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Biomedical subjects

L Qin

Publications and source records attributed to L Qin.

At least 109 records · Page 6Linked to original sources

Dose-related effect of irradiation on circadian rhythm of cellular messengers in neural and immune system of mouse.

OBJECTIVE: To explore toxic effect of gamma-irradiation on circadian rhythms of cAMP and cGMP in signal pathway between the central nuclei and peripheral lymphocyte. METHODS: 60Co gamma-ray of 0.5 Gy and 5.0 Gy was applied to groups of mice at each circadian timepoint of a day. 24 hours after the irradiation, the pineal and suprachiasmatic nuclei (SCN) were removed, and the T lymphocytes in blood were separated by a step-centrifugal and nylon-filter treatment, for measurements of cAMP and cGMP by using the RIA procedure. The results were expressed as circadian rhythms of the cAMP/cGMP ratio derived from the Cosinor analysis. RESULTS: The daily average cAMP/cGMP ratio in cells of SCN, pineal, serum and lymphocyte changed according to the dose of irradiation at which the mice were exposed. The high dose of 5 Gy increased the ratio, and the low dose of 0.5 Gy decreased the ratio. There was a significant difference of cAMP/cGMP levels between the irradiated and the control groups, as well as between CT00:00 and CT12:00 of a day. In addition, the peak phases of the cAMP/cGMP ratio at the low-dose groups appeared in advance from about 2 to 8 hours, whereas those at the high-dose groups were delayed from about 3 to 6 hours in comparison to that of the normal mice. CONCLUSION: Toxic effect of gamma-irradiation on the cAMP/cGMP circadian rhythm in the central nuclei and peripheral lymphocyte could be characterized by a low-dose hormesis.

Animals↗

Surgical treatment of hepatocellular carcinoma and related basic research with special reference to recurrence and metastasis.

OBJECTIVE: To summarize the progress of surgical treatment of hepatocellular carcinoma (HCC) and related basic research at the Liver Cancer Institute of Shanghai Medical University in the recent years, with special reference to recurrence and metastasis. METHODS: Published and unpublished update clinical and experimental data in the above-mentioned areas are summarized. RESULTS: Surgical resection has played an important role in improving prognosis of HCC, the 5-year survival were 63.4% for small HCC resection (n = 806), 39.6% for large HCC resection (n = 1061), 64.7% for cytoreduction (using hepatic artery cannulation and ligation) and sequential resection of initially unresectable HCC (n = 93), 56.0% for cytoreduction using transcatheter arterial chemoembolization (TACE) and followed by resection (n = 65), and 22.4% for hepatic resection with removal of tumor thrombi in portal vein (n = 103). Unfortunately, the 5-year recurrent rate after curative resection of HCC was up to 61.5%, which was mainly a result of intrahepatic "metastasis" and multicentric origin of HCC. Clinically, re-resection of subclinical recurrence yielded 56% of 5-year survival (n = 202); prevention of recurrence by transcatheter arterial chemoembolization (TACE) + Interferon, or LAK/IL-2 therapy have decreased 3-year recurrent rate from 33% to 11%-18%. In experimental aspect, metastatic human HCC model in nude mice (LCI-D20) and HCC cell line with metastatic potential (MHCC97) have been established; studies on HCC invasiveness in the molecular level revealed similar results that reported in other solid cancers, and small HCC showed slightly better biological characteristics as compared with large HCC; microvessel density (MVD) that reflecting angiogenesis adversely correlated with 5-year survival of small HCC; experimental interventions using antisense H-ras, bispecific antibody, BB94, as well as anti-angiogenic agents (TNP470, suramin, CAI, heparin, antisense VEGF, etc.) have been demonstrated to inhibit tumor growth and lung metastasis in nude mice model. CONCLUSIONS: Recurrence and metastasis are the major obstacle to further improve prognosis of HCC, studies should be conducted both in clinical and experimental aspects, "HCC invasiveness" will be the major target to be studied, particularly in the molecular level, and anti-angiogenesis will be one of the important approach.

Angiogenesis Inhibitors↗

[Analysis of bone mineral density and relevant factors in 781 healthy people aged 15 to 50].

OBJECTIVE: To determine further the age to form peak bone mass (PBM) and the factor influencing it and bone mineral density (BMD) and to find an effective way to prevent from osteoporosis in the elderly. METHODS: BMD was measured in 781 people aged 15 to 50 years and relevant factors in lifestyle were investigated. Multivariate regression was used to analyze the relationship between BMD and lifestyles and to identify both risk and benefit factors for osteoporosis. RESULTS: For every ten-kilogram increase in body weight, BMD at varied sites increased by an amount of 0.028 - 0.056 g/cm(2) for males and 0.050 - 0.086 g/cm(2) for females, respectively. During their adolescence for males, for every increase of one grade in physical exercise, BMD at varied sites increased by an amount of 0.034 - 0.078 g/cm(2) in males and BMD at lumbar vertebra in males aged 15 - 24 correlated negatively with their total amount of alcohol drinking, and that at lumbar vertebra and of the whole body increased by about 0.035 g/cm(2) in females, which correlated negatively with their total amount of cigarette smoking. Female BMD at lumbar vertebra correlated reversely with their age of menarche and correlated positively with their average time of breast feeding. CONCLUSION: Increase in physical exercise during puberty could increase PBM for the adolescents and keeping adequate body weight and reducing cigarette smoking and alcohol drinking would benefit for the prevention from age-related osteoporosis.

Absorptiometry, Photon↗

NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ.

Bacteria live in capricious environments, in which they must continuously sense external conditions in order to adjust their shape, motility and physiology. The histidine-aspartate phosphorelay signal-transduction system (also known as the two-component system) is important in cellular adaptation to environmental changes in both prokaryotes and lower eukaryotes. In this system, protein histidine kinases function as sensors and signal transducers. The Escherichia coli osmosensor, EnvZ, is a transmembrane protein with histidine kinase activity in its cytoplasmic region. The cytoplasmic region contains two functional domains: domain A (residues 223-289) contains the conserved histidine residue (H243), a site of autophosphorylation as well as transphosphorylation to the conserved D55 residue of response regulator OmpR, whereas domain B (residues 290-450) encloses several highly conserved regions (G1, G2, F and N boxes) and is able to phosphorylate H243. Here we present the solution structure of domain B, the catalytic core of EnvZ. This core has a novel protein kinase structure, distinct from the serine/threonine/tyrosine kinase fold, with unanticipated similarities to both heatshock protein 90 and DNA gyrase B.

Amino Acid Sequence↗

Cloning of a trans-spliced glyceraldehyde-3-phosphate-dehydrogenase gene from the potato cyst nematode Globodera rostochiensis and expression of its putative promoter region in Caenorhabditis elegans.

Reverse genetics to determine the relative importance of individual pathogenicity factors of the potato cyst nematode Globodera rostochiensis depends, apart from an efficient transformation protocol for this obligatory plant parasite, on the availability of an efficient promoter. PCR-based cloning was used to isolate a cDNA encoding glyceraldehyde-3-phosphate-dehydrogenase (GAPDH, a crucial enzyme in glycolysis and gluconeogenesis; this gene was designated gpd) and its 5'-flanking region. The cDNA includes 1047 nucleotides encoding an open reading frame that shows high homology with GAPDHs from Caenorhabditis elegans and other species. Analysis of the 745 bp 5'-flanking region of the gpd gene showed no homology with a similar region in C. elegans. In this region several eukaryotic promoter elements are present. 5' Rapid amplification of cDNA ends revealed this gene was trans-spliced with a SL1 spliced leader. The 5'-flanking region of the gpd gene was fused to green fluorescent protein reporter gene and microinjected into the gonads of C. elegans. Green fluorescent protein expression, under the transcriptional control of the 5'-flanking region of gpd, was mainly observed in body wall muscles of transgenic animals. This putative promoter region of GAPDH could be a valuable tool to drive gene expression in transgenic G. rostochiensis and other related plant-parasitic nematode species.

Amino Acid Sequence↗

Genomic organization of four beta-1,4-endoglucanase genes in plant-parasitic cyst nematodes and its evolutionary implications.

The genomic organization of genes encoding beta-1,4-endoglucanases (cellulases) from the plant-parasitic cyst nematodes Heterodera glycines and Globodera rostochiensis (HG-eng1, Hg-eng2, GR-eng1, and GR-eng2) was investigated. HG-eng1 and GR-eng1 both contained eight introns and structural domains of 2151 and 2492bp, respectively. HG-eng2 and GR-eng2 both contained seven introns and structural domains of 2324 and 2388bp, respectively. No significant similarity in intron sequence or size was observed between HG-eng1 and HG-eng2, whereas the opposite was true between GR-eng1 and GR-eng2. Intron positions among all four cyst nematode cellulase genes were conserved identically in relation to the predicted amino acid sequence. HG-eng1, GR-eng1, and GR-eng2 had several introns demarcated by 5'-GCellipsisAG-3' in the splice sites, and all four nematode cellulase genes had the polyadenylation and cleavage signal sequence 5'-GAUAAA-3'-both rare occurences in eukaryotic genes. The 5'- flanking regions of each nematode cellulase gene, however, had signature sequences typical of eukaryotic promoter regions, including a TATA box, bHLH-type binding sites, and putative silencer, repressor, and enhancer elements. Database searches and subsequent phylogenetic comparison of the catalytic domain of the nematode cellulases placed the nematode genes in one group, with Family 5, subfamily 2, glycosyl hydrolases from Scotobacteria and Bacilliaceae as the most homologous groups. The overall amino acid sequence identity among the four nematode cellulases was from 71 to 83%, and the amino acid sequence identity to bacterial Family 5 cellulases ranged from 33 to 44%. The eukaryotic organization of the four cyst nematode cellulases suggests that they share a common ancestor, and their strong homology to prokaryotic glycosyl hydrolases may be indicative of an ancient horizontal gene transfer.

3' Untranslated Regions↗

Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2.

Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was identified as a potent inhibitor of hepatocyte growth factor activator (HGF activator). The primary translation product of HAI-2 contains two Kunitz domains. To characterize their function, we introduced a point mutation into the reactive site of each Kunitz domain, and assayed the mutants for their HGF activator inhibitory activity. A point mutation in the COOH-terminal Kunitz domain did not affect the activity of HAI-2, whereas a point mutation in the NH2-terminal Kunitz domain markedly reduced the activity. These results suggest that the NH2-terminal Kunitz domain is mainly responsible for the HGF activator inhibitory activity of HAI-2.

Amino Acid Sequence↗

Tolerance induction by anti-CD2 plus anti-CD3 monoclonal antibodies: evidence for an IL-4 requirement.

Anti-CD2 mAb plus anti-CD3 mAb induce alloantigen specific tolerance. We sought to determine whether Th2 cytokines are involved in the induction of tolerance in this model. Addition of anti-IL-4 mAb or anti-IL-10 mAb to anti-CD2 plus anti-CD3 treatment abrogated tolerance and resulted in graft survivals of 26+/-4 and 25+/-5 days, respectively. Splenocytes from the anti-IL-4 mAb and anti-IL-10 groups had greater proliferation in response to alloantigen than either tolerant or naive groups. Cytokine analysis of MLR supernatants showed increased IL-10 in the tolerant group and increased IFN-gamma in the anti-IL-4 mAb treated group. Donor-specific alloantibody responses in untreated immune animals had a predominantly Th1 (IgG2a) alloantibody response, while the tolerogenic regimen reduced the ratio of IgG2a:IgG1 titers. The addition of anti-IL-4 mAb to the tolerogenic regimen partly restored the Th1-related IgG2a response. Tolerance did not develop in IL-4 knockout animals treated with anti-CD2 plus anti-CD3 (mean graft survival, 27+/-5 days). Restoration of IL-4 to IL-4 knockout animals by gene transfer with plasmid DNA resulted in prolongation of survival to 46+/-7 days, while adoptive transfer of wild-type splenocytes into IL-4 knockout recipients resulted in indefinite graft survival (>60 days) and indefinite survival of second donor-type grafts. IL-10 gene transfer to IL-4 knockout recipients did not prolong graft survival (28+/-4). These results demonstrate that tolerance in this model is mediated at least in part by Th2-type cells that secrete IL-4, promote IL-10 and IgG1 production, and inhibit alloantigen reactivity.

Animals↗

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1.

The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(-3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.

Chromosome Mapping↗

Energetics of two-step binding of a chromophoric reaction product, trans-3-indoleacryloyl-CoA, to medium-chain acyl-coenzyme-A dehydrogenase.

We previously demonstrated that the UV/visible spectrum of a chromophoric ligand, trans-3-indoleacryloyl-coenzyme-A (IACoA), is red-shifted (due to polarization of its carbonyl group) upon binding to pig kidney medium-chain acyl-CoA dehydrogenase (MCAD). The transient kinetic data revealed that the overall binding occurred in two steps. The first (fast) step involved the formation of an MCAD-IACoA collision complex in which the electronic structure of IACoA remained unchanged (the "colorless" complex), followed by a slow isomerization step with a concomitant red-shift in the IACoA spectrum (the "colored" complex) [Johnson, J. K., Wang, Z. X., and Srivastava, D. K. (1992) Biochemistry 31, 10564-10575]. To ascertain the energetics of the above two-step process, we investigated the temperature dependence of the spectral changes, binding constant of the MCAD-IACoA complex, and the rate constants for the conversion between the colorless and colored complexes. The data revealed that as the temperature of the incubation mixture of MCAD and IACoA ([IACoA] >> [MCAD] > Kd) increases from 12 to 35 degrees C, the resultant spectral peak of the MCAD-IACoA complex (lambda max = 417 nm) decreases. However, in this temperature range, the equilibrium constant for the second (isomerization) step remains unaffected. Isothermal titration calorimetric studies for the binding of IACoA to MCAD reveal that the overall binding energy at 25 degrees C (delta G degree = -7.4 kcal/mol) is contributed almost equally by the enthalpic (delta H degree = -3.7 kcal/mol) and entropic (T delta S degree = 3.7 kcal/mol) changes. As the temperature increases, both delta H degree and T delta S degree decrease proportionately, resulting in a strong enthalpy-entropy compensation effect. The temperature dependence of delta H degree yields a delta Cp degree value of -0.24 kcal/mol. The data presented herein throw light on the energetic consequences for the binding of IACoA to MCAD, the apparent similarity between the van't Hoff and calorimetric enthalpies, enthalpic and entropic contributions during the polarization of the carbonyl group of IACoA, and the overall structural-functional features of the enzyme-ligand complex as well as enzyme catalysis.

Acyl Coenzyme A↗

Efficient transfer of genes into murine cardiac grafts by Starburst polyamidoamine dendrimers.

Starburst dendrimer, a structurally defined, spherical macromolecule composed of repeating polyamidoamino subunits, was investigated to augment plasmid-mediated gene transfer efficiency in a murine cardiac transplantation model. The grafts were directly injected with naked pCH110, a plasmid encoding beta-galactosidase (beta-Gal), or pCH110-dendrimer complex, and reporter gene expression determined by X-Gal staining. The grafts injected with pCH110-dendrimer demonstrated widespread and extended beta-Gal expression in both myocytes and the graft infiltrating cells from 7 to 28 days, compared to the grafts injected with naked pCH110 that expressed beta-Gal only in myocytes for less than 14 days. p alphaMHC-vIL-10, as plasmid encoding viral interleukin-10 (vIL-10) under the control of alpha-myosin heavy chain promoter, was able to prolong allograft survival from 13.9 +/- 0.9 days to 21.4 +/- 2.3 days (p < 0.005). When dendrimer G5EDA was used with p alphaMHC-vIL-10, 60-fold less DNA resulted in significant prolongation of graft survival to 38.6 +/- 4.7 days (p < 0.0005). The dose of DNA, the charge ratio of DNA to dendrimer, and the size generation of the dendrimers were all determined to be critical variables for prolongation of allograft survival in this model system. Thus, the use of the Starburst dendrimer dramatically increased the efficiency of plasmid-mediated gene transfer and expression. Production of immunosuppressive cytokines at higher amounts for longer periods of time in a greater expanse of tissue enhanced the immunosuppressive effect and prolonged graft survival further.

Animals↗

Pyridinoline in relation to ultimate stress of the patellar tendon during healing: an animal study.

The ultimate stress of the central one-third of the patellar tendon was studied in a gap wound-healing model in the rat. The specimens were also analyzed for collagen and nonreducible crosslinks, as measured by hydroxyproline and pyridinoline content, respectively. Thirty days after injury, the ultimate stress of the healing patellar tendon was restored to an average of 71% of the control value and remained constant over time. The pyridinoline content of the healing tendon was twice the control value by 30 days after injury and reached a plateau; however, the hydroxyproline content did not change significantly over time. Stepwise regression analysis demonstrated that pyridinoline was a better biochemical marker for ultimate stress than was hydroxyproline. The current study provides insights into the functional behaviour of the healing patellar tendon by establishing the relationship between the two biochemical components and the ultimate stress of the healing patellar tendon. This study also suggests the possibility of using pyridinoline content as an indirect marker of the ultimate stress because in vivo assessment is impossible.

Amino Acids↗

Moloney murine leukemia virus protease expressed in bacteria is enzymatically active.

Replication of Moloney murine leukemia virus requires a readthrough translation mechanism to generate the Gag-Pol polyprotein. One of the final products of this polyprotein is the protease (PR), which is required to generate the mature virion proteins. The assembly of Gag and Gag-Pol polyprotein into a virion followed by activation of the viral protease is necessary to produce a mature, infectious particle. These events are believed to occur near the cell membrane just prior to the budding of the virion. We report here the autoproteolytic activity of the viral PR when a Gag-PR fusion protein is expressed in E. coli. Efficient cleavage at the p12/CA, CA/NC and NC/PR junctions was observed. Thus the Moloney murine leukemia virus PR is capable of cleaving its substrates in the absence of specific host factors.

Endopeptidases↗

Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses.

The gene encoding the immunosuppressive cytokine viral interleukin-10 (vIL-10) was introduced into BALB/c (H-2d) vascularized cardiac allografts by perfusing the graft vasculature with DNA-liposome complexes, utilizing the experimental cationic lipid gamma AP DLRIE/DOPE and a plasmid encoding vIL-10 under the control of the HCMVie promoter. The DNA to lipid ratio and DNA dose were critical factors in obtaining optimal biologic effects. Gene transfer of vIL-10 with a 3:1 DNA to lipid weight ratio using 375 micrograms DNA significantly prolonged allograft survival in MHC-mismatched C57BL/6 (H-2b) recipients (16.00 days) compared with both unmodified allografts (8.14 days) and vIL-10 antisense controls (8.28 days). Enhanced graft survival was specific to vIL-10 expression since treatment with antisense plasmid or anti-vIL-10 monoclonal antibody (mAb) abrogated the effect. Prolonged survival was associated with a novel histology characterized by a moderate mononuclear infiltrate, edema, and diffuse fibrillar/collagen deposition in the interstitium. Despite these morphologic changes, myocytes remained viable and vessels were patent. Limiting dilution analysis revealed transient infiltration of IL-2 secreting, donor-reactive, helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) in vIL-10 expressing grafts on day 7, that decreased significantly by day 14. Similarly, vIL-10 gene transfer inhibited the accumulation of donor-specific HTL and CTL in the spleen, compared with antisense controls. Prolonged survival was also associated with a marked decrease in IgM and IgG alloantibody production, with little to no IgG isotype switching. These results show that viral IL-10 gene transfer inhibits graft rejection in a clinically relevant model by inhibiting donor-specific cellular and humoral immune responses.

Animals↗

Hierarchical and co-operative binding of OmpR to a fusion construct containing the ompC and ompF upstream regulatory sequences of Escherichia coli.

BACKGROUND: OmpR is a transcription factor that regulates the expression of the porin genes ompF and ompC in Escherichia coli. The phosphorylation state of OmpR, directed by the osmosensor EnvZ, determines its ability to bind to the upstream regulatory regions of these genes, a total of 14 phospho-OmpR binding sites. While it has been possible to study the stoichiometry and hierarchy of the OmpR-DNA interaction in the upstream regions of ompF and ompC, their disunited location on the bacterial chromosome has made it difficult to compare the individual binding affinities of respective sites. RESULTS: Using 1,10-phenanthroline-Cu+ footprinting on a fused construct containing both the ompF and ompC upstream regulatory sequences, and gel shift experiments on oligomers corresponding to individual sites, we have established a comparative hierarchy for OmpR binding, as F1, C1 > F2, F3 > C2 > C3. In addition, the binding patterns reveal an apparent co-operative relationship between OmpR molecules bound at several upstream motifs. Densitometric analyses of the footprinted regions provide support for these observations. Mutational analysis of this construct reveals that the alteration of a conserved cytidine in the F1 motif (-86) causes a loss of OmpR affinity and disrupts hierarchical OmpR-binding in the entire ompF region. CONCLUSIONS: The present results provide a unique view of the OmpR interaction with the two respective promoters, ompF and ompC, and an insight into the question of how the expression of ompF and ompC are reciprocally regulated by medium osmolarity.

Bacterial Proteins↗

Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures. Consequences for prophylaxis and treatment.

The importance of serial examinations over time with peripheral quantitative computed tomography (pQCT) is that they enable the detection of patients at high risk of osteoporosis, and the individualisation of prophylaxis and treatment. We have shown that postmenopausal patients with high bone turnover evaluated by biochemical markers are identical to fast bone losers as determined by pQCT. As a consequence, we use agents that inhibit bone resorption in patients who are fast bone losers and agents that stimulate bone formation in patients who are slow bone losers. To visualise bone microarchitecture, and to evaluate bone density and the rate of bone loss, we used a highly sensitive pQCT system (DENSISCAN 1000, reproducibility of 0.3% in a mixed population of normal individuals and patients with osteopenia or osteoporosis). This system enabled us to separately assess trabecular and cortical bone density in the radius and tibia, and to differentiate between fast and slow bone losers within a few months (threshold: 3% loss of trabecular bone density in the radius per year). We have shown that the lower the trabecular bone density in the distal radius, the higher the relative bone loss. To classify patients as slow and fast losers in the future, we may need only one measurement. With this highly precise measurement method, we have shown that calcitonin and etidronate are more effective in fast than in slow bone losers, and that vitamin D metabolites (calcitriol or 1 alpha-calcidol) and estrogens can halt fast bone loss. In conclusion, highly sensitive pQCT enables us to adapt the treatment to different forms of osteoporosis and bone turnover, resulting in an increase in the number of patients successfully treated and also in patient compliance. Because our treatment is based on precise, objective measurements, treatment modifications--especially in those who change from a slow to a fast bone-loser state--can be easily justified.

Adult↗

Alterations of oncogenes, tumor suppressor genes and growth factors in hepatocellular carcinoma: with relation to tumor size and invasiveness.

OBJECTIVE: To make a better understanding of the molecular mechanisms involved in recurrence and metastasis of the hepatocellular carcinoma (HCC), some invasion related oncogenes, and growth factors have been investigated. METHODS: The studies were separately carried out, the results of which were summarized in this article with relation to tumor size and invasiveness of HCC. RESULTS: The aberration rates of p53 and CDKN2 in HCC were 45.9% and 36.4% respectively, which were higher in invasive HCC compared with non-invasive HCC. H-ras expression was positive in 29.3% of HCC, which was associated with recurrence and extrahepatic metastasis of HCC. Intralesional injection of H-ras antisense gene markedly inhibited the tumor growth and metastasis of HCC in nude mice. The positive rates of transforming growth factor (TGF)-alpha, epidermal growth factor receptor (EGFR) and c-erbB-2 were 45.7%, 47.1% and 92.3% respectively. The expression of EGFR was closely related to TGF-alpha, which was related to HCC recurrence. But no obvious difference of TGF-alpha or c-erbB-2 expression was found between HCC with and without recurrence, or with and without extrahepatic metastasis. Expression of nm23/tissue inhibitor of metalloproteinase (TIMP)-2 was positively associated with the prognosis of HCC patients (Log-rank, P < 0.001). The alterative rates of above-mentioned genes and growth factors in small HCC were slightly lower than that in large ones, but no significant difference was shown except the p53 mutation. CONCLUSIONS: The p53/CDKN2 mutation, over-expression of H-ras/EGFR, were associated with the invasiveness and recurrence of HCC. H-ras antisense gene might be of potential implication in the control of HCC recurrence and metastasis. Expression of nm23/TIMP-2 was closely related to the prognosis of HCC patients. Biological characteristics remained critical points to the prognosis even in small HCC.

Animals↗

[Experimental study on preventive effect of traditional Chinese medicine replenishing recipe on acute oxygen toxicity caused by hyperbaric oxygen].

OBJECTIVE: To seek for the effective traditional Chinese medicine (TCM) replenishing recipe (RR) prescription that being able to prevent the onset of oxygen convulsion and to offer some clues in preventing the oxygen convulsion with TCM-RR. METHODS: Mice were administered orally with four respective representative RR, Sijunzi Decoction, Siwu Decoction, Liuwei Dihuang Decoction, and Renshen Dihuang Decoction. Then the convulsion latent periods were recorded and SOD vitalities in brain and lung were determined. RESULTS: Compared with the control groups, the convulsion latent period of Sijunzi Decoction group was prolonged significantly (P < 0.01) and its SOD vitality in lung was maintained higher (P < 0.01) after convulsion, while the other three RR results have no significant difference (P < 0.05). CONCLUSION: Sijunzi Decoction has certain preventive effect on acute oxygen convulsion.

Animals↗