bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Herpesvirus 1
UL24
Gene Encodes a Potential PD-(D/E)XK Endonuclease
Authors: Kniżewski Łukasz , Kinch Lisa , Grishin Nick V. , Rychlewski Leszek , Ginalski Krzysztof 
Published: February 2006

ABSTRACT

Using Meta-BASIC, a highly sensitive method for detection of distant similarity between proteins, we have identified another potential PD-(D/E)XK endonuclease in human herpesvirus 1 (HHV-1) encoded by the
UL24
gene. The universal presence of
UL24
in completed herpesviral genomes of three major subfamilies,
Alphaherpesvirinae
,
Betaherpesvirinae
, and
Gammaherpesvirinae
, suggests a fundamental role for this predicted PD-(D/E)XK endonuclease activity in the viral life cycle.
The Level of Reverse Transcriptase (RT) in Human Immunodeficiency Virus Type 1 Particles Affects Susceptibility to Nonnucleoside RT Inhibitors but Not to Lamivudine
Authors: Ambrose Zandrea , Julias John G. , Boyer Paul L. , KewalRamani Vineet N. , Hughes Stephen H. 
Published: February 2006

ABSTRACT
We investigated the relationship between the level of reverse transcriptase (RT) in human immunodeficiency virus type 1 (HIV-1) particles and susceptibility to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 virions containing different active levels of RT were generated. Susceptibility to the NNRTIs efavirenz and nevirapine was inversely proportional to the level of enzymatically active RT. However, the sensitivity of HIV-1 to the nucleoside analog 3TC was not affected by the level of RT per particle. These data indicate that the susceptibility of HIV-1 to NNRTIs is influenced by RT activity.
Herpes Simplex Virus Tegument Protein VP16 Is a Component of Primary Enveloped Virions
Authors: Naldinho-Souto Raquel , Browne Helena , Minson Tony 
Published: February 2006

ABSTRACT
Immunogold electron microscopy was used to determine whether the tegument proteins VP13/14, VP22, and VP16 of herpes simplex virus type 1 (HSV1) are components of primary enveloped virions. Whereas VP13/14 and VP22 were not detected in virus particles in the perinuclear space and were present in only mature extracellular virions, VP16 was acquired prior to primary envelopment of the virus at the inner nuclear membrane. This finding highlights potential similarities and differences between HSV1 and the related alphaherpesvirus, pseudorabies virus, in which the homologues of all three of these tegument proteins are not incorporated into the virion until secondary envelopment.
EpCAM and gpA33 are markers of Barrett’s metaplasia
Authors: Wong N A C S , Warren B F , Piris J , Maynard N , Marshall R , Bodmer W F 
Published: February 2006

Aims:To characterise a specific and sensitive marker of Barrett’s metaplasia (BM).Methods:Cases of normal oesophageal squamous mucosa (11 fresh endoscopic biopsies and 10 formalin fixed, paraffin embedded tissue blocks), BM (11 biopsies and 11 tissue blocks), and normal gastric body mucosa (five biopsies and five tissue blocks) were analysed using reverse transcriptase PCR, Western blotting, and immunohistochemistry for EpCAM, and reverse transcriptase PCR for gpA33.Results:Strong EpCAM mRNA expression was detected in all the BM cases, in contrast to weak expression in all the normal gastric mucosal samples and no expression in any of the normal oesophageal mucosal samples tested. Strong gpA33 mRNA expression was detected in all the BM cases, in contrast to weak expression in a quarter of the normal gastric mucosal samples and no expression in any of the normal oesophageal mucosal samples tested. Western blotting showed EpCAM protein expression in all the BM cases and in none of the normal gastric or oesophageal mucosal samples tested. Immunohistochemistry showed strong EpCAM protein expression in BM and complete absence of expression in normal oesophageal squamous epithelium. Scattered EpCAM expressing cells were found in the gland bases of normal gastric body mucosa.Conclusions:EpCAM protein and gpA33 mRNA expressions are specific and sensitive markers of BM.
Carriage of group B streptococcus in pregnant women from Oxford, UK
Authors: Jones N , Oliver K , Jones Y , Haines A , Crook D 
Published: February 2006

Objective:To investigate asymptomatic vagino-rectal carriage of group B streptococcus (GBS) in pregnant women.Methods:Women in the final trimester of pregnancy were recruited. A single vagino-rectal swab was taken, with consent, for culture of GBS. Two microbiological methods for isolation of GBS from vagino-ractal swabs were compared. The distribution of capsular serotypes of the GBS identified was determined. Epidemiological data for a subset (n = 167) of the pregnant women participating were examined.Results:21.3% were colonised vagino-rectally with GBS. Risk factors for neonatal GBS disease (maternal fever, prolonged rupture of membranes, and preterm delivery) were present in 34 of 167 women (20.4%), and the presence of these factors correlated poorly with GBS carriage. Capsular serotypes III (26.4%), IA (25.8%), V (18.9%), and IB (15.7%) were prevalent in the GBS isolates. Selective broth culture of vagino-rectal swabs was superior to selective plate culture, but the combination of both methods was associated with increased detection of GBS (7.5%). An algorithm for the identification of GBS from vagino-rectal swabs was developed.Conclusions:GBS carriage is prevalent in pregnant women in Oxfordshire, UK. The poor correlation between risk factors and GBS carriage requires further investigation in larger groups, given that the identification of these surrogate markers is recommended to guide administration of intrapartum antibiotic prophylaxis by the Royal College of Obstetricians of the UK. A selective broth culture detected more GBS carriers than a selective plate culture.
Relationship of p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis
Authors: Hosaka N , Ryu T , Cui W , Li Q , Nishida A , Miyake T , Takaki T , Inaba M , Ikehara S 
Published: February 2006

Aims:To study the relationship between comedonecrosis formation and morphology, apoptosis, and p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancer.Experimental design:Early invasive breast cancers were first divided into two groups according to the presence (CN+ tumours) or absence (CN− tumours) of comedonecrosis. The histological grade, apoptosis, and expression of E-cadherin, Ki-67, p53 and Bcl-2 in the cancer-affected area, and in normal ducts from the specimen, were then examined.Results:Less tubule and gland formation was seen in CN+ tumours than in CN− tumours, although the histological grade between the groups was not different. During early comedonecrosis, cells undergo apoptosis and subsequent necrosis. p53 was higher in CN+ tumours than in CN− tumours and normal ducts, whereas Bcl-2 was lower in CN+ tumours than in CN− tumours and normal ducts. Both tumours had higher Ki-67 than in normal ducts, but no difference was evident between the tumours. CN+ tumours had slightly higher E-cadherin than that in CN− tumours, but lower than that in normal ducts. The level of comedonecrosis was positively correlated with p53, but inversely correlated with Bcl-2 in all tumours, and p53 and Bcl-2 were inversely correlated with each other. Furthermore, comedonecrosis and p53 were correlated with Ki-67 in CN+ tumours, and Bcl-2 was correlated with Ki-67 in CN− tumours.Conclusion:Comedonecrosis may be actively regulated through an apoptotic procedure in massive cancers for their survival and progression, and the above proteins may be associated cooperatively in this process. CN+ and CN− tumours may have opposite proliferative systems under the p53–Bcl-2 pathway.
Retinoic acid can induce markers of endocrine transdifferentiation in pancreatic ductal adenocarcinoma: preliminary observations from an in vitro cell line model
Authors: El-Metwally T H , Hussein M R , Abd-El-Ghaffar S Kh , Abo-El-Naga M M , Ulrich A B , Pour P M 
Published: February 2006

Background and hypothesis:The pancreatic ductal adenocarcinoma (HPAF) cells have a multipotent stem cell potential. It was hypothesised that all-trans-retinoic acid (atRA) can induce transdifferentiation of these cells into cells with an endocrine phenotype.Material and methods:To explore this hypothesis, an in vitro system of cells was established. Some cells were treated with atRA at concentrations of 100 nmol/l (non-apoptosis-inducing) and 5 μmol/l (apoptosis-inducing) and harvested. Cells were examined for cell cycle kinetics, apoptosis (terminal deoxynucleotidyl transferase assay and p53 protein expression) and immunomorphological features of redifferentiation (MUC1 and DUPAN-2) and endocrine transdifferentiation (insulin, somatostatin, glucagon, neurone-specific enolase) by using immunoperoxidase staining methods. Levels of insulin, transforming growth factor (TGF) β2, TGFα and epidermal growth factor receptor (EGFR) were measured by enzyme-linked immunosorbent assay (ELISA). The vehicle-treated cells served as a control group.Results:When compared with untreated cells, cells treated with 100 nmol/l and 5 μmol/l atRA were observed to show (1) decreased proliferative activity (cpm) as indicated by decreased incorporation of thymidine labelled with hydrogen-3; (2) cell cycle arrest; (3) increased apoptotic activity associated with p53 protein overexpression; (4) upregulated expression of the transdifferentiation and redifferentiation markers; (5) morphological changes indicative of transdifferentiation (increased cell size and appearance of dendrites); (6) decreased production of EGFR; (7) upregulation of TGFα and TGFβ2; and (8) increase in basal and glucose-induced insulin secretion.Conclusions:Functional endocrine transdifferentiation can be induced in HPAF lines by atRA. Further investigations are mandated to explore the underlying mechanisms of this transdifferentiation and to explore its in vivo extrapolation.
Patched1 Functions as a Gatekeeper by Promoting Cell Cycle Progression
Authors: Adolphe Christelle , Hetherington Rehan , Ellis Tammy , Wainwright Brandon 
Published: February 2006

Abstract
Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of β-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G1-S phase and G2-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a “gatekeeper.” In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors. (Cancer Res 2006; 66(4): 2081-8)
The Homeoprotein Six1 Transcriptionally Activates Multiple Protumorigenic Genes but Requires Ezrin to Promote Metastasis
Authors: Yu Yanlin , Davicioni Elai , Triche Timothy J. , Merlino Glenn 
Published: February 2006

AbstractThe vast majority of deaths associated with cancer are a consequence of a complex phenotypic behavior, metastasis, by which tumor cells spread from their primary site of origin to regional and distant sites. This process requires the tumor cell to make numerous adjustments, both subtle and dramatic, to successfully reach, survive, and flourish at favorable secondary sites. It has been suggested that molecular mechanisms accounting for metastatic behavior can recapitulate those employed during embryogenesis. We have shown that the homeodomain transcription factor Six1, known to be required for normal development of migratory myogenic progenitor cells, is sufficient to promote metastatic spread in a mouse model of the pediatric skeletal muscle cancer rhabdomyosarcoma. Here, we report that Six1 is able to activate the expression of a set of protumorigenic genes (encoding cyclin D1, c-Myc, and Ezrin) that can control cell proliferation, survival, and motility. Although the role of Ezrin in cytoskeletal organization and adhesion has been well studied, the means by which its expression is regulated are poorly understood. We now show that the gene encoding Ezrin is a direct transcriptional target of Six1. Moreover, Ezrin is indispensable for Six1-induced metastasis and highly expressed in a panel of representative pediatric cancers. Our data indicate that Ezrin represents a promising therapeutic target for patients with advanced-stage rhabdomyosarcoma and perhaps other malignancies. (Cancer Res 2006; 66(4): 1982-9)
Melanosomal Targeting Sequences from gp100 Are Essential for MHC Class II–Restricted Endogenous Epitope Presentation and Mobilization to Endosomal Compartments
Authors: Lepage Stéphanie , Lapointe Réjean 
Published: February 2006

AbstractCD4+ T lymphocytes play an important role in CD8+ T cell–mediated responses against tumors. Considering that ∼20% of melanomas express MHC class II, it is plausible that concomitant presentation by MHC class I and class II shapes positive (helper T cells) or negative (regulatory T cells) antitumor responses. Interestingly, gp100, a melanoma antigen, can be presented by both MHC class I and class II when expressed endogenously, suggesting that it can reach endosomal/MHC class II compartments (MIIC). Here, we showed that gp100 putative NH2-terminal signal sequence and the last 70 residues in COOH terminus are essential for MIIC localization and MHC class II presentation. Confocal microscopy analyses confirmed that gp100 was localized in LAMP-1+/HLA-DR+ endosomal/MIIC. Gp100 targeting sequences were characterized by deleting different sections in the COOH terminus (last 70 residues). Transfection in 293T cells, expressing MHC class I and class II molecules, revealed that specific deletions in COOH terminus resulted in decreased MHC class II presentation, without effects on class I presentation, suggesting a role in MIIC trafficking for these deleted sections. Then, we used these gp100 targeting sequences to mobilize green fluorescent protein to endosomal compartments and to allow MHC class II and class I presentation of minimal endogenous epitopes. We conclude that these specific sequences are MIIC-targeting motifs, which could be included in expression cassettes for endogenously expressed tumor or viral antigens for MHC class II and class I presentation and optimize in vivo T-cell responses or as an in vitro tool for characterization of new MHC class II epitopes. (Cancer Res 2006; 66(4): 2423-32)
BRCA1 DNA-Binding Activity Is Stimulated by BARD1
Authors: Simons Amanda M. , Horwitz Andrew A. , Starita Lea M. , Griffin Karen , Williams R. Scott , Glover J.N. Mark , Parvin Jeffrey D. 
Published: February 2006

Abstract
The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 binds to DNA, an interesting functional observation in light of the genetic data linking BRCA1 to DNA repair pathways. In this work, we reexamine the DNA-binding properties of BRCA1, comparing them with the DNA-binding properties of the BRCA1/BARD1 heterodimer. Because nuclear BRCA1 exists as a heterodimer with BARD1, it is likely that in vitro studies of the heterodimer will provide a more accurate model of physiologic conditions. Our results indicate that whereas BARD1 cannot directly bind DNA, it does enhance DNA binding by BRCA1. This is a surprising observation as both DNA-binding domains are distal to the BARD1-interacting RING domain of BRCA1. Further analysis of the dimerization reveals that the BRCA1/BARD1 interaction is not limited to the amino-terminal RING domains of each protein. The carboxyl terminus of BRCA1 contributes significantly to the stability of the heterodimer. We also show that the presence of BARD1 has a secondary effect, as autoubiquitination of BRCA1/BARD1 heterodimers additionally enhances the affinity of BRCA1 for DNA. Together, these data suggest that BRCA1 and BARD1 heterodimerization is stabilized via domains not previously thought to interact and that BARD1 acts in both ubiquitination-dependent and ubiquitination-independent ways to influence the role of BRCA1 in DNA repair. (Cancer Res 2006; 66(4): 2012-8)
Association between Plasma Prolactin Concentrations and Risk of Breast Cancer among Predominately Premenopausal Women
Authors: Tworoger Shelley S. , Sluss Patrick , Hankinson Susan E. 
Published: February 2006

Abstract
Recent evidence suggests that prolactin may be positively associated with postmenopausal breast cancer risk; however, little data are available in younger women. Therefore, we conducted a prospective, nested case-control study to examine the relationship between plasma prolactin concentrations and breast cancer risk in predominately premenopausal women from the Nurses' Health Study II. Blood samples were collected from 1996 to 1999. The analysis includes 316 cases of breast cancer diagnosed after blood donation and before June 1, 2003, who had two controls matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. Sixty-three percent of participants provided a timed follicular and luteal menstrual phase blood sample; other women provided a single untimed sample. When including all women, we observed a positive association between prolactin and breast cancer risk [relative risk (RR), top quartile versus bottom quartile, 1.5; 95% confidence interval (95% CI), 1.0-2.3; Ptrend = 0.03] that was slightly stronger among estrogen receptor–positive/progesterone receptor–positive tumors (comparable RR, 1.9; 95% CI, 1.1-3.3; Ptrend = 0.04). Associations were similar among premenopausal women only. However, we did not find an association between prolactin and breast cancer risk among the subset of women who only provided timed samples (comparable RR, average of timed samples, 1.3; 95% CI, 0.8-2.3; Ptrend = 0.40). The association seemed stronger among women ≥45 years old and for cases diagnosed within ∼4 years of blood collection. Our data suggest a modest positive association between prolactin and breast cancer risk among predominately premenopausal women; however, further follow-up is needed to increase power for subgroup analyses. (Cancer Res 2006; 66(4): 2476-82)
Cooperation between FGF8b Overexpression and PTEN Deficiency in Prostate Tumorigenesis
Authors: Zhong Chen , Saribekyan Gohar , Liao Chun-Peng , Cohen Michael B. , Roy-Burman Pradip 
Published: February 2006

Abstract
Two commonly occurring genetic aberrations of human prostate cancer [i.e., overexpression of a mitogenic polypeptide (fibroblast growth factor 8, isoform b or FGF8b) and loss of function of PTEN tumor suppressor] were recapitulated into a new combinatorial mouse model. This model harboring the Fgf8b transgene and haploinsufficiency in Pten, both in a prostate epithelium–specific manner, yielded prostatic adenocarcinoma with readily detectable lymph node metastases, whereas single models with each of the defects were shown earlier to progress generally only up to prostatic intraepithelial neoplasia (PIN). In addition to late age-related development of typical adenocarcinoma, the model also displayed a low incidence of mucinous adenocarcinoma, a rare variant type of human prostatic adenocarcinoma. The cooperation between FGF8b activation and PTEN deficiency must be linked to acquisition of additional genetic alterations for the progression of the lesions to primary adenocarcinoma. Here, we identified loss of heterozygosity at the Pten gene leading to bialleic loss, as a necessary secondary event, indicating that a complete loss of PTEN function is required in the development of invasive cancer in the model. Analyses of expression of downstream mediators phospho-AKT (p-AKT) and p27KIP1, in various types of lesions, however, revealed a complex picture. Although PIN lesions displayed relatively strong expression of p-AKT and p27KIP1, there was a notable heterogeneity with variable decrease in their immunostaining in adenocarcinomas. Together, the results further underscore the notion that besides activation of AKT by loss of PTEN function, other PTEN-regulated pathways must be operative for progression of lesions from PIN to adenocarcinoma. (Cancer Res 2006; 66(4): 2188-94)
The Novel Tumor Suppressor p33ING2 Enhances Nucleotide Excision Repair via Inducement of Histone H4 Acetylation and Chromatin Relaxation
Authors: Wang Jing , Chin Mei Yieng , Li Gang 
Published: February 2006

Abstract
p33ING2 is a novel candidate tumor suppressor, which has been shown to be involved in the regulation of gene transcription, cell cycle arrest, and apoptosis in a p53-dependent manner for maintaining the genomic stability. Previously, we showed that p33ING2 promoted UV-induced apoptosis in human melanoma cells. To further reveal the role of p33ING2 in cellular stress response to UV irradiation, we hypothesized that p33ING2 may enhance the repair of UV-damaged DNA, similarly to its homologue p33ING1b. Using the host-cell reactivation assay, we show that overexpression of p33ING2 significantly enhances nucleotide excision repair of UV-induced DNA damage in melanoma cells in a p53-dependent manner. Furthermore, DNA repair is completely abolished in cells treated with p33ING2 small interfering RNA, suggesting that a physiologic level of p33ING2 is required for nucleotide excision repair. In addition, we found that p33ING2 is an essential factor for UV-induced rapid histone H4 acetylation, chromatin relaxation, and the recruitment of damage recognition protein, xeroderma pigmentosum group A protein, to the photolesions. These observations suggest that p33ING2 is required for the initial DNA damage sensing and chromatin remodeling in the nucleotide excision repair process. (Cancer Res 2006; 66(4): 1906-11)