bluuebunny/crossref_metadata_2025_split huggingface dataset:
A long-term "memory" of HIF induction in response to chronic mild decreased oxygen after oxygen normalization
Authors: Kamat Chandrashekhar D , Thorpe Jessica E , Shenoy Satyendra S , Ceriello Antonio , Green Dixy E , Warnke Linda A , Ihnat Michael A 
Published: January 2007

Abstract

Background
Endothelial dysfunction (ED) is functionally characterized by decreased vasorelaxation, increased thrombosis, increased inflammation, and altered angiogenic potential, has been intimately associated with the progression and severity of cardiovascular disease. Patients with compromised cardiac function oftentimes have a state of chronic mild decreased oxygen at the level of the vasculature and organs, which has been shown to exacerbate ED. Hypoxia inducible factor (HIF) is a transcription factor complex shown to be the master regulator of the cellular response to decreased oxygen levels and many HIF target genes have been shown to be associated with ED.

Methods
Human endothelial and aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood oxygen levels in patients with heart failure, or to C) mild decreased oxygen for two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF signaling genes (HIF-1α, HIF-2α, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS) were measured both at the protein and mRNA levels.

Results
It was found that chronic exposure to mild decreased oxygen resulted in significantly increased HIF signaling. There was also a "memory" of HIF-1α and HIF target gene induction when oxygen levels were normalized for one week, and this "memory" could be interrupted by adding a small molecule HIF inhibitor to the last week of normalized oxygen. Finally, levels of ubiquitylated HIF-1α were reduced in response to chronic mild decreased oxygen and were not full restored after oxygen normalization.

Conclusion
These data suggest that HIF signaling may be contributing to the pathogenesis of endothelial dysfunction and that normalization of oxygen levels may not be enough to reduce vascular stress.
Construction and characterization of new piggyBac vectors for constitutive or inducible expression of heterologous gene pairs and the identification of a previously unrecognized activator sequence in piggyBac
Authors: Shi Xianzong , Harrison Robert L , Hollister Jason R , Mohammed Ahmed , Fraser Malcolm J , Jarvis Donald L 
Published: January 2007

AbstractBackgroundWe constructed and characterized several newpiggyBacvectors to provide transposition of constitutively- or inducibly-expressible heterologous gene pairs. The dual constitutive control element consists of back-to-back copies of a baculovirus immediate early (ie1) promoter separated by a baculovirus enhancer (hr5). The dual inducible control element consists of back-to-back copies of a minimal cytomegalovirus (CMVmin) promoter separated by a synthetic operator (TetO7), which drives transcription in the presence of a mutant transcriptional repressor plus tetracycline.ResultsCharacterization of these vectors revealed an unexpected position effect, in which heterologous genes adjacent to the 3'- terminal region ("rightward" genes) were consistently expressed at higher levels than those adjacent to the 5'-terminal region ("leftward" genes) of thepiggyBacelement. This position effect was observed with all six heterologous genes examined and with both transcriptional control elements. Further analysis demonstrated that this position effect resulted from stimulation of rightward gene expression by the internal domain sequence of the 3'-terminal region ofpiggyBac. Inserting a copy of this sequence into the 5'- terminal repeat region of our newpiggyBacvectors in either orientation stimulated leftward gene expression. RepresentativepiggyBacvectors designed for constitutive or inducible expression of heterologous gene pairs were shown to be functional as insect transformation vectors.ConclusionThis study is significant because (a) it demonstrates the utility of a strategy for the construction ofpiggyBacvectors that can provide constitutive or inducible heterologous gene pair expression and (b) it reveals the presence of a previously unrecognized transcriptional activator inpiggyBac, which is an important and increasingly utilized transposable element.
Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells
Authors: Pisano Marina , Pagnan Gabriella , Loi Monica , Mura Maria Elena , Tilocca Maria Giovanna , Palmieri Giuseppe , Fabbri Davide , Dettori Maria Antonietta , Delogu Giovanna , Ponzoni Mirco , Rozzo Carla 
Published: January 2007

Abstract

Background
Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic activity on melanoma cells. We tested eugenol together with six natural and synthetic eugenol-related compounds for their capability to inhibit cell growth on primary melanoma cell lines established from patients' tissue samples.

Results
Eugenol and isoeugenol monomers and their respective O-methylated forms did not show to inhibit melanoma cells proliferation. Conversely, the dimeric forms (biphenyls) showed some antiproliferative activity which was mild for dehydrodieugenol, higher for its O,O'- methylated form (O,O'-dimethyl-dehydrodieugenol), and markedly pronounced for the racemic mixture of the brominated biphenyl (6,6'-dibromo-dehydrodieugenol) (S7), being its enantiomeric form (S) the most effective compared to the other compounds. Such activity resulted to be selective against tumour cells, without affecting cultured normal human skin fibroblasts. Dose and time dependence curves have been obtained for the enantiomeric form S7-(S). Then IC50 and minimal effective doses and times have been established for the melanoma cell lines tested. TUNEL and phosphatidylserine exposure assays demonstrated the occurrence of apoptotic events associated with the antiproliferative activity of S7-(S). Cytotoxic activity and apoptosis induced by treating melanoma cells with eugenol-related biphenyls was partially dependent by caspase activation.

Conclusion
Our findings demonstrate that the eugenol related biphenyl (S)-6,6'-dibromo-dehydrodieugenol elicits specific antiproliferative activity on neuroectodermal tumour cells partially triggering apoptosis and its activity should be further investigated on in vivo melanoma models in order to evaluate the real anticancer effectiveness on such tumour.
M ulticenter randomi zed trial of cell the rapy in car diopat hies – MiHeart Study
Authors: Tura Bernardo R , Martino Helena F , Gowdak Luis H , dos Santos Ricardo Ribeiro , Dohmann Hans F , Krieger José E , Feitosa Gilson , Vilas-Boas Fábio , Oliveira Sérgio A , Silva Suzana A , Bozza Augusto Z , Borojevic Radovan , de Carvalho Antonio C Campos 
Published: January 2007

Abstract

Background
Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials.

Method/Design
We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group.

Discussion
Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies.
The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).
Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis
Authors: Wang Dong , Miller Scott C , Liu Xin-Ming , Anderson Brian , Wang Xu Sherry , Goldring Steven R 
Published: January 2007

Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology. Effective treatment of this disorder has been hampered by the lack of availability of agents that selectively target affected joint tissue. We developed a novel pH-sensitive drug delivery system of dexamethasone (Dex) based on an N-(2-hydroxypropyl)methacrylamide copolymer (P-Dex) and have shown that the delivery system specifically accumulates in inflamed joints in an animal model of arthritis. We hypothesize that the arthrotropism of the delivery system and the local acidosis-mediated drug release provide superior therapeutic efficacy and potentially reduced side effects in RA treatment. The initial in vitro drug-release study confirmed that the Dex release is indeed dependent upon the environmental pH. At pH 5, 37°C, the conjugate shows the highest level of drug release. When administered systemically in an adjuvant-induced arthritis rat model, P-Dex offers superior and longer-lasting anti-inflammatory effects compared with systemically administered free Dex. In addition, greater bone and cartilage preservation was observed with the P-Dex treatment compared with free Dex treatment. Our data indicate that the differential effect of the conjugate is related to its selective accumulation, potential macrophage-mediated retention, and pH-sensitive drug release (extracellular and intracellular) in arthritic joints. This newly developed drug delivery system provides a unique method for selective targeting of glucocorticoids to inflamed joints which may potentially reduce systemic side effects.
Phase III Randomized Trial of Conventional-Dose Chemotherapy With or Without High-Dose Chemotherapy and Autologous Hematopoietic Stem-Cell Rescue As First-Line Treatment for Patients With Poor-Prognosis Metastatic Germ Cell Tumors
Authors: Motzer Robert J. , Nichols Craig J. , Margolin Kim A. , Bacik Jennifer , Richardson Paul G. , Vogelzang Nicholas J. , Bajorin Dean F. , Lara Primo N. , Einhorn Lawrence , Mazumdar Madhu , Bosl George J. 
Published: January 2007

Purpose To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome. Patients and Methods In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT). Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were correlated with treatment outcome as a secondary end point. Results Two hundred nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone. The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after BEP alone (P = .53). Patients with slow serum tumor marker decline (alpha-fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of chemotherapy had a shorter progression-free survival and overall survival compared with patients with satisfactory marker decline (P = .02 and P = .03, respectively). Among 67 patients with unsatisfactory marker decline, the 1-year durable complete response proportion was 61% for patients who received HDCT versus 34% for patients receiving BEP alone (P = .03). Conclusion The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.
Patterns and Correlates of Patient Referral to Surgeons for Treatment of Breast Cancer
Authors: Katz Steven J. , Hofer Timothy P. , Hawley Sarah , Lantz Paula M. , Janz Nancy K. , Schwartz Kendra , Liu Lihua , Deapen Dennis , Morrow Monica 
Published: January 2007

Purpose Characteristics of surgeons and their hospitals have been associated with cancer treatments and outcomes. However, little is known about factors that are associated with referral pathways. Methods We analyzed tumor registry and survey data from women with breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries (n = 1,844; response rate, 77.4%) and their attending surgeons (n = 365; response rate 80.0%). Results About half of the patients (54.3%) reported that they were referred to the surgeon by another provider or health plan; 20.3% reported that they selected the surgeon; and 21.9% reported that they both were referred and were involved in selecting the surgeon. Patients who selected the surgeon based on reputation were more likely to have received treatment from a high-volume surgeon (adjusted odds ratio [OR], 2.2; 95% CI, 1.5 to 3.4) and more likely to have been treated in an American College of Surgeons–approved cancer program or a National Cancer Institute (NCI) –designated cancer center (adjusted OR, 2.0; 95% CI, 1.3 to 3.1; adjusted OR, 3.4; 95% CI, 1.9 to 6.2, respectively). Patients who were referred to the surgeon were less likely to be treated in an NCI-designated cancer center (adjusted OR, 0.5; 95% CI, 0.3 to 0.9). Conclusion Women with breast cancer who actively participate in the surgeon selection process are more likely to be treated by more experienced surgeons and in hospitals with cancer programs. Patients should be aware that provider or health plan–based referral may not connect them with the most experienced surgeon or comprehensive practice setting in their community.
Open-Label Phase II Study Evaluating the Efficacy and Safety of Two Doses of Pertuzumab in Castrate Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer
Authors: de Bono Johann Sebastian , Bellmunt Joaquim , Attard Gerhardt , Droz Jean Pierre , Miller Kurt , Flechon Aude , Sternberg Cora , Parker Chris , Zugmaier Gerhard , Hersberger-Gimenez Veronica , Cockey Louise , Mason Malcolm , Graham John 
Published: January 2007

Purpose To determine the prostate-specific antigen (PSA) 50% decline rate within 24 weeks of starting treatment with single-agent pertuzumab in castrate patients with hormone-refractory prostate cancer (HRPC). Patients and Methods Two independent Simon's two-stage designs were used to evaluate two doses of pertuzumab administered intravenously once every 3 weeks. An interim analysis of the first 23 assessable patients in the first cohort treated at 420 mg (loading dose of 840 mg) allowed termination of additional enrollment if ≤ three patients had a ≥ 50% decline in PSA after all patients had completed at least three cycles of therapy or withdrew due to insufficient therapeutic response, death, or study-related toxicity before completing three cycles. A second cohort of patients treated at 1,050 mg could be enrolled with the same design, and if more than three patients had a ≥ 50% decline in PSA, 27 more patients would be treated at 1,050 mg. Results Sixty-eight castrate, chemotherapy-naive men with HRPC were enrolled. A total of 35 patients were treated at 420 mg; no PSA declines ≥ 50% were observed at the interim analysis and recruitment was stopped. A total of 33 patients were then treated at 1,050 mg, and no PSA declines ≥ 50% were observed at the interim analysis. Pertuzumab was well tolerated. Conclusion Pertuzumab has no clinically significant single-agent activity in castrate patients with HRPC at either of the tested dose levels. This may reflect the continued presence of significant levels of intraprostatic androgen driving androgen receptor signaling.
Peritumoral Fibroblast SPARC Expression and Patient Outcome With Resectable Pancreatic Adenocarcinoma
Authors: Infante Jeffrey R. , Matsubayashi Hiroyuki , Sato Norihiro , Tonascia James , Klein Alison P. , Riall Taylor A. , Yeo Charles , Iacobuzio-Donahue Christine , Goggins Michael 
Published: January 2007

Purpose SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma. Patients and Methods The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status. Results By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% CI, 0.73 to 1.42). Conclusion The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.
Final Results of a Prospective Clinical Trial With VAMP and Low-Dose Involved-Field Radiation for Children With Low-Risk Hodgkin's Disease
Authors: Donaldson Sarah S. , Link Michael P. , Weinstein Howard J. , Rai Shesh N. , Brain Sam , Billett Amy L. , Hurwitz Craig A. , Krasin Matthew , Kun Larry E. , Marcus Karen C. , Tarbell Nancy J. , Young Jeffrey A. , Hudson Melissa M. 
Published: January 2007

Purpose To evaluate outcome and assess complications in children and adolescents with low-risk Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field radiation therapy (IFRT). Patients and Methods One hundred ten children with low-risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for those who achieved a complete response (CR) or 25.5 Gy for those with a partial response after two cycles of VAMP. Results With median follow-up of 9.6 years (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%, respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%. Factors contributing to 10-year EFS were: early CR (P = .02), absence of B symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less than three initial sites of disease (P = .02). Organ toxicity has been limited to correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac dysfunction. Seventeen healthy babies have been born to 106 survivors. There have been two malignant tumors: one thyroid cancer within the radiation therapy field and one Ewing's sarcoma outside the radiation therapy field. Conclusion Risk-adapted, combined-modality therapy using VAMP chemotherapy with radiation is effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease can be cured with therapy without an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiotherapy. Thus, these children are expected to retain normal fertility, organ function, and be at low risk of a second malignant tumor.
Acting ”Cool” and ”Appropriate”: Toward a Framework for considering Literacy Classroom Interactions When Race is a Factor
Authors: Rex Lesley A. 
Published: January 2007

In this article I draw on 3 incidents to investigate how teachers and students purposefully negotiate to manage incipient conflict when race is a confounding factor. I do so to propose a methodology and theoretical framework for researching multiracial classroom teaching and learning that could inform White literacy teachers' pedagogy with students of color. The approach construes race as a dynamic part of classroom social life in which expressions of race are affected by and affect teachers' and students' classroom norms of conduct. Race is observed in discursive practices that interactively and in fluentially construct social relationships, personal identity, and academic knowledge. I demonstrate the approach by illustrating how students manage problems and boundaries within commonplace classroom interactions. The language experience of the African diaspora is enmeshed with issues of culture, identity, memory, and citizenship. (Morgan, 1994, p. 339) For the sake of all children, it is time to act in ways that reflect genuine valuation of language diversity and to implement policies fostering multilingualism and dialect awareness. (Smitherman, 2004, p. 186)