 residues, and a mature toxin of 31 residues with three disulfide bridges. The precursor of BmKK(4) is composed of 55 amino acid residues including a signal peptide of 23 residues, a mature toxin of 30 residues cross-linked by three disulfide bridges, and an extra Gly-Lys tail which should be removed in the processing step. The four peptides displayed 24-97% sequence identity with each other, and less than 27% homology with any other scorpion toxins described. However, they shared a common disulfide bridge pattern, which was consistent with that of most short-chain K(+)-toxins, suggesting they represent a new class of scorpion toxins and their target receptors may be a subfamily of K(+) channels. We classified the BmKK toxin subfamily as alpha-KTx14 according to the classification rules. The genomic sequence of BmKK(2) was also cloned and sequenced. It consisted of two exons, disrupted by an intron of 79 bp inserted in the region encoding the C-terminal part of the signal peptide. This structure was very similar to that of other K(+)-toxins described previously.

3' Untranslated Regions↗
PubMed2001

Precursor of a novel scorpion venom peptide (BmKn1) with no disulfide bridge from Buthus martensii Karsch.

A full-length cDNA sequence encoding the precursor of a novel venom peptide (named BmKn1) with no disulfide bridge was first isolated from the venom gland cDNA library of Chinese scorpion Buthus martensii Karsch. The encoded precursor consisted of 70 amino acid residues including two parts: a signal peptide of 23 residues, and a putative mature venom peptide (BmKn1) of 47 residues. The sequence of BmKn1 showed no similarity to those of other scorpion venom peptides. BmKn1 may be the first member of a new venom peptide family from scorpion. Future research will be interesting to unravel further the pharmacological function of this novel scorpion venom peptide.

Amino Acid Sequence↗
PubMed2001

[Anti-tumor immune response against mouse melanoma to xenogeneic vaccination].

OBJECTIVE: To study the inhibition of melanoma growth in mice by vaccination with xenogeneic melanocytes. METHODS: Xenogeneic vaccine was prepared from pig eye melanocytes. It was used before or after B16 melanoma challenge in C57 mice. The size of tumor was monitored. Cytotoxic T lymphocyte (CTL) activity of mouse spleen cells was measured by 51Cr release assay. Antibody response against pig melanocytes and B16 melanoma cells were detected by indirect ELISA. RESULTS: Preventive vaccination resulted in inhibition of tumor growth in 90% of the immunized mice, while therapeutic vaccination inhibited tumor growth in 50% of the treated mice. Specific CTL activity and antibodies in the immunized mice were detected. CONCLUSION: Anti-tumor immune response capable of inhibiting melanoma growth can be induced by xenogeneic melanocyte vaccination.

Animals↗
PubMed2001

[Multivariate analysis of prognosis of patients with stage IE non-Hodgkin's lymphomas of the nasal cavity].

OBJECTIVE: To analyze the factors affecting prognosis of patients with primary non-Hodgkin's lymphomas (NHL) of the nasal cavity. METHODS: From Jan. 1968 to Dec. 1997, a total of 71 patients with stage IE(Ann Arbor staging system, 1971) primary non-Hodgkin's lymphomas of the nasal cavity were treated in the Tumor Hospital of Sun Yat-sen University of Medical Sciences. In 37 of the 71 patients, the lesions were limited in the nasal cavity (limited IE), and in 34, the lesions were locally extended involving the adjacent structures (extended IE) Forty-four patients were treated with radiotherapy and 27 with radiotherapy plus chemotherapy. Survival analysis was done by the Kaplan-Meier method, and multivariate analysis was carried out using Cox proportional hazard model. RESULTS: The 5- and 10-year survival rate was 71.9% and 59.7% respectively in patients who had complete response to radiotherapy. The 5- and 10-year survival rate was both 13.9% in patients who had residual tumors after treatment. The 5- and 10-year survival rate was 69.8% and 56.7% in patients with limited IE lesions, but 40.7% and 35.6% in those with extended IE lesions. The prognosis was better in younger (< 44 years) than in older patients. The 10-year survival rate of patients received radiotherapy alone and those combined with chemotherapy was 52.0% and 75.0% respectively for limited IE as compared to 37.6% and 45.0% for extended IE. B symptoms did not significantly affect clinical outcome. Multivariate analysis showed that the immediate response to radiotherapy, invasion of the primary tumor outside of nasal cavity and patients' age were independent prognostic factors. CONCLUSION: Radiotherapy is the main treatment method for stage IE non-Hodgkin's lymphoma of the nasal cavity. Addition of chemotherapy can improve long-term survival. The local tumor response to radiotherapy, clinical staging and age of patients have significant influence on patients' prognosis.

Adolescent↗
PubMed2001

[Expression of GM-CSF in patients with pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) protein and mRNA in four patients with pulmonary alveolar proteinosis (PAP). METHODS: GM-CSF levels were measured with a commercial ELISA kit. RT-PCR was employed to detect the expression of the GM-CSF mRNA in peripheral blood mononuclear cells (PBMC) and alveolar macrophages. To discover the possible mutations, the entire coding region of the GM-CSF cDNA was sequenced by the Sanger dideoxy-mediated chain termination method. RESULTS: All patients, except for the one with secondary PAP showed no release of GM-CSF either from PBMC or from alveolar macrophages. The expression of the GM-CSF mRNA was normal in all patients, whereas a point mutation at position 382 of the GM-CSF cDNA from "T" to "C" was revealed by cDNA sequencing in one idiopathic PAP patient, which caused a change from isoleucine to threonine in amino acid 117 of the protein. CONCLUSIONS: Decreased GM-CSF production is associated with the pathogenesis of idiopathic PAP. A point mutation of the GM-CSF cDNA may partly contribute to the decreased GM-CSF production.

Adult↗
PubMed2001

[The change of tear secretion and tear film stability in castrated male rabbits].

OBJECTIVE: To evaluate the effect of androgen on tear secretion and tear film stability by observing the changes of ocular surface and tear film in the castrated male rabbit. METHODS: Sixteen male rabbits were selected and randomly divided into the normal control group (8 rabbits) and the castrated group (8 rabbits). Schirmer's tests, tear film break-up time (BUT) and rose bangle (rb) staining were performed on the eyes of two groups at 1, 2, 3, 4 weeks, 2 and 3 months. The Chiron Diagnostics ACS: 180 Automato Chemilluminescence Systems was used to determine the two groups' testosterone level in serum at pre-castrate and post-castrate. Results were analyzed statistically. Lacrimal gland, Harder's gland, conjunctiva, cornea and limbus were removed for observation histopathologically after three months. RESULTS: Both Schirmer's test and break-up time scores were significantly lower in the castrated group compared with the control group. The difference became more and more prominent in the course of observation. Rose bangle staining was positive in the castrated group. Testosterone level in serum was significantly lower in the post-castrate than that in the pre-cartrate. Histopathological observation showed that lacrimal glandular epithelial cells were atrophic and flat, the lumen of gland was enlarged and vesicular mucous in acinus cells disappeared. PAS positive material and conjunctival globlet cells were significantly decreased in the castrated group. Compared with the control group there were no significant morphologic changes in the corneal epithelium and limbal stem cells. CONCLUSIONS: The low level of testosterone in castrated rabbit may contribute to the atrophy and applanation of lacrimal glandular epithelium, disappearance of vesicular mucous in acinar cells and the significant decrease of the number of conjunctival globlet cells. All these can lead to decrease of both the quantity and quality of tear secretion and thus cause the instability of tear film.

Androgens↗
PubMed2001

[Frequency-specific responses of human brain to peripheral transcutaneous electric nerve stimulation: a functional magnetic resonance imaging study].

The purpose of the present investigation was to determine the responses of human brain to transcutaneous electric nerve stimulation (TENS) at different frequencies by functional magnetic resonance imaging (fMRI) examinations covering the whole brain of eleven healthy volunteers. Each subject received TENS at acupoints ST36 and SP6 of the left leg at the frequencies of 2 and 100 Hz. Frequency-specific responses were found in motor-related areas, thalamus, limbic system and associated cortex to stimulation of the two frequencies, while the primary somatosensory areas were activated by both. Therefore, it appears that 2 and 100 Hz TENS act through different neuro-pathways in the central nervous system.

Acupuncture↗
PubMed2001

[Progress in the study of pain by brain imaging].

This review deals with the recent functional brain imaging studies of pain. In summary, the sensory-discriminative component of pain is related with the lateral thalamus, primary and secondary somatosensory area and insular cortices, while the posterior parietal and prefrontal cortices seem to play a role in the cognitive-attentional process of nociceptive information. Different parts of anterior cingulate gyrus are correlated with cognitive and emotional aspects of pain. Brain imaging data obtained from clinical patients suffering from various kinds of pain especially neuropathic pain, were discussed at the end of this article.

Animals↗
PubMed2000

Stress or drug priming induces reinstatement of extinguished conditioned place preference.

To construct a model for the relapse of drug use, we investigated the reinstatement of morphine-induced conditioned place preference (CPP) in rats. After the morphine CPP paradigm was established, rats were left extinguishing for 9 days, then exposed to 15 min of random foot shock or s.c. drug priming with different doses of morphine or amphetamine, respectively. Foot shock or a higher dose (0.25 mg/kg) of both drugs could reinstate the CPP induced by 4 mg/kg of morphine after a 9-day extinction, while a lower dose (0.125 mg/kg) of both drugs had no effect. It is concluded that the CPP extinction-reinstatement paradigm might be used as a model to investigate the mechanism of relapse in addicts.

Amphetamine↗