Biomedical subjects

L Gong

Publications and source records attributed to L Gong.

At least 37 records · Page 2Linked to original sources

PubMed2000

Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins.

Covalent conjugation of proteins by ubiquitin or ubiquitin-like molecules is an important form of post-translational modification and plays a critical role in many cellular processes. Similar to the concept of phosphorylation and dephosphorylation, these conjugates are regulated by a large number of deconjugating enzymes. Here, we report the cloning of a 2,141-base pair DNA fragment from human placenta cDNA library by a strategy that involves expressed sequence tag data base searching, polymerase chain reaction, and rapid amplification of cDNA ends. Nucleotide sequence analysis revealed that the cloned cDNA contains an open reading frame of 1,143 base pairs encoding a novel protease, USP21, which is composed of 381 residues with a calculated molecular mass of 43 kDa. The human USP21 gene is located on chromosome 1q21 and encodes a member of the ubiquitin-specific protease family with highly conserved Cys and His domains. The activity and specificity of USP21 were determined by using a COS cell expression system in vivo. We showed that USP21 is capable of removing ubiquitin from ubiquitinated proteins as expected. Furthermore, USP21 is capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates. As expected from its biochemical activity, overexpression of USP21 has a profound growth inhibitory effect on U2OS cells. Thus, USP21 is the first ubiquitin-specific protease shown to have dual specificity for both ubiquitin and NEDD8 and may play an important role in the regulation of cell growth.

Amino Acid Sequence↗

PubMed2000

Ubiquitin-like proteins: new wines in new bottles.

Ubiquitin is a small polypeptide that covalently modifies other cellular proteins and targets them to the proteasome for degradation. In recent years, ubiquitin-dependent proteolysis has been demonstrated to play a critical role in the regulation of many cellular processes, such as cell cycle progression, cell signaling, and immune recognition. The recent discovery of three new ubiquitin-like proteins, NEDD8, Sentrin/SUMO, and Apg12, has further broadened the horizon of this type of post-translational protein modification. This review will focus on the biology and biochemistry of the Sentrin/SUMO and NEDD8 modification pathways, which are clearly distinct from the ubiquitination pathway and have unique biological functions.

Amino Acid Sequence↗

PubMed2000

Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9.

The basic helix-loop-helix/leucine zipper (bHLH/ZIP) microphthalmia-associated transcription factor (MITF) regulates transcription of genes encoding enzymes essential for melanin biosynthesis in melanocytes and retinal pigmented epithelial cells. To determine how MITF activity is regulated, we used the yeast two-hybrid system to identify proteins expressed by human melanoma cells that interact with MITF. The majority of clones that showed positive interaction with a 158-amino-acid region of MITF containing the bHLH/ZIP domain (aa 168-325) encoded the ubiquitin conjugating enzyme hUBC9. The association of MITF with hUBC9 was further confirmed by an in vitro GST pull-down assay. Although hUBC9 is known to interact preferentially with SENTRIN/SUMO1, in vitro transcription/translation analysis demonstrated greater association of MITF with ubiquitin than with SENTRIN. Importantly, cotransfection of MITF and hUBC9 expression vectors resulted in MITF protein degradation. MITF protein was stabilized by the proteasome inhibitor MG132, indicating the role of the ubiquitin-proteasome system in MITF degradation. Serine 73, which is located in a region rich in proline, glutamic acid, serine, and threonine (PEST), regulates MITF protein stability, since a serine to alanine mutation prevented hUBC9-mediated MITF (S73A) degradation. Furthermore, we identified lysine 201 as a potential ubiquitination site. A lysine to arginine mutation abolished MITF (K201R) degradation by hUBC9 in vivo. Our experiments indicate that by targeting MITF for proteasome degradation, hUBC9 is a critical regulator of melanocyte differentiation.

DNA-Binding Proteins↗

PubMed2000

Identification of a superimmunoglobulin gene family member overexpressed in benign prostatic hyperplasia .

BACKGROUND: Benign prostate hyperplasia (BPH), a nonmalignant disease with an increasing rate of occurrence associated with advancing age, requires auxiliary markers to help identify its presence and distinguish its progression from prostate cancer. METHODS: Hybridoma technology was used to generate an antibody against a BPH antigen, which was subsequently characterized by Western blot analysis, sequence homology, and RT-PCR. RESULTS: A BPH-associated protein, designated P25/26, was identified that showed a strong sequence similarity with superimmunoglobulin family members, overexpressed in BPH, with lower expression observed in both normal and prostate cancer tissues. CONCLUSIONS: Further studies appear warranted to assess the role that this and other superimmunoglobulin family members may have in the pathogenesis of BPH, and to determine if these glycoproteins have any clinical utility in the differential diagnosis or therapeutic monitoring of BPH.

Adult↗

PubMed2000

Differential regulation of sentrinized proteins by a novel sentrin-specific protease.

Sentrin-1, also called SUMO-1, is a protein of 101 residues that is distantly related to ubiquitin and another ubiquitin-like protein, NEDD8. Here we report the cloning of a novel sentrin-specific protease, SENP1, which has no homology to the known de-ubiquitinating enzymes or ubiquitin C-terminal hydrolases. However, SENP1 is distantly related to the yeast Smt3-specific protease, Ulp1. A COS cell expression system was used to demonstrate the activity of SENP1 in vivo. When HA-tagged sentrin-1 was co-expressed with SENP1, the higher molecular weight sentrin-1 conjugates were completely removed. Surprisingly, the major sentrinized band at 90 kDa remained intact. The disappearance of the high molecular weight sentrin-1 conjugates also coincided with an increase in free sentrin-1 monomers. SENP1 is also active against proteins modified by sentrin-2, but not those modified by ubiquitin or NEDD8. In addition, sentrinized PML, a tumor suppressor protein that resides in the nucleus, was selectively affected by SENP1, whereas sentrinized RanGAP1, which is associated with the cytoplasmic fibrils of the nuclear pore complex, remained intact. The inability of SENP1 to process sentrinized RanGAP1 in vivo is most likely due to its nuclear localization because SENP1 is active against sentrinized RanGAP1 in vitro. The identification of a nuclear-localized, sentrin-specific protease will provide a unique tool to study the role of sentrinization in the biological function of PML and in the pathogenesis of acute promyelocytic leukemia.

Amino Acid Sequence↗

PubMed2000

Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group.

BACKGROUND: In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group initiated the placebo-controlled Syst-China trial to investigate whether antihypertensive drug treatment could reduce the incidence of fatal and nonfatal stroke in older Chinese patients with isolated systolic hypertension. OBJECTIVES: To explore (1) whether the benefits of active treatment were evenly distributed across 4 strata, prospectively defined according to sex and previous cardiovascular complications, and (2) whether the morbidity and mortality results were influenced by age, level of systolic or diastolic blood pressure (BP), smoking or drinking habits, or diabetes mellitus at enrollment. METHODS: Eligible patients had to be 60 years or older with a sitting systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg. After stratification for center, sex, and previous cardiovascular complications, 1253 patients were assigned to active treatment starting with nitrendipine (10-40 mg/d), with the possible addition of captopril (12.5-50.0 mg/d), and/or hydrochlorothiazide (12.5-50 mg/d). In the 1141 control patients, matching placebos were used similarly. RESULTS: Male sex, previous cardiovascular complications, older age, higher systolic BP or lower diastolic BP, living in northern China, smoking, and diabetes mellitus significantly and independently increased the risk of 1 or more of the following end points: total or cardiovascular mortality, all fatal and nonfatal cardiovascular end points, all strokes, and all cardiac end points. In the placebo-control group diabetes raised the risk of all end points 2- to 3-fold (P< or =.05). However, active treatment reduced the excess risk associated with diabetes to a nonsignificant level (P values ranging from .12-.86) except for cardiovascular mortality (P = .04). Cox regression with adjustments applied for significant covariates suggested that active treatment may reduce total mortality more (P = .06) in women and stroke more (P = .07) in men and that it may provide better protection against cardiac end points in nonsmokers than smokers (P = .04). Otherwise, the benefits of active treatment were equally manifest, regardless of the enrollment characteristics of the patients, and regardless of whether active treatment consisted of only nitrendipine or of nitrendipine associated with other active drugs. CONCLUSIONS: In elderly Chinese patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improved prognosis. The benefit was particularly evident in diabetic patients; for cardiac end points it tended to be larger in nonsmokers. Otherwise, the benefit of active treatment was not significantly influenced by the characteristics of the patients at enrollment in the trial.

Aged↗

PubMed2000

Dopamine induces cell death, lipid peroxidation and DNA base damage in a catecholaminergic cell line derived from the central nervous system.

Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopamine on cell death, lipid peroxidation and DNA base damage. Dopamine produces cell death in CATH.a cells and this is associated with an increase in annexin binding, which is an early indicator of apoptosis. Incubation of CATH.a cells with deferoximine, an iron chealator, partially antagonizes dopamine-induced cell death. In CATH.a cells, dopamine produces an increase in both lipid peroxidation, as measured by cis-parinaric acid fluorescence, and DNA oxidative base damage, as measured by 8-hydroxy-2'-deoxyguanosine formation. Cell death was inhibited 84-92% by the hydrophilic antioxidants, dithiothreitol, L-cysteine, and N-acetylcysteine. The lipophilic vitamins, retinol and vitamin E and the vitamin E analog, Trolox, inhibited dopamine-induced cell death by 18-33%. The lipophilic antioxidants probucol, propyl glycol and butylated hydroxyanisone had no inhibitory effect on dopamine-induced cell death. These data suggest that damage to DNA and lipids may be partially responsible for dopamine-induced cell death in CATH.a cells.

Journal Article↗

PubMed2000

Reversal of aberrant splicing of beta-thalassaemia allele (IVS-2-654 C-->T) by antisense RNA expression vector in cultured human erythroid cells.

The antisense fragment targeting the aberrant splice sites of the beta-thalassaemia allele, IVS-2-654 C-->T (beta654), pretranscript was cloned into the mammalian expression vector, pcDNA3. The recombinant construct, pCMVA, was then used to repair the defective splicing of the beta654 mutant pretranscript in cultured beta654 erythroid cells by the lipofectin-mediated DNA transfection method. The total RNA was extracted at given time points after transfection and the effect of antisense RNA was studied by reverse transcription polymerase chain reaction (RT-PCR)-mediated mRNA quantitative assay, as well as globin chain microbiosynthesis. The antisense fragment transcribed from pCMVA effectively improved the beta654 splicing pattern in cultured erythroid cells. The level of correctly spliced transcript increased from 0.19 (day 0 after transfection) to 0.58 (day 8) in beta654/beta654 homozygous erythroid cells, and from 0.45 (day 0) to 0.83 (day 8) in beta654/betaA heterozygous erythroid cells, as determined by the ratio of normally spliced beta-globin transcript over total beta-globin transcript. Correspondingly, the ratios of globin chain biosynthesis (beta/alpha) increased from 0.16 (day 0) to 0.52 (day 8) in beta654/beta654 erythroid cells, and from 0.39 (day 0) to 0.84 (day 8) in beta654/betaA erythroid cells. Antisense RNA had no significant effect on the splicing pattern in betaA/betaA erythroid cells. The splicing pattern in transfected cells with pCMVA showed significant changes compared with that in untransfected cells and that in transfected cells with the control antisense fragment (human SRY gene sequence). In addition, we did not observe side-effects on cytological features after the introduction of pCMVA. All these results indicated that the antisense RNA transcribed from the mammalian expression vector pCMVA could efficiently and specifically suppress the aberrant splicing pattern of beta654 mutant pretranscript and restore the correct splicing pathway in vivo, leading to the improvement of globin chain biosynthesis in thalassaemic cells.

Adult↗

PubMed2000

Modified lactone/carboxylate salt equilibria in vivo by liposomal delivery of 9-nitro-camptothecin.

The lactone stability of camptothecins is critical for their anticancer activity. A stable liposomal 9-nitro-camptothecin formulation was developed to circumvent the drawbacks of low aqueous solubility and lactone instability and to provide sustained release of the agent in blood circulation. The potential merits of the formulation were demonstrated by its profoundly improved lactone stability in vivo, favorable pharmacokinetic and biodistribution characteristics in rats, and enhanced preclinical efficacy in tumor-bearing athymic mice.

Animals↗

PubMed2000

Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York.

To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out.

Adipose Tissue↗

PubMed2000

Soluble cell adhesion molecules in patients with acute coronary syndrome.

OBJECTIVE: To observe the changes in serum soluble intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), E-selectin and von Willebrand factor (vWf) in patients with acute coronary syndrome. METHODS: Serial venous blood samples were taken from 21 patients with acute myocardial infarction (AMI) before and 4, 8, 12, 24, 48 and 72 h after thrombolytic treatment or direct PTCA. One blood sample was drawn from 16 patients with unstable angina and 16 control subjects. Serum concentrations of ICAM-1, VCAM-1, E-selectin and vWf were determined using a double antibody sandwich enzyme-linked immunosorbent assay. RESULTS: Serum levels of ICAM-1, VCAM-1, E-selectin and vWf were higher in patients with acute coronary syndrome than in controls. Patients with AMI and successful reperfusion therapy had a significant reduction in the serum concentration of ICAM-1 and E-selectin at 24 and 48 h, VCAM-1 at 24 and 72 h and vWf at 12, 24, 48 and 72 h, but had peak in serum levels of ICAM-1 and E-selectin at 4 h. The number of diseased coronary arteries was not related to the levels of ICAM-1, VCAM-1 and E-selecin. CONCLUSION: The serum concentration of soluble cell adhesion molecules was elevated significantly in patients with acute coronary syndrome. Successful reperfusion therapy was associated with a reduction in the serum concentrations of soluble cell adhesion molecules in patients with AMI.

Aged↗

PubMed2000

Arg485Lys polymorphism of factor V increases the risk of coronary artery disease in a Chinese population.

OBJECTIVE: To explore the relationship between genetic variation in coagulation factor V and the occurrence of coronary arterial disease (CAD). METHODS: Unrelated 86 patients with CAD and 102 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) to detect variations in the entire twenty-five exons of the factor V gene. RESULTS: Polymorphisms in exon 4 [642 G-->T (Ser156)], exon 10 [1628 G-->A (Arg485Lys)], exon 13 [4070 A-->G (His1299Arg)] and exon 16 [5380 G-->A (Val1736Met)] were documented. The study also identified a novel polymorphism in exon 2 (327 A-->G) which did not result in amino acid residue substitution. The Leiden mutation (Arg506Gln) was not detected in any of our 188 subjects. Among the 5 polymorphisms, the allele frequency of 1628 G-->A was significantly different between CAD patients and controls (0.69 vs 0.81, chi 2 = 6.908, P < 0.01). This is the first report of this finding in a Chinese population. CONCLUSION: 1628 G-->A polymorphism is associated with CAD and it may be a risk factor for CAD morbidity in the Chinese population.

Aged↗

PubMed1999

Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.

NEDD8 is a ubiquitin-like molecule that can be covalently conjugated to a limited number of cellular proteins, such as Cdc53/cullin. We have previously reported that the C terminus of NEDD8 is efficiently processed to expose Gly-76, which is required for conjugation to target proteins. A combination of data base searches and polymerase chain reaction cloning was used to identify a cDNA encoding human UBA3, which is 38% identical to the yeast homologue, 22% identical to human UBA2, and 19% identical to the C-terminal region of human UBE1. The human UBA3 gene is located on chromosome 3p13 and gave rise to a 2.2-kilobase pair transcript that was detected in all tissues. Human UBA3 could be precipitated with glutathione S-transferase (GST)-NEDD8, but not with GST-ubiquitin or GST-sentrin-1. Moreover, human UBA3 could form a beta-mercaptoethanol-sensitive conjugate with NEDD8 in the presence of APP-BP1, a protein with sequence homology to the N-terminal half of ubiquitin-activating enzyme. We have also cloned human UBC12 and demonstrated that it could form a thiol ester linkage with NEDD8 in the presence of the activating enzyme complex. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway should allow for a more detailed study of the role of NEDD8 modification in health and disease.

Amino Acid Sequence↗

PubMed1999

Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex.

Sentrin-1/SUMO-1 is a novel ubiquitin-like protein, which can covalently modify a limited number of cellular proteins. Here we report the identification of the sentrin-activating enzyme complex, which consists of two proteins AOS1 and UBA2. Human AOS1 is homologous to the N-terminal half of E1, whereas human UBA2 is homologous to the C-terminal half of E1. The human UBA2 gene is located on chromosome 19q12. Human UBA2 could form a beta-mercaptoethanol-sensitive conjugate with members of the sentrin family, but not with ubiquitin of NEDD8, in the presence of AOS1. Identification of human UBA2 and AOS1 should allow a more detailed analysis of the enzymology of the activation of ubiquitin-like proteins.

Amino Acid Sequence↗

PubMed1999

Brain-derived and glial cell line-derived neurotrophic factors protect a catecholaminergic cell line from dopamine-induced cell death.

Brain-derived neurotrophic factor (BDNF) promotes the survival of dopaminergic neurons in primary cultures and protects these neurons from the neurotoxic effects of 6-hydroxydopamine. The protective mechanism of BDNF on neurotoxicity was evaluated using CATH.a cells, a clonal catecholaminergic cell line derived from the central nervous system. Dopamine produced a dose-dependent cell death in CATH.a cells. Treatment of CATH.a cells with BDNF or glia cell line-derived neurotrophic factor (GDNF) reduced dopamine-induced cell death by approximately 60-70%. Nerve growth factor, basic fibroblast growth factor, neurotrophin-4/5 and insulin had no protective effect on dopamine-induced cell death. Dopamine decreased the activity of superoxide dismutase and the levels of glutathione in the CATH.a cells and these decreases were reversed by BDNF. In addition, BDNF treatment alone increased superoxide dismutase activity by 108%. These results suggest that BDNF may safeguard CATH.a cells from dopamine-induced cell death by maintaining or enhancing components of the cell, which protect from oxidative stress.

Animals↗

PubMed1999

Proteinchip(R) surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures.

Improving early detection, diagnosis, treatment monitoring and prognosis of cancer will require rapid and high throughput detection, identification, and measurement of multiple biomarkers. In this study, we demonstrate the versatility of the innovative SELDI ProteinChip(R) MS technology for the rapid, reproducible and simultaneous identification of four well-characterized prostate cancer-associated (PCA) biomarkers, prostate specific antigen (free and complexed forms), prostate specific peptide, prostate acid phophatase and prostate specific membrane antigen in cell lysates, serum and seminal plasma. Proteins corresponding to the mass of these biomarkers could readily be captured and detected using either chemically defined or antibody coated ProteinChip(R) arrays. Several (yet to be identified) proteins were found upregulated in cell lysates of pure populations of PCA cells procured by laser capture microdissection (LCM) when compared with mass spectra of normal cell lysates. Coupling LCM with SELDI provides tremendous opportunities to discover and identify the signature proteins associated with each stage of tumor development. Collectively, these observations demonstrate the potential of SELDI for the discovery and simultaneous detection of and clinical assay development for PCA biomarkers in complex biological mixtures.

Journal Article↗

PubMed1999

Reversal of aberrant splicing of beta-thalassemia allele by antisense RNA in vitro and in vivo.

OBJECTIVE: To investigate the reversal of aberrant splicing of beta-thalassemia allele (IVS-2-654 C-->T, beta 654) by antisense RNA in vitro and in vivo. METHODS: The vector expressing antisense RNA which targeted against the aberrant splice sites of beta 654 pre-mRNA was constructed in pcDNA3, and then used to repair the defective splicing of the mutant pre-mRNA in an in vitro transcription and splicing system, as well as in HeLa beta 654 cells and cultured beta 654 erythroid cells by lipid-mediated DNA-transfection method. The effect of the antisense RNA was identified by RT-PCR mediated mRNA quantitative assay as well as globin chain microbiosynthesis. RESULTS: The antisense RNA decreased the aberrant splicing product and restored the correct splicing pattern in vitro and in vivo efficiently. In the in vitro transcription and splicing system, the level of normally spliced mRNA [beta/(beta + beta*)] increased from 0.25 to 0.60. In cultured HeLa beta 654 cells, the level of beta/(beta + beta*) increased from 0.07 to 0.43 on the 15th day after transfection. In cultured beta 654 erythroid cells, the level of mRNA [beta/(beta + beta*)] increased from 0.19 to 0.58 on the 8th day after transfection in beta 654/beta 654 erythroid cells, from 0.02 to 0.38 in beta 654/beta 41-42 erythroid cells, and from 0.45 to 0.83 in beta 654/beta A erythroid cells, respectively. Correspondingly, the ratios of globin chain (beta/alpha) biosynthesis increased from 0.16 to 0.52 on the 8th day after transfection in beta 654/beta 654 erythroid cells, 0.05 to 0.36 in beta 654/beta 41-42 erythroid cells, and 0.42 to 0.81 in beta 654/beta A erythroid cells, respectively. The splicing pattern did not show significant changes as compared to the untreated, as well as to the control antisense fragment. CONCLUSIONS: Antisense RNA transcribed from the expression vector described here could efficiently suppress the aberrant splicing pattern of beta 654 mutant mRNA and restore the correct splicing pathway in vitro and in vivo, leading to the improvement of globin chain biosynthesis in thalassemic cells. Our antisense strategy provides an alternative approach to the gene therapy of beta-thalassemia.

Adolescent↗

PubMed1999

Comparison of some antineoplastic drugs on inhibiting thrombin catalizing fibrinogen clotting in vitro.

OBJECTIVE: To classify the effect of thrombin, the key enzyme which enables fibrinogen to form fibrin (fibrinogen clotting) on the formation of metastasis by comparing the inhibition of some antineoplastic drugs on fibrinogen clotting in vitro. METHODS: Time intervals of different drugs to reach a maximum OD (340 nm) data in fibrinogen solution added with thrombin were used in this work. RESULTS: It was found that L-4-oxalysine (8-40 micrograms/ml) and arabinosyl cytosine (10-50 micrograms/ml) could inhibit the effect of thrombin by extending the fibrinogen clotting time to 100%-150% (P < 0.001) and 61%-100% (P < 0.001) while the other antimetastatic drugs razoxane, probimane, adriamycin, harringtonine homoharringtonine and alpha-anordrin at the treatment concentrations showed no such activity. The positive rate of drugs to thrombin activity was approximately 25%. CONCLUSION: It suggests that L-4-oxalysine and arabinosyl cytosine may even exhibit antimetastatic effect through thrombin-fibrinogen pathway, and thrombin might operate in tumor metastasis for only limited step but crucial to fibrin formation in tumor nodules.

Amino Acids, Dicarboxylic↗