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Biomedical subjects

Z Lian

Publications and source records attributed to Z Lian.

At least 19 recordsLinked to original sources

Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma.

Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of beta-catenin in the cytoplasm and/or nuclei in tissues and cell lines, which is characteristic of activated beta-catenin. Additional work showed that HBxAg-activated beta-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of beta-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.

Cadherins↗

Outcome of fertility-preserving treatment in young women with endometrial carcinomas.

OBJECTIVE: To evaluate the outcome of conservative treatment of young women with endometrial cancer. DESIGN: Observational study. SETTING: Gifu University Hospital, Japan from 1988 to 2002. POPULATION: Twelve women with endometrial cancer, FIGO IA estimated by MRI under 35 years. METHODS: Patients were treated with medroxyprogestreone acetate (400-600 mg/day) for 6-10 months, with endometrial curettage performed every four weeks. MAIN OUTCOME MEASURES: Response to therapy, pregnancies and reoccurrence of disease during follow up over a 30-month period. RESULTS: All cases had pathological complete remissions within 6-10 months. Seven of 10 wishing to have babies conceived, and five of them were delivered of full-term babies. Eight of nine cases receiving long term follow up (over 30 months) developed recurrent disease, with four opting for hysterectomy. No patient developed distant metastases or had disease-related death. CONCLUSION: Conservative therapy is feasible in carefully selected young women with endometrial cancer. Recurrence rates were high during long term observation even after pathological complete remissions. Therefore, close follow up is recommended.

Adenocarcinoma↗

Soybean isoflavones inhibit estrogen-stimulated gene expression in mouse uteri.

This study was performed to examine the inhibitory effects of soybean isoflavones on estrogen-stimulated gene expression of the uteri in ovarectomized mice. Especially when compared with the inhibitory effect of genistein and daidzein as aglycosides described in our previous report, subcutaneous administration of the glycoside genistin significantly decreased the levels of estradiol-17beta (E2)-induced expressions of c-jun, interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha mRNAs (p < 0.005, p < 0.05 and p < 0.05, respectively) and seemingly proteins in the mice uteri, whereas the glycoside daidzin weakly inhibited E2-stimulated expressions of c-fos and IL-1alpha. Both genistin and daidzin seemed to have a weaker inhibitory effect than that of genistein and daidzein on the expression of estrogen-stimulated genes. It is suggested that those glycosides are naturally derived and generally absorbed from plant foods and might prevent E2-related endometrial carcinogenesis.

Animals↗

Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice.

We have previously demonstrated, using chimeric resistant MRL/lpr mice, that a fractionated total body irradiation (FTBI) (5 Gy x 2 with a 4 h interval on the day before allogeneic bone marrow transplantation (BMT)) is the best conditioning regimen for the treatment of autoimmune diseases in radiosensitive MRL/lpr mice. In the present study, using various standard strains of mice (not radiosensitive mice), we explore the best protocol for irradiation (doses and intervals) as the conditioning regimen for allogeneic BMT. Recipient mice were exposed to various irradiation regimens: a single total body irradiation (TBI) of 9.5 or 12 Gy and FTBI of (5+5) Gy to (7+7) Gy with a 1 to 24 h interval. The method generally utilized for humans ((2+2) Gy with a 4 h interval for 3 days (total 12 Gy)) was also used. One day after the last irradiation, donor BMCs from BALB/c, C3H, or C57BL/6 (B6) mice were transplanted into C3H or B6 mice. The irradiation protocol of (2+2) Gy for 3 days was found to be insufficient to enable the complete removal of recipient immunocompetent cells, since donor-reactive T cells were observed in the recipient spleens and many recipient-type NK and CD4(+) cells were also detected in the recipient hematolymphoid tissues. In all the combinations, the highest survival rate was achieved in the recipients irradiated with (6+6) or (6.5+6.5) Gy with a 4 h interval. In the surviving mice, the hematolymphoid tissues had been fully reconstituted with donor cells.

Animals↗

Direct interaction with contactin targets voltage-gated sodium channel Na(v)1.9/NaN to the cell membrane.

The mechanisms that target various sodium channels within different regions of the neuronal membrane, which they endow with different physiological properties, are not yet understood. To examine this issue we studied the voltage-gated sodium channel Na(v)1.9/NaN, which is preferentially expressed in small sensory neurons of dorsal root ganglia and trigeminal ganglia and the nonmyelinated axons that arise from them. Our results show that the cell adhesion molecule contactin binds directly to Na(v)1.9/NaN and recruits tenascin to the protein complex in vitro. Na(v)1.9/NaN and contactin co-immunoprecipitate from dorsal root ganglia and transfected Chinese hamster ovary cell line, and co-localize in the C-type neuron soma and along nonmyelinated C-fibers and at nerve endings in the skin. Co-transfection of Chinese hamster ovary cells with Na(v)1.9/NaN and contactin enhances the surface expression of the sodium channel over that of Na(v)1.9/NaN alone. Thus contactin binds directly to Na(v)1.9/NaN and participates in the surface localization of this channel along nonmyelinated axons.

Animals↗

Genomic and proteomic analysis of the myeloid differentiation program.

Although the mature neutrophil is one of the better characterized mammalian cell types, the mechanisms of myeloid differentiation are incompletely understood at the molecular level. A mouse promyelocytic cell line (MPRO), derived from murine bone marrow cells and arrested developmentally by a dominant-negative retinoic acid receptor, morphologically differentiates to mature neutrophils in the presence of 10 microM retinoic acid. An extensive catalog was prepared of the gene expression changes that occur during morphologic maturation. To do this, 3'-end differential display, oligonucleotide chip array hybridization, and 2-dimensional protein electrophoresis were used. A large number of genes whose mRNA levels are modulated during differentiation of MPRO cells were identified. The results suggest the involvement of several transcription regulatory factors not previously implicated in this process, but they also emphasize the importance of events other than the production of new transcription factors. Furthermore, gene expression patterns were compared at the level of mRNA and protein, and the correlation between 2 parameters was studied. (Blood. 2001;98:513-524)

Animals↗

A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein.

A new strategy for organ allografts that does not require recourse to immunosuppressants is established in mice. The strategy includes sublethal (7 Gy) irradiation followed by the injection of donor bone marrow cells (BMCs) via the portal vein (P.V.) and organ allografts 1 day after irradiation. Irradiation doses (< or =7 Gy) are found to allow the recipients to survive without the need to reconstitute the BMCs, as the recipient hematolymphoid cells can gradually recover. One hundred percent of recipients irradiated with 7 Gy followed by either P.V. or i.v. injection of donor BMCs accept organ allografts (the skin, pancreas, and adrenal glands) for more than 1 year. However, organ allograft survival rates decrease when irradiation doses are reduced; the skin graft survival rate of mice treated with 6.5 Gy and P.V. injection of BMCs is 79%, whereas that of mice treated with 6.5 Gy and i.v. injection is 50%, indicating that the P.V. injection of BMCs induces persistent tolerance more effectively than the i.v. injection. H-2 typing reveals that almost all the hematolymphoid cells (>98%) in the peripheral blood and hematolymphoid organs are donor-derived even 1 year after the treatment (7 Gy and P.V.). The T cells are tolerant to both donor-type and host-type MHC determinants. The major mechanism underlying the persistent tolerance induced by this strategy seems to be because of clonal deletion. This simple and safe strategy would be of great advantage for human organ transplantation.

Adrenal Glands↗

A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival.

Polymerase chain reaction (PCR) select complementary DNA (cDNA) subtraction of hepatitis B x antigen (HBxAg)-positive compared with -negative HepG2 cells resulted in the up-regulated expression of a cellular gene that encodes a transcript of 745 bases and a polypeptide 99 amino acids long. GenBank analysis revealed extensive homology with the amino terminal domain of cellular multidrug resistant proteins (MRP), although overexpression of this gene did not confer an MRP phenotype. In situ hybridization and immunostaining showed colocalized expression with HBxAg in the liver of hepatitis B carriers. Overexpression of this protein stimulated the growth of HepG2 cells in serum-free medium, and partially protected cells from anti-Fas-mediated killing, but did not promote growth in soft agar or tumor formation in nude mice. Introduction of the dominant negative inhibitor of nuclear factor kappaB (IkappaBalpha) into HBxAg-positive HepG2 cells decreased the levels of messenger RNA (mRNA) and protein, suggesting that its up-regulation is nuclear factor kappaB (NF-kappaB) dependent. Hence, HBxAg activation of NF-kappaB may result in the up-regulation of a cellular protein that promotes growth factor-independent survival and protects against Fas-mediated killing. This factor may contribute to the persistence of infected hepatocytes during chronic infection, which is important for the later development of hepatocellular carcinoma (HCC).

ATP-Binding Cassette Transporters↗

The use of psychoactive substances among adolescent students in an area in the south-west of China.

AIM: To survey drug/psychoactive substance use among adolescent students in a south-west province of China. DESIGN: A cluster sample was drawn from this province of nine districts or cities. Each district/city provided two schools from grade 11 senior high school, A total of 18 schools were selected randomly. FINDINGS: A total of 2649 students completed this self-report questionnaire, mean age 17.1 +/- 0.9 years. The response rate was 92.7-95.6% for each of the specific substances or drugs. The 'life-time prevalences of regular substance use' (at least 15 times during in any one month) were, in rank order of prevalence: tobacco 6.3%, non-steroid anti-inflammatory drugs (NSAID) 2.9%, alcohol 2.9%, solvent 0.3%, sedative/hypnotic 0.2% and cannabis 0.04%. The life-time prevalences of at least some use were: alcohol 66.1%, NSAID 59.3%, tobacco 27.4%, sedative/hypnotic 5.2%, heroin 3.1%, solvents 2.8%, amphetamine-type stimulants (ATS) 0.7% and cannabis 0.3%. The 'prevalences of current regular use' (at least 15 times in the past month) were: tobacco 4.2%, alcohol 1.6%, NSAID 0.8%, sedative/hypnotic 0.1%, solvents 0.1% and cannabis 0.1%. The 'prevalences of current use at any level' were: alcohol 15.2%, NSAID 9.6%, tobacco 7.1%, sedative/hypnotic 0.5%, solvents 0.4%, cannabis 0.1%, heroin 0.1%, and ATS 0.04%. The median age at onset substance use was between 10.7 and 13.4 9.6%. CONCLUSIONS: Drug misuse has appeared among teenage students in this area. The most widely used substances were alcohol and cigarettes. The rates of solvent, tobacco and alcohol use among males were substantially higher than in females.

Adolescent↗

Preventive effects of Juzen-taiho-to on N-methyl-N-nitrosourea and estradiol-17beta-induced endometrial carcinogenesis in mice.

Two experiments were conducted to determine effects of Juzen-taiho-to on endometrial carcinogenesis in mice. In the first experiment, Juzen-taiho-to treatment (2 weeks) decreased the levels of estradiol-17beta (E(2))-stimulated expression of c-fos/jun mRNA and their oncoproteins, determined by reverse transcription-polymerase chain reaction and Southern blot analysis, and the immunohistochemical method, in the uteri of ovarectomized mice. For the second experiment, 93 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and were divided into four groups. Group 1 was given a diet containing 0.2% Juzen-taiho-to and 5 p.p.m. E(2). Group 2 was given a diet containing 5 p.p.m. E(2) alone. Group 3 was given a diet containing 0.2% Juzen-taiho-to alone. Group 4 was kept on the basal diet alone and treated as a control. Juzen-taiho-to treatment significantly decreased incidences of the uterine endometrial atypical (P<0.01), complex (P<0.05) and simple hyperplasias (P<0.01), under estrogenic stimulation. It is suggested that Juzen-taiho-to has an inhibitory effect on E2-related endometrial carcinogenesis in mice, relevantly through suppression of estrogen-induced c-fos/jun-expression.

Animals↗

Preventive effects of isoflavones, genistein and daidzein, on estradiol-17beta-related endometrial carcinogenesis in mice.

The effects of isoflavones (genistein and daidzein) on endometrial carcinogenesis in mice were investigated in two experiments. In the short-term experiment (2 weeks), single subcutaneous (s.c.) administration of genistein [1 mg / 30 g body weight (b.w.)] significantly decreased the levels of estradiol-17beta (E(2)) (5 ppm in diet)-induced expression of c-jun, interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) mRNAs in the uteri of ovariectomized mice (P < 0.005, P < 0.05 and P < 0.01, respectively). Daidzein significantly inhibited E(2)-induced expression of c-fos and IL-1alpha (P < 0.01, P < 0.01 respectively). In the long-term experiment (30 weeks), 140 female ICR mice were given N-methyl-N-nitrosourea-containing solution (1 mg / 100 g b.w.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into six groups; group 1 was given E(2) (in diet) alone. Group 2 was given E(2) and genistein (1 mg / 30 g b.w., s.c., every four weeks). Group 3 was exposed to E(2) and daidzein (1 mg / 30 g b.w., s.c., every four weeks). Groups 4 and 5 respectively received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical endometrial hyperplasia of the group given E(2) and genistein or daidzein were significantly lower than of the group with E(2) alone (P < 0.01 and P < 0.05, respectively). It is suggested that both genistein and daidzein have an inhibitory effect on estrogen-related endometrial carcinogenesis in mice, possibly by suppressing expression of estrogen-induced estrogen-related genes c-fos and c-jun, and internal cytokines IL-1alpha and TNF-alpha through a cytokine and estrogen receptor-mediated pathway.

Adenocarcinoma↗

Herbal complex suppresses telomerase activity in chemo-endocrine resistant cancer cell lines.

A herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix suppressed cell viability and telomerase activity in hormone-refractory and chemo-resistant cancer cell lines, namely poorly differentiated uterine endometrial cancer cell line AN3 CA, adriamycin-resistant breast cancer cell line MCF7/ADR and cisplatin-resistant ovarian cancer cell line A2780. Furthermore, the herbal complex suppressed the expression of the full length of human telomerase reverse transcriptase (hTERT), which is related to telomerase activity. This indicates that the herbal complex can suppress the tumor growth of chemoendocrine resistant cancers, at least in part via suppression of telomerase activity associated with down-regulated hTERT.

Antineoplastic Agents↗

National survey on prevalence of cancer pain.

OBJECTIVE: To collect nationwide basic data about cancer related pain. METHODS: Sixty cancer patients in each province were randomly selected to participate in this survey. The subjects represented all stages of cancer, tumor sites, and different demographic characteristics. Two self-designed structured questionnaires including reasons, types of pain and pain management were used by patients and physicians respectively. Subjects were asked to report whether he/she had experienced any type of cancer related pain and filled out the equivalent questionnaire. The severity of pain was assessed by using "visual analogue scale". Original data input and analysis were using EPI-INFO software package. RESULTS: The result showed that 61.6% (958/1555) of patients had different types of cancer related pain. Majority of pain (85.1%) were caused by advanced cancer. The major reasons (64.4%) for poor management or impedimental factors of pain care are due to patient including over-concern on opioid analgesic addiction, reluctance to report pain or refused to use opioid analgesic until at times when pain is intolerable; 26.8% belonged to physician's reasons including fear to cause addiction on opioid and lack of knowledge about cancer pain management; 16.2% are due to lack of different kinds of opioid analgesic for use and 16.1% belonged to drug regulation. CONCLUSIONS: The results showed that majority of patients (61.6%) had different types of cancer related pain. In most of patients, cancer pain was relieved when they were treated. The major reason for under-treatment or impeded factors for effective relief of cancer pain was fear of opioid addiction by both medical professionals and patients.

Adolescent↗

Preventive effects of danazol on endometrial carcinogenesis in mice.

Short and long-term experiments were designed to determine effects of danazol on estrogen-related endometrial carcinogenesis in mice. The short-term assays showed that danazol decreased expression levels of c-fos/jun mRNA and their oncoproteins induced by estradiol-17beta (E2). For the long-term assay, 85 female ICR mice were given N-methyl-N-nitrsourea solution into their uterine corpora. The animals were divided into three groups as follows: Group 1, E2-diet (5 ppm) plus danazol (2 mg/body (s.c.), every 4 weeks); Group 2, E2-diet alone, Group 3, basal diet alone. At 30 weeks, incidences of atypical and complex endometrial hyperplasia were significantly decreased by danazol-treatment. These results suggest that danazol has preventive effects on estrogen-related endometrial carcinogenesis in mice, through the suppression of estrogen-induced c-fos/jun-expression.

Administration, Oral↗

Candidate Neisseria meningitidis NspA vaccine.

The highly conserved NspA protein has been found in the outer membrane of every Neisseria meningitidis strain tested so far. Two monoclonal antibodies (MAbs) directed against this protein were used to demonstrate that biologically important epitopes of the NspA protein are exposed at the surface of serologically distinct meningococcal strains. Analysis of sera collected from mice that survived a deadly meningococcal challenge following immunization with recombinant NspA protein (rNspA) revealed the presence of cross-reactive antibodies which efficiently attached to and killed the four serogroup B strains tested. These data are additional proof that the NspA protein is exposed at the surface of intact meningococcal cells, which is an important characteristic for a vaccine candidate.

Amino Acid Sequence↗

Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection.

Intrathymic T-cell differentiation is characterized by two selection events: positive and negative selection. It has been shown that thymic epithelial cells in the cortex are involved in the positive selection, while macrophages and dendritic cells, derived from hemopoietic stem cells, are involved in the negative selection. Here we investigate whether donor-derived bone marrow stromal cells can migrate into the thymus and participate there in positive selection after bone marrow transplantation plus bone grafts (to recruit bone marrow stromal cells). Allogeneic bone marrow transplantation with or without bone grafts was carried out in the [C57BL/6-->C3H] combination. Fluorescence-activated cell sorter analyses of recipient thymic adherent cells showed that donor-type bone marrow stromal cells exist in the thymus of mice that received bone marrow plus bone grafts but not in the mice that received bone marrow cells alone. Histological examination using confocal microscopy also confirmed the existence of donor-type stromal cells in the thymus of mice that received bone marrow cells plus bones. Both T-cell proliferation and plaque-forming cell assays indicated that the T cells of such mice show donor-type major histocompatibility complex-restriction. These findings strongly suggest that stromal cells can migrate from the bone marrow to the thymus, where they participate in the positive selection of thymocytes.

Animals↗

Epidemiological survey and follow-up of transfusion-transmitted virus after an outbreak of enterically transmitted infection.

An outbreak of enterically transmitted hepatitis occurred during 1996 among students at a vocational school. Viral fragments homologous to transfusion-transmitted virus (TTV) were detected in faeces. To elucidate the endemic status, an epidemiological survey and case follow-up after the outbreak were carried out. During and after the outbreak, virus carriers among staff were, respectively, 32.1% and 31.3% in serum, and 24.6% and 18.2% in faeces. After the last outbreak, attacks were still occurring among new students with an incidence of 2.4% in 1997 and 2.3% in 1998. There was also a small-scale outbreak in 1998 with a prevalence of 17.9%. On follow-up at 6 and 18 months after onset, alanine aminotransferase (ALT) elevation was found in 29.7% and 13.9% of patients. At 6 months, viral fragments were detected in serum in 78.1% and 46.7% of patients, with and without ALT elevation, respectively. At 18 months the corresponding figures were 55.6% and 19.2%, respectively. At the 18-month follow-up, viral fragments were detected in faeces in 29.6% and 19.3% of patients with and without ALT elevation. In conclusion, this disease might be transmitted from asymptomatic virus carriers. According to the laboratory data, both parenteral and non-parenteral transmissions are involved, and the faecal-oral route might be more important.

Alanine Transaminase↗