Oxidation and interaction of DJ-1 with 20S proteasome in the erythrocytes of early stage Parkinson's disease patients.

Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress.

Radiosensitivity uncertainty evaluation for the in vitro biophysical modeling of EMT6 cells.

Background/aim: The aims of this study were to evaluate the cell survival uncertainty distribution of radiation and to assess the accuracy of predictions of tumor response by using three different in vitro experimental cell cultures with radiosensitizers (including etanidazole).

Materials And Methods: Using EMT6 cells and X-rays, the cell survival fraction was obtained from 15, 34, and 21 different experiments under normoxic, hypoxic, and hypoxic-plus-radiosensitizer culture, respectively.

Results: The α coefficients were 0.

[Impact of multileaf collimator leaf positioning accuracy on intensity modulated radiation therapy].

In multileaf collimator (MLC)-based intensity modulated radiation therapy (IMRT), the dose is influenced by the uncertainty of MLC driving control. In this study, we examined the influence of MLC driving control accuracy on dose evaluation (gamma analysis) by evaluating 60-day MLC driving control accuracy (stationary positioning accuracy and positioning reproducibility) once a week as well as measuring IMRT dose distribution. The MLC positioning accuracy accompanied variation over time and tended to expand by 0.

[Comparison of dose distribution on radiographic film and radiochromic film for intensity modulated radiation therapy].

Purpose: Radiographic film is generally used for inspection of dose distribution in intensity modulated radiation therapy (IMRT) at many institutions. However, the distribution of filmless systems can be expected to be used increasingly in the future. Therefore, we confirmed the utility of radiochromic film by comparing it with radiographic film that does not need an automatic processor.

Use of a diagnostic positron emission tomography-computed tomography system for planning radiotherapy positioning: distortion of the tabletop.

Purpose: The aim of this study was to evaluate distortion of the tabletop in a diagnostic positron emission tomography-computed tomography (PET-CT) system to determine its suitability for planning radiotherapy positioning.

Materials And Methods: Distortion of the tabletop was compared among PET-CT, lineac CT, and CT simulator systems. A phantom or angiography catheter was fixed to the tabletop and imaged after iron plate weight loading.

Preparation and application of monoclonal antibodies against oxidized DJ-1. Significant elevation of oxidized DJ-1 in erythrocytes of early-stage Parkinson disease patients.

DJ-1 was initially identified as a novel oncogene and has recently been found to be a causative gene for a familial form of Parkinson's disease (PD), viz, PARK7. Cysteine residue at position 106 (Cys-106) in DJ-1 was found to be oxidized preferentially under oxidative stress. In the present study, we developed specific antibodies against Cys-106-oxidized DJ-1 using baculovirus particles displaying the surface glycoprotein gp64-fusion protein as the immunizing agent.

Expression of estrogen receptor beta wild-type and its variant ERbetacx/beta2 is correlated with better prognosis in breast cancer.

Background: The clinical value of estrogen receptor (ER) beta and its variants has been investigated. However, reported results have frequently been discordant.

Methods: We investigated mRNA and protein expression of ERbeta wild type (ERbeta1) and its variant, ERbetacx/beta2, by quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry in 150 breast cancer tissues, and analyzed association between their expression and clinicopathological factors and prognosis.

Clinical analysis of paraneoplastic encephalitis associated with ovarian teratoma.

Background: Recently, paraneoplastic encephalitis associated with ovarian teratoma has been described and related to an autoantibody.

Methods: We describe four patients with ovarian teratoma-associated encephalitis (OTE) and compared their clinical pictures with those of 17 previously reported patients with OTE.

Results: Clinically, OTE was characterized by the development of acute prominent psychiatric symptoms (20 of 21 patients), seizures (15 of 21 patients), and central hypoventilation (13 of 21 patients).

Clinical usefulness of oral combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide for metastatic breast cancer.

Background: It has been reported that 5'-deoxy-5-fluorouridine (5'-DFUR), the pro-drug of 5-FU, is effective treatment for breast cancer that express thymidine phosphorylase (dThdPase). Since oral cyclophosphamide (CPA) induces dThdPase, a synergistic effect can be expected by combining CPA with 5'-DFUR. We evaluated the usefulness of combination chemotherapy using CPA and 5'-DFUR in patients with relapsed breast cancer in this prospective phase II study.

Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*.

Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha (ERalpha). Recent data indicate that chromatin inactivation mediated by histone deacetylation (HDAC) and DNA methylation is a critical component of ERalpha silencing in human breast cancer cells. The aim of this study was to determine the expression of the HDAC1 gene in malignant human breast tissue and to correlate our observations with available clinical information.

NCOR1 mRNA is an independent prognostic factor for breast cancer.

The transcriptional function of estrogen receptor alpha (ERalpha) can be modulated by co-regulatory proteins. In the present study, therefore, the level of expression of one of the co-regulator Nuclear Receptor Co-repressor 1 (NCOR1) mRNA has been assessed by quantitative real-time RT-PCR in 160 cases of invasive breast carcinoma. It was found that NCOR1 mRNA was expressed at significantly higher levels in patients over 50 years of age, without axillary lymph node involvement, with tumor size less than 2 cm, with low or intermediate histological grade, with ERalpha/PgR-positive and with HER2 negative tumors.

Biweekly paclitaxel in patients with metastatic breast cancer.

Background: This study was conducted to evaluate the efficacy and the toxicity of paclitaxel administered as a biweekly 1-h infusion (120 mg/m2).

Methods: Twenty patients with metastatic breast cancer were enrolled in this study. Paclitaxel was administered at a dose of 120 mg/m2 by an intravenous 1-h infusion every 2 weeks.

p33(ING1b) stimulates the transcriptional activity of the estrogen receptor alpha via its activation function (AF) 2 domain.

The ING1 gene was originally cloned as a candidate tumor suppressor of human breast cancer, and recent studies suggest that ING1 proteins are involved in chromatin remodeling functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigated whether p33(ING1b), one of the major ING1 isoforms, modulated the transcriptional activity of estrogen receptor (ER) alpha. In Cos-7 cells transfected with increasing concentrations of a mammalian expression vector encoding for p33(ING1b), estrogen-induced ERalpha transcriptional activity was found to increase in a dose-dependent manner.

Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast.

Background: Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-alpha. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor.

ING1 represses transcription by direct DNA binding and through effects on p53.

The ING family of proteins is involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis. These effects are most likely through activation of acetylation-dependent pathways that ultimately alter gene expression. Despite reports linking ING to p53 activation, the molecular basis of how ING activates p53 function has not been elucidated.

ING1 and p53 tumor suppressor gene alterations in adenocarcinomas of the esophagogastric junction.

The aim of this study was to characterize molecular alterations of the recently reported candidate tumor suppressor gene, ING1, and to explore the relationship between ING1 and p53 in a well-defined series of adenocarcinomas of the esophagogastric junction (AdEGJ). Polymerase chain reaction (PCR)-based assays were used to characterize ING1 and p53 alterations, relative to histologically normal esophageal mucosa. Two tumors were found to have ING1 mutations: one novel missense mutation (AGC(Ser)-->ATC(Ile)) at codon 147, and one silent mutation (TCG(Ser)-->TCA(Ser)) at codon 173.

Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women.

Background: An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha.

Methods: To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC).

Different HATS of the ING1 gene family.

The ING family of proteins are involved in chromatin remodelling, and bind to and affect the activity of histone acetyltransferase, histone deacetylase, and factor acetyltransferase protein complexes. Some family members affect transcription, including the expression of p53-inducible genes such as p21 and Bax, and ING2 induces p53 acetylation on a site implicated in the regulation of p53 activity. ING1 promotes DNA repair and interacts with proliferating cell nuclear antigen, thus linking DNA repair, apoptosis and chromatin remodelling.

Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer.

Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear.

ING1 isoforms differentially affect apoptosis in a cell age-dependent manner.

Recently, several novel human ING1 isoforms have been cloned. However,the biochemical functions and the involvement of these proteins in apoptosis remain uncharacterized. We have examined the apoptotic effects and biochemical functions of the two major human ING1 isoforms p47(ING1a) and p33(ING1b) in young and senescent human diploid fibroblasts induced to enter into apoptosis by diverse treatments.

Semi-quantitative immunohistochemical analysis of aromatase expression in ductal carcinoma in situ of the breast.

Although estrogens whose production is catalyzed by aromatase are considered to play a role in human breast carcinogenesis, it remains unclear whether aromatase expression occurs in ductal carcinoma in situ (DCIS) of the breast. Aromatase expression in 61 cases of pure DCIS and 101 cases of invasive ductal carcinoma (IDC) was investigated by immunohistochemical analysis using a polyclonal anti-aromatase antibody. The level of aromatase expression was semiquantified by the H-score which was estimated by the percentage of positive-staining cells and the intensity of staining.