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Biomedical subjects

F Peng

Publications and source records attributed to F Peng.

At least 19 recordsLinked to original sources

Systemic inhibition of tumor growth by soluble Flk-1 gene therapy combined with cisplatin.

Soluble Flk-1, a soluble vascular endothelial growth factor (VEGF) receptor, is a potent inhibitor of angiogenesis, which could restrain growth and metastasis of some experimental tumors. However, antiangiogenic agents alone cannot eradicate tumor completely, and should be combined with other therapy to enhance their effects. In this study, we evaluated the antitumor activity of the combination therapy in the immunocompetent BALB/c mice bearing H22 hepatoma and Meth A fibrosarcoma, respectively. Mice were treated with either msFlk-1 i.m. at 100 microg/mouse once every 3 days for four times from day 3 after the tumor cell injection, cisplatin cycled twice (2 mg/kg i.p. on days 4 and 11 after the tumor cell inoculation), or both agents together. Tumor growth and survival time were continually observed. Antiangiogenesis in vivo was determined by CD31 immunohistochemistry. Assessment of apoptotic cells and histological analysis was also conducted in tumor tissues. Our results showed that the combination therapy could evidently improve antitumor efficacy, including tumor growth suppression, mice survival prolongation, tumor cell apoptosis augmentation as well as neovascularization inhibition as compared with controls, without serious adverse effects. Our data suggest that the combination of DDP with msFlk-1 is more effective to suppress tumor growth in mice than either agent alone, and this combination regimen showed its potential for future clinical application.

Animals↗

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↗

Clinical application of ipsilateral C7 nerve root transfer for treatment of C5 and C6 avulsion of brachial plexus.

We applied a nerve transfer, using the ipsilateral C7 nerve root to treat the C5 and C6 root avulsion of the brachial plexus. Four patients with C5 and C6 preganglionic injury were operated on with this new technique from 1998-2000. Transfer of the spinal accessory nerve to the suprascapular nerve was simultaneously done in 2 these patients. After a follow-up of 1-2.5 years, the muscle strength of elbow flexors recovered to M4 (Lovett) in all cases, shoulder abduction of >90 degrees with external rotation of 30-40 degrees was gained in two cases, and that of 15-45 degrees with no external rotation in the other two cases. No remarkable impairment was found in all C7-innervated muscles except for decrease of muscle power of 1 grade (Lovett) in the short run. This new technique shows promise as an efficacious and safe treatment for C5 and C6 root avulsion of the brachial plexus. However, it should be applied prudently when incomplete injuries of the lower trunk are involved.

Adult↗

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↗

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↗

Inhibitory effects of gynostemma pentaphyllum on the UV induction of bacteriophage lambda in lysogenic Escherichia coli.

Effects of gynostemma pentaphyllum (GP) on the bacteriophage lambda induced by ultraviolet (UV) irradiation have been studied. The results showed that GP could inhibit the UV induction of bacteriophage lambda in lysogenic cells. The inhibitory effects were dependent on the concentration and the reaction time of GP, and were efficient at 40 to approximately 125 microg ml(-1) for 10 min. The inhibitory rate was higher than 70% when the GP concentration was 50 microg ml(-1). By electron spin resonance (ESR) and spin-trapping techniques, the signals of free radicals were detected in the suspension of the lambda lysogenic bacteria induced by ultraviolet irradiation, but after the addition of GP the signals were decreased. These results indicate that gynostemma pentaphyllum not only is a scavenger of free radicals, but also possesses the biological function of anti-irradiation, and that there is a close relation between the UV irradiation of the bacteriaphage lambda and free radicals.

Bacteriophage lambda↗

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↗

Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.

BACKGROUND & AIMS: This study was designed to characterize [D-F(5)Phe(6)D-Ala(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5-500 microg. kg(-1). h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. METHODS: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. RESULTS: Intravenous BIM26226 potently inhibited gastric lag time (114 +/- 7 vs. 41 +/- 6 minutes [control]) and gastric emptying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 +/- 41 vs. 262 +/- 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t(50%), 35 +/- 4 minutes), which BIM26226 inhibited significantly (t(50%), 64 +/- 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. CONCLUSIONS: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.

Adult↗

Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations.

To investigate the prevalence of the C677T and A1298C single nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in Caucasian and Hispanic populations, EDTA-anticoagulated whole blood specimens were collected from a total of 100 random patients, 50 Caucasians and 50 Hispanics of Puerto Rican dissent. The prevalence of the two MTHFR SNPs was determined by polymerase chain reaction (PCR) mediated restriction fragment length polymorphism analysis. In the Caucasian population, homozygosity for the MTHFR A1298C SNP was detected in 4% (2/50) of the individuals tested, while 42% (21/50) were heterozygous for this SNP. Among Hispanics, 4% (2/50) were homozygous and 38% (19/50) heterozygous for the A1298C SNP. Homozygosity for the C677T MTHFR SNP was detected in 16% (8/50) and 10% (5/50) of Caucasians and Hispanics, respectively. In this study, the frequency of the C677T heterozygotes was very high at 56% (28/50) and 52% (26/50) Caucasians and Hispanics, respectively. C677T and A1298C are common SNPs in the MTHFR gene. The high prevalence of these SNPs in both Caucasian and Hispanic populations demonstrates the possibility of compounding effects of these SNPs in the pathogenesis of human diseases. While subgroups of patients may exhibit some clinical phenotype linked to these SNPs, our analysis demonstrates the need for careful interpretation of SNP data in the context of population screening.

DNA↗

[Anatomical study and clinical application of long head of triceps muscle for reconstruction of shoulder abduction].

OBJECTIVE: To study the morphological character of long head of triceps muscle for clinical application in reconstruction of shoulder abduction. METHODS: Forty-four upper extremities of fixed human adult cadavers were carefully dissected. The origins and the pedicles of blood vessels and nerves of long head of triceps muscle, as well as the maximum available size of the muscles, were measured. Six cases of clinical application of long head of triceps muscle for reconstruction of shoulder abduction were followed up for 3 to 11 months. RESULTS: The origins in the dorsal side of long head of triceps muscle were muscular and the ventral side were tendinous, which was 7.6 to 13.3 cm in length and 1.6 to 3.4 cm in width. The distance from the origin to the neurovascular pedicle was 5.7 to 11.4 cm. The radial nerve, which innervated the muscles, could be dissected for 2.9 to 11.8 cm in length. The blood supplies to the triceps muscle were from humeral artery (43.2%), 1.0 to 6.0 cm in length and 1.6 to 2.4 mm in diameter, and from humeral profundus artery (45.5%), 1.5 to 4.4 cm in length and 0.9 to 2.4 mm in diameter, if the vessel was separated to the humeral artery, the length was 1.5 to 6.3 cm. The neurovascular pedicles were multiple branched. In the 6 cases of clinical application of the triceps muscles, the operated shoulder could abduct from 5 degrees preoperatively (0 degree to 10 degrees) to 77.3 degrees (50 degrees to 90 degrees) postoperatively. CONCLUSION: In accordance to the anatomical character of the triceps muscles, the long head of triceps muscle is a suitable choice for reconstruction of shoulder abduction with optimistic outcomes.

Adolescent↗

[Dominant selecting culture medium of Peucedanum decursivum by orthogonal design].

OBJECTIVE: To select the optimum medium for callus culture of Peucedanum decursivum. METHOD: Orthogonal design was applied in determination of hormonal kinds and concentration, and qualitative analysis of callus was done initially. RESULTS: The MS basic medium with 1 mg/L 2,4-D was the best one; coumarin was detected in callus preliminarily. CONCLUSION: It was effective that orthogonal design applied in screening medium; feasible foundation was offered for Peucedanum decursivum cell culture producing active ingredient.

Apiaceae↗

Effect of copper aspirinate on contraction of isolated rabbit aortic strips.

AIM: To investigate the effect of copper aspirinate on contraction of vascular smooth muscle. METHODS: Isolated rabbit aortic strips, including intact endothelium strips and endothelial cell-denuded aortic strips, were suspended in modified Krebs'solution to determine effects of copper aspirinate on the contraction induced by norepinephrine (NE), KCl, and CaCl2, while CuSO4, aspirin, and vehicle were used as controls. RESULTS: Copper aspirinate possessed antagonistic effect on contraction of rabbit aortic strips induced by NE with an IC50 value of 31 nmol/L, while CuSO4 had much l ess antagonistic effect with an IC50 value of 0.29 micromol/L, and aspirin did not work in the same preparation. No effect of copper aspirinate were found on the contraction induced by KCl and CaCl2. Effects on endothelial cell denuded aortic strips were similar to those in the normal aortic strips. CONCLUSION: Copper aspirinate possessed different effects from aspirin and CuSO4 on vascular smooth muscles. It inhibited contraction induced by NE with an activity stronger than CuSO4 at the same Cu2+ concentration, this action might be due to blockade of the receptor-operated Ca2+ channels, and it might not be linked to the endothelium.

Animals↗

Primary studies on heroin abuse and injury induced by oxidation and lipoperoxidation.

OBJECTIVE: To further reveal serious risks of heroin abuse to human body and clarify grave injuries of oxidation, peroxidation and lipoperoxidation induced by nitric oxide and other free radicals to heroin abusers. METHODS: Determined and compared plasma levels of nitric oxide (P-NO), vitamin C (P-VC), vitamin E (P-VE), beta-carotene (P-beta-CAR), lipoperoxides (P-LPO) and erythrocyte activities of superoxide dismutase (E-SOD), catalase (E-CAT), glutathione peroxidase (E-GSH-Px) and erythrocyte level of lipoperoxides (E-LPO) in 137 cases of heroin abusers (HAs) and 100 cases of healthy volunteers (HVs), used linear regression and correlation, stepwise regression and correlation to analyze correlation among heroin-abusing-duration (HAD), daily-heroin-abusing-quantity (DHAQ) with above determination values in the HAs. RESULTS: Compared with the above average values in the HVs group, the average values of P-NO, P-LPO, E-LPO in the HAs group were significantly increased (P < 0.0001), the average values of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px were significantly decreased (P < 0.0001); the analysis of linear regression and correlation showed that with ascending of the HAD and DHAQ in the HAs, the values of P-NO, P-LPO, E-LPO were gradually increased (P < 0.0001), the values of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT, E-GSH-Px were gradually decreased (P < 0.0001); the analysis of stepwise regression and correlation suggested that the correlation among the HAD, DHAQ with the values of P-NO, P-VC, P-VE was the closest. CONCLUSION: The balance between oxidation and antioxidation in the HAs was seriously destroyed, and the injuries induced by nitric oxide and other free radicals, oxidation, peroxidation and lipoperoxidation reactions to the body of HAs gravely exacerbated. In the abstaining from heroin dependence, therefore, it should consider that sufficient quantum antioxidants such as VC, VE and beta-CAR are dosed to the HAs so as to abate the injuries to their bodies.

Adult↗

The abnormality of glucose transporter in the erythrocyte membrane of Chinese type 2 diabetic patients.

Type 2 diabetes mellitus is characterized by impaired glucose uptake. With a photometric method of recording the erythrocyte suspension absorption during the course of glucose transport across the membranes, we observed that the initial rate of glucose zero-trans entry was decreased significantly in 30 Chinese type 2 diabetic patients as compared to 25 healthy controls. The rate of glucose infinite-cis efflux exhibited no difference between the patients and controls. The measurement of temperature dependence of glucose transport showed that the activation energy for glucose entry was increased in diabetic patients. The inhibitory constant of glucose entry by cytochalasin B (CB) in patients was similar to that of the controls. However, we found that the inhibitory constant was increased significantly in the patient erythrocytes after phloretin treatment. After the erythrocytes were made into stripped white ghosts, the fluorescence quenching experiment was performed. Glucose, CB and phloretin can quench the fluorescence of tryptophan residues in the glucose transporter 1, GLUT1. The abnormality of fluorescence quenching in the erythrocyte membranes of patients was observed. The transfer tendency of tryptophan residues from the hydrophilic environment to the hydrophobic environment was decreased in patient ghosts as binding with glucose, and the opposite tendency appeared as CB and phloretin instead of glucose. We conclude that the decreased in glucose entry in the erythrocyte membranes of diabetic patients was due to the GLUT1 change in structure - mostly the outer domain of the glucose transporter.

Asian People↗

Cloning and characterization of the cDNA sequences of two venom peptides from Chinese scorpion Buthus martensii Karsch (BmK).

From a cDNA library made from venom glands of Chinese scorpions of Buthus martensii Karsch, full-length cDNAs encoding precursors of two venom peptides have been isolated using a cDNA probe synthesized by polymerase chain reaction. Sequence analysis of the cDNAs revealed that one encoded precursor was 85 amino acid residues long including a signal peptide of 19 residues and a mature peptide (named BmK T) of 66 residues, and another encoded precursor was 84 residues long containing the same length signal peptide and a mature peptide (BmK M4 isoform, named BmK M4') of 64 residues. The analysis of amino acid sequence similarity indicated that the BmK T was homologous with both mammalian and insect toxins from BmK scorpion or other scorpions, and the BmK M4' was highly homologous with the members of the mammalian neurotoxin family of BmK, having two point mutations in amino acid residue sequence compared to BmK M4, a natural toxin from BmK.

Animals↗

Cloning and characterization of a cDNA sequence encoding the precursor of a chlorotoxin-like peptide from the Chinese scorpion Buthus martensii Karsch.

A full-length cDNA sequence encoding the precursor of a venom peptide with homology to chlorotoxin (named BmKCT) was isolated from a cDNA library made from the venom glands of the Chinese Scorpion Buthus martensii Karsch. The encoded precursor of BmKCT was 59 amino acid residues long including a signal peptide of 24 residues and a mature toxin of 35 residues with four disulfide bridges. The sequence of BmKCT is similar (68% identities) to that of chlorotoxin isolated from Leiurus quinguestriatus quinquestriatus. BmKCT is the first report of the cDNA sequences encoding four-disulfide-bridged short-chain toxins from Buthus martensuii Karsch so far.

Amino Acid Sequence↗

Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine.

The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.

Amino Acid Sequence↗