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Biomedical subjects

Y Y Lu

Publications and source records attributed to Y Y Lu.

At least 19 recordsLinked to original sources
PubMed2001

Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.

We have shown previously that the AKT2 pathway is essential for cell survival and important in malignant transformation. In this study, we demonstrate elevated kinase levels of AKT2 and phosphatidylinositol-3-OH kinase (PI3K) in 32 of 80 primary breast carcinomas. The majority of the cases with the activation are estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether AKT2 regulates ERalpha activity. We found that constitutively activated AKT2 or AKT2 activated by epidermal growth factor or insulin-like growth factor-1 promotes the transcriptional activity of ERalpha. This effect occurred in the absence or presence of estrogen. Activated AKT2 phosphorylates ERalpha in vitro and in vivo, but it does not phosphorylate a mutant ERalpha in which ser-167 was replaced by Ala. The PI3K inhibitor, wortmannin, abolishes both the phosphorylation and transcriptional activity of ERalpha induced by AKT2. However, AKT2-induced ERalpha activity was not inhibited by tamoxifen but was completely abolished by ICI 164,384, implicating that AKT2-activated ERalpha contributes to tamoxifen resistance. Moreover, we found that ERalpha binds to the p85alpha regulatory subunit of PI3K in the absence or presence of estradiol in epithelial cells and subsequently activates PI3K/AKT2, suggesting ERalpha regulation of PI3K/AKT2 through a nontranscriptional and ligand-independent mechanism. These data indicate that regulation between the ERalpha and PI3K/AKT2 pathway (ERalpha-PI3K/AKT2-ERalpha) may play an important role in pathogenesis of human breast cancer and could contribute to ligand-independent breast cancer cell growth.

Androstadienes↗
PubMed2001

Human hepatocellular carcinoma is characterized by a highly consistent pattern of genomic imbalances, including frequent loss of 16q23.1-24.1.

Comparative genomic hybridization (CGH) analysis was used to identify chromosomal imbalances in 52 human primary hepatocellular carcinomas (HCCs). The most prominent changes were gains of part or all of chromosome arms 8q (83% of cases) and 1q (73%) and loss of 16q (63%). Other commonly overrepresented sites were 5p, 7q, and Xq. Recurrent sites of DNA sequence amplification included 8q23--24 (five cases) and 11q13--14 (four cases). Other frequently underrepresented sites were 4q, 8p, 16p, and 17p. Taken collectively, these findings and data from other CGH studies of HCCs define a subset of chromosome segments that are consistently over- or underrepresented and highlight sites of putative oncogenes and tumor suppressor genes, respectively, involved in hepatocellular oncogenesis. Loss of heterozygosity analysis with a panel of polymorphic microsatellite markers distributed along 16q defined a minimal region of chromosomal loss at 16q23.1--24.1, suggesting that this region harbors a tumor suppressor gene whose loss/inactivation may contribute to the pathogenesis of many HCCs.

Allelic Imbalance↗
PubMed2000

The suppression effect of light rare earth elements on proliferation of two cancer cell lines.

To study the suppression effect of light rare earth elements (RE) on proliferation of two cancer cell lines. Two cancer cell lines PAMC82 and K562 were used to examine their colony-forming ability in soft agar, microtubule structure, calmodulin levels and regulation of some gene expressions by Northern blot analysis with and without treatment by RE. The results showed that on soft agar culture the colony-forming ability of human gastric cancer cell line PAMC82 treated by RE chloride decreased and the PAMC82 cell microtubule abnormal structure became normal. The calmodulin (CaM) levels decreased in human leukemia cells (K562) treated with cerium chloride and neodymium chloride. The Northern blot analysis revealed marked up-regulation of p53, p16(MTS1), p21 (WAF1) gene expressions in PAMC82 cells treated with lanthanum chloride and cerium chloride, as compared to control PAMC82 cells. The light rare earth elements studied have certain suppression effects on proliferation of cancer cells. This effect might be related to the decrease of calmodulin and up-regulation of some gene expressions in cancer cells.

Calmodulin↗
PubMed2000

[Effects of total flavones of metasequosia on left ventricular hypertrophy due to pressure overload in rats].

OBJECTIVE: To determine the preventive and regressive effects of total flavones of metasequosia (TFM) on left ventricular hypertrophy in rats. METHOD: Left ventricular hypertrophy was inducedin by partial ligation of abdominal aorta. The rats were given ig TFM(4, 40, 400 mg.kg-1.d-1) for six weeks. RESULT: TFM markedly reduced the HW/BW, LVW/BW, myofibril diameter and Ca2+ content in left ventricles but the systolic blood pressure (SBP) in rats wasn't obviously influenced. CONCLUSION: TFM can prevent and reverse the left ventricular hypertrophy due to pressure overload in rats. The mechanism may be related to its calcium antagonistic properties.

Animals↗
PubMed2000

[Study on the relationship between microvascular density and prognosis in laryngeal cancer].

OBJECTIVE: To study the relationship between the microvascular density(MVD) and the prognosis in laryngeal cancer. METHOD: Microvessel quantitation in 31 cases of laryngeal cancer was done with factor VIII-related antibody and SABC method. RESULT: The quantitation of microvessels in laryngeal cancer were negative of histologic grade and type, but were significantly different (P < 0.05) between metastasis (10.23 +/- 0.78) and without metastasis(6.38 +/- 0.33) two years after operation. CONCLUSION: The angiogenesis of laryngeal cancer is correlated with the lymph node metastasis and prognosis.

Adult↗
PubMed1999

Depth of anesthesia estimation and control.

A fully automated system was developed for the depth of anesthesia estimation and control with the intravenous anesthetic, Propofol. The system determines the anesthesia depth by assessing the characteristics of the mid-latency auditory evoked potentials (MLAEP). The discrete time wavelet transformation was used for compacting the MLAEP which localizes the time and the frequency of the waveform. Feature reduction utilizing step discriminant analysis selected those wavelet coefficients which best distinguish the waveforms of those responders from the nonresponders. A total of four features chosen by such analysis coupled with the Propofol effect-site concentration were used to train a four-layer artificial neural network for classifying between the responders and the nonresponders. The Propofol is delivered by a mechanical syringe infusion pump controlled by Stanpump which also estimates the Propofol effect-site and plasma concentrations using a three-compartment pharmacokinetic model with the Tackley parameter set. In the animal experiments on dogs, the system achieved a 89.2% accuracy rate for classifying anesthesia depth. This result was further improved when running in real-time with a confidence level estimator which evaluates the reliability of each neural network output. The anesthesia level is adjusted by scheduled incrementation and a fuzzy-logic based controller which assesses the mean arterial pressure and/or the heart rate for decrementation as necessary. Various safety mechanisms are implemented to safeguard the patient from erratic controller actions caused by external disturbances. This system completed with a friendly interface has shown satisfactory performance in estimating and controlling the depth of anesthesia.

Algorithms↗
PubMed1996

Decreased accumulation and dephosphorylation of the mitosis-specific form of nucleophosmin/B23 in staurosporine-induced chromosome decondensation.

Nucleophosmin/B23 is highly phosphorylated by cdc2 kinase during mitosis, and this phosphorylation most probably has a role in initiating and controlling the entry of cells into mitosis [Peter, Nakagawa, Doree, Labbe and Nigg (1990) Cell 60, 791-801]. In the present study, the protein kinase inhibitor staurosporine has been used to examine possible changes in nucleophosmin/B23 at mitosis in HeLa cells. Addition of staurosporine to HeLa cells already arrested at mitosis by nocodazole causes: (i) decreased accumulation of the mitosis-specific form of nucleophosmin/B23, (ii) dephosphorylation of nucleophosmin/ B23, (iii) redistribution of nucleophosmin/B23 to the cytosol, and (iv) concomitant decondensation of chromosomes. These results suggest that the mitosis-specific phosphorylated form of nucleophosmin/B23 may play a role in maintaining mitotic chromosomes in their condensed state.

Alkaloids↗
PubMed1995

Long-term exposure to chromium(VI) oxide leads to defects in sulfate transport system in Chinese hamster ovary cells.

Chromium(VI) resistant Chinese hamster ovary (CHO) cell lines were established in this study by exposing parental CHO-K1 cells to sequential increases in CrO3 concentration. The final concentration of CrO3 used for selection was 7 microM for Cr7 and 16 microM for Cr16 cells. Cr16-1 was a subclone derived from Cr16 cells. Next, these resistant cells were cultured in media without CrO3 for more than 6 months. The resistance of these cells to CrO3 was determined by colony-forming ability following a 24-h treatment. The LD50 of CrO3 for chromium(VI) resistant cells was at least 25-fold higher than that of the parental cells. The cellular growth rate, chromosome number, and the hprt mutation frequency of these chromium(VI) resistant cells were quite similar to their parental cells. The glutathione level, glutathione S-transferase, catalase activity, and metallothionine mRNA level in Cr7 and Cr16-1 cells were not significantly different from their parental cells. Furthermore, Cr16-1 cells were as sensitive as CHO-K1 cells to free-radical generating agents, including hydrogen peroxide, nickel chloride, and methanesulfonate methyl ester, and emetine, i.e., a protein synthesis inhibitor. The uptake of chromium(VI) and the remaining amount of this metal in these resistant and the parental cell lines were assayed by atomic absorption spectrophotometry. Experimental results indicated that a vastly smaller amount of CrO3 entered the resistant cell lines than their parental cells did. A comparison was made of the sulfate uptake abilities of CHO-K1 and chromium(VI) resistant cell lines. These results revealed that the uptake of sulfate anion was substantially reduced in Cr7 and Cr16-1 cells. Extracellular chloride reduced sulfate uptake in CHO-K1 but not in Cr16-1 cells. Therefore, the major causative for chromium(VI) resistance in these resistant cells could possibly be due to the defects in SO4(2-)/C1- transport system for uptake chromium(VI).

Animals↗
PubMed1995

[Amplification of oncogenes HER2, mdm-2 and myc in breast cancer determined by modified competitive PCR].

The amplification of oncogenes HER2, mdm-2 and myc was determined with a modified competitive PCR. The HER2, mdm-2 and myc genes were found to amplify in 5, 6 and 6 out of 15 patients with breast cancer respectively. The amplification of HER2 and mdm-2 correlated with advanced tumors and lymph node involvement respectively, indicating that the amplification of the oncogenes is a useful indicator for the prognosis of patients with breast cancer and for the study of the biological behaviors of tumors. This modified non-radioactive competitive PCR is simple to handle (even for DNA samples with low quantity and low quality), and accurate for measuring the copy numbers of genes.

Base Sequence↗
PubMed1995

The synthesis and biological activities of oligodeoxynucleotides that are covalently linked to psoralen at their 5' ends.

Four oligodeoxynucleotides (15-mers), designated 13 through 16, and the corresponding conjugates, designated 17 through 20, in which psoralen was covalently linked to the 5' end of each oligonucleotide were synthesized. Compounds 16 and 20 contained a sequence that was complementary to part of the first four codons and the upstream sequence close to the ribosome-binding site of c-Ha-ras mRNA. Compounds 16 and 20 inhibited the growth of cells that had been transformed by the c-Ha-ras plasmid, with accompanying suppression of the expression of the activated c-Ha-ras oncogene. The antisense oligonucleotides 16 and 20 also appeared to cause partial reversion of the major phenotypic characteristics of transformed cells, which included inhibition of anchorage-independent growth. Compound 20, which contained psoralen, was a more efficient inhibitor of the growth of transformed cells than compound 16 without psoralen, a result that suggests psoralen might have increased the ability of the oligodeoxynucleotides to enter the cells.

Amino Acid Sequence↗
PubMed1994

Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma.

Previous cytogenetic investigations have revealed frequent deletions and other unbalanced structural rearrangements of 3p in human malignant mesothelioma. We have performed a restriction fragment length polymorphism analysis by using the polymerase chain reaction and primer sets for seven DNA markers to examine loss of heterozygosity (LOH) from 3p in 25 malignant mesotheliomas. Among 24 cases informative at one or more 3p loci, 15 (62.5%) exhibited LOH with at least one marker. Deletion mapping in these tumors indicates that the common region of chromosomal loss resides within band 3p21, in the vicinity of the D3F15S2 locus. These results suggest that allelic loss from 3p21 is a frequent occurrence in malignant mesothelioma and that one or more putative tumor suppressor genes at this site contribute to the pathogenesis of this malignancy.

Alleles↗
PubMed1994

Apoptosis induced in CD4+ cells expressing gp160 of human immunodeficiency virus type 1.

In a previous study (Y. Koga, M. Sasaki, H. Yoshida, H. Wigzell, G. Kimura, and K. Nomoto, J. Immunol. 144:94-102, 1990), we demonstrated that the expression of gp160, a precursor form of envelope glycoprotein of human immunodeficiency virus type 1, in CD4+ cells causes the downregulation of surface CD4 and single-cell killing by forming intracellular gp160-CD4 complex. In the present study we investigated the events that lead to cell death in CD4+ cells expressing gp160. We found that apoptosis is induced in cells undergoing single-cell death. Moreover, even the cell clone, which expresses so little gp160 that it does not exhibit any apparent cytopathic effects, such as the inhibition of cell growth, was found to be highly susceptible to the apoptosis induction by the anti-Fas monoclonal antibody.

Antigens, Surface↗
PubMed1994

Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus.

Cytomegalovirus (CMV) causes severe clinical manifestations in immunocompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an opportunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-positive thymocytes of BALB/c mice inoculated with a sublethal dose of murine CMV (MCMV) were extensively depleted by a 10-micrograms amount of anti-CD3 monoclonal antibody, while such an amount was unable to induce any apparent elimination of thymocytes in noninfected mice. In immature thymocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal antibody. Analysis of the signal transduction pathway of such double-positive thymocytes demonstrated a profound elevation of the intracellular Ca2+ level after anti-CD3 stimulation, implying that this aberrant mobilization of Ca2+ plays a crucial role in the signaling pathway leading these cells to an extensive apoptosis. Examination of the thymus by PCR was able to detect a low copy number of MCMV DNAs in thymic stromal cells but none at all in thymocytes. Therefore, it is suggested that a mechanism which is not associated with virus replication within the cells exerts a critical effect on rendering the thymocytes highly apoptosis sensitive in hosts infected with MCMV.

Animals↗
PubMed1994

Murine cytomegalovirus-associated pneumonitis in the lungs free of the virus.

At 4 wk after intraperitoneal inoculation of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable only in the salivary glands. When T cells of these mice were activated by a single injection of anti-CD3 epsilon monoclonal antibody, mice died of interstitial pneumonitis at 24-48 h after injection, accompanied by elevation of serum levels of TNF-alpha and IFN-gamma. However, MCMV remained undetectable in the lungs during the period. Simultaneous injection of cyclosporin A reduced such effects of anti-CD3. In conclusion, although the presence of MCMV in the host may be required, MCMV-associated pneumonitis is not mediated by virus in the lung but probably by the cytokines released from T cells, of which responsiveness to stimulation via CD3 molecule has been presumably modified by MCMV infection.

Animals↗
PubMed1994

[Studies on the reduction of malignant phenotypes in a highly metastatic human lung carcinoma--correlated changes of intercellular communication, cytoskeletons, oncogenes and antioncogene].

Human lung giant cell carcinoma cell line PG is characterized by its highly metastatic (100%) behavior in nude mice. When compared with cultured normal human fetal lung cells, PG cells were deficient in gap junctional intercellular communication (GJIC) function as detected by Scrape Loading and Dye Transfer method. Tubulin immunofluorescent and rhodamine-phalloidin staining revealed disorganization of microtubules and disruption of stress fibers with appearance of reorganized F-actin-bodies in PG cells. Northern or dot blot hybridization results showed that PG expressed high levels of c-myc and c-Ha-ras oncogenes and low level of antioncogene P53. Southern hybridization demonstrated that PG also exhibited c-myc gene amplification. When PG was treated with calmodulin antagonist calmidazolium (CDZ, 100-200nmol/L) or a Chinese medicinal mixture L2 (3-13mg/ml), cell proliferation was inhibited, GJIC function restored, and microtubule network recovered. But only L2 was efficient in (1) improving the stress fiber organization, (2) inhibiting the colony formation in soft agar, (3) reduction of c-myc amplification and expression, and (4) up-regulation of P53 mRNA level. The correlation between markers of malignant phenotypes and the reversion of PG cells is discussed.

Animals↗