Specific immunotherapy in renal cancer: a systematic review.

Science.gov (United States)

Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

2017-02-01

Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

Sequential Ground Motion Effects on the Behavior of a Base-Isolated RCC Building

Directory of Open Access Journals (Sweden)

Zhi Zheng

2017-01-01

Full Text Available The sequential ground motion effects on the dynamic responses of reinforced concrete containment (RCC buildings with typical isolators are studied in this paper. Although the base isolation technique is developed to guarantee the security and integrity of RCC buildings under single earthquakes, seismic behavior of base-isolated RCC buildings under sequential ground motions is deficient. Hence, an ensemble of as-recorded sequential ground motions is employed to study the effect of including aftershocks on the seismic evaluation of base-isolated RCC buildings. The results indicate that base isolation can significantly attenuate the earthquake shaking of the RCC building under not only single earthquakes but also seismic sequences. It is also found that the adverse aftershock effect on the RCC can be reduced due to the base isolation applied to the RCC. More importantly, the study indicates that disregarding aftershocks can induce significant underestimation of the isolator displacement for base-isolated RCC buildings.

Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

Science.gov (United States)

Thiesen, H-J; Steinbeck, F; Maruschke, M; Koczan, D; Ziems, B; Hakenberg, O W

2017-01-01

Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

Material report in support to RCC-MRX code 2010 stainless steel parts and products

International Nuclear Information System (INIS)

Ancelet, Olivier; Lebarbe, Thierry; Dubiez-Le Goff, Sophie; Bonne, Dominique; Gelineau, Odile

2012-01-01

This paper presents the Material Report dedicated to stainless steels parts and products issued by AFCEN (Association Francaise pour les regles de Conception et de Construction des Materiels des Chaudieres Electro-Nucleaires) in support to RCC-MRx 2010 Code. The RCC-MRx Code is the result of the merger of the RCC-MX 2008, developed in the context of the research reactor Jules Horowitz Reactor project, in the RCC-MR 2007, which set up rules applicable to the design of components operating at high temperature and to the Vacuum Vessel of ITER (a presentation of RCC-MRx 2010 Code is the subject of another paper proposed in this Congress; it explains in particular the status of this Code). This Material Report is part of a set of Criteria of RCC-MRx (this set of Criteria is under construction). The Criteria aim at explaining the design and construction rules of the Code. They cover analyses rules as well as part procurement, welding, methods of tests and examination and fabrication rules. The Material Report particularly provides justifications and explanations on requirements and features dealing with parts and products proposed in the Code. The Material Report contains the following information: Introduction of the grade(s): codes and standards and Reference Procurement Specifications covering parts and products, applications and experience gained, - Physical properties, - Mechanical properties used for design calculations (base metal and welds): basic mechanical properties, creep mechanical properties, irradiated mechanical properties, - Fabrication: experience gained, metallurgy, - Welding: weldability, experience gained during welding and repair procedure qualifications, - Non-destructive examination, - In-service behaviour. In the article, examples of data supplied in the Material Report dedicated to stainless steels will be exposed. (authors)

RCC-E: Design and construction rules for electrical equipment of PWR nuclear islands

International Nuclear Information System (INIS)

2016-01-01

RCC-E describes the rules for designing, building and installing electrical and I and C systems and equipment for pressurized water reactors. The code was drafted in partnership with industry, engineering firms, manufacturers, building control firms and operators, and represents a collection of best practices in accordance with IAEA requirements and IEC standards. The code's scope covers: architecture and the associated systems, materials engineering and the qualification procedure for normal and accidental environmental conditions, facility engineering and management of common cause failures (electrical and I and C) and electromagnetic interference, testing and inspecting electrical characteristics, quality assurance requirements supplementing ISO 9001 and activity monitoring. Use: RCC-E has been used to build the following power plants: France's last 12 nuclear units (1,300 MWe (8) and 1,450 MWe (4)), 2 M310 reactors in Korea (2), 44 M310 (4), CPR-1000 (28), CPR-600 (6), HPR-1000 (4) and EPR (2) reactors in service or undergoing construction in China, 1 EPR reactor in France. RCC-E is used for maintenance operations in French power plants (58 units) and Chinese M310 and CPR-1000 power plants. RCC-E has been chosen for the construction of the EPR plants in Hinkley Point, UK. Contents of the 2016 edition of the RCC-E code: Volume 1 - General requirements and quality assurance; Volume 2 - Specification of requirements; Volume 3 - I and C systems; Volume 4 - Electrical systems; Volume 5 - Materials engineering; Volume 6 - Installation of electrical and I and C systems; Volume 7 - Inspection and test methods

Radiometer Calibration and Characterization (RCC) User's Manual: Windows Version 4.0

Energy Technology Data Exchange (ETDEWEB)

Andreas, Afshin M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wilcox, Stephen M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-02-29

The Radiometer Calibration and Characterization (RCC) software is a data acquisition and data archival system for performing Broadband Outdoor Radiometer Calibrations (BORCAL). RCC provides a unique method of calibrating broadband atmospheric longwave and solar shortwave radiometers using techniques that reduce measurement uncertainty and better characterize a radiometer's response profile. The RCC software automatically monitors and controls many of the components that contribute to uncertainty in an instrument's responsivity. This is a user's manual and guide to the RCC software.

Active smoking may negatively affect response rate, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma treated with sunitinib.

Science.gov (United States)

Keizman, Daniel; Gottfried, Maya; Ish-Shalom, Maya; Maimon, Natalie; Peer, Avivit; Neumann, Avivit; Hammers, Hans; Eisenberger, Mario A; Sinibaldi, Victoria; Pili, Roberto; Hayat, Henry; Kovel, Svetlana; Sella, Avishay; Boursi, Ben; Weitzen, Rony; Mermershtain, Wilmosh; Rouvinov, Keren; Berger, Raanan; Carducci, Michael A

2014-01-01

Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p 3 (HR: 2.95, p smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.

Directory of Open Access Journals (Sweden)

Kevin Bray

Full Text Available mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.

Retrofitting Of RCC Piles By Using Basalt Fiber Reinforced Polymer BFRP Composite Part 1 Review Papers On RCC Structures And Piles Retrofitting Works.

OpenAIRE

R. Ananda Kumar; Dr. C. Selvamony; A. Seeni; Dr. T. R. Sethuraman

2015-01-01

Abstract Retrofitting works are immensely essential for deteriorated and damaged structures in Engineering and Medical fields in order to keep or return to the originality for safe guarding the structures and consumers. In this paper different types of methods of retrofitting review notes are given based on the experimental numerical and analytical methods results on strengthening the Reinforced cement concrete RCC structures including RCC piles. Soil-pile interaction on axial load lateral lo...

Results of a Phase 1/2 Study in Metastatic Renal Cell Carcinoma Patients Treated with a Patient-specific Adjuvant Multi-peptide Vaccine after Resection of Metastases.

Science.gov (United States)

Rausch, Steffen; Gouttefangeas, Cécile; Hennenlotter, Jörg; Laske, Karoline; Walter, Kerstin; Feyerabend, Susan; Chandran, Premachandran Anoop; Kruck, Stephan; Singh-Jasuja, Harpreet; Frick, Annemarie; Kröger, Nils; Stevanović, Stefan; Stenzl, Arnulf; Rammensee, Hans-Georg; Bedke, Jens

2017-10-04

Treatment of metastatic renal cell carcinoma comprises metastasectomy±systemic medical treatment. Specific immunotherapy after metastasectomy could be a complementary option. In this phase 1/2 study, safety and tolerability of an adjuvant multi-peptide vaccine (UroRCC) after metastasectomy was evaluated together with immune response and efficacy, compared with a contemporary cohort of patients (n=44) treated with metastasectomy only. Nineteen metastatic renal cell carcinoma patients received UroRCC via intradermal or subcutaneous application randomized to immunoadjuvants (granulocyte-macrophage colony-stimulating factor or Montanide). Adverse events of UroRCC were mainly grade I and II; frequency of immune response was higher for major histocompatibility complex class II peptides (17/19, 89.5%) than for major histocompatibility complex class I peptides (8/19, 42.1%). Median overall survival was not reached in the UroRCC group (mean: 112.6 mo, 95% confidence interval [CI]: 92.1-133.1) and 58.0 mo (95% CI: 32.7-83.2) in the control cohort (p=0.015). UroRCC was an independent prognosticator of overall survival (hazard ratio=0.19, 95% CI: 0.05-0.69, p=0.012). Adjuvant UroRCC multi-peptide vaccine after metastasectomy was well tolerated, immunogenic, and indicates potential clinical benefit when compared with a contemporary control cohort (NCT02429440). The application of a patient-specific peptide vaccine after complete resection of metastases in metastatic renal cell carcinoma patients resulted in favorable tolerability and outcome. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

High volume fly ash RCC for dams - I : mixture optimization and mechanical properties

Energy Technology Data Exchange (ETDEWEB)

Jacobsen, S. [PEAB Construction Co., Oslo (Norway); Lahus, O. [Norwegian Building Research Inst., Oslo (Norway)

2001-07-01

Roller compacted concretes (RCC) were developed for the Norwegian Skjerka hydropower project. RCCs were developed to have a high-volume fly ash content to address environmental issues, including the reduction of carbon dioxide emissions associated with dam construction. They also makes good use of waste product and conserve natural resources. This study examined a series of mixtures to determine the appropriateness of using RCC as a competing alternative to the traditional rock fill dam proposed for the Skjerka hydropower project. The main advantage of RCC is speed, allowing a relatively large dam to be constructed in just one summer season, saving financial costs and providing early return on the investment. In addition, fly ash can be used in the structure, using clean and renewable energy. Several procedures to proportion RCC mixtures were proposed, including the optimal paste volume method which is based on the assumption that an optimal RCC should have just enough paste to fill the space between particles when the granular skeleton has reached its maximum density under compaction. With this assumption, RCC tests began in 1998 in the laboratories of the Norwegian Building Research Institute. An ordinary portland cement was used and combined with ordinary low lime fly ash. Both coarse and fine aggregate were used. The tests determined the optimum paste-mortar ratio, the content of coarse aggregates and the production of specimens for test on hardened and fresh concrete. The study showed that the compressive strength of RCC increased with increasing cement/(cement + fly ash) ratio. The permeability coefficient decreased with increasing cement-content and increasing cement/(cement + fly ash) ratio due to the slow pozzolanic reaction of fly ash making a more open pore structure. It was concluded that an optimized mixture can result in a high performance RCC in terms of fresh and hardened concrete properties. 15 refs., 5 tabs., 11 figs.

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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Christopher J. Ricketts

2018-04-01

Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation.

Science.gov (United States)

Wu, Nan; Ren, Dong; Li, Su; Ma, Wenli; Hu, Shaoyan; Jin, Yan; Xiao, Sheng

2018-01-10

Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.

RCC-F: Design and construction rules for PWR fire protection systems

International Nuclear Information System (INIS)

2013-01-01

The RCC-F code defines the rules for designing, building and installing the fire protection systems used to manage the nuclear hazards inherent in the outbreak of a fire inside the facility and thereby control the fundamental nuclear functions. The code provides fire protection recommendations in terms of: the industrial risk (loss of assets and/or operation), personnel safety, the environment. The code is divided into five main sections: generalities, design safety principles, fire protection design bases, construction provisions, rules for installing the fire protection components and equipment. The RCC-F code is available as an ETC-F version specifically for EPR projects (European pressurized reactor). Contents of the 2013 edition of the ETC-F code: Volume A - Generalities: Structure of ETC-F general points, documentation (in progress), chapter (provision) quality assurance; Volume B - Design safety principles: design nuclear safety principles; Volume C - Fire protection design bases: fire protection design bases; Volume D - Construction provisions: construction provisions; Volume E - Installation rules for fire protection: rules for installing the fire protection, components and equipment

A PHASE II STUDY OF GEMCITABINE AND CAPECITABINE IN PATIENTS WITH ADVANCED RENAL CELL CANCER (RCC): SOUTHWEST ONCOLOGY GROUP STUDY S0312

Science.gov (United States)

Van Veldhuizen, Peter J.; Hussey, Michael; Lara, Primo N.; Mack, Philip C.; Gandour-Edwards, Regina; Clark, Joseph I.; Lange, Marianne K.; Crawford, E. David

2010-01-01

Background Gemcitabine plus capecitabine has modest efficacy in patients with advanced RCC but has considerable toxicity. We evaluated the efficacy and toxicity of a modified dose-schedule of this doublet in patients with advanced unresectable or metastatic RCC. Methods Chemotherapy-naïve patients were treated with gemcitabine at 900mg/m2 on days 1,8,15 and capecitabine at 625mg/m2 twice daily on days 1 through 21, every 28 days. Eligible patients must have adequate performance status and end-organ function. The primary endpoint was tumor response rate (RR). No further evaluation of this regimen would be pursued if the RR was ≤ 5%. In an exploratory manner using archival specimens, we also evaluated potential markers of prognosis and treatment response including thymidylate synthase (TS) gene polymorphisms and tumor expression of p53, PTEN, pAKT, pmTOR, and ERCC1. Results Of 43 patients registered, 1 was ineligible and 2 were not analyzable. There was 1 confirmed complete response (CR) and three unconfirmed partial responses (PR), for an overall response rate of 10% (95% CI: 3, 24). Nineteen patients (48%) had stable disease (SD). The six-month freedom-from-treatment-failure and overall survival rates were 20% (95% CI: 8, 32) and 75% (95% CI: 62, 88), respectively. Median survival time was 23 months (95% CI: 10, 37). One patient each experienced Grade 4 neutropenia, fatigue, thrombocytopenia and hemolysis with renal failure. The most common Grade 3 toxicities were neutropenia (12 patients), fatigue (5), and leucopenia (4). Patients with a best response of stable disease or better were more likely to have a decrease in expression of PTEN and an increased expression of pmTOR. Conclusions Gemcitabine plus capecitabine at this reduced dose-schedule benefits a small percentage of patients with RCC with an acceptable toxicity profile. The combination of gemcitabine and capecitabine may serve as a base regimen for combination therapy with targeted agents in select RCC

Simulation analysis of temperature control on RCC arch dam of hydropower station

Science.gov (United States)

XIA, Shi-fa

2017-12-01

The temperature analysis of roller compacted concrete (RCC) dam plays an important role in their design and construction. Based on three-dimensional finite element method, in the computation of temperature field, many cases are included, such as air temperature, elevated temperature by cement hydration heat, concrete temperature during placing, the influence of water in the reservoir, and boundary temperature. According to the corresponding parameters of RCC arch dam, the analysis of temperature field and stress field during the period of construction and operation is performed. The study demonstrates that detailed thermal stress analysis should be performed for RCC dams to provide a basis to minimize and control the occurrence of thermal cracking.

Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

Science.gov (United States)

McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

2015-06-20

Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

Harmonization of welding qualification provisions in RCC-M and European standards

International Nuclear Information System (INIS)

Lemoine, M.; Lainez, B.; Anastassiades, P.

2007-01-01

Since a long time, numerous precautions for welding have been integrated in the nuclear codes, in particular in the RCC-M applicable to pressurized water reactors, in order to guarantee a high quality level of permanent assemblies. In parallel, European and ISO standardization works have led to a harmonisation of practices on qualification of welding processes, welders and operators. In the context of the regulatory evolutions presented during this conference, it was judged appropriate to bring closer the RCC-M practices and those of EN and ISO standards, while taking the precaution of specifying, if necessary, the complementary provisions allowing maintaining guarantees of quality consistent with the prior experience feedback. This paper presents the amendments brought to the RCC-M Code by the 2005 and 2007 addenda, in order to respond to this objective, and develops their motivations. (authors) [fr

Retrofitting Of RCC Piles By Using Basalt Fiber Reinforced Polymer BFRP Composite Part 1 Review Papers On RCC Structures And Piles Retrofitting Works.

Directory of Open Access Journals (Sweden)

R. Ananda Kumar

2015-01-01

Full Text Available Abstract Retrofitting works are immensely essential for deteriorated and damaged structures in Engineering and Medical fields in order to keep or return to the originality for safe guarding the structures and consumers. In this paper different types of methods of retrofitting review notes are given based on the experimental numerical and analytical methods results on strengthening the Reinforced cement concrete RCC structures including RCC piles. Soil-pile interaction on axial load lateral load reviews are also presented. This review paper is prepared to find out the performance of basalt fibre reinforced polymer BFRP composite retrofitted reinforced cement concrete single end bearing piles.

Longterm results in the therapy of 100 cases of metastatic renal cell carcinoma (RCC)

International Nuclear Information System (INIS)

Falk, W.; Halama, J.M.; Halama, J.

1990-01-01

The success of renal cell carcinoma (RCC)-nephrectomy with radical lymph node dissection in stage I and II disease is undisputed. Through these measures 23% of metastases are controlled. The five-year survival time in stage III disease, however, stagnates at 35%±14% despite radical surgery. Also, the additional tumor-vaccine-therapy of the Mainz-Joint-Study-Group was successful only in stage I and II disease, whereas stage III disease did not benefit from this therapy. As 50% of all radically operated patients developed metastases within three years after surgery, the call by radiooncologists for supplementary radiotherapy beginning with stage III disease must be put foreward. The problems of therapy and chances of survival in generalized disease are demonstrated in 100 of our cases treated by surgery, radiotherapy and with MPA (medroxyprogesteroneacetate). Whereas Schmiedt et al. show a total survival time of 10.3 months after diagnosis of metastatic disease, the Offenbach patients achieved 16.5 months with a median survival time of 11.75 months. The necessity of therapeutic intervention is confirmed by the fact that the most favorable median survival time, 15.75 months, was achieved in metastatic disease involving three organs. We present here the special features of the individual organ manifestations and point out that not only the mean and median survival time, but also the very widely varying survival times in individual cases, make conscientious oncological post-treatment follow up and management a requirement. (orig.) [de

Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.

Science.gov (United States)

Bailey, Erin B; Tantravahi, Srinivas K; Poole, Austin; Agarwal, Archana M; Straubhar, Alli M; Batten, Julia A; Patel, Shiven B; Wells, Chesley E; Stenehjem, David D; Agarwal, Neeraj

2015-06-01

Hypothyroidism is a common adverse effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in patients with metastatic renal cell carcinoma (mRCC). Some studies have shown an association with improved survival. However, hypothyroidism severity has not been correlated with survival outcomes. We report the incidence and severity of VEGFR-TKI therapy-associated hypothyroidism in correlation with the survival outcomes of patients with mRCC. A retrospective analysis of patients with mRCC who received VEGFR-TKIs (2004 through 2013) was conducted from a single institutional database. Hypothyroidism, progression-free survival (PFS), and overall survival (OS) were assessed. Univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazard models. Of 125 patients with mRCC, 65 were eligible. Their median age was 59 years (range, 45-79 years), and 46 (70.8%) were male. Hypothyroidism occurred in 25 patients (38.5%), of whom 13 had a peak thyroid-stimulating hormone (TSH) level > 10 mIU/L during treatment. The median OS was significantly longer in patients with a peak TSH > 10 mIU/L than in patients with a peak TSH of ≤ 10 mIU/L (not reached vs. 21.4 months, P = .005). On multivariate analysis, risk criteria, number of previous therapies, and severe hypothyroidism (TSH > 10 mIU/L) during VEGFR-TKI therapy remained significant for improvements in PFS and OS. The severity of VEGFR-TKI therapy-associated hypothyroidism (TSH > 10 mIU/L) was associated with improved survival outcomes in patients with mRCC and should not necessitate a dose reduction or therapy discontinuation. Copyright © 2015 Elsevier Inc. All rights reserved.

RCC-C: Design and construction rules for fuel assemblies of PWR nuclear power plants

International Nuclear Information System (INIS)

2015-01-01

The RCC-C code contains all the requirements for the design, fabrication and inspection of nuclear fuel assemblies and the different types of core components (rod cluster control assemblies, burnable poison rod assemblies, primary and secondary source assemblies and thimble plug assemblies). The design, fabrication and inspection rules defined in RCC-C leverage the results of the research and development work pioneered in France, Europe and worldwide, and which have been successfully used by industry to design and build nuclear fuel assemblies and incorporate the resulting feedback. The code's scope covers: fuel system design, especially for assemblies, the fuel rod and associated core components, the characteristics to be checked for products and parts, fabrication methods and associated inspection methods. The RCC-C code is used by the operator of the PWR nuclear power plants in France as a reference when sourcing fuel from the world's top two suppliers in the PWR market, given that the French operator is the world's largest buyer of PWR fuel. Fuel for EPR projects is manufactured according to the provisions of the RCC-C code. The code is available in French and English. The 2005 edition has been translated into Chinese. Contents of the 2015 edition of the RCC-C code: Chapter 1 - General provisions: 1.1 Purpose of the RCC-C, 1.2 Definitions, 1.3 Applicable standards, 1.4 Equipment subject to the RCC-C, 1.5 Management system, 1.6 Processing of non-conformances; Chapter 2 - Description of the equipment subject to the RCC-C: 2.1 Fuel assembly, 2.2 Core components; Chapter 3 - Design: Safety functions, operating functions and environment of fuel assemblies and core components, design and safety principles; Chapter 4 - Manufacturing: 4.1 Materials and part characteristics, 4.2 Assembly requirements, 4.3 Manufacturing and inspection processes, 4.4 Inspection methods, 4.5 Certification of NDT inspectors, 4.6 Characteristics to be inspected for the

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Energy Technology Data Exchange (ETDEWEB)

Yuan, J.L.; Wang, F.L.; Yi, X.M.; Qin, W.J.; Wu, G.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Huan, Y. [Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, L.J.; Zhang, G.; Yu, L.; Zhang, Y.T.; Qin, R.L.; Tian, C.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China)

2014-10-31

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Plutonium recycle concept for RCC - type PWRs

International Nuclear Information System (INIS)

Bonet, H.; Charlier, A.; Deramaix, P.; Vanderberg, C.

1975-01-01

Self-generated Pu recycling schemes in RCC-type PWRs have been defined. The main results of survey studies performed to compare the relative merits of various Pu recycle strategies and the merits of alternative solutions of the assembly design such as the Pu-island assembly or the all-Pu assembly are presented [fr

Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma.

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Witold Wiecek

Full Text Available Renal-cell carcinoma (RCC affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]. However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months. The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real

Creep-fatigue rules in the RCC-MR code

International Nuclear Information System (INIS)

Drubay, B.

1988-01-01

In 1978, CEA, Electricite de France (EDF) and NOVATOME decided to draw up a complete set of design and construction rules for LMFBR components. This RCC-MR code issued in June 1985 and completed in November 1987 was chosen as a sound basis for the next European Fast Reactor (EFR). The purpose of this paper is to describe the present RCC-MR creep-fatigue design rules to be applied with elastic analysis including the modifications adopted in the first addenda. This method is based on a separate evaluation of a fatigue usage fraction V and creep rupture usage fraction W with the common linear summation rule. The fatigue usage fraction is obtained from continuous fatigue curves (without hold times) and from total strain ranges (elastic + plastic + creep). The creep rupture usage fraction W is obtained from stress to rupture curves and a stress σk evaluating the stress generated during the cycle. (author)

Test and Analysis Correlation of Form Impact onto Space Shuttle Wing Leading Edge RCC Panel 8

Science.gov (United States)

Fasanella, Edwin L.; Lyle, Karen H.; Gabrys, Jonathan; Melis, Matthew; Carney, Kelly

2004-01-01

Soon after the Columbia Accident Investigation Board (CAIB) began their study of the space shuttle Columbia accident, "physics-based" analyses using LS-DYNA were applied to characterize the expected damage to the Reinforced Carbon-Carbon (RCC) leading edge from high-speed foam impacts. Forensic evidence quickly led CAIB investigators to concentrate on the left wing leading edge RCC panels. This paper will concentrate on the test of the left-wing RCC panel 8 conducted at Southwest Research Institute (SwRI) and the correlation with an LS-DYNA analysis. The successful correlation of the LS-DYNA model has resulted in the use of LS-DYNA as a predictive tool for characterizing the threshold of damage for impacts of various debris such as foam, ice, and ablators onto the RCC leading edge for shuttle return-to-flight.

Consideration of creep in design rules of AFCEN RCC-MRx 2012 code

International Nuclear Information System (INIS)

Lebarbe, T.; Petesch, C.; Lejeail, Y.; Lamagnere, P.; Dubiez-Le Goff, S.

2014-01-01

The 2012 edition of the RCC-MRx Code has been issued in French and English versions by AFCEN (Association Francaise pour les regles de Conception et de Construction des Materiels des Chaudieres Electro-nucleaires). This Code is the result of the merger of the RCC-MX 2008 developed in the context of the research reactor Jules Horowitz Reactor project, in the RCC-MR 2007 which set up rules applicable to the design of components operating at high temperature and to the Vacuum Vessel of ITER. This new edition is the opportunity to publish also the background of the rules. This paper is one illustration of what may be such a document, on a dedicated example, the creep rules. It contains an overview of the design rules associated to the creep damage and explains the purpose and the origins of these rules. This type of exercise is going to be generalized to all the parts of the code in AFCEN technical publications, the criteria. (authors)

Attributing death to cancer: cause-specific survival estimation.

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Mathew A

2002-10-01

Full Text Available Cancer survival estimation is an important part of assessing the overall strength of cancer care in a region. Generally, the death of a patient is taken as the end point in estimation of overall survival. When calculating the overall survival, the cause of death is not taken into account. With increasing demand for better survival of cancer patients it is important for clinicians and researchers to know about survival statistics due to disease of interest, i.e. net survival. It is also important to choose the best method for estimating net survival. Increase in the use of computer programmes has made it possible to carry out statistical analysis without guidance from a bio-statistician. This is of prime importance in third- world countries as there are a few trained bio-statisticians to guide clinicians and researchers. The present communication describes current methods used to estimate net survival such as cause-specific survival and relative survival. The limitation of estimation of cause-specific survival particularly in India and the usefulness of relative survival are discussed. The various sources for estimating cancer survival are also discussed. As survival-estimates are to be projected on to the population at large, it becomes important to measure the variation of the estimates, and thus confidence intervals are used. Rothman′s confidence interval gives the most satisfactory result for survival estimate.

French RSE-M and RCC-MR code appendices for flaw analysis: Presentation of the fracture parameters calculation-Part I: General overview

International Nuclear Information System (INIS)

Marie, S.; Chapuliot, S.; Kayser, Y.; Lacire, M.H.; Drubay, B.; Barthelet, B.; Le Delliou, P.; Rougier, V.; Naudin, C.; Gilles, P.; Triay, M.

2007-01-01

Two French nuclear codes include flaw assessment procedures: the RSE-M code 'Rules for In-service Inspection of Nuclear Power Plant Components' and the RCC-MR code 'Design and Construction rules for mechanical components of FBR nuclear islands and high temperature applications'. An important effort of development of these analytical methods has been made for the last 10 years in the frame of a collaboration between CEA, EDF and AREVA-NP, and in the frame of R and D actions involving CEA and IRSN. These activities have led to a unification of the common methods of the two codes. The calculation of fracture mechanics parameters, and in particular the stress intensity factor K I and the J integral, has been widely developed for industrial configurations. All developments have been integrated in the 2005 edition of RSE-M and in the 2007 edition of RCC-MR. This series of articles is composed of five parts: this first one presents an overview of the methods proposed in the RCC-MR and RSE-M codes. Parts II-IV provide compendia for specific components: plates (part II), pipes (part III) and elbows (part IV). Finally, part V presents the validation elements of the methods, with details on the process followed for their development and on evaluation of the accuracy of the proposed analytical methods. This first article of the series presents an overview of the calculation of K I and J in these two codes and describes briefly the defect assessment analyses. Specific details in the Appendix A16 of RCC-MR (LBB procedure and creep analyses) are also introduced in this article

Design and Construction Rules for Mechanical components of FBR nuclear islands: RCC-MR. Tome 1, Volume A: generalities

International Nuclear Information System (INIS)

1985-06-01

The French Rules of Mechanical equipments of Fast Neutron nuclear Reactors (RCC-MR) aims at equipments included in a safety classification. The equipments concerned are those of the nuclear boiler and its auxiliaries: tanks, vessels, internal equipments of the reactor, exchangers, pumps, fittings, pipes, and supports. The present edition of the RCC-MR comprises 12 books presented in the present one in the volume A. The chapter RA 3000 defines the documents to be established in application of the RCC-MR rules. The chapter RA 5000 defines the requirements to take into account to establish and carry out quality Assurance programs according to the RCC-MR rules [fr

Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

DEFF Research Database (Denmark)

Sørensen, Anne V.; Donskov, Frede; Hermann, Gregers G.

2014-01-01

AbstractAim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between...

ASME and RCC-MR comparison for the prevention of fatigue analysis

International Nuclear Information System (INIS)

Autrusson, B.; Acker, D.

1989-01-01

The purpose of this survey is to compare the simplified methods, without reference to the safety factor allowed for the mechanical properties. An application of both codes, RCC-MR and ASME, on the design of the wall mock-up of the NET project is made and also an estimation with an elastoplastic analysis. In the case of fatigue analysis according to ASME in the plastic field, the elastic stress is magnified by a K e factor derived from stress variation, S n , disregarding geometrical discontinuities. According to RCC-MR, the elastic maximum strain will magnified by two coefficients accounting for plasticity and variation of Poisson ratio

Noncoding RNA Expression and Targeted Next-Generation Sequencing Distinguish Tubulocystic Renal Cell Carcinoma (TC-RCC) from Other Renal Neoplasms.

Science.gov (United States)

Lawrie, Charles H; Armesto, María; Fernandez-Mercado, Marta; Arestín, María; Manterola, Lorea; Goicoechea, Ibai; Larrea, Erika; Caffarel, María M; Araujo, Angela M; Sole, Carla; Sperga, Maris; Alvarado-Cabrero, Isabel; Michal, Michal; Hes, Ondrej; López, José I

2018-01-01

Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in  600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

An overview of Pazopanib in metastatic renal cell carcinoma (mRCC in Ministry of Health (MOH, Malaysia: A multicentre experience

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May Feng Chen

2017-12-01

Full Text Available Background: Pazopanib was listed in MOH, Malaysia’s drug formulary on July 2013 for the treatment of mRCC. Two landmark trials were used to support the listing i.e. VEG105192 and COMPARZ which showed a median progression free survival (PFS of 9.2 and 8.4 months respectively. The efficacy and tolerability of Pazopanib in patients with mRCC have been found to differ in Western and Asian populations. Due to the difference in tolerability, dose adjustment in Asian patients is required. In most MOH hospitals in Malaysia, we tend to start mRCC patients with a lower dose as most patients can’t tolerate 800 mg of Pazopanib. We aim to prognosticate and evaluate PFS in patients with mRCC treated in MOH, Malaysia. We also aim to correlate PFS of patients on different doses of Pazopanib. Methods: The largest referral centre in central and southern Malaysia was selected namely Hospital Kuala Lumpur and Hospital Sultan Ismail. A retrospective analysis was done for patients using hospital supply of Pazopanib from 2010 to 2016. PFS is defined as the time of Pazopanib initiation till 1st documented disease progression. Prognostic variables such as age, sex, race, histology, common sites of metastasis, number of organs involved, ECOG, modified MSKCC risk category, prior history of nephrectomy or systemic treatment and initial dose of Pazopanib was analysed. Results: There was a total of 87 patients with mRCC registered. Median time since diagnosis to initiation of Pazopanib was 5 months. PFS for the overall study population was 8.0 months (95%CI, 5.6–10.4 months. PFS based on dose showed 400 mg vs. 800 mg of Pazopanib was 9.0 months (95%CI 4.5–13.4 months vs. 6.0 months (95%CI 1.9–10.1 months respectively (p = 0.209. Modified MSKCC risk category was a significant prognostic variable (p = 0.045. Conclusion: This retrospective review shows no significant difference in PFS between 400 mg vs. 800 mg of Pazopanib. MOH hospitals in Malaysia have similar PFS

Creep design rules in french ''RCC-MR'' code

International Nuclear Information System (INIS)

Roche, H.

1986-04-01

In this paper, four points enlightening the originality of the ''RCC-MR'' analysis rules in the creep range will be discussed. The three first points will concern elastic analysis, the fourth one materials data. The rules given in this paper are applicable for class 1 components and level A conditions. They are given by way of illustration in a simplified form

Creep-fatigue damage evaluation for SS-316LN (ORNL PLATES): - RCC-MR vs. ASME SEC III - NH

International Nuclear Information System (INIS)

Sati, Bhuwan Chandra; Jalaldeen, S.; Velusamy, K.; Selvaraj, P.

2016-01-01

Investigations of high temperature tests done on ORNL plate with deformation control loading, under creep-fatigue damage have been presented. The test results with methodology of RCC-MR and ASME-NH life prediction under creep-fatigue loading have been assessed. The stress relaxation effect in calculating the life using RCC-MR under creep-fatigue damage is found to be significant in presence of secondary stress. RCC-MR: 2007 is more realistic number of cycles (predicts 51 number of cycles) as compared to ASME-NH (predicts 312 number of cycles) which is demonstrated by the experimental work (observed 86 numbers of cycles). Between RCC-MR and experimental work, design code seems to be more conservative for life prediction due to creep-fatigue damage. For fatigue damage, the approaches are same and the difference comes from material properties and the starting stress for applying Neuber's rule. ASME approach has the limitation of stress range magnitude. ASME approach predicts lower elastic plus plastic strain for the cases having S* above the linear stress limit. For creep strain and creep damage evaluation, ASME and RCC-MR have different approaches for calculating the stress at the beginning and during the hold period. The RCC-MR takes account of cyclic hardening or softening effects (hardening in the present case of 316 LN) by means of the cyclic stress-strain curve and the benefit of symmetrization effects which are significant for this material. The ASME code neglects these effects and instead relies on an approach based on the isochronous stress-strain curves. (author)

MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

Energy Technology Data Exchange (ETDEWEB)

Zhao, Jun [Foshan Maternal and Child Health Care Hospital, Foshan (China); Lei, Ting [Zhongshan People’s Hospital, Zhongshan (China); Xu, Congjie [Department of Urology, Pepole’s Hospital of Hainan Province, Haikou (China); Li, Huan; Ma, Wenmin; Yang, Yunxia; Fan, Shuming [Foshan Maternal and Child Health Care Hospital, Foshan (China); Liu, Yuchen, E-mail: s_ycliu1@stu.edu.cn [Anhui Medical University, Hefei (China)

2013-08-23

Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC.

MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

International Nuclear Information System (INIS)

Zhao, Jun; Lei, Ting; Xu, Congjie; Li, Huan; Ma, Wenmin; Yang, Yunxia; Fan, Shuming; Liu, Yuchen

2013-01-01

Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC

The RCC-MR design code for LMFBR components. A useful basis for fusion reactor design tools development

International Nuclear Information System (INIS)

Acker, D.; Chevereau, G.

1986-01-01

LMFBR and fusion reactors exhibit common features with regard to structural materials, temperature service level, loading types. So, design and construction rules used in France for LMFBR, that is to say RCC-MR Code, can constitute a good basis for fusion reactors design. Some original aspects of RCC-MR design rules are described, relating to unsignificant creep, ratchetting effect, fatigue and creep damage limits, creep damage evaluation, fatigue damage evaluation, buckling. The main originality of RCC-MR consists to propose comprehensive simplified rules based on elastic calculations and extended from classical cold temperatures to the elevated temperature domain. (author)

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

Science.gov (United States)

Ito, Ryuichi; Narita, Shintaro; Huang, Mingguo; Nara, Taketoshi; Numakura, Kazuyuki; Takayama, Koichiro; Tsuruta, Hiroshi; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Habuchi, Tomonori

2017-01-01

Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the "obesity paradox" of RCC.

The RCC-MR design code for LMFBR components. A useful basic for fusion reactor design tools development

International Nuclear Information System (INIS)

Acker, D.; Chevereau, G.

1985-11-01

LMFBR and fusion reactors exhibit common features with regard to structural materials (Stainless steels), temperature service level (550-600 0 C), loading types. So, design and construction rules used in France for LMFBR, that is to say RCC-MR Code, can constitute a good basis for fusion reactors design. Some original aspects of RCC-MR design rules are described, relating to unsignificant creep, ratchetting effect, fatigue and creep damage limits, creep damage evaluation, fatigue damage evaluation, buckling. The main originality of RCC-MR consists to propose comprehensive simplified rules based on elastic calculations and extended from classical cold temperatures to the elevated temperature domain

Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure

Science.gov (United States)

Williamson, Rosalind C.; Cowell, Christopher A. M.; Hammond, Christina L.; Bergen, Dylan J. M.; Roper, James A.; Feng, Yi; Rendall, Thomas C. S.; Race, Paul R.; Bass, Mark D.

2014-01-01

ABSTRACT Sustained forward migration through a fibrillar extracellular matrix requires localization of protrusive signals. Contact with fibronectin at the tip of a cell protrusion activates Rac1, and for linear migration it is necessary to dampen Rac1 activity in off-axial positions and redistribute Rac1 from non-protrusive membrane to the leading edge. Here, we identify interactions between coronin-1C (Coro1C), RCC2 and Rac1 that focus active Rac1 to a single protrusion. Coro1C mediates release of inactive Rac1 from non-protrusive membrane and is necessary for Rac1 redistribution to a protrusive tip and fibronectin-dependent Rac1 activation. The second component, RCC2, attenuates Rac1 activation outside the protrusive tip by binding to the Rac1 switch regions and competitively inhibiting GEF action, thus preventing off-axial protrusion. Depletion of Coro1C or RCC2 by RNA interference causes loss of cell polarity that results in shunting migration in 1D or 3D culture systems. Furthermore, morpholinos against Coro1C or RCC2, or mutation of any of the binding sites in the Rac1–RCC2–Coro1C complex delays the arrival of neural crest derivatives at the correct location in developing zebrafish, demonstrating the crucial role in migration guidance in vivo. PMID:25074804

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

Directory of Open Access Journals (Sweden)

Ryuichi Ito

Full Text Available Although obesity increases the risk of renal cell carcinoma (RCC, obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively. Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035. There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002. Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035. Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the "obesity paradox" of RCC.

Twelve-year survival after multiple recurrences and repeated metastasectomies for renal cell Carcinoma

Directory of Open Access Journals (Sweden)

Wang Jue

2011-11-01

Full Text Available Abstract Background Metastatic renal cell carcinoma (RCC presents a therapeutic challenge for clinicians because of the unpredictable clinical course, resistance to chemotherapy or radiotherapy and the limited response to immunotherapy. Patients and Methods We report a case of a 62-year-old woman who underwent nephrectomy for T4N0 RCC, clear cell type, Fuhrman grade 3/4 in 1999. The patinet subsequently had multiple tumor recurrences. Results The patient underwent eight metastasectomies, including multiple partial left nephrectomies, right adrenalectomy, a complete left nephrectomy, and distal pancreatectomy. She remains well and tumor free 12 years after initial diagnosis. Conclusion Repeated resections after initial metastasectomy can be carried out safely and provide long-term survival in selected patients with recurrent metastasis from RCC. The findings from our case indicate that close follow-up for the early detection of recurrence and complete resection of metastases can improve the results after repeated resection.

RCC Plug Repair Thermal Tools for Shuttle Mission Support

Science.gov (United States)

Rodriguez, Alvaro C.; Anderson, Brian P.

2010-01-01

A thermal math model for the Space Shuttle Reinforced Carbon-Carbon (RCC) Plug Repair was developed to increase the confidence in the repair entry performance and provide a real-time mission support tool. The thermal response of the plug cover plate, local RCC, and metallic attach hardware can be assessed with this model for any location on the wing leading edge. The geometry and spatial location of the thermal mesh also matches the structural mesh which allows for the direct mapping of temperature loads and computation of the thermoelastic stresses. The thermal model was correlated to a full scale plug repair radiant test. To utilize the thermal model for flight analyses, accurate predictions of protuberance heating were required. Wind tunnel testing was performed at CUBRC to characterize the heat flux in both the radial and angular directions. Due to the complexity of the implementation of the protuberance heating, an intermediate program was developed to output the heating per nodal location for all OML surfaces in SINDA format. Three Design Reference Cases (DRC) were evaluated with the correlated plug thermal math model to bound the environments which the plug repair would potentially be used.

A Framework for RFID Survivability Requirement Analysis and Specification

Science.gov (United States)

Zuo, Yanjun; Pimple, Malvika; Lande, Suhas

Many industries are becoming dependent on Radio Frequency Identification (RFID) technology for inventory management and asset tracking. The data collected about tagged objects though RFID is used in various high level business operations. The RFID system should hence be highly available, reliable, and dependable and secure. In addition, this system should be able to resist attacks and perform recovery in case of security incidents. Together these requirements give rise to the notion of a survivable RFID system. The main goal of this paper is to analyze and specify the requirements for an RFID system to become survivable. These requirements, if utilized, can assist the system in resisting against devastating attacks and recovering quickly from damages. This paper proposes the techniques and approaches for RFID survivability requirements analysis and specification. From the perspective of system acquisition and engineering, survivability requirement is the important first step in survivability specification, compliance formulation, and proof verification.

Common germline polymorphisms associated with breast cancer-specific survival

DEFF Research Database (Denmark)

Pirie, Ailith; Guo, Qi; Kraft, Peter

2015-01-01

in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached...... evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated......-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes...

French RSE-M and RCC-MR code appendices for flaw analysis: Presentation of the fracture parameters calculation-Part V: Elements of validation

International Nuclear Information System (INIS)

Marie, S.; Chapuliot, S.; Kayser, Y.; Lacire, M.H.; Drubay, B.; Barthelet, B.; Le Delliou, P.; Rougier, V.; Naudin, C.; Gilles, P.; Triay, M.

2007-01-01

French nuclear codes include flaw assessment procedures: the RSE-M Code 'Rules for In-service Inspection of Nuclear Power Plant Components' and the RCC-MR code 'Design and Construction Rules for Mechanical Components of FBR Nuclear Islands and High Temperature Applications'. Development of analytical methods has been made for the last 10 years in the framework of a collaboration between CEA, EDF and AREVA-NP, and by R and D actions involving CEA and IRSN. These activities have led to a unification of the common methods of the two codes. The calculation of fracture mechanics parameters, in particular the stress intensity factor K I and the J integral, has been widely developed for industrial configurations. All the developments have been integrated in the 2005 edition of RSE-M and in 2007 edition of RCC-MR. This series of articles consists of 5 parts: the first part presents an overview of the methods proposed in the RCC-MR and RSE-M codes. Parts II-IV provide the compendia for specific components. The geometries are plates (part II), pipes (part III) and elbows (part IV). This part presents validation of the methods, with details on the process followed for their development and of the evaluation accuracy of the proposed analytical methods

Dynamic contrast-enhanced CT (DCE-CT) as a potential biomarker in patients with metastatic renal cell carcinoma (mRCC)

DEFF Research Database (Denmark)

Mains, Jill Rachel; Donskov, Frede; Pedersen, Erik Morre

Purpose To explore the impact of DCE-CT as a biomarker in mRCC.  Methods and Materials 12 patients with mRCC participating in a phase II trial with immunotherapy and bevacizumab and with a follow-up time of at least 2 years were included in this preliminary analysis. DCE-CT interpretation (max s...

Nano-Phase Powder Based Exothermic Braze Repair Technology For RCC Materials, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The Phase II project will advance innovative, cost effective and reliable nano-phase exothermic RCC joining processes (ExoBrazeTM) in order to be able to reinforce...

Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

DEFF Research Database (Denmark)

de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

2014-01-01

Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

Nano-Phase Powder Based Exothermic Braze Repair Technology For RCC Materials, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — MRi is proposing, with its partner, Exotherm Corp (Camden, NJ) to demonstrate the feasibility of using exothermic brazing to join RCC (or C:SiC) composites to itself...

A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma

Science.gov (United States)

Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang

2015-01-01

Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Science.gov (United States)

2009-01-01

Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On

Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Qing Zhang

2017-01-01

Full Text Available The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR- specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92 against renal cell carcinoma (RCC cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Farnebo, Jacob; Grybäck, Per; Harmenberg, Ulrika; Laurell, Anna; Wersäll, Peter; Blomqvist, Lennart K; Ullén, Anders; Sandström, Per

2014-01-01

To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival. Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival. Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC

French RSE-M and RCC-MR code appendices for flaw analysis: Presentation of the fracture parameters calculation-Part IV: Cracked elbows

International Nuclear Information System (INIS)

Marie, S.; Chapuliot, S.; Kayser, Y.; Lacire, M.H.; Drubay, B.; Barthelet, B.; Le Delliou, P.; Rougier, V.; Naudin, C.; Gilles, P.; Triay, M.

2007-01-01

Two French nuclear codes include flaw assessment procedures: the RSE-M Code 'Rules for In-service Inspection of Nuclear Power Plant Components' and the RCC-MR code 'Design and Construction rules for mechanical components of FBR nuclear islands and high temperature applications'. Development of analytical methods has been made for the last 10 years through a collaboration between CEA, EDF and AREVA-NP, and through R and D actions involving CEA and IRSN. These activities have led to unification of the common methods of the two codes. The calculation of fracture mechanics parameters, and in particular the stress intensity factor K I and the J integral, has been widely developed for industrial configurations. All the developments have been integrated in the 2005 edition of RSE-M and in 2007 edition of RCC-MR. This series of papers is composed of five parts: the first presents an overview of the methods proposed in the RCC-MR and RSE-M codes. Parts II-IV provide compendia for specific components. The geometries are plates (part II), pipes (part III) and elbows (part IV). Part V presents validation of the methods, with details on their accuracy. This paper presents the stress intensity factor and J calculation for cracked elbows. General data applicable for all defect geometries are first presented, and then, compendia for K I and σ ref calculations are provided for the available defect geometries

RCC-MRx: Design and construction rules for mechanical components in high-temperature structures, experimental reactors and fusion reactors

International Nuclear Information System (INIS)

2015-01-01

The RCC-MRx code was developed for sodium-cooled fast reactors (SFR), research reactors (RR) and fusion reactors (FR-ITER). It provides the rules for designing and building mechanical components involved in areas subject to significant creep and/or significant irradiation. In particular, it incorporates an extensive range of materials (aluminum and zirconium alloys in response to the need for transparency to neutrons), sizing rules for thin shells and box structures, and new modern welding processes: electron beam, laser beam, diffusion and brazing. The RCC-MR code was used to design and build the prototype Fast Breeder Reactor (PFBR) developed by IGCAR in India and the ITER Vacuum Vessel. The RCC-Mx code is being used in the current construction of the RJH experimental reactor (Jules Horowitz reactor). The RCC-MRx code is serving as a reference for the design of the ASTRID project (Advanced Sodium Technological Reactor for Industrial Demonstration), for the design of the primary circuit in MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) and the design of the target station of the ESS project (European Spallation Source). Contents of the 2015 edition of the RCC-MRx code: Section I General provisions; Section II Additional requirements and special provisions; Section III Rules for nuclear installation mechanical components: Volume I: Design and construction rules: Volume A (RA): General provisions and entrance keys, Volume B (RB): Class 1 components and supports, Volume C (RC): Class 2 components and supports, Volume D (RD): Class 3 components and supports, Volume K (RK): Examination, handling or drive mechanisms, Volume L (RL): Irradiation devices, Volume Z (Ai): Technical appendices; Volume II: Materials; Volume III: Examinations methods; Volume IV: Welding; Volume V: Manufacturing operations; Volume VI: Probationary phase rules

Stage-specific predictive models for breast cancer survivability.

Science.gov (United States)

Kate, Rohit J; Nadig, Ramya

2017-01-01

Survivability rates vary widely among various stages of breast cancer. Although machine learning models built in past to predict breast cancer survivability were given stage as one of the features, they were not trained or evaluated separately for each stage. To investigate whether there are differences in performance of machine learning models trained and evaluated across different stages for predicting breast cancer survivability. Using three different machine learning methods we built models to predict breast cancer survivability separately for each stage and compared them with the traditional joint models built for all the stages. We also evaluated the models separately for each stage and together for all the stages. Our results show that the most suitable model to predict survivability for a specific stage is the model trained for that particular stage. In our experiments, using additional examples of other stages during training did not help, in fact, it made it worse in some cases. The most important features for predicting survivability were also found to be different for different stages. By evaluating the models separately on different stages we found that the performance widely varied across them. We also demonstrate that evaluating predictive models for survivability on all the stages together, as was done in the past, is misleading because it overestimates performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Application of the active flexible fixture with passive RCC function to peg-in-hole task

International Nuclear Information System (INIS)

Yamaguchi, Tomomi; Higuchi, Masahiro

2005-01-01

This paper describes the application of the active flexible fixture (AFLEF) with passive RCC to the peg-in-hole task on the disk in the X-band accelerator. The AFLEF can fix any work and position the fixed work at short range. In this paper, the 2-dimensional AFLEF is proposed as the simplified type and is provided with passive RCC function to be equipped with dexterity for a peg-in-hole task. As results of the experiment on the peg-in-hole task on the X-band accelerator disks with the AFLEF, we make the ability of the AFLEF for the task clear and also the boundary conditions to the complete task clear. (author)

Triiodothyronine regulates cell growth and survival in renal cell cancer.

Science.gov (United States)

Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

2016-10-01

Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

Neuronal survival in the brain: neuron type-specific mechanisms

DEFF Research Database (Denmark)

Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

2017-01-01

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

The Clinical Presentation, Survival Outcomes, and Management of Patients With Renal Cell Carcinoma and Cardiac Metastasis Without Inferior Vena Cava Involvement: Results From a Pooled Clinical Trial Database and Systematic Review of Reported Cases.

Science.gov (United States)

Viteri Malone, Mariuxi A; Ares, Gustavo Ruiz; De Velasco, Guillermo; Brandão, Raphael; Lin, Xun; Norton, Craig; Simantov, Ronit; Moslehi, Javid; Krajewski, Katherine M; Choueiri, Toni K; McKay, Rana R

2018-04-01

Cardiac metastases from renal cell carcinoma (RCC) are uncommon and there are limited data regarding the presentation and outcomes of this population. The objective of this study was to evaluate the characteristics and outcomes of patients with RCC with cardiac metastasis without inferior vena cava (IVC) involvement. We conducted a pooled retrospective analysis of metastatic RCC patients treated in 4 clinical trials. Additionally, we conducted a systematic review of cases reported in the literature from 1973 to 2015. Patients with cardiac metastases from RCC without IVC involvement were included. Patient and disease characteristics were described. Additionally, treatments, response to therapy, and survival outcomes were summarized. Of 1765 metastatic RCC patients in the clinical trials database, 10 had cardiac metastases without IVC involvement. All patients received treatment with targeted therapy. There was 1 observed partial response (10%) and 6 patients showed stable disease (60%). The median progression-free survival was 6.9 months. The systematic review of reported clinical cases included 39 patients. In these patients, the most common cardiac site of involvement was the right ventricle (51%; n = 20). Patients were treated with medical (28%; n = 11) and/or surgical treatment (49%; n = 19) depending on whether disease was isolated (n = 13) or multifocal (n = 26). To our knowledge, this is the first series to report on the presentation and outcomes of patients with cardiac metastasis without IVC involvement in RCC. We highlight that although the frequency of patients with cardiac metastases without IVC involvement is low, these patients have a unique clinical presentation and warrant special multidisciplinary management. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparative study of physical and chemical properties of different pozzolanic materials used for roller compacted concrete RCC dams

OpenAIRE

Husein Malkawi Abdallah I.; Shatnawi Ehab; Husein Malkawi Dima A.

2017-01-01

This paper addresses the feasibility and the efficiency of using Natural Pozzolan and/or Rock flour in Roller Compacted Concrete (RCC) gravity dams. For this purpose, five identical mortar trial mixes were prepared using five different supplementary materials, i.e., fly ash produced in South Africa (proven to be effective in RCC construction), fly ash produced in Turkey, Jordanian natural pozzolan, Saudi natural pozzolan, and rock flour from Mujib Dam basalt quarry. The physical and chemical ...

Telemetry Standards, RCC Standard 106-17, Chapter 4, Pulse Code Modulation Standards

Science.gov (United States)

2017-07-01

A-4 Appendix 4-B. Citations ...investigation can be found in a paper by J. L. Maury, Jr. and J. Styles , “Development of Optimum Frame Synchronization Codes for Goddard Space Flight Center...Standards, RCC Standard 106-17 Chapter 4, July 2017 B-1 APPENDIX 4-B Citations Aeronautical Radio, Inc. Mark 33 Digital Information Transfer

Mouse RC/BTB2, a Member of the RCC1 Superfamily, Localizes to Spermatid Acrosomal Vesicles

Science.gov (United States)

Shen, Xuening; Nagarkatti-Gude, David R.; Hess, Rex A.; Henderson, Scott C.; Strauss, Jerome F.; Zhang, Zhibing

2012-01-01

Mouse RC/BTB2 is an unstudied protein of the RCC1 (Regulator of Chromosome Condensation) superfamily. Because of the significant remodeling of chromatin that occurs during spermiogenesis, we characterized the expression and localization of mouse RC/BTB2 in the testis and male germ cells. The Rc/btb2 gene yields two major transcripts: 2.3 kb Rc/btb2-s, present in most somatic tissues examined; and 2.5 kb Rc/btb2-t, which contains a unique non-translated exon in its 5′-UTR that is only detected in the testis. During the first wave of spermatogenesis, Rc/btb2-t mRNA is expressed from day 8 after birth, reaching highest levels of expression at day 30 after birth. The full-length protein contains three RCC1 domains in the N-terminus, and a BTB domain in the C-terminus. In the testis, the protein is detectable from day 12, but is progressively up-regulated to day 30 and day 42 after birth. In spermatids, some of the protein co-localizes with acrosomal markers sp56 and peanut lectin, indicating that it is an acrosomal protein. A GFP-tagged RCC1 domain is present throughout the cytoplasm of transfected CHO cells. However, both GFP-tagged, full-length RC/BTB2 and a GFP-tagged BTB domain localize to vesicles in close proximity to the nuclear membrane, suggesting that the BTB domain might play a role in mediating full-length RC/BTB2 localization. Since RCC1 domains associate with Ran, a small GTPase that regulates molecular trafficking, it is possible that RC/BTB2 plays a role in transporting proteins during acrosome formation. PMID:22768142

77 FR 17569 - United States-Canada Regulatory Cooperation Council (RCC)-Transportation-Dangerous Goods Working...

Science.gov (United States)

2012-03-26

... identified in the Joint Action Plan, the Transportation--Dangerous Goods Working Group led by senior...)-- Transportation--Dangerous Goods Working Group AGENCY: Pipeline and Hazardous Materials Safety Administration...--Dangerous Goods Working Group, of the United States-Canada Regulatory Cooperation Council (RCC). Comments...

Analysis of Pumphouse RCC Frame Structure for Soil Structure Interaction

OpenAIRE

Mr A.S. Thombare; Prof. V.P. Kumbhar; Prof. A.H. Kumbhar

2016-01-01

When structure is built on ground some elements of structure are direct contact with soil. When loads are applied on structure internal forces are developed in both the structure as well as in soil. It results in deformation of both the components which are independent to each other. This are called soil structure interaction. The analysis is done by using (Bentley STAAD.Pro V8i Version 2007) software. The analysis carried out been pump house structure R.C.C. frame structure find ...

The association between socioeconomic factors and breast cancer-specific survival varies by race.

Directory of Open Access Journals (Sweden)

Shailesh Agarwal

Full Text Available Although racial disparity is well described for oncologic outcomes, factors associated with survival within racial groups remains unexplored. The objective of this study is to determine whether breast cancer survival among White or Black patients is associated with differing patient factors. Women diagnosed with breast cancer from 1998 through 2012 were identified in the Surveillance, Epidemiology, and End Results (SEER database. Cox proportional hazard logistic regression was used to estimate cause-specific survival in the combined cohort, and separate cohorts of Black or White patients only. Main outcomes included cause-specific survival in cohorts of Black only, White only, or all patients adjusted for demographic and oncologic factors. A total of 406,907 Black (10.8% or White (89.2% patients diagnosed with breast cancer from 1998 through 2012 were isolated. Cancer-specific survival analysis of the combined cohort showed significantly decreased hazard ratio (H.R. in patients from the higher economic quartiles (Q1: 1.0 (ref, Q2: 0.95 (p<0.01, Q3: 0.94 (p<0.01, Q4: 0.87 (p<0.001. Analysis of the White only cohort showed a similar relationship with income (Q1: 1.0 (ref, Q2: 0.95 (p<0.01, Q3: 0.95 (p<0.01, Q4: 0.86 (p<0.001. However, analysis of the Black only cohort did not show a relationship with income (Q1: 1.0 (ref, Q2: 1.04 (p = 0.34, Q3: 0.97 (p = 0.53, Q4: 1.04 (p = 0.47. A test of interaction confirmed that the association between income and cancer-specific survival is dependent on patient race, both with and without adjustment for demographic and oncologic characteristics (p<0.01. While median county income is positively associated with cancer-specific survival among White patients, this is not the case with Black patients. Similar findings were noted for education level. These findings suggest that the association between socioeconomic status and breast cancer survival commonly reported in the literature is specific to White patients

A comparative study of physical and chemical properties of different pozzolanic materials used for roller compacted concrete RCC dams

Directory of Open Access Journals (Sweden)

Husein Malkawi Abdallah I.

2017-01-01

Full Text Available This paper addresses the feasibility and the efficiency of using Natural Pozzolan and/or Rock flour in Roller Compacted Concrete (RCC gravity dams. For this purpose, five identical mortar trial mixes were prepared using five different supplementary materials, i.e., fly ash produced in South Africa (proven to be effective in RCC construction, fly ash produced in Turkey, Jordanian natural pozzolan, Saudi natural pozzolan, and rock flour from Mujib Dam basalt quarry. The physical and chemical properties of these pozzolanic materials were determined. The effectiveness of each one of these mineral admixtures used as a cement replacement material in controlling alkali silica reaction are studied and analyzed. Correlations were made between the mechanical properties for the five proposed mixes and a control mix using the Jordanian Portland Cement. The results demonstrate that the performance of Natural Pozzolana and/or rock flour as compared with that of fly ash and other pozzolanic material is very satisfactory and can be effectively used in RCC construction.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

Science.gov (United States)

Kramar, A; Negrier, S; Sylvester, R; Joniau, S; Mulders, P; Powles, T; Bex, A; Bonnetain, F; Bossi, A; Bracarda, S; Bukowski, R; Catto, J; Choueiri, T K; Crabb, S; Eisen, T; El Demery, M; Fitzpatrick, J; Flamand, V; Goebell, P J; Gravis, G; Houédé, N; Jacqmin, D; Kaplan, R; Malavaud, B; Massard, C; Melichar, B; Mourey, L; Nathan, P; Pasquier, D; Porta, C; Pouessel, D; Quinn, D; Ravaud, A; Rolland, F; Schmidinger, M; Tombal, B; Tosi, D; Vauleon, E; Volpe, A; Wolter, P; Escudier, B; Filleron, T

2015-12-01

In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in

Evaluation of KALIMER IHTS piping using French RCC-MR code

International Nuclear Information System (INIS)

Lee, Hyeong Yeon; Kim, J. B.; Lee, J. H.

2001-12-01

In the present report, the evaluation of design integrity for the liquid metal reactor(LMR) of KALIMER IHTS(intermediate heat transport system) piping according to the French design guideline of RCC-MR RC3600 developed for secondary piping of LMR and the evaluation procedure was presented. The evaluation results showed that the results by the simple RC-3600 procedure of design by formula were more conservative than those of ASME section III subsection NH of the design by analysis for the class I structural components

A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

Directory of Open Access Journals (Sweden)

McCooke John K

2012-08-01

Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

French RSE-M and RCC-MR code appendices for flaw analysis: Presentation of the fracture parameters calculation-Part II: Cracked plates

International Nuclear Information System (INIS)

Marie, S.; Chapuliot, S.; Kayser, Y.; Lacire, M.H.; Drubay, B.; Barthelet, B.; Le Delliou, P.; Rougier, V.; Naudin, C.; Gilles, P.; Triay, M.

2007-01-01

French nuclear codes include flaw assessment procedures: the RSE-M Code 'Rules for In-service Inspection of Nuclear Power Plant Components' and the RCC-MR code 'Design and Construction rules for mechanical components of FBR nuclear islands and high temperature applications'. An important effort of development of these analytical methods has been made for the last 10 years in the frame of a collaboration between CEA, EDF and AREVA-NP, and in the frame of R and D actions involving CEA and IRSN. These activities have led to a unification of the common methods of the two codes. The calculation of fracture mechanics parameters, and in particular the stress intensity factor K I and the J integral, has been widely developed for industrial configurations. All the developments have been integrated in the 2005 edition of RSE-M and in the 2007 edition of RCC-MR. This series of articles is composed of 5 parts: the first part presents an overview of the methods proposed in the RCC-MR and RSE-M codes. Parts II-IV provide compendia for specific components. The geometries are plates (part II), pipes (part III) and elbows (part IV). Finally, part V presents the validation elements of the methods, with details on the process followed for the development and evaluation of the accuracy of the proposed analytical methods. This second article in the series presents all details for the stress intensity factor and J calculations for cracked plates. General data applicable for all defect geometries are first presented, and then, available defect geometries where compendia for K I and σ ref calculation are provided are given

Is there racial/ethnic variance in cervical cancer- specific survival of ...

African Journals Online (AJOL)

incident cervical carcinoma, between 1992 and 1999, in the Surveillance Epidemiology and End Results (SEER) Data was linked with Medicare to examine the impact of race/ethnicity on overall and cancer-specific survival, using Kaplan Meier survival estimates and multivariable Cox Regression model. Results: There was ...

RCC-M: Design and construction rules for mechanical components of PWR nuclear islands

International Nuclear Information System (INIS)

2017-01-01

AFCEN's RCC-M code concerns the mechanical components designed and manufactured for pressurized water reactors (PWR). It applies to pressure equipment in nuclear islands in safety classes 1, 2 and 3, and certain non-pressure components, such as vessel internals, supporting structures for safety class components, storage tanks and containment penetrations. RCC-M covers the following technical subjects: sizing and design, choice of materials and procurement. Fabrication and control, including: associated qualification requirements (procedures, welders and operators, etc.), control methods to be implemented, acceptance criteria for detected defects, documentation associated with the different activities covered, and quality assurance. The design, manufacture and inspection rules defined in RCC-M leverage the results of the research and development work pioneered in France, Europe and worldwide, and which have been successfully used by industry to design and build PWR nuclear islands. AFCEN's rules incorporate the resulting feedback. Use: France's last 16 nuclear units (P'4 and N4); 4 CP1 reactors in South Africa (2) and Korea (2); 44 M310 (4), CPR-1000 (28), CPR-600 (6), HPR-1000 (4) and EPR (2) reactors in service or undergoing construction in China; 4 EPR reactors in Europe: Finland (1), France (1) and UK (2). Content: Section I - nuclear island components, subsection 'A': general rules, subsection 'B': class 1 components, subsection 'C': class 2 components, subsection 'D': class 3 components, subsection 'E': small components, subsection 'G': core support structures, subsection 'H': supports, subsection 'J': low pressure or atmospheric storage tanks, subsection 'P': containment penetration, subsection 'Q': qualification of active mechanical components, subsection 'Z': technical appendices; section II - materials; section III - examination

Parent–offspring resemblance in colony-specific adult survival of cliff swallows

Science.gov (United States)

Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

2015-01-01

Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

Telemetry Standards, RCC Standard 106-17. Chapter 3. Frequency Division Multiplexing Telemetry Standards

Science.gov (United States)

2017-07-01

Standard 106-17 Chapter 3, July 2017 3-5 Table 3-4. Constant-Bandwidth FM Subcarrier Channels Frequency Criteria\\Channels: A B C D E F G H Deviation ...Telemetry Standards , RCC Standard 106-17 Chapter 3, July 2017 3-i CHAPTER 3 Frequency Division Multiplexing Telemetry Standards Acronyms...Frequency Division Multiplexing Telemetry Standards ................................ 3-1 3.1 General

Characterizing the outcomes of metastatic papillary renal cell carcinoma

DEFF Research Database (Denmark)

Connor Wells, John; Donskov, Frede; Fraccon, Anna P

2017-01-01

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis.

Science.gov (United States)

Rajan, Saju; Vyas, Dinesh; Clark, Andrew T; Woolsey, Cheryl A; Clark, Jessica A; Hotchkiss, Richard S; Buchman, Timothy G; Coopersmith, Craig M

2008-04-01

Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.

Genome-wide association study of prostate cancer-specific survival

DEFF Research Database (Denmark)

Szulkin, Robert; Karlsson, Robert; Whitington, Thomas

2015-01-01

BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,...

The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma.

Science.gov (United States)

Steffens, Sandra; Janssen, Martin; Roos, Frederik C; Becker, Frank; Steinestel, Julie; Abbas, Mahmoud; Steinestel, Konrad; Wegener, Gerd; Siemer, Stefan; Thüroff, Joachim W; Hofmann, Rainer; Stöckle, Michael; Schrader, Mark; Hartmann, Arndt; Hasenfus, Andrea; Kuczyk, Markus A; Junker, Kerstin; Schrader, Andres J

2014-12-01

The prognostic value of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma (chRCC) because this subtype frequently displays nuclear and nucleolar pleomorphism. The present study reevaluates this grading system in a series of patients with nonsarcomatoid chRCC. We identified 176 patients (3.6%) with nonsarcomatoid chRCC in a total of 4897 patients who underwent surgery for renal cell carcinoma at 5 centers in Germany between 1990 and 2010. The mean follow-up was 51.1 months. The 3 groups (G1 versus G2 versus G3/4) were comparable in terms of age, sex, tumor diameter, and lymph node metastasis. They only differed significantly in tumor stage (P = .01) and the incidence of synchronous visceral metastasis (P = .04). The 5-year cancer-specific survival rates were 84.4% for G1 (n = 32), 84.3% for G2 (n = 108), and 74.1% for G3/4 tumors (n = 33) (P = .58). Accordingly, multivariate analysis including age, sex, tumor stage, and metastatic disease did not identify Fuhrman grading as an independent predictor of cancer-specific survival in patients with chRCC (P = .4). We were able to demonstrate in a large multicenter cohort that the Fuhrman grading system does not qualify as a prognostic tool in patients with chRCC. Copyright © 2014 Elsevier Inc. All rights reserved.

Whether regional lymph nodes evaluation should be equally required for both right and left colon cancer.

Science.gov (United States)

Guan, Xu; Chen, Wei; Liu, Zheng; Jiang, Zheng; Hu, Hanqing; Zhao, Zhixun; Wang, Song; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

2016-09-13

Despite the adequacy of nodal evaluation was gradually improved for colon cancer, the disparity in nodal examination for right colon cancer (RCC) and left colon cancer (LCC) still begs the question of whether 12 nodes is an appropriate threshold for both RCC and LCC. From Surveillance, Epidemiology, and End-Results (SEER) database, we identified 53897 RCC patients and 11822 LCC patients. Compared with LCC patients, RCC patients examined more lymph nodes (18.7 vs 16.3), and more likely to examine ≥12 nodes (Pcancer specific survival (CSS) was calculated according to the optimal node number in RCC and LCC patients, Cox's regression model were used to further assess the prognostic value of this revised nodal evaluation. The results showed that 5-year CSSs were significantly improved for RCC patients with ≥15 lymph nodes, and also for LCC patients with ≥11 lymph nodes (Pcolon cancer as a whole.

Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

International Nuclear Information System (INIS)

Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A.; Gauler, T.; Bauer, S.; Antoch, G.; Schuette, J.

2008-01-01

Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq 111 In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR registered -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

2006-01-01

Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

Science.gov (United States)

Hinnen, Karel A; Monninkhof, Evelyn M; Battermann, Jan J; van Roermund, Joep G H; Frank, Steven J; van Vulpen, Marco

2012-02-01

To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Proper understanding of relevant articles in RCC-M and PANE G-7-002

International Nuclear Information System (INIS)

Sun Zaozhan

2005-01-01

The French code, 'Design and construction rules for mechanical components of PWR nuclear island' RCC-M and the Russian code 'Regulations for strength analysis of equipment and pipelines of atomic power plants' PANE G-7-002, both for nuke plant design, are sometimes used in China, and discrepancies in understanding some articles of such foreign design codes will some times give different conclusions as 'acceptable' or 'unacceptable' the concerned material or product. Section IV of RCC-M concerns with qualification and performance of welding operations. Article S 3150 in this section covers the retesting procedures and article S 3152 in it relates to destructive tests. One sentence in Article S 3152 reads like this, 'Where an unsatisfactory result is due to the poor execution of the test or the presence of a defect in the specimen, the relevant result must be discarded and the test shall be repeated.' The 'presence of a defect' arose discrepancies in understanding the sentence because there is no definition in RCC-M to clarify their scopes such as how big a defect should be considered as a 'defect' that can invalidate the test results. Section 5.5 of PANE G-7-002 concerns the determination of critical brittle temperature. It stipulates that critical brittle temperature T k is a temperature at which the impact strength values must be higher than the specified ones. The specified criterion values of impact strength are related to the yield strength but it is not quite definite that the yield strength values in the table should be the documented minimum values for different materials or that they should be the tested results of the concerned lots of materials the specimen represents. The two different understandings of the yield strength values will sometimes give contrary conclusions. This paper introduces the different opinions in understanding the code texts, makes clear what it supports, and states in detail the reasons it so believes. (authors)

Right Sided Colon Cancer as a Distinct Histopathological Subtype with Reduced Prognosis.

Science.gov (United States)

Nitsche, Ulrich; Stögbauer, Fabian; Späth, Christoph; Haller, Bernhard; Wilhelm, Dirk; Friess, Helmut; Bader, Franz G

2016-01-01

Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RCC revealed a higher cause-specific mortality risk (hazard ratio 1.36, 95% CI 1.10-1.68, p = 0.005) and lower 5-year cause-specific (RCC 64.9%, 95% CI 60.4-69.4, LCC 70.7%, 95% CI 67.2-74.2, p = 0.032) and disease-free (RCC 56.0%, 95% CI 51.5-60.5, LCC 59.9%, 95% CI 56.2-63.6, p = 0.025) survival rates. RCCs were more often microsatellite instable (RCC 37.2%, LCC 13.0%, p clinical, histopathological and molecular genetic features and can be considered as distinct entities. The reduced prognosis of RCC may be caused by higher rates of microsatellite instability, KRAS and BRAF mutations. © 2016 S. Karger AG, Basel.

Telemetry Standards, RCC Standard 106-17, Chapter 27, RF Network Access Layer

Science.gov (United States)

2017-07-01

to the physical media (i.e., the wireless RF network). On the transmission side, it is responsible for framing IP packets for physical transmission ...resolution bandwidth of 30 kHz. It was measured during the steady power condition during a burst transmission . Telemetry Standards, RCC Standard... power levels available for modulated burst transmission . Table 27-1. Transceiver Phase Noise Mask dBc/Hz Frequency Offset −30 dBc/Hz 10 Hz −60 dBc

Adaptive memory: the survival scenario enhances item-specific processing relative to a moving scenario.

Science.gov (United States)

Burns, Daniel J; Hart, Joshua; Griffith, Samantha E; Burns, Amy D

2013-01-01

Nairne, Thompson, and Pandeirada (2007) found that retention of words rated for their relevance to survival is superior to that of words encoded under numerous other deep processing conditions. They suggested that our memory systems might have evolved to confer an advantage for survival-relevant information. Burns, Burns, and Hwang (2011) suggested a two-process explanation of the proximate mechanisms responsible for the survival advantage. Whereas most control tasks encourage only one type of processing, the survival task encourages both item-specific and relational processing. They found that when control tasks encouraged both types of processing, the survival processing advantage was eliminated. However, none of their control conditions included non-survival scenarios (e.g., moving, vacation, etc.), so it is not clear how this two-process explanation would explain the survival advantage when scenarios are used as control conditions. The present experiments replicated the finding that the survival scenario improves recall relative to a moving scenario in both a between-lists and within-list design and also provided evidence that this difference was accompanied by an item-specific processing difference, not a difference in relational processing. The implications of these results for several existing accounts of the survival processing effect are discussed.

Influence of specific comorbidities on survival after early-stage breast cancer

DEFF Research Database (Denmark)

Ewertz, Marianne; Land, Lotte Holm; Dalton, Susanne Oksbjerg

2018-01-01

elevated for patients with prior myocardial infarction, congestive heart failure, cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes. The similar effect of adjuvant treatment in patients with and without comorbidity underlines the importance of adhering to guideline therapy.......BACKGROUND: While comorbidity indices are useful for describing trends in survival, information on specific comorbidities is needed for the clinician advising the individual breast cancer patient on her treatment. Here we present an analysis of overall survival, breast cancer-specific mortality......, and effect of medical adjuvant treatment among breast cancer patients suffering from 12 major comorbidities compared with breast cancer patients without comorbidities. MATERIAL AND METHODS: The study population was identified from the Danish Breast Cancer Cooperative Group and included 59,673 women without...

Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience.

Science.gov (United States)

Bates, James E; Youn, Paul; Peterson, Carl R; Usuki, Kenneth Y; Walter, Kevin A; Okunieff, Paul; Milano, Michael T

2017-10-01

Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

SEISMIC B E H AV I OUR OF R.C.C BUILDING WITH AND WITHOUT FLOATING COLUMNS

OpenAIRE

E. ANUSHA; E. V. RAGHVA RAO; N. CHENNA KESAVA

2018-01-01

The main purpose of the project is to study the seismic behaviour of R.C.C building with and without floating column,G+5 structures has been selected for carrying out the project work. The building models are generated using software STAAD.

Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes.

Science.gov (United States)

Haddad, Mustafa M; Schmit, Grant D; Kurup, A Nicholas; Schmitz, John J; Boorjian, Stephen A; Geske, Jennifer; Thompson, R Houston; Callstrom, Matthew R; Atwell, Thomas D

2018-06-07

To evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. Patients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution's renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. Of the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3-4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). Percutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Telemetry Standards, RCC Standard 106-17. Chapter 8. Digital Data Bus Acquisition Formatting Standard

Science.gov (United States)

2017-07-01

incorrect word count/message and illegal mode codes are not considered bus errors. 8.6.2 Source Signal The source of data is a signal conforming to...Telemetry Standards, RCC Standard 106-17 Chapter 8, July 2017 CHAPTER 8 Digital Data Bus Acquisition Formatting Standard Acronyms...check FCS frame check sequence HDDR high-density digital recording MIL-STD Military Standard msb most significant bit PCM pulse code modulation

PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

Science.gov (United States)

Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

2015-06-01

Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

Science.gov (United States)

Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

2018-01-01

Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

Local Control Rates of Metastatic Renal Cell Carcinoma (RCC) to Thoracic, Abdominal, and Soft Tissue Lesions Using Stereotactic Body Radiotherapy (SBRT)

International Nuclear Information System (INIS)

Altoos, Basel; Amini, Arya; Yacoub, Muthanna; Bourlon, Maria T.; Kessler, Elizabeth E.; Flaig, Thomas W.; Fisher, Christine M.; Kavanagh, Brian D.; Lam, Elaine T.; Karam, Sana D.

2015-01-01

We report the radiographic response rate of SBRT compared to conventional fractionated radiotherapy (CF-EBRT) for thoracic, abdominal, skin and soft tissue RCC lesions treated at our institution. Fifty three lesions where included in the study (36 SBRT, 17 CF-EBRT), treated from 2004 to 2014 at our institution. We included patients that had thoracic, skin & soft tissue (SST), and abdominal metastases of histologically confirmed RCC. The most common SBRT fractionation was 50 Gy in 5 fractions. The median time of follow-up was 16 months (range 3–97 months). Median BED was 216.67 (range 66.67–460.0) for SBRT, and 60 (range 46.67–100.83) for CF-EBRT. Median radiographic local control rates at 12, 24, and 36 months were 100, 93.41, and 93.41 % for lesions treated with SBRT versus 62.02, 35.27 and 35.27 % for those treated with CF-EBRT (p < 0.001). Predictive factors for radiographic local control under univariate analysis included BED ≥ 100 Gy (HR, 0.048; 95 % CI, 0.006–0.382; p = 0.005), dose per fraction ≥ 9 Gy (HR, 0.631; 95 % CI, 0.429–0.931; p = 0.021), and gender (HR, 0.254; 95 % CI, 0.066–0.978; p = 0.048). Under multivariate analysis, there were no significant predictors for local control. Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 side effects reported. SBRT is safe and effective for the treatment of RCC metastases to thoracic, abdominal and integumentary soft tissues. Radiographic response rates were greater and more durable using SBRT compared to CF-EBRT. Further prospective trials are needed to evaluate efficacy and safety of SBRT for RCC metastases

Exposure-response relationships in patients with metastatic renal cell carcinoma receiving sunitinib: maintaining optimum efficacy in clinical practice.

Science.gov (United States)

Ravaud, Alain; Bello, Carlo L

2011-06-01

Targeted agents such as sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, have greatly improved the prognosis for patients with metastatic renal cell carcinoma (mRCC). In this review we analyse data from sunitinib preclinical and clinical studies in detail and consider the key implications for the effective use of sunitinib in clinical practice. Sunitinib has shown efficacy and acceptable tolerability in patients with mRCC in phase II and III clinical studies. In a pivotal phase III study in treatment-naïve patients with mRCC, median progression-free survival for sunitinib-treated patients was double of that with interferon-α (P relationship between clinical end points and sunitinib exposure showed that increased sunitinib exposure was associated with a greater probability of objective response, longer time to tumour progression and overall survival, as well as some increased risk of specific adverse events. It is important to consider the relationship between exposure and response to maximize clinical benefit from sunitinib treatment.

A dose-response relationship for time to bone pain resolution after stereotactic body radiotherapy (SBRT) for renal cell carcinoma (RCC) bony metastases

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Jhaveri, Pavan M. [Dept. of Radiology, Section of Radiation Oncology, Baylor College of Medicine, Houston (United States); Teh, Bin S.; Paulino, Arnold C.; Blanco, Angel I.; Butler, E. Brian [Dept. of Radiation Oncology, The Methodist Hospital/The Methodist Hospital Research Inst., Houston (United States)], email: bteh@tmhs.org; Lo, Simon S. [Dept. of Radiation Oncology, Univ. Hospitals Seidman Cancer Center, Case Western Reserve Univ., Cleveland (United States); Amato, Robert J. [Dept. of Internal Medicine, Div. of Oncology, Univ. of Texas Health Sciences Center, Houston (United States)

2012-05-15

Background. To investigate the utility of stereotactic body radiotherapy (SBRT) in the treatment of painful renal cell carcinoma (RCC) bone metastases, and for a possible dose effect on time to symptom relief. Material and methods. Eighteen patients with 24 painful osseous lesions from metastatic RCC were treated with SBRT. The most common treatment regimens were 24 Gy in 3 fractions and 40 Gy in 5 fractions. The times from treatment to first reported pain relief and time to symptom recurrence were evaluated. Median follow-up was 38 weeks (1-156 weeks). Results. Seventy-eight percent of all patients had pain relief. Patients treated with a BED > 85 Gy achieved faster and more durable pain relief compared to those treated with a BED < 85 Gy. There was decrease in time to pain relief after a change in treatment regimen to 8 Gy x 5 fractions (BED = 86). There was only one patient with grade 1 skin toxicity. No neurological or other toxicity was observed. Conclusions. SBRT can safely and effectively treat painful RCC bony metastases. There appears to be a relationship between radiation dose and time to stable pain relief.

Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

Science.gov (United States)

Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

2017-08-08

Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Analyzing age-specific genetic effects on human extreme age survival in cohort-based longitudinal studies

DEFF Research Database (Denmark)

Tan, Qihua; Jacobsen, Rune; Sørensen, Mette

2013-01-01

The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic...... effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies...

Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome?

Science.gov (United States)

Lim, Dae Ro; Kuk, Jung Kul; Kim, Taehyung; Shin, Eung Jin

2017-10-01

There are embryological origins, anatomical, histological, genetic, and immunological differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Many studies have sought to determine the survival and prognosis according to tumor location. This study aimed to analyze outcomes between RCC and LCC. Between January 2000 and December 2012, data on 414 patients who underwent curative resection for RCC and LCC were retrieved from a retrospective database. Propensity score matching (1:1) was performed and RCC was identified in 207 and LCC in 207 patients. On average, RCC exhibited a more advanced N stage, increased tumor size, more frequently poorly differentiated tumors, more harvested lymph nodes, and more positivity of lymphovascular invasion than LCC. With a median follow-up of 66.7 months, the 5-year overall survival (OS) rates for RCC and LCC were 82.1% and 88.7%, respectively, (P cancers, the DFS rates were 61.1% (RCC) and 81.9% (LCC; P colon cancer is needed.

First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

Energy Technology Data Exchange (ETDEWEB)

Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Ricke, Jens, E-mail: jens.Ricke@med.ovgu.de; Pech, Maciej, E-mail: macej.pech@med.ovgu.de; Fischbach, Frank, E-mail: frank.fischbach@med.ovgu.de; Jürgens, Julian, E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology (Germany); Siedentopf, Sandra, E-mail: sandra.siedentopf@med.ovgu.de; Roessner, Albert, E-mail: albert.roessner@med.ovgu.de [University of Magdeburg, Institute of Pathology (Germany); Porsch, Markus, E-mail: markus.porsch@med.ovgu.de; Baumunk, Daniel, E-mail: daniel.baumunk@med.ovgu.de; Schostak, Martin, E-mail: martin.schostak@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Köllermann, Jens, E-mail: jens.koellermann@sana.de [Sana Klinikum Offenbach Am Main, Institute of Pathology (Germany); Liehr, Uwe-Bernd, E-mail: uwe-bernd.liehr@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany)

2016-02-15

IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol.

Characteristics of Differently Located Colorectal Cancers Support Proximal and Distal Classification: A Population-Based Study of 57,847 Patients.

Directory of Open Access Journals (Sweden)

Jiao Yang

Full Text Available It has been suggested that colorectal cancer be regarded as several subgroups defined according to tumor location rather than as a single entity. The current study aimed to identify the most useful method for grouping colorectal cancer by tumor location according to both baseline and survival characteristics.Cases of pathologically confirmed colorectal adenocarcinoma diagnosed from 2000 to 2012 were identified from the Surveillance, Epidemiology, and End Results database and categorized into three groups: right colon cancer (RCC, left colon cancer (LCC, and rectal cancer (ReC. Adjusted hazard ratios for known predictors of disease-specific survival (DSS in colorectal cancer were obtained using a Cox proportional hazards regression model.The study included 57847 patients: 43.5% with RCC, 37.7% with LCC, and 18.8% with ReC. Compared with LCC and ReC, RCC was more likely to affect old patients and women, and to be at advanced stage, poorly differentiated or un-differentiated, and mucinous. Patients with LCC or ReC had better DSS than those with RCC in subgroups including stage III or IV disease, age ≤70 years and non-mucinous adenocarcinoma. Conversely, patients with LCC or ReC had worse DSS than those with RCC in subgroups including age ˃70 years and mucinous adenocarcinoma.RCC differed from both LCC and ReC in several clinicopathologic characteristics and in DSS. It seems reasonable to group colorectal cancer into right-sided (i.e., proximal and left-sided (i.e., distal ones.

Overall survival after prostate-specific-antigen-detected recurrence following conformal radiation therapy

International Nuclear Information System (INIS)

Sandler, Howard M.; Dunn, Rodney L.; McLaughlin, P. William; Hayman, James A.; Sullivan, Molly A.; Taylor, Jeremy M.G.

2000-01-01

Purpose: To study the significance, in terms of overall and cause-specific survival, of biochemical failure after conformal external-beam radiation therapy (RT) for prostate cancer. Methods and Materials: Of the 1844 patients in the Radiation Oncology prostate cancer database, 718 were deemed eligible. Patients excluded were those with N1 or M1 disease, those treated after radical prostatectomy, those who received hormone therapy before radiation therapy, and those who died, failed clinically, or had no PSA response in the first 6 months after RT. Patients included were required to have a minimum of 2 post-RT PSAs separated by at least 1 week. Biochemical relapse was defined as 3 consecutive PSA rises. This resulted in 154 patients with biochemical failure. Survival was calculated from the third PSA elevation. The rate of rise of PSA was calculated by fitting a regression line to the four rising PSAs on a ln PSA vs. time plot. Results: There were 41 deaths among the 154 patients with failure in 23 of the 41 due to prostate cancer. The overall survival after failure was 58% at 5 years, while the cause-specific failure was 73% at 5 years. Among the 154 failures, several factors were evaluated for an association with overall survival: age at failure, pre-RT PSA, PSA at second rise, PSA nadir, time from RT to failure, time to nadir, Gleason score, T-stage, and rate of rise, both from the nadir and from the beginning of the rise. None of these factors were significantly associated with an increased risk of death. As expected, the group of patients with biochemical failure have significantly worse prognostic factors than those without biochemical failure: median pre-RT PSA 15.9 vs. 9.0 (p < 0.001), and Gleason score of 7 or greater for 48% of subjects vs. 40% (p 0.1). Relative PSA rise and slope of ln PSA vs. time were associated with cause-specific mortality (p < 0.001 and p = 0.007, respectively). Conclusion: Overall survival after conformal radiotherapy for prostate

Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

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Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

2015-07-15

To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

Metastasis is promoted by a bioenergetic switch: New targets for progressive renal cell cancer

NARCIS (Netherlands)

Langbein, Sigrun; Frederiks, Wilma M.; zur Hansen, Axel; Popa, Juljane; Lehmann, Jan; Weiss, Christel; Alken, Peter; Coy, Johannes F.

2008-01-01

Targeted therapies have demonstrated clinical benefit with limited impact on long-term disease specific survival in the treatment of renal cell cancer (RCC). New opportunities for the treatment of tumors that are resistant or have relapsed, are needed. Increased anaerobic glucose fermentation to

Editor’s Pick: Targeted Agents in Patients with Metastatic Renal Cell Carcinoma on Dialysis: Myths and Reality

Directory of Open Access Journals (Sweden)

Annalisa Guida

2016-07-01

Full Text Available Agents targeting the vascular endothelial growth factor (VEGF/VEGF receptor (VEGFR pathway, as well as mammalian target of rapamycin (mTOR inhibitors have revolutionised the therapeutic landscape of metastatic renal cell carcinoma (mRCC in the past decade, greatly improving the survival rates of these patients. However, translating results of registrative Phase III trials into everyday clinical practice is often troublesome, since real-world patients are completely different from those enrolled in randomised controlled Phase III trials. Prospective data on active oncological treatments in mRCC patients on dialysis are dramatically lacking. This literature review summarises and critically comments on available data relative to mRCC patients on dialysis receiving either VEGF/VEGFR-targeting agents, or mTOR inhibitors. Although prospective studies would definitely be warranted in these specific patient populations, all the available data suggest that mRCC patients on dialysis have the same outcome, both in terms of efficacy and safety, as mRCC patients with normal or marginally impaired kidney function, when treated with VEGF/VEGFR-targeting agents and/or mTOR inhibitors.

Management of metastatic renal cell carcinoma in patients with poor prognosis

International Nuclear Information System (INIS)

Bullock, Andrea; McDermott, David F; Atkins, Michael B

2010-01-01

An improved understanding of renal cell carcinoma (RCC) biology has translated into major advances in the treatment of patients with metastatic RCC in recent years. Clinical and pathologic criteria can be used to identify RCC patients with poor prognoses. Such patients, however, are often excluded from the cancer clinical trials that guide treatment recommendations. This article reviews available information on the management of patients with metastatic RCC and poor risk features, focusing on the role of vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with poor risk features have a more guarded outcome, treatment with temsirolimus has produced meaningful improvements in overall survival for this population. Definitive phase III trial data are lacking for the VEGF pathway inhibitors in patients with poor prognostic features. However, available data suggest that such patients tolerate VEGF pathway blockade reasonably well and are likely to achieve some benefit relative to treatment with interferon. Ongoing translational research efforts may help to define novel treatment approaches specific for patients with metastatic RCC and poor prognostic features

Renal cell carcinoma: incidental detection and pathological staging.

Science.gov (United States)

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Sex-specific differential survival of extra-pair and within-pair offspring in song sparrows, Melospiza melodia.

Science.gov (United States)

Sardell, Rebecca J; Arcese, Peter; Keller, Lukas F; Reid, Jane M

2011-11-07

It is widely hypothesized that the evolution of female extra-pair reproduction in socially monogamous species reflects indirect genetic benefits to females. However, a critical prediction of this hypothesis, that extra-pair young (EPY) are fitter than within-pair young (WPY), has rarely been rigorously tested. We used 18 years of data from free-living song sparrows, Melospiza melodia, to test whether survival through major life-history stages differed between EPY and WPY maternal half-siblings. On average, survival of hatched chicks to independence from parental care and recruitment, and their total lifespan, did not differ significantly between EPY and WPY. However, EPY consistently tended to be less likely to survive, and recruited EPY survived for significantly fewer years than recruited WPY. Furthermore, the survival difference between EPY and WPY was sex-specific; female EPY were less likely to survive to independence and recruitment and lived fewer years than female WPY, whereas male EPY were similarly or slightly more likely to survive and to live more years than male WPY. These data indicate that extra-pair paternity may impose an indirect cost on females via their female offspring and that sex-specific genetic, environmental or maternal effects may shape extra-pair reproduction.

Design and Construction Rules for Mechanical components of FBR nuclear islands: RCC-MR. Tome 1, Volume H: Supports

International Nuclear Information System (INIS)

1985-06-01

The present book is the fifth one of a whole set of 12 which constitute the present edition of the RCC-MR. The volume H applies to supports of equipments when these equipments are concerned by the RCC-MR rules in application of the chapter RA 4000 of the Tome 1, Vol A. One defines the field of application of this volume and the classification rules of supports in two levels. One defines the different types of supports and fasteners, as also the classification of the support elements in primary or resistance (or structure) elements and secondary (stability) elements. One defines the documents to be established for the components and their constitutive elements, the modalities of identification of pieces and welded joints, the rules to choose the materials of the support elements, the rules to follow for the support conception, the rules to follow for fabrication and tests, as also other rules than those given in the chapters RH 2000 to RH 4000, to homologate a standard support or a component of a standard support [fr

Structural damages prevention of the ITER vacuum vessel and ports by elasto-plastic analysis with regards to RCC-MR

Energy Technology Data Exchange (ETDEWEB)

Martinez, Jean-Marc, E-mail: jean-marc.martinez@iter.org [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Jun, Chang Hoon; Portafaix, Christophe; Alekseev, Alexander; Sborchia, Carlo; Choi, Chang-Ho [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Albin, Vincent [SOM Calcul – Groupe ORTEC, 121 ancien Chemin de Cassis – Immeuble Grand Pré, 13009 Marseille (France); Borrelly, Stephane [Sogeti High Tech, RE2, 180 rue René Descartes, Le Millenium – Bat C, 13857 Aix en Provence (France); Cambazar, Magali [Assystem EOS, 117 rue Jacquard, 84120 Pertuis (France); Gaucher, Thomas [SOM Calcul – Groupe ORTEC, 121 ancien Chemin de Cassis – Immeuble Grand Pré, 13009 Marseille (France); Sfarni, Samir; Tailhardat, Olivier [Assystem EOS, 117 rue Jacquard, 84120 Pertuis (France)

2015-10-15

Highlights: • ITER vacuum vessel (VV) is a part of the first barrier to confine the plasma. • ITER VV as NPE necessitates a third party organization authorized by the French nuclear regulator to assure design, fabrication, and conformance testing and quality assurance, i.e. ANB. • Several types of damages have to be prevented in order to guarantee the structural integrity with regards to RCC-MR. • It is usual to employ non-linear analysis when the “classical” elastic analysis reaches its limit of linear application. • Several structural analyses were performed with many different global and local models of the whole ITER VV. - Abstract: Several types of damages have to be prevented in order to guarantee the structural integrity of a structure with regards to RCC-MR; the P-type damages which can result from the application to a structure of a steadily and regularly increasing loading or a constant loading and the S-type damages during operational loading conditions which can only result from repeated application of loadings associated to the progressive deformations and fatigue. Following RCC-MR, the S-type damages prevention has to be started only when the structural integrity is guaranteed against P-type damages. The verification of the last one on the ITER vacuum vessel and ports has been performed by limit analysis with elasto-(perfectly)plastic material behavior. It is usual to employ non-linear analysis when the “classical” elastic analysis reaches its limit of linear application. Some elasto-plastic analyses have been performed considering several cyclic loadings to evaluate also more realistic structural margins of the against S-type damages.

Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals.

Science.gov (United States)

Wang, Kefeng; Sun, Yin; Tao, Wei; Fei, Xiang; Chang, Chawnshang

2017-05-28

Increasing evidence has demonstrated that the androgen receptor (AR) plays important roles to promote the metastasis of clear cell renal cell carcinoma (ccRCC). The detailed mechanisms, especially how AR functions via altering the circular RNAs (circRNAs) remain unclear. Here we identified a new circRNA (named as circHIAT1) whose expression was lower in ccRCCs than adjacent normal tissues. Targeting AR could suppress ccRCC cell progression via increasing circHIAT1 expression. ChIP assay and luciferase assay demonstrated that AR suppressed circHIAT1 expression via regulating its host gene, Hippocampus Abundant Transcript 1 (HIAT1) expression at the transcriptional level. The consequences of AR-suppressed circHIAT1 resulted in deregulating miR-195-5p/29a-3p/29c-3p expressions, which increased CDC42 expression to enhance ccRCC cell migration and invasion. Increasing this newly identified signal via circHIAT1 suppressed AR-enhanced ccRCC cell migration and invasion. Together, these results suggested that circHIAT1 functioned as a metastatic inhibitor to suppress AR-enhanced ccRCC cell migration and invasion. Targeting this newly identified AR-circHIAT1-mediated miR-195-5p/29a-3p/29c-3p/CDC42 signals may help us develop potential new therapies to better suppress ccRCC metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Single classifier, OvO, OvA and RCC multiclass classification method in handheld based smartphone gait identification

Science.gov (United States)

Raziff, Abdul Rafiez Abdul; Sulaiman, Md Nasir; Mustapha, Norwati; Perumal, Thinagaran

2017-10-01

Gait recognition is widely used in many applications. In the application of the gait identification especially in people, the number of classes (people) is many which may comprise to more than 20. Due to the large amount of classes, the usage of single classification mapping (direct classification) may not be suitable as most of the existing algorithms are mostly designed for the binary classification. Furthermore, having many classes in a dataset may result in the possibility of having a high degree of overlapped class boundary. This paper discusses the application of multiclass classifier mappings such as one-vs-all (OvA), one-vs-one (OvO) and random correction code (RCC) on handheld based smartphone gait signal for person identification. The results is then compared with a single J48 decision tree for benchmark. From the result, it can be said that using multiclass classification mapping method thus partially improved the overall accuracy especially on OvO and RCC with width factor more than 4. For OvA, the accuracy result is worse than a single J48 due to a high number of classes.

Study on Flexural Behaviour of Ternary Blended Reinforced Self Compacting Concrete Beam with Conventional RCC Beam

Science.gov (United States)

Marshaline Seles, M.; Suryanarayanan, R.; Vivek, S. S.; Dhinakaran, G.

2017-07-01

The conventional concrete when used for structures having dense congested reinforcement, the problems such as external compaction and vibration needs special attention. In such case, the self compacting concrete (SCC) which has the properties like flow ability, passing and filling ability would be an obvious answer. All those SCC flow behavior was governed by EFNARC specifications. In present study, the combination type of SCC was prepared by replacing cement with silica fume (SF) and metakaolin (MK) along with optimum dosages of chemical admixtures. From the fresh property test, cube compressive strength and cylinder split tensile strength, optimum ternary mix was obtained. In order to study the flexural behavior, the optimum ternary mix was taken in which beam specimens of size 1200 mm x 100 mm x 200 mm was designed as singly reinforced section according to IS: 456-2000, Limit state method. Finally the comparative experimental analysis was made between conventional RCC and SCC beams of same grade in terms of flexural strength namely yield load & ultimate load, load- deflection curve, crack size and pattern respectively.

Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Fengju Chen

2016-03-01

Full Text Available On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression, we classified 894 renal cell carcinomas (RCCs of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

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Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Design and Construction Rules for Mechanical components of FBR nuclear islands: RCC-MR. Tome II: materials

International Nuclear Information System (INIS)

1985-06-01

This book is the 8th of a whole set of 12 ones which constitute the edition 1985 of the RCC-MR. One deals with alloy and non-alloy steels on one hand, and with pieces and products (bars, plates, tubes, forgings and castings) on the other hand. The requirements concerning the mechanical properties, the chemical composition, the search of defects and their repair, the heat treatments, the tests to carry out and the delivery state are specified [fr

Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy

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Anbalagan, Selvakumar; Pires, Isabel M.; Blick, Christopher; Hill, Mark A.; Ferguson, David J.P.; Chan, Denise A.; Hammond, Ester M.

2012-01-01

Background and purpose: For patients diagnosed with advanced renal cell carcinoma (RCC), there are few therapeutic options. Radiation therapy is predominantly used to treat metastasis and has not proven effective in the adjuvant setting for renal cancer. Furthermore, RCC is resistant to standard cytotoxic chemotherapies. Targeted anti-angiogenics are the standard of care for RCC but are not curative. Newer agents, such as mTOR inhibitors and others that induce autophagy, have shown great promise for treating RCC. Here, we investigate the potential use of the small molecule STF-62247 to modulate radiation. Materials and methods: Using RCC cell lines, we evaluate sensitivity to radiation in addition to agents that induce autophagic cell death by clonogenic survival assays. Furthermore, these were also tested under physiological oxygen levels. Results: STF-62247 specifically induces autophagic cell death in cells that have lost VHL, an essential mutation in the development of RCC. Treatment with STF-62247 did not alter cell cycle progression but when combined with radiation increased cell killing under oxic and hypoxic/physiological conditions. Conclusions: This study highlights the possibility of combining targeted therapeutics such as STF-62247 or temsirolimus with radiation to reduce the reliance on partial or full nephrectomy and improve patient prognosis.

CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

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Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Lemm, G.; Hohenstein, E. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany); Bellemann, N.; Stampfl, U. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Goezen, A. S.; Rassweiler, J. [Clinic for Urology, SLK Kliniken Heilbronn GmbH (Germany); Kauczor, H. U.; Radeleff, B. A. [University Hospital Heidelberg, INF 110, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P. L. [Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Clinic for Radiology (Germany)

2013-06-15

Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 {+-} 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 {+-} 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 {+-} 13.6 min and 43.7 {+-} 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 {+-} 8.8 months, local recurrence-free survival was 14.4 {+-} 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 {+-} 16.6 ml/min/1.73 m{sup 2} before RF ablation vs. 47.2 {+-} 11.9 ml/min/1.73 m{sup 2} after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients.

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Sobotka, Roman; Čapoun, Otakar; Kalousová, Marta; Hanuš, Tomáš; Zima, Tomáš; Koštířová, Milada; Soukup, Viktor

2017-07-01

To assess the prognostic importance of serum levels of retinol, retinol-binding protein 4 (RBP4) and vitamin E at the time of diagnosis in patients with renal cell carcinoma (RCC). In this prospective study, in a cohort of 102 renal cell carcinoma patients, relationships between serum levels of the aforementioned markers and recurrence-free survival (RFS), overall survival (OS), as well as cancer-specific survival (CSS), were evaluated. The vitamin A and vitamin E levels were determined by high-performance liquid chromatography (HPLC), while the RBP4 level by enzyme-linked immunosorbent assay (ELISA). The median follow-up period was 39 months. Renal cell carcinoma recurred in 9 patients; 23 patients died with 12 of them from RCC. The preoperative vitamin E level was associated to RFS (p=0.02). We found a significant relationship between OS and the level of RBP4 (p=0.002), retinol (p=0.037) and vitamin E (p=0.007). The CSS period was significantly associated with the level of RBP4 (p=0.0001) and retinol (p=0.0003). Patients with an RBP4 level less than 21.0 mg/l at the time of diagnosis had a 13.5-times higher risk of death due to RCC progression; this risk was up to 7.7-times higher with vitamin A levels under 0.52 mg/l. Low levels of vitamin A, E and RBP4 at the time of RCC diagnosis are associated with a poorer prognosis after surgery. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Metastatic renal cell carcinoma management

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Flavio L. Heldwein

2009-06-01

Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

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Steven M Yip

2016-03-01

Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma

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Paly, Jonathan J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Biggs, Peter J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Roeder, Falk [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Martínez-Monge, Rafael [Radiation Oncology Division, University of Navarre, Pamplona (Spain); Whitson, Jared [Department of Urology, University of California San Francisco, San Francisco, California (United States); Calvo, Felipe A. [Departamento de Oncología, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Fastner, Gerd; Sedlmayer, Felix [Department of Radiotherapy and Radio-Oncology, Paracelsus Medical University Clinics, Salzburg (Austria); Wong, William W. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, Arizona (United States); Ellis, Rodney J. [Department of Radiation Oncology, Seidman Cancer Center University Hospitals Case Medical Center, Cleveland, Ohio (United States); Haddock, Michael G.; Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Shipley, William U.; Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-03-01

Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P<.01), presence of sarcomatoid features (HR 3.7-6.9, P<.05), and higher IORT dose (HR 1.3, P<.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to

Age-specific survival of reintroduced swift fox in Badlands National Park and surrounding lands

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Sasmal, Indrani; Klaver, Robert W.; Jenks, Jonathan A.; Schroeder, Greg M.

2016-01-01

In 2003, a reintroduction program was initiated at Badlands National Park (BNP), South Dakota, USA, with swift foxes (Vulpes velox) translocated from Colorado and Wyoming, USA, as part of a restoration effort to recover declining swift fox populations throughout its historical range. Estimates of age-specific survival are necessary to evaluate the potential for population growth of reintroduced populations. We used 7 years (2003–2009) of capture–recapture data of 243 pups, 29 yearlings, and 69 adult swift foxes at BNP and the surrounding area to construct Cormack–Jolly–Seber model estimates of apparent survival within a capture–mark–recapture framework using Program MARK. The best model for estimating recapture probabilities included no differences among age classes, greater recapture probabilities during early years of the monitoring effort than later years, and variation among spring, winter, and summer. Our top ranked survival model indicated pup survival differed from that of yearlings and adults and varied by month and year. The apparent annual survival probability of pups (0.47, SE = 0.10) in our study area was greater than the apparent annual survival probability of yearlings and adults (0.27, SE = 0.08). Our results indicate low survival probabilities for a reintroduced population of swift foxes in the BNP and surrounding areas. Management of reintroduced populations and future reintroductions of swift foxes should consider the effects of relative low annual survival on population demography.

Prognostic Significance of Blood Type A in Patients with Renal Cell Carcinoma.

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Ko, Kyungtae; Park, Young Hyun; Jeong, Chang Wook; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2016-08-25

In this study, we evaluated the prognostic significance of the ABO blood type in patients with renal cell carcinoma (RCC) who had undergone partial or radical nephrectomy. Information on the ABO blood type was obtained from 1750 patients with RCC. A total of 1243 men and 507 women (mean age, 55.41 ± 12.43 years) with RCC who had undergone partial or radical nephrectomy were enrolled in this study. The median follow-up duration was 35.0 months (interquartile range [IQR], 16.0-67.0). During the follow-up period, 271 patients experienced RCC recurrence, and 137 patients died from RCC. Type A was the most common blood type (568, 32.5%), followed by type O (525, 30.0%), type B (464, 26.5%), and type AB (193, 11.0%). Generally, blood type was not associated with any clinicopathological factors. Unlike blood type O, the multivariate analysis of progression-free survival (PFS) showed that blood type non-O (A, B, and AB) was an independent prognostic factor for a worse outcome (95% confidence interval [CI]: 1.24- 2.37, hazard ratio [HR] = 1.71, P = .001; 95% CI: 1.08-2.13, HR = 1.51, P = .016; 95% CI: 1.03-2.43, HR = 1.58, P = .037, respectively). Cancer-specific survival (CSS) analysis showed that blood type A was an independent factor associated with a worse prognosis for CSS (95% CI: 1.05-2.64, HR 1.66, P = .031, respectively). The ABO blood type is significantly associated with PFS and CSS in patients with RCC following partial or radical nephrectomy. Blood type non-O (A, B, and AB) is an independent prognostic factor for a worse PFS outcome, and blood type A is an independent factor associated with a worse CSS prognosis. .

Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

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Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

2016-09-01

To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

The option value of innovative treatments for non-small cell lung cancer and renal cell carcinoma.

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Thornton Snider, Julia; Batt, Katharine; Wu, Yanyu; Tebeka, Mahlet Gizaw; Seabury, Seth

2017-10-01

To develop a model of the option value a therapy provides by enabling patients to live to see subsequent innovations and to apply the model to the case of nivolumab in renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). A model of the option value of nivolumab in RCC and NSCLC was developed and estimated. Data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and published clinical trial results were used to estimate survival curves for metastatic cancer patients with RCC, squamous NSCLC, or nonsquamous NSCLC. To estimate the conventional value of nivolumab, survival with the pre-nivolumab standard of care was compared with survival with nivolumab assuming no future innovation. To estimate the option value of nivolumab, long-term survival trends in RCC and squamous and nonsquamous NSCLC were measured in SEER to forecast mortality improvements that nivolumab patients may live to see. Compared with the previous standard of care, nivolumab extended life expectancy by 6.3 months in RCC, 7.5 months in squamous NSCLC, and 4.5 months in nonsquamous NSCLC, according to conventional methods. Accounting for expected future mortality trends, nivolumab patients are likely to gain an additional 1.2 months in RCC, 0.4 months in squamous NSCLC, and 0.5 months in nonsquamous NSCLC. These option values correspond to 18%, 5%, and 10% of the conventional value of nivolumab, respectively. Option value is important when valuing therapies like nivolumab that extend life in a rapidly evolving area of care.

Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages.

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Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

2015-01-01

To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (pstage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate.

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

NARCIS (Netherlands)

Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to

Expression of minichromosome maintenance genes in renal cell carcinoma

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Zhong HB

2017-11-01

Full Text Available Hongbin Zhong,1,* Bin Chen,1,* Henrique Neves,2 Jinchun Xing,1 Youxin Ye,1 Ying Lin,1 Guohong Zhuang,3 Shu-Dong Zhang,4 Jiyi Huang,1,5 Hang Fai Kwok2 1Xiang’an Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Faculty of Health Sciences, University of Macau, Taipa, Macau SAR; 3Medical College of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry, UK; 5The First Clinical School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China *These authors contributed equally to this work Abstract: Minichromosome maintenance (MCM proteins play an essential role in DNA replication. They have been shown to be overexpressed in various types of cancer. However, the role of this family in renal cell carcinoma (RCC is widely unknown. In this study, we have identified a number of RCC datasets in the Gene Expression Omnibus database and also investigated the correlation between the expression levels of MCM genes and clinicopathological parameters. We found that the expression levels of MCM genes are positively correlated with one another. Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were higher in RCC compared to paired adjacent normal tissue. Only the expression level of MCM4, but not of other MCMs, was positively correlated with tumor grade. In addition, a high-level expression of MCM2 in either primary tumor or metastases of RCC predicted a shorter disease-free survival time, while a high-level expression of MCM4 or MCM6 in primary tumor was also associated with poorer disease-free survival. Interestingly, we also demonstrated that patients with their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free survival time, while those with RCC metastases overexpressing 3 or more MCM genes had a shorter

Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas

International Nuclear Information System (INIS)

Yao, Masahiro; Murakami, Takayuki; Shioi, Koichi; Mizuno, Nobuhiko; Ito, Hiroki; Kondo, Keiichi; Hasumi, Hisashi; Sano, Futoshi; Makiyama, Kazuhide; Nakaigawa, Noboru; Kishida, Takeshi; Nagashima, Yoji; Yamanaka, Shoji; Kubota, Yoshinobu

2014-01-01

High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs

Sex-specific effects of yolk testosterone on survival, begging and growth of zebra finches

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von Engelhardt, N; Carere, C; Dijkstra, C; Groothuis, TGG

2006-01-01

Yolk androgens affect offspring hatching, begging, growth and survival in many bird species. If these effects are sex-specific, yolk androgen deposition may constitute a mechanism for differential investment in male and female offspring. We tested this hypothesis in zebra finches. In this species,

Prognostic significance of multidrug-resistance protein (MDR-1 in renal clear cell carcinomas: A five year follow-up analysis

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Strazzullo Viviana

2006-12-01

Full Text Available Abstract Background A large number of renal cancer patients shows poor or partial response to chemotherapy and the mechanisms have not been still understood. Multi-drug resistance is the principal mechanism by which many cancers develop resistance to chemotherapic drugs. The role of the multi-drug resistant transporter (MDR-1/P-glycoprotein, the gene product of MDR-1, and that one of the so-called multi-drug resistance associated protein (MRP, two energy-dependent efflux pumps, are commonly known to confer drug resistance. We studied MDR-1 expression in selected cases of renal cell carcinoma (RCC, clear cell type, with long-term follow-up, in order to establish its prognostic role and its possible contribution in the choice of post-surgical therapy. Methods MDR-1 has been studied by standard LSAB-HRP immunohistochemical technique, in paraffin embedded RCC samples. Protein expression has been compared to clinical and histopathological data and to disease specific survival of RCC patients, by Kaplan-Meier curve and Cox multivariate regression analyses. Results Two groups of RCCs were obtained by esteeming MDR-1 expression and disease specific survival (obtained with Kaplan-Meier curve and Cox multivariate regression analyses: the first one presents low or absent MDR-1 expression and good survival; the second one is characterized by high MDR-1 expression and significant poor outcome (p p p p Conclusion In our opinion, the results of this study well prove the relationship between MDR-1 expression and worse clinical prognosis in RCC, because MDR-1 over-expressing RCCs can be considered a group of tumours with a more aggressive behavior. This finding outlines a possible role of MDR-1 as prognostic factor, dependent and independent of multidrug resistance. These results could be useful to predict cancer evolution and to choose the appropriate treatment: this is another step that can stimulate further promising and interesting investigations on broader

Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

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Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

2016-04-26

The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.

Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

International Nuclear Information System (INIS)

Beyer, David C.; McKeough, Timothy; Thomas, Theresa

2005-01-01

Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

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Saad, Fred; Eastham, James A

2010-06-01

Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

International Nuclear Information System (INIS)

Lobo, Nazleen C.; Gedye, Craig; Apostoli, Anthony J.; Brown, Kevin R.; Paterson, Joshua; Stickle, Natalie; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J.; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Moffat, Jason; Jewett, Michael A. S.; Ailles, Laurie

2016-01-01

Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels. Furthermore, ccRCC exhibits significant intertumor genetic heterogeneity, and the limited cell lines available fail to represent this aspect of ccRCC. Our objective was to generate accurate preclinical in vitro models of ccRCC using tumor tissues from ccRCC patients. ccRCC primary single cell suspensions were cultured in fetal bovine serum (FBS)-containing media or defined serum-free media. Established cultures were characterized by genomic verification of mutations present in the primary tumors, expression of renal epithelial markers, and transcriptional profiling. The apparent efficiency of primary cell culture establishment was high in both culture conditions, but genotyping revealed that the majority of cultures contained normal, not cancer cells. ccRCC characteristically shows biallelic loss of the von Hippel Lindau (VHL) gene, leading to accumulation of hypoxia-inducible factor (HIF) and expression of HIF target genes. Purification of cells based on expression of carbonic anhydrase IX (CA9), a cell surface HIF target, followed by culture in FBS enabled establishment of ccRCC cell cultures with an efficiency of >80 %. Culture in serum-free conditions selected for growth of normal renal proximal tubule epithelial cells. Transcriptional profiling of ccRCC and matched normal cell cultures identified up- and down-regulated networks in ccRCC and comparison to The Cancer Genome Atlas confirmed the clinical validity of our cell cultures. The ability

Strain-specific responses of Emiliania huxleyi to changing seawater carbonate chemistry

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P. Ziveri

2009-11-01

Full Text Available Four strains of the coccolithophore E. huxleyi (RCC1212, RCC1216, RCC1238, RCC1256 were grown in dilute batch culture at four CO2 levels ranging from ~200 μatm to ~1200 μatm. Growth rate, particulate organic carbon content, and particulate inorganic carbon content were measured, and organic and inorganic carbon production calculated. The four strains did not show a uniform response to carbonate chemistry changes in any of the analysed parameters and none of the four strains displayed a response pattern previously described for this species. We conclude that the sensitivity of different strains of E. huxleyi to acidification differs substantially and that this likely has a genetic basis. We propose that this can explain apparently contradictory results reported in the literature.

CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

International Nuclear Information System (INIS)

Sommer, C. M.; Lemm, G.; Hohenstein, E.; Bellemann, N.; Stampfl, U.; Goezen, A. S.; Rassweiler, J.; Kauczor, H. U.; Radeleff, B. A.; Pereira, P. L.

2013-01-01

Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m 2 before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m 2 after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma.

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Naito, Sei; Makhov, Peter; Astsaturov, Igor; Golovine, Konstantin; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G; Kolenko, Vladimir M

2017-04-25

Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib. The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells. Furthermore, RCC xenograft tumours resist TKIs in mice fed a high-fat/high-cholesterol diet. The ability of renal tumours to maintain their cholesterol homoeostasis may be a critical component of TKI resistance in RCC patients.

NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20.

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Drennan, Michael B; Govindarajan, Srinath; Verheugen, Eveline; Coquet, Jonathan M; Staal, Jens; McGuire, Conor; Taghon, Tom; Leclercq, Georges; Beyaert, Rudi; van Loo, Geert; Lambrecht, Bart N; Elewaut, Dirk

2016-09-19

Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells. © 2016 Drennan et al.

Study on Viscoelastic Deformation Monitoring Index of an RCC Gravity Dam in an Alpine Region Using Orthogonal Test Design

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Yaoying Huang

2018-01-01

Full Text Available The main objective of this study is to present a method of determining viscoelastic deformation monitoring index of a Roller-compacted concrete (RCC gravity dam in an alpine region. By focusing on a modified deformation monitoring model considering frost heave and back analyzed mechanical parameters of the dam, the working state of viscoelasticity for the dam is illustrated followed by an investigation and designation of adverse load cases using orthogonal test method. Water pressure component is then calculated by finite element method, while temperature, time effect, and frost heave components are obtained through deformation statistical model considering frost heave. The viscoelastic deformation monitoring index is eventually determined by small probability and maximum entropy methods. The results show that (a with the abnormal probability 1% the dam deformation monitoring index for small probability and maximum entropy methods is 23.703 mm and 22.981 mm, respectively; thus the maximum measured displacement of the dam is less than deformation monitoring index, which indicates that the dam is currently in a state of safety operation and (b the obtained deformation monitoring index using orthogonal test method is more accurate due to the full consideration of more random factors; the method gained from this study will likely be of use to diagnose the working state for those RCC dams in alpine regions.

Pattern of failure following surgical resection of renal cell carcinoma

International Nuclear Information System (INIS)

Aref, I.; Bociek, G.; Salhani, D.

1996-01-01

Purpose/objective: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and Methods: The records of 116 patients with unilateral non-metastatic RCC, who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988, were reviewed. Distribution by stage included: T1 = 3 patients, T2 = 42 patients, T3 =71 patients. The median follow-up was 44 months, with a range of 4-267 months. Results: Loco-regional failure (LRF) developed in 8 patients, yielding a 7-year actuarial incidence of 8% for LRF, as first event. Nine patients developed local or regional recurrence + distant failure, and 58 patients had distant metastases only. Seven-year actuarial incidence of distant failure was 55%. The overall 7-year actuarial survival rate was 40%, and cause-specific survival was 45%. Conclusion: LRF was rare following nephrectomy. This data does not support the role of adjuvant radiation therapy in this disease

Is post-operative radiation for renal cell carcinoma justified?

International Nuclear Information System (INIS)

Aref, Ibrahim; Bociek, R. Gregory; Salhani, Douglas

1997-01-01

Purpose: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and methods: The records of 116 patients with unilateral, non-hematogenous metastatic RCC who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988 were reviewed. Distribution by stage included T1 (3 patients), T2 (42 patients) and T3 (71 patients). The median follow-up was 44 months, with a range of 4-267 months. Results: Local regional failure (LRF) developed in 8 patients. Nine patients developed local or regional recurrence, plus distant failure. Fifty-eight patients had distant metastases (DM) only. The 7-year actuarial rate for LRF and DM were 12%, and 67%, respectively. The overall 7-year actuarial survival rate was 35%, and cause-specific survival was 42%. Conclusions: LRF alone is rare following nephrectomy. DM is the main pattern of failure. This data does not support the role of adjuvant radiation therapy in this disease

Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

NARCIS (Netherlands)

Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

2013-01-01

Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had

Unusual Metastases in Renal Cell Carcinoma: A Single Institution Experience and Review of Literature

Science.gov (United States)

Villarreal-Garza, Cynthia; Perez-Alvarez, Sandra I.; Gonzalez-Espinoza, Ivan R.; Leon-Rodriguez, Eucario

2010-01-01

Background To report location and management of atypical metastases from renal cell carcinoma (RCC) in the Instituto Nacional de Ciencias Medicas e Investigacion Salvador Zubiran (INCMNSZ) in Mexico City. Methods Between 1987 to 2009, 545 patients with RCC were retrospectively identified at the INCMNSZ. Patients with unusual metastases confirmed by histopathology were analyzed. Epidemiological, clinical, diagnosis, treatment and outcome data were reviewed. Results Sixty patients developed 98 unusual metastases secondary to RCC. The group was comprised of 35 men (58.3%), with a median age of 60 years at diagnosis. Metachronous unusual metastases with primary renal cancer were observed in 37 individuals (61.7%). Median time from primary RCC diagnosis to the first unusual metastasis was 16.5 months. Median survival from diagnosis of the first unusual metastasis to death was 5.0 months (CI 95%: 2.8-7.2 months). Patients with an initial solitary metastatic lesion in an unusual site (28.3%) had a better survival compared to patients who primarily presented with multiple metastases, 17.0 (CI 95%: 6.1-27.9) Vs 3.0 months (CI 95%: 0.9-5.1), p = 0.001. Unusual metastasis resection (21 patients) improved survival, 25.0 (CI 95%: 5.1-44.9) Vs 3.0 months (CI 95%: 0.8-5.2), p < 0.0001. No survival difference was observed between localization of unsual metastases (p = 0.72). Conclusions In patients with advanced RCC we suggest an individual diagnostic and surgical approach to achieve complete resection with disease-free margins, even in the presence of unusual metastatic sites, multifocality, or history of metastasectomy. These strategy might provide not only palliation for symptoms, but an opportunity for meaningful disease free and overall survival. PMID:29147198

RCC-E a Design Code for I and C and Electrical Systems

International Nuclear Information System (INIS)

Haure, J.M.

2015-01-01

The paper deals with the stakes and strength of the RCC-E code applicable to Electrical and Instrumentation and control systems and components as regards dealing with safety class functions. The document is interlacing specifications between Owners, safety authorities, designers, and suppliers IAEA safety guides and IEC standards. The code is periodically updated and published by French Society for Design and Construction rules for Nuclear Island Components (AFCEN). The code is compliant with third generation PWR nuclear islands and aims to suit with national regulations as needed in a companion document. The Feedback experience of Fukushima and the licensing of UKEPR in the framework of Generic Design Assessment are lessons learnt that should be considered in the upgrading of the code. The code gathers a set of requirements and relevant good practices of several PWR design and construction practices related to the electrical and I and C systems and components, and electrical engineering documents dealing with systems, equipment and layout designs. Comprehensive statement including some recent developments will be provided about: - Offsite and onsite sources requirements including sources dealing the total loss of off sites and main onsite sources. - Highlights of a relevant protection level against high frequencies disturbances emitted by lightning strokes, Interfaces data used by any supplier or designer such as site data, rooms temperature, equipment maximum design temperature, alternative current and direct current electrical network voltages and frequency variation ranges, environmental conditions decoupling data, - Environmental Qualification process including normal, mild (earthquake resistant), harsh and severe accident ambient conditions. A suit made approach based on families, which are defined as a combination of mission time, duration and abnormal conditions (pressure, temperature, radiation), enables to better cope with Environmental Qualifications

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

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Shi-Wen Jiang

2013-11-01

Full Text Available We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.

Gestational age specific neonatal survival in the State of Qatar (2003-2008) - a comparative study with international benchmarks.

Science.gov (United States)

Rahman, Sajjad; Salameh, Khalil; Al-Rifai, Hilal; Masoud, Ahmed; Lutfi, Samawal; Salama, Husam; Abdoh, Ghassan; Omar, Fahmi; Bener, Abdulbari

2011-09-01

To analyze and compare the current gestational age specific neonatal survival rates between Qatar and international benchmarks. An analytical comparative study. Women's Hospital, Hamad Medical Corporation, Doha, Qatar, from 2003-2008. Six year's (2003-2008) gestational age specific neonatal mortality data was stratified for each completed week of gestation at birth from 24 weeks till term. The data from World Health Statistics by WHO (2010), Vermont Oxford Network (VON, 2007) and National Statistics United Kingdom (2006) were used as international benchmarks for comparative analysis. A total of 82,002 babies were born during the study period. Qatar's neonatal mortality rate (NMR) dropped from 6/1000 in 2003 to 4.3/1000 in 2008 (p Qatar were comparable with international benchmarks. The survival of Qatar (p=0.01 and p 32 weeks babies was better in UK (p=0.01) as compared to Qatar. The relative risk (RR) of death decreased with increasing gestational age (p Qatar. The current total and gestational age specific neonatal survival rates in the State of Qatar are comparable with international benchmarks. In Qatar, persistently high rates of low birth weight and lethal chromosomal and congenital anomalies significantly contribute towards neonatal mortality.

Role of RPLND and Metastasectomy in the Management of Oligometastatic Renal Cell Carcinoma.

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Nagaraja, H; Srivatsa, N; Hemalatha, S; Shweta, S; Raghunath, S K

2018-03-01

Although lymphadenectomy is currently accepted as most accurate and reliable staging procedure for lymph node metastases, its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Review the available literature concerning the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. A PubMed search was conducted to identify original articles, review articles, and editorials addressing the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. Keywords included renal tumors, renal cell cancer, kidney cancer, lymphadenectomy, metastasectomy, and oligometastases. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy and RPLND. To date, the available evidence suggests that RPLND and metastasectomy may be beneficial when technically feasible in patients with locally advanced (unfavorable clinical and pathologic characteristics) and oligometastatic disease. A proportion of patients will achieve long-term survival with aggressive surgical resection.

Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

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Rachna Raman

2015-01-01

Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients.

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Wang, Jiajun; Liu, Li; Qu, Yang; Xi, Wei; Xia, Yu; Bai, Qi; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

2018-01-01

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort. In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.

A nationwide Danish cohort study challenging the categorisation into right-sided and left-sided colon cancer

DEFF Research Database (Denmark)

Jess, Per; Hansen, Iben Onsberg; Gamborg, Michael

2013-01-01

The categorisation of colon cancer (CC) into right-sided (RCC) and left-sided (LCC) disease may not capture more subtle variances in aetiology and prognosis. In a nationwide study, we investigated differences in clinical characteristics and survival of RCC versus LCC and of the complete range of CC...

High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

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Babbitt, Christopher J; Cooper, Michael C; Nussbaum, Eliezer; Liao, Eileen; Levine, Glenn K; Randhawa, Inderpal S

2012-12-01

Multiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity. A retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality. A total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05). High-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV.

Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I125 Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

International Nuclear Information System (INIS)

Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

2011-01-01

Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I 125 brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I 125 monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I 125 monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

Survival after Liver Transplantation in the United States: A Disease-Specific Analysis of the UNOS database

Czech Academy of Sciences Publication Activity Database

Roberts, M.S.; Angus, D.C.; Bryce, C.L.; Valenta, Zdeněk; Weissfeld, L.

2004-01-01

Roč. 10, č. 7 (2004), s. 886-897 ISSN 1527-6465 Source of funding: V - iné verejné zdroje Keywords : disease-specific survival * liver transplantation * cox PH model Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 3.984, year: 2004

Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

Science.gov (United States)

Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

2011-01-01

Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

The role of apoptosis repressor with a CARD domain (ARC) in the therapeutic resistance of renal cell carcinoma (RCC): the crucial role of ARC in the inhibition of extrinsic and intrinsic apoptotic signalling.

Science.gov (United States)

Toth, Csaba; Funke, Sarah; Nitsche, Vanessa; Liverts, Anna; Zlachevska, Viktoriya; Gasis, Marcia; Wiek, Constanze; Hanenberg, Helmut; Mahotka, Csaba; Schirmacher, Peter; Heikaus, Sebastian

2017-05-02

Renal cell carcinomas (RCCs) display broad resistance against conventional radio- and chemotherapies, which is due at least in part to impairments in both extrinsic and intrinsic apoptotic pathways. One important anti-apoptotic factor that is strongly overexpressed in RCCs and known to inhibit both apoptotic pathways is ARC (apoptosis repressor with a CARD domain). Expression and subcellular distribution of ARC in RCC tissue samples and RCC cell lines were determined by immunohistochemistry and fluorescent immunohistochemistry, respectively. Extrinsic and intrinsic apoptosis signalling were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT-263 or topotecan. ARC knock-down was performed in clearCa-12 cells using lentiviral transduction of pGIPZ. shRNAmir constructs. Extrinsic respectively intrinsic apoptosis were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT263 or topotecan. Potential synergistic effects were tested by pre-treatment with topotecan and subsequent treatment with ABT263. Activation of different caspases and mitochondrial depolarisation (JC-1 staining) were analysed by flow cytometry. Protein expression of Bcl-2 family members and ARC in RCC cell lines was measured by Western blotting. Statistical analysis was performed by Student's t-test. Regarding the extrinsic pathway, ARC knockdown strongly enhanced TRAIL-induced apoptosis by increasing the activation level of caspase-8. Regarding the intrinsic pathway, ARC, which was only weakly expressed in the nuclei of RCCs in vivo, exerted its anti-apoptotic effect by impairing mitochondrial activation rather than inhibiting p53. Topotecan- and ABT-263-induced apoptosis was strongly enhanced following ARC knockdown in RCC cell lines. In addition, topotecan pre-treatment enhanced ABT-263-induced apoptosis and this effect was amplified in ARC-knockdown cells. Taken together, our results are the first to demonstrate the importance of ARC protein in the inhibition of both the extrinsic

Climatic variation and age-specific survival in Asian elephants from Myanmar.

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Mumby, Hannah S; Courtiol, Alexandre; Mar, Khyne U; Lummaa, Virpi

2013-05-01

Concern about climate change has intensified interest in understanding how climatic variability affects animal life histories. Despite such effects being potentially most dramatic in large, long-lived, and slowly reproducing terrestrial mammals, little is known of the effects of climatic variation on survival in those species. Asian elephants (Elephas maximus) are endangered across their distribution, and inhabit regions characterized by high seasonality of temperature and rainfall. We investigated the effects of monthly climatic variation on survival and causes of death in Asian elephants using a unique demographic data set of 1024 semi-captive, longitudinally monitored elephants from four sites in Myanmar between 1965 and 2000. Temperature had a significant effect on survival in both sexes and across all ages. For elephants between 1 month and 17 years of age, maximal survival was reached at -24 degrees C, and any departures from this temperature increased mortality, whereas neonates and mature elephants had maximal survival at even lower temperatures. Although males experienced higher mortality overall, sex differences in these optimal temperatures were small. Because the elephants spent more time during a year in temperatures above 24 degrees C than in temperatures below it, most deaths occurred at hot (temperatures>24 degrees C) rather than cold periods. Decreased survival at higher temperatures resulted partially from increased deaths from infectious disease and heat stroke, whereas the lower survival in the coldest months was associated with an increase in noninfectious diseases and poor health in general. Survival was also related to rainfall, with the highest survival rates during the wettest months for all ages and sexes. Our results show that even the normal-range monsoon variation in climate can exert a large impact on elephant survival in Myanmar, leading to extensive absolute differences in mortality; switching from favorable to unfavorable climatic

Factors associated with disease-specific survival of patients with non-small cell lung cancer.

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Souza, Mirian Carvalho de; Cruz, Oswaldo Gonçalves; Vasconcelos, Ana Glória Godoi

2016-01-01

Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer. O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na

Validation of the 16-Gene Recurrence Score in patients with locoregional, high-risk renal cell carcinoma from a phase 3 trial of adjuvant sunitinib.

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Rini, Brian I; Escudier, Bernard; Martini, Jean-Francois; Magheli, Ahmed; Svedman, Christer; Lopatin, Margarita; Knezevic, Dejan; Goddard, Audrey D; Febbo, Phillip G; Li, Rachel; Lin, Xun; Valota, Olga; Staehler, Michael; Motzer, Robert J; Ravaud, Alain

2018-05-17

Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit. The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Copyright ©2018, American Association for Cancer Research.

Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

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Nakanishi, Hiromi; Miyata, Yasuyoshi; Mochizuki, Yasushi; Yasuda, Takuji; Nakamura, Yuichiro; Araki, Kyohei; Sagara, Yuji; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

2018-05-19

The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index (PI), apoptotic index (AI), and microvessel density (MVD) were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multi-variate analyses (hazard ratio=1.41, 95% confidential interval=1.03-1.93, P=.031), and was significantly correlated with PI, AI, and MVD (r=.47; P <. 001, r=-.31, P<.001, and r=.40, P<.001, respectively). In conclusion, CD57+ cell, CD68+ cell, and mast cell played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. Copyright © 2018. Published by Elsevier Inc.

Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

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Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

2017-10-01

We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human renal cell carcinoma cell growth.

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Su, Ying; Zhao, An; Cheng, Guoping; Xu, Jingjing; Ji, Enming; Sun, Wenyong

2017-07-04

Renal cell carcinoma (RCC) is the highest mortality rate of the genitourinary cancers, and the treatment options are very limited. Thus, identification of molecular mechanisms underlying RCC tumorigenesis, is critical for identifying biomarkers for RCC diagnosis and prognosis. To validate whether the IGF-I/JAK2-STAT3/miR-21 signaling pathway is associated with human RCC cell growth. qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels, respectively. The MTT assay was performed to determine cell survival rate. The Annexin V-FITC/PI apoptosis detection kit was used to detect cell apoptosis. We employed RCC tissues and cell lines (A498; ACHN; Caki-1; Caki-2 and 786-O) in the study. IGF-I, and its inhibitor (NT-157) were administrated to detect the effects of IGF-I on the expression of miR-21 and p-JAK2. JAK2 inhibitor (AG490), and si-STAT3 were used to detect the effects of JAK2/STAT3 signaling pathway on the expression of miR-21. In our study, we firstly showed that the expression levels of IGF-I and miR-21 were up-regulated in RCC tissues and cell lines. After exogenous IGF-I treatment, the expression levels of miR-21, p-IGF-IR and p-JAK2 were significantly increased, whereas NT-157 treatment showed the reversed results. Further study indicated that JAK2 inhibitor or si-STAT3 significantly reversed the IGF-I-induced miR-21 expression level. Finally, we found that IGF-I treatment significantly prompted human RCC cell survival and inhibited cell apoptosis, and NT-157 treatment showed the reversed results. The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human RCC cell growth.

The Expression of BTS-2 Enhances Cell Growth and Invasiveness in Renal Cell Carcinoma.

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Pham, Quoc Thang; Oue, Naohide; Yamamoto, Yuji; Shigematsu, Yoshinori; Sekino, Yohei; Sakamoto, Naoya; Sentani, Kazuhiro; Uraoka, Naohiro; Tiwari, Mamata; Yasui, Wataru

2017-06-01

Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients.

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Roseweir, Antonia K; Qayyum, Tahir; Lim, Zhi; Hammond, Rachel; MacDonald, Alasdair I; Fraser, Sioban; Oades, Grenville M; Aitchison, Michael; Jones, Robert J; Edwards, Joanne

2016-03-16

8000 cases of renal cancer are diagnosed each year in the UK, with a five-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the Src family kinases (SFKs). SFKs have roles in multiple oncogenic processes and promote metastases in solid tumours. The aim of this study was to investigate SFKs as potential therapeutic targets for clear cell renal cell carcinoma (ccRCC). SFKs expression was assessed in a tissue microarray consisting of 192 ccRCC patients with full clinical follow-up. SFK inhibitors, dasatinib and saracatinib, were assessed in early ccRCC cell lines, 786-O and 769-P and a metastatic ccRCC cell line, ACHN (± Src) for effects on protein expression, apoptosis, proliferation and wound healing. High nuclear expression of Lyn and the downstream marker of activation, paxillin, were associated with decreased patient survival. Conversely, high cytoplasmic expression of other SFK members and downstream marker of activation, focal adhesion kinase (FAK) were associated with increased patient survival. Treatment of non-metastatic 786-O and 769-P cells with dasatinib, dose dependently reduced SFK activation, shown via SFK (Y(419)) and FAK (Y(861)) phosphorylation, with no effect in metastatic ACHN cells. Dasatinib also increased apoptosis, while decreasing proliferation and migration in 786-O and 769-P cell lines, both in the presence and absence of Src protein. Our data suggests that nuclear Lyn is a potential therapeutic target for ccRCC and dasatinib affects cellular functions associated with cancer progression via a Src kinase independent mechanism.

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

DEFF Research Database (Denmark)

Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

2015-01-01

BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......% intermediate risk, and 40% vs. 24% poor risk; P system metastases (6...... of second- (P = .018) and third-line (P systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P

Effect of ABO blood type on the outcomes of patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

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Omae, Kenji; Fukuma, Shingo; Ikenoue, Tatsuyoshi; Kondo, Tsunenori; Takagi, Toshio; Ishihara, Hiroki; Tanabe, Kazunari; Fukuhara, Shunichi

2017-09-01

To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). Patients who received TKIs as first-line therapy for mRCC between 2008 and 2015 at our hospital were included in the study (n = 136). Patients were divided into 2 groups based on their blood type as O and non-O. Survival outcomes and AEs were compared according to blood type. Cox regression models were used for univariate and multivariate survival analyses. Of the 136 patients, 34 (25%) and 102 (75%) had O and non-O blood types, respectively. Blood type O was associated with an increased number of disease sites. There were no differences between the 2 groups with respect to other baseline characteristics. The progression-free survival in patients with O and non-O blood types was 12.1 and 11.6 months, respectively; the overall survival was 34.4 and 24.8 months, respectively. On univariate and multivariate analyses, the ABO blood type was not a significant prognostic factor for progression-free survival or overall survival. Furthermore, the incidences of serious AEs were similar in the 2 blood groups. ABO blood type was not associated with survival outcomes or incidences of serious AEs in mRCC patients treated with TKIs. However, blood type O may be associated with an increased number of disease sites. Copyright © 2017. Published by Elsevier Inc.

Design and Construction Rules for Mechanical equipments of FBR nuclear islands: RCC-MR. Tome 1, Volume Z: Other technical appendixes

International Nuclear Information System (INIS)

1985-06-01

This book is the 7th of a whole set of 12 which constitute the present edition of the RCC-MR. The technical appendixes of this volume deal with the following characteristics and rules: calculation of screwed assemblies, analysis taking into account creep, welded joint characteristics, elastoplastic analysis of a structure under cyclic loads, elasto-visco-plastic analysis under cyclic loads, calculation rules of revolution shells under external presure and of cylinders under axial compression, design rules of linear supports, calculation rules of convex bottoms under internal pressure [fr

Vimentin 3, the New Hope, Differentiating RCC versus Oncocytoma

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Melanie von Brandenstein

2015-01-01

Full Text Available Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients’ survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients’ tumor samples may result.

Stage-specific appearance of cytoplasmic microtubules around the surviving nuclei during the third prezygotic division of Paramecium.

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Wang, Yi-Wen; Yuan, Jin-Qiang; Gao, Xin; Yang, Xian-Yu

2012-12-01

There are six micronuclear divisions during conjugation of Paramecium caudatum: three prezygotic and three postzygotic divisions. Four haploid nuclei are formed during the first two meiotic prezygotic divisions. Usually only one meiotic product is located in the paroral cone (PC) region at the completion of meiosis, which survives and divides mitotically to complete the third prezygotic division to yield a stationary and a migratory pronucleus. The remaining three located outside of the PC degenerate. The migratory pronuclei are then exchanged between two conjugants and fuse with the stationary pronuclei to form synkarya, which undergo three successive divisions (postzygotic divisions). However, little is known about the surviving mechanism of the PC nuclei. In the current study, stage-specific appearance of cytoplasmic microtubules (cMTs) was indicated during the third prezygotic division by immunofluorescence labeling with anti-alpha tubulin antibodies surrounding the surviving nuclei, including the PC nuclei and the two types of prospective pronuclei. This suggested that cMTs were involved in the formation of a physical barrier, whose function may relate to sequestering and protecting the surviving nuclei from the major cytoplasm, where degeneration of extra-meiotic products occurs, another important nuclear event during the third prezygotic division.

Radiodiagnostic methods in determining the structure of tumor thrombus in the inferior vena cava in kidney cancer

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N. B. Vikhrova

2015-01-01

Full Text Available Renal cell carcinoma (RCC is the most common primary tumor of the renal parenchyma. Venous involvement is one of the most important anatomic characteristics of tumor. It is known that venous spread influences the survival of patients with RCC. Tumor thrombosis of IVC in patients with renal cell carcinoma has been reported in 4–10 %. The reference standard for RCC with tumor thrombus remains surgical resection. The structure of thrombus determines some technical difficulties in the management of tumor. Spongeous thrombus correlate with higher risk of thrombus detachment during surgery resulting in PE. Therefore determination of IVC thrombus consistency is very important part of preoperative radiologic assessment of tumor in patients with RCC.

Ovatodiolide Targets β-Catenin Signaling in Suppressing Tumorigenesis and Overcoming Drug Resistance in Renal Cell Carcinoma

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Jar-Yi Ho

2013-01-01

Full Text Available Dysregulated β-catenin signaling is intricately involved in renal cell carcinoma (RCC carcinogenesis and progression. Determining potential β-catenin signaling inhibitors would be helpful in ameliorating drug resistance in advanced or metastatic RCC. Screening for β-catenin signaling inhibitors involved in silico inquiry of the PubChem Bioactivity database followed by TCF/LEF reporter assay. The biological effects of ovatodiolide were evaluated in 4 RCC cell lines in vitro and 2 RCC cell lines in a mouse xenograft model. The synergistic effects of ovatodiolide and sorafenib or sunitinib were examined in 2 TKI-resistant RCC cell lines. Ovatodiolide, a pure compound of Anisomeles indica, inhibited β-catenin signaling and reduced RCC cell viability, survival, migration/invasion, and in vitro cell or in vivo mouse tumorigenicity. Cytotoxicity was significantly reduced in a normal kidney epithelial cell line with the treatment. Ovatodiolide reduced phosphorylated β-catenin (S552 that inhibited β-catenin nuclear translocation. Moreover, ovatodiolide decreased β-catenin stability and impaired the association of β-catenin and transcription factor 4. Ovatodiolide combined with sorafenib or sunitinib overcame drug resistance in TKI-resistant RCC cells. Ovatodiolide may be a potent β-catenin signaling inhibitor, with synergistic effects with sorafenib or sunitinib, and therefore, a useful candidate for improving RCC therapy.

Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas. More than a 24-month median follow-up

International Nuclear Information System (INIS)

Takeda, Naoki; Isu, Kazuo; Hiraga, Hiroaki; Shinohara, Nobuo; Minami, Akio; Kamata, Hajime

2012-01-01

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT+Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT+Z groups, respectively. Three patients (three lesions) in the RT+Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC. (author)

Age-specific haemosporidian infection dynamics and survival in Seychelles warblers

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Hammers, Martijn; Komdeur, Jan; Kingma, Sjouke A.; Hutchings, Kimberly; Fairfield, Eleanor A.; Gilroy, Danielle L.; Richardson, David S.

2016-01-01

Parasites may severely impact the fitness and life-history of their hosts. After infection, surviving individuals may suppress the growth of the parasite, or completely clear the infection and develop immunity. Consequently, parasite prevalence is predicted to decline with age. Among elderly individuals, immunosenescence may lead to a late-life increase in infection prevalence. We used a 21-year longitudinal dataset from one population of individually-marked Seychelles warblers (Acrocephalus sechellensis) to investigate age-dependent prevalence of the GRW1 strain of the intracellular protozoan blood parasite Haemoproteus nucleocondensus and whether infections with this parasite affect age-dependent survival. We analyzed 2454 samples from 1431 individuals and found that H. nucleocondensus infections could rarely be detected in nestlings. Prevalence increased strongly among fledglings and peaked among older first year birds. Prevalence was high among younger adults and declined steeply until ca 4 years of age, after which it was stable. Contrary to expectations, H. nucleocondensus prevalence did not increase among elderly individuals and we found no evidence that annual survival was lower in individuals suffering from an infection. Our results suggest that individuals clear or suppress infections and acquire immunity against future infections, and provide no evidence for immunosenescence nor an impact of chronic infections on survival. PMID:27431430

How can survival processing improve memory encoding?

Science.gov (United States)

Luo, Meng; Geng, Haiyan

2013-11-01

We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.

Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

Science.gov (United States)

Pesch, B; Haerting, J; Ranft, U; Klimpel, A; Oelschlägel, B; Schill, W

2000-12-01

This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery

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Kocot Arkadius

2012-06-01

Full Text Available Abstract Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC and tumor thrombus involving inferior vena cava (IVC treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42% distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%, thoracoabdominal (14 patients/28% or midline abdominal approach (21 patients/42%, depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB was performed in 10 patients (20% with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10 even had a better outcome (overall survival at 5 years of 58.33% than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal

Characterizing the Impact of Lymph Node Metastases on the Survival Outcome for Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapies

DEFF Research Database (Denmark)

Kroeger, Nils; Pantuck, Allan J; Wells, J Connor

2015-01-01

by its retrospective design and the lack of pathologic evaluation of LNM in all cases. CONCLUSIONS: The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT. PATIENT SUMMARY: The presence of lymph node metastases below the diaphragm is associated...

Fatigue assessment by the RCC-MR design rules: remarks on the elastic analysis

International Nuclear Information System (INIS)

Taleb, L.; Sidoroff, F.

1999-01-01

According to RCC--MR (French rules for mechanical engineering design of FBR), fatigue life assessment is based on the evaluation of the equivalent elastoplastic strain range resulting from a given cyclic loading. Two methods can be used according to whether an elastoplastic or an elastic structure analysis is performed. The elastic analysis is of course more attractive for it avoids a heavy iterative elastoplastic analysis and an expensive identification of the material behavior from mechanical tests. On the other hand it relies on some empirical extrapolation rules from the elastic to the real case. The purpose of the present paper is to draw attention to some limitations of this procedure. In particular attention will be focused on two points: 1, the classification of the applied stress into primary and secondary parts is essential and it is shown that the thermal stresses which are often considered as secondary may in some cases play a primary role; 2. the Neuber's rule which is used to evaluate the plastic strain from the elastic stress will be shown to be significantly wrong for some special configurations. This is in fact essentially related to situations where the elastic follow up effect is important. (authors)

Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT

International Nuclear Information System (INIS)

Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Zattoni, Fabio; Spallino, Marianna; Saladini, Giorgio; Evangelista, Laura

2016-01-01

The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision-making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC). From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome. FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74 % and 80 %, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43 %). After a median follow-up period of 37 months (± standard deviation 12.9), 51 (49 %) patients had recurrence of disease, and 26 (25 %) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19 % vs. 69 %, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III-IV or nuclear grading 3-4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p < 0.05). FDG PET/CT is a valuable tool both in treatment decision-making and for

Recurrent renal cell carcinoma: clinical and prognostic value of FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi [IRCCS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Zattoni, Fabio [University of Padua, Department of Oncological and Surgical Sciences, Urology Clinic, Padua (Italy); Spallino, Marianna [University of Milano-Bicocca, Milan (Italy); Saladini, Giorgio; Evangelista, Laura [Veneto Institute of Oncology IOV - IRCCS, Padua, Italy, Radiotherapy and Nuclear Medicine Unit, Padua (Italy)

2016-03-15

The purpose of our study was 1) to evaluate the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 2) to assess the impact of FDG PET/CT on treatment decision-making, and 3) to estimate the prognostic value of FDG PET/CT in the restaging process among patients with renal cell carcinoma (RCC). From the FDG PET/CT databases of San Raffaele Hospital in Milan, Italy, and the Veneto Institute of Oncology in Padua, Italy, we selected 104 patients with a certain diagnosis of RCC after surgery, and for whom at least 24 months of post-surgical FDG PET/CT, clinical, and instrumental follow-up data was available. The sensitivity and specificity of FDG PET/CT were assessed by histology and/or other imaging as standard of reference. Progression-free survival (PFS) and overall survival (OS) were computed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to identify predictors of outcome. FDG PET/CT resulted in a positive diagnosis in 58 patients and a negative diagnosis in 46 patients. Sensitivity and specificity were 74 % and 80 %, respectively. FDG PET/CT findings influenced therapeutic management in 45/104 cases (43 %). After a median follow-up period of 37 months (± standard deviation 12.9), 51 (49 %) patients had recurrence of disease, and 26 (25 %) had died. In analysis of OS, positive versus negative FDG PET/CT was associated with worse cumulative survival rates over a 5-year period (19 % vs. 69 %, respectively; p <0.05). Similarly, a positive FDG PET/CT correlated with a lower 3-year PFS rate. In addition, univariate and multivariate analysis revealed that a positive scan, alone or in combination with disease stage III-IV or nuclear grading 3-4, was associated with high risk of progression (multivariate analysis = hazard ratios [HRs] of 4.01, 3.7, and 2.8, respectively; all p < 0.05). FDG PET/CT is a valuable tool both in treatment decision-making and for

Validation of the CPS + EG Staging System for Disease-Specific Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Science.gov (United States)

Abdelsattar, Jad M; Al-Hilli, Zahraa; Hoskin, Tanya L; Heins, Courtney N; Boughey, Judy C

2016-10-01

CPS + EG staging, which incorporates estrogen receptor (ER) status and tumor grade with pretreatment clinical stage (CS) and post-treatment pathologic stage (PS), has been reported to have better correlation with outcome than classic TNM staging for patients treated with neoadjuvant chemotherapy (NAC). Our goal was to evaluate the performance of CPS + EG staging system in an external cohort treated with NAC. We reviewed patients with stages I-IIIC breast cancer treated with NAC and surgery at our institution between 1988 and 2014. ER status, Nottingham grade, treatment, American Joint Committee on Cancer (AJCC) CS before NAC and PS after NAC, and follow-up data were collected. The discrimination of CPS + EG and pathologic AJCC stage were assessed using area under the curve (AUC) for survival data. A total of 769 patients were analyzed with a median follow-up of 2.6 (range 0.0-19.4) years; 103 patients died of breast cancer. Overall, the 5-year breast cancer cause-specific survival was 81.5 % [95 % confidence interval (CI) 77.6-85.5]. The 5-year, cause-specific survival by CPS + EG score was 93.8 % score 0, 89.9 % score 1, 90.7 % score 2, 84.8 % score 3, 67.7 % score 4, and 43.4 % score 5/6. CPS + EG score was significantly associated with cause-specific survival (p < 0.001) with an AUC of 0.69 (95 % CI 0.62-0.77) at 5 years. This was higher than the AUC of 0.63 (95 % CI 0.56-0.70) for AJCC PS (p = 0.10). This study validates the CPS + EG staging system using Nottingham grade in an external cohort. Addition of tumor biology and treatment response shows promise in improving survival estimates for patients treated with NAC.

Dying to remember, remembering to survive: mortality salience and survival processing.

Science.gov (United States)

Burns, Daniel J; Hart, Joshua; Kramer, Melanie E; Burns, Amy D

2014-01-01

Processing items for their relevance to survival improves recall for those items relative to numerous other deep processing encoding techniques. Perhaps related, placing individuals in a mortality salient state has also been shown to enhance retention of items encoded after the morality salience manipulation (e.g., in a pleasantness rating task), a phenomenon we dubbed the "dying-to-remember" (DTR) effect. The experiments reported here further explored the effect and tested the possibility that the DTR effect is related to survival processing. Experiment 1 replicated the effect using different encoding tasks, demonstrating that the effect is not dependent on the pleasantness task. In Experiment 2 the DTR effect was associated with increases in item-specific processing, not relational processing, according to several indices. Experiment 3 replicated the main results of Experiment 2, and tested the effects of mortality salience and survival processing within the same experiment. The DTR effect and its associated difference in item-specific processing were completely eliminated when the encoding task required survival processing. These results are consistent with the interpretation that the mechanisms responsible for survival processing and DTR effects are overlapping.

Pulse-echo ultrasonic inspection system for in-situ nondestructive inspection of Space Shuttle RCC heat shields.

Energy Technology Data Exchange (ETDEWEB)

Roach, Dennis Patrick; Walkington, Phillip D.; Rackow, Kirk A.

2005-06-01

The reinforced carbon-carbon (RCC) heat shield components on the Space Shuttle's wings must withstand harsh atmospheric reentry environments where the wing leading edge can reach temperatures of 3,000 F. Potential damage includes impact damage, micro cracks, oxidation in the silicon carbide-to-carbon-carbon layers, and interlaminar disbonds. Since accumulated damage in the thick, carbon-carbon and silicon-carbide layers of the heat shields can lead to catastrophic failure of the Shuttle's heat protection system, it was essential for NASA to institute an accurate health monitoring program. NASA's goal was to obtain turnkey inspection systems that could certify the integrity of the Shuttle heat shields prior to each mission. Because of the possibility of damaging the heat shields during removal, the NDI devices must be deployed without removing the leading edge panels from the wing. Recently, NASA selected a multi-method approach for inspecting the wing leading edge which includes eddy current, thermography, and ultrasonics. The complementary superposition of these three inspection techniques produces a rigorous Orbiter certification process that can reliably detect the array of flaws expected in the Shuttle's heat shields. Sandia Labs produced an in-situ ultrasonic inspection method while NASA Langley developed the eddy current and thermographic techniques. An extensive validation process, including blind inspections monitored by NASA officials, demonstrated the ability of these inspection systems to meet the accuracy, sensitivity, and reliability requirements. This report presents the ultrasonic NDI development process and the final hardware configuration. The work included the use of flight hardware and scrap heat shield panels to discover and overcome the obstacles associated with damage detection in the RCC material. Optimum combinations of custom ultrasonic probes and data analyses were merged with the inspection procedures needed to

Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

Directory of Open Access Journals (Sweden)

Çetin Ordu

2016-06-01

Full Text Available Aim of the study : Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods : Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results : Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54% patients were alive and 32 (46% patients died. The median time of overall survival (OS and progression-free survival (PFS was 27 months (12–61 and 19 months (5–45, respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC, hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2 vs. continuous treatment dosing schedules. Conclusions : As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients.

CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma.

Science.gov (United States)

Escudier, Bernard; Sharma, Padmanee; McDermott, David F; George, Saby; Hammers, Hans J; Srinivas, Sandhya; Tykodi, Scott S; Sosman, Jeffrey A; Procopio, Giuseppe; Plimack, Elizabeth R; Castellano, Daniel; Gurney, Howard; Donskov, Frede; Peltola, Katriina; Wagstaff, John; Gauler, Thomas C; Ueda, Takeshi; Zhao, Huanyu; Waxman, Ian M; Motzer, Robert J

2017-12-01

The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time.

Directory of Open Access Journals (Sweden)

Ingrid M M Schellens

Full Text Available BACKGROUND: T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8(+ and CD4(+ T cells producing IFNgamma and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8(+ T cells early in infection was associated with AIDS-free survival time. METHODS AND FINDINGS: The number and percentage of IFNgamma and IL-2 producing CD8(+ T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8(+ T cells (IFNgamma, IL-2 or both shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4(+ T-cell decline. CONCLUSIONS: These data show that high numbers of functional HIV-specific CD8(+ T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression.

A PKA survival pathway inhibited by DPT-PKI, a new specific cell permeable PKA inhibitor, is induced by T. annulata in parasitized B-lymphocytes.

Science.gov (United States)

Guergnon, Julien; Dessauge, Frederic; Traincard, François; Cayla, Xavier; Rebollo, Angelita; Bost, Pierre Etienne; Langsley, Gordon; Garcia, Alphonse

2006-08-01

T. annulata, an intracellular pathogenic parasite of the Aplicomplexa protozoan family infects bovine B-lymphocytes and macrophages. Parasitized cells that become transformed survive and proliferate independently of exogenous growth factors. In the present study, we used the isogenic non parasitized BL3 and parasitized TBL3 B cell lines, as a model to evaluate the contribution of two-major PI3-K- and PKA-dependent anti-apoptotic pathways in the survival of T. annulata parasitized B lymphocytes. We found that T. annulata increases PKA activity, induces over-expression of the catalytic subunit and down-regulates the pro-survival phosphorylation state of Akt/PKB. Consistent with a role of PKA activation in survival, two pharmacological inhibitors H89 and KT5720 ablate PKA-dependent survival of parasitized cells. To specifically inhibit PKA pro-survival pathways we linked the DPTsh1 peptide shuttle sequence to PKI(5-24) and we generated DPT-PKI, a cell permeable PKI. DPT-PKI specifically inhibited PKA activity in bovine cell extracts and, as expected, also inhibited the PKA-dependent survival of T. annulata parasitized TBL3 cells. Thus, parasite-dependent constitutive activation of PKA in TBL3 cells generates an anti-apoptotic pathway that can protect T. annulata-infected B cells from apoptosis. These results also indicate that DPT-PKI could be a powerful tool to inhibit PKA pathways in other cell types.

Wing Leading Edge RCC Rapid Response Damage Prediction Tool (IMPACT2)

Science.gov (United States)

Clark, Robert; Cottter, Paul; Michalopoulos, Constantine

2013-01-01

This rapid response computer program predicts Orbiter Wing Leading Edge (WLE) damage caused by ice or foam impact during a Space Shuttle launch (Program "IMPACT2"). The program was developed after the Columbia accident in order to assess quickly WLE damage due to ice, foam, or metal impact (if any) during a Shuttle launch. IMPACT2 simulates an impact event in a few minutes for foam impactors, and in seconds for ice and metal impactors. The damage criterion is derived from results obtained from one sophisticated commercial program, which requires hours to carry out simulations of the same impact events. The program was designed to run much faster than the commercial program with prediction of projectile threshold velocities within 10 to 15% of commercial-program values. The mathematical model involves coupling of Orbiter wing normal modes of vibration to nonlinear or linear springmass models. IMPACT2 solves nonlinear or linear impact problems using classical normal modes of vibration of a target, and nonlinear/ linear time-domain equations for the projectile. Impact loads and stresses developed in the target are computed as functions of time. This model is novel because of its speed of execution. A typical model of foam, or other projectile characterized by material nonlinearities, impacting an RCC panel is executed in minutes instead of hours needed by the commercial programs. Target damage due to impact can be assessed quickly, provided that target vibration modes and allowable stress are known.

Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma: Results of a Randomised Phase III Trial (METEOR

Directory of Open Access Journals (Sweden)

Toni Choueiri

2015-11-01

Full Text Available The METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma (RCC was reported by Prof Choueiri at the European Cancer Congress 2015. This presentation follows the publication in the New England Journal of Medicine of the METEOR trial back-to-back with the CheckMate 025 trial of nivolumab versus everolimus in the same patient setting. Excitingly, these trials demonstrated, for the first time, significant benefits over the standard of care for heavily pre-treated patients with advanced RCC. Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI aims to address the challenge of resistance to targeted therapy with TKIs. While the METEOR trial has not yet reached its final analysis of overall survival (OS, the clear progression-free survival (PFS benefit, acceptable safety profile, and similar tolerability to other TKIs shown by cabozantinib indicate that this represents a promising new treatment option for second-line or subsequent therapy for patients with advanced RCC.

Cytoreductive nephrectomy vs medical therapy as initial treatment: a rational approach to the sequence question in metastatic renal cell carcinoma.

Science.gov (United States)

Spiess, Philippe E; Fishman, Mayer N

2010-10-01

Renal cell carcinoma (RCC) can be considered as two distinct entities: localized and metastatic disease. We conducted a review of the scientific literature published within the past decade pertaining to cytoreductive nephrectomy for metastatic RCC. Retrospective data and historical prospective series have demonstrated the survival benefit of debulking nephrectomy in well-selected RCC patients. New medical therapies, including vascular endothelial growth factor and mTOR pathway blocking drugs, are active biological agents, with survival improvement and potential regression of metastatic and primary tumors. Our current therapeutic challenge is the optimal integration of multimodal therapy consisting of systemic therapy and surgery including cytoreductive nephrectomy, debulking, and metastasectomy. Empiric data to guide this decision are limited. The decision concerning whether medical or surgical therapy should be the primary treatment approach selected must be made on an individual basis, taking into account patient performance status, clinical parameters, and physician expertise and recommendations, thus making each case a unique therapeutic challenge.

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy

OpenAIRE

Langius, J.A.E.; Bakker, S.; Rietveld, D.H.F.; Kruizenga, H.M.; Langendijk, J.A.; Weijs, P.J.M.; Leemans, C.R.

2013-01-01

Background:Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients.Methods:In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until ...

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

Science.gov (United States)

Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

2018-01-01

To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy

International Nuclear Information System (INIS)

Ito, Hiroki; Kishida, Takeshi; Miura, Takeshi; Kubota, Yoshinobu; Yao, Masahiro; Shioi, Koichi; Murakami, Takayuki; Takizawa, Akitoshi; Sano, Futoshi; Kawahara, Takashi; Mizuno, Nobuhiko; Makiyama, Kazuhide; Nakaigawa, Noboru

2012-01-01

C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study. Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC

Validation of DAB2IP methylation and its relative significance in predicting outcome in renal cell carcinoma

Science.gov (United States)

Zhao, Liang-Yun; Kapur, Payal; Wu, Kai-Jie; Wang, Bin; Yu, Yan-Hong; Liao, Bing; He, Da-Lin; Chen, Wei; Margulis, Vitaly; Hsieh, Jer-Tsong; Luo, Jun-Hang

2016-01-01

We have recently reported tumor suppressive role of DAB2IP in RCC development. In this study, We identified one CpG methylation biomarker (DAB2IP CpG1) located UTSS of DAB2IP that was associated with poor overall survival in a cohort of 318 ccRCC patients from the Cancer Genome Atlas (TCGA). We further validated the prognostic accuracy of DAB2IP CpG methylation by pyrosequencing quantitative methylation assay in 224 ccRCC patients from multiple Chinese centers (MCHC set), and 239 patients from University of Texas Southwestern Medical Center at Dallas (UTSW set) by using FFPE samples. DAB2IP CpG1 can predict the overall survival of patients in TCGA, MCHC, and UTSW sets independent of patient age, Fuhrman grade and TNM stage (all p<0.05). DAB2IP CpG1 successfully categorized patients into high-risk and low-risk groups with significant differences of clinical outcome in respective clinical subsets, regardless of age, sex, grade, stage, or race (HR: 1.63-7.83; all p<0.05). The detection of DAB2IP CpG1 methylation was minimally affected by ITH in ccRCC. DAB2IP mRNA expression was regulated by DNA methylation in vitro. DAB2IP CpG1 methylation is a practical and repeatable biomarker for ccRCC, which can provide prognostic value that complements the current staging system. PMID:27129174

Cancer survival among Alaska Native people.

Science.gov (United States)

Nash, Sarah H; Meisner, Angela L W; Zimpelman, Garrett L; Barry, Marc; Wiggins, Charles L

2018-03-26

Recent cancer survival trends among American Indian and Alaska Native (AN) people are not well understood; survival has not been reported among AN people since 2001. This study examined cause-specific survival among AN cancer patients for lung, colorectal, female breast, prostate, and kidney cancers. It evaluated whether survival differed between cancers diagnosed in 1992-2002 (the earlier period) and cancers diagnosed in 2003-2013 (the later period) and by the age at diagnosis (<65 vs ≥65 years), stage at diagnosis (local or regional/distant/unknown), and sex. Kaplan-Meier and Cox proportional hazards models were used to estimate univariate and multivariate-adjusted cause-specific survival for each cancer. An improvement was observed in 5-year survival over time from lung cancer (hazard ratio [HR] for the later period vs the earlier period, 0.83; 95% confidence interval [CI], 0.72-0.97), and a marginally nonsignificant improvement was observed for colorectal cancer (HR, 0.81; 95% CI, 0.66-1.01). Site-specific differences in survival were observed by age and stage at diagnosis. This study presents the first data on cancer survival among AN people in almost 2 decades. During this time, AN people have experienced improvements in survival from lung and colorectal cancers. The reasons for these improvements may include increased access to care (including screening) as well as improvements in treatment. Improving cancer survival should be a priority for reducing the burden of cancer among AN people and eliminating cancer disparities. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Isoform-specific interactions of the von Hippel-Lindau tumor suppressor protein

OpenAIRE

Minervini, Giovanni; Mazzotta, Gabriella M.; Masiero, Alessandro; Sartori, Elena; Corr?, Samantha; Potenza, Emilio; Costa, Rodolfo; Tosatto, Silvio C. E.

2015-01-01

Deregulation of the von Hippel-Lindau tumor suppressor protein (pVHL) is considered one of the main causes for malignant renal clear-cell carcinoma (ccRCC) insurgence. In human, pVHL exists in two isoforms, pVHL19 and pVHL30 respectively, displaying comparable tumor suppressor abilities. Mutations of the p53 tumor suppressor gene have been also correlated with ccRCC insurgence and ineffectiveness of treatment. A recent proteomic analysis linked full length pVHL30 with p53 pathway regulation t...

Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

DEFF Research Database (Denmark)

Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

2016-01-01

OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict...

Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer.

Science.gov (United States)

He, X; Esteva, F J; Ensor, J; Hortobagyi, G N; Lee, M-H; Yeung, S-C J

2012-07-01

Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer. We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed. A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively). Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

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Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

2016-07-01

The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of elevated temperature design codes of ASME Subsection NH and RCC-MRx

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Lee, Hyeong-Yeon, E-mail: hylee@kaeri.re.kr

2016-11-15

Highlights: • Comparison of elevated temperature design (ETD) codes was made. • Material properties and evaluation procedures were compared. • Two heat-resistant materials of Grade 91 steel and austenitic stainless steel 316 are the target materials in the present study. • Application of the ETD codes to Generation IV reactor components and a comparison of the conservatism was conducted. - Abstract: The elevated temperature design (ETD) codes are used for the design evaluation of Generation IV (Gen IV) reactor systems such as sodium-cooled fast reactor (SFR), lead-cooled fast reactor (LFR), and very high temperature reactor (VHTR). In the present study, ETD code comparisons were made in terms of the material properties and design evaluation procedures for the recent versions of the two major ETD codes, ASME Section III Subsection NH and RCC-MRx. Conservatism in the design evaluation procedures was quantified and compared based on the evaluation results for SFR components as per the two ETD codes. The target materials are austenitic stainless steel 316 and Mod.9Cr-1Mo steel, which are the major two materials in a Gen IV SFR. The differences in the design evaluation procedures as well as the material properties in the two ETD codes are highlighted.

Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

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George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

2018-04-01

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

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Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques; Pandha, Hardev S; George, Daniel J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Casey, Michelle; Serfass, Lucile; Pantuck, Allan J; Staehler, Michael

2018-01-01

Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. Most subgroups of patients at high risk of recurrent renal cell carcinoma after

Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

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Zhang, Lu; Yu, Qingzhao; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Loch, Michelle; Chen, Vivien W; Fontham, Elizabeth; Ferguson, Tekeda

2018-05-01

To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

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Karalexi, Maria A; Georgakis, Marios K; Dessypris, Nick; Ryzhov, Anton; Zborovskaya, Anna; Dimitrova, Nadya; Zivkovic, Snezana; Eser, Sultan; Antunes, Luis; Sekerija, Mario; Zagar, Tina; Bastos, Joana; Demetriou, Anna; Agius, Domenic; Florea, Margareta; Coza, Daniela; Bouka, Evdoxia; Dana, Helen; Hatzipantelis, Emmanuel; Kourti, Maria; Moschovi, Maria; Polychronopoulou, Sophia; Stiakaki, Eftichia; Pourtsidis, Apostolos; Petridou, Eleni Th

2017-12-01

Childhood (0-14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern-Eastern European (SEE) countries and those in the United States. Average age-standardized mortality rates and time trends of Hodgkin (HL) and non-Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990-2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990-2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan-Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/10 6 ), which presented a sizeable (-4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non-HL was associated with a poorer outcome and an amphi-directional age-specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28-1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46-0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype-specific, and age-specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs. Copyright © 2016 John Wiley & Sons, Ltd.

Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

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Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

2013-11-01

Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

Effect of Temperature on the Survival of F-Specific RNA Coliphage, Feline Calicivirus, and Escherichia coli in Chlorinated Water

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Sagar M. Goyal

2005-12-01

Full Text Available We compared the survival of F-specific RNA coliphage MS2, feline calicivirus, and E. coli in normal tap water and in tap water treated to an initial concentration of 50 ppm free chlorine and held at 4°C, 25°C, or 37°C for up to 28 days. Our aim was to determine which of these two organisms (coliphage or E. coli was better at indicating norovirus survival under the conditions of the experiment. There was a relatively rapid decline of FCV and E. coli in 50 ppm chlorine treated water and both organisms were undetectable within one day irrespective of the temperature. In contrast, FRNA phage survived for 7 to 14 days in 50 ppm chlorine treated water at all temperatures. All organisms survived for 28 days in tap water at 4°C, but FCV was undetectable on day 21 and day 7 at 25°C and 37°C, respectively. Greater survival of FRNA phage compared to E. coli in 50 ppm chlorine treated water suggests that these organisms should be further investigated as indicators of norovirus in depurated shellfish, sanitized produce, and treated wastewater which are all subject to high-level chlorine treatment.

Inhibiting prenylation augments chemotherapy efficacy in renal cell carcinoma through dual inhibition on mitochondrial respiration and glycolysis.

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Huang, Jiangrong; Yang, Xiaoyu; Peng, Xiaochun; Huang, Wei

2017-11-18

Prenylation is a posttranslational lipid modification required for the proper functions of a number of proteins involved in cell regulation. Here, we show that prenylation inhibition is important for renal cell carcinoma (RCC) growth, survival and response to chemotherapy, and its underlying mechanism may be contributed to mitochondrial dysfunction. We first demonstrated that a HMG-CoA reductase inhibitor pitavastatin inhibited mevalonate pathway and thereby prenylation in RCC cells. In addition, pitavastatin is effective in inhibiting growth and inducing apoptosis in a panel of RCC cell lines. Combination of pitavastatin and paclitaxel is significantly more effective than pitavastatin or paclitaxel alone as shown by both in vitro cell culture system and in vivo RCC xenograft model. Importantly, pitavastatin treatment inhibits mitochondrial respiration via suppressing mitochondrial complex I and II enzyme activities. Interestingly, different from mitochondrial inhibitor phenformin that inhibits mitochondrial respiration but activates glycolytic rate in RCC cells, pitavastatin significantly decreases glycolytic rate. The dual inhibitory action of pitavastatin on mitochondrial respiration and glycolysis results in remarkable energy depletion and oxidative stress in RCC cells. In addition, inhibition of prenylation by depleting Isoprenylcysteine carboxylmethyltransferase (Icmt) also mimics the inhibitory effects of pitavastatin in RCC cells. Our work demonstrates the previously unappreciated association between prenylation inhibition and energy metabolism in RCC, which can be therapeutically exploited, likely in tumors that largely rely on energy metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Breast density and mode of detection in relation to breast cancer specific survival: a cohort study

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Olsson, Åsa; Sartor, Hanna; Borgquist, Signe; Zackrisson, Sophia; Manjer, Jonas

2014-01-01

The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could

Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.

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Mihalj, Martina; Kellermayer, Zoltán; Balogh, Peter

2013-07-01

Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.

Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer: A Systematic Review and Meta-analysis.

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Vrieling, Alina; Kampman, Ellen; Knijnenburg, Nathalja C; Mulders, Peter F; Sedelaar, J P Michiel; Baracos, Vickie E; Kiemeney, Lambertus A

2016-12-04

Several studies suggest that body composition (ie, body proportions of muscle and fat defined by computed tomography) is associated with clinical outcomes of several cancer types, including renal cell cancer (RCC). To conduct a systematic review and meta-analysis of the evidence on body composition in relation to clinical outcomes in RCC. Literature was reviewed through October 2016 using PubMed and Embase. We included studies investigating computed tomography-measured cross-sectional areas of visceral adipose tissue (VAT), perinephric fat, subcutaneous adipose tissue (SAT), skeletal muscle index (SMI), and skeletal muscle radiodensity (SMD) in relation to perioperative outcomes, treatment toxicity, and survival in RCC patients. We included 28 studies with a total of 6608 patients. Binary classification of body composition was used in most studies. In metastatic RCC (mRCC) patients treated with antiangiogenic drugs, dose-limiting toxicity was more frequent in patients with low versus high SMI (four studies, risk difference = 16%, 95% confidence interval [CI]: 2-31%, p = 0.03, I 2 = 26%). Low versus high SMI (six studies, hazard ratio = 1.48, 95% CI: 1.08-2.03, p = 0.02, I 2 = 28%) and SMD (four studies, HR = 1.56, 95% CI: 1.20-2.03, p = 0.0008, I 2 = 0%) were associated with an increased risk of overall mortality in mRCC. Low versus high VAT and perinephric fat were not consistently associated with perioperative outcomes and survival. No associations for SAT were found. Low SMI is associated with increased dose-limiting toxicity, and low SMI and SMD are associated with increased overall mortality in mRCC. The association of VAT, perinephric fat, and SAT with clinical outcomes needs further investigation, also in localized RCC. We reviewed studies assessing the association of body composition with clinical outcomes in renal cell cancer. We demonstrated higher risk of dose-limiting toxicity and overall mortality for metastatic renal cell cancer patients with low

Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models.

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Cui, Shujin

2017-07-11

BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo. RESULTS Our results showed that many commonly used chemotherapy agents can induce immunogenic marker release in RCC cell lines. Importantly, the RCC xenograft mouse model mice who received the combination treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD-L1) antibodies (Abs) had longer survival times compared to those who received 5-FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor immunity, such as IL-2, IFN-γ, and TNF-α, as well as tumor-infiltrating cytotoxic T cells, were also increased after the combination treatment. CONCLUSIONS We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by releasing the immune suppression in the tumor microenvironment.

Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

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Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

2017-02-21

The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

Benign meningiomas: primary treatment selection affects survival

International Nuclear Information System (INIS)

Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

1997-01-01

Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

Nuclear localization of the CK2α-subunit correlates with poor prognosis in Clear Cell Renal Cell Carcinoma

DEFF Research Database (Denmark)

Rabjerg, Maj; Guerra, Barbara; Oliván-Viguera, Aida

2017-01-01

Protein kinase CK2a, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell...... Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2a expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal...... renal cortex. Nuclear protein expression of CK2a correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest...

Cytokines affecting CD4+T regulatory cells in transplant tolerance. III. Interleukin-5 (IL-5) promotes survival of alloantigen-specific CD4+ T regulatory cells.

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Hall, Bruce M; Plain, Karren M; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine M; Nomura, Masaru; Boyd, Rochelle; Hodgkinson, Suzanne J

2017-08-01

CD4 + T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4 + CD25 + FOXP3 + Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg. This study examined if recombinant IL-5(rIL-5) promoted survival of tolerant CD4 + , especially CD4 + CD25 + T cells. CD4 + T cells, from DA rats tolerant to fully allogeneic PVG heart allografts surviving over 100days without on-going immunosuppression, were cultured with PVG alloantigen and rIL-5. The ability of these cells to adoptively transfer tolerance to specific-donor allograft and suppress normal CD4 + T cell mediated rejection in adoptive DA hosts was examined. Tolerant CD4 + CD25 + T cells' response to rIL-5 and expression of IL-5Rα was also assessed. rIL-5 was sufficient to promote transplant tolerance mediating CD4 + T cells' survival in culture with specific-donor alloantigen. Tolerant CD4 + T cells cultured with rIL-5 retained the capacity to transfer alloantigen-specific tolerance and inhibited naïve CD4 + T cells' capacity to effect specific-donor graft rejection. rIL-5 promoted tolerant CD4 + CD25 + T cells' proliferation in vitro when stimulated with specific-donor but not third-party stimulator cells. Tolerant CD4 + CD25 + T cells expressed IL-5Rα. This study demonstrated that IL-5 promoted the survival of alloantigen-specific CD4 + CD25 + T cells that mediate transplant tolerance. Copyright © 2017 Elsevier B.V. All rights reserved.

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma.

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Fisel, Pascale; Stühler, Viktoria; Bedke, Jens; Winter, Stefan; Rausch, Steffen; Hennenlotter, Jörg; Nies, Anne T; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Kruck, Stephan; Schwab, Matthias; Schaeffeler, Elke

2015-10-13

Cluster of differentiation 147 (CD147/BSG) is a transmembrane glycoprotein mediating oncogenic processes partly through its role as binding partner for monocarboxylate transporter MCT4/SLC16A3. As demonstrated for MCT4, CD147 is proposed to be associated with progression in clear cell renal cell carcinoma (ccRCC). In this study, we evaluated the prognostic relevance of CD147 in comparison to MCT4/SLC16A3 expression and DNA methylation. CD147 protein expression was assessed in two independent ccRCC-cohorts (n = 186, n = 59) by immunohistochemical staining of tissue microarrays and subsequent manual as well as automated software-supported scoring (Tissue Studio, Definien sAG). Epigenetic regulation of CD147 was investigated using RNAseq and DNA methylation data of The Cancer Genome Atlas. These results were validated in our cohort. Relevance of prognostic models for cancer-specific survival, comprising CD147 and MCT4 expression or SLC16A3 DNA methylation, was compared using chi-square statistics. CD147 protein expression generated with Tissue Studio correlated significantly with those from manual scoring (P CD147 in ccRCC. Association of CD147 expression with patient outcome differed between cohorts. DNA methylation in the CD147/BSG promoter was not associated with expression. Comparison of prognostic relevance of CD147/BSG and MCT4/SLC16A3, showed higher significance for MCT4 expression and superior prognostic power for DNA methylation at specific CpG-sites in the SLC16A3 promoter (e.g. CD147 protein: P = 0.7780,Harrell's c-index = 53.7% vs. DNA methylation: P = 0.0076, Harrell's c-index = 80.0%). Prognostic significance of CD147 protein expression could not surpass that of MCT4, especially of SLC16A3 DNA methylation, corroborating the role of MCT4 as prognostic biomarker for ccRCC.

Age-specific survival of tundra swans on the lower Alaska Peninsula

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Meixell, Brandt W.; Lindberg, Mark S.; Conn, Paul B.; Dau, Christian P.; Sarvis, John E.; Sowl, Kristine M.

2013-01-01

The population of Tundra Swans (Cygnus columbianus columbianus) breeding on the lower Alaska Peninsula represents the southern extremity of the species' range and is uniquely nonmigratory. We used data on recaptures, resightings, and recoveries of neck-collared Tundra Swans on the lower Alaska Peninsula to estimate collar loss, annual apparent survival, and other demographic parameters for the years 1978–1989. Annual collar loss was greater for adult males fitted with either the thinner collar type (0.34) or the thicker collar type (0.15) than for other age/sex classes (thinner: 0.10, thicker: 0.04). The apparent mean probability of survival of adults (0.61) was higher than that of immatures (0.41) and for both age classes varied considerably by year (adult range: 0.44–0.95, immature range: 0.25–0.90). To assess effects of permanent emigration by age and breeding class, we analyzed post hoc the encounter histories of swans known to breed in our study area. The apparent mean survival of known breeders (0.65) was generally higher than that of the entire marked sample but still varied considerably by year (range 0.26–1.00) and indicated that permanent emigration of breeding swans was likely. We suggest that reductions in apparent survival probability were influenced primarily by high and variable rates of permanent emigration and that immigration by swans from elsewhere may be important in sustaining a breeding population at and near Izembek National Wildlife Refuge.

Resection for secondary malignancy of the pancreas.

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Hung, Jui-Hsia; Wang, Shin-E; Shyr, Yi-Ming; Su, Cheng-Hsi; Chen, Tien-Hua; Wu, Chew-Wun

2012-01-01

This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method

International Nuclear Information System (INIS)

Esik, Olga; Tusnady, Gabor; Daubner, Kornel; Nemeth, Gyoergy; Fuezy, Marton; Szentirmay, Zoltan

1997-01-01

Purpose: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. Materials and methods: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. Results: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be

Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

Directory of Open Access Journals (Sweden)

Weber T

2014-05-01

Full Text Available Thomas Weber,1,2 Matthias Meinhardt,3 Stefan Zastrow,1 Andreas Wienke,4 Kati Erdmann,1 Jörg Hofmann,1 Susanne Fuessel,1 Manfred P Wirth11Department of Urology, Technische Universität Dresden, Dresden, Germany; 2Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany; 3Institute of Pathology, Technische Universität Dresden, Dresden, Germany; 4Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale, GermanyPurpose: To enhance prognostic information of protein biomarkers for clear cell renal cell carcinomas (ccRCCs, we analyzed them within prognostic groups of ccRCC harboring different tumor characteristics of this clinically and molecularly heterogeneous tumor entity.Methods: Tissue microarrays from 145 patients with primary ccRCC were immunohistochemically analyzed for VHL (von Hippel-Lindau tumor suppressor, Ki67 (marker of proliferation 1, p53 (tumor protein p53, p21 (cyclin-dependent kinase inhibitor 1A, survivin (baculoviral IAP repeat containing 5, and UEA-1 (ulex europaeus agglutinin I to assess microvessel-density.Results: When analyzing all patients, nuclear staining of Ki67 (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04–1.12 and nuclear survivin (nS; HR 1.04, 95% CI 1.01–1.08 were significantly associated with disease-specific survival (DSS. In the cohort of patients with advanced localized or metastasized ccRCC, high staining of Ki67, p53 and nS predicted shorter DSS (Ki67: HR 1.07, 95% CI 1.02–1.11; p53: HR 1.05, 95% CI 1.01–1.09; nS: HR 1.08, 95% CI 1.02–1.14. In organ-confined ccRCC, patients with high p21-staining had a longer DSS (HR 0.96, 95% CI 0.92–0.99. In a multivariate model with stepwise backward elimination, tumor size and p21-staining showed a significant association with DSS in patients with "organ-confined" ccRCCs. The p21-staining increased the concordance index of tumor size from

Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma.

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Wang, P-Q; Wu, Y-X; Zhong, X-D; Liu, B; Qiao, G

2017-01-01

The long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. However, little is known about the pathological role of lncRNA TUG1 in clear cell renal cell carcinoma (ccRCC) patients. This study attempted to investigate the association of lncRNA TUG1 expression with progression and prognosis in ccRCC patients. Using qRT-PCR, the expression of TUG1 was measured in 203 ccRCC tissues and 45 adjacent non-cancerous tissues. Then, the relationships between TUG1 level and the clinicopathological factors of patients with ccRCC were analyzed. The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. The relative level of TUG1was significantly higher in ccRCC tissues compared to the adjacent non-tumor tissues (p TUG1 was associated significantly with histological grade, tumor stage, lymph node metastasis and distant metastasis (all p TUG1 expression levels were associated with a shorter overall survival (p TUG1 expression was an independent prognostic marker of poor outcome. These findings suggested that TUG1 may act as a tumor promoter in ccRCC and could serve as a potential therapeutic target for this tumor.

Predictors of successful weaning from prolonged mechanical ventilation in Taiwan.

Science.gov (United States)

Wu, Yao-Kuang; Kao, Kuo-Chin; Hsu, Kuang-Hung; Hsieh, Meng-Jer; Tsai, Ying-Huang

2009-08-01

For adult patients on prolonged mechanical ventilation (PMV, >/=21 days), successful weaning has been attributed to various factors. The purpose of this study was to describe patient outcomes, weaning rates and factors in successful weaning at a hospital-based respiratory care center (RCC) in Taiwan. This was a retrospective observational study performed in a 24-bed RCC over six years. A total of 1307 patients on PMV were included in the study. The overall survival rate was 62%. Fifty-six percent of patients were successfully weaned. Unsuccessfully weaned patients had higher MICU transfer rates, higher Acute Physiology and Chronic Health Evaluation II scores, longer duration of RCC stay, higher rates of being bed-ridden prior to admission, increased hemodialysis rates, higher modified Glasgow Coma Scale scores, higher rapid shallow breathing index, lower inspiratory pressure at residual volume (PImax) and lower blood urea nitrogen (BUN) and creatinine levels. Factors found to be associated with unsuccessful weaning were length of RCC stay (OR=1.04, Pventilator independence can be achieved in an RCC setting as an alternative to ICU care. Factors associated with unsuccessful weaning included longer duration of RCC stay, elevated BUN levels and lower modified GCS scores, serum albumin and PImax levels.

Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.

Science.gov (United States)

Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

2018-03-16

The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

Cancer survival for Aboriginal and Torres Strait Islander Australians: a national study of survival rates and excess mortality.

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Condon, John R; Zhang, Xiaohua; Baade, Peter; Griffiths, Kalinda; Cunningham, Joan; Roder, David M; Coory, Michael; Jelfs, Paul L; Threlfall, Tim

2014-01-31

National cancer survival statistics are available for the total Australian population but not Indigenous Australians, although their cancer mortality rates are known to be higher than those of other Australians. We aimed to validate analysis methods and report cancer survival rates for Indigenous Australians as the basis for regular national reporting. We used national cancer registrations data to calculate all-cancer and site-specific relative survival for Indigenous Australians (compared with non-Indigenous Australians) diagnosed in 2001-2005. Because of limited availability of Indigenous life tables, we validated and used cause-specific survival (rather than relative survival) for proportional hazards regression to analyze time trends and regional variation in all-cancer survival between 1991 and 2005. Survival was lower for Indigenous than non-Indigenous Australians for all cancers combined and for many cancer sites. The excess mortality of Indigenous people with cancer was restricted to the first three years after diagnosis, and greatest in the first year. Survival was lower for rural and remote than urban residents; this disparity was much greater for Indigenous people. Survival improved between 1991 and 2005 for non-Indigenous people (mortality decreased by 28%), but to a much lesser extent for Indigenous people (11%) and only for those in remote areas; cancer survival did not improve for urban Indigenous residents. Cancer survival is lower for Indigenous than other Australians, for all cancers combined and many individual cancer sites, although more accurate recording of Indigenous status by cancer registers is required before the extent of this disadvantage can be known with certainty. Cancer care for Indigenous Australians needs to be considerably improved; cancer diagnosis, treatment, and support services need to be redesigned specifically to be accessible and acceptable to Indigenous people.

Chemosensitization of Human Renal Cell Cancer Using Antisense Oligonucleotides Targeting the Antiapoptotic Gene Clusterin

Directory of Open Access Journals (Sweden)

Tobias Zellweger

2001-01-01

Full Text Available BACKGROUND: Renal cell cancer (RCC is a chemoresistant disease with no active chemotherapeutic agent achieving objective response rates higher than 15%. Clusterin is a cell survival gene that increases in human renal tubular epithelial cells after various states of injury and disease. Downregulation of clusterin, using antisense oligonucleotides (ASO, has recently been shown to increase chemosensitivity in several prostate cancer models. The objectives in this study were to evaluate clusterin expression levels in human RCC and normal kidney tissue, and to test whether clusterin ASO could also enhance chemosensitivity in human RCC Caki-2 cells both in vitro and in vivo. METHODS: Immunohistochemical staining was used to characterize clusterin expression in 67 RCC and normal kidney tissues obtained from radical nephrectomy specimens. Northern blot analysis was used to assess changes in clusterin mRNA expression after ASO and paclitaxel treatment. The effects of combined clusterin ASO and paclitaxel treatment on Caki-2 cell growth was examined using an MTT assay. Athymic mice bearing Caki-2 tumors were treated with clusterin ASO alone, clusterin ASO plus paclitaxel, and mismatch control oligonucleotides plus paclitaxel, over a period of 28 days with measurement of tumor volumes once weekly over 8 weeks. RESULTS: Immunohistochemistry of normal and malignant kidney tissue sections of 67 patients demonstrated positive clusterin staining for almost all RCC (98% and an overexpression, compared to normal tissue, in a majority of RCC (69%. Clusterin ASO, but not mismatch control oligonucleotides, decreased clusterin mRNA expression in Caki-2 cells in a dosedependent and sequence-specific manner. Pretreatment of Caki-2 cells with clusterin ASO significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo

Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine.

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Shinagare, Atul B; Krajewski, Katherine M; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H

2017-08-01

For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC. State-of-the-art knowledge of the molecular basis of RCC and its treatment and imaging will help ensure that the radiology community remains relevant and central in the care of patients with advanced RCC. This article will review developments in management of advanced RCC from a radiologist's perspective to highlight our clinical role. It will describe how the underlying molecular mechanisms of RCC provide specific targets for novel anticancer agents. The relationship between the mechanisms of action of these novel anticancer agents and the imaging appearance of tumor response will be discussed, along with the available tumor response criteria and their strengths and weaknesses, thus assisting radiologists in response assessment in the setting of clinical trials or routine practice. The class- and drug-specific toxicities and complications associated with the novel anticancer agents will be summarized, since these are frequently missed or misinterpreted and require the radiologist's input in prompt detection and management. The potential role of radiogenomics and texture analysis in the management of advanced RCC will also be discussed. © RSNA, 2017.

Gender Inequality in Survival at Older Ages

OpenAIRE

Sanderson, W.; Scherbov, S.

2017-01-01

Gender gaps are typically measured by subtracting the survival rates for women from that of men. In most countries and at most ages, these gender gaps indicate a survival rate disadvantage for men. This method is not informative because it is unclear whether larger or smaller gaps would be more equitable. Here we reconceptualize the gender gap in survival based on differences from gender-specific best practice rates and express those gender gaps in the metric years of age. If the age-specific...

Applied survival analysis using R

CERN Document Server

Moore, Dirk F

2016-01-01

Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner.

Science.gov (United States)

Xie, Liang; Duncan, Michael B; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O; Hanahan, Douglas; Kalluri, Raghu

2011-06-14

Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis.

Microwave treatment of renal cell carcinoma adjacent to renal sinus

International Nuclear Information System (INIS)

Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

2016-01-01

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Microwave treatment of renal cell carcinoma adjacent to renal sinus

Energy Technology Data Exchange (ETDEWEB)

Gao, Yongyan, E-mail: gaoyongyan7@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Department of Ultrasound, The General Hospital of Chinese People’s Armed Police Forces, 69 Yongding Road, Beijing, 100039 (China); Liang, Ping, E-mail: liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Xiaoling, E-mail: 784107477@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Jie, E-mail: 1411495161@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Cheng, Zhigang, E-mail: 13691367317@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Han, Zhiyu, E-mail: hanzhiyu122@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Duan, Shaobo, E-mail: Dustin2662@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Huang, Hui, E-mail: 309hh@sina.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

2016-11-15

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Update on contemporary management of clinically localized renal cell carcinoma.

Science.gov (United States)

Jorns, J J; Thiel, D D; Castle, E P

2012-12-01

Renal cell carcinoma (RCC) continues to increase in incidence with the largest increase manifesting in small, organ-confined tumors. This review outlines the epidemiology and current data pertaining to the management of clinically-localized RCC. In this manuscript, the current data outlining the benefit of nephron sparing to the overall survival of the patient is described. The data pertaining to minimally invasive nephron sparing is also explained in detail. From laparoscopic and robotic partial nephrectomy to watchful waiting and percutaneous ablation, the urologist is continually assaulted with new data for the management of clinically-localized RCC. The data can be confusing, and much of it is conflicting. The addition of new scoring systems or nomograms may aid in predicting which therapy would be most beneficial in certain patient groups. New scoring systems may also predict the difficulty of surgical resection and predict surgical complications. The limitations of the data pertaining to the management of clinically-localized RCC are also outlined.

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

Energy Technology Data Exchange (ETDEWEB)

Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de [Department of Radiation Oncology, University Hospital Ulm (Germany); Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard [Department of Radiation Oncology, University Hospital Ulm (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Stöckle, Michael [Department of Urology, University Hospital Homburg/Saar (Germany); Rübe, Christian [Department of Radiation Oncology, University Hospital Homburg/Saar (Germany); Semjonow, Axel [Department of Urology, University Hospital Münster (Germany); Wirth, Manfred [Department of Urology, University Hospital Dresden (Germany); Störkel, Stephan; Golz, Reinhard [Department of Pathology, HELIOS Hospital Wuppertal (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University Hospital Giessen-Marburg (Germany); Hofmann, Rainer [Department of Urology, University Hospital Giessen-Marburg (Germany); Feldmann, Horst-Jürgen [Department of Radiation Oncology, General Hospital Fulda (Germany); Kälble, Tilman [Department of Urology, General Hospital Fulda (Germany); Siegmann, Alessandra; Hinkelbein, Wolfgang [Department of Radiation Oncology, University Hospital Berlin (Germany); Steiner, Ursula; Miller, Kurt [Department of Urology, University Hospital Berlin (Germany)

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

Pattern of Care Study in Metastatic Renal-Cell Carcinoma in the Preimmunotherapy Era in Switzerland.

Science.gov (United States)

Sandmeier, Nadja; Rothschild, Sacha I; Rothermundt, Christian; Cathomas, Richard; Schardt, Julian; Berthold, Dominik; von Burg, Philippe; Müller, Beat; Beyer, Jörg; Vogt, Deborah R; Stenner, Frank

2018-02-02

In metastatic renal-cell carcinoma (mRCC), physicians have a plethora of therapeutic choices, with the latest addition of checkpoint inhibitors. However, many questions regarding the best use of the respective drugs remain unanswered. Therefore, it is important to examine and summarize the outcome of real-world experiences to understand the practical value of the various drugs in daily use and foster optimal treatment algorithms for patients with renal-cell carcinoma. We sought to describe the pattern of care in mRCC under circumstances with access to all therapeutic options for patients. We examined the outcome of patients with mRCC who were treated at 8 major centers in Switzerland, mainly with vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibitors. Data from 110 patients with mRCC who had undergone more than one systemic therapy were collected and analyzed. We assessed the pattern of care for patients with mRCC in an unrestricted health care system and outcomes with regard to the respective treatment sequences. We also studied the compliance of individual therapies with published guidelines and correlated the adherence to outcome. Finally, immediate versus deferred treatment and the number of received therapeutic drug lines were analyzed. Median survival of patients treated with targeted agents for mRCC was 2.0 years. Exposure to more than 2 lines of systemic drugs did not improve outcome of patients with mRCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Combination of mTOR and MAPK Inhibitors—A Potential Way to Treat Renal Cell Carcinoma

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Ashutosh Chauhan

2016-10-01

Full Text Available Renal cell carcinoma (RCC is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC.

Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

Science.gov (United States)

Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

2018-02-23

Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Survival and death causes in differentiated thyroid carcinoma

NARCIS (Netherlands)

Eustatia-Rutten, Carmen F. A.; Corssmit, Eleonora P. M.; Biermasz, Nienke R.; Pereira, Alberto M.; Romijn, Johannes A.; Smit, Johannes W.

2006-01-01

Survival studies in differentiated thyroid carcinoma (DTC) may be biased because they have been performed in heterogeneous populations. In addition, specific death causes in DTC have not been documented well in the literature. The aim of our study was to investigate survival and specific death

Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Keshaviah, Aparna; Manola, Judith; Cote, Kerri; Loffredo, Marian; Iskrzytzky, Olga; Renshaw, Andrew A.

2002-01-01

Purpose: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. Methods and Materials: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. Results: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of ≤50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p=0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p 50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings

A protected area influences genotype-specific survival and the structure of a Canis hybrid zone.

Science.gov (United States)

Benson, John F; Patterson, Brent R; Mahoney, Peter J

2014-02-01

It is widely recognized that protected areas can strongly influence ecological systems and that hybridization is an important conservation issue. However, previous studies have not explicitly considered the influence of protected areas on hybridization dynamics. Eastern wolves are a species of special concern and their distribution is largely restricted to a protected population in Algonquin Provincial Park (APP), Ontario, Canada, where they are the numerically dominant canid. We studied intrinsic and extrinsic factors influencing survival and cause-specific mortality of hybrid and parental canids in the three-species hybrid zone between eastern wolves, eastern coyotes, and gray wolves in and adjacent to APP. Mortality risk for eastern wolves in areas adjacent to APP was significantly higher than for other sympatric Canis types outside of APP, and for eastern wolves and other canids within APP. Outside of APP, the annual mortality rate of all canids by harvest (24%) was higher than for other causes of death (4-7%). Furthermore, eastern wolves (hazard ratio = 3.5) and nonresidents (transients and dispersing animals, hazard ratio = 2.7) were more likely to die from harvest relative to other Canis types and residents, respectively. Thus, eastern wolves dispersing from APP were especially vulnerable to harvest mortality. For residents, eastern wolf survival was more negatively influenced by increased road density than for other Canis types, further highlighting the sensitivity of eastern wolves to human disturbance. A cycle of dispersal from APP followed by high rates of mortality and hybridization appears to maintain eastern wolves at low density adjacent to APP, limiting the potential for expansion beyond the protected area. However, high survival and numerical dominance of eastern wolves within APP suggest that protected areas can allow rare hybridizing species to persist even if their demographic performance is compromised and barriers to hybridization are largely

Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

Science.gov (United States)

Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2017-06-01

CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Renal cell carcinomas mass of <4 cm are not always indolent

DEFF Research Database (Denmark)

Azawi, Nessn H; Lund, Lars; Fode, Mikkel

2017-01-01

CONTEXT: The rate of progression to metastatic disease in patients undergoing active surveillance for small renal tumors varies in the literature between 1% and 8%. AIMS: This study aims to examine the incidence of metastasis in small renal tumors of cm in a Danish cohort. SETTINGS AND DESIGN......: Retrospective. MATERIALS AND METHODS: Data on 106 patients who were diagnosed with renal cancer (RCC) of cm by CT scan from January 2005 to December 2013 were collected retrospectively in January 2016 from patient charts and analyzed. STATISTICAL ANALYSIS USED: The cancer-specific survival (CSS) and overall...

Sex-specific patterns in abundance, temporary emigration and survival of Indo-Pacific bottlenose dolphins (Tursiops aduncus in coastal and estuarine waters

Directory of Open Access Journals (Sweden)

Kate R Sprogis

2016-02-01

Full Text Available Inherent difficulties in determining the sex of free-ranging sexually monomorphic species often prevents a sex-specific focus on estimating abundance, movement patterns and survival rates. This study provides insights into sex-specific population parameters of Indo-Pacific bottlenose dolphins (Tursiops aduncus. Systematic, boat-based photo-identification surveys (n = 417 were conducted year-round from 2007-2013 in coastal and estuarine waters off Bunbury, Western Australia. Pollock’s Robust Design was used to quantify population parameters for three datasets: i adults and juveniles combined, ii adult females and iii adult males. For all datasets, abundance estimates varied seasonally, with general highs during summer and/or autumn, and lows during winter. Dolphins had seasonally structured temporary emigration rates with similar trends between sexes. The derived return rate (1-γ’ of temporary emigrants into the study area was highest from winter to spring, indicating that dolphins had a high probability of return into the study area during spring. We suggest that the return of dolphins into the study area and increase in abundance is influenced by the breeding season (summer/autumn. Prey availability is likely a main driver responsible for the movement of dolphins out of the study area during winter. Seasonal apparent survival rates were constant and high (0.98-0.99 for all datasets. High apparent survival rates suggest there is no permanent emigration from the study area. Our sex-specific modeling approach offers a comprehensive interpretation of the population dynamics of a top predator in a coastal and estuarine environment and acts as a model for future sex-based population studies on sexually monomorphic species.

Clustered survival data with left-truncation

DEFF Research Database (Denmark)

Eriksson, Frank; Martinussen, Torben; Scheike, Thomas H.

2015-01-01

Left-truncation occurs frequently in survival studies, and it is well known how to deal with this for univariate survival times. However, there are few results on how to estimate dependence parameters and regression effects in semiparametric models for clustered survival data with delayed entry....... Surprisingly, existing methods only deal with special cases. In this paper, we clarify different kinds of left-truncation and suggest estimators for semiparametric survival models under specific truncation schemes. The large-sample properties of the estimators are established. Small-sample properties...

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report

Directory of Open Access Journals (Sweden)

Yuki H

2014-02-01

Full Text Available Hideo Yuki,1,* Takao Kamai,1,* Keiichi Kubota,2 Hideyuki Abe,1 Daisaku Nishihara,1 Tomoya Mizuno,1 Akinori Masuda,1 Hironori Betsunoh,1 Masahiro Yashi,1 Yoshitatsu Fukabori,1 Ken-Ichiro Yoshida1 1Department of Urology, 2Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan *These authors contributed equally to this manuscript Background: Renal cell carcinoma (RCC with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. Methods: We present a 73-year-old man who had a large (13 cm in diameter right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. Results: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy

HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

International Nuclear Information System (INIS)

Ramakrishnan, Swathi; Ku, ShengYu; Ciamporcero, Eric; Miles, Kiersten Marie; Attwood, Kris; Chintala, Sreenivasulu; Shen, Li; Ellis, Leigh; Sotomayor, Paula; Swetzig, Wendy; Huang, Ray; Conroy, Dylan; Orillion, Ashley; Das, Gokul; Pili, Roberto

2016-01-01

Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student’s T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results

Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Li, Siming; Kong, Yan; Si, Lu; Chi, Zhihong; Cui, Chuanliang; Sheng, Xinan; Guo, Jun

2014-01-01

The incidence of renal cell cancer (RCC) has been increasing for the past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is rather low. Everolimus (RAD001), a new inhibitor for mammalian target of rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit to patients with anti-VEGF-refractory mRCC. However, factors for selection of patients who may benefit from everolimus remain largely unknown. Here we aimed to explore potential molecular indicators for mRCC patients who may benefit from everolimus treatment. Paraffin-embedded tumor tissue specimens derived from 18 mRCC patients before everolimus treatment, who participated the phase 1b trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR], partial response [PR], plus stable disease [SD] ≥ 6 months) and progression-free survival time (PFS) were correlated with expression levels of these mTOR-associated molecules. In these 18 patients, there were 1 PR, 15 SDs (including 9 SDs ≥ 6 months), and 2 progressive diseases (PD). The clinical benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months. Patients with positive expression of phospho-mTOR showed a better CBR (71.4% versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those patients with negative expression. The median PFS of patients with positive phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that of patients negative for phospho-S6RP expression. However, expression levels of phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus treatment with respect to CBR and PFS. Co-expression of

Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner

Science.gov (United States)

Xie, Liang; Duncan, Michael B.; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O.; Hanahan, Douglas; Kalluri, Raghu

2011-01-01

Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis. PMID:21622854

Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures.

Science.gov (United States)

Bohlen, Christopher J; Bennett, F Chris; Tucker, Andrew F; Collins, Hannah Y; Mulinyawe, Sara B; Barres, Ben A

2017-05-17

Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiovascular disease incidence and survival

DEFF Research Database (Denmark)

Byberg, Stine; Agyemang, Charles; Zwisler, Ann Dorthe

2016-01-01

Studies on cardiovascular disease (CVD) incidence and survival show varying results between different ethnic groups. Our aim was to add a new dimension by exploring the role of migrant status in combination with ethnic background on incidence of-and survival from-CVD and more specifically acute...... of some types of cardiovascular disease compared to Danish-born. Family-reunified migrants on the other hand had lower rates of CVD. All migrants had better survival than Danish-born indicating that migrants may not always be disadvantaged in health....

High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features.

Science.gov (United States)

Achkar, Tala; Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J; Friedland, David; Parikh, Rahul A

2017-01-01

High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12-20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10-15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer's exact test and Wilcoxon rank sum test. Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0-21.3). Median OS was 30.5 months (95% CI 13.3-57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3-35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4-10.2). In

Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

International Nuclear Information System (INIS)

Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu; Li, Hai; Wu, Jiang-Fen

2017-01-01

To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

Energy Technology Data Exchange (ETDEWEB)

Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu [First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Li, Hai [First Affiliated Hospital of Nanjing Medical University, Department of Pathology, Nanjing (China); Wu, Jiang-Fen [GE Healthcare, Shanghai (China)

2017-11-15

To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

Quebra do grão em Resíduos de Construção Civil (RCC induzida pelo processo de compactação

Directory of Open Access Journals (Sweden)

Nathália Marques da Silva

Full Text Available Resumo Nas últimas décadas a geração de resíduos de construção civil (RCC tornou-se um fator relevante em todo o mundo. Dessa forma, é cada vez mais importante o reaproveitamento desse material, sobretudo em obras de grande consumo, tais como as obras rodoviárias. No entanto, a aplicação desses resíduos depende do conhecimento das propriedades químicas e mecânicas do material. Entre esses parâmetros destaca-se que a susceptibilidade à quebra do grão é de fundamental importância. Isso porque esse parâmetro influencia diretamente no comportamento do material através da resistência e da permeabilidade. O presente trabalho avaliou a quebra do grão em RCC induzida pelo processo de compactação através da aplicação das energias normal e modificada. Para isso o material foi dividido em frações com granulometrias diferentes. Dessa forma, foi analisada a influência da energia, do tamanho do grão, da mineralogia, do teor de umidade e da densidade da amostra. Os resultados indicaram que a ocorrência da quebra do grão está diretamente relacionada com a constituição mineralógica, observando-se que a maior fração estudada foi aquela que sofreu a menor quebra dos grãos. Adicionalmente, os resultados indicaram que a densidade de compactação da amostra também possui significativa influência no processo de quebra dos grãos.

Kidney cancer

International Nuclear Information System (INIS)

Rajer, M.

2007-01-01

The purpose of this paper is to present the epidemiology, diagnostic workup and treatment of renal cell carcinoma (RCC) with an emphasis on the Slovenian epidemiological data. RCC represents 2% of all cancers and is the third most common genitourinary tract tumour. It most frequently occurs among people of ages, between 50 and 60 years. Male patients are more prone to it than female. A number of environmental, occupational and genetic factors have been found to be associated with the development of RCC. Patients often have nonspecific symptoms and this is the reason why for half of them the disease is already metastatic when diagnosed. The most common sites of metastases are lungs (75%), followed by soft tissues (36%), bones (20%), liver (18%), skin (8%) and central nerve system (8%). In the evaluation of RCC multiple diagnostic procedures are needed with obligatory image diagnostics. Radical nephrectomy is still the mainstream treatment of localized disease. Nephron sparing techniques have been used in cases, where radical operation would result in an anephric patient. Efficient adjuvant therapy has not been discovered yet. Until recently interpherone and interleukin were the only known effective treatments for metastatic disease, but now new and more efficient biologic agents are being discovered. The most important prognostic factor for survival is stage at the beginning of treatment. The 5-year survival rate is 95% for patients with stage I disease, 88% for stage II, 59% for stage III and 20% for stage IV. (author)

Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.

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Zahoor, Haris; Rini, Brian I

2016-12-01

The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.

Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

International Nuclear Information System (INIS)

Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

1988-01-01

We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

Directory of Open Access Journals (Sweden)

Hidenori Kawashima

2015-03-01

Full Text Available Metastatic lesions of renal cell carcinoma (RCC occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets. 

Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

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Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

2016-01-01

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

Fledgling survival increases with development time and adult survival across north and south temperate zones

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Lloyd, Penn; Martin, Thomas E.

2016-01-01

Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

Clay mineral type effect on bacterial enteropathogen survival in soil.

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Brennan, Fiona P; Moynihan, Emma; Griffiths, Bryan S; Hillier, Stephen; Owen, Jason; Pendlowski, Helen; Avery, Lisa M

2014-01-15

Enteropathogens released into the environment can represent a serious risk to public health. Soil clay content has long been known to have an important effect on enteropathogen survival in soil, generally enhancing survival. However, clay mineral composition in soils varies, and different clay minerals have specific physiochemical properties that would be expected to impact differentially on survival. This work investigated the effect of clay materials, with a predominance of a particular mineral type (montmorillonite, kaolinite, or illite), on the survival in soil microcosms over 96 days of Listeria monocytogenes, Salmonella Dublin, and Escherichia coli O157. Clay mineral addition was found to alter a number of physicochemical parameters in soil, including cation exchange capacity and surface area, and this was specific to the mineral type. Clay mineral addition enhanced enteropathogen survival in soil. The type of clay mineral was found to differentially affect enteropathogen survival and the effect was enteropathogen-specific. © 2013.

Immunohistochemical expression of CD44s in renal cell carcinoma lacks independent prognostic significance

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Walter Henriques da Costa

2012-08-01

Full Text Available PURPOSE: To analyze the immunohistochemical expression of the standard isoform of CD44 (CD44s adhesion molecule in clear cell renal cell carcinoma (CCRCC and its impact on clinical outcomes. MATERIALS AND METHODS: Ninety-nine consecutive patients treated surgically for RCC between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determine the most representative tumor areas for construction of a tissue microarray. The same pathologist, who was blinded to the outcome of the cases, semi-quantitatively scored the staining intensity of CD44s in all specimens. The counting was done using the H-Score algorithm. RESULTS: Of the 99 immunostained RCC specimens, 57(57.7% showed low expression, and 42(42.4% showed high expression levels of CD44s. The expression of CD44s was directly associated with tumor size (p = 0.03, clinical stage (p = 0.02 and Fuhrman grade (p = 0.02. Disease specific survival (DSS rates for patients whose specimens expressed low and high levels of CD44s was 88.1% and 67.5%, respectively (p = 0.009. Progression free survival (PFS rates in patients with low and high expression of CD44s were 78.8% and 61.7%, respectively (p = 0.05. Classical features such as the presence of metastasis and clinical stage remained isolated predictors of survival. CONCLUSIONS: Immunohistochemical expression of CD44s was associated with important clinical variables such as stage and Fuhrman grade. However, it was not an independent predictor of survival. Therefore, we believe it has a limited role as a prognostic marker in patients with CCRCC.

Fatores críticos para a produção de agregado reciclado em usinas de reciclagem de RCC da região nordeste do Brasil

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Adriana Virgínia Santana Melo

Full Text Available As usinas de reciclagem de resíduos da construção civil (RCC no Brasil produzem agregado reciclado com alta variabilidade mineral e baixa empregabilidade. Suas atividades dependem da construção civil e das diretrizes para produção do agregado reciclado, com foco na substituição ao agregado natural. Este trabalho identifica fatores críticos para a produção de agregado reciclado em usinas de reciclagem de RCC por meio da avaliação das usinas da região Nordeste do Brasil, conforme a norma NBR 15114 (ABNT, 2004b. A pesquisa foi dividida em três etapas. Na primeira, foi estabelecida a fundamentação teórica do estudo. Na segunda fase, foram realizadas visitas às usinas para entrevistas, levantamento fotográfico e observação visual. Na última, os dados coletados foram analisados à luz das diretrizes brasileiras para produção de agregado reciclado. Como resultado, identificou-se que as usinas visitadas sofrem interferências negativas na produção decorrente da gestão dos resíduos da construção civil. Observou-se, ainda, que as usinas avaliadas apresentaram não conformidades em relação aos requisitos da NBR 15114. A contribuição principal deste trabalho é a identificação de fatores críticos e proposições para a produção do agregado reciclado com pureza mineral e maior empregabilidade.

Body mass index and breast cancer survival

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Guo, Qi; Burgess, Stephen; Turman, Constance

2017-01-01

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival...... from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between...... the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER...

Challenges in the estimation of Net SURvival: The CENSUR working survival group.

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Giorgi, R

2016-10-01

Net survival, the survival probability that would be observed, in a hypothetical world, where the cancer of interest would be the only possible cause of death, is a key indicator in population-based cancer studies. Accounting for mortality due to other causes, it allows cross-country comparisons or trends analysis and provides a useful indicator for public health decision-making. The objective of this study was to show how the creation and formalization of a network comprising established research teams, which already had substantial and complementary experience in both cancer survival analysis and methodological development, make it possible to meet challenges and thus provide more adequate tools, to improve the quality and the comparability of cancer survival data, and to promote methodological transfers in areas of emerging interest. The Challenges in the Estimation of Net SURvival (CENSUR) working survival group is composed of international researchers highly skilled in biostatistics, methodology, and epidemiology, from different research organizations in France, the United Kingdom, Italy, Slovenia, and Canada, and involved in French (FRANCIM) and European (EUROCARE) cancer registry networks. The expected advantages are an interdisciplinary, international, synergistic network capable of addressing problems in public health, for decision-makers at different levels; tools for those in charge of net survival analyses; a common methodology that makes unbiased cross-national comparisons of cancer survival feasible; transfer of methods for net survival estimations to other specific applications (clinical research, occupational epidemiology); and dissemination of results during an international training course. The formalization of the international CENSUR working survival group was motivated by a need felt by scientists conducting population-based cancer research to discuss, develop, and monitor implementation of a common methodology to analyze net survival in order

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

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Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques

2018-01-01

BACKGROUND: Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). OBJECTIVE: To report...... sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman...... grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. CONCLUSIONS...

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

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Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

2018-04-01

When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

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Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

2017-10-01

To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.

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Haque, Inamul; Subramanian, Arvind; Huang, Chao H; Godwin, Andrew K; Van Veldhuizen, Peter J; Banerjee, Snigdha; Banerjee, Sushanta K

2017-12-31

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC.

A pilot study of denileukin diftitox (DD) in combination with high-dose interleukin-2 (IL-2) for patients with metastatic renal cell carcinoma (RCC).

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Atchison, Elizabeth; Eklund, John; Martone, Brenda; Wang, Lili; Gidron, Adi; Macvicar, Gary; Rademaker, Alfred; Goolsby, Charles; Marszalek, Laura; Kozlowski, James; Smith, Norm; Kuzel, Timothy M

2010-09-01

High-dose (HD) IL-2 is approved to treat renal cell carcinoma (RCC) with modest response rates and significant toxicity. Enhancement of cytotoxic T-cell activity by IL-2 is 1 mechanism of action. IL-2 also stimulates regulatory T lymphocytes (Tregs), which are associated with poor prognosis. Favorable outcomes are associated with greater rebound absolute lymphocyte count (Fumagalli 2003). DD depletes IL-2 receptor (CD25 component) expressing cells. We hypothesized that sequential therapy could complement each other; DD would deplete Tregs so IL-2 could more effectively stimulate proliferation and activity of cytotoxic T lymphocytes. Patients (n=18) received standard HD IL-2 and 1 dose of DD daily for 3 days; periodic flow cytometry and complete blood counts were performed. Group A included 3 patients to assess safety only with DD 6 μg/kg between the IL-2 courses. Group B included 9 patients at 9 μg/kg DD before the IL-2 courses. Group C included 6 patients at 9 μg/kg DD between the IL-2 courses. Efficacy using the RECIST criteria was assessed after the treatment. Fifteen patients from a study of IL-2 without DD served as controls for toxicity comparison and 13 of these for flow cytometry comparisons. No unusual toxicity was noted. For group B/C patients receiving DD, the median decline in Tregs was 56.3% from pre-DD to post-DD (P=0.013). Peak absolute lymphocyte count change from baseline was +9980/μL for group B, +4470/μL for group C, and +4720/μL for the controls (P=0.005 B vs. C). The overall response rate was 5 of 15 (33%); 3 of 9 (33%) and 2 of 6 (33%) for groups B and C, respectively, including 2 patients with sarcomatoid RCC and 1 with earlier sunitinib therapy.

Effects of perineural invasion on biochemical recurrence and prostate cancer-specific survival in patients treated with definitive external beam radiotherapy.

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Peng, Luke C; Narang, Amol K; Gergis, Carol; Radwan, Noura A; Han, Peijin; Marciscano, Ariel E; Robertson, Scott P; He, Pei; Trieu, Janson; Ram, Ashwin N; McNutt, Todd R; Griffith, Emily; DeWeese, Theodore A; Honig, Stephanie; Singh, Harleen; Greco, Stephen C; Tran, Phuoc T; Deville, Curtiland; DeWeese, Theodore L; Song, Daniel Y

2018-03-15

Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test. Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01). PNI was an independently significant predictor of adverse survival

Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis.

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Liu, Kevin X; Edwards, Benjamin; Lee, Sheena; Finelli, Mattéa J; Davies, Ben; Davies, Kay E; Oliver, Peter L

2015-05-01

Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron-specific antioxidant modulator of pathogenesis and disease progression in SOD1-mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a novel target for future therapeutic strategies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Impact of Physical Activity on Cancer-Specific and Overall Survival of Patients with Colorectal Cancer

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Gaetan Des Guetz

2013-01-01

Full Text Available Background. Physical activity (PA reduces incidence of colorectal cancer (CRC. Its influence on cancer-specific (CSS and overall survival (OS is controversial. Methods. We performed a literature-based meta-analysis (MA of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower was 0.61 (0.44–0.86. The corresponding HR OS was 0.62 (0.54–0.71. HR CSS for prediagnosis PA was 0.75 (0.62–0.91. The corresponding HR OS was 0.74 (0.62–0.89. Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk.

Methylation of 10 miRNA genes in clear cell renal cell carcinoma and their diagnostic value

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V. I. Loginov

2017-01-01

Full Text Available Introduction. Clear cell renal cell carcinoma (ccRCC is characterized by the high (30–40 % of cases frequency of lethal outcomes which at metastasis reaches 90 %. Lack of efficient diagnostics at early stages of a disease indicates the need of searching on new ccRCC markers.Objective: for definition of methylation role of some tumor suppressor microRNA (miRNA genes in ccRCC pathogenesis and progression and marker identification for ccRCC diagnostics and metastasis predictions.Materials and methods. The alterations of methylation status of 10 miRNA genes were determined by methylation specific polymerase chain reaction in tumor DNA samples and matched histologically unchanged tissues from 70 patients with ccRCC, as well as in DNA samples of kidney tissues from 19 post-mortal individuals without cancer history. Methylation of MIR MIR-107, -130b and -148a genes in ccRCC was studied for the first time.Results. It was shown that 8 miRNA genes (MIR-9-1/3, -34b/c, -124a-1/2/3, -129-2, -130b were methylated in ccRCC tumors with significantly higher frequency than in the matched histologically unchanged kidney tissues. It was established the association of methylation of 4 miRNA genes (MIR-107, -124a-3, -129-2, -130b with ccRCC progression (stage, tumor size, differentiation grade, including metastasis in the lymph nodes or distant organs, revealed for MIR-107 and -129-2. The association of MIR-107 and -130b methylation with progression of ccRCC is shown for the first time. Potential marker systems are made for ccRCC diagnostics using tumor biopsy; according to the ROC analysis, systems from 4 and 5 genes (MIR-9-1, -4b/c, -124a-3, -129-2/with addition of MIR-130b are characterized by high clinical sensitivity of 90 % and specificity of 94 % (area under ROC curve 0.93 and 0.94. Conclusion. The received results will form the basis of noninvasive ccRCC diagnostics further development. To conclude, it is shown the association of methylation of 9

Commentary on: "An integrated metabolic atlas of clear cell renal cell carcinoma." Hakimi AA, Reznik E, Lee CH, Creighton CJ, Brannon AR, Luna A, Aksoy BA, Liu EM, Shen R, Lee W, Chen Y, Stirdivant SM, Russo P, Chen YB, Tickoo SK, Reuter VE, Cheng EH, Sander C, Hsieh JJ.: Cancer Cell. 2016 Jan 11;29(1):104-16.

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Lee, Byron H

2017-09-01

Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort. Copyright © 2017 Elsevier Inc. All rights reserved.

Epistaxis as the First Manifestation of Silent Renal Cell Carcinoma: A Case Report with Relevant Literature Review

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Lee, Seung Min; Kim, You Me; Kim, Bong Man

2016-01-01

The paranasal sinuses are known to be a rare location for metastasis. Renal cell carcinoma (RCC) is the most frequent primary tumor to metastasize to the sinonasal region, followed by lung and breast cancer. In particular, clear cell type RCC, which represents approximately 85% of RCCs, is characterized by early metastasis, and it sometimes spreads to unusual sites (1, 2). Metastatic tumors in the paranasal sinuses are distributed in the maxillary, sphenoid, ethmoid, and frontal sinuses, in order of decreasing frequency. Symptoms are usually nonspecific, but epistaxis is the most common sign, due to the hypervascularity of the primary tumor. The prognosis is uncertain, but the 5-year survival rate fluctuates between 15% and 30%. The purpose of this case report is to document a rare case of silent RCC that first presented as epistaxis due to nasal cavity and ethmoid sinus metastasis

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience.

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Coelho, Rafael Corrêa; Reinert, Tomás; Campos, Franz; Peixoto, Fábio Affonso; de Andrade, Carlos Augusto; Castro, Thalita; Herchenhorn, Daniel

2016-01-01

The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. Copyright© by the International Brazilian Journal of Urology.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA experience

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Rafael Corrêa Coelho

Full Text Available ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC treated by the Brazilian Unified Health System (SUS at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%, with a median age of 58 years. Nephrectomy was performed in 41 (71% patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2% patients. In 50 patients (86%, sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%, hypothyroidism (43%, mucositis (33% and diarrhea (29%. Grade 3 and 4 adverse effects were infrequent: fatigue (12%, hypertension (12%, thrombocytopenia (7%, neutropenia (5% and hand-foot syndrome (5%. Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Metastatic Renal Cell Carcinoma Presenting as Gastric Ulcer: Case Report and Literature Review

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Alhareth Al Juboori

2017-01-01

Full Text Available Renal cell carcinoma (RCC accounts for approximately 3% of all adult malignancies. True gastrointestinal metastases, specifically to gastric wall, have been rarely observed. Herein we describe a case of delayed metastasis to gastric wall occurring more than a decade after previously curative nephrectomy for RCC. A 67-year-old male with history of right radical nephrectomy in 2001 for RCC was found to have an asymptomatic right lower lobe solitary lung mass upon routine follow-up in 2011, with final biopsy results showing metastatic RCC for which he was treated accordingly. In 2014, patient was evaluated for dyspepsia with microcytic anemia and underwent an esophagogastroduodenoscopy and colonoscopy. EGD revealed a solitary one-centimeter atypical ulcer in the posterior mid gastric body with biopsy results being consistent with metastatic RCC. Our literature review has yielded thirty-six reported cases of RCC in association with gastric wall metastases.

Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

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Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

2017-08-01

To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

Renal Cell Cancer: What Can We Learn from Pre-Operative Studies?

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Fisher, Rosalie; Larkin, James, E-mail: james.larkin@rmh.nhs.uk [Department of Medical Oncology, Royal Marsden Hospital, London (United Kingdom)

2011-12-08

Renal cell carcinoma (RCC) affects approximately 60,000 people in Europe and in the United States each year (Ferlay et al., 2007; Jemal et al., 2010), and is associated with high rates of morbidity and mortality. The incidence of RCC is rising, perhaps because of the widespread use of abdominal imaging, resulting in an increased detection of small renal masses, and surgical intervention for these (Hollingsworth et al., 2006; Falebita et al., 2009). Surgery remains an integral part of the management of RCC, and is the only curative treatment in patients with disease confined to the kidney and its regional vasculature and lymph nodes. However, about 30% of patients are diagnosed with metastatic renal cell carcinoma (mRCC) at presentation (Motzer et al., 1996) and a similar proportion will later develop metastases (Leibovich et al., 2003). Until 2007, a combination of cytoreductive nephrectomy (CN) and immunotherapy, usually interferon-α, was considered to be the standard of care for those patients presenting with mRCC deemed fit enough, although cytokine therapy was associated with modest benefits and much toxicity (Coppin et al., 2005). The basis for nephrectomy in the context of metastatic disease was provided by two similar prospective trials which randomized patients to CN plus interferon or interferon alone. Combined analysis of the two trials demonstrated a median survival of 13.6 months for surgery plus interferon, and 7.8 months for interferon alone (HR = 0.69, 95% CI = 0.55–0.87, p = 0.002; Flanigan et al., 2004). The simplest rationale for why CN might improve survival in mRCC is a reduction in overall tumor burden, thus delaying time to a lethal burden of disease; other theories include a decrease in the amount of tumor shedding and systemic signaling from the primary renal mass, effective palliation of pain, bleeding and paraneoplastic syndromes, and removal of a source of significant immunosuppression. The latter was proposed on the basis of reports

Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America.

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Stadler, Walter M; Figlin, Robert A; McDermott, David F; Dutcher, Janice P; Knox, Jennifer J; Miller, Wilson H; Hainsworth, John D; Henderson, Charles A; George, Jeffrey R; Hajdenberg, Julio; Kindwall-Keller, Tamila L; Ernstoff, Marc S; Drabkin, Harry A; Curti, Brendan D; Chu, Luis; Ryan, Christopher W; Hotte, Sebastien J; Xia, Chenghua; Cupit, Lisa; Bukowski, Ronald M

2010-03-01

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. The most common grade > or =2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

Trends in Testicular Cancer Survival: A Large Population-based Analysis.

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Sui, Wilson; Morrow, David C; Bermejo, Carlos E; Hellenthal, Nicholas J

2015-06-01

To determine whether discrepancies in testicular cancer outcomes between Caucasians and non-Caucasians are changing over time. Although testicular cancer is more common in Caucasians, studies have shown that other races have worse outcomes. Using the Surveillance, Epidemiology, and End Results registry, we identified 29,803 patients diagnosed with histologically confirmed testicular cancer between 1983 and 2011. Of these, 12,650 patients (42%) had 10-year follow-up data. We stratified the patients by age group, stage, race, and year of diagnosis and assessed 10-year overall and cancer-specific survival in each cohort. Cox proportional hazard models were used to determine the relative contributions of each stratum to cancer-specific survival. Predicted overall 10-year survival of Caucasian patients with testicular cancer increased slightly from 88% to 89% over the period studied, whereas predicted cancer-specific 10-year survival dropped slightly from 94% to 93%. In contrast, non-Caucasian men demonstrated larger changes in 10-year overall (84%-86%) and cancer-specific (88%-91%) survival. On univariate analysis, race was significantly associated with testicular cancer death, with non-Caucasian men being 1.69 times more likely to die of testicular cancer than Caucasians (hazard ratio, 1.33-2.16; 95% confidence interval, testicular cancer. These data show a convergence in cancer-specific survival between racial groups over time, suggesting that diagnostic and treatment discrepancies may be improving for non-Caucasians. Copyright © 2015 Elsevier Inc. All rights reserved.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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Marcelo Zerati

2013-07-01

Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

Use of common analgesic medications and ovarian cancer survival

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Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas

2017-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

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Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

2014-11-15

Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

A case–control study of occupation/industry and renal cell carcinoma risk

International Nuclear Information System (INIS)

Karami, Sara; Rothman, Nathanial; Chow, Wong-Ho; Purdue, Mark P; Colt, Joanne S; Schwartz, Kendra; Davis, Faith G; Ruterbusch, Julie J; Munuo, Stella S; Wacholder, Sholom; Stewart, Patricia A; Graubard, Barry I

2012-01-01

The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC). Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC risk using adjusted unconditional logistic regression models. Employment in the agricultural crop production industry for five years or more was associated with RCC (OR = 3.3 [95% CI = 1.0-11.5]) and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for trend with duration of employment = 0.0050). Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (OR RCC = 2.1 [95% CI = 1.0-4.5]; OR ccRCC = 3.1 [95% CI = 1.4-6.8]). Employment in the dry-cleaning industry was also associated with elevated risk (OR RCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; OR ccRCC = 3.0 [95% CI = 1.2-7.4], P for trend = 0.031). Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries. Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and suggest that these associations may be stronger for the ccRCC subtype. Additional studies are needed to confirm

Cross-Validation of Survival Bump Hunting by Recursive Peeling Methods.

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Dazard, Jean-Eudes; Choe, Michael; LeBlanc, Michael; Rao, J Sunil

2014-08-01

We introduce a survival/risk bump hunting framework to build a bump hunting model with a possibly censored time-to-event type of response and to validate model estimates. First, we describe the use of adequate survival peeling criteria to build a survival/risk bump hunting model based on recursive peeling methods. Our method called "Patient Recursive Survival Peeling" is a rule-induction method that makes use of specific peeling criteria such as hazard ratio or log-rank statistics. Second, to validate our model estimates and improve survival prediction accuracy, we describe a resampling-based validation technique specifically designed for the joint task of decision rule making by recursive peeling (i.e. decision-box) and survival estimation. This alternative technique, called "combined" cross-validation is done by combining test samples over the cross-validation loops, a design allowing for bump hunting by recursive peeling in a survival setting. We provide empirical results showing the importance of cross-validation and replication.

Subtype Differentiation of Small (≤ 4 cm) Solid Renal Mass Using Volumetric Histogram Analysis of DWI at 3-T MRI.

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Li, Anqin; Xing, Wei; Li, Haojie; Hu, Yao; Hu, Daoyu; Li, Zhen; Kamel, Ihab R

2018-05-29

The purpose of this article is to evaluate the utility of volumetric histogram analysis of apparent diffusion coefficient (ADC) derived from reduced-FOV DWI for small (≤ 4 cm) solid renal mass subtypes at 3-T MRI. This retrospective study included 38 clear cell renal cell carcinomas (RCCs), 16 papillary RCCs, 18 chromophobe RCCs, 13 minimal fat angiomyolipomas (AMLs), and seven oncocytomas evaluated with preoperative MRI. Volumetric ADC maps were generated using all slices of the reduced-FOV DW images to obtain histogram parameters, including mean, median, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and SD ADC values, as well as skewness, kurtosis, and entropy. Comparisons of these parameters were made by one-way ANOVA, t test, and ROC curves analysis. ADC histogram parameters differentiated eight of 10 pairs of renal tumors. Three subtype pairs (clear cell RCC vs papillary RCC, clear cell RCC vs chromophobe RCC, and clear cell RCC vs minimal fat AML) were differentiated by mean ADC. However, five other subtype pairs (clear cell RCC vs oncocytoma, papillary RCC vs minimal fat AML, papillary RCC vs oncocytoma, chromophobe RCC vs minimal fat AML, and chromophobe RCC vs oncocytoma) were differentiated by histogram distribution parameters exclusively (all p histogram parameters yielded the highest AUC (0.851; sensitivity, 80.0%; specificity, 86.1%). Quantitative volumetric ADC histogram analysis may help differentiate various subtypes of small solid renal tumors, including benign and malignant lesions.

Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

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Beleut Manfred

2012-07-01

Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

2007-01-01

Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score ≥8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage ≥T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA ≤0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT ≤6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS

Operational slack and venture survival

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Azadegan, Arash; Patel, Pankaj; Parida, Vinit

2013-01-01

Slack can act as a double-edged sword. While it can buffer against environmental threats to help ensure business continuity, slack canalso be costly and reduce profitability. In this study, we focus on operational slack, the form related to the firm’s production processes. We investigate the role of operational slack on firm survival during its venture stage, when its survival is significantly challenged by environmental threats. Specifically, we explore how change in three types of environme...

Survival of Sami cancer patients

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Leena Soininen

2012-07-01

Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

Specific Monoclonal Antibody Overcomes the Salmonella enterica Serovar Typhimurium's Adaptive Mechanisms of Intramacrophage Survival and Replication.

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Swarmistha Devi Aribam

Full Text Available Salmonella-specific antibodies play an important role in host immunity; however, the mechanisms of Salmonella clearance by pathogen-specific antibodies remain to be completely elucidated since previous studies on antibody-mediated protection have yielded inconsistent results. These inconsistencies are at least partially attributable to the use of polyclonal antibodies against Salmonella antigens. Here, we developed a new monoclonal antibody (mAb-449 and identified its related immunogen that protected BALB/c mice from infection with Salmonella enterica serovar Typhimurium. In addition, these data indicate that the mAb-449 immunogen is likely a major protective antigen. Using in vitro infection studies, we also analyzed the mechanism by which mAb-449 conferred host protection. Notably, macrophages infected with mAb-449-treated S. Typhimurium showed enhanced pathogen uptake compared to counterparts infected with control IgG-treated bacteria. Moreover, these macrophages produced elevated levels of pro-inflammatory cytokine TNFα and nitric oxide, indicating that mAb-449 enhanced macrophage activation. Finally, the number of intracellular bacteria in mAb-449-activated macrophages decreased considerably, while the opposite was found in IgG-treated controls. Based on these findings, we suggest that, although S. Typhimurium has the potential to survive and replicate within macrophages, host production of a specific antibody can effectively mediate macrophage activation for clearance of intracellular bacteria.

Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-κB signaling pathway.

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Li, Gang; Wang, Ziming; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen

2017-10-01

The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by western blot analysis. The results showed that curcumin significantly increased radiosensitivity of ACHN cells by inhibiting the cell proliferation and DNA damage repair, causing cell cycle arrest at G2/M phase, inducing apoptosis in vitro, and suppressing the growth of xenografts in vivo. In addition, curcumin enhanced radiosensitivity was through markedly inhibiting IR-induced NF-κB signaling by modulating the related protein expressions including NF-κBP65, I-κB, VEGF, COX2, and Bcl-2 in ACHN cells, which was further strengthened by NF-κB inhibitor PDTC treatment. Thus, curcumin may confer radiosensitivity on RCC via inhibition of NF-κB activation and its downstream regulars, suggesting the potential application of curcumin as an adjuvant in radiotherapy of RCC. Copyright © 2017. Published by Elsevier Masson SAS.

Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target.

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Chen, C-H; Fong, L W R; Yu, E; Wu, R; Trott, J F; Weiss, R H

2017-06-22

Targeted therapeutics, such as those abrogating hypoxia inducible factor (HIF)/vascular endothelial growth factor signaling, are initially effective against kidney cancer (or renal cell carcinoma, RCC); however, drug resistance frequently occurs via subsequent activation of alternative pathways. Through genome-scale integrated analysis of the HIF-α network, we identified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) as a potential target molecule for kidney cancer. In a screen of nephrectomy samples from 56 patients with RCC, we found that MARCKS expression and its phosphorylation are increased and positively correlate with tumor grade. Genetic and pharmacologic suppression of MARCKS in high-grade RCC cell lines in vitro led to a decrease in cell proliferation and migration. We further demonstrated that higher MARCKS expression promotes growth and angiogenesis in vivo in an RCC xenograft tumor. MARCKS acted upstream of the AKT/mTOR pathway, activating HIF-target genes, notably vascular endothelial growth factor-A. Following knockdown of MARCKS in RCC cells, the IC50 of the multikinase inhibitor regorafenib was reduced. Surprisingly, attenuation of MARCKS using the MPS (MARCKS phosphorylation site domain) peptide synergistically interacted with regorafenib treatment and decreased survival of kidney cancer cells through inactivation of AKT and mTOR. Our data suggest a major contribution of MARCKS to kidney cancer growth and provide an alternative therapeutic strategy of improving the efficacy of multikinase inhibitors.

Dose-rate dependent stochastic effects in radiation cell-survival models

International Nuclear Information System (INIS)

Sachs, R.K.; Hlatky, L.R.

1990-01-01

When cells are subjected to ionizing radiation the specific energy rate (microscopic analog of dose-rate) varies from cell to cell. Within one cell, this rate fluctuates during the course of time; a crossing of a sensitive cellular site by a high energy charged particle produces many ionizations almost simultaneously, but during the interval between events no ionizations occur. In any cell-survival model one can incorporate the effect of such fluctuations without changing the basic biological assumptions. Using stochastic differential equations and Monte Carlo methods to take into account stochastic effects we calculated the dose-survival rfelationships in a number of current cell survival models. Some of the models assume quadratic misrepair; others assume saturable repair enzyme systems. It was found that a significant effect of random fluctuations is to decrease the theoretically predicted amount of dose-rate sparing. In the limit of low dose-rates neglecting the stochastic nature of specific energy rates often leads to qualitatively misleading results by overestimating the surviving fraction drastically. In the opposite limit of acute irradiation, analyzing the fluctuations in rates merely amounts to analyzing fluctuations in total specific energy via the usual microdosimetric specific energy distribution function, and neglecting fluctuations usually underestimates the surviving fraction. The Monte Carlo methods interpolate systematically between the low dose-rate and high dose-rate limits. As in other approaches, the slope of the survival curve at low dose-rates is virtually independent of dose and equals the initial slope of the survival curve for acute radiation. (orig.)

Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

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Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

2012-12-01

The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review

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Haque, Inamul; Subramanian, Arvind; Huang, Chao H.; Godwin, Andrew K.; Van Veldhuizen, Peter J.; Banerjee, Snigdha; Banerjee, Sushanta K.

2017-01-01

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC. PMID:29301217

Renal cell carcinoma in India demonstrates early age of onset & a late stage of presentation

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Shalini Agnihotri

2014-01-01

Full Text Available Background & objectives: Clinical spectrum of most of the diseases in developing countries is different from the west. Similarly whether renal cell carcinomas (RCC in a developing country like India is seen in the same spectrum in relation to the age at presentation as in the west is not described in the literature. This study was carried out to investigate the spectrum of RCC in India with regards to age of onset, stage at presentation and survival. Methods: Patients with renal tumour, treated between January 2000 to December 2012 in a tertiary care hospital in north India, were analyzed for age at presentation, clinical features and histopathological characteristics. Clinical diagnosis was made by contrast enhanced computerized tomography (CECT scans and/or magnetic resonance imaging (MRI. Renal masses diagnosed as angiomyolipoma, infective masses and hydatid cysts were excluded from the analysis. Impact of various age groups on gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph node, inferior vena cava (IVC involvement and survival was analyzed. Patients were grouped in five age groups i.e. ≤39, 40-49, 50-59, 60-69 and more than 70 yr of age. Results: Of the total 617 patients with 617 renal tumours (2 patients had bilateral tumours but only the larger tumour was considered clinically suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non epithelial cell tumour. The mean tumour size was 8.08±3.5 cm (median 7, range 1-25 cm. Tumour of less than 4 cm size was present in only 10.4 per cent patients. The mean age at diagnosis was 55.15±13.34 (median 56, range 14-91 yr years. A total of 30.03 per cent of renal tumours presented in patients younger than 50 yr of age. Though there was no difference in stage, Fuhrman′s grade, IVC involvement and lymph nodal spread among various age groups, younger patients had higher proportion of non clear cell RCC and only 48.59 per cent of them presented

HU participates in expression of a specific set of genes required for growth and survival at acidic pH in Escherichia coli.

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Bi, Hongkai; Sun, Lianle; Fukamachi, Toshihiko; Saito, Hiromi; Kobayashi, Hiroshi

2009-05-01

The major histone-like Escherichia coli protein, HU, is composed of alpha and beta subunits respectively encoded by hupA and hupB in Escherichia coli. A mutant deficient in both hupA and hupB grew at a slightly slower rate than the wild type at pH 7.5. Growth of the mutant diminished with a decrease in pH, and no growth was observed at pH 4.6. Mutants of either hupA or hupB grew at all pH levels tested. The arginine-dependent survival at pH 2.5 was diminished approximately 60-fold by the deletion of both hupA and hupB, whereas the survival was slightly affected by the deletion of either hupA or hupB. The mRNA levels of adiA and adiC, which respectively encode arginine decarboxylase and arginine/agmatine antiporter, were low in the mutant deficient in both hupA and hupB. The deletion of both hupA and hupB had little effect on survival at pH 2.5 in the presence of glutamate or lysine, and expression of the genes for glutamate and lysine decarboxylases was not impaired by the deletion of the HU genes. These results suggest that HU regulates expression of the specific set of genes required for growth and survival in acidic environments.

Pretreatment tumor SUV{sub max} predicts disease-specific and overall survival in patients with head and neck soft tissue sarcoma

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Ha, Seung Cheol; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon [University of Ulsan College of Medicine, Departments of Otolaryngology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Oh, Jungsu S.; Moon, Hyojeong; Kim, Jae Seung [University of Ulsan College of Medicine, Departments of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Cho, Kyung-Ja [University of Ulsan College of Medicine, Departments of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

2017-01-15

Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. {sup 18}F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using {sup 18}F-FDG PET/CT in patients with HNSTS. This study included 36 consecutive patients with HNSTS who underwent {sup 18}F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUV{sub max}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment {sup 18}F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS). Univariate analyses showed that SUV{sub max}, MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P < 0.05). After controlling for clinicopathological factors, SUV{sub max}, MTV, and TLG were significantly associated with DSS and OS (all P < 0.05). Patients with a tumor SUV{sub max} value of >7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUV{sub max} <7.0. Quantitative metabolic measurements on pretreatment {sup 18}F-FDG PET/CT can yield values that are significantly predictive of survival after treatment for HNSTS. (orig.)

MoSI (Monitoreo de Sobrevivencia Invernal): assessing habitat-specific overwintering survival of neotropical migratory landbirds

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David F. DeSante; T. Scott Sillett; Rodney B. Siegel; James F. Saracco; Claudia A. Romo de Vivar Alvarez; Salvadora Morales; Alexis Cerezo; Danielle R. Kaschube; Manuel Grosselet; Borja Mila

2005-01-01

Recent evidence suggests that population declines in many Neotropical-wintering migratory landbird species are caused by habitat loss and degradation on their wintering grounds. Such habitat loss and degradation can lower overwintering survival rates and cause surviving birds to leave their wintering grounds in poor physical condition, leading to high mortality during...

Brazilian data of renal cell carcinoma in a public university hospital.

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Aguiar, Pedro; Padua, Tiago Costa; Guimaraes, Daiane Pereira

2016-01-01

Among renal malignancies, renal cell carcinoma (RCC) accounts for 85% of cases. Stage is a relevant prognostic factor; 5-year survival ranges from 81% to 8% according to the stage of disease. The treatment is based on surgery and molecularly targeted therapy has emerged as a choice for metastatic disease. Retrospective study by reviewing the medical records of patients with RCC treated in the last 10 years at UNIFESP. The primary end point of this trial was to evaluate the overall survival (OS) of the patients. The secondary end point was to evaluate the progression-free survival (PFS) after nephrectomy. 118 patients with RCC were included. The mean age was 58.3 years, 61.9% men; nephrectomy was performed in 90.7%, clear cell was the histology in 85.6%, 44 patients were classified as stage IV at diagnosis. Among these, 34 had already distant metastasis. 29 patients were treated with sunitinib. The median OS among all patients was 55.8 months. The median PFS after nephrectomy was 79.1 months. Sarcomatoid differentiation HR29.74 (95% CI, 4.31-205.26), clinical stage IV HR1.94 (95% CI, 1.37-2.75) and nephrectomy HR0.32 (95% CI, 0.15-0.67) were OS prognostic factors. Sunitinib had clinical activity. Patients treated in our hospital achieved median OS compatible with literature. Nevertheless, this study has shown a high number of patients with advanced disease. For patients with advanced disease, treatment with sunitinib achieved median OS of 28.7 months, consistent with the literature.

Identification of novel genetic markers of breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Schmidt, Marjanka K; Kraft, Peter

2015-01-01

BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis ......BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta......-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference...... panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24...

Probabilistic Survivability Versus Time Modeling

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Joyner, James J., Sr.

2016-01-01

This presentation documents Kennedy Space Center's Independent Assessment work completed on three assessments for the Ground Systems Development and Operations (GSDO) Program to assist the Chief Safety and Mission Assurance Officer during key programmatic reviews and provided the GSDO Program with analyses of how egress time affects the likelihood of astronaut and ground worker survival during an emergency. For each assessment, a team developed probability distributions for hazard scenarios to address statistical uncertainty, resulting in survivability plots over time. The first assessment developed a mathematical model of probabilistic survivability versus time to reach a safe location using an ideal Emergency Egress System at Launch Complex 39B (LC-39B); the second used the first model to evaluate and compare various egress systems under consideration at LC-39B. The third used a modified LC-39B model to determine if a specific hazard decreased survivability more rapidly than other events during flight hardware processing in Kennedy's Vehicle Assembly Building.

Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival

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Gergana Metodieva

2016-06-01

Full Text Available SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.

A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.

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Kelly Broen

Full Text Available Nonmyeloablative allogeneic stem cell transplantation (SCT can induce remission in patients with renal cell carcinoma (RCC, but this graft-versus-tumor (GVT effect is often accompanied by graft-versus-host disease (GVHD. Here, we evaluated minor histocompatibility antigen (MiHA-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI. One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.

Identification and validation of novel prognostic markers in Renal Cell Carcinoma.

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Rabjerg, Maj

2017-10-01

prognostic molecular markers in RCC and to identify novel targeted therapies by in-vitro studies. This was specifically conducted by investigating; 1) The impact of symptom presentation of RCC on prognosis, 2) The expression of Calcium-activated potassium channels in RCC, the correlation of KCa3.1 to prognosis in ccRCC and the ability of TRAM-34, RA-2 and Paxilline to inhibit the proliferation of ccRCC cell lines in-vitro, 3) The gene expression and prognostic value of 19 selected genes in ccRCC and 4) The expression of the protein kinase CK subunits in subtypes of RCC, the prognostic impact of high protein expression of the CK2α subunit in ccRCC and the ability of CX-4945 and E9 to inhibit ccRCC growth in-vitro. Our molecular study cohort consisted of 155 patients with different subtypes of RCC and the benign renal neoplasm, oncocytoma. They were diagnosed in Region of Southern Denmark in 2001-2013. Frozen tissue from tumor and normal renal cortex parenchyma, together with paraffin-embedded tissue was available for every patient. We performed gene expression analysis by qRT-PCR, immunohistochemical staining of Tissue Micro Arrays, protein kinase activity analysis and functional studies. Study I was performed as a descriptive observational study focusing on the prognostic impact of symptom presentation in RCC. We included 204 patients with renal neoplasms diagnosed in 2011-2012. Incidentally discovered RCC without symptomatic presentation had overall a better prognosis, and presented with smaller tumors, a lower T-stage, lower Fuhrman grade and lower Leibovich score. In addition, the non-symptomatic patient group experienced metastatic disease less frequently. In study II we focused on the expression of two calcium-activated potassium channels in ccRCC and oncocytoma. Both KCa3.1 and KCa1.1 were higher expressed in ccRCC compared to oncocytoma. High expression of KCa3.1 was moreover correlated with poor progression free survival of ccRCC. Functional studies provided new

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure

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Wulff, N B; Andersen, E; Kristensen, C A

2017-01-01

with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.......OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142...... survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease...

The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma

International Nuclear Information System (INIS)

Clayton Smith, D.; Kenneth Macdonald, O.; Gaffney, David K.

2008-01-01

Background and purpose: Uterine carcinosarcoma is an aggressive neoplasm and the benefit of adjuvant radiation therapy (RT) is unclear. This retrospective study analyzes the influence of RT on survival using a large population database. Materials and methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute. Women with uterine carcinosarcoma who underwent primary surgery were eligible. Survival rates and multivariate analyses were performed by standard methods. Results: Of the 2461 women in the analysis, 890 received adjuvant RT. Five-year rates of overall survival were 41.5% and 33.2% (P < 0.001) and uterine-specific survival were 56.0% and 50.8% (P = 0.005), for women receiving RT compared to those who did not. Women with stages I-III disease experienced a benefit in overall survival (HR 0.87, P = 0.03) while women with stage IV disease experienced benefits in overall (HR 0.63, P < 0.001) and uterine-specific survival (HR 0.63, P = 0.004) with RT. Conclusions: RT predicted for improved overall and disease specific survival in women with uterine carcinosarcoma within the SEER database. The benefit in disease specific survival was restricted to stage IV disease. These benefits may indicate a role for adjuvant RT in future prospective trials in the treatment of uterine carcinosarcoma

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Biomarkers of Kidney Cancer.

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Song, Yimeng; Zhong, Lijun; Zhou, Juntuo; Lu, Min; Xing, Tianying; Ma, Lulin; Shen, Jing

2017-12-01

Renal cell carcinoma (RCC) is a malignant and metastatic cancer with 95% mortality, and clear cell RCC (ccRCC) is the most observed among the five major subtypes of RCC. Specific biomarkers that can distinguish cancer tissues from adjacent normal tissues should be developed to diagnose this disease in early stages and conduct a reliable prognostic evaluation. Data-independent acquisition (DIA) strategy has been widely employed in proteomic analysis because of various advantages, including enhanced protein coverage and reliable data acquisition. In this study, a DIA workflow is constructed on a quadrupole-Orbitrap LC-MS platform to reveal dysregulated proteins between ccRCC and adjacent normal tissues. More than 4000 proteins are identified, 436 of these proteins are dysregulated in ccRCC tissues. Bioinformatic analysis reveals that multiple pathways and Gene Ontology items are strongly associated with ccRCC. The expression levels of L-lactate dehydrogenase A chain, annexin A4, nicotinamide N-methyltransferase, and perilipin-2 examined through RT-qPCR, Western blot, and immunohistochemistry confirm the validity of the proteomic analysis results. The proposed DIA workflow yields optimum time efficiency and data reliability and provides a good choice for proteomic analysis in biological and clinical studies, and these dysregulated proteins might be potential biomarkers for ccRCC diagnosis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Survival Processing and the Stroop Task

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Stephanie A. Kazanas

2015-11-01

Full Text Available This study was designed to investigate the impact of survival processing with a novel task for this paradigm: the Stroop color-naming task. As the literature is mixed with regard to task generalizability, with survival processing promoting better memory for words, but not better memory for faces or paired associates, these types of task investigations are important to a growing field of research. Using the Stroop task provides a unique contribution, as identifying items by color is an important evolutionary adaptation and not specific to humans as is the case with word recall. Our results indicate that survival processing, with its accompanying survival-relevance rating task, remains the best mnemonic strategy for word memory. However, our results also indicate that presenting the survival passage does not motivate better color-naming performance than color-naming alone. In addition, survival processing led to a larger amount of Stroop interference, though not significantly larger than the other conditions. Together, these findings suggest that considering one’s survival when performing memory and attention-based tasks does not enhance cognitive performance generally, although greater allocation of attentional resources to color-incongruent concrete objects could be considered adaptive. These findings support the notion that engaging in deeper processing via survival-relevance ratings may preserve these words across a variety of experimental manipulations.

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

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Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

Age-specific survival of male golden-cheeked warblers on the Fort Hood Military Reservation, Texas

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Duarte, Adam; Hines, James E.; Nichols, James D.; Hatfield, Jeffrey S.; Weckerly, Floyd W.

2014-01-01

Population models are essential components of large-scale conservation and management plans for the federally endangered Golden-cheeked Warbler (Setophaga chrysoparia; hereafter GCWA). However, existing models are based on vital rate estimates calculated using relatively small data sets that are now more than a decade old. We estimated more current, precise adult and juvenile apparent survival (Φ) probabilities and their associated variances for male GCWAs. In addition to providing estimates for use in population modeling, we tested hypotheses about spatial and temporal variation in Φ. We assessed whether a linear trend in Φ or a change in the overall mean Φ corresponded to an observed increase in GCWA abundance during 1992-2000 and if Φ varied among study plots. To accomplish these objectives, we analyzed long-term GCWA capture-resight data from 1992 through 2011, collected across seven study plots on the Fort Hood Military Reservation using a Cormack-Jolly-Seber model structure within program MARK. We also estimated Φ process and sampling variances using a variance-components approach. Our results did not provide evidence of site-specific variation in adult Φ on the installation. Because of a lack of data, we could not assess whether juvenile Φ varied spatially. We did not detect a strong temporal association between GCWA abundance and Φ. Mean estimates of Φ for adult and juvenile male GCWAs for all years analyzed were 0.47 with a process variance of 0.0120 and a sampling variance of 0.0113 and 0.28 with a process variance of 0.0076 and a sampling variance of 0.0149, respectively. Although juvenile Φ did not differ greatly from previous estimates, our adult Φ estimate suggests previous GCWA population models were overly optimistic with respect to adult survival. These updated Φ probabilities and their associated variances will be incorporated into new population models to assist with GCWA conservation decision making.

Identification of novel genetic markers of breast cancer survival

NARCIS (Netherlands)

Q. Guo (Qi); M.K. Schmidt (Marjanka); P. Kraft (Peter); S. Canisius (Sander); C. Chen (Constance); S. Khan (Sofia); J.P. Tyrer (Jonathan); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); M. Lush (Michael); S. Kar (Siddhartha); J. Beesley (Jonathan); A.M. Dunning (Alison); M. Shah (Mitul); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); D. Lambrechts (Diether); C. Weltens (Caroline); K. Leunen; S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); C. Blomqvist (Carl); K. Aittomäki (Kristiina); R. Fagerholm (Rainer); T.A. Muranen (Taru); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); A.M.W. van den Ouweland (Ans); F. Marme (Federick); A. Schneeweiss (Andreas); R. Yang (Rongxi); B. Burwinkel (Barbara); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); B. Holleczek (B.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); J. Li (Jingmei); J.S. Brand (Judith S.); M.K. Humphreys (Manjeet); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); P. Mariani (Paolo); P.A. Fasching (Peter); M.W. Beckmann (Matthias); R. Hein (Rebecca); A.B. Ekici (Arif); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); K.-A. Phillips (Kelly-Anne); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); U. Hamann (Ute); M. Kabisch (Maria); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); S. Margolin (Sara); V. Kristensen (Vessela); S. Nord (Silje); D.G. Evans (Gareth); J. Abraham (Jean); H. Earl (Helena); L. Hiller (Louise); J.A. Dunn (J.); S. Bowden (Sarah); C.D. Berg (Christine); D. Campa (Daniele); W.R. Diver (Ryan); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); S.E. Hankinson (Susan); R.N. Hoover (Robert); A. Hüsing (Anika); R. Kaaks (Rudolf); M.J. Machiela (Mitchell J.); W.C. Willett (Walter C.); M. Barrdahl (Myrto); F. Canzian (Federico); S.-F. Chin (Suet-Feung); C. Caldas (Carlos); D. Hunter (David); S. Lindstrom (Stephen); M. García-Closas (Montserrat); P. Hall (Per); D.F. Easton (Douglas); D. Eccles (Diana); N. Rahman (Nazneen); H. Nevanlinna (Heli); P.D.P. Pharoah (Paul)

2015-01-01

textabstractBackground: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large

Superior target delineation for stereotactic body radiotherapy of bone metastases from renal cell carcinoma on MRI compared to CT

NARCIS (Netherlands)

Prins, Fieke M.; Van Der Velden, Joanne M.; Gerlich, Anne S.; Kotte, Alexis N.T.J.; Eppinga, Wietse S.C.; Kasperts, Nicolien; Verlaan, Jorrit J.; Pameijer, Frank A.; Kerkmeijer, Linda G.W.

2017-01-01

Background: In metastatic renal cell carcinoma (mRCC) there has been a treatment shift towards targeted therapy, which has resulted in improved overall survival. Therefore, there is a need for better local control of the tumor and its metastases. Image-guided stereotactic body radiotherapy (SBRT) in

Targeted therapies for renal cell carcinoma: review of adverse event management strategies.

NARCIS (Netherlands)

Eisen, T.; Sternberg, C.N.; Robert, C.; Mulders, P.F.; Pyle, L.; Zbinden, S.; Izzedine, H.; Escudier, B.

2012-01-01

With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted

mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

Energy Technology Data Exchange (ETDEWEB)

Lamuraglia, M. [Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France); Raslan, S.; Penna, R.R.; Wagner, M. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Elaidi, R.; Oudard, S. [APHP, Oncology Unit, Georges-Pompidou Hospital, Paris (France); Escudier, B. [Gustave-Roussy Institute, Medical Oncology Department, Villejuif (France); Slimane, K. [Novartis Pharma, Rueil-Malmaison (France); Lucidarme, O. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France)

2016-01-15

To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. (orig.)

Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma.

Science.gov (United States)

Liu, Qingqing; Cornejo, Kristine M; Cheng, Liang; Hutchinson, Lloyd; Wang, Mingsheng; Zhang, Shaobo; Tomaszewicz, Keith; Cosar, Ediz F; Woda, Bruce A; Jiang, Zhong

2018-04-01

Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor-suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Landscape‐level patterns in fawn survival across North America

Science.gov (United States)

Gingery, Tess M.; Diefenbach, Duane R.; Wallingford, Bret D.; Rosenberry, Christopher S.

2018-01-01

A landscape‐level meta‐analysis approach to examining early survival of ungulates may elucidate patterns in survival not evident from individual studies. Despite numerous efforts, the relationship between fawn survival and habitat characteristics remains unclear and there has been no attempt to examine trends in survival across landscape types with adequate replication. In 2015–2016, we radiomarked 98 white‐tailed deer (Odocoileus virginianus) fawns in 2 study areas in Pennsylvania. By using a meta‐analysis approach, we compared fawn survival estimates from across North America using published data from 29 populations in 16 states to identify patterns in survival and cause‐specific mortality related to landscape characteristics, predator communities, and deer population density. We modeled fawn survival relative to percentage of agricultural land cover and deer density. Estimated average survival to 3–6 months of age was 0.414 ± 0.062 (SE) in contiguous forest landscapes (no agriculture) and for every 10% increase in land area in agriculture, fawn survival increased 0.049 ± 0.014. We classified cause‐specific mortality as human‐caused, natural (excluding predation), and predation according to agriculturally dominated, forested, and mixed (i.e., both agricultural and forest cover) landscapes. Predation was the greatest source of mortality in all landscapes. Landscapes with mixed forest and agricultural cover had greater proportions and rates of human‐caused mortalities, and lower proportions and rates of mortality due to predators, when compared to forested landscapes. Proportion and rate of natural deaths did not differ among landscapes. We failed to detect any relationship between fawn survival and deer density. The results highlight the need to consider multiple spatial scales when accounting for factors that influence fawn survival. Furthermore, variation in mortality sources and rates among landscapes indicate the potential for

NSS for an RCC in a patient with renal insufficiency after heart transplant because of right ventricular tumor.

Science.gov (United States)

Prokopowicz, Grzegorz; Zyczkowski, Marcin; Nowakowski, Krzysztof; Bryniarski, Piotr; Paradysz, Andrzej

2013-01-01

The effect of the immunosuppressive therapy on the development of neoplasms has become the object of an ever increasing interest for clinicians all over the world. The literature on neoplasms development in the course of therapy following transplants has confirmed a considerable increase in the incidence of neoplasms of the skin and lymph nodes. Organ neoplasms developing in patients after transplants are characterized by increased progression, poor cellular diversification and a more unfavorable prognosis than in the general population The aim of the study is to present the case of a nephron-sparing surgery of a renal tumor (NSS) without any intraoperative ischaemia in a 55-year-old female patient with an orthotopic heart transplant and renal insufficiency following a prolonged immune suppression. It is estimated that the patients at the highest risk of neoplasm development are those in the first months after transplant, especially heart transplant. They require maximum doses of immunosuppressive drugs. In the case of patients with initial renal insufficiency the duration of ischaemia of the organ operated on should be minimized, and if possible, surgery should be conducted without clamping the renal pedicle. The surgical treatment of RCC (renal cell carcinoma) in transplant patients does not require any reduction in the amount of the immunosuppressive drugs.

Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

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Clara E. Jäkel

2012-01-01

Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

Does Your Domestic Photovoltaic Energy System Survive Grid Outages?

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Marijn R. Jongerden

2016-09-01

Full Text Available Domestic renewable energy systems, including photovoltaic energy generation, as well as local storage, are becoming increasingly popular and economically feasible, but do come with a wide range of options. Hence, it can be difficult to match their specification to specific customer’s needs. Next to the usage-specific demand profiles and location-specific production profiles, local energy storage through the use of batteries is becoming increasingly important, since it allows one to balance variations in production and demand, either locally or via the grid. Moreover, local storage can also help to ensure a continuous energy supply in the presence of grid outages, at least for a while. Hybrid Petri net (HPN models allow one to analyze the effect of different battery management strategies on the continuity of such energy systems in the case of grid outages. The current paper focuses on one of these strategies, the so-called smart strategy, that reserves a certain percentage of the battery capacity to be only used in case of grid outages. Additionally, we introduce a new strategy that makes better use of the reserved backup capacity, by reducing the demand in the presence of a grid outage through a prioritization mechanism. This new strategy, called power-save, only allows the essential (high-priority demand to draw from the battery during power outages. We show that this new strategy outperforms previously-proposed strategies through a careful analysis of a number of scenarios and for a selection of survivability measures, such as minimum survivability per day, number of survivable hours per day, minimum survivability per year and various survivability quantiles.

Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival.

Science.gov (United States)

White, Michael G; Cipriani, Nicole A; Abdulrasool, Layth; Kaplan, Sharone; Aschebrook-Kilfoy, Briseis; Angelos, Peter; Kaplan, Edwin L; Grogan, Raymon H; Onel, Kenan

2016-08-01

Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC

Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma

Science.gov (United States)

WANG, DONGCHUN; WANG, CHANGSONG; PI, XIN; GUO, LEI; WANG, YUE; LI, MINGJUAN; FENG, YUE; LIN, ZIWEI; HOU, WEI; LI, ENYOU

2016-01-01

Currently, there is no adequate, sensitive, reproducible, specific and noninvasive biomarker that can reliably be used to detect renal cell carcinoma (RCC). Previous studies have elucidated the urinary non-volatile metabolic profile of RCC. However, whether urinary volatile organic compound (VOC) profiles are able to identify RCC remains to be elucidated. In the present study, urine was collected from 22 patients with RCC and 25 healthy subjects. Principal component analysis and orthogonal partial least square discriminant analysis were used to compare the data of patients and healthy subjects, and preoperative and postoperative patients undergoing radical nephrectomy. In total, 11 VOC biomarkers were elevated in the RCC patients compared to the healthy subjects, which were phenol; decanal; 1,6-dioxacyclododecane-7,12-dione; 1-bromo-1-(3-methyl-1-pentenylidene)-2,2,3,3-tetramethyl-cyclopropane; nonanal; 3-ethyl-3-methylheptane; isolongifolene-5-ol; 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethylethyl); tetradecane; aniline; and 2,6,10,14-tetramethyl-pentadecane. Three biomarkers were decreased in RCC patients: styrene, 4-heptanone and dimethylsilanediol. In preoperative patients, 2-ethyl-1-hexanol and cyclohexanone were elevated, while 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne were decreased when compared to postoperative patients. Compared with the healthy subjects, RCC has a unique VOC profile, suggesting that VOC profiles may be a useful diagnostic assay for RCC. PMID:27347408

Harnessing the p53-PUMA Axis to Overcome DNA Damage Resistance in Renal Cell Carcinoma

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Xiaoguang Zhou

2014-12-01

Full Text Available Resistance to DNA damage–induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC. This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage–induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA. We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage–induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients.

Clinical efficacy of sunitinib combined with autologous DC and CIK for patients with metastatic renal cell carcinoma

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Liang ZHANG

2014-01-01

Full Text Available Objective　To analyze the clinical efficacy and safety of sunitinib combined with autologous dentritic cell (DC and cytokine induced killer cell (CIK for patients suffering from metastatic renal cell carcinoma (mRCC. Methods　Clinical data of 27 mRCC patients treated with sunitinib combined with autologous DC and CIK were reviewed retrospectively. Efficacy, quality of life, immunology and safety of this treatment were evaluated. Results　Follow-up time ranged from 4 to 25 months. Out of all the patients, sunitinib was reduced in 1 and discontinued in 2 due to side effects; 1 patient quit for personal reasons; 14 patients developed progressive disease. The progression-free survival (PFS was 4 to 19.5 months. Ten patients died from tumor, the overall survival time (OS was 6 to 21 months. The median PFS was 16 months (95%CI 12.5-19.5. The OS was not achieved. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST. All the patients received treatment over 1 cycle. After one course of treatment, among 27 patients, 0 had complete remission (CR, 4 had partial remission (PR, 17 had stable disease (SD, and 6 had progressive disease (PD. The overall objective remission rate (ORR and disease control rate (DCR were 14.8% (4/27 and 77.8% (21/27, respectively. Sunitinib and autologous transfusion of DC and CIK improved the immune function and quality of life. The major adverse events were fatigue, hand-foot syndrome, hypertension, hypothyroidism, thrombocytopenia, neutropenia and fever. Most of the adverse events were ameliorated by supportive treatment or dose reduction. Conclusions　 Sunitinib combined with autologous DC and CIK may be beneficial in the treatment of mRCC with acceptable toxic reactions, and it may be considered as a new approach for the comprehensive treatment of RCC. DOI: 10.11855/j.issn.0577-7402.2013.12.06

C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis.

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Wang, Zhun; Peng, Shuanghe; Wang, Aixiang; Xie, Hui; Guo, Linpei; Jiang, Ning; Niu, Yuanjie

2017-12-01

The prognostic value of C-reactive protein (CRP) in metastatic renal cell carcinoma (RCC) patients receiving tyrosine kinase inhibitors (TKIs) has been investigated in previous studies; however, the results remain inconclusive. This study investigated the prognostic value of pretreatment CRP in patients with metastatic RCC treated with TKIs. PubMed, Embase, Web of Science, and Cochrane databases were searched for studies investigating the relationships between pretreatment CRP and prognosis in patients with metastatic RCC. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted from eligible studies. Heterogeneity was assessed using the I 2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1199 patients from nine studies were included in the analysis. The results showed that an elevated CRP level was an effective prognostic marker of both OS (pooled HR=2.87, 95% confidence interval [CI]: 2.34-3.54, p<0.001) and PFS (pooled HR=2.39, 95% CI: 1.75-3.26, p<0.001). Subgroup analysis revealed that an elevated CRP level significantly predicted poor OS and PFS in studies conducted in Japan (OS, pooled HR=3.03, 95% CI: 2.29-4.01, p<0.001; PFS, pooled HR=3.6, 95% CI: 1.62-8.0, p=0.002), and in cut-off value of CRP <0.8 (OS, pooled HR=2.93, 95% CI: 2.21-3.88, p<0.001; PFS, pooled HR=2.57, 95% CI: 1.82-3.65, p<0.001). This study suggests that an elevated CRP level is correlated with poor prognosis in patients with metastatic RCC receiving TKIs treatment. Copyright © 2017. Published by Elsevier B.V.

Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

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Sandy Azzi

2015-06-01

Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

Patients undergoing radical prostatectomy have a better survival than the background population

DEFF Research Database (Denmark)

Andreas Røder, Martin; Brasso, Klaus; Drimer Berg, Kasper

2013-01-01

underwent radical prostatectomy. Patients were followed prospectively per protocol. No patients were lost to follow-up. Overall and cause-specific survival were described using Kaplan-Meier plots. Standardized relative survival and mortality ratio were calculated based on expected survival in the age......INTRODUCTION: The objective of this study was to investigate standardised relative survival and mortality ratio for patients undergoing radical prostatectomy for localized prostate cancer at our institution. MATERIAL AND METHODS: Between 1995 and 2010, a total of 1,350 consecutive patients......-matched Danish population using the methods and macros described by Dickmann. The country-specific population mortality rates used for calculation of the expected survival were based on data from The Human Mortality Database. RESULTS: The median follow-up was 3.4 years (range: 0-14.3 years). A total of 59 (4...

A generic RNA-pulsed dendritic cell vaccine strategy for renal cell carcinoma

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Geiger, Christiane; Regn, Sybille; Weinzierl, Andreas; Noessner, Elfriede; Schendel, Dolores J

2005-01-01

We present a generic dendritic cell (DC) vaccine strategy for patients with renal cell carcinoma (RCC) based on the use of RNA as a source of multiplex tumor-associated antigens (TAAs). Instead of preparing RNA from tumor tissue of each individual RCC patient, we propose to substitute RNA prepared from a well characterized highly immunogenic RCC cell line (RCC-26 tumor cells) as a generic source of TAAs for loading of DCs. We demonstrate here that efficient RNA transfer can be achieved using lipofection of immature DCs, which are subsequently matured with a cytokine cocktail to express high levels of MHC and costimulatory molecules as well as the chemokine receptor CCR7. Neither RNA itself nor the lipid component impacted on the phenotype or the cytokine secretion of mature DCs. Following RNA loading, DCs derived from HLA-A2-positive donors were able to activate effector-memory cytotoxic T lymphocytes (CTLs) specific for a TAA ligand expressed by the RCC-26 cell line. CTL responses to RNA-loaded DCs reached levels comparable to those stimulated directly by the RCC-26 tumor cells. Furthermore, DCs expressing tumor cell RNA primed naïve T cells, yielding T cell lines with cytotoxicity and cytokine secretion after contact with RCC tumor cells. RCC-26 cell lines are available as good manufacturing practice (GMP)-certified reagents enabling this source of RNA to be easily standardized and adapted for clinical testing. In addition, well defined immune monitoring tools, including the use of RNA expressing B cell lines, are available. Thus, this DC vaccine strategy can be directly compared with an ongoing gene therapy trial using genetically-engineered variants of the RCC-26 cell line as vaccines for RCC patients with metastatic disease. PMID:16045799

A generic RNA-pulsed dendritic cell vaccine strategy for renal cell carcinoma

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Noessner Elfriede

2005-07-01

Full Text Available Abstract We present a generic dendritic cell (DC vaccine strategy for patients with renal cell carcinoma (RCC based on the use of RNA as a source of multiplex tumor-associated antigens (TAAs. Instead of preparing RNA from tumor tissue of each individual RCC patient, we propose to substitute RNA prepared from a well characterized highly immunogenic RCC cell line (RCC-26 tumor cells as a generic source of TAAs for loading of DCs. We demonstrate here that efficient RNA transfer can be achieved using lipofection of immature DCs, which are subsequently matured with a cytokine cocktail to express high levels of MHC and costimulatory molecules as well as the chemokine receptor CCR7. Neither RNA itself nor the lipid component impacted on the phenotype or the cytokine secretion of mature DCs. Following RNA loading, DCs derived from HLA-A2-positive donors were able to activate effector-memory cytotoxic T lymphocytes (CTLs specific for a TAA ligand expressed by the RCC-26 cell line. CTL responses to RNA-loaded DCs reached levels comparable to those stimulated directly by the RCC-26 tumor cells. Furthermore, DCs expressing tumor cell RNA primed naïve T cells, yielding T cell lines with cytotoxicity and cytokine secretion after contact with RCC tumor cells. RCC-26 cell lines are available as good manufacturing practice (GMP-certified reagents enabling this source of RNA to be easily standardized and adapted for clinical testing. In addition, well defined immune monitoring tools, including the use of RNA expressing B cell lines, are available. Thus, this DC vaccine strategy can be directly compared with an ongoing gene therapy trial using genetically-engineered variants of the RCC-26 cell line as vaccines for RCC patients with metastatic disease.

Surgical Treatment of Renal Cell Carcinoma with Inferior Vena Cava Thrombus: Using Liver Mobilization Technique to Avoid Cardiopulmonary Bypass

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Tawatchai Taweemonkongsap

2008-04-01

CONCLUSION: These results support the aggressive surgical removal of RCC with IVC thrombus as the initial treatment. Most of the thrombi can be approached and safely controlled by a transabdominal approach without any form of bypass. Tumour thrombus removal provides a high survival chance and offers improvement in quality of life.

Neoadjuvant targeted therapy in patients with renal cell carcinoma

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B. Ya. Alekseev

2015-01-01

surgery. Unquestionably, elaboration of precise recommendations for neoadjuvant therapy calls for further larger prospective studies estimating progression and survival rates in high-risk patients with localized and locally advanced RCC and in those with mRCC.

Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

International Nuclear Information System (INIS)

Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

2007-01-01

Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses

Linking age, survival, and transit time distributions

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Calabrese, Salvatore; Porporato, Amilcare

2015-10-01

Although the concepts of age, survival, and transit time have been widely used in many fields, including population dynamics, chemical engineering, and hydrology, a comprehensive mathematical framework is still missing. Here we discuss several relationships among these quantities by starting from the evolution equation for the joint distribution of age and survival, from which the equations for age and survival time readily follow. It also becomes apparent how the statistical dependence between age and survival is directly related to either the age dependence of the loss function or the survival-time dependence of the input function. The solution of the joint distribution equation also allows us to obtain the relationships between the age at exit (or death) and the survival time at input (or birth), as well as to stress the symmetries of the various distributions under time reversal. The transit time is then obtained as a sum of the age and survival time, and its properties are discussed along with the general relationships between their mean values. The special case of steady state case is analyzed in detail. Some examples, inspired by hydrologic applications, are presented to illustrate the theory with the specific results. This article was corrected on 11 Nov 2015. See the end of the full text for details.

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

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Naik, Mihir, E-mail: naikm@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Garcia, Jorge; Grivas, Petros [Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephenson, Andrew J.; Klein, Eric A. [Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Tendulkar, Rahul D. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

2016-11-01

Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early

Malignant lipogenesis defined by {sup 11}C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy

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Regula, Naresh [Uppsala University, Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala (Sweden); Haeggman, Michael [Uppsala University, Section of Urology, Department of Surgical Sciences, Uppsala (Sweden); Johansson, Silvia [Uppsala University, Section of Oncology, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Soerensen, Jens [Uppsala University, Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala (Sweden); PET Center Research Department, Uppsala (Sweden)

2016-11-15

Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. {sup 11}C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse {sup 11}C-acetate PET/CT image metrics in relation to survival. All patients undergoing {sup 11}C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding {sup 11}C-acetate uptake intensity (SUV{sub max}) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUV{sub max} x TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis. A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 ± 4.35 ng/mL. The median follow-up of the study population was 79 ± 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUV{sub max} (r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045). Malignant {sup 11}C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a

Age-specific survival of male Golden-cheeked Warblers on the Fort Hood Military Reservation, Texas

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Adam Duarte

2014-12-01

Full Text Available Population models are essential components of large-scale conservation and management plans for the federally endangered Golden-cheeked Warbler (Setophaga chrysoparia; hereafter GCWA. However, existing models are based on vital rate estimates calculated using relatively small data sets that are now more than a decade old. We estimated more current, precise adult and juvenile apparent survival (Φ probabilities and their associated variances for male GCWAs. In addition to providing estimates for use in population modeling, we tested hypotheses about spatial and temporal variation in Φ. We assessed whether a linear trend in Φ or a change in the overall mean Φ corresponded to an observed increase in GCWA abundance during 1992-2000 and if Φ varied among study plots. To accomplish these objectives, we analyzed long-term GCWA capture-resight data from 1992 through 2011, collected across seven study plots on the Fort Hood Military Reservation using a Cormack-Jolly-Seber model structure within program MARK. We also estimated Φ process and sampling variances using a variance-components approach. Our results did not provide evidence of site-specific variation in adult Φ on the installation. Because of a lack of data, we could not assess whether juvenile Φ varied spatially. We did not detect a strong temporal association between GCWA abundance and Φ. Mean estimates of Φ for adult and juvenile male GCWAs for all years analyzed were 0.47 with a process variance of 0.0120 and a sampling variance of 0.0113 and 0.28 with a process variance of 0.0076 and a sampling variance of 0.0149, respectively. Although juvenile Φ did not differ greatly from previous estimates, our adult Φ estimate suggests previous GCWA population models were overly optimistic with respect to adult survival. These updated Φ probabilities and their associated variances will be incorporated into new population models to assist with GCWA conservation decision making.

FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

International Nuclear Information System (INIS)

Chen, James L; Appelbaum, Daniel E; Kocherginsky, Masha; Cowey, Charles L; Kimryn Rathmell, Wendy; McDermott, David F; Stadler, Walter M

2013-01-01

The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([ 18 F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability. In this phase II trial, FDG-PET was explored as a predictive biomarker

Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

Science.gov (United States)

Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

2016-10-01

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-x L , and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-x L overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

Trends in adult leukemia incidence and survival in Denmark, 1943-2003

DEFF Research Database (Denmark)

Thygesen, Lau Caspar; Nielsen, Ove Juul; Johansen, Christoffer

2009-01-01

The etiology of leukemia is largely unknown. Ecological data indicating trends in incidence and survival can provide information about changes in risk factors, can reflect underlying changes in diagnostic classification, and can measure therapeutic advances. From the records of the Danish Cancer...... Registry with registration starting from 1943, we calculated age-specific, period-specific, and age-standardized (world standard) incidence rates of chronic lymphoid leukemia (CLL), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and acute myeloid leukemia (AML) for persons above the age...... of 18. Kaplan-Meier survival curves and median survival times were calculated. Between 1943 and 2003, there were 26,036 cases of leukemia reported. The age-specific incidence rates of CLL, CML, and AML were higher for older men and women, while the incidence rates of ALL by age were more homogeneous...

Genetic basis of cancer of the kidney: disease-specific approaches to therapy.

Science.gov (United States)

Linehan, W Marston; Vasselli, James; Srinivasan, Ramaprasad; Walther, McClellan M; Merino, Maria; Choyke, Peter; Vocke, Cathy; Schmidt, Laura; Isaacs, Jennifer S; Glenn, Gladys; Toro, Jorge; Zbar, Berton; Bottaro, Donald; Neckers, Len

2004-09-15

Studies during the past two decades have shown that kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in this organ. Clear cell renal carcinoma is characterized by mutation of the VHL gene. The VHL gene product forms a heterotrimeric complex with elongin C, elongin B, and Cul-2 to target hypoxia-inducible factors 1 and 2alpha for ubiquitin-mediated degradation. VHL-/- clear cell renal carcinoma overexpresses epidermal growth factor receptor and transforming growth factor alpha. Both hypoxia-inducible factor 1alpha and the epidermal growth factor receptor are potential therapeutic targets in clear cell renal carcinoma. Studies of the hereditary form of renal cell carcinoma (RCC) associated with hereditary papillary renal carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the gene for HPRC and for a number of sporadic papillary RCCs. The HPRC c-Met mutations are activating mutations in the tyrosine kinase domain of the gene. The gene for a new form of hereditary RCC (Birt Hogg Dubé syndrome) associated with cutaneous tumors, lung cysts, and colon polyps or cancer has recently been identified. Studies are currently under way to determine what type of gene BHD is and how damage to this gene leads to kidney cancer. Individuals affected with hereditary leiomyomatosis renal cell carcinoma are at risk for the development of cutaneous leiomyomas, uterine leiomyomas (fibroids), and type 2 papillary RCC. The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase. Studies are under way to understand the downstream pathway of this cancer gene.

Dramatic impact of blood transfusion on cancer-specific survival after radical cystectomy irrespective of tumor stage.

Science.gov (United States)

Buchner, Alexander; Grimm, Tobias; Schneevoigt, Birte-Swantje; Wittmann, Georg; Kretschmer, Alexander; Jokisch, Friedrich; Grabbert, Markus; Apfelbeck, Maria; Schulz, Gerald; Gratzke, Christian; Stief, Christian G; Karl, Alexander

2017-04-01

The aim of the present study was to determine the influence of intraoperative and postoperative blood transfusion on cancer-specific outcome. Follow-up data were collected from 722 patients undergoing radical cystectomy for urothelial carcinoma of the bladder (UCB) between 2004 and 2014. Median follow-up was 26 months (interquartile range 12-61 months). Outcome was analyzed in relation to the amount of intraoperative and postoperative blood transfusion and different tumor stages. The primary endpoint was cancer-specific survival (CSS) after cystectomy. Kaplan-Meier analysis with log-rank test and Cox regression models were used. Intraoperative blood transfusion was given in 36% (263/722) and postoperative blood transfusion in 18% (132/722). In patients with and without intraoperative blood transfusion, 5 year CSS was 48% and 67%, respectively (p blood transfusion, 5 year CSS was 48% and 63%, respectively (p transfused red blood cell (RBC) units [intraoperatively: hazard ratio (HR) = 1.08, 95% confidence interval (CI) 1.01-1.15, p = .023; postoperatively: HR = 1.14, 95% CI 1.07-1.21, p transfusions was also found in favorable subgroups (pT1 tumor, hemoglobin ≥13 mg/dl, p = .004) and in a high-volume surgeon subgroup (n = 244, p Blood transfusions during and after radical cystectomy were independent prognostic factors for CSS in this retrospective study. Therefore, efforts should be made to reduce the necessity of intraoperative and postoperative blood transfusion in cystectomy patients.

Estramustine-binding protein (EMBP) in renal cell carcinoma immunohistochemistry, immunoscintigraphy and in vitro estramustine effects

International Nuclear Information System (INIS)

Edgren, M.; Westlin, J.E.; Letocha, H.; Nordgren, H.; Kaelkner, K.M.; Nilsson, S.

1996-01-01

The present report shows that the human renal cell carcinoma (RCC) cell lines, A498 and CAKI-2, express the estramustine-binding protein (EMBP). The RCC cell lines investigated were highly sensitive for estramustine, with cell arrest in atypical metaphase. In vitro experiments using a fluorimetric cytotoxicity assay (FMCA) showed a pronounced cytotoxic effect mediate by estramustine. Immunohistochemical analysis of tumoru specimens from patients with RCC showed positive staining for EMBP in 12/16 cases. Immunoscintigraphy was performed in an experimental system in nude mice, heterotransplanted with the CAKI-2 cell line. A radiolabelled monoclonal anti-EMBP antibody was used. The results show a specific uptake of the antibody in the RCC tumour, expressed as a percentage of the injected dose per gram tissue, which ranged from 4.03 to 6.9. The results obtained from the basis for clinical studies on the feasibility of utilizing estramustine in the management of RCC. Immunoscintigraphy using the monoclonal anti-EMBP antibody is of potential use for in vivo characterization of the malignancy and in the selection patients suitable for treatment with estramustine. (orig.)

Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

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Adrien eFrançois

2013-12-01

Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

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Oliveira Jorge

2007-07-01

Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT)

DEFF Research Database (Denmark)

Schou Karlsen, Nikoline Marie; Karlsen, Mona Aarenstrup; Høgdall, Estrid

2016-01-01

.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour...... presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. CONCLUSIONS...

CT-guided radiofrequency ablation of T1a renal cell carcinma in Korea; Mid-erm outcomes

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Kim, Hae Jin; Park, Byung Kwan; Park, Jung Jae; Kim, Chan Kyo [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2016-09-15

To evaluate the mid-term outcomes of percutaneous radiofrequency ablation (RFA) treatment in patients with small (< 4 cm) renal cell carcinoma (RCC) in Korea. Between 2010 and 2015, 51 patients (40 men and 11 women; median age, 57 years) with biopsyproven 51 RCC were treated using CT-guided RFA. All patients were clinically staged T1aN0M0 prior to RFA. The median tumor size and follow-up period were 2.1 cm (range, 1.0–3.9 cm) and 26 months (4–60 months), respectively. Local tumor progression, distant metastasis, primary and secondary effectiveness rates, and major complication rates were recorded. Estimated glomerular filtration rates (GFRs) between pre-RFA and last follow-up were compared using paired t tests. The 2-year recurrence-free survival rate was calculated using Kaplan-Meier survival analysis. Of the 51 patients, 2 (3.9%) experienced local tumor progression, and 1 (2.0%) had lymph node metastasis after the first RFA session. Primary and secondary effectiveness rates were 96.1% (49/51) and 100% (1/1), respectively. Only 1 patient experienced a major complication (uretero-pelvic stricture) after the second RFA session for treating a local tumor progression, and the major complication rate was 1.9% (1/52). The median pre-RFA and last follow-up GFRs were 87.1 mL/ min/1.73 m{sup 2} (14.2–142.7 mL/min/1.73 m{sup 2}) and 72.0 mL/min/1.73 m{sup 2} (7.2–112.6 mL/min/1.73 m{sup 2}), respectively (p < 0.0001). The 2-year recurrence-free survival rate was 96.0%. CT-guided RFA is a safe and effective treatment in Korean patients with T1a RCC because of excellent mid-term outcomes.

CT-Guided Radiofrequency Ablation of T1a Renal Cell Carcinoma in Korea: Mid-Term Outcomes

Energy Technology Data Exchange (ETDEWEB)

Kim, Hae Jin; Park, Byung Kwan; Park, Jung Jae; Kim, Chan Kyo [Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of)

2016-11-01

To evaluate the mid-term outcomes of percutaneous radiofrequency ablation (RFA) treatment in patients with small (< 4 cm) renal cell carcinoma (RCC) in Korea. Between 2010 and 2015, 51 patients (40 men and 11 women; median age, 57 years) with biopsyproven 51 RCC were treated using CT-guided RFA. All patients were clinically staged T1aN0M0 prior to RFA. The median tumor size and follow-up period were 2.1 cm (range, 1.0–3.9 cm) and 26 months (4–60 months), respectively. Local tumor progression, distant metastasis, primary and secondary effectiveness rates, and major complication rates were recorded. Estimated glomerular filtration rates (GFRs) between pre-RFA and last follow-up were compared using paired t tests. The 2-year recurrence-free survival rate was calculated using Kaplan-Meier survival analysis. Of the 51 patients, 2 (3.9%) experienced local tumor progression, and 1 (2.0%) had lymph node metastasis after the first RFA session. Primary and secondary effectiveness rates were 96.1% (49/51) and 100% (1/1), respectively. Only 1 patient experienced a major complication (uretero-pelvic stricture) after the second RFA session for treating a local tumor progression, and the major complication rate was 1.9% (1/52). The median pre-RFA and last follow-up GFRs were 87.1 mL/ min/1.73 m{sup 2} (14.2–142.7 mL/min/1.73 m{sup 2}) and 72.0 mL/min/1.73 m{sup 2} (7.2–112.6 mL/min/1.73 m{sup 2}), respectively (p < 0.0001). The 2-year recurrence-free survival rate was 96.0%. CT-guided RFA is a safe and effective treatment in Korean patients with T1a RCC because of excellent mid-term outcomes.

CT-Guided Radiofrequency Ablation of T1a Renal Cell Carcinoma in Korea: Mid-Term Outcomes

International Nuclear Information System (INIS)

Kim, Hae Jin; Park, Byung Kwan; Park, Jung Jae; Kim, Chan Kyo

2016-01-01

To evaluate the mid-term outcomes of percutaneous radiofrequency ablation (RFA) treatment in patients with small (< 4 cm) renal cell carcinoma (RCC) in Korea. Between 2010 and 2015, 51 patients (40 men and 11 women; median age, 57 years) with biopsyproven 51 RCC were treated using CT-guided RFA. All patients were clinically staged T1aN0M0 prior to RFA. The median tumor size and follow-up period were 2.1 cm (range, 1.0–3.9 cm) and 26 months (4–60 months), respectively. Local tumor progression, distant metastasis, primary and secondary effectiveness rates, and major complication rates were recorded. Estimated glomerular filtration rates (GFRs) between pre-RFA and last follow-up were compared using paired t tests. The 2-year recurrence-free survival rate was calculated using Kaplan-Meier survival analysis. Of the 51 patients, 2 (3.9%) experienced local tumor progression, and 1 (2.0%) had lymph node metastasis after the first RFA session. Primary and secondary effectiveness rates were 96.1% (49/51) and 100% (1/1), respectively. Only 1 patient experienced a major complication (uretero-pelvic stricture) after the second RFA session for treating a local tumor progression, and the major complication rate was 1.9% (1/52). The median pre-RFA and last follow-up GFRs were 87.1 mL/ min/1.73 m 2 (14.2–142.7 mL/min/1.73 m 2 ) and 72.0 mL/min/1.73 m 2 (7.2–112.6 mL/min/1.73 m 2 ), respectively (p < 0.0001). The 2-year recurrence-free survival rate was 96.0%. CT-guided RFA is a safe and effective treatment in Korean patients with T1a RCC because of excellent mid-term outcomes

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro.

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Calkoen, F G J; Vervat, C; van Pel, M; de Haas, V; Vijfhuizen, L S; Eising, E; Kroes, W G M; 't Hoen, P A C; van den Heuvel-Eibrink, M M; Egeler, R M; van Tol, M J D; Ball, L M

2015-03-01

Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets. Copyright © 2015. Published by Elsevier B.V.

Clinical and economic analysis of effectiveness of Nivolumab (Opdivo® use as second-line monotherapy in adult patients with advanced renal cell carcinoma after previous systemic therapy

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M. Yu. Frolov

2017-01-01

Full Text Available Objecktive. To conduct a comparative pharmacoeconomic analysis of using nivolumab (Opdivo® as monotherapy in advanced renal cell carcinoma (RCC in adult patients 2-line therapy.Materials and methods. “Cost–effectiveness” was assessed using a Markov model for one patient with advanced RCC. “Cost–effectiveness” analysis, “cost–utility” analysis “budget impact” analysis were performed. Overall survival and QALYs were included into the model as the effectiveness criteria. All the direct costs were calculated from the Russian healthcare system perspective.Results. Treatment with nivolumab was associated with lower total direct costs, less frequent adverse events compared with the combination lenvatinib + everolimus. Total costs per patient were 2 451 712 rubles and 5232592 rubles for nivolumab and the combination lenvatinib + everolimus, respectively. The incremental “cost–effectiveness” ratio was 5 561760 rubles per life-months gained and 2339823 rubles per quality-adjusted life month. A sensitivity analysis confirmed the base case results. “Budget impact” analysis showed that the using of nivolumab allows to save budget costs and to treat additional 198 patients without spending healthcare resources.Conclusion. The results of the study showed that using nivolumab (Opdivo® as monotherapy in advanced RCC in adult patients as 2-line therapy is clinically effective and “cost–effective” method of treatment of adult patients with RCC in theRussian Federation. 

Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy

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Bellesoeur A

2017-09-01

Full Text Available Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard Department of Medical Oncology, Hopital Cochin AP-HP, Paris, France Abstract: Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs targeting the vascular endothelial growth factor receptors (VEGFRs. Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval. In the first-line setting, axitinib failed to demonstrate improved efficacy over sorafenib, but the field of RCC treatment is rapidly changing with novel TKIs as cabozantinib or the emergence of check point inhibitors as nivolumab and the place of axitinib in therapy is therefore challenged. In this review, we focus on axitinib pharmacological and clinical properties in RCC patients and discuss its place in the treatment of patients with RCC. Keywords: renal cell carcinoma, tyrosine kinase inhibitors, vascular endothelial growth factor, axitinib, pharmacology

Hilar location is an independent prognostic factor for recurrence in T1 renal cell carcinoma after nephrectomy.

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Shim, Myungsun; Song, Cheryn; Park, Sejun; Kim, Aram; Choi, Seung-Kwon; Kim, Choung-Soo; Ahn, Hanjong

2015-01-01

We investigated the prognostic significance of tumor location at the renal hilum near the sinus structure on the recurrence in T1 renal cell carcinoma (RCC). A total of 1,818 T1 RCC patients who underwent radical (RN) or partial nephrectomy (PN) from 1997 to 2011 were retrospectively reviewed. A hilar tumor was defined as a tumor abutting the main renal artery and/or vein or its segmental branches, without invasion. We compared the recurrence-free survival (RFS) rates between hilar and nonhilar T1 RCC and analyzed predictors of RFS after nephrectomy. Patients with hilar tumors showed a poorer 5-year RFS compared with nonhilar tumors both in T1a (89.7 vs. 98.5 %, p hilar tumors were associated with lower 5-year RFS (87.6 vs. 97.2 % for RN, 78.1 vs. 98.2 % for PN, both p hilar tumor, PN was associated with poorer 5-year RFS than RN (79.5 vs. 93.0 %, p hilar location remained as an independent predictor of recurrence in both T1a and T1b tumors (both p = 0.001). Hilar tumors show a higher recurrence rate than nonhilar counterparts in T1 RCC. In T1a hilar tumors, PN demonstrated poorer RFS than RN. Potential intrinsic renal anatomical or lymphovascular structural differences as well as differences in cancer characteristics need further investigations.

Nomogram incorporating PSA level to predict cancer-specific survival for men with clinically localized prostate cancer managed without curative intent

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Kattan, Michael W.; Cuzick, Jack; Fisher, Gabrielle; Berney, Daniel M.; Oliver, Tim; Foster, Christopher S.; Møller, Henrik; Reuter, Victor; Fearn, Paul; Eastham, James; Scardino, Peter T.

2012-01-01

Introduction The prognosis of men with clinically localized prostate cancer is highly variable, and it is difficult to counsel a man who may be considering avoiding, or delaying, aggressive therapy. After collecting data on a large cohort of men who received no initial active prostate cancer therapy, we sought to develop, and to internally validate, a nomogram for prediction of disease-specific survival. Methods Working with 6 cancer registries within England and numerous hospitals in the region, we constructed a population-based cohort of men diagnosed with prostate cancer between 1990 and 1996. All men had baseline serum prostate specific antigen (PSA) measurements, centralized pathologic grading, and centralized review of clinical stage assignment. Based upon the clinical and pathological data from 1,911 men, we developed and validated a statistical model that served as the basis for the nomogram. The discrimination and calibration of the nomogram were assessed with use of one third of the men, who were omitted from modeling and used as a test sample. Results The median age of the included men was 70.4 years. The 25th and 75th percentiles of PSA were 7.3 and 32.6 ng/ml respectively, and the median was 15.4 ng/ml. Forty-two percent of the men had high grade disease. The nomogram predicted well with a concordance index of 0.73 and had good calibration. Conclusions We have developed an accurate tool for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counseling and clinical trial design. PMID:18000803

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome with Nephron-sparing Surgery in a Patient with von Hippel-Lindau

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John M. DiBianco

2017-07-01

Full Text Available A patient with germline von Hippel-Lindau (VHL gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS associated with renal cell carcinoma (RCC. She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.

Prognostic and survival analysis of 837 Chinese colorectal cancer patients.

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Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong

2013-05-07

To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.

Does HPV status influence survival after vulvar cancer?

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Rasmussen, Christina Louise; Sand, Freja Laerke; Hoffmann Frederiksen, Marie

2018-01-01

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV...... status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic...... search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2...

Activation of Stat3 in renal tumors.

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Guo, Charles; Yang, Guanyu; Khun, Kyle; Kong, Xiantian; Levy, David; Lee, Peng; Melamed, Jonathan

2009-02-28

Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target.

Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.

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Gu, Yi-Feng; Cohn, Shannon; Christie, Alana; McKenzie, Tiffani; Wolff, Nicholas; Do, Quyen N; Madhuranthakam, Ananth J; Pedrosa, Ivan; Wang, Tao; Dey, Anwesha; Busslinger, Meinrad; Xie, Xian-Jin; Hammer, Robert E; McKay, Renée M; Kapur, Payal; Brugarolas, James

2017-08-01

Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl ) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1 -deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1 -deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1 , in Pbrm1 -deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells. Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900-17. ©2017 AACR. See related commentary by Leung and Kim, p. 802 This article is highlighted in the In This Issue feature, p. 783 . ©2017 American Association for Cancer Research.

The value of blood oxygenation level-dependent (BOLD MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC: analysis based on the largest cross-sectional area versus the entire whole tumour.

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Guang-Yu Wu

Full Text Available To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.Ninety-five patients with 139 renal masses (93 malignant and 46 benign who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest and from the whole tumour (R2*whole. Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8. The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79 was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68, as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2] and R2*largest (AUC=0.75[observer1] was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p 0.7 and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1].BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross

Contribution of screening and survival differences to racial disparities in colorectal cancer rates

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Lansdorp-Vogelaar, Iris; Kuntz, Karen M.; Knudsen, Amy B.; van Ballegooijen, Marjolein; Zauber, Ann G.; Jemal, Ahmedin

2012-01-01

Background Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the US. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival. Methods We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks aged 50 years and older from 1975 to 2007 assuming they had: 1) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); and 2) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and 3) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates. Results Differences in screening account for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. 36% of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little over 50% of the disparity in CRC mortality between blacks and whites. Conclusion Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites. Impact Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. PMID:22514249

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

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Zhenjiang, Liu; Rao, Martin; Luo, Xiaohua

2017-01-01

BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune ...... of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies....... were tested for interferon gamma (IFN-γ) production, after which univariate and multivariate analyses (Cox stepwise regression model) were performed to identify independent clinical and immunological factors associated with patient survival. Patients were followed-up for at least 500days after surgery...

A case–control study of occupation/industry and renal cell carcinoma risk

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Karami Sara

2012-08-01

Full Text Available Abstract Background The role of occupation in the etiology of renal cell carcinoma (RCC is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC. Methods Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs and 95% confidence intervals (CIs relating occupation and industry to RCC risk using adjusted unconditional logistic regression models. Results Employment in the agricultural crop production industry for five years or more was associated with RCC (OR = 3.3 [95% CI = 1.0-11.5] and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for trend with duration of employment = 0.0050. Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (ORRCC = 2.1 [95% CI = 1.0-4.5]; ORccRCC = 3.1 [95% CI = 1.4-6.8]. Employment in the dry-cleaning industry was also associated with elevated risk (ORRCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; ORccRCC = 3.0 [95% CI = 1.2-7.4], P for trend = 0.031. Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries. Conclusions Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and

Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo.

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Chang, De-Kuan; Moniz, Raymond J; Xu, Zhongyao; Sun, Jiusong; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

2015-06-11

Carbonic anhydrase (CA) IX is a surface-expressed protein that is upregulated by the hypoxia inducible factor (HIF) and represents a prototypic tumor-associated antigen that is overexpressed on renal cell carcinoma (RCC). Therapeutic approaches targeting CAIX have focused on the development of CAIX inhibitors and specific immunotherapies including monoclonal antibodies (mAbs). However, current in vivo mouse models used to characterize the anti-tumor properties of fully human anti-CAIX mAbs have significant limitations since the role of human effector cells in tumor cell killing in vivo is not directly evaluated. The role of human anti-CAIX mAbs on CAIX(+) RCC tumor cell killing by immunocytes or complement was tested in vitro by antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) as well as on CAIX(+) RCC cellular motility, wound healing, migration and proliferation. The in vivo therapeutic activity mediated by anti-CAIX mAbs was determined by using a novel orthotopic RCC xenograft humanized animal model and analyzed by histology and FACS staining. Our studies demonstrate the capacity of human anti-CAIX mAbs that inhibit CA enzymatic activity to result in immune-mediated killing of RCC, including nature killer (NK) cell-mediated ADCC, CDC, and macrophage-mediated ADCP. The killing activity correlated positively with the level of CAIX expression on RCC tumor cell lines. In addition, Fc engineering of anti-CAIX mAbs was shown to enhance the ADCC activity against RCC. We also demonstrate that these anti-CAIX mAbs inhibit migration of RCC cells in vitro. Finally, through the implementation of a novel orthotopic RCC model utilizing allogeneic human peripheral blood mononuclear cells in NOD/SCID/IL2Rγ(-/-) mice, we show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in

Disparities in survival after Hodgkin lymphoma: a population-based study

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Keegan, Theresa H.M.; Clarke, Christina A.; Chang, Ellen T.; Shema, Sarah J.; Glaser, Sally L.

2009-01-01

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census block group at diagnosis. For 12,492 classical HL patients ≥15 years diagnosed in California during 1988-2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15-44 years) and 36% (≥45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15-44 years) and 40% and 17% (≥45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes. PMID:19557531

PROGNOSTIC FACTORS IN PATIENTS WITH RENAL-CELL CARCINOMA AND A ROLE OF ONCOPHAGE IN INCREASING SURVIVAL RATES AFTER SURGICAL TREATMENT

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B. Ya. Alekseyev

2014-08-01

Full Text Available The prognostic value of the Fuhrman renal-cell carcinoma (RCC gradation system has been supported by numerous studies. The high RCC  grade after Fuhrman is a sign of the high risk of recurrence even in patients with the early stages of the disease, in clear-cell tumor in par-  ticular. The anticancer vaccine Oncophage is recommended to prevent a recurrence and/or to increase a relapse-free period in patients with  early stages of RCC. While using this vaccine, one should follow the Fuhrman histological gradation system and use a coordinated multi-  disciplinary approach to treating this group of patients. This paper describes the Fuhrman histological gradation system, indications for the  use of Oncophage in patients with the early stages of ECC and a moderate risk of a recurrence. The role of urological surgeons, oncologists,  and pathomorphologists in the treatment of patients with early stages of ECC is also considered.    

Impact of anastomotic leak on recurrence and survival after colorectal cancer surgery: a BioGrid Australia analysis.

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Sammour, Tarik; Hayes, Ian P; Jones, Ian T; Steel, Malcolm C; Faragher, Ian; Gibbs, Peter

2018-01-01

There is conflicting evidence regarding the oncological impact of anastomotic leak following colorectal cancer surgery. This study aims to test the hypothesis that anastomotic leak is independently associated with local recurrence and overall and cancer-specific survival. Analysis of prospectively collected data from multiple centres in Victoria between 1988 and 2015 including all patients who underwent colon or rectal resection for cancer with anastomosis was presented. Overall and cancer-specific survival rates and rates of local recurrence were compared using Cox regression analysis. A total of 4892 patients were included, of which 2856 had completed 5-year follow-up. The overall anastomotic leak rate was 4.0%. Cox regression analysis accounting for differences in age, sex, body mass index, American Society of Anesthesiologists score and tumour stage demonstrated that anastomotic leak was associated with significantly worse 5-year overall survival (χ 2 = 6.459, P = 0.011) for colon cancer, but only if early deaths were included. There was no difference in 5-year colon cancer-specific survival (χ 2 = 0.582, P = 0.446) or local recurrence (χ 2 = 0.735, P = 0.391). For rectal cancer, there was no difference in 5-year overall survival (χ 2 = 0.266, P = 0.606), cancer-specific survival (χ 2 = 0.008, P = 0.928) or local recurrence (χ 2 = 2.192, P = 0.139). Anastomotic leak may reduce 5-year overall survival in colon cancer patients but does not appear to influence the 5-year overall survival in rectal cancer patients. There was no effect on local recurrence or cancer-specific survival. © 2016 Royal Australasian College of Surgeons.

Survival of Salmonella enterica in poultry feed is strain dependent.

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Andino, Ana; Pendleton, Sean; Zhang, Nan; Chen, Wei; Critzer, Faith; Hanning, Irene

2014-02-01

Feed components have low water activity, making bacterial survival difficult. The mechanisms of Salmonella survival in feed and subsequent colonization of poultry are unknown. The purpose of this research was to compare the ability of Salmonella serovars and strains to survive in broiler feed and to evaluate molecular mechanisms associated with survival and colonization by measuring the expression of genes associated with colonization (hilA, invA) and survival via fatty acid synthesis (cfa, fabA, fabB, fabD). Feed was inoculated with 1 of 15 strains of Salmonella enterica consisting of 11 serovars (Typhimurium, Enteriditis, Kentucky, Seftenburg, Heidelberg, Mbandanka, Newport, Bairely, Javiana, Montevideo, and Infantis). To inoculate feed, cultures were suspended in PBS and survival was evaluated by plating samples onto XLT4 agar plates at specific time points (0 h, 4 h, 8 h, 24 h, 4 d, and 7 d). To evaluate gene expression, RNA was extracted from the samples at the specific time points (0, 4, 8, and 24 h) and gene expression measured with real-time PCR. The largest reduction in Salmonella occurred at the first and third sampling time points (4 h and 4 d) with the average reductions being 1.9 and 1.6 log cfu per g, respectively. For the remaining time points (8 h, 24 h, and 7 d), the average reduction was less than 1 log cfu per g (0.6, 0.4, and 0.6, respectively). Most strains upregulated cfa (cyclopropane fatty acid synthesis) within 8 h, which would modify the fluidity of the cell wall to aid in survival. There was a weak negative correlation between survival and virulence gene expression indicating downregulation to focus energy on other gene expression efforts such as survival-related genes. These data indicate the ability of strains to survive over time in poultry feed was strain dependent and that upregulation of cyclopropane fatty acid synthesis and downregulation of virulence genes were associated with a response to desiccation stress.

Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

NARCIS (Netherlands)

Be͉ević, Jelena; Gunter, Marc J.; Fortner, Renee T.; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Onland-Moret, N. Charlotte; Dossus, Laure; TjØnneland, Anne; Hansen, Louise; Overvad, Kim; Mesrine, Sylvie; Baglietto, Laura; Clavel-Chapelon, Francoise; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Masala, Giovanna; Agnoli, Claudia; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvatore; Bueno-de-Mesquita, H. B.; Peeters, Petra H.; Jareid, Mie; Quirós, J. Ramon; Duell, Eric J.; Sánchez, Maria Jose; Larrañaga, Nerea; Chirlaque, Maria Dolores; Barricarte, Aurelio; Dias, Joana A.; Sonestedt, Emily; Idahl, Annika; Lundin, Eva; Wareham, Nicholas J.; Khaw, Kay Tee; Travis, Ruth C.; Rinaldi, Sabina; Romieu, Isabelle; Riboli, Elio; Merritt, Melissa A.

2015-01-01

Background:Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European

The Impact of Demographic and Socioeconomic Factors on Major Salivary Gland Cancer Survival.

Science.gov (United States)

Olarte, Lucia S; Megwalu, Uchechukwu C

2014-06-01

This study aimed to investigate the impact of demographic and socioeconomic factors on survival in patients with major salivary gland malignancies. Population-based study using the Surveillance, Epidemiology, and End Results (SEER) cancer database. The study cohort consisted of 10,735 men and women ages 20 and older who were diagnosed with major salivary gland carcinoma from 1973 to 2009. Kaplan-Meier analysis revealed that the overall and disease-specific survival was higher for women than for men (P impact on overall survival. Male sex (HR = 1.38; 95% CI, 1.27-1.49), increasing age, and single status (HR = 1.29; 95% CI, 1.19-1.39) had poor prognostic impact on disease-specific survival. For patients with salivary gland malignancies, there is a survival benefit for younger patients, female patients, and married patients. This highlights the significance of demographic factors on survival outcomes for patients with salivary gland malignancies and highlights areas for further research on health disparities. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Trends in scale and shape of survival curves.

Science.gov (United States)

Weon, Byung Mook; Je, Jung Ho

2012-01-01

The ageing of the population is an issue in wealthy countries worldwide because of increasing costs for health care and welfare. Survival curves taken from demographic life tables may help shed light on the hypotheses that humans are living longer and that human populations are growing older. We describe a methodology that enables us to obtain separate measurements of scale and shape variances in survival curves. Specifically, 'living longer' is associated with the scale variance of survival curves, whereas 'growing older' is associated with the shape variance. We show how the scale and shape of survival curves have changed over time during recent decades, based on period and cohort female life tables for selected wealthy countries. Our methodology will be useful for performing better tracking of ageing statistics and it is possible that this methodology can help identify the causes of current trends in human ageing.

Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

DEFF Research Database (Denmark)

Pøhl, Mette; Olsen, Karen Ege; Holst, Rene

2016-01-01

proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7...... that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p overall survival (p ...: Keratin 34βE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival....

Survival prediction model for postoperative hepatocellular carcinoma patients.

Science.gov (United States)

Ren, Zhihui; He, Shasha; Fan, Xiaotang; He, Fangping; Sang, Wei; Bao, Yongxing; Ren, Weixin; Zhao, Jinming; Ji, Xuewen; Wen, Hao

2017-09-01

This study is to establish a predictive index (PI) model of 5-year survival rate for patients with hepatocellular carcinoma (HCC) after radical resection and to evaluate its prediction sensitivity, specificity, and accuracy.Patients underwent HCC surgical resection were enrolled and randomly divided into prediction model group (101 patients) and model evaluation group (100 patients). Cox regression model was used for univariate and multivariate survival analysis. A PI model was established based on multivariate analysis and receiver operating characteristic (ROC) curve was drawn accordingly. The area under ROC (AUROC) and PI cutoff value was identified.Multiple Cox regression analysis of prediction model group showed that neutrophil to lymphocyte ratio, histological grade, microvascular invasion, positive resection margin, number of tumor, and postoperative transcatheter arterial chemoembolization treatment were the independent predictors for the 5-year survival rate for HCC patients. The model was PI = 0.377 × NLR + 0.554 × HG + 0.927 × PRM + 0.778 × MVI + 0.740 × NT - 0.831 × transcatheter arterial chemoembolization (TACE). In the prediction model group, AUROC was 0.832 and the PI cutoff value was 3.38. The sensitivity, specificity, and accuracy were 78.0%, 80%, and 79.2%, respectively. In model evaluation group, AUROC was 0.822, and the PI cutoff value was well corresponded to the prediction model group with sensitivity, specificity, and accuracy of 85.0%, 83.3%, and 84.0%, respectively.The PI model can quantify the mortality risk of hepatitis B related HCC with high sensitivity, specificity, and accuracy.

MMP-7 expression may influence the rate of distant recurrences and disease-specific survival in HPV-positive oropharyngeal squamous cell carcinoma.

Science.gov (United States)

Vento, Seija I; Jouhi, Lauri; Mohamed, Hesham; Haglund, Caj; Mäkitie, Antti A; Atula, Timo; Hagström, Jaana; Mäkinen, Laura K

2018-05-02

The objective of this study was to determine if matrix metalloproteinase-7 (MMP-7) expression is related to human papilloma virus (HPV) status, clinical parameters, and outcome in oropharyngeal squamous cell carcinoma (OPSCC). Tumor tissue specimens from 201 OPSCC patients treated with curative intent were available for immunohistochemistry, and the samples were stained with monoclonal MMP-7 antibody. All the patients were followed up at least 3 years or until death. MMP-7 expression did not differ between HPV-positive and HPV-negative patients. MMP-7 was not prognostic among patients with HPV-negative OPSCC. In the HPV-positive subgroup, patients with moderate, high, or very high MMP-7 expression had significantly worse 5-year disease-specific survival (DSS) (56.6%) than patients with absent, or low MMP-7 expression (77.2%), and MMP-7 expression appeared as a prognostic factor in the multivariate analysis. In addition, among HPV-positive OPSCC with moderate, high, or very high MMP-7 expression, the 5-year distant recurrence-free survival was significantly lower (69.6%) than in those who had low or absent MMP-7 expression (97.5%). Our results suggest that among HPV-positive OPSCC patients, high MMP-7 expression is related to worse 5-year DSS and increased rate of distant recurrences.

Biologically inspired rate control of chaos.

Science.gov (United States)

Olde Scheper, Tjeerd V

2017-10-01

The overall intention of chaotic control is to eliminate chaos and to force the system to become stable in the classical sense. In this paper, I demonstrate a more subtle method that does not eliminate all traces of chaotic behaviour; yet it consistently, and reliably, can provide control as intended. The Rate Control of Chaos (RCC) method is derived from metabolic control processes and has several remarkable properties. RCC can control complex systems continuously, and unsupervised, it can also maintain control across bifurcations, and in the presence of significant systemic noise. Specifically, I show that RCC can control a typical set of chaotic models, including the 3 and 4 dimensional chaotic Lorenz systems, in all modes. Furthermore, it is capable of controlling spatiotemporal chaos without supervision and maintains control of the system across bifurcations. This property of RCC allows a dynamic system to operate in parameter spaces that are difficult to control otherwise. This may be particularly interesting for the control of forced systems or dynamic systems that are chaotically perturbed. These control properties of RCC are applicable to a range of dynamic systems, thereby appearing to have far-reaching effects beyond just controlling chaos. RCC may also point to the existence of a biochemical control function of an enzyme, to stabilise the dynamics of the reaction cascade.

Demisability and survivability sensitivity to design-for-demise techniques

Science.gov (United States)

Trisolini, Mirko; Lewis, Hugh G.; Colombo, Camilla

2018-04-01

The paper is concerned with examining the effects that design-for-demise solutions can have not only on the demisability of components, but also on their survivability that is their capability to withstand impacts from space debris. First two models are introduced. A demisability model to predict the behaviour of spacecraft components during the atmospheric re-entry and a survivability model to assess the vulnerability of spacecraft structures against space debris impacts. Two indices that evaluate the level of demisability and survivability are also proposed. The two models are then used to study the sensitivity of the demisability and of the survivability indices as a function of typical design-for-demise options. The demisability and the survivability can in fact be influenced by the same design parameters in a competing fashion that is while the demisability is improved, the survivability is worsened and vice versa. The analysis shows how the design-for-demise solutions influence the demisability and the survivability independently. In addition, the effect that a solution has simultaneously on the two criteria is assessed. Results shows which, among the design-for-demise parameters mostly influence the demisability and the survivability. For such design parameters maps are presented, describing their influence on the demisability and survivability indices. These maps represent a useful tool to quickly assess the level of demisability and survivability that can be expected from a component, when specific design parameters are changed.

Efficacy of targeted therapy for advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Chao Wei

Full Text Available ABSTRACT We conducted a systematic review and meta-analysis of the literature on the efficacy of the targeted therapies in the treatment of advanced RCC and, via an indirect comparison, to provide an optimal treatment among these agents. A systematic search of Medline, Scopus, Cochrane Library and Clinical Trials unpublished was performed up to Jan 1, 2015 to identify eligible randomized trials. Outcomes of interest assessing a targeted agent included progression free survival (PFS, overall survival (OS and objective response rate (ORR. Thirty eligible randomized controlled studies, total twentyfourth trails (5110 cases and 4626 controls were identified. Compared with placebo and IFN-α, single vascular epithelial growth factor (receptor tyrosine kinase inhibitor and mammalian target of rapamycin agent (VEGF(r-TKI & mTOR inhibitor were associated with improved PFS, improved OS and higher ORR, respectively. Comparing sorafenib combination vs sorafenib, there was no significant difference with regard to PFS and OS, but with a higher ORR. Comparing single or combination VEGF(r-TKI & mTOR inhibitor vs BEV + IFN-α, there was no significant difference with regard to PFS, OS, or ORR. Our network ITC meta-analysis also indicated a superior PFS of axitinib and everolimus compared to sorafenib. Our data suggest that targeted therapy with VEGF(r-TKI & mTOR inhibitor is associated with superior efficacy for treating advanced RCC with improved PFS, OS and higher ORR compared to placebo and IFN-α. In summary, here we give a comprehensive overview of current targeted therapies of advanced RCC that may provide evidence for the adequate targeted therapy selecting.

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

Science.gov (United States)

Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin; Choi, Peter  S.; Casey, Stephanie  C.; Dill, David  L.; Felsher, Dean  W.

2014-01-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin

2014-08-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

Survival analysis

International Nuclear Information System (INIS)

Badwe, R.A.

1999-01-01

The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

Beta-1,3-1,6-glucan modulate the non-specific immune response to enhance the survival in the Vibrio alginolyticus infection of Taiwan abalone (Haliotis diversicolor supertexta).

Science.gov (United States)

Wu, Yu-Sheng; Tseng, Tzu-Yu; Nan, Fan-Hua

2016-07-01

This research aims to investigate the non-specific immune response of Taiwan abalone (Haliotis diversicolor supertexta) which was treated with the beta-1,3-1,6-glucan to be observed in the survival impact after the Vibrio alginolyticus infection. The non-specific immune and physiological response of superoxide anion radical (O2(-)), phenoloxidase (PO), phagocytic index (PI), phagocytic rate (PR) and lucigenin-chemiluminescence for reactive oxygen intermediates (ROIs) were enhanced via in-vitro experiment. In the in-vivo experiment, the observed data presented that the haemolymph lysate supernatant (HLS), superoxide dismutase (SOD), glutamate oxalacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) were not significant enhanced, but the total haemocyte count (THC), O2(-), PO, phagocytic index (PI), phagocytic ratio (PR) and other parameters of immune were significantly promoted after treated with beta-1,3-1,6-glucan. In the challenge experiment, the survival rates of abalone in the 40 and 80 μl/ml groups of beta-1,3-1,6-glucan were observed from 6.67% up to 33.33% and 36.67% after injection with Vibrio alginolyticus, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Survival Advantage: Underlying Mechanisms and Extant Limitations

Directory of Open Access Journals (Sweden)

Stephanie A. Kazanas

2015-04-01

Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

Poor survival of treatment-related acute nonlymphocytic leukemia

International Nuclear Information System (INIS)

Neugut, A.I.; Nieves, J.; Murray, T.; Tsai, Weiyann; Robinson, E.

1990-01-01

Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients

Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Wersaell, Peter J.; Blomgren, Henric; Lax, Ingmar; Kaelkner, Karl-Mikael; Linder, Christina; Lundell, Goeran; Nilsson, Bo; Nilsson, Sten; Naeslund, Ingemar; Pisa, Pavel; Svedman, Christer

2005-01-01

Background and purpose: We investigated the results of using stereotactic radiotherapy (SRT) for 58 patients with renal cell carcinomas (RCC) who were evaluated restrospectively for response rates, local control rates and side effects. Patients and methods: From October 1997 to January 2003, 50 patients suffering from metastatic RCC and eight patients with inoperable primary RCC received high-dose fraction SRT while placed in a stereotactic body-frame. The most common dose/fractionation schedules used were 8 Gyx4, 10 Gyx4 and 15 Gyx3 during approximately 1 week. Results: SRT-treated tumor lesions regressed totally in 30% of the patients at 3-36 months, whereas 60% of the patients had a partial volume reduction or no change after a median follow-up of 37 months (SD 17.4) for censored and 13 months (SD 12.9) for uncensored patients. Side effects were generally mild. Of 162 treated tumors, only three recurred, yielding a local control rate of 90-98%, considering the 8% non-evaluable sites as defined here. For patients with one to three metastases, the time to new spread was 9 months. Conclusions: Our use of SRT for patients with primary and metastatic RCC yielded a high local control rate with low toxicity. Patients with one to three metastases, local recurrences after nephrectomy or inoperable primary tumors benefited the most, i.e. had fewer distant recurrences (13/23) and longer survival times compared to patients with >3 metastases (24/27 recurrences)

Management of Spinal Metastases From Renal Cell Carcinoma Using Stereotactic Body Radiotherapy

International Nuclear Information System (INIS)

Nguyen, Quynh-Nhu; Shiu, Almon S.; Rhines, Laurence D.; Wang He; Allen, Pamela K.; Wang, Xin Shelley; Chang, Eric L.

2010-01-01

Purpose: To evaluate the outcomes associated with stereotactic body radiotherapy (SBRT) in the management of spinal metastases from renal cell carcinoma (RCC). Methods and Materials: SBRT was used in the treatment of patients with spinal metastases from RCC. Patients received either 24 Gy in a single fraction, 27 Gy in three fractions, or 30 Gy delivered in five fractions. Effectiveness of SBRT with respect to tumor control and palliation of pain was assessed using patient-reported outcomes. Results: A total of 48 patients with 55 spinal metastases were treated with SBRT with a median follow-up time of 13.1 months (range, 3.3-54.5 months). The actuarial 1-year spine tumor progression free survival was 82.1%. At pretreatment baseline, 23% patients were pain free; at 1 month and 12 months post-SBRT, 44% and 52% patients were pain free, respectively. No Grade 3-4 neurologic toxicity was observed. Conclusions: The data support SBRT as a safe and effective treatment modality that can be used to achieve good tumor control and palliation of pain associated with RCC spinal metastases. Further evaluation with randomized trials comparing SBRT to conventional radiotherapy may be warranted.

[11C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy

International Nuclear Information System (INIS)

Giovacchini, Giampiero; Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria; Kirienko, Margarita; Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco

2015-01-01

Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [ 11 C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [ 11 C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [ 11 C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Median follow-up was 7.2 years (1.4 - 18.9 years). [ 11 C]Choline PET/CT was positive in 101 of 302 patients (33 %). Median PCa-specific survival after prostatectomy was 14.9 years (95 % CI 9.7 - 20.1 years) in patients with positive [ 11 C]choline PET/CT. Median survival was not achieved in patients with negative [ 11 C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4 % (95 % CI 31.7 - 53.1 %) in patients with positive [ 11 C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [ 11 C]choline PET/CT. In multivariate analysis, [ 11 C]choline PET/CT (hazard ratio 6.36, 95 % CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95 % CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80 %. Positive [ 11 C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone

Do ducks and songbirds initiate more nests when the probability of survival is greater?

Science.gov (United States)

Grant, Todd A.; Shaffer, Terry L.

2015-01-01

Nesting chronology in grassland birds can vary by species, locality, and year. The date a nest is initiated can influence the subsequent probability of its survival in some grassland bird species. Because predation is the most significant cause of nest loss in grassland birds, we examined the relation between timing of nesting and nest survival. Periods of high nest survival that correspond with the peak of nesting activity might reflect long-term adaptations to specific predation pressures commonly recurring during certain periods of the nesting cycle. We evaluated this theory by comparing timing of nesting with date-specific nest survival rates for several duck and passerine species breeding in north-central North Dakota during 1998–2003. Nest survival decreased seasonally with date for five of the seven species we studied. We found little evidence to support consistent relations between timing of nesting, the number of nest initiations, and nest survival for any species we studied, suggesting that factors other than nest predation may better explain nesting chronology for these species. The apparent mismatch between date-specific patterns of nest survival and nest initiation underscores uncertainty about the process of avian nest site selection driven mainly by predation. Although timing of nesting differed among species, the general nesting period was fairly predictable across all years of study, suggesting the potential for research activities or management actions to be timed to take advantage of known periods when nests are active (or inactive). However, our results do not support the notion that biologists can take advantage of periods when many nests are active and survival is also high.

Survival outcomes of younger men (< 55 years undergoing radical prostatectomy

Directory of Open Access Journals (Sweden)

Lynn Tan

2018-03-01

Conclusion: Men aged 45–54 years undergoing RP had better overall survival compared to men aged 55–74 years, but these effects were not seen in men aged 35–44 years. There were no differences in prostate cancer specific survival in these groups.

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

Science.gov (United States)

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

Directory of Open Access Journals (Sweden)

Steve R. Martinez

2013-02-01

Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

Network survivability performance

Science.gov (United States)

1993-11-01

This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

Sunitinib in mRCC: A systematic review of UK Real World Data

Directory of Open Access Journals (Sweden)

David Andrew Montgomery

2015-08-01

Full Text Available BackgroundReal world data are increasingly used to inform drug reimbursement decisions, but it is unclear how well outcomes from real world studies compare to those of clinical trials. This systematic review seeks to compare outcomes for sunitinib in routine UK clinical practice with the sunitinib registrational and expanded access program clinical trials. MethodSystematic review of the real world published literature was undertaken. UK observational studies recording first or second line sunitinib efficacy were included. A qualitative summary of the results and comparison to the controlled clinical trials was conducted. 15 real world studies were included, 14 of which were only available as posters/presentations. ResultsReal world study reporting quality was generally low, making comparisons with the clinical trials difficult. Practice relating to starting dose, dose modification, timing of therapy initiation and other factors varied between centres. Median progression free survival and adverse events were generally comparable to the clinical trial outcomes, but overall survival was not. ConclusionsThere are few published data on sunitinib use in UK clinical practice. Studies are characterised by lack of peer reviewed publication and heterogeneity in design, reporting and analysis. For use of real world data in the reimbursement setting, data collection and reporting will need to improve.

Individual social capital and survival

DEFF Research Database (Denmark)

Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

2014-01-01

BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

ER and PR expression and survival after endometrial cancer.

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Smith, Deborah; Stewart, Colin J R; Clarke, Edward M; Lose, Felicity; Davies, Claire; Armes, Jane; Obermair, Andreas; Brennan, Donal; Webb, Penelope M; Nagle, Christina M; Spurdle, Amanda B

2018-02-01

To measure association between endometrial carcinoma ER and PR status and endometrial cancer (EC) survival, accounting for inter-observer variation. The intensity and proportion of tumor cell expression of ER and PR in ECs were assessed independently and semi-quantitatively by two pathologists using digital images of duplicate tumor tissue microarrays (TMAs). Cases with inconsistent initial assessment were reviewed and final scoring agreed. The association between overall and EC-specific survival and hormone receptor expression (intensity, proportion and combined) was assessed using Cox regression analysis. The C-index was used to evaluate model discrimination with addition of ER and PR status. Tumor ER and PR analysis was possible in 659 TMAs from 255 patients, and in 459 TMAs from 243 patients, respectively. Initial ER and PR scoring was consistent in 82% and 80% of cases, respectively. In multivariate analyses decreased ER and PR expression was associated with increased tumor-related mortality. Associations reached statistical significance for ER proportion score (P=0.05), ER intensity score (P=0.003), and PR combined score (P=0.04). Decreased expression of combined ER/PR expression was associated with poorer EC-specific survival than decreased expression of either hormone receptor alone (P=0.005). However, hormone receptor status did not significantly improve mortality prediction in individual cases. ER and PR expression combined, using cut-points that capture variation in scoring and across cores, is significantly associated with EC-specific survival in analyses adjusting for known prognostic factors. However, at the individual level, ER and PR expression does not improve mortality prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

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Magdalena B Wozniak

Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

Evaluation of renal cell carcinoma histological subtype and fuhrman grade using {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography

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Nakajima, Reiko; Nozaki, Sayumi; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan); Nagashima, Yoji [Tokyo Women' s Medical University, Department of Surgical Pathology, Tokyo (Japan)

2017-11-15

We evaluated {sup 18}F-fluorodeoxyglucose (FDG) uptake by renal cell carcinomas (RCCs) to determine whether different histological subtypes and Fuhrman grades can be distinguished. We retrospectively reviewed the records and maximum standardised uptake value (SUVmax) of 147 patients with 154 RCCs who underwent FDG-positron emission tomography (PET)/computed tomography (CT) prior to tumour resection. The SUVmax was significantly lower in chromophobe RCC (chRCC) tumours than in clear cell RCC (ccRCC; p = 0.003) and papillary RCC (pRCC; p = 0.034) tumours. The mean tumour SUVmax was 4.58 ± 4.1 (range, 1.29-30.4) for ccRCC, 3.98 ± 1.9 (range, 0.49-6.72) for pRCC, and 1.93 ± 0.9 (range, 0.89-3.41) for chRCC. The SUVmax was not significantly different between the ccRCC and pRCC groups. In ccRCC and pRCC tumours, high-grade tumours had a significantly greater SUVmax (p < 0.001 and p < 0.05) than low-grade tumours by analysis of variance (ANOVA) and the Mann-Whitney U test. In ccRCC, multivariate regression analysis indicated that the SUVmax was a significant indicator of Fuhrman grade. No significant differences in uptake were observed between high- and low-grade chRCC tumours. The SUVmax obtained using FDG-PET/CT may be an important indicator for predicting tumour grade in ccRCC and pRCC. (orig.)

Kidney cancer in Lebanon: a specific histological distribution?

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Khafaja, Sarah; Kourie, Hampig Raphael; Matar, Dany; Sader-Ghorra, Claude; Kattan, Joseph

2015-01-01

Kidney cancer is the third most frequent urologic cancer in Lebanon after prostate and bladder cancer, accounting for 1.5% of all diagnosed cancers. In this paper, we report the histologic characteristics and distribution of kidney cancer, never described in Lebanon or the Middle East. Pathology results of operated kidney cancer were collected during a two year period (2010-2011) from two different Lebanese hospitals (Hotel-Dieu de France University Hospital and Saint Joseph Hospital). A total of 124 reports were reviewed and analyzed according to WHO classification of 2009. The 124 patients diagnosed with kidney cancer had a median age of 62.4 [18-86], 75% being men and 25% women. Some 71 % of the lesions were renal cell carcinoma (RCC), 25.8% had a urothelial histology, 1.6% were lymphomas and 1.6% were metastases to the kidney. Patients having RCC had a median age of 60.3 [18-85], 77.3% were men and 22.7% women. Of the RCCs, 59.1% were clear cell carcinoma, 22.7% papillary, 11.4% chromophobic, 3.4% rom the collecting ducts of Bellini and 3.4% were not otherwise classified. Histological distribution of Lebanese kidney cancer seems unusual when compared to the literature. The percentage of urothelial renal pelvis tumors is strikingly high. Moreover, clear cell carcinoma accounts for only 59.1% of RCCS in contrast to the 75% described elsewhere, while papillary carcinoma represents more than 22.7% compared to 10%.

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

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Seikkula, Heikki A; Kaipia, Antti J; Ryynänen, Heidi; Seppä, Karri; Pitkäniemi, Janne M; Malila, Nea K; Boström, Peter J

2018-03-01

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period. © 2017 UICC.

Acylcarnitines profile best predicts survival in horses with atypical myopathy.

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François Boemer

Full Text Available Equine atypical myopathy (AM is caused by hypoglycin A intoxication and is characterized by a high fatality rate. Predictive estimation of survival in AM horses is necessary to prevent unnecessary suffering of animals that are unlikely to survive and to focus supportive therapy on horses with a possible favourable prognosis of survival. We hypothesized that outcome may be predicted early in the course of disease based on the assumption that the acylcarnitine profile reflects the derangement of muscle energetics. We developed a statistical model to prognosticate the risk of death of diseased animals and found that estimation of outcome may be drawn from three acylcarnitines (C2, C10:2 and C18 -carnitines with a high sensitivity and specificity. The calculation of the prognosis of survival makes it possible to distinguish the horses that will survive from those that will die despite severe signs of acute rhabdomyolysis in both groups.

Acylcarnitines profile best predicts survival in horses with atypical myopathy

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Detilleux, Johann; Cello, Christophe; Amory, Hélène; Marcillaud-Pitel, Christel; Richard, Eric; van Galen, Gaby; van Loon, Gunther; Lefère, Laurence; Votion, Dominique-Marie

2017-01-01

Equine atypical myopathy (AM) is caused by hypoglycin A intoxication and is characterized by a high fatality rate. Predictive estimation of survival in AM horses is necessary to prevent unnecessary suffering of animals that are unlikely to survive and to focus supportive therapy on horses with a possible favourable prognosis of survival. We hypothesized that outcome may be predicted early in the course of disease based on the assumption that the acylcarnitine profile reflects the derangement of muscle energetics. We developed a statistical model to prognosticate the risk of death of diseased animals and found that estimation of outcome may be drawn from three acylcarnitines (C2, C10:2 and C18 -carnitines) with a high sensitivity and specificity. The calculation of the prognosis of survival makes it possible to distinguish the horses that will survive from those that will die despite severe signs of acute rhabdomyolysis in both groups. PMID:28846683

Marital Status and Survival in Patients with Carcinoid Tumors.

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Greenleaf, Erin K; Cooper, Amanda B; Hollenbeak, Christopher S

2016-01-01

Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan-Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR]), controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed) patients. Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08-1.33] and 1.34 [95% CI, 1.22-1.46], respectively) and cancer-related survival (HR, 1.15 [95% CI, 1.00-1.31] and 1.15 [95% CI, 1.03-1.29], respectively) than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08-1.33] and 1.62 [95% CI, 1.25-2.11], respectively) than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means

Pretreatment oral hygiene habits and survival of head and neck squamous cell carcinoma (HNSCC) patients.

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Friemel, Juliane; Foraita, Ronja; Günther, Kathrin; Heibeck, Mathias; Günther, Frauke; Pflueger, Maren; Pohlabeln, Hermann; Behrens, Thomas; Bullerdiek, Jörn; Nimzyk, Rolf; Ahrens, Wolfgang

2016-03-11

The survival time of patients with head and neck squamous cell carcinoma (HNSCC) is related to health behavior, such as tobacco smoking and alcohol consumption. Poor oral health (OH), dental care (DC) and the frequent use of mouthwash have been shown to represent independent risk factors for head and neck cancerogenesis, but their impact on the survival of HNSCC patients has not been systematically investigated. Two hundred seventy-six incident HNSCC cases recruited for the ARCAGE study were followed through a period of 6-10 years. Interview-based information on wearing of dentures, gum bleeding, teeth brushing, use of floss and dentist visits were grouped into weighted composite scores, i.e. oral health (OH) and dental care (DH). Use of mouthwash was assessed as frequency per day. Also obtained were other types of health behavior, such as smoking, alcohol drinking and diet, appreciated as both confounding and study variables. Endpoints were progression-free survival, overall survival and tumor-specific survival. Prognostic values were estimated using Kaplan-Meier analysis and Cox proportional hazards regression models. A good dental care score, summarizing annual dental visits, daily teeth cleaning and use of floss was associated with longer overall survival time (p = .001). The results of the Cox regression models similarly suggested a higher risk of tumor progression and shortened overall survival in patients with poor dental care, but the results lost their statistical significance after other types of health behavior had been controlled for. Frequent use of mouthwash (≥ 2 times/day) significantly increased the risk of tumor-specific death (HR = 2.26; CI = 1.19-4.32). Alcohol consumption and tobacco smoking were dose-dependently associated with tumor progression and shorter overall survival. Frequent mouthwash use of ≥ 2 times/day seems to elevate the risk of tumor-specific death in HNSCC patients. Good dental care scores are associated with longer overall

Targeting CXCR4 reverts the suppressive activity of T-regulatory cells in renal cancer.

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Santagata, Sara; Napolitano, Maria; D'Alterio, Crescenzo; Desicato, Sonia; Maro, Salvatore Di; Marinelli, Luciana; Fragale, Alessandra; Buoncervello, Maria; Persico, Francesco; Gabriele, Lucia; Novellino, Ettore; Longo, Nicola; Pignata, Sandro; Perdonà, Sisto; Scala, Stefania

2017-09-29

With the intent to identify biomarkers in renal cell carcinoma (RCC) the functional status of T-regulatory cells (Tregs) was investigated in primary RCC. Tregs were isolated from tumoral-(TT), peritumoral tissue-(PT) and peripheral blood-(PB) of 42 primary RCC patients and function evaluated through effector T cells (Teff) proliferation, cytokines release and demethylation of Treg Specific Region (TSDR). The highest value of Tregs was detected in TT with the uppermost amount of effector-Tregs-(CD4 + CD25 hi FOXP3 hi CD45RA - ). PB-RCC Tregs efficiently suppress Teff proliferation compared to healthy donor (HD)-Tregs and, at the intrapatient evaluation, TT-derived Tregs were the most suppressive. Higher demethylation TSDR was detected in TT- and PB-RCC Tregs vs HD-Tregs ( P <0,001). CXCR4 is highly expressed on Tregs, thus we wished to modulate Tregs function through CXCR4 inhibition. CXCR4 antagonism, elicited by a new peptidic antagonist, Peptide-R29, efficiently reversed Tregs suppression of Teff proliferation. Thus Tregs functional evaluation precisely reflects Tregs status and may be a reliable biomarker of tumoral immune response. In addition, treatment with CXCR4 antagonist, impairing Tregs function, could improve the anticancer immune response, in combination with conventional therapy and/or immunotherapy such as checkpoints inhibitors.

Effect of blood transfusion and cyclophosphamide on cardiac allograft survival in sensitized mice

International Nuclear Information System (INIS)

Lasek, Witold; Sora, Magdalena; Jakobisiak, Marek

1994-01-01

In the H-2-incompatible donor-recipient model in mice (BALB/c → CBA/H), combination of donor-specific blood transfusion (DST) on the day -9 before transplantation with both pre- and post transplant immunosuppression with cyclophosphamide (CY) interacted beneficially to produce significant donor-specific prolongation of cardiac graft survival. However, in recipients presensitized with donor-specific blood on the day -21, combination of DST with pre- and post transplant CY immunosuppression did not act synergistically and graft survival in this group did not differ from that in presentized mice treated with 2 doses of CY alone. (author). 21 refs, 1 fig., 3 tabs

An overview of equipment survivability studies at Sandia National Laboratories (SNL)

International Nuclear Information System (INIS)

Bonzon, L.L.; Craft, Ch.M.; McCulloch, W.H.; Sebrell, W.A.

1983-01-01

The USNRC sponsors a number of programs at Sandia National Laboratories (SNL) specifically addressing safety-related equipment survivability. The major thrust of these programs has been the physical testing of equipment. Test results illustrate the importance of a dedicated equipment design effort giving particular attention to the safety implications of the equipment operation. Several equipment survivability tests here have revealed equipment design and test-related deficiencies

Climate policy, asymmetric information and firm survival

International Nuclear Information System (INIS)

Hagem, C.

2001-02-01

The purpose of this paper is to compare the effect of different domestic climate policy instruments under asymmetric information when the regulator wants to secure the survival of a specific firm. It is a well-known result from economic theory that emission taxes lead to a cost-effective distribution of abatement across polluters. However, if the regulator wants to ensure the survival of a specific firm, it may need to design policy instruments that reduce the firm's cost of complying with an emission tax regime. The climate policy instruments considered in this paper are tradable emission permits with distribution of free permits, emission taxes in combination with a fixed subsidy, and two types of voluntary agreements. It demonstrates first that if distributing free tradable permits shall have a preventing effect, the allocation of permits has to be made contingent on production. It further shows that a voluntary agreement where a specific abatement target is set by the regulator can prevent a shutdown but leads to lower welfare than the use of emission taxes in combination with a fixed subsidy. And finally it illustrates that a voluntary agreement designed as a menu of abatement contracts increases social welfare compared to an emission tax regime