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L Yu

Publications and source records attributed to L Yu.

At least 55 records · Page 3Linked to original sources
PubMed2003

Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice.

Ovarian hormones were well documented to modulate the dopamine release in the central dopaminergic systems. The dopamine-releasing effects in the nucleus accumbens, a major target of the mesolimbicortical dopaminergic system, were closely associated with the reinforcing effects of two psychomotor stimulants, cocaine and methamphetamine. This study aimed to examine the sex differences in the cocaine- and methamphetamine-reinforcing behavior, conditioned place preference. In addition, the modulating effects of estradiol and progesterone on methamphetamine-induced conditioned place preference were investigated in both sexes of adult gonadectomized mice. There was no sex difference in the sensitivity to the cocaine (5 mg/kg)-induced conditioned place preference. However, female mice exhibited a more potent methamphetamine (1 mg/kg)-induced conditioned place preference than did male mice. Moreover, pretreatment with estradiol for two consecutive days before the beginning of the conditioning and throughout the four daily conditionings (0.47 microg/day for totally six days) effectively facilitated methamphetamine-induced conditioned place preference in gonadectomized female mice, but not in gonadectomized male mice. Progesterone, under a similar treatment regimen (0.47 microg/day for six consecutive days), did not alter the methamphetamine-induced conditioned place preference in either sex of gonadectomized mice. Taken together, we conclude that the facilitating effects of estradiol on methamphetamine-induced conditioned place preference could be sex-dependent with an eminent sensitivity associated with the adult female mice.

Animals↗
PubMed2003

Effects of iron deficiency on the secretion of interleukin-10 by mitogen-activated and non-activated murine spleen cells.

Interleukin (IL)-10 plays crucial regulatory roles in immune responses by inhibiting the secretion of several cytokines (IL-2, IL-12, interferon-gamma (IFN-gamma)) and lymphocyte proliferation. Iron deficiency, a public health problem for children, alters these immune responses. To determine whether these changes are related to altered IL-10 secretion, we measured IL-10 in 24 and 48 h supernatant of spleen cell cultures from iron deficient (ID), control (C), pairfed (PF), and ID mice fed the control diet (iron repletion) for 3 (R3) and 14 (R14) days (d, n = 12/group). Mean levels of hemoglobin, hematocrit, and liver iron stores varied as follows: C approximately equal PF approximately equal R14 > R3 > ID (P < 0.01). Mean baseline IL-10 levels of ID mice tended to be higher than those of other groups (P > 0.05, ANOVA). Mean IL-10 levels secreted by concanavalin A (Con A) and antibody raised against cluster of differentiation molecule 3 (anti-CD3)-treated cells (+/-background) were lower in ID than in C (48 h) and iron replete mice (P < 0.05). Underfeeding also reduced IL-10 secretion by anti-CD3-treated cells (48 h, P < 0.05). Lymphocyte proliferative responses to anti-CD3 +/- anti-CD28 antibodies were lower in ID than in C and PF mice, and they were corrected by iron repletion (P < 0.05). IL-10 levels negatively correlated with indicators of iron status (r <or= -0.285) and lymphocyte proliferation (r <or= -0.379 [r <or= -0.743 for ID mice]), but positively correlated with IFN-gamma levels (r <or= 0.47; P < 0.05). Data suggest that iron deficiency has a generalized deleterious effect on cells that secrete both cytokines. Reduced IL-10 secretion by activated cells does not overcome the inhibition of lymphocyte proliferation due to other factors of T cell activation that are regulated by iron.

Animals↗
PubMed2003

A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the alpha-fetoprotein promoter.

We examined the expression of the midkine (MK) and alpha-fetoprotein (AFP) genes in 15 paired human specimens obtained from hepatocellular carcinoma (HCC) and the corresponding noncancerous regions of the same patients. A total of 14 HCC but none of the noncancerous specimens were positive for the MK mRNA. In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene. A 2.3-kb genomic fragment in the regulatory region of the MK gene could activate a fused reporter gene in both AFP-producing and -nonproducing HCC lines, and the MK fragment-mediated transcriptional activity was comparable to the AFP enhancer-linked AFP promoter in AFP-producing cell lines. The AFP-producing but not AFP-nonproducing HCC cell lines that were transfected with the MK promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene became susceptible to a prodrug ganciclovir to a similar degree of the HCC transfected with the enhancer-linked AFP promoter-fused HSV-TK gene. These data suggest that the MK promoter can activate a therapeutic gene preferentially in HCC and is as useful as the AFP promoter in clinical settings.

Aged↗
PubMed2003

Effects of the Dzyaloshinskii-Moriya interaction on low-energy magnetic excitations in copper benzoate.

We have investigated the physical effects of the Dzyaloshinskii-Moriya (DM) interaction in copper benzoate. In the low-field limit, the spin gap is found to vary as H(2/3)ln((1/6)(J/mu(B)H(s)) (H(s): an effective staggered field induced by the external field H) in agreement with the prediction of conformal field theory, while the staggered magnetization varies as H(1/3) and the ln((1/3)(J/mu(B)H(s)) correction predicted by conformal field theory is not confirmed. The linear scaling relation between the momentum shift and the magnetization is broken. We have determined the coupling constant of the DM interaction and have given a complete quantitative account for the field dependence of the spin gaps along all three principal axes, without resorting to additional interactions such as interchain coupling. A crossover to strong applied field behavior is predicted for further experimental verification.

Journal Article↗
PubMed2003

Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine.

Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 +/- 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 +/- 4.3, 27.3 +/- 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.

Animals↗
PubMed2003

Prevalence of adrenal antibodies in Addison's disease among north Indian Caucasians.

OBJECTIVE: The prevalence of antibodies in different organ-specific autoimmune diseases can vary depending on the racial group studied. Data on the prevalence of antibodies against steroidogenic enzymes in Addison's disease is available only for white Caucasians. We have evaluated the frequency of antibodies against adrenal cytoplasm, 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzyme in a cohort of Indian patients with Addison's disease of idiopathic and granulomatous aetiology. DESIGN: Study of all patients with Addison's disease on whom serum samples were available (84% of total), presenting to the Endocrinology Department in a teaching hospital in India, between 1990 and 1999. PATIENTS: Thirty-eight patients with Addison's disease (19 idiopathic, 19 granulomatous). METHODS: A radiobinding assay using in vitro transcribed and translated recombinant human 35S-labelled 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzymes was utilized to detect the respective antibodies. Adrenal cytoplasmic antibodies were measured by indirect immunofluorescence on cryostatic sections of human adrenal cortex. RESULTS: Of the 19 patients with idiopathic Addison's disease, adrenal cytoplasmic antibodies were present in five (26%) patients, while 21-hydroxylase antibodies were present in four (21%) subjects. The frequency of 21-hydroxylase antibodies was similar among patients with isolated idiopathic Addison's disease (3/13, 23%), and those associated with other organ-specific autoimmune diseases (1/6, 17%). 17-alpha-hydroxylase and side-chain cleavage antibodies were present in four (21%) and three (16%) patients, respectively. Overall, at least one of the three antibodies was present in eight (42%) subjects. All four female patients with premature ovarian failure had antibodies against 17-alpha-hydroxylase and/or side-chain cleavage enzyme. Two (11%) patients with granulomatous Addison's disease had adrenal antibodies. Of these, one patient with enlarged and calcified adrenal gland secondary to tuberculosis had a high titre of antibodies against all three steroidogenic enzymes. CONCLUSIONS: Antibodies to 21-hydroxylase enzyme are less frequent in idiopathic Addison's disease in north Indians, when compared with other Caucasians. In contrast, the prevalence of 17-alpha-hydroxylase and side-chain cleavage enzyme antibodies is similar to those reported. High titre antibodies against steroidogenic enzymes may occasionally be present in patients with clinical evidence of tuberculous Addison's disease.

Addison Disease↗
PubMed2003

Factors influencing the non-recovery of renal function after the relief of urinary tract obstruction in women with cancer of cervix.

OBJECTIVES: To identify factors associated with non-recovery of renal function after the relief of urinary tract obstruction in women with cancer of cervix. PATIENTS AND METHODS: Thirty-seven women with cancer of cervix and obstructive renal failure were prospectively studied. Patients were evaluated in the day before nephrostomy (D0); and in the 1st (D1), 7th (D7), and 30th day (D30) after unilateral nephrostomy. The following parameters were analyzed: age serum urea, and serum creatinine (S(creat)), in D0, D7, and D30. Renal cortical thickness was measured by ultrasonography in D0. During nephrostomy procedure, urine samples for urinalysis and culture were collected and renal biopsy was attempted. Patients were divided in two groups according to S(creat) in D30: patients with S(creat) < 1, 4mg/dL (R group) and those with S(creat) > or = 1, 4mg/dL (nR group). RESULTS: Ten patients died before D30 and were not studied. R group (n = 12) was younger (43 +/- 9 vs. 52 +/- 10 years, p < 0.05) than nR group (n = 15), and presented lower serum urea in D0 (134 +/- 67 vs. 212 +/- 51 mg/dL, p < 0.01) and in D7 (94 +/- 20 vs. 155 +/- 18 mg/dL, p < 0.05). Renal cortex was thicker in R group (17 +/- 1 vs. 13 +/- 1 mm, p < 0.05). Survival was higher in R group (11/12) than in nR group (0/15, p < 0.01). All urine samples showed leukocyturia but culture was positive in only two. In three out of nine biopsy attempts enough material was obtained. Light microscopy revealed interstitial fibrosis plus tubular atrophy, and partial glomerular fibrosis was present in two biopsies. CONCLUSIONS: The non-recovery of renal function after the relief of obstruction in human obstructive renal failure is associated with older age and decreased renal cortical thickness. The complete renal recovery improves patient survival despite malignancy.

Adult↗
PubMed2003

In silico analysis indicates a similar gene expression pattern between human brain and testis.

OBJECTIVES: Previous data has reported similarity between human brain and testis gene expression patterns. Brain is the most important tissue in human speciation. Hence, it means that human testis could also play a crucial role in human speciation if these two tissues exhibit similar gene expression patterns. However, previous reports were based on only limited and scattered data. Determining the large scale anatomy of gene expression patterns of various human tissues could draw a more convincing conclusion, and better our understanding of the correlation/inter-correlation among different tissues. Furthermore, it could also provide a clue for evolutionary study. METHODS: To obtain gene expression information for large-scale data analysis, expression data of 760 Unigenes in seventeen human tissues (liver, lung, testis, brain, ovary, uterus, colon, stomach, heart, eye, kidney, spleen, gall bladder, breast, thymus, prostate and pancreas) were retrieved by DDD (differential digital display) analysis, and this expression data was subjected to clustering analysis. These Unigenes represent a wide range of genes classified according to their characterization and function. RESULTS: Among the 17 tissues, the highest similarity in gene expression patterns was between human brain and testis, based on DDD and clustering analysis. Genes contributing to the similarity include ribosomal protein (RP) genes as well as genes involved in transcription, translation and cell division. CONCLUSIONS: Present results provide evidence to support the proposal that human testis and brain share the highest similarity of gene expression patterns. The implications of the similarity regarding that both brain and testis contributed to human speciation are discussed.

Brain↗
PubMed2003

Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report.

LRP16 is a novel gene cloned from lymphocytic cells, and its function is not known. The expression level of LRP16 mRNA was up-regulated by estrogen in breast cancer MCF-7 cells based on the computed aided serial analysis of gene expression (SAGE) analysis. In this study, we investigate the effect of 17beta-estradiol (17beta-E(2)) on the expression of LRP16 mRNA and the effects of overexpression of LRP16 on the proliferation of cultured MCF-7 cells and the possible mechanisms involved. The expression level of LRP16 mRNA induced by 17beta-E(2) was determined by Northern blot analysis. LRP16 promoter-controlled luciferase expression vector (pGL3-S(0)) was co-transfected with various nuclear receptors, including estrogen receptor alpha and beta (ERalpha and ERbeta), glucocorticoid receptor alpha (GRalpha), androgen receptor (AR) and peroxisome-proliferator activated receptor gamma and alpha (PPARgamma and PPARgamma) into COS-7 cells, and the relative luciferase activity was measured using Dual-luciferase report assay systems. The effect of overexpression of LRP16 on MCF-7 proliferation was examined by the Trypan Blue exclusion method, and the cell cycle was analyzed by flow cytometry. The expression levels of cyclin E, p53 and p21(WAF1/CIP1) proteins were determined by Western blot analysis. The results showed (1) 17beta-E(2) induced a five- to eightfold increase in LRP16 mRNA levels in MCF-7 cells; (2) the relative luciferase activities in the COS-7 cells co-transfected by pGL3-S(0) and ERalpha or AR were 7.8-fold and 11-fold respectively of those in the control cells transfected by pGL3-S(0) alone; (3) overexpression of LRP16 stimulated MCF-7 cell proliferation, and the numbers of cells in the S-phase of the cell cycle in cells transfected with LRP16 increased about 10% compared with the control cells; and (4) cyclin E levels were much higher in cells with overexpression of LRP16 than in the control cells, while the expression levels of p53 and p21(WAF1/CIP1) were not different between the two groups of cells. From these results we concluded that estrogen up-regulates the expression level of LRP16 mRNA through activation of ERalpha and that overexpression of LRP16 promotes MCF-7 cell proliferation probably by increasing cyclin E.

Animals↗
PubMed2002

Facial subdermal vascular network flap: anatomic study and clinical application.

Despite the numerous flaps for facial reconstruction that have been described, the search for the ideal flap with good color matching and minimal donor-site morbidity continues. In the past 3 years we have repaired 13 facial defects with success using the lateral genicervical flap - a type of facial subdermal vascular network flap (SVNF) - with a pedicle located on the preauricular region. An anatomic study of the facial SVNF, including blood supply and vascular distribution of the face and anatomic characteristics of facial vessels, based on 14 cadaver dissections, was carried out. The blood supply of the facial skin basically originated from the branches of the facial, superficial temporal and infraorbital arteries. The lateral genicervical skin was supplied basically by the branches of the facial, superficial temporal and occipital arteries, but also by the terminal branches of the superior thyroid artery. The branches diverging from these arteries became superficial and formed a subcutaneous arterial network. The arterioles from the network went to the corium layer and formed a subdermal arterial network whose arterioles anastomosed with each other in a honeycomb-like structure. The vascular distribution presented certain directivity on different areas. The blood supply of the pedicle originated from the subdermal vascular network formed by the perforator branches of these arteries. The arterioles from the facial and superficial temporal arteries anastomosed in the lateral genicervical region. From the anatomic study, we think that the viability of the facial SVNF depends basically on the subdermal vascular network formed by the perforator branches of the pedicle, and that the anastomoses between the facial and superficial temporal arteries provide a solid anatomic basis to the lateral genicervical flap. The clinical data also indicated that this flap is a useful alternative for facial, especially superficial temporal, defects. But the directivity must be taken into account in its clinical application.

Adolescent↗
PubMed2002

Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.

The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.

Animals↗
PubMed2002

Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease.

Intra-MHC sequences including MHC class I chain-related genes (MICAs), D6S273 and D6S2223 are associated with autoimmune diseases in addition to HLA class II. In the current study, we ascertained the haplotypes of 57 Caucasian patients with Addison's disease composed of these genetic markers and compared them either with 72 general population controls or with 105 child controls carrying Addison's disease high-risk DR3-DQ2/DR4-DQ8 genotypes. The MICA-A5.1/A5.1 genotype as well as HLA DR3/4 especially with DRB1*0404 were the main susceptibility markers. The homozygous MICA-A5.1/A5.1 genotype was significantly more frequent in the patients with Addison's disease (61%) than in the healthy controls (6%). The MICA-A5.1 allele was increased on both the DR3 and DR4 haplotypes, independent of DQ and DRB1 subtyping, in the patients with Addison's disease compared with the controls. Furthermore, the D6S273*140 allele on the DR3 haplotype and the D6S273*134 allele on the DR4 haplotype in the DR3/4 heterozygotes influenced susceptibility relative to the DR3/4 controls. The risk for Addison's disease was increased for the DR3-D6S273*140-MICA-A5.1/DRB1*0404-D6S273*134-MICA-A5.1 genotypes compared with that conferred by the DR3/4 controls. Susceptibility to Addison's disease is influenced by the genes around MICA and D6S273 for both the HLA DR3-DQ2 and DR4-DQ8 haplotypes.

Addison Disease↗
PubMed2002

Pharmacogenomic analysis: correlating molecular substructure classes with microarray gene expression data.

Genomic studies are producing large databases of molecular information on cancers and other cell and tissue types. Hence, we have the opportunity to link these accumulating data to the drug discovery processes. Our previous efforts at 'information-intensive' molecular pharmacology have focused on the relationship between patterns of gene expression and patterns of drug activity. In the present study, we take the process a step further-relating gene expression patterns, not just to the drugs as entities, but to approximately 27,000 substructures and other chemical features within the drugs. This coupling of genomic information with structure-based data mining can be used to identify classes of compounds for which detailed experimental structure-activity studies may be fruitful. Using a systematic substructure analysis coupled with statistical correlations of compound activity with differential gene expression, we have identified two subclasses of quinones whose patterns of activity in the National Cancer Institute's 60-cell line screening panel (NCI-60) correlate strongly with the expression patterns of particular genes: (i) The growth inhibitory patterns of an electron-withdrawing subclass of benzodithiophenedione-containing compounds over the NCI-60 are highly correlated with the expression patterns of Rab7 and other melanoma-specific genes; (ii) the inhibitory patterns of indolonaphthoquinone-containing compounds are highly correlated with the expression patterns of the hematopoietic lineage-specific gene HS1 and other leukemia genes. As illustrated by these proof-of-principle examples, we introduce here a set of conceptual tools and fluent computational methods for projecting directly from gene expression patterns to drug substructures and vice versa. The analysis is presented in terms of the NCI-60 cell lines and microarray-based gene expression patterns, but the concept and methods are broadly applicable to other large-scale pharmacogenomic database sets as well. The approach (SAT for Structure-Activity-Target) provides a systematic way to mine databases for the design of further structure-activity studies, particularly to aid in target and lead identification.

Algorithms↗
PubMed2002

Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots.

Cyclooxygenase enzyme inhibitory assay-guided purification of ethyl acetate extract of Piper methysticum (kava kava) roots yielded six biologically active compounds (1-7), which were purified using MPLC, preparative TLC and HPLC methods. These compounds were also evaluated for antioxidant activities. Dihydrokawain (1) and yangonin (6) showed the highest COX-I and COX-II inhibitory activities at 100 microg/ml, respectively. The lipid oxidation assay did not reveal antioxidant activities for demethoxyangonin (2), dihydrokawain (1), kawain (4), dihydromethysticin (5) or methysticin (7) at 50 microg/ml. The antioxidant activities of flavokawain A (3) and yangonin (6) could not be tested in the lipid oxidation assay due to solubility problems. However, yangonin and methysticin showed moderate antioxidant activities in the free radical scavenging assay at 2.5 mg/ml.

Anti-Inflammatory Agents↗
PubMed2002

Effect of estrogen on scavenger receptor BI expression in the rat.

High-dose 17alpha-ethinyl estradiol treatment is associated with increased adrenal and decreased hepatic levels of scavenger receptor class B type 1 (SR-BI) in rats. In this paper we explored the mechanisms responsible for the differential regulation of SR-BI by estrogen in these two tIssues. Previously it was shown that estrogen-treated rats are profoundly hypolipidemic due to increased hepatic low density lipoprotein receptor (LDLR) activity, and that this effect is not maintained with hypophysectomy. To determine if the reduction in hepatic SR-BI was a direct or indirect effect of estrogen, we treated hypophysectomized rats with high-dose estrogen; the levels of SR-BI expression did not change in the livers or adrenals of these animals. To determine if the absence of response to estrogen in the adrenals of hypophysectomized animals was due to the absence of adrenocorticotropic hormone (ACTH), we examined the effect of estrogen treatment on SR-BI expression in animals treated with dexamethasone, which inhibits endogenous ACTH production. The administration of dexamethasone completely inhibited the increase in SR-BI expression in the adrenals of estrogen-treated rats. From these studies we conclude that estrogen does not have a direct effect on SR-BI expression in either the liver or the adrenals. In the liver, the decrease in SR-BI is dependent on the estrogen-induced increase in LDLR activity, and in the adrenal glands, ACTH is required for the estrogen-associated increase in expression of SR-BI.

Adrenal Glands↗
PubMed2001

Identification of two novel human dynein light chain genes, DNLC2A and DNLC2B, and their expression changes in hepatocellular carcinoma tissues from 68 Chinese patients.

Two full-length cDNAs, DNLC2A and DNLC2B, were cloned and characterized. Their open reading frames respectively encode 96 amino acids which are most closely homologous to roadblock/LC7, one member of an ancient dynein light chain protein family, conserved in nematode, fruit fly, mouse and rat. The DNLC2A was expressed in 12 of 16 human tissues examined, with especially strong expression in heart, liver and brain, whereas there was weak expression in lung, prostate, testis, small intestine and colon. The expression of DNLC2B was generally high compared with that of DNLC2A except in liver. Northern blotting and/or semi-quantitative RT-PCR analysis examined the expression changes of DNLC2A and DNLC2B in 68 hepatocellular carcinoma tissue samples. It was revealed that DNLC2A was up-regulated (45 out of the 68 cases) while DNLC2B was down-regulated (44 out of 68 cases), compared with their adjacent tumor-free liver tissues. Interestingly, among the total 68 liver cancer samples tested, DNLC2A was up-regulated while DNLC2B was down-regulated in 28 cases; DNLC2A was up-regulated while no obvious change was observed for DNLC2B in 10 cases; no obvious change was observed for DNLC2A while DNLC2B was down-regulated in 14 cases. Although the underlying mechanism is not clear to date, the apparent up-regulation of DNLC2A and down-regulation of DNLC2B suggest that these genes might be involved in tumor progression. On the other hand, the different expression changes of the two homologous genes indicate that hepatocellular carcinomas are caused by different pathological mechanisms. In addition, DNLC2A was assigned to human chromosome 20q12-q13.11 near the marker D20S106 by radiation hybrid mapping.

Adult↗
PubMed2001

LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model.

The N-nitroso-N-methylurea-induced rat mammary tumor model was used to conduct two types of studies: a prevention study designed to test the ability of the novel selective estrogen receptor modulator lasofoxifene (LAS) to inhibit the development of mammary tumors, and a treatment study designed to test the inhibitory effect of LAS on the growth of established tumors. The prevention study indicated that LAS markedly delayed the emergence of N-nitroso-N-methylurea-induced tumors to an extent similar to that obtained by the established antiestrogen tamoxifen (TAM). At the highest dose administered, both TAM and LAS reduced tumor incidence by 75% and total tumor number by 90% relative to the controls. LAS also reduced the multiplicity of tumors, i.e., the mean number of tumors per rat, and resulted in substantially smaller total tumor burden. In the treatment study, LAS significantly inhibited tumor growth compared with the controls. In addition, whereas none of the untreated tumors regressed completely over the experimental period, 40% of LAS-treated tumors regressed by >50% at the highest dose (10 mg/kg daily). The results of this study in a rat mammary tumor model indicate that LAS has both chemopreventive and chemotherapeutic effects quantitatively comparable with those of TAM.

Animals↗