bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of B7-H1 Expression in Clear Cell Carcinoma of the Kidney for Prognostication and Therapy
Authors: Thompson R. Houston , Dong Haidong , Kwon Eugene D. 
Published: January 2007

AbstractB7-H1 encompasses a recently discovered cell surface glycoprotein within the B7 family of T-cell coregulatory molecules. B7-H1 expression can be induced on activated T lymphocytes and is normally expressed by macrophage lineage cells. In addition, some human tumors acquire the ability to aberrantly express B7-H1. Tumor-associated B7-H1, as well as B7-H1 on activated lymphocytes, has been shown to impair antigen-specific T-cell function and survival in vitro. In contrast, in vivo monoclonal antibody–mediated blockade of B7-H1 has been shown to potentiate antitumoral responses in several murine cancer models. Consequently, tumor-associated B7-H1 has garnered much attention in the recent literature as a potential inhibitor of host antitumoral immunity. Our group has recently reported that B7-H1 is aberrantly expressed in both primary and metastatic renal cell carcinoma (RCC) as revealed via immunohistochemical staining of both fresh-frozen and paraffin-embedded nephrectomy specimens. In addition, we have shown that B7-H1 expression by clear cell RCC tumors (or infiltrating mononuclear cells) correlates with aggressive pathologic features, including advanced tumor-node-metastasis stage, tumor size, higher nuclear grade, and coagulative necrosis. In one study of 306 patients, with a median clinical follow-up of 11 years, we reported that RCC B7-H1 expression correlates with increased risk of disease progression, cancer-specific death, and overall mortality even after multivariate adjustment. Five-year cancer-specific survival rates in this study were 42% and 83% for patients harboring B7-H1+ versus B7-H1− RCC tumors, respectively. Such associations may relate to the recognized ability of B7-H1 to inhibit T-cell–mediated antitumoral immunity. In summary, B7-H1 encompasses a potent independent predictor of prognosis for patients with RCC and an extremely promising target to facilitate immunotherapeutic responses during the management of this treatment-refractory tumor.
Identification of the Genes for Kidney Cancer: Opportunity for Disease-Specific Targeted Therapeutics
Authors: Linehan W. Marston , Pinto Peter A. , Srinivasan Ramaprasad , Merino Maria , Choyke Peter , Choyke Lynda , Coleman Jonathan , Toro Jorge , Glenn Gladys , Vocke Cathy , Zbar Bert , Schmidt Laura S. , Bottaro Donald , Neckers Len 
Published: January 2007

Abstract
Recent advances in understanding the kidney cancer gene pathways has provided the foundation for the development of targeted therapeutic approaches for patients with this disease. Kidney cancer is not a single disease; it includes a number of different types of renal cancers, each with different histologic features, a different clinical course, a different response to therapy, and different genes causing the defects. Most of what is known about the genetic basis of kidney cancer has been learned from study of the inherited forms of kidney cancer: von Hippel Lindau (VHL gene), hereditary papillary renal carcinoma (c-Met gene), Birt Hogg Dubé (BHD gene), and hereditary leiomyomatosis renal cell cancer (fumarate hydratase gene). These Mendelian single-gene syndromes provide a unique opportunity to evaluate the effectiveness of agents that target the VHL, c-Met, BHD, and fumarate hydratase pathways.
Prospective Early Response Imaging Biomarker for Neoadjuvant Breast Cancer Chemotherapy
Authors: Lee Kuei C. , Moffat Bradford A. , Schott Anne F. , Layman Rachel , Ellingworth Steven , Juliar Rebecca , Khan Amjad P. , Helvie Mark , Meyer Charles R. , Chenevert Thomas L. , Rehemtulla Alnawaz , Ross Brian D. 
Published: January 2007

Abstract
Purpose: The American Cancer Society estimates that in 2006, 212,920 women will be diagnosed with breast cancer and that 40,970 women will die from the disease. The development of more efficacious chemotherapies has improved outcomes, but the rapid assessment of clinical benefit from these agents remains challenging. In breast cancer patients receiving neoadjuvant chemotherapy, treatment response is traditionally assessed by physical examination and volumetric-based measurements, which are subjective and require macroscopic changes in tumor morphology. In this study, we evaluate the feasibility of using diffusion magnetic resonance imaging (MRI) as a reliable and quantitative measure for the early assessment of response in a breast cancer model.
Experimental Design: Mice implanted with human breast cancer (MX-1) were treated with cyclophosphamide and evaluated using diffusion MRI and growth kinetics. Histologic analyses using terminal nucleotidyl transferase–mediated nick end labeling and H&E were done on tumor samples for correlation with imaging results.
Results: Cyclophosphamide treatment resulted in a significant reduction in tumor volumes compared with controls. The mean apparent diffusion change for treated tumors at days 4 and 7 posttreatment was 44 ± 5% and 94 ± 7%, respectively, which was statistically greater (P &lt; 0.05) than the control tumors at the same time intervals. The median time-to-progression for control and treated groups was 11 and 32 days, respectively (P &lt; 0.05).
Conclusion: Diffusion MRI was shown to detect early changes in the tumor microenvironment, which correlated with standard measures of tumor response as well as overall outcome. Moreover, these findings show the feasibility of using diffusion MRI for assessing treatment response of a breast tumor model in a neoadjuvant setting.
Biomarkers for Monitoring Antiangiogenic Therapy
Authors: Bhatt Rupal S. , Seth Pankaj , Sukhatme Vikas P. 
Published: January 2007

Abstract
A variety of antiangiogenic agents are currently available for the treatment of renal cell carcinoma. With these exciting new therapeutic agents comes the challenge of elucidating useful biomarkers to monitor patients receiving these therapies. Although many patients benefit from antiangiogenic therapies, it is often by achieving stability of their disease. Thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in the management of patients. The current technologies being explored in this field include circulating plasma proteins, cells, and nucleic acids and novel imaging techniques. Surrogate markers of angiogenesis could help with selecting patients for therapy, determining optimal dosing of therapy, deciding whether to change therapy, and assessing appropriate salvage therapy.
Reversal of Tumor-Mediated Immunosuppression
Authors: Vieweg Johannes , Su Zhen , Dahm Philipp , Kusmartsev Sergei 
Published: January 2007

AbstractTherapeutic cancer vaccines, one form of active immunotherapy, have long been under investigation; consequently, several vaccine-based strategies have now moved from the bench to the clinical arena. Despite their tremendous promise, current vaccine strategies have shown only limited success in clinical settings, even in renal cell carcinoma (RCC), a prototypical malignancy for the application of immunotherapy. There is ample evidence that, especially in RCC, multiple immunosuppressive mechanisms exist that considerably dampen antitumor responses and weaken the activity of current immunotherapeutic regimens. Therefore, it will be necessary to reverse tumor-mediated immunosuppression before immunotherapies can successfully be applied. Recent insights into the nature and characteristics of the regulatory elements of the immune system have provided new opportunities to enhance vaccine-mediated antitumor immunity and, thereby, increase the chance for improving patient outcome. These new insights represent important considerations for the future design and application of more effective cancer vaccines against RCC and other cancers.
PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Mellinghoff Ingo K. , Cloughesy Tim F. , Mischel Paul S. 
Published: January 2007

Abstract
Molecularly targeted therapies are transforming the treatment of cancer. Elucidating the dynamic signaling networks that underlie sensitivity and resistance to these inhibitors is critical for successful clinical application. There is considerable evidence to suggest that constitutively activating mutations in kinases that regulate cellular growth may result in tumor cell “addiction” and favorable response to targeted inhibition. However, there is emerging evidence to suggest that clinical response may also be determined by other changes in the molecular circuitry of cancer cells, such as loss of key tumor-suppressor proteins. Here, we will discuss resistance to epidermal growth factor receptor tyrosine kinase inhibitors in glioblastoma patients that is mediated by loss of the PTEN tumor-suppressor protein.
Sorafenib in Renal Cell Carcinoma
Authors: Flaherty Keith T. 
Published: January 2007

AbstractSorafenib is an orally available inhibitor of vascular endothelial growth factor receptors, platelet-derived growth factor receptor-β, and RAF kinases. A dose of 400 mg twice daily administered continuously was selected for phase 2 testing, although 600 mg twice daily formally met criteria for a maximum tolerated dose. It is well tolerated compared with cytokine therapy. Antitumor activity was shown clearly in the context of a randomized discontinuation phase 2 trial. In this setting, even disease stabilization was established as a treatment-related phenomenon. A phase 3 trial with sorafenib confirmed a benefit of therapy across the vast majority of patients treated with sorafenib as opposed to placebo. Limited investigations into the mechanism of action of sorafenib in renal cell carcinoma support vascular endothelial growth factor receptor antagonism as the primary mediator of effect. The toxicity profile of sorafenib allows for its use in combination regimens. The focus of efforts to improve on the efficacy of sorafenib is on use with IFN, bevacizumab, or temsirolimus. Preliminary evidence with this approach is promising and will be the subject of the next generation of randomized trials in renal cell carcinoma.
Prognostic Role of the Reduced Folate Carrier, the Major Membrane Transporter for Methotrexate, in Childhood Acute Lymphoblastic Leukemia: A Report from the Children's Oncology Group
Authors: Ge Yubin , Haska Christina L. , LaFiura Katherine , Devidas Meenakshi , Linda Stephen B. , Liu Mingjun , Thomas Ronald , Taub Jeffrey W. , Matherly Larry H. 
Published: January 2007

AbstractPurpose: The value of measuring expression of individual genes relevant to particular chemotherapy drugs and encoding metabolizing enzymes, transporters, or drug targets, as predictors of treatment response and outcome in pediatric acute lymphoblastic leukemia (ALL), remains controversial.Experimental Design: In a case-control population of 91 pediatric B-precursor ALL patients [42 relapsed within 4 years (cases) and 49 did not relapse (controls)], we used real-time reverse transcription-PCR to measure transcript levels for 20 genes relevant to chemotherapy with the five major drugs used to treat this disease, including asparaginase, 6-mercaptopurine, methotrexate, prednisone, and vincristine. Results were confirmed in a separate case-control population of 26 patients.Results: Only the human reduced folate carrier (hRFC) gene, encoding the major membrane transporter for methotrexate, showed a significant difference in median transcript levels between the 42 cases and the 49 controls (P = 0.0278, Wilcoxon test). Using cutoffs for hRFC expression levels (based on Akaike information criterion), there were statistically significant associations between hRFC transcripts and treatment relapse (P = 0.0052). hRFC-B, corresponding to the major hRFC transcript form in ALL, was also measured by real-time reverse transcription-PCR and was prognostic. The association between treatment relapse and hRFC levels was validated in a separate study population of 14 cases and 12 controls from an earlier case-control study (P = 0.0221).Conclusions: Our results strongly suggest the prognostic importance of hRFC gene expression to treatment outcomes in pediatric ALL. They validate our previous studies of hRFC transcriptional regulation in pediatric ALL and provide further compelling evidence for the critical role for methotrexate in the successful treatment of this disease.
Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma
Authors: Ochoa Augusto C. , Zea Arnold H. , Hernandez Claudia , Rodriguez Paulo C. 
Published: January 2007

AbstractTumor-induced tolerance is a well-established phenomenon in cancer patients that can severely impair the therapeutic efficacy of immunotherapy. One mechanism leading to T-cell tolerance is the generation of myeloid-derived suppressor cells (MDSC) by soluble factors produced by the tumor. MDSC express CD11b+ as a common marker but may vary in their stage of maturation, depending on the tumor factors being produced. Arginase production by MDSC depletes arginine from the tumor microenvironment and impairs T-cell signal transduction and function. We studied whether an increase in MDSC could explain the molecular alterations and dysfunction found in T cells of patients with renal cell carcinoma (RCC). Arginase activity in the peripheral blood mononuclear cells of 117 RCC patients was increased between 6- to 8-fold compared with normal controls. The increased arginase activity was limited to the CD11b+CD14− myeloid cells and resulted in significantly decreased serum levels of arginine and increased ornithine in patients. Depletion of MDSC restored IFN-γ production and T-cell proliferation. Preliminary data suggest that prostaglandin E2 produced by the tumor induces arginase I expression in MDSC. Therefore, blocking MDSC activity may enhance the therapeutic efficacy of immunotherapy in RCC.
Innovations and Challenges in Renal Cell Carcinoma: Summary Statement from the Second Cambridge Conference
Authors: Atkins Michael B. , Ernstoff Marc S. , Figlin Robert A. , Flaherty Keith T. , George Daniel J. , Kaelin William G. , Kwon Eugene D. , Libermann Towia A. , Linehan W. Marston , McDermott David F. , Ochoa Augusto C. , Pantuck Allan J. , Rini Brian I. , Rosen Mark A. , Sosman Jeffrey A. , Sukhatme Vikas P. , Vieweg Johannes W. , Wood Christopher G. , King Laura 
Published: January 2007

Abstract
Innovations and Challenges in Renal Cancer, chaired by Michael B. Atkins, was held April 28 to 29, 2006 in Cambridge, Massachusetts. The conference brought together leading experts in the fields of cancer research, medical oncology, urology, immunology, radiology, and immunotherapy, with the goal of advancing the field of renal cancer treatment by critiquing new data from ongoing clinical trials and stimulating communication among those involved in basic and clinical research. The conference proceedings published in this educational supplement to Clinical Cancer Research are intended to provide timely information and recommendations on important aspects of renal cancer genetics and biology and advances in prognostic classification and treatment.
Remote Sensing of Water Cloud Parameters Using Neural Networks
Authors: Cerdeña Abidán , González Albano , Pérez Juan C. 
Published: January 2007

Abstract
In this work a method for determining the micro- and macrophysical properties of oceanic stratocumulus clouds is presented. It is based on the inversion of a radiative transfer model that computes the albedos and brightness temperatures in the NOAA Advanced Very High Resolution Radiometer (AVHRR) channels. This inversion is performed using artificial neural networks (ANNs), which are trained and optimized by genetic algorithms to fit theoretical computations. A detailed study of the ANN parameters and training algorithms demonstrates the convenience of using the “backpropagation with momentum” method. The proposed retrieval method is applied to daytime and nighttime imagery and was validated using ground data collected in Tenerife (Canary Islands), obtaining a good agreement.
Wideband Reception and Processing for Dual-Polarization Radars with Dual Transmitters
Authors: Choudhury Sutanay , Chandrasekar V. 
Published: January 2007

Abstract
Oversampling pulsed Doppler radar returns at a rate larger than the pulse bandwidth, whitening the range samples, and subsequent averaging has been pursued as a potential way to decrease the measured standard deviation of signal parameter estimates. It has been shown that the application of oversampling, whitening, and subsequent averaging improves the quality of reflectivity, mean velocity, and spectral width estimates in agreement with theory. Application of this procedure to a dual-polarization radar with dual transmitters is evaluated in this paper. Oversampled data collected from the Colorado State University (CSU)-University of Chicago–Illinois State Water Survey (CHILL) radar using a wideband receiver are analyzed to evaluate the performance of dual-polarization parameter estimators, such as differential reflectivity and differential phase. The negative impact of relative phase characteristics of the transmitted pulses in two polarizations on the copolar correlation, and subsequently on polarimetric parameter estimation, is analyzed. CSU-CHILL radar’s transmitted pulse sampling capability is used to evaluate the impact of the transmitted waveform’s mismatch on whitening and estimation.
Reasons given by high school students for refusing sexually transmitted disease screening
Authors: Sanders Ladatra S , Nsuami Malanda , Cropley Lorelei D , Taylor Stephanie N 
Published: January 2007

Objective To determine reasons given by high school students for refusing to participate in a school-based noninvasive chlamydia and gonorrhea screening that was offered at no cost to students, using the health belief model as theoretical framework. Design Cross-sectional survey. Setting Public high schools in a southern urban United States school district. Methods Every year since the school year 1995–1996, students in the school district have been offered free and confidential chlamydia and gonorrhea screening using nucleic acid amplification tests in urine specimens. All youth in the participating schools are eligible for screening if they have parental consent or are aged 18 years or older and provide consent. In 2004–2005, 50 males and 106 females who had consent but chose not to participate were asked to fill out a self-administered confidential survey about their reasons for refusing participation. Results The most frequent single reason males gave for refusing to participate in the screening was that they just did not want to take the test ( n = 24); females most frequently refused because they have never had sex ( n = 32) or they just did not want to take the test ( n = 26). Respectively, 22 males (44.0 per cent) and 63 females (59.4 per cent) perceived themselves not being susceptible to chlamydia or gonorrhea, 2 males (4.0 per cent) and 2 females (1.9 per cent) felt chlamydia and gonorrhea were not serious diseases, 11 males (22.0 per cent) and 37 females (34.9 per cent) perceived barriers and 4 males (8.0 per cent) and 1 female (0.9 per cent) saw no benefi t to chlamydia or gonorrhea screening. Conclusion Respondents most frequently refused to participate because they simply did not want to take the test. Most females refused because they had never had sex. Many perceived themselves as not being susceptible to chlamydia and gonorrhea solely on the basis of misconceptions that are amenable to correction through health education.
Schoolchildren who are victims of bullying report benefit from health dialogues with the school health nurse
Authors: Borup Ina , Holstein Bjørn E 
Published: January 2007

Background School health services are important tools for health promotion among schoolchildren, but little is known about their effects. This article addresses the effects of dialogues with school health nurses among schoolchildren who were victims of bullying. Study population and methods Cross-sectional and school-based survey, the Danish contribution to the international Health Behaviour in School-aged Children (HBSC) study. The study included all students in the fifth, seventh, and ninth grade (11, 13, and 15 year olds) in a random sample of schools. The participation rate was 98 per cent of the students present on the day of data collection and 88 per cent of the enrolled students, n = 5205. Measurements Bullying was measured as recommended by Olweus. Outcome of the dialogue with the school health nurse was measured as self-reports of five responses: (1) reflected on the dialogue, (2) discussed the content with parents, (3) followed the advice from the school health nurse, (4) did what he (she) himself (herself) thought was best, and (5) visited the school health nurse again. Results All outcome measures were more prevalent among students who were victims of bullying. The most pronounced association was that the odds ratio for visiting the school health nurse again was 1.8 (95 per cent CI 1.3–2.5) for students who were bullied at least weekly. Conclusion Schoolchildren who are victims of bullying benefit from health dialogues with the school health nurse.
A study of the gender-specific mortality rates in Korea and Japan for the formation of health promotion policy
Authors: Nam Eun-Woo , Song Yea-Li-A 
Published: January 2007

Objective This study attempts to provide fundamental information to help with the development of health policy and health services by looking at the trends of the gender-specific mortality rates in Korea and Japan. Design The death statistics of Korea and Japan over the 21-year period from 1983 to 2003 are analyzed. Setting We used the death statistics and estimated population fi gures published by the Korean National Statistical Office, and the vital statistics published by Ministry of Health and Welfare of Japan. Method Mortality data are standardized ×100,000 to 2001/2003. specific mortality rates from 12 selected causes are considered: tuberculosis, malignant neoplasms, diabetes mellitus, hypertensive diseases, heart diseases, cerebrovascular disease, pneumonia, diseases of the liver, renal failure, transport accidents, falls and suicide. Results In Korea, the mortality rates from malignant neoplasms, diabetes mellitus, renal failure, falls and suicide have increased. The proportion of the mortality rates from chronic diseases is higher than from acute diseases. In Japan, the mortality rate from pneumonia increased more than that from diabetes mellitus. The gap in mortality rates between males and females in Korea is greater, especially in terms of malignant neoplasms, diseases of the liver, transport accidents and suicide. Conclusion The mortality rates from these diseases are higher in males than in females. For the recent health promotion policies in Korea such as Health Plan 2010, a more intensive and objective management drawing on the findings of this study concerning gender-specific mortality rates should be implemented.