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Biomedical subjects

L G Wang

Publications and source records attributed to L G Wang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo.

Meisoindigo, a second generation derivative of indirubin, is an effective chemotherapeutic agent with very low toxicity used in the treatment of chronic myeloid leukemia. To determine the nature of this activity, the effect of a nontoxic concentration (0.72 micrograms/mL) of this compound on ML-1 human myeloblastic leukemic cells was examined. At such a concentration, differentiation induction was found to be the most pronounced drug effect. During the 3-day drug incubation period, the viable cell number remained essentially constant, with approximately 48% of the cells demonstrating a mature phenotype with increased acid phosphatase activity and nitroblue tetrazolium dye reduction. As observed with other DNA-specific agents, induction of ML-1 differentiation by meisoindigo was accompanied by the down-regulation of c-myb gene expression. These data suggest that induction of leukemic cell differentiation associated with decreased c-myb expression may be one of the mechanisms of the antitumor action of meisoindigo.

Antineoplastic Agents↗
PubMed1995

Evidence that lipid peroxidation products bind to DNA in liver cells.

Three lines of evidence are presented indicating the association of lipid peroxidation products with DNA in liver cells, labeled with [3H]arachidonic acid, in the presence of Fe(2+)-DTPA: (1) the nuclear DNA isolated from treated cells had higher radioactivity, compared to controls and the radioactivity increased with longer incubation times, (2) lipid-DNA adducts with a characteristic fluorescence spectrum were formed during the incubation with Fe(2+)-DTPA; (3) the association of peroxidation products with DNA could be inhibited by vitamin E and BHT. Compared with control DNA, purified lipid-DNA adducts showed a decrease of hyperchromicity and melting point, and partial resistance to hydrolysis by DNase I. On the other hand, the repair test shows that the lipid-DNA adducts in cells were not repaired by 4 h after removal of Fe(2+)-DTPA. A decrease in cell viability and in the activity of O6-alkylguanine acceptor protein was also observed with increasing incubation time. These data suggest that the lipid-DNA association, an oxidative DNA damage, occurs in cells treated by Fe(2+)-DTPA and could result in cytotoxicity if not repaired.

Animals↗
PubMed1995

Activation of casein kinase II in ML-1 human myeloblastic leukemia cells requires IGF-1 and transferrin.

Casein kinase II (CK II), a key enzyme involved in the regulation of cell growth, has been variously reported to be activated by diverse mitogens, including insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). Activation of the enzyme is generally carried out in the presence of serum, and we examined the question whether serum components participate in the activation process. We demonstrated previously that ML-1 cells require IGF-1 plus transferrin (TF) for growth and transforming growth factor beta or tumor necrosis factor alpha plus TF for differentiation. We now found that CK II is activated only when the cells are exposed to both IGF-1 and TF or when TF is replaced in this combination with relatively high levels of iron salts. Induction of differentiation with TGF-beta and TF did not result in CK II activation. These results show that CK II activation in ML-1 cells requires the application of both components of the growth signal, IGF-1 and TF, demonstrating that the growth factor alone is incapable of enhancing the activity of the enzyme.

Amino Acid Sequence↗
PubMed1995

Regulation of c-myb expression in ML-1 human myeloblastic leukemia cells by c-ets-1 protein.

C-myb and c-ets-1 have variously been demonstrated to function as protooncogenes. Using a human leukemic cell line, ML-1, we have examined the mechanism by which these genes participate in establishing the sustained proliferation mode that is characteristic of the transformed cell. In the absence of serum, ML-1 cells were found to require IGF-1 and transferrin (TF) for growth and TGF-beta or TNF-alpha plus TF for differentiation. Upon administration of the growth factors, c-myb expression increased within 60 min, whereas after addition of the differentiation factors c-myb expression ceased completely within 3 hr. A correlation was found to exist between the level of c-ets-1 protein in the cells, the extent to which that protein is bound to intron I of the myb gene and the amount of c-myb mRNA that is expressed. Upon administration of growth factors, a sizable increase in the intracellular, and particularly, in the intranuclear level of c-ets-1 protein was observed, whereas a pronounced decrease in the level of this protein occurred after exposure to the differentiation factors. These data demonstrated that the level at which an oncogene-specified transcription factor is expressed can affect the expression of other target oncogenes involved in the regulation of cell proliferation. Stimulated expression of such transcription factor can then lead to the continuous proliferation cycle characteristic of the cancer cell.

Blotting, Western↗
PubMed1994

Formalin induced FOS-like immunoreactive neurons in the trigeminal spinal caudal subnucleus project to contralateral parabrachial nucleus in the rat.

By combining the retrograde-labeling method of injecting Fluoro-Gold (FG) into the parabrachial nucleus (PB) and the immunocytochemical staining of the FOS-like immunoreactive neurons (FLNs) in the trigeminal spinal caudal subnucleus (TSCS) induced by s.c. formalin injection into the perioral region in the rat, it was demonstrated that there are FLNs, FG-labeled neurons and neurons containing both FOS-like immunoreactivity and FG fluorescence in the TSCS. The three kinds of labeled neurons are distributed mainly in laminae I, II and V of the TSCS and there are also some neurons containing both FOS-like immunoreactivity and FG distributed in the adjacent ventrolateral reticular formation. The retrograde-labeling of FG- and double-labeled neurons showed contralateral predominance. In addition, we found that there are retrogradely labeled neurons in bilateral nuclei of the solitary tract with a contralateral predominance. The results suggest that FOS-like immunoreactivity might serve as an indicator for the nociceptive response after formalin injection into the trigeminal region and that the PB might be an important relay station for the further processing of the nociceptive information relayed from the trigeminal afferents. As the PB is known as a relay structure for visceral sensory pathway, it is proposed that there might be viscero-somatic convergence in this nucleus.

Animals↗
PubMed1994

Differential binding of nuclear c-ets-1 protein to an intron I fragment of the c-myb gene in growth versus differentiation.

For growth, ML-1 human myeloblastic leukemia cells require insulin-like growth factor 1 together with transferrin, whereas for differentiation they depend upon transforming growth factor beta in combination with transferrin. As shown in this study, growth stimulation is accompanied by c-myb expression, whereas initiation of differentiation results in the cessation of c-myb expression through premature termination of transcription in the first intron of the myb gene. Growth factor-stimulated c-myb elongation was found to correlate with an elevated level of nuclear c-ets-1 protein and with increased binding of this protein to an 18-base pair sequence in intron 1 of the c-myb gene containing the putative regulatory element PEA 3. In contrast, differentiation factor-initiated ML-1 cell maturation was accompanied by a very low level of nuclear c-ets-1 protein, by the inability to detect binding of the protein to the 18-base pair sequence, and by the cessation of c-myb expression. These results show a correlation to exist between c-ets-1 binding to intron 1 of the c-myb gene and c-myb expression. The mechanism underlying this correlation is under further study.

Base Sequence↗
PubMed1993

Prenatal ontogeny of substance P-like immunoreactivity in the nucleus tractus solitarii and dorsal motor nucleus of the vagus nerve of the human fetus: an immunocytochemical study.

By using immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the dorsal motor nucleus of the vagus nerve (nX) and the nucleus tractus solitarii (nTS) of the human fetus at fetal age (menstruation age) of 11.5 weeks to 40 weeks. The time of initial appearance of SP-LI in the human brainstem nTS was between the fetal age 11.5 weeks and 16 weeks. At fetal age 16 weeks, the nTS showed moderate density of SP-LI fibers and terminals in subnucleus dorsalis of the nTS and nX. While the fetus grew, the density of SP-LI in the human fetus brainstem nTS and nX increased gradually from fetal age 16 weeks to 40 weeks. According to the Nissl staining, at fetal age 23 weeks, the nTS of human fetus can be subdivided into dorsal, medial, dorsolateral, ventrolateral, ventral and gelatinosus subnuclei. The cytoarchitectonic subdivisions of human fetus nTS is in good agreement with the results obtained by immunocytochemical staining. These findings indicated that substance P (SP) might play an important role in the development of human brainstem nX, nTS, their related cranial nerves, and in their functional establishment during the prenatal period.

Benzoxazines↗
PubMed1992

Prenatal ontogeny of substance P-like immunoreactivity in the parabrachial nucleus of the human fetus--an immunocytochemical study.

Using an immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the parabrachial nucleus (PB) of human fetus, fetal age (menstruation age) 11.5 to 40 weeks. The time of initial appearance of SP-LI in the human brainstem PB was between fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SP-LI fibers and terminals in the human fetus brainstem PB increased constantly from fetal age 16 weeks to 40 weeks. These findings indicate that substance P (SP) might play an important role in the human parabrachial nucleus development and in its functional establishment during the prenatal period.

Brain Stem↗
PubMed1992

Prenatal ontogeny of substance P-like immunoreactivity in the trigeminal spinal caudal subnucleus of the human fetus--an immunocytochemical study.

Using an immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the trigeminal spinal caudal subnucleus (TSCS) of human fetus, fetal age (menstruation age) 11.5-40 weeks. The time of initial appearance of SP-LI in the human brainstem TSCS was between the fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SPLI fibers and terminals in the human fetus brainstem TSCS increased constantly from fetal age 16 weeks to 40 weeks. These findings indicated that substance P (SP) might play an important role in the human trigeminal nerve system development and in its functional establishment during the prenatal period.

Brain Stem↗
PubMed1991

Determination of DNA topoisomerase II activity from L1210 cells--a target for screening antitumor agents.

DNA topoisomerase II was isolated from mouse leukemia L1210 cells and the activity was determined by using P4 phage knotted DNA and pBR 322 DNA as the substrates. Based on these results, a method for screening antitumor agents by using DNA topoisomerase II as a target was established. The experiments showed that DNA topoisomerase II catalyzed pBR 322 DNA breaking and relaxing which were reversible and dependent on ATP. The activity was increased 2-4 times in the presence of ATP 1 mmol.L-1. In contrast with type II enzyme, the activity of DNA topoisomerase I was completely inhibited in the presence of ATP 1 mmol.L-1 and had full activity in the absence of ATP. Type II enzyme also showed the unknotting activity by using p4 phage knotted DNA as a substrate. DNA cleavage and relaxing reaction induced by type II enzyme increased 5-fold in the presence of Doxorubicin (Dox) 1 microgram.ml-1 or daunorubicin (Dau). Etoposide (Eto) and aclarubicin B (Acl B) also stimulated the reaction at 100 micrograms.ml-1. The cleavage reaction resulted from topoisomerase II was inhibited by other agents, such as frankincense extracts, terpenic compounds (BC series).

Animals↗
PubMed1991

Pharmacological studies of meisoindigo: absorption and mechanism of action.

Meisoindigo, an indirubin derivative, is a new type of cancer chemotherapeutic agent. It exhibited higher activity against rodent tumors than indirubin itself. Experiments have shown the improved absorption of meisoindigo, compared to indirubin to be one of the major reasons for the enhancement of antitumor activity. Studies on the mechanism of meisoindigo action indicate that it strongly inhibits DNA biosynthesis in tumor cells. Strong inhibition of the drug on assembly of microtubule protein was also obtained. By means of FCM technique the effects of meisoindigo on mouse leukemia L1210 cell cycle were examined. Experimental results showed that under the action of meisoindigo the S phase cells accumulated and the traverse of the cells in G2 + M phase to G1 phase may also be blocked to some extent.

Animals↗
PubMed1991

[Depletion of O6-alkylguanine alkyltransferase and chromosome damage induced by cisplatin, ning xin platin and carboplatin].

O6-Alkylguanine-DNA-alkyltransferase (O6-AGT) is a very important DNA repair protein known to carry out the transfer of alkyl groups from the O6 position of guanine in alkylated DNA to a cysteine acceptor site contained within its own protein sequence. In this work, the activity of O6-AGT in different cell lines and the relationship between the depletion of the enzyme and the frequency of micronuclei induced by cisplatin (DDP), Ning Xin platin (camphoramine chloroacetic platinum, CCP) or carboplatin (JM-8) in KB and CHL cells were studied. Experiments indicate that KB cells showed higher O6-AGT activity (greater than 400 dpm/300 micrograms protein extracts) which belonged to Mer+ cells, but CHL, HL-60 and L1210 cells showed very low O6-AGT activity (less than 50 dpm/300 micrograms protein extracts) which can be considered to be Mer- cells. Cytotoxicity studies indicated that no mer- selection was observed in these platinum complexes for KB, HL-60, CHL and L1210 cells. However, a good relationship between the depletion of O6-AGT and the frequency of micronuclei induced by the platinum complexes was obtained. CCP caused the highest depletion of the enzyme and exhibited highest potency in damaging chromosome.

Animals↗
PubMed1989

Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin.

Inactivation of O6-alkylguanine-DNA alkyltransferase (O6-AGT) in HeLa CCL2 cells by cisplatin was studied. HeLa CCL2 cells treated with cisplatin showed a dose-dependent decline in O6-AGT activity. After cisplatin was removed and replaced with fresh medium, the transferase level began to rise slowly. By 72 h slightly more than 80% of the activity was recovered. It seems that the activity of the alkyltransferase can be inactivated by platinated DNA adducts. The data suggest that the O6-platinum-guanine formation and the O6-alkyltransferase depletion are not responsible for cytotoxicity but may result in a base substitution mutation in mammalian cells.

Cell Survival↗
PubMed1989

DNA-protein, DNA interstrand cross-links induced by camphoramine chloroacetic platinum in vitro.

Effects of camphoramine chloroacetic platinum (CCP) on DNA migration and transcription, DNA-protein and DNA interstrand cross-links induced by CCP were investigated by using agarose gel electrophoresis, alkaline elution and enzymatic techniques, respectively. Chromosome break down and migration alteration of DNa modified by CCP were observed. Plasmid pAR 436 DNA transcription was also blocked when the DNA was treated with CCP. The cross-links took place 8 h after HeLa cells were exposed to CCP 10 mumol/L and higher number of cross-links were obtained after treatment with the agent 20 mumol/L. The number of cross-links was also found to be decreased when the cell lysis was digested with proteinase K. These results suggest that CCP can also induce DNA-protein cross links. Enzymatic studies indicated that CCP preferentially attacks guanine in DNA and restriction enzymes are unable to cleave G-platinated at interval of one base to the restriction sequence.

Animals↗
PubMed1988

Application of hydroelastic waves of the Chinese traditional medicine solution to the traumatotherapy.

We have used hydroelastic waves to treat the closed trauma of the soft tissue. The Shu Huo Jiu (S. H. J.) which is the Chinese traditional medicine alcohol, was used as the fluid medium for generating the pressure waves. The biomechanical model was established and analysed. Both animal and human tests have been made. A practical system was designed, constructed and clinically tested to treat the closed trauma, such as the bruise, contusion, sprain etc.. This system was found to be effective.

Biomechanical Phenomena↗