SEARCH · PubMed Health

Results for “RB1”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed2001

Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide.

1. Panax ginseng is used to enhance stamina and relieve fatigue as well as physical stress. Ginsenoside, the effective component of ginseng, regulates cardiovascular function. This study was to examine the effect of ginsenosides Rb1 and Re on cardiac contractile function at the cellular level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz. Contractile properties analysed included: peak shortening (PS), time-to-90%PS (TPS), time-to-90% relengthening (TR90), and fluorescence intensity change (DeltaFFI). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay. 2. Both Rb1 and Re exhibited dose-dependent (1-1000 nM) inhibition in PS and DeltaFFI, with maximal inhibitions between 20-25%. Concurrent application Rb1 and Re did not produce any additive inhibition on peak shortening amplitude (with a maximal inhibition of 24.9+/-6.1%), compared to Rb1 or Re alone. Pretreatment with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished the effect of Rb1 and Re. Both Rb1 and Re significantly (P<0.05) stimulated NOS activity concentration-dependently. 3. This study demonstrated a direct depressant action of ginsenosides on cardiomyocyte contraction, which may be mediated in part through increased NO production.

Animals↗

PubMed2006

Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell lymphomas suggesting impaired cell cycle control in disease pathogenesis.

Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of nine Sézary syndrome (SS) cases but gain in two cases, and RB1 loss in four of seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23 mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF, seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1. These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in which dysregulated CCND and RB1 may lead to impaired cell cycle control.

Cell Nucleus↗

PubMed2006

Inhibitory effects of ginsenoside-Rb1 on activation of the 12-O-tetradecanoylphorbol 13-acetate-induced cyclooxygenase-2 promoter.

We studied the inhibitory effects of ginsenoside-Rb1 (1) on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transcriptional activation of the cyclooxygenase-2 (COX-2) promoter. The suppressive activity of ginsenoside-Rb1 was characterized using COX-2 promoter-driven luciferase reporter plasmids in a transient transfection system. Ginsenoside-Rb1 at 100 microM inhibited TPA-induced transcriptional activation of the COX-2 promoter. To identify the cis-acting elements responsible for this inhibition, the effects of site-specific mutations in the COX-2 promoter region were examined. Inhibition by ginsenoside-Rb1 was not affected by mutations in nuclear factor-kappaB- or cAMP-responsive elements. However, the effects were abolished when the nuclear factor-interleukin-6 binding site was mutated, indicating that ginsenoside-Rb1 exerts its effects via this element. In conclusion, ginsenoside-Rb1 inhibits TPA-induced COX-2 promoter activity through the nuclear factor interleukin-6 binding site and not through the nuclear factor-kappaB or cAMP-responsive elements.

Animals↗

PubMed1998

Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite.

The antimetastatic effects of orally administered ginsenoside Rb1 (Rb1) and an active metabolite by intestinal bacteria, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (I), were studied, by using a spontaneous metastasis model produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by intestinal bacteria) was first done and the data found were positively correlated to the antimetastatic effect of Rb1 through the medium of I. The transformation rate by 41% fecal specimens was less than 10% and consecutive Ginseng administrations were ineffective for the mice with hydrolyzing potential of less than 10%, which limited the antimetastatic efficacy of Rb1- In contrast, the efficacy of I was greater than that of Rb1 and at least comparable to that of S-FU. No effect of I on the primary tumor growth was found, indicating a specific antimetastatic activity. In a leg amputation model with the LLC-line, an effect on survival time of I (8 mg/kg/day) equal to that of 5-FU (10 mg/kg/day) was seen and 38% mice were cured as compared with 13% cured by amputation alone. These findings suggest that the active drug is the bacterial metabolite I which should be administered rather than Rb1.

Administration, Oral↗

PubMed1997

Constitutively methylated CpG dinucleotides as mutation hot spots in the retinoblastoma gene (RB1).

A wide spectrum of mutations, ranging from point mutations to large deletions, have been described in the retinoblastoma gene (RB1). Mutations have been found throughout the gene; however, these genetic alterations do not appear to be homogeneously distributed. In particular, a significant proportion of disease-causing mutations results in the premature termination of protein synthesis, and the majority of these mutations occur as C-->T transitions at CpG dinucleotides (CpGs). Such recurrent CpG mutations, including those found in RB1, are likely the result of the deamination of 5-methylcytosine within these CpGs. In the present study, we used the sodiumbisulfite conversion method to detect cytosine methylation in representative exons of RB1. We analyzed DNA from a variety of tissues and specifically targeted CGA codons in RB1, where recurrent premature termination mutations have been reported. We found that DNA methylation within RB1 exons 8, 14, 25, and 27 appeared to be restricted to CpGs, including six CGA codons. Other codons containing methylated cytosines have not been reported to be mutated. Therefore, disease-causing mutations at CpGs in RB1 appear to be determined by several factors, including the constitutive presence of DNA methylation at cytosines within CpGs, the specific codon within which the methylated cytosine is located, and the particular region of the gene within which that codon resides.

DNA↗

PubMed2001

A microsatellite fluorescent method for linkage analysis in familial retinoblastoma and deletion detection at the RB1 locus in retinoblastoma and osteosarcoma.

Linkage analysis at the retinoblastoma locus (RB1) is essential for identifying individuals at risk and to offer adequate genetic counseling in familial retinoblastoma. It can also be used to detect large deletions involving RB1, which accounts for 15% of the genetic alterations in hereditary retinoblastoma. These studies are usually carried out with lengthy Southern blot analyses of relatively uninformative restriction fragment length polymorphisms. The authors report an alternative, reliable protocol for genotyping the RB1 locus using two pairs of highly informative intragenic and flanking microsatellites linked closely to the RB1 gene, and analysis of the fluorescent-labeled polymerase chain reaction products with automatic sizing technology. This methodology has successfully identified high risk carriers in five of the five pedigrees of familial retinoblastoma studied. In addition, gross deletions affecting the RB1 gene were identified in two of 12 sporadic bilateral retinoblastomas, and loss of heterozygosity at the RB1 locus has been detected in one of three osteosarcomas using the same experimental protocol. The described protocol is simpler and faster than conventional Southern blot methodologies and can identify a larger number of informative cases.

Bone Neoplasms↗

PubMed1989

Mutations in the RB1 gene and their effects on transcription.

Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. To identify the mutations which inactivate RB1, 21 RB tumors isolated from 19 patients were analyzed with the polymerase chain reaction or an RNase protection assay or both. Mutations were identified in 13 of 21 RB tumors; in 8 tumors, the precise errors in nucleotide sequence were characterized. Each of four germ line mutations involved a small deletion or duplication, while three somatic mutations were point mutations leading to splice alterations and loss of an exon from the mature RB1 mRNA. We were unable to detect expression of the mutant allele in lymphoblasts of three bilaterally affected patients, although the mutation was present in the genomic DNA and transcripts containing the mutations were obvious in the RB tumors in the absence of a normal RB1 allele. The variations in the level of expression of mutant transcripts suggest deregulation of RB1 transcription in the absence of a functional RB1 gene product.

Alleles↗

PubMed2005

RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database.

BACKGROUND: Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships. RESULTS: A searchable database (RBGMdb) has been constructed with 932 published RB1 mutations. The spectrum of these mutations has been analyzed with the following results: 1) the retinoblastoma protein is frequently inactivated by deletions and nonsense mutations while missense mutations are the main inactivating event in most genetic diseases. 2) Near 40% of RB1 gene mutations are recurrent and gather in sixteen hot points, including twelve nonsense, two missense and three splicing mutations. The remainder mutations are scattered along RB1, being most frequent in exons 9, 10, 14, 17, 18, 20, and 23. 3) The analysis of RB1 mutations by country of origin of the patients identifies two groups in which the incidence of nonsense and splicing mutations show differences extremely significant, and suggest the involvement of predisposing ethnic backgrounds. 4) A significant association between late age at diagnosis and splicing mutations in bilateral retinoblastoma patients suggests the occurrence of a delayed-onset genotype. 5) Most of the reported mutations in low-penetrance families fall in three groups: a) Mutations in regulatory sequences at the promoter resulting in low expression of a normal Rb; b) Missense and in-frame deletions affecting non-essential sequence motifs which result in a partial inactivation of Rb functions; c) Splicing mutations leading to the reduction of normal mRNA splicing or to alternative splicing involving either true oncogenic or defective (weak) alleles. CONCLUSION: The analysis of RB1 gene mutations logged in the RBGMdb has shown relevant phenotype-genotype relationships and provided working hypothesis to ascertain mechanisms linking certain mutations to ethnicity, delayed onset of the disease and low-penetrance. Gene profiling of tumors will help to clarify the genetic background linked to ethnicity and variable expressivity or delayed onset phenotypes.

Codon, Nonsense↗

PubMed2004

Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-alpha and -beta, independent of ligand binding.

We studied the estrogenic activity of a component of Panax ginseng, ginsenoside-Rb1. The activity of ginsenoside-Rb1 was characterized in a transient transfection system, using estrogen receptor isoforms and estrogen-responsive luciferase plasmids, in COS monkey kidney cells. Ginsenoside-Rb1 activated both alpha and beta estrogen receptors in a dose-dependent manner with maximal activity observed at 100 microm, the highest concentration examined. Activation was inhibited by the estrogen receptor antagonist ICI 182,780, indicating that the effects were mediated through the estrogen receptor. Treatment with 17beta-estradiol or ginsenoside-Rb1 increased expression of the progesterone receptor, pS2, and estrogen receptor in MCF-7 cells and of AP-1-driven luciferase genes in COS cells. Although these data suggest that it is functionally very similar to 17beta-estradiol, ginsenoside-Rb1 failed to displace specific binding of [(3)H]17beta-estradiol from estrogen receptors in MCF-7 whole-cell ligand binding assays. Our results indicate that the estrogen-like activity of ginsenoside-Rb1 is independent of direct estrogen receptor association.

Animals↗

PubMed1988

[Ginsenoside-Rb1 as a suppressor in central modulation of feeding in the rat].

Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb1 on feeding behavior and endogenous chemical substances. Rb1 infusion into the rat third cerebroventricle was started at 1930 hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000 hr. Rb1 at doses of 0.05, 0.10 and 0.20 mumol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 mumol. Ambulatory activity was not affected in the doses tested. Infusion of Rb1 increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 mumol Rb1 into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb1 was found to have a suppressive effect on feeding partly through the VMH.

Animals↗

PubMed2000

Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island.

We recently showed loss of pRb in a proportion of pituitary tumors that was not associated with loss of heterozygosity of an RB1 intragenic marker. To further define the mechanism responsible for loss of retinoblastoma protein (pRb) expression, we have investigated the methylation status of the CpG island contained within the promoter region of the RB1 gene, together with sequence analysis of the essential promoter region and exons coding for the protein-binding pocket domain. Methylation of the CpG island within the RB1 promoter region was detected in 6 of 10 tumors that failed to express pRb. In contrast, 18 of 20 tumors and all six histologically normal postmortem pituitaries that expressed pRb were unmethylated. No inactivating mutations were found within the RB1 promoter region in the four unmethylated tumors that failed to express pRB. However, one or more exons comprising the coding region for the protein-binding pocket domain were shown to be homozygously deleted in three of four tumors available for analysis. This study describes an additional tumor type, in addition to retinoblastoma, in which methylation of the RB1 promoter is associated with loss of pRb expression. Furthermore, we show that in addition to methylation of the RB1 promoter region, deletion within the protein-binding pocket domain is associated with a loss of detectable pRb expression. The reactivation of tumor suppressor genes, silenced through methylation, represents a promising therapeutic target in sporadic pituitary adenomas.

Adenoma↗

PubMed2001

[Metabolism of ginsenoside Rb1 and panaxadiol saponins by fungi].

AIM: To study the metabolic process of ginsenoside Rb1 (G-Rb1) and panaxadiol saponins (PDS) by fungi. METHODS: Ten strains of fungi were incubated with G-Rb1 and PDS at a certain temperature with shaking. A portion was taken out at different time and mixed up with butanol. The butanol extract was analysed by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and electrospray ionazition mass spectrometry (ESI-MS). RESULTS: It was found that there were ginsenoside-Rd (G-Rd), ginsenoside-F2 (G-F2), compound K (CK) and 20(S) protopanaxadiol (Ppd) metabolites beside the prodrug G-Rb1 induced by fungi (No. 1, 2, 3, 6, 8, 9). CONCLUSION: The six strains of fungi have different degrees of ability to metabolize G-Rb1 and PDS. The possible metabolic process could be as follows: G-Rb1 (or PDS)-->G-Rd-->G-F2-->CK-->Ppd.

Aspergillus fumigatus↗

PubMed2003

[Experimental study of proliferation of Schwann cells cultured with ginsenoside Rb1].

OBJECTIVE: To investigate the effects of Ginsenoside Rb1 on the proliferation of Schwann cell cultured. METHODS: The sciatic nerve from SD rats was cultured in vitro; 10 micrograms/ml, 20 micrograms/ml, 200 micrograms/ml and 1 mg/ml Ginsenoside Rb1 was applied on the fifth day of culture. The proliferation of Schwann cells of sciatic nerves was determined in different time by MTT assay and thymidine incorporation assay. RESULTS: 10 micrograms/ml of Ginsenoside Rb1 significantly induced Schwann cell proliferation better than DMEM cell culture medium, but higher concentrations of Ginsenoside Rb1 at 1 mg/ml significantly inhibited the proliferation of Schwann cells, whereas 200 micrograms/ml of Ginsenoside Rb1 had similar effects to DMEM culture medium. CONCLUSION: Ginsenoside Rb1 at the optimal concentration is effective on inducing the proliferation of Schwann cells, but at higher concentration is cytotoxic for Schwann cells.

Animals↗

PubMed2003

RB1CC1 suppresses cell cycle progression through RB1 expression in human neoplastic cells.

RB1-inducible Coiled-Coil 1 (RB1CC1) is a putative transcription factor that functions as a key regulator of retinoblastoma 1 (RB1). RB1CC1 mutations lacking this function are involved in the tumorigenesis of breast cancers. RB1CC1 is distributed in various tissues other than the breast, and is thought to play a biological role in controlling cell growth and progression of various cancers. The present study examined the correlation between RB1CC1 and cell cycle-related molecules in human neoplastic cells, and the ratios of cells at various phases of the cell cycle were verified in the RB1CC1-transduced human leukemic cell lines, K562 and Jurkat. The results showed that RB1CC1 was synchronously expressed with RB1 in various cell lines and that introducing RB1CC1 induced RB1 expression in human leukemic cell lines, although independently of the other molecules. Western blotting showed that underphosphorylated forms of RB1 were elicited by RB1CC1, whereas E2F1 was not affected. Cell cycle analysis demonstrated that G2-M phases were suppressed in RB1CC1-transduced cells. These data suggested that RB1CC1 induces the expression of RB1, especially of underphosphorylated forms, then suppresses cell cycle progression in human neoplastic cells.

Autophagy-Related Proteins↗

PubMedDate not supplied

Methylation status of the retinoblastoma gene (RB1) in osteosarcoma: no evidence for hypermethylation.

Alterations of the retinoblastoma (RB1) tumor suppressor gene are not only associated with retinoblastoma but also with several other malignancies including osteosarcoma. Besides direct sequence alterations, hypermethylation of a CpG island in the promoter region can cause inactivation of the RB1 gene as it has been shown in retinoblastomas. We examined the methylation status of the RB1 gene in 25 osteosarcoma specimens by using the methylation-sensitive restriction enzymes SacII and SmaI. The restriction fragments were hybridized with clone p123, which is a 1.8-kb genomic subclone that spans the RB1 CpG island including the promoter region and exon 1. Whereas we reconfirmed hypermethylation of the RB1 gene in a sporadic retinoblastoma, no hypermethylation could be detected in the 25 osteosarcoma specimens, suggesting that hypermethylation of the RB1 promoter is not of major importance during osteosarcoma genesis.

DNA Methylation↗

PubMed1994

Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias.

The role of loss or inactivation of the retinoblastoma (Rb1) and p53 tumor suppressor genes in the pathogenesis of various human malignancies has been well established, yet little is known regarding plasma cell dyscrasias. In the present study, the loss of Rb1 protein expression, and the presence of Rb1 gene rearrangements as well as the presence of p53 somatic mutations (exons 5 through 9) were investigated in a panel of plasma cell dyscrasias, including 15 monoclonal gammopathies of undetermined significance (MGUS), 63 multiple myelomas (MM), and 18 plasma cell leukemias (PCL). In the same panel of cases, we established the frequency of ras oncogene mutations, the main genetic lesion associated with MM. We report that loss of Rb1 protein and p53 mutations are detectable in 34.7 and 9.8% of MM and PCL primary cases; no lesion was found in MGUS. In advanced stage MM, and PCL cases, Rb1 and p53 inactivation, as well as ras mutations were detected. Our findings show that Rb1 and p53 inactivation are associated with aggressive plasma cell dyscrasias, suggesting a role for these lesions in tumor progression rather than initiation.

Base Sequence↗

PubMed1993

Activation of gene transcription by the amino terminus of the N-Myc protein does not require association with the protein encoded by the retinoblastoma suppressor gene RB1.

N-Myc encodes a nuclear phosphoprotein that contains a basic region (BR), a helix-loop-helix (HLH) and a leucine zipper (Zip). These motifs are hallmarks of certain transcription factors. In pursuit of the question if N-Myc can activate transcription, we have employed an experimental model involving the yeast transcription factor Gal4. We have first generated fusion proteins containing the Gal4 DNA-binding domain joined to portions of N-Myc. Subsequently we have analysed if chimeric proteins can transactivate the transcription of a reporter under the control of Gal4 binding sites. Here we show that the amino terminal portion of N-Myc activates transcription. Activation maps to a domain highly conserved among Myc-proteins and to other non-conserved sequences, suggesting functional redundancy. Previous studies had documented in vitro association of the RB1 protein with N-Myc (Rustig et al., 1991). We here confirm this observation and identify the region encompassing the transactivation domain as responsible for RB1 binding. Analyses of N-Myc transactivation in retinoblastoma cell line WERI lacking a function RB1 protein gave results similar to those with cell lines having an intact RB1 protein, showing that RB1 protein is not required for transactivation by N-Myc. The present findings leave open the question if deregulated expression of N-Myc contributes to tumorigenesis by transcriptional activation of as yet unidentified target genes or by functionally inactivating the protein encoded by the tumor suppressor gene RB1, or by a combination of both.

DNA-Binding Proteins↗

PubMed1996

Allelic imbalance on chromosome 13q: evidence for the involvement of BRCA2 and RB1 in sporadic breast cancer.

Recently, the breast cancer susceptibility gene BRCA2 has been identified in chromosome 13q, a region that also contains the retinoblastoma gene RB1. To elucidate a possible role of BRCA2 and RB1 in sporadic breast tumorigenesis, allelic imbalance (AI) at 13q loci was examined in 78 primary sporadic breast tumors. AI was found in 52-63% of tumors. Nine tumors showed AI only in the BRCA2 region but not at RB1. Six tumors showed AI at RB1 but not in the BRCA2 region. AI in the BRCA2 region correlated significantly with aneuploidy (P = 0.032) and AI at RB1 with small tumor size (P = 0.025). Our data suggest that BRCA2 and RB1 may be both distinct target loci for AI on chromosome 13 in sporadic breast cancer.

Alleles↗