bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation to the Ionizing Radiation–Induced G2 Checkpoint Occurs in Human Cells and Depends on Checkpoint Kinase 1 and Polo-like Kinase 1 Kinases
Authors: Syljuåsen Randi G. , Jensen Sanne , Bartek Jiri , Lukas Jiri 
Published: November 2006

Abstract
Checkpoint adaptation was originally defined in yeast as the ability to divide despite the presence of damaged DNA. An important unanswered question is whether checkpoint adaptation also occurs in human cells. Here, we show that following the ionizing radiation–induced G2 checkpoint, human osteosarcoma cells entered mitosis with γ-H2AX foci, a marker for unrepaired DNA double-strand breaks. Exit from the G2 checkpoint was accelerated by inhibiting the checkpoint kinase 1 (Chk1) and delayed by overexpressing wild-type Chk1 or depleting the Polo-like kinase 1 (Plk1). Chk1 and Plk1 controlled this process, at least partly, via independent signaling pathways. Our results suggest that human cells are able to exit the checkpoint arrest and divide before the damage has been fully repaired. Such cell division in the presence of damaged DNA may be detrimental for genetic stability and could potentially contribute to cancer development. (Cancer Res 2006; 66(21): 10253-7)
Expression and Regulatory Role of GAIP-Interacting Protein GIPC in Pancreatic Adenocarcinoma
Authors: Muders Michael H. , Dutta Shamit K. , Wang Ling , Lau Julie S. , Bhattacharya Resham , Smyrk Thomas C. , Chari Suresh T. , Datta Kaustubh , Mukhopadhyay Debabrata 
Published: November 2006

Abstract
Regulator of G-protein signaling–GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy. (Cancer Res 2006; 66(21): 10264-8)
Potentiation of the Effect of Erlotinib by Genistein in Pancreatic Cancer: The Role of Akt and Nuclear Factor-κB
Authors: El-Rayes Basil F. , Ali Shadan , Ali Ifrah F. , Philip Philip A. , Abbruzzese James , Sarkar Fazlul H. 
Published: November 2006

Abstract
The epidermal growth factor receptor (EGFR) is a target of new therapies in most nonhematologic cancers. EGFR blockade alone may not be sufficient for the control of growth and invasion of human pancreas cancer because of the independent activation of Akt and nuclear factor-κB (NF-κB). The expression of EGFR, Akt, and NF-κB was determined in six human pancreatic cancer cell lines. Selected cells for specific expression were treated with erlotinib, genistein, gemcitabine, or the combination. Growth inhibition was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was assayed by ELISA. EGFR, phosphorylated EGFR, phosphorylated Akt, and survivin expressions were determined by immunoblotting. Electrophoretic mobility shift assay was used to evaluate the DNA binding activity of NF-κB. Genistein significantly increased (P &lt; 0.05) erlotinib-induced growth inhibition and apoptosis in BxPC-3, CAPAN-2, and AsPC-1 cells. In the BxPC-3 cell line, significant down-regulation of EGFR, phosphorylated Akt, NF-κB activation, and survivin was observed in the cells treated with the combination compared with the erlotinib-treated cells. In the HPAC and MIAPaCa cell line, no potentiation of the effects of erlotinib by genistein on cell growth or inhibition of the EGFR/Akt/NF-κB was observed. Genistein potentiated growth inhibition and apoptosis of the gemcitabine and erlotinib combination in COLO-357 cell line. Genistein potentiates the growth inhibition and apoptosis induced by erlotinib and gemcitabine in certain pancreatic cancer cells. Akt and NF-κB inhibition represents one of the mechanisms for the potentiation of erlotinib- and gemcitabine-induced cell death by genistein. (Cancer Res 2006; 66(21): 10553-9)
Global values shift and social work in America
Authors: Gross Emma 
Published: November 2006

English Advanced post-industrial countries manifest values change in the direction of greater secularity and self-actualization. Since 1980, however, America has shown evidence of regression towards authoritarian and anti-democratic values. This article explores why the regression is occurring and its negative implications for social welfare policy development and practice. French Les nations post-industrielles avancées manifestent des changements de valeurs dans la direction d'une plus grande sécularité et de l'actualisation de son potentiel personnel. Toutefois, depuis 1980 l'Amérique fait preuve évidente de régression vers des valeurs autoritaires et anti-démocratiques. Cet article explore les raisons de cette régression et ses répercussions négatives sur le développement des politiques sociales et sur les pratiques sociales. Spanish Los países avanzados post-industriales muestran un cambio de valores hacia mayor secularizad y autorrealización. Sin embargo, desde 1980 América muestra evidencia de una regresión hacia valores autoritarios y antidemocráticos. Se explora el por qué de esta regresión y las implicaciones negativas para el desarrollo y la práctica de la política de bienestar social.
A Strategy for Computer-Assisted Mental Practice in Stroke Rehabilitation
Authors: Gaggioli Andrea , Meneghini Andrea , Morganti Francesca , Alcaniz Mariano , Riva Giuseppe 
Published: November 2006

Objective. To investigate the technical and clinical viability of using computer-facilitated mental practice in the rehabilitation of upper-limb hemiparesis following stroke. Design.A single-case study. Setting. Academic-affiliated rehabilitation center. Participant. A 46-year-old man with stable motor deficit of the upper right limb following subcortical ischemic stroke. Intervention. Three computer-enhanced mental practice sessions per week at the rehabilitation center, in addition to usual physical therapy. A custom-made virtual reality system equipped with arm-tracking sensors was used to guide mental practice. The system was designed to superimpose over the (unseen) paretic arm a virtual reconstruction of the movement registered from the nonparetic arm. The laboratory intervention was followed by a 1-month home-rehabilitation program, making use of a portable display device. Main outcome measures. Pretreatment and posttreatment clinical assessment measures were the upper-extremity scale of the Fugl-Meyer Assessment of Sensorimotor Impairment and the Action Research Arm Test. Performance of the affected arm was evaluated using the healthy arm as the control condition. Results. The patient’s paretic limb improved after the first phase of intervention, with modest increases after home rehabilitation, as indicated by functional assessment scores and sensors data. Conclusion. Results suggest that technology-supported mental training is a feasible and potentially effective approach for improving motor skills after stroke.
Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience
Authors: Mazzucconi Maria Gabriella , Fazi Paola , Bernasconi Sayla , De Rossi Giulio , Leone Giuseppe , Gugliotta Luigi , Vianelli Nicola , Avvisati Giuseppe , Rodeghiero Francesco , Amendola Angela , Baronci Carlo , Carbone Cecilia , Quattrin Stefano , Fioritoni Giuseppe , D'Alfonso Giulio , Mandelli Franco ,   for the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party
Published: November 2006

Abstract
In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (< 18 years, 36 of 42 = 85.7%; ≥ 18 years, 41 of 48 = 85.4%, P = not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P = .018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial.
Transcriptional interference among the murine β-like globin genes
Authors: Hu Xiao , Eszterhas Susan , Pallazzi Nicolas , Bouhassira Eric E. , Fields Jennifer , Tanabe Osamu , Gerber Scott A. , Bulger Michael , Engel James Douglas , Groudine Mark , Fiering Steven 
Published: November 2006

AbstractMammalian β-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity. To investigate the influence of transcription by the murine embryonic genes on transcription of the other β-like genes, we generated mice with deletions of the promoter regions of Ey and βh1 and measured transcription of the remaining genes. Deletion of the Ey and βh1 promoters increased transcription of βmajor and βminor 2-fold to 3-fold during primitive erythropoiesis. Deletion of Ey did not affect βh1 nor did deletion of βh1 affect Ey, but Ey deletion uniquely activated transcription from βh0, a β-like globin gene immediately downstream of Ey. Protein analysis showed that βh0 encodes a translatable β-like globin protein that can pair with alpha globin. The lack of transcriptional interference between Ey and βh1 and the gene-specific repression of βh0 did not support LCR competition among the embryonic genes and suggested that direct transcriptional interference from Ey suppressed βh0.
Suppression of breast cancer cell growth by Na+/H+ exchanger regulatory factor 1 (NHERF1)
Authors: Pan Yong , Wang Lei , Le Dai Jia 
Published: November 2006

Abstract
Introduction
Na+/H+ exchanger regulatory factor 1 (NHERF1, also known as EBP50 or NHERF) is a putative tumour suppressor gene in human breast cancer. Located at 17q25.1, NHERF1 is frequently targeted during breast tumourigenesis. Loss of heterozygosity (LOH) at the NHERF1 locus is found in more than 50% of breast tumours. In addition, NHERF1 is mutated in a subset of primary breast tumours and breast cancer cell lines. LOH at the NHERF1 locus is strongly associated with aggressive features of breast tumours, implicating NHERF1 as a haploinsufficiency tumour suppressor gene. However, the putative NHERF1 tumour suppressor activity has not been functionally verified.

Methods
To confirm the NHERF1 tumour suppressor activity suggested by our genetic analyses, we used retrovirus-transduced short hairpin RNA (shRNA) to knock down NHERF1 expression in breast cancer cell lines MCF7 and T47D. These cells were then assessed for cell growth in vitro and in vivo. The control and NHERF1 knockdown cells were also serum-starved and re-fed to compare their cell cycle progression as measured by fluorescence-activated cell sorting analyses.

Results
We found that downregulation of the endogenous NHERF1 in T47D or MCF7 cells resulted in enhanced cell proliferation in both anchorage-dependent and -independent conditions compared with that of the vector control cells. NHERF1 knockdown T47D cells implanted at mammary fat pads of athymic mice formed larger tumours than did control cells. We found that serum-starved NHERF1 knockdown cells had a faster G1-to-S transition after serum re-stimulation than the control cells. Immunoblotting showed that the accelerated cell cycle progression in NHERF1 knockdown cells was accompanied by increased expression of cyclin E and elevated Rb phosphorylation level.

Conclusion
Our findings suggested that the normal NHERF1 function in mammary epithelial cells involves blockage of cell cycle progression. Our study affirmed the tumour suppressor activity of NHERF1 in breast which may be related to its regulatory effect on cell cycle. It warrants future investigation of this novel tumour suppressor pathway in human breast cancer which may turn up therapeutic opportunities.
GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
Authors: Abba Martín C , Nunez María I , Colussi Andrea G , Croce María V , Segal-Eiras Amada , Aldaz C Marcelo 
Published: November 2006

Abstract
Introduction
Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells.

Methods
Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5' flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays.

Results
We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas.

Conclusion
Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.
Monocytes infected withMycobacterium tuberculosisregulate MAP kinase-dependent astrocyte MMP-9 secretion
Authors: Harris James E , Green Justin A , Elkington Paul T , Friedland Jon S 
Published: November 2006

AbstractTuberculosis (TB) of the CNS (CNS-TB) carries a high mortality. Disease pathology is characterized by widespread destruction of CNS tissues. Matrix metalloproteinase-9 (MMP-9) is able to catabolyze specific components of the CNS tissue matrix and blood-brain barrier. Increased cerebrospinal fluid MMP-9 concentrations are associated with tissue damage, leukocyte infiltration, and death in CNS-TB. Using zymography, Western analysis, and transcription factor assays, we investigated mechanisms regulating MMP-9 activity in CNS-TB. We demonstrate that conditioned media from monocytes infected with Mycobacterium tuberculosis (CoMTB) induce MMP-9 secretion from astrocytes (U373-MG). IL-1β and TNF-α are necessary but not sufficient for such induction of astrocyte MMP-9 secretion. CoMTB up-regulates AP-1 DNA-binding activity, and the c-Jun, FosB, and JunB subunits are particularly increased. MMP-9 secretion from CoMTB-stimulated astrocytes is dependent on the activity of p38, Erk, and Jnk MAPKs. Phosphorylation of p38, Erk, and Jnk is activated rapidly, peaking 30 min poststimulation with CoMTB. Inhibition of IL-1β but not TNF-α in CoMTB decreases p38, Erk, and Jnk activity in astrocytes. Consistently, IL-1β signals through the MAPK cascade at physiological levels, whereas TNF-α, IL-6, IL-10, CCL-2, CCL-5, and CXCL-8 (all present in CoMTB) do not. In summary, the data suggest that monocyte-dependent cytokine networks may play a key role in the development of a matrix-degrading environment during CNS-TB.
Sequence of Atlantic cod (Gadus morhua) GLUT4, GLUT2 and GPDH:developmental stage expression, tissue expression and relationship to starvation-induced changes in blood glucose
Authors: Hall Jennifer R. , Short Connie E. , Driedzic William R. 
Published: November 2006

SUMMARYcDNAs of putative glucose transporters, GLUT4 and GLUT2, were cloned from Atlantic cod (Gadus morhua). The GLUT4 cDNA encodes a 503 amino acid and the GLUT2 cDNA a 506 amino acid protein. Phylogenetic analysis, amino acid sequence alignment, and tissue distribution support categorizing them as homologues of mammalian GLUT4 and 2. GLUT4 clusters with GLUT4s from fish and other vertebrates. It shows 84% amino acid identity to GLUT4 from coho salmon and brown trout and 65% identity with other vertebrates. It is most highly expressed in heart, strongly expressed in red and white skeletal muscle and present at lower levels in gill, gonad, intestine, and kidney. GLUT2 clusters with GLUT2 from rainbow trout and other vertebrates. It shows 75% amino acid identity with rainbow trout and 62% identity with chicken GLUT2. In Atlantic cod, GLUT2 is most highly expressed in liver with lower levels noted in intestine and kidney.Food deprivation for 2 months was used as a vehicle to monitor GLUT expression at different blood glucose levels. Starvation resulted in a decrease in blood glucose and liver glycogen that recovered following 20 days of re-feeding. GLUT4 expression in heart was decreased with starvation and increased with re-feeding. GLUT4 mRNA level in heart correlated with blood glucose. It is suggested that this relationship is related to insulin responsiveness. GLUT4 expression in white muscle increased with starvation and decreased with re-feeding. It is proposed that this is due to the necessity to maintain high levels of the glucose transporter protein in the face of starvation-associated proteolysis. GLUT2 expression in liver correlated with blood glucose, consistent with higher rates of glucose transport from liver to blood in the fed state than in the food-deprived state.Glycerol-3-phosphate dehydrogenase (GPDH) cDNA was also cloned. It encodes a 351 amino acid protein, which is 73-90% identical to GPDH from numerous other fish species. GPDH is ubiquitously expressed. Expression in heart decreased with starvation and increased with refeeding, whereas expression in liver did not change with starvation.In other studies, gene expression was monitored at nine time points from fertilization of eggs to larval development. GLUT4 is detectable in fertilized eggs and is fully expressed by the halfway to hatching point. GLUT2 is not evident at fertilization, is detectable at halfway to hatching, and fully expressed at hatching. GPDH expression was evident from fertilization.
Laryngeal pseudosarcoma
Authors: Giordano Anthony M. , Ewing Steve , Adams George , Maisel Robert 
Published: November 2006

AbstractIn the past laryngeal pseudosarcomas have been diagnosed as a. carcinosarcomas, b. pleomorphic or spindle cell carcinomas, or c. squamous cell carcinomas with pseudosarcomatous reactive stroma. Arguments have centered around the nature of the sarcomatous stroma. Because of this confusion there is disagreement as to the treatment and prognosis of these tumors.Seven pseudosarcomas were treated between 1969–1979, 4 were pedunculated and 3 exophytic. Treatment consisted of primary CO60 irradiation in 2 patients, surgery in 3 cases and combined therapy in 2 cases with no recurrences. Three of the 7 have died, 1 of a poorly differentiated adenosquamous carcinoma of the right main stem bronchus and the other 2 of natural causes at ages 77 and 85.From a review of the literature as well as our experience, we have reached the following conclusions. 1. Stromal cells are a malignant morphologic variant of the squamous cell and are best termed spindled cells. 2. Neck metastasis at any time is a poor prognostic sign. 3. The pattern of metastasis and survival seems to parallel laryngeal squamous cell carcinoma, and thus treatment should be similar for given stages.
Application of posterior neck dissection in treating malignant melanoma of the posterior scalp
Authors: Fisher Samuel R. , Cole T. Boyce , Seigler Hilliard F. 
Published: November 2006

AbstractUtilization of a posterior neck dissection in the treatment of nine patients with malignant melanoma of the posterior scalp is presented. Seven of nine patients presented with metastatic disease present in the posterior neck after initial treatment elsewhere. Four of the seven patients developed regional disease 4 months to 4 years following initial diagnosis. Variables dictating surgical treatment included the Clark's level, Breslow depth of invasion of original lesion, evidence of metastatic disease, and type of melanoma. The surgical technique of the posterior neck dissection is graphically depicted and the indications outlined. The posterior neck dissection is mandatory to adequately resect the primary lymphatics of the posterior scalp. Controlled studies are urged to determine the efficacy of prophylactic surgical lymphadenectomy in malignant melanoma of the head and neck.