p53 bcl-2 bax: Topics by WorldWideScience.org

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of #gamma# -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in #gamma# -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic ...

2002-10-20

Conformational Changes in BAK, a Pore-forming Proapoptotic Bcl-2 Family Member, upon Membrane Insertion and Direct Evidence for the Existence of BH3-BH3 Contact Interface in BAK Homo-oligomers*

During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage...Full Text Available

2003-04-01

The Prognostic Significance of p53, Bcl-2, Cytokeratin 20 and Ki-67 in Primary Superficial Papillary Transitional Bladder Carcinoma

During apoptosis, the pro-apoptotic Bcl-2 family proteins BAK and BAX form large oligomeric pores in the mitochondrial outer membrane. Apoptotic factors, including cytochrome c, are...Full Text Available

2010-09-10

Reactive oxygen species production and Bax/Bcl-2 regulation in honokiol-induced apoptosis in human hepatocellular carcinoma SMMC-7721 cells.

Identification of factors that determine individual patient risk for recurrence and progression in superficial papillary carcinoma of the bladder is a subject of extensive research as it would be a major outcome in patient management. It has been well recognized that traditional prognostic markers as tumor grade and stage are not accurate enough in predicting biological behavior. A large number of markers have been investigated as potential prognostic factors and relatively few can help in predicting outcome. Material and Methods: Forty-nine cases undergoing complete transurethral resection for primary superficial papillary transitional cell carcinoma were subjected to clinicopathologic evaluation as well as immunohistochemical staining for p53, bcl-2, cytokeratin 20 and Ki-67. The CAS-200 image analyzer was used to estimate the Ki-67 labeling index. Results: Recurrence was observed in 19 cases (38.8%) ...

2003-03-01

Bax Activation by Engagement with, Then Release from, the BH3 Binding Site of Bcl-x_L?

We investigated possible mechanism(s) where honokiol induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells. MTT assay showed that honokiol has strong inhibition on SMMC-7721 cells in a dose-dependent manner. SMMC-7721 cells after honokiol treatment display morphological characteristics such as cell shrinkage, detachment from the culture plate, formation of apoptotic bodies, change to a round shape, and marked nuclear condensation and fragmentation after 32258 staining. Cell apoptosis was measured by Annexin-V/PI staining and alternatively, by the subG0/G1 percentage of the cell cycle analysis followed by FACS. An obvious loss of ??(m) and a quick burst of ROS was detected when honokiol reached 4?g/ml, which was coincident with the high apoptosis percentage in our previous research. Up-regulation of Bax and down-regulation of Bcl-2 were observed, suggesting that honokiol-induced apoptosis was associated with ...

2009-03-17

Interplay Between Oncoproteins and Antioxidant Enzymes in Esophageal Carcinoma Treated Without and With Chemoradiotherapy: A Prospective Study

Bcl-2 homologues (such as Bcl-x_L) promote survival in part through sequestration of “activator” BH3-only proteins (such as Puma), preventing them from directly activating...Full Text Available

2011-02-01

The mitochondrial p53 pathway

Purpose: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. Methods and Materials: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. Results: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue ...

2008-02-01

Targeting the p53 Pathway in Ewing Sarcoma

p53 is one of the most mutated tumor suppressors in human cancers and as such has been intensively studied for a long time. p53 is a major orchestrator of the cellular response to a broad array...Full Text Available

2009-05-01

IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53...Full Text Available

2011-01-01

p53 protein in aggressive and non-aggressive basal cell carcinoma.

IL-4-induced Stat6 signaling is active in a variety of cell types and plays a role in cell proliferation/growth and resistance to apoptosis. Using EMSA, we identified differential IL-4/Stat6 activities in colorectal cancer cell lines, HT-29 being active Stat6"h"i"g"h phenotype and Caco-2 being defective Stat6"n"u"l"l phenotype, respectively. Active Stat6"h"i"g"h HT-29 cells exhibited resistance to apoptosis by flowcytometry and aggressive metastasis by Transwell assay compared with defective Stat6"n"u"l"l Caco-2 cells. Comparing one another using RT-PCR, Stat6"h"i"g"h HT-29 cells expressed more mRNA of anti-apoptotic and pro-metastatic genes Survivin, MDM2, and TMPRSS4, while Stat6"n"u"l"l Caco-2 cells expressed more mRNA of pro-apoptotic and anti-metastatic genes BAX, CAV1, and P53, respectively. This is the first study describing correlations of IL-4/Stat6 activities with apoptosis and metastasis in colon cancer. These ...

2008-05-02

Ubiquitin-Dependent Degradation of p53 Protein despite Phosphorylation at its N-Terminus by Acetaminophen

Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low ...

1993-10-01

The promises and perils of p53

We previously reported that acetaminophen (APAP) caused apoptosis of C6 glioma cells. Therefore, we hypothesized that the level of p53, which usually stimulates apoptosis, might be increased...Full Text Available

2006-04-01

The Regulation of Aging and Longevity

Five studies show that disabling p53, an essential tumour-suppressor protein, improves the efficiency of stem-cell production. Are these results a ‘heads up’ that cancer cells...Full Text Available

2009-08-27

Investigation and prediction of the severity of p53 mutants using parameters from structural calculations

p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest,...Full Text Available

2011-04-01

Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67

A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important...Full Text Available

2009-08-01

Coordination of PAD4 and HDAC2 in the regulation of p53 target gene expression

Aim—To study p53 expression in relation to proliferative status in normal and nondysplastic, dysplastic and malignant lesions of the oral mucosa.Method—The...Full Text Available

1996-06-01

Vitamin C increases the apoptosis via up-regulation p53 during cisplatin treatment in human colon cancer cells

Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available

2010-05-27

KoreaScience (Korea)

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2011-03-01

Wild-type p53 is not a negative regulator of simian virus 40 DNA replication in infected monkey cells.

A Small-Molecule p53 Activator Induces Apoptosis through Inhibiting MDMX Expression in Breast Cancer Cells12

To analyze the proposed growth-inhibitory function of wild-type p53, we compared simian virus 40 (SV40) DNA replication in primary rhesus monkey kidney (PRK) cells, which express wild-type p53, and...Full Text Available

1993-02-01

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

The tumor suppressor p53 is often inactivated in breast cancer cells because the overexpression of its repressors (e.g., MDM2 and MDMX). Restoration of p53 activity by small molecules through counteracting...Full Text Available

2011-07-01

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Extracellular Administration of BCL2 Protein Reduces Apoptosis and Improves Survival in a Murine Model of Sepsis

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional...Full Text Available

2011-06-01

Effect of Resveratrol on the Induction of Cdk Inhibitor p21 and Pro-apoptotic Bax Expression by amyloid-? in Astroglioma C6 Cells

BackgroundSevere sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic...Full Text Available

KoreaScience (Korea)

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2005-04-01

Spatial model of the horizontal steam generator of the WWER-1000 reactor within the framework of the ATHLET code

Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells

Russian 2004 p. 53 Russian Federation Kotsarev, AV Nikonov, SP FGU

2004-03-01

British Library Electronic Table of Contents (United Kingdom)

Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by ...

2008-01-01

Apoptotic pathways as regulators of recombination

Apoptosis induced by high- and low-LET radiations

Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 ...

2003-08-17

The EGFR antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1? and Bcl-2 and activating the beclin-1/hVps34 complex

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.).

p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin

Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here we report that autophagy is induced by cetuximab, a therapeutic...Full Text Available

2010-07-15

p53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism for Chemotherapy-Induced Cardiac Injury

Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available

2002-06-01

Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available

Polymorphisms in the p53 gene in thyroid tumours and blood samples of children from areas in Belarus

AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb,...Full Text Available

1999-12-01

Onset of Quiescence Following p53 Mediated Down-Regulation of H2AX in Normal Cells

We present changes in the p53 gene in a group of 70 thyroid tumours and 40 blood samples obtained from children from Belarus. Three thyroid tumours show a polymorphism in exon 6 (codon 213) and 5 tumours show a polymorphism in intron 6, 37 bp upstream to the 5'-end of exon 7. Only one patient has a mutation in exon 7 (codon 258) resulting in an amino acid substitution in the protein p53. The distribution of polymorphisms in the 40 blood samples was as follows: three patients had a polymorphism in exon 6 and two persons had a polymorphism in intron 6. One polymorphism in intron 6 was also found in the group of 30 healthy children from Belarus. The fact that the differences in the sequence in p53 found in the tumours was also seen in the blood of these patients demonstrates that they are polymorphisms not induced by radiation exposure. It is difficult to conclude, ...

Expression and prognostic significance of cox-2 and p-53 in hodgkin lymphomas: a retrospective study

Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability,...Full Text Available

Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy

BackgroundCyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2...Full Text Available

Expression and Redistribution of Cellular Bad, Bax, and Bcl-xL Protein Is Associated with VCD-Induced Ovotoxicity in ...

Purpose: To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). Methods and Materials: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using ...

2000-11-01

Identification of tumor-initiating cells in a p53-null mouse model of breast cancer.

... were given daily i.p. injections of either sesame oil (2.5 ml/kg, vehicle control) or VCD dissolved in sesame oil (80 mg/kg, 0.57 mmol/kg) for ... ...

Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: an immunohistochemical and immunoelectron microscopic study

Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this ...

2008-06-15

British Library Electronic Table of Contents (United Kingdom)

TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin se...

2011-01-01

Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila

Malignant solitary fibrous tumor of the thyroid gland: Report of a case and review of the literature

A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila....Full Text Available

2011-03-15

British Library Electronic Table of Contents (United Kingdom)

Abstract Solitary fibrous tumors of the thyroid gland (T-SFT) are rarely described, with only 21 cases being reported in the English literatures, all showing benign clinical characteristics. We herein present a 76-year-old woman presenting with a 3-month history of rapidly enlarging neck masses and the CT showed masses with partial calcification in the right thyroid lobe. We performed right hemithyroidectomy and isthmectomy with negative margin under general anesthesia. Histologically, the masses consisted of pleomorphic spindle cells with high mitoses and collagen bands. Immunohistochemically, the tumor cells showed positive reactions for CD34, vimentin and bcl-2, then a diagnosis of malignant solitary fibrous tumor of the right thyroid was made. Six months postoperatively, the CT showed ...

2011-01-01

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Benzo[a]pyrene diol epoxide-DNA cis adduct formation through a trans?chlorohydrin?intermediate

Phosphorylation of proteins in Clostridium thermohydrosulfuricum

Alkylation of DNA by 7r,8t-dihydroxy,9t,10t-epoxy-7,8,9,10-tetrahydrobenzob;a]pyrene (anti-BPDE) forms mainly trans adducts (with respect to the C-9/10...Full Text Available

1997-03-04

Energy Technology Data Exchange (ETDEWEB)

Cell extracts of the thermophile Clostridium thermohydrosulfuricum catalyzed the phosphorylation by (..gamma..-/sup 32/P)ATP of several endogenous proteins with M/sub r/s between 13,000 and 100,000. Serine and tyrosine were the main acceptors. Distinct substrate proteins were found in the soluble (e.g., proteins p66, p63, and p53 of M/sub r/s 66,000, 63,000, and 53,000, respectively) and particulate (p76 and p30) fractions, both of which contained protein kinase and phosphatase activity. The soluble fraction suppressed the phosphorylation of particulate proteins and contained a protein kinase inhibitor. Phosphorylation of p53 was promoted by 10..mu..M fructose 1,6-bisphosphate or glucose 1,6-bisphosphate and suppressed by hexose monophosphates, whereas p30 and p13 were suppressed by 5 ..mu..M brain (but not spinach) calmodulin. Polyamines, including the odd polyamines characteristic of thermophiles, ...

1986-02-01

A novel small-molecule inhibitor of NF-#kappa#B signaling

Regulation of Redd1 Expression by Hypoxia

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by ...

2008-04-18

p73 protein regulates DNA damage repair.

Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.

2006-05-25

Title of paper: the induction of P-53 independent programmed cell death (apoptosis) with ionizing radiation and 5-fluorouracil (5-FU) in the HT-29 human colon carcinoma cell line

Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision ...

2011-09-01

HSP70, the earliest-induced gene in the zebrafish retina during optic nerve regeneration: Its role in cell survival

Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce ...

1996-09-01

British Library Electronic Table of Contents (United Kingdom)

Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I s...

2011-01-01

Effect of sintering optimization on the electrical properties of bulk BaxSr1-xTiO3 ceramics

British Library Electronic Table of Contents (United Kingdom)

BaxSr1-xTiO3 (x=0.6, 0.75, 0.80, 0.85 and 0.9) compositions are prepared by solid-state reaction route using controlled heating and cooling. Density optimization by varying sintering temperature was achieved. X-ray diffraction (XRD) analysis shows the phase pure materials. The lattice constant decreases from 3.9868A (x=0.90) to 3.9449A (x=0.60) with increasing Sr2+; the tetragonal distortion also decreases. Dielectric constant show sharp peaks for samples having low strontium content (0.10, 0.15) and gets smeared out as the strontium content is increased (0.20, 0.25). For further higher Sr2+ composition (0.40), the dielectric peak could not be observed in the measured temperature range. The peak broadening in Sr2+ rich compositions indicates that diffused transitions and is attributed to t...

2008-01-01

The DFNA5 gene, responsible for hearing loss and involved in cancer, encodes a novel apoptosis-inducing protein

British Library Electronic Table of Contents (United Kingdom)

DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...

2011-01-01

[F-18]FDG PET metabolic indices for the evluation of glioma

Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

[F-18]FDG PET brain imaging is an accurate predictor of primary brain tumor grading and prognosis. The purpose of this study was to evaluate simplified [F-18]FDG PET metabolic indices as indicators of proliferative activity of brain tumor cells. Twenty-five patients with glioma were studied with [F-18]FDG PET. From the tissue radioactivity ratios, following tumor metabolic indices were calculated: 1) the tumor-to-whole brain ratio (T/WB), 2) the ratio of tumor-to-contralateral gray matter at the level of centrum semiovale (T/GM), 3) the ratio of tumor-to-contralateral white matter at the level of centrum semiovale (T/WM), 4) the tumor-to-ipsilateral cerebella ratio (T/iCB) and 5) the tumor-to-contralateral cerebellar ratio (T/cCB). A standardized threshold method was used to define ROIs in the tumor areas having representative metabolic activites. Correlations of the tumor metabolic indices with histologic grade, Ki-67 labeling index (Ki-67 LI), ...

1997-05-16

Energy Technology Data Exchange (ETDEWEB)

Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can ...

2003-11-27

Comparison of the radiobiological effect of carbon ion beam therapy and conventional radiation therapy on cervical cancer

Primary adenocarcinoma of the urinary bladder: value of cell cycle biomarkers.

Little clinical evidence has been provided to show the minimization of radiation resistance of tumors using high linear energy transfer radiation. We therefore investigated the radiobiological and molecular pathological aspects of carbon beam therapy. A total of 27 patients with squamous cell carcinoma (SCC) of the cervix were treated using a carbon beam and 50 control patients with SCC of the cervix using a photon beam. The expression of Ki-67, p53, and p27 proteins before radiotherapy and 5 and 15 days after therapy initiation were investigated using immunohistochemistry. Similar changes were observed in Ki-67 labeling index (LI) and p53 LI during carbon and photon beam therapies. However, for carbon beam therapy, the mean p27 LI significantly decreased from 25.2% before treatment to 18.6% on the 5th day after treatment initiation, followed by a significant increase to 36.1% on the 15th day. In ...

2008-09-01

Final report of the specific research. Investigations on the analysis of bio-protective factors against radiation. 1998-2000 FY (Research Group of NIRS)

Primary adenocarcinomas of the urinary bladder are uncommon, and the molecular pathways are currently not well defined. In this study, we assessed the association between biologic markers and clinicopathologic characteristics in a cohort of 21 patients with primary urinary bladder adenocarcinoma. Immunohistochemical staining for cell cycle-specific markers, including p53, p21, p27, Ki-67, and cyclin E, were performed on sections of a tissue microarray construct. The tumors were high grade in 12 (57%) and pT2 or higher in 18 (86%); lymph nodes were involved in 6 cases (29%); and there was pathologic evidence of schistosomiasis in 14 (67%). The best prognostic combination of markers was combined alterations in p27 and Ki-67 and was associated with stage (P = .012), grade (P = .005), DNA ploidy (P = .005), and lymph node involvement (P = .04). Stage, lymph node involvement, combined alterations of p27 and Ki-67, and combined alterations of all 5 ...

2011-06-01

Energy Technology Data Exchange (ETDEWEB)

This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also ...

2002-03-01

Effect of Nucleus Pulposus Cells Having Different Phenotypes on Chondrogenic Differentiation of Adipose-Derived Stromal Cells in a Coculture System Using Porous Membranes

British Library Electronic Table of Contents (United Kingdom)

In this study, adipose-derived stem cells (ASCs) were cocultured with nucleus pulposus (NP) cells using a porous membrane to investigate the effect of NP cell phenotype on ASC chondrogenic differentiation. Human NP cells were collected from 14 patients and classified into two groups (normal vs. degenerative) depending on the level of type II collagen, aggrecan (AGG), type I collagen, and bax gene expression. Human ASCs were then cocultured with each group of NP cells on porous membranes in the absence of chondrogenic supplements. After 2 weeks, real-time-polymerase chain reaction results showed that ASCs cocultured with normal NP cells had much higher type II collagen and AGG gene expression than ASCs cocultured with degenerative NP cells. The production of AGG was also observed only in th...

2011-01-01

Friend Spleen Focus-Forming Virus Activates the Tyrosine Kinase sf-Stk and the Transcription Factor PU.1 to Cause a Multi-Stage Erythroleukemia in Mice.