The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

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2011-01-01

Background Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results. PMID:21827707

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

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Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

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Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

2011-01-01

Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

Survivin -31 G/C polymorphism might contribute to colorectal cancer (CRC) risk: a meta-analysis.

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Yao, Linhua; Hu, Yi; Deng, Zhongmin; Li, Jingjing

2015-01-01

Published data has shown inconsistent findings about the association of survivin -31 G/C polymorphism with the risk of colorectal cancer (CRC). This meta-analysis quantitatively assesses the results from published studies to provide a more precise estimate of the association between survivin -31 G/C polymorphism as a possible predictor of the risk of CRC. We conducted a literature search in the PubMed, Web of Science, and Cochrane Library databases. Stata 12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) based on the available data from each article. Six studies including 1840 cases with CRC and 1804 controls were included in this study. Survivin -31 G/C polymorphism was associated with a significantly increased risk of CRC (OR = 1.78; 95% CI, 1.53-2.07; I(2) = 0%). In the race subgroup analysis, both Asians (OR = 1.72; 95% CI, 1.44-2.05; I(2) = 0%) and Caucasians (OR = 1.93; 95% CI, 1.46-2.55; I(2) = 0%) with survivin -31 G/C polymorphism had increased CRC risk. In the subgroup analysis according to site of CRC, survivin -31 G/C polymorphism was not associated with colon cancer risk (OR = 2.02; 95% CI, 0.79-5.22; I(2) = 82%). However, this polymorphism was significantly associated with rectum cancer risk (OR = 1.98; 95% CI, 1.42-2.74; I(2) = 0%). In the subgroup analysis by clinical stage, both early stage (I+II) and advanced stage (III+IV) were associated with survivin -31 G/C polymorphism (OR = 1.61; 95% CI, 1.20-2.16; I(2) = 0% and OR = 2.30; 95% CI, 1.70-3.13; I(2) = 0%, respectively). In the subgroup analysis by smoke status, both smokers and non-smokers with survivin -31 G/C polymorphism showed increased CRC risk (OR = 1.47; 95% CI, 1.01-2.13; I(2) = 60% and OR = 1.71; 95% CI, 1.28-2.30; I(2) = 0%, respectively). In the subgroup analysis by drink status, both drinkers and non-drinkers with survivin -31 G/C polymorphism showed increased CRC risk (OR = 1.58; 95% CI, 1.06-2.37; I(2) = 8% and OR = 1.61; 95% CI, 1

Advances in CRC Prevention: Screening and Surveillance.

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Dekker, Evelien; Rex, Douglas K

2018-05-01

Colorectal cancer (CRC) is among the most commonly diagnosed cancers and causes of death from cancer across the world. CRC can, however, be detected in asymptomatic patients at a curable stage, and several studies have shown lower mortality among patients who undergo screening compared with those who do not. Using colonoscopy in CRC screening also results in the detection of precancerous polyps that can be directly removed during the procedure, thereby reducing the incidence of cancer. In the past decade, convincing evidence has appeared that the effectiveness of colonoscopy as CRC prevention tool is associated with the quality of the procedure. This review aims to provide an up-to-date overview of recent efforts to improve colonoscopy effectiveness by enhancing detection and improving the completeness and safety of resection of colorectal lesions. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance.

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Krzystek-Korpacka, Malgorzata; Diakowska, Dorota; Kapturkiewicz, Bartosz; Bębenek, Marek; Gamian, Andrzej

2013-08-28

Alternate colorectal cancer (CRC) screening and surveillance strategies are needed to pre-select candidates for invasive methods. We compared systemic inflammatory profiles in CRC (n=99), health (n=98), high CRC-risk conditions (n=48) and overt inflammation (n=69) by multiplexed analysis of IL-1β, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-B and CEA. Cytokines corresponded with CRC advancement. FGF2, GM-CSF, IL-1β, IL-6, MIP-1α, PDGF-BB, TNF-α, and VEGF-A were higher than in controls already in stage I CRC with FGF2, IL1-β, and MIP-1α higher than in high CRC-risk individuals as well. Cytokine panels devised to differentiate early CRC from controls, adenomas, or inflammatory bowel disease patients (IBD) had good accuracy but only IBD panel had promising specificity at 95% sensitivity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

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de Cuba, E. M. V.; Snaebjornsson, P.; Heideman, D. A. M.; van Grieken, N. C. T.; Bosch, L. J. W.; Fijneman, R. J. A.; Belt, E.; Bril, H.; Stockmann, H. B. A. C.; Hooijberg, E.; Punt, C. J. A.; Koopman, M.; Nagtegaal, I. D.; Coupé, V. H. M.; Carvalho, B.; Meijer, G. A.

2016-01-01

Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear

Two small RNAs, CrcY and CrcZ, act in concert to sequester the Crc global regulator in Pseudomonas putida, modulating catabolite repression.

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Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2012-01-01

The Crc protein is a translational repressor that recognizes a specific target at some mRNAs, controlling catabolite repression and co-ordinating carbon metabolism in pseudomonads. In Pseudomonas aeruginosa, the levels of free Crc protein are controlled by CrcZ, a sRNA that sequesters Crc, acting as an antagonist. We show that, in Pseudomonas putida, the levels of free Crc are controlled by CrcZ and by a novel 368 nt sRNA named CrcY. CrcZ and CrcY, which contain six potential targets for Crc, were able to bind Crc specifically in vitro. The levels of CrcZ and CrcY were low under conditions generating a strong catabolite repression, and increased strongly when catabolite repression was absent. Deletion of either crcZ or crcY had no effect on catabolite repression, but the simultaneous absence of both sRNAs led to constitutive catabolite repression that compromised growth on some carbon sources. Overproduction of CrcZ or CrcY significantly reduced repression. We propose that CrcZ and CrcY act in concert, sequestering and modulating the levels of free Crc according to metabolic conditions. The CbrA/CbrB two-component system activated crcZ transcription, but had little effect on crcY. CrcY was detected in P. putida, Pseudomonas fluorescens and Pseudomonas syringae, but not in P. aeruginosa. © 2011 Blackwell Publishing Ltd.

Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome.

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Zhang, Dandan; Li, Zhenli; Xu, Xiaohong; Zhou, Dan; Tang, Shunli; Yin, Xiaoyang; Xu, Fangying; Li, Hui; Zhou, Yuan; Zhu, Tao; Deng, Hong; Zhang, Shuai; Huang, Qiong; Wang, Jing; Yin, Wei; Zhu, Yimin; Lai, Maode

2017-10-26

Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Colorectal cancer stages transcriptome analysis.

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Tianyao Huo

Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

The Crc/CrcZ-CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida.

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La Rosa, Ruggero; Nogales, Juan; Rojo, Fernando

2015-09-01

In metabolically versatile bacteria, carbon catabolite repression (CCR) facilitates the preferential assimilation of the most efficient carbon sources, improving growth rates and fitness. In Pseudomonas putida, the Crc and Hfq proteins and the CrcZ and CrcY small RNAs, which are believed to antagonize Crc/Hfq, are key players in CCR. Unlike that seen in other bacterial species, succinate and glucose elicit weak CCR in this bacterium. In the present work, metabolic, transcriptomic and constraint-based metabolic flux analyses were combined to clarify whether P. putida prefers succinate or glucose, and to identify the role of the Crc protein in the metabolism of these compounds. When provided simultaneously, succinate was consumed faster than glucose, although both compounds were metabolized. CrcZ and CrcY levels were lower when both substrates were present than when only one was provided, suggesting a role for Crc in coordinating metabolism of these compounds. Flux distribution analysis suggested that, when both substrates are present, Crc works to organize a metabolism in which carbon compounds flow in opposite directions: from glucose to pyruvate, and from succinate to pyruvate. Thus, our results support that Crc not only favours the assimilation of preferred compounds, but balances carbon fluxes, optimizing metabolism and growth. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

System applications CRC -Biomass + Coal; Aplicaciones Sistema CRC-Biomasa+Carbon

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

Main object of Phase I of the project is to analyse the technical-economic feasibility of the combined use of biomass and coal for power generation in the Spanish region of Andalusia, by means of new medium-size independent power plants or using biomass as supplementary fuel in existing large coal power plants, including: -Analysis and classification of biomass and coal resources in the region -Technical-economic study of conventional alternatives using the steam cycle -Analysis of efficiency improvement provided by advanced Rankine-cycle technologies, like the SMR cycle -Analysis of alternatives based on parallel combined cycles using gas turbines, including advanced solutions, like the EAPI and CRC-EAPI systems. -Description and evaluation of different biomass drying systems. -Description and evaluation of the three main biomass gasification systems currently under development: atmospheric direct, atmospheric indirect and pressurized. Main objects of Phase II of the project are to analyse a specific application of the EAPI system to a real cogeneration plant project and to analyse the application of the CRC2 system to a commercial supercritical power plant, including technical-economic study of both applications. (Author)

High Rab27A expression indicates favorable prognosis in CRC.

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Shi, Chuanbing; Yang, Xiaojun; Ni, Yijiang; Hou, Ning; Xu, Li; Zhan, Feng; Zhu, Huijun; Xiong, Lin; Chen, Pingsheng

2015-06-13

Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet. One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients. The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients. The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

Attitudes towards colorectal cancer (CRC) and CRC screening tests among elderly Malay patients.

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Al-Naggar, Redhwan A; Al-Kubaisy, Waqar; Yap, Bee W; Bobryshev, Yuri V; Osman, Muhamed T

2015-01-01

Colorectal cancer (CRC) is the third most common malignancy in Malaysia, where data are limited regarding knowledge and barriers in regard to CRC and screening tests. The aim of the study was to assess these parameters among Malaysians. The questionnaires were distributed in the Umra Private Hospital in Selangor. The questionnaire had four parts and covered social-demographic questions, respondent knowledge about CRC and colorectal tests, attitude towards CRC and respondentaction regarding CRC. More than half of Malay participants (total n=187) were female (57.2%) and 36.9% of them were working as professionals. The majority of the participants (93.6%) never had a CRC screening test. The study found that only 10.2% of the study participants did not consider that their chances of getting CRC were high. A high percentage of the participants (43.3%) believed that they would have good chance of survival if the cancer would be found early. About one third of the respondents did not want to do screening because of fear of cancer, and concerns of embarrassment during the procedure adversely affected attitude to CRC screening as well. Age, gender, income, family history of CRC, vegetable intake and physical activity were found to be significant determinants of knowledge on CRC. The major barriers identified towards CRC screening identified in our study were fear of pain and embarrassment. The findings have implications for understanding of similarities and differences in attitude to CRC amongst elderly patients in other cultural/ geographic regions.

Pseudomonas putida growing at low temperature shows increased levels of CrcZ and CrcY sRNAs, leading to reduced Crc-dependent catabolite repression.

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Fonseca, Pilar; Moreno, Renata; Rojo, Fernando

2013-01-01

The Crc protein of Pseudomonas inhibits the expression of genes involved in the transport and assimilation of a number of non-preferred carbon sources when preferred substrates are available, thus coordinating carbon metabolism. Crc acts by binding to target mRNAs, inhibiting their translation. In Pseudomonas putida, the amount of free Crc available is controlled by two sRNAs, CrcY and CrcZ, which bind to and sequester Crc. The levels of these sRNAs vary according to metabolic conditions. Pseudomonas putida grows optimally at 30°C, but can also thrive at 10°C. The present work shows that when cells grow exponentially at 10°C, the repressive effect of Crc on many genes is significantly reduced compared with that seen at 30°C. Total Crc levels were similar at both temperatures, but those of CrcZ and CrcY were significantly higher at 10°C. Therefore, Crc-mediated repression may, at least in part, be reduced at 10°C because the fraction of Crc protein sequestered by CrcZ and CrcY is larger, reducing the amount of free Crc available to bind its targets. This may help P. putida to face cold stress. The results reported might help understanding the behaviour of this bacterium in bioremediation or rhizoremediation strategies at low temperatures. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells.

Science.gov (United States)

Fan, F; Bellister, S; Lu, J; Ye, X; Boulbes, D R; Tozzi, F; Sceusi, E; Kopetz, S; Tian, F; Xia, L; Zhou, Y; Bhattacharya, R; Ellis, L M

2015-02-03

Isolation of colorectal cancer (CRC) cell populations enriched for cancer stem cells (CSCs) may facilitate target identification. There is no consensus regarding the best methods for isolating CRC stem cells (CRC-SCs). We determined the suitability of various cellular models and various stem cell markers for the isolation of CRC-SCs. Established human CRC cell lines, established CRC cell lines passaged through mice, patient-derived xenograft (PDX)-derived cells, early passage/newly established cell lines, and cells directly from clinical specimens were studied. Cells were FAC-sorted for the CRC-SC markers CD44, CD133, and aldehyde dehydrogenase (ALDH). Sphere formation and in vivo tumorigenicity studies were used to validate CRC-SC enrichment. None of the markers studied in established cell lines, grown either in vitro or in vivo, consistently enriched for CRC-SCs. In the three other cellular models, CD44 and CD133 did not reliably enrich for stemness. In contrast, freshly isolated PDX-derived cells or early passage/newly established CRC cell lines with high ALDH activity formed spheres in vitro and enhanced tumorigenicity in vivo, whereas cells with low ALDH activity did not. PDX-derived cells, early passages/newly established CRC cell lines and cells from clinical specimen with high ALDH activity can be used to identify CRC-SC-enriched populations. Established CRC cell lines should not be used to isolate CSCs.

ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

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Lee Su-Chen

2008-02-01

Full Text Available Abstract Background Early relapse in colorectal cancer (CRC patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes. Methods Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R or triple (3R tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0 or III (any T N1 and 2 M0 and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU and leucovorin (LV. The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated. Results In this study, the distributions of GSTP1 (P = 0.003, ABCB1 (P = 0.001, TYMS (P ERCC2 (P XRCC1 (P = 0.006 genotypes in the Asian population, with the exception of MTHFR (P = 0.081, differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006, tumor invasion depth (P = 0.025, lymph node metastasis (P = 0

Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease.

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Murphy, Caitlin C; Sanoff, Hanna K; Stitzenberg, Karyn B; Baron, John A; Lund, Jennifer L; Sandler, Robert S

2017-01-01

Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 ( n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age age 50-69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50-69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years.

Performance Analysis of CRC Codes for Systematic and Nonsystematic Polar Codes with List Decoding

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Takumi Murata

2018-01-01

Full Text Available Successive cancellation list (SCL decoding of polar codes is an effective approach that can significantly outperform the original successive cancellation (SC decoding, provided that proper cyclic redundancy-check (CRC codes are employed at the stage of candidate selection. Previous studies on CRC-assisted polar codes mostly focus on improvement of the decoding algorithms as well as their implementation, and little attention has been paid to the CRC code structure itself. For the CRC-concatenated polar codes with CRC code as their outer code, the use of longer CRC code leads to reduction of information rate, whereas the use of shorter CRC code may reduce the error detection probability, thus degrading the frame error rate (FER performance. Therefore, CRC codes of proper length should be employed in order to optimize the FER performance for a given signal-to-noise ratio (SNR per information bit. In this paper, we investigate the effect of CRC codes on the FER performance of polar codes with list decoding in terms of the CRC code length as well as its generator polynomials. Both the original nonsystematic and systematic polar codes are considered, and we also demonstrate that different behaviors of CRC codes should be observed depending on whether the inner polar code is systematic or not.

Main: CRC101 [AT Atlas

Lifescience Database Archive (English)

Full Text Available CRC101 CRC1 Establishment of Chemical Library and Development of Protein Regulation... Technology Chemical library Tetsuo Nagano Graduate School of Pharmaceutical Sciences, The University CRC101.csml ...

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

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Tsuruta A

2016-11-01

Full Text Available Atsushi Tsuruta,1,* Kazuki Yamashita,2,* Hiroaki Tanioka,3 Akihito Tsuji,4,5 Michio Inukai,6 Toshiki Yamakawa,7 Tomoki Yamatsuji,8 Masanori Yoshimitsu,9 Kazuhiro Toyota,10 Taketoshi Yamano,11 Takeshi Nagasaka,12 Masazumi Okajima13 On behalf of the Japan Southwest Oncology Group (JSWOG 1Department of Digestive Surgery, Kawasaki Medical School Hospital, 2Department of Surgery, 3Department of Medical Oncology, Okayama Rosai Hospital, Okayama, 4Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, 5Department of Clinical Oncology, Faculty of Medicine, Kagawa University Hospital, Kagawa, 6Department of Medicine, Okayama Saiseikai General Hospital, Okayama, 7Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu, 8Department of General Surgery, Kawasaki Medical School, Okayama, 9Department of Surgery, Hiroshima City Asa Hospital, Hiroshima, 10Department of Surgery, National Hospital Organization Higashihirosima Medical Center, Higashihiroshima, 11Department of Surgery, Kurashiki Medical Center, 12Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 13Department of Surgery, Hiroshima City Hospital, Hiroshima, Japan *These authors contributed equally to this work Background: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC. Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were

Slender CRC Columns

DEFF Research Database (Denmark)

Aarup, Bendt; Jensen, Lars Rom; Ellegaard, Peter

2005-01-01

CRC is a high-performance steel fibre reinforced concrete with a typical compressive strength of 150 MPa. Design methods for a number of structural elements have been developed since CRC was invented in 1986, but the current project set out to further investigate the range of columns for which...

How does the serrated polyp pathway alter CRC screening and surveillance?

Science.gov (United States)

Kahi, Charles J

2015-03-01

Screening and surveillance for colorectal cancer (CRC) reduces mortality through the detection of early-stage adenocarcinoma, and more importantly the detection and removal of premalignant polyps. While adenomas have historically been considered the most common and screening-relevant precursor lesions, there is accumulating evidence showing that the serrated pathway is an important contributor to CRC, and a disproportionate contributor to interval or postcolonoscopy CRC, particularly in the proximal colon. The serrated pathway is characterized by mutations in the BRAF gene, high levels of methylation of promoter CpG islands (CIMP-high), and the sessile serrated adenoma/polyp (SSA/P) is the most important precursor lesion. The study of serrated polyps has been complicated by evolving nomenclature, substantial variation among pathologists in the identification of SSA/Ps, high variability in endoscopic detection rates, and uncertainty regarding the relation to synchronous and metachronous colonic neoplasia. This paper presents an overview of the serrated polyp pathway and discusses its clinical implications including its impact on CRC screening.

Effect of Crc and Hfq proteins on the transcription, processing, and stability of the Pseudomonas putida CrcZ sRNA.

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Hernández-Arranz, Sofía; Sánchez-Hevia, Dione; Rojo, Fernando; Moreno, Renata

2016-12-01

In Pseudomonas putida, the Hfq and Crc proteins regulate the expression of many genes in response to nutritional and environmental cues, by binding to mRNAs that bear specific target motifs and inhibiting their translation. The effect of these two proteins is antagonized by the CrcZ and CrcY small RNAs (sRNAs), the levels of which vary greatly according to growth conditions. The crcZ and crcY genes are transcribed from promoters PcrcZ and PcrcY, respectively, a process that relies on the CbrB transcriptional activator and the RpoN σ factor. Here we show that crcZ can also be transcribed from the promoter of the immediate upstream gene, cbrB, a weak constitutive promoter. The cbrB-crcZ transcript was processed to render a sRNA very similar in size to the CrcZ produced from promoter PcrcZ The processed sRNA, termed CrcZ*, was able to antagonize Hfq/Crc because, when provided in trans, it relieved the deregulated Hfq/Crc-dependent hyperrepressing phenotype of a ΔcrcZΔcrcY strain. CrcZ* may help in attaining basal levels of CrcZ/CrcZ* that are sufficient to protect the cell from an excessive Hfq/Crc-dependent repression. Since a functional sRNA can be produced from PcrcZ, an inducible strong promoter, or by cleavage of the cbrB-crcZ mRNA, crcZ can be considered a 3'-untranslated region of the cbrB-crcZ mRNA. In the absence of Hfq, the processed form of CrcZ was not observed. In addition, we show that Crc and Hfq increase CrcZ stability, which supports the idea that these proteins can form a complex with CrcZ and protect it from degradation by RNases. © 2016 Hernández-Arranz et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Evolving concepts in staging and treatment of colorectal cancer

NARCIS (Netherlands)

Sloothaak, D.A.M.

2015-01-01

For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases

Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives.

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Kahouli, Imen; Tomaro-Duchesneau, Catherine; Prakash, Satya

2013-08-01

Colorectal cancer (CRC) is the third most common form of cancer. Diverse therapies such as chemotherapy, immunotherapy and radiation have shown beneficial effects, but are limited because of their safety and toxicity. Probiotic formulations have shown great promise in CRC as preventive and early stage therapeutics. This review highlights the importance of a balanced intestinal microbiota and summarizes the recent developments in probiotics for treating CRC. Specifically, this report describes evidence of the role of probiotics in modulating the microbiota, in improving the physico-chemical conditions of the gut and in reducing oxidative stress. It also discusses the mechanisms of probiotics in inhibiting tumour progression, in producing anticancer compounds and in modulating the host immune response. Even though some of these effects were observed in several clinical trials, when probiotic formulations were used as a supplement to CRC therapies, the application of probiotics as biotherapeutics against CRC still needs further investigation.

Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

Directory of Open Access Journals (Sweden)

Caitlin C. Murphy

2017-01-01

Full Text Available Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC in younger (age < 50 populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute’s Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n=6,862. Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50 and older (age 50–69, age ≥ 70 CRC patients. Results. Younger patients were more likely to be black (13% and Hispanic (15% than patients aged 50–69 years (11% and 10%, resp. and ≥70 years (7% each. A larger proportion of young white (41% and Hispanic (33% patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%. The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%. Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years.

Assessment of Jordanian Patient's Colorectal Cancer Awareness and Preferences towards CRC Screening: Are Jordanians Ready to Embrace CRC Screening?

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Omran, Suha; Barakat, Husam; Muliira, Joshua Kanaabi; Bashaireh, Ibrahim; Batiha, Abdul-Moni'm

2015-01-01

Colorectal cancer (CRC is increasingly becoming a major cause of cancer morbidity and mortality in Jordan. However the population's level of awareness about CRC, CRC screening test preferences and willingness to embrace screening are not known. The aim of this study was to assess the level of CRC awareness and screening preferences among Jordanian patients. A survey assessing the CRC knowledge levels was distributed among patients attending outpatient gastroenterology clinics in public hospitals throughout Jordan. A total of 800 surveys were distributed and of these 713 (89.1%) were returned. Only 22% of the participants correctly judged CRC among the choices provided as the commonest cause of cancer related deaths. The majority of participants (68.3%) underestimated their risk for CRC. Only 26.8% correctly judged their life time risk while 5% overestimated their risk. Two thirds of participants (66%) were willing to pay 500 Jordanian Dinars (equivalent to 706 US$) in order to get a prompt colonoscopy if recommended by their physician, while 25.5% reported that they would rather wait for 6 months in order to get a free colonoscopy. Although the participants tended to underestimate their risk for CRC, they were mostly aware of CRC as a major cause of mortality and were willing to embrace the concept of CRC screening and bear the related financial costs. These findings about CRC awareness and propensity for screening provide a good foundation as the Jordanian health system moves forward with initiatives to promote CRC screening and prevention.

CRC-cards for Product Modelling

DEFF Research Database (Denmark)

Hvam, Lars; Riis, Jesper; Hansen, Benjamin Loer

2003-01-01

, transportation, service and decommissioning. A main challenge when building product models is to collect and document the product related data, information and knowledge in a structured way. CRC cards are index cards (or computerized versions of these) which are used to record proposed classes, the behavior......This paper describes the CRC (class, responsibility, collaboration) modelling process for building product models. A product model is normally represented in an IT system which contains data, information and knowledge on industrial products and their life cycle properties e.g. manufacturing...... of the classes, their responsibilities, and their relationship to other classes (collaboration). CRC modelling gives an effective, low-tech method for domain-experts, programmers and users to work closely together to identify, structure, understand and document a product model. CRC cards were originally...

Micro satellite instability in colorectal cancer stage II. Hospital Central de las fuerzas armadas

International Nuclear Information System (INIS)

Della Valle, A; Santander G; Camejo, N; Spera, G.

2010-01-01

Introduction: micro satellite instability (MSI) is a good prognostic factor in colorectal cancer (CRC) located. Its value as a predictive marker against adjuvant treatment of chemotherapy (CT) has been shown fluoropyrimidine in various publications. The MSI occurs in 15% of colorectal tumors and sporadic in 90% of tumors in the context of colorectal cancer syndrome hereditary nonpolyposis. In Uruguay there are no studies about this phenomenon. Objective: To determine the incidence of micro satellite instability in a sample of patients using the Hospital Central de las fuerzas armadas oncology service, association with a compatible family history and the histological features of the tumors associated therewith. Methods: The medical records of patients were analyzed with CRC diagnosed stage II between 01/2001 and 12/2009. Data of the patients were analyzed which had complete histology and evolution. Results: 30/52 patients (57.6%) were analyzed. 40% had a detected MSI by kits for Pcr (polymerase chain reaction) to D2S123, D5S250, D17S346, BAT25 and BAT26 according to the Bethesda criteria. In those patients they filed a MSI: the median age was 70 years; 58.3% male. No patient had a family history consistent with HNPCC. 5.6% (3) they received Adjuvant chemotherapy treatment. Regarding tumor characteristics: 75% (9) were T3, and T4 were 25% (3); 8.3% histologic grade I (1) II 58.3% (7) 8.3% III (1) without Data 33% (6). This tumor lymphocyte infiltration was reported in 25% (3), absent 33.3% (4), not reported in 41.6% (5). Conclusions: This is the first analysis of these characteristics carried out in Uruguay. The same has been detected MSI percentage higher than reported in the literature International. In either case a compatible family history met HNPCC

Post orchiectomy management in stage II testicular seminoma

International Nuclear Information System (INIS)

Singhal, S.; Dixit, S.; Ramana Murthy, R.; Neema, J.P.; Vyas, R.K.; Baboo, H.A.

1994-01-01

Twenty eight patients with stage II A and twenty patients with stage II B testicular seminoma were treated at this institute between January 1982 and December 1988. The three year crude survival observed in this retrospective analysis was 82% and 75% respectively. Post orchiectomy infradiaphragmatic radiotherapy was the mainstay of the treatment. In stage II A, 4 patients were administered adjuvant chemotherapy as well. Prophylactic mediastinal irradiation (PMI) was not employed as a routine in this subgroup. Eight patients (28%) relapsed (mediastinal nodes - 4, pulmonary - 3, scrotal - 1). In stage II B, twelve patients were treated with primary abdominal radiotherapy and of them 4 were delivered PMI as well. Induction chemotherapy was administered in remaining 8 patients. Seven patients (35%) relapsed (pulmonary-4, mediastinal nodes-3). Mediastinal recurrence was noted only in those who were treated with abdominal radiotherapy alone. Though salvage chemotherapy proved successful in 5 of the seven patients (70%) with nodal relapse, none of the patients with extranodal relapse responded to subsequent chemotherapy. For stage II A abdominal radiotherapy alone is recommended and for stage II B induction chemotherapy is advised keeping radiotherapy reserved for residual mass. PMI as a routine in stage II testicular seminoma is not advocated as no survival benefit is observed. (author) 15 refs., 6 tabs

Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC) is achievable for a high proportion of familial CRC by exome sequencing.

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Chubb, Daniel; Broderick, Peter; Frampton, Matthew; Kinnersley, Ben; Sherborne, Amy; Penegar, Steven; Lloyd, Amy; Ma, Yussanne P; Dobbins, Sara E; Houlston, Richard S

2015-02-10

Knowledge of the contribution of high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant to the counseling, treatment, and surveillance of CRC patients and families. To quantify the impact of germline mutation to familial CRC, we sequenced the mismatch repair genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases ascertained through a population-based United Kingdom national registry. In addition, we evaluated the contribution of mutations in the exonuclease domain (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC risk. Overall mutations (pathogenic, likely pathogenic) in MMR genes make the highest contribution to familial CRC (10.9%). Mutations in the other established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were identified in three patients with family histories consistent with dominant transmission of CRC. Collectively, mutations in the known genes account for 14.2% of familial CRC (89 of 626 cases; 95% CI = 11.5, 17.2). A genetic diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such analysis in clinical practice should enable the medical management of patients and their families to be optimized. Findings suggest CRC screening of POLE and POLD1 mutation carriers should be comparable to that afforded to those at risk of HNPCC. Although the risk of CRC associated with unexplained familial CRC is in general moderate, in some families the risk is substantive and likely to be the consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings have utility in the design of genetic analyses to identify such novel CRC risk genes. © 2015 by American Society of Clinical Oncology.

Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells.

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Zhang, G-Y; Yang, W-H; Chen, Z

2016-05-01

We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

Tape Storage and CRC Protection

CERN Document Server

Ha, Karel

2014-01-01

Over 100 Petabytes of data is stored on several kind of physical support, namely disks and tapes. Data on any physical support or traveling on a data link (network, fibre channel...) can be subject to silent data corruption. A possible improvement is introducing end-to-end data integrity from the filesystem down to the tape layer. For the tape back-end it can be done by using Logical Block Protection, which computes and compares CRC checksum of every single block of data. During my work, I improved on-the-fly CRC calculation for the tape storage system, which was achieved by introducing a multithreaded implementation - a technique applicable to arbitrary CRC algorithm. Finally, I per...

Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

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Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

2015-08-03

Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

The "Interval Walking in Colorectal Cancer" (I-WALK-CRC) study: Design, methods and recruitment results of a randomized controlled feasibility trial.

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Banck-Petersen, Anna; Olsen, Cecilie K; Djurhuus, Sissal S; Herrstedt, Anita; Thorsen-Streit, Sarah; Ried-Larsen, Mathias; Østerlind, Kell; Osterkamp, Jens; Krarup, Peter-Martin; Vistisen, Kirsten; Mosgaard, Camilla S; Pedersen, Bente K; Højman, Pernille; Christensen, Jesper F

2018-03-01

Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st , 2015, and February 1st , 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, P CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.

Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

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Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

2017-02-01

Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

The influence of marital status on stage at diagnosis and survival of patients with colorectal cancer.

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Li, Qingguo; Gan, Lu; Liang, Lei; Li, Xinxiang; Cai, Sanjun

2015-03-30

Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been fully studied in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status in each stage. In total, 112, 776 eligible patients were identified. Patients in the widowed group were more frequently elderly women, more common of colon cancer, and more stage I/II in tumor stage (P married group (94.72% VS 94.10%). Married CRC patients had better 5year cause-specific survival (CSS) than those unmarried (P married patients at stage I (94.8% vs 89.8%, P vs 76.5%, P vs 53.9%, P VS 8.2%, P unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

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Sobhani, I; Itti, E; Luciani, A; Baumgaertner, I; Layese, R; André, T; Ducreux, M; Gornet, J-M; Goujon, G; Aparicio, T; Taieb, J; Bachet, J-B; Hemery, F; Retbi, A; Mons, M; Flicoteaux, R; Rhein, B; Baron, S; Cherrak, I; Rufat, P; Le Corvoisier, P; de'Angelis, N; Natella, P-A; Maoulida, H; Tournigand, C; Durand Zaleski, I; Bastuji-Garin, S

2018-04-01

[18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13  €, P CRC. The control group had very close follow

Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability

International Nuclear Information System (INIS)

Yashiro, Masakazu; Hirakawa, Kosei; Boland, C Richard

2010-01-01

Microsatellite instability (MSI) occurs in 15% of colorectal cancers (CRC). The genetic targets for mutation in the MSI phenotype include somatic mutations in the transforming growth factor beta receptor typeII (TGFbetaRII), BAX, hMSH3 and hMSH6. It is not clear how mutations of these genes mediate tumor progression in the MSI pathway, and the temporal sequence of these mutations remains uncertain. In this study, early stage CRCs were examined for frameshift mutations in these target genes, and compared with late stage tumors and CRC cell lines. We investigated 6 CRC cell lines and 71 sporadic CRCs, including 61 early stage cancers and 10 late stage cancers. Mutations of repetitive mononucleotide tracts in the coding regions of TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR and Fas antigen were identified by direct sequencing. Thirteen (18.3%) of 71 CRC, including 9/61 (14.7%) early stage cancers and 4/10 (40%) late stage cancers, were identified as MSI and analyzed for frameshift mutations. No mutation in the target genes was observed in any of the 9 early stage MSI CRCs. In contrast, frameshift mutations of TGFbetaRII, BAX, hMSH3 and hMSH6 were present in 3/4 late stage MSI tumors. There is a statistical association (p = 0.014) between mutation in any one gene and tumor stage. TGFbetaRII, BAX, hMSH3 and hMSH6 mutations are relatively late events in the genesis of MSI CRCs. The frameshift mutations in these target genes might mediate progression from early to late stage cancer, rather than mediating the adenoma to carcinoma transition

Mucin Expression in Colorectal Cancer (CRC): Systematic Review and Meta-Analysis.

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Niv, Yaron; Rokkas, Theodore

2018-05-18

A body of evidence has suggested that mucins play an important role in adhesion, invasion, and cancer metastasis. However, this evidence is scarce and sometimes confusing. We performed a systematic review and meta-analysis of available studies to better define the role of mucins in the behavior of colorectal cancer (CRC). Medical literature was searched through November 30, 2017, using suitable keywords. Pooled estimates, that is, odd ratios (ORs), were obtained using fixed or random-effects models, as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test and I values, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger regression test. A total of 2234 CRC patients were included in 12 studies, eligible for meta-analysis. There was a significant difference concerning total mucin expression between CRC patients and controls [pooled ORs (95% confidence interval)=8.156 (2.624-25.354), test for overall effect Z=3.627, PCRC, that is advanced stage versus localized disease [ORs (95% confidence interval)=2.724 (1.211-6.127), Z= 2.423, P=0.015], as opposed to MUC2 and MUC4. MUC1 is overexpressed in CRC tissue comparing with healthy mucosa, and may have a role in the neoplastic transformation and metastatic process. MUC2 has probably no role in carcinogenesis.

More comprehensive discussion of CRC screening associated with higher screening.

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Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

2013-04-01

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

Directory of Open Access Journals (Sweden)

Bumpers Harvey L

2011-05-01

Full Text Available Abstract Background Although evaluation of at least 12 lymph nodes (LNs is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs. Methods To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected. Results For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91, but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64, examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87 and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26 decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p Conclusions Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.

Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC.

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Hu, Jianxia; Liu, Xiaoyi; Chi, Jingwei; Che, Kui; Feng, Yan; Zhao, Shihua; Wang, Zhongchao; Wang, Yangang

2018-01-01

Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (PCRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (PCRC, including tumor size, distant metastasis and advanced stages (III/IV) (PCRC.

Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.

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Nakamura, Kazunori; Yamashita, Keishi; Sawaki, Hiromichi; Waraya, Mina; Katoh, Hiroshi; Nakayama, Nobukazu; Kawamata, Hiroshi; Nishimiya, Hiroshi; Ema, Akira; Narimatsu, Hisashi; Watanabe, Masahiko

2015-03-01

Glycoprotein expression profile is dramatically altered in human cancers; however, specific glycogenes have not been fully identified. A comprehensive real-time polymerase chain reaction (PCR) system for glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of particular interest after GCNT2 expression and epigenetics were rigorously investigated in primary colorectal cancer (CRC). The highlights of this work can be summarized as follows: (i) Expression of GCNT2 was remarkably suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the normal tissues also showed a close association with that in the tumor tissues and reflected lymph node metastasis. We identified aberrant expression of GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and normal tissues. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Hereditary Colorectal Cancer (CRC Program in Latvia

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Irmejs Arvids

2003-12-01

Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer.

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Angela Chew

Full Text Available BACKGROUND: SPARC is a matricellular protein involved in tissue remodelling, cell migration and angiogenesis, while forkhead box P3 (FOXP3 protein functions as a transcription factor involved in immune cell regulation. Both SPARC and FOXP3 can play an anti-tumorigenic role in cancer progression. The aim was to determine if SPARC, FOXP3, CD8 and CD45RO expression levels are associated with colorectal cancer (CRC stage, disease outcome and long-term cancer-specific survival (CSS in stage II and III CRC. METHODS AND FINDINGS: SPARC expression was initially assessed in 120 paired normal and stage I-IV CRCs. Subsequently, approximately 1000 paired patient samples of stage II or III CRCs in tissue microarrays were stained for SPARC, FOXP3, CD8 or CD45RO. Proportional hazards modelling assessed correlations between these markers and clinicopathological data, including disease outcome and cancer specific survival (CSS. Both SPARC and FOXP3 expression were significantly greater in CRC than normal colon (p<0.0001. High SPARC expression correlated with good disease outcome (≥60 mths without disease recurrence, p = 0.0039 and better long-term CSS in stage II CRC (<0.0001. In stage III CRC, high SPARC expression correlated with better long-term CSS (p<0.0001 and less adjuvant chemotherapy use (p = 0.01. High FOXP3 correlated with a good disease outcome, better long-term CSS and less adjuvant chemotherapy use in stage II (p<0.0037, <0.0001 and p = 0.04 respectively, but not in stage III CRC. High CD8 and CD45RO expression correlated with better disease outcome in stage II CRC, and better CSS, but the differences were not as marked as for SPARC and FOXP3. CONCLUSIONS: These data suggest that high SPARC and FOXP3 are associated with better disease outcome in stage II CRC and may be prognostic indicators of CSS. Further assessment of whether these markers predict patients at high risk of recurrence with stage II CRC and functional studies of these

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients.

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De Monte, Ariella; Brunetti, Davide; Cattin, Luigi; Lavanda, Francesca; Naibo, Erica; Malagoli, Maria; Stanta, Giorgio; Bonin, Serena

2018-03-01

Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non-diabetic patients, have an inhibitory effect on cancer cell survival. The present population-based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health information system. CRC-specific and relative survival probabilities were computed for each group of patients defined by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five-year relative survival for stage III CRC was 101% [95% confidence interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2 treated with metformin, however not with ASA. The findings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis.

Gene expression profiles in stages II and III colon cancers

DEFF Research Database (Denmark)

Thorsteinsson, Morten; Kirkeby, Lene T; Hansen, Raino

2012-01-01

PURPOSE: A 128-gene signature has been proposed to predict outcome in patients with stages II and III colorectal cancers. In the present study, we aimed to reproduce and validate the 128-gene signature in external and independent material. METHODS: Gene expression data from the original material...... were retrieved from the Gene Expression Omnibus (GEO) (n¿=¿111) in addition to a Danish data set (n¿=¿37). All patients had stages II and III colon cancers. A Prediction Analysis of Microarray classifier, based on the 128-gene signature and the original training set of stage I (n¿=¿65) and stage IV (n...... correctly predicted as stage IV-like, and the remaining patients were predicted as stage I-like and unclassifiable, respectively. Stage II patients could not be stratified. CONCLUSIONS: The 128-gene signature showed reproducibility in stage III colon cancer, but could not predict recurrence in stage II...

Fault isolation through no-overhead link level CRC

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Chen, Dong; Coteus, Paul W.; Gara, Alan G.

2007-04-24

A fault isolation technique for checking the accuracy of data packets transmitted between nodes of a parallel processor. An independent crc is kept of all data sent from one processor to another, and received from one processor to another. At the end of each checkpoint, the crcs are compared. If they do not match, there was an error. The crcs may be cleared and restarted at each checkpoint. In the preferred embodiment, the basic functionality is to calculate a CRC of all packet data that has been successfully transmitted across a given link. This CRC is done on both ends of the link, thereby allowing an independent check on all data believed to have been correctly transmitted. Preferably, all links have this CRC coverage, and the CRC used in this link level check is different from that used in the packet transfer protocol. This independent check, if successfully passed, virtually eliminates the possibility that any data errors were missed during the previous transfer period.

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

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Visser Otto

2010-06-01

Full Text Available Abstract Background Diagnosing colorectal cancer (CRC at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear. Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. Methods Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B and late stage (Dukes C or D cancer. Patients were followed up for 3.5 years after diagnosis. Results In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE was 31 (1.5 weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27. In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93. In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01. In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median versus short delay (≤median was 1.8 (95% confidence interval (CI 1.1 to 3.0; p = 0.01. Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors. Conclusion In symptomatic CRC patients, a longer diagnostic and

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

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García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

2017-09-07

Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced

Is Travel Time to Colonoscopy Associated With Late-Stage Colorectal Cancer Among Medicare Beneficiaries in Iowa?

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Charlton, Mary E; Matthews, Kevin A; Gaglioti, Anne; Bay, Camden; McDowell, Bradley D; Ward, Marcia M; Levy, Barcey T

2016-09-01

Colorectal cancer (CRC) screening has been shown to decrease the incidence of late-stage colorectal cancer, yet a substantial proportion of Americans do not receive screening. Those in rural areas may face barriers to colonoscopy services based on travel time, and previous studies have demonstrated lower screening among rural residents. Our purpose was to assess factors associated with late-stage CRC, and specifically to determine if longer travel time to colonoscopy was associated with late-stage CRC among an insured population in Iowa. SEER-Medicare data were used to identify individuals ages 65 to 84 years old diagnosed with CRC in Iowa from 2002 to 2009. The distance between the centroid of the ZIP code of residence and the ZIP code of colonoscopy was computed for each individual who had continuous Medicare fee-for-service coverage for a 3- to 4-month period prior to diagnosis, and a professional claim for colonoscopy within that time frame. Demographic characteristics and travel times were compared between those diagnosed with early- versus late-stage CRC. Also, demographic differences between those who had colonoscopy claims identified within 3-4 months prior to diagnosis (81%) were compared to patients with no colonoscopy claims identified (19%). A total of 5,792 subjects met inclusion criteria; 31% were diagnosed with early-stage versus 69% with late-stage CRC. Those divorced or widowed (vs married) were more likely to be diagnosed with late-stage CRC (OR: 1.20, 95% CI: 1.06-1.37). Travel time was not associated with diagnosis of late-stage CRC. Among a Medicare-insured population, there was no relationship between travel time to colonoscopy and disease stage at diagnosis. It is likely that factors other than distance to colonoscopy present more pertinent barriers to screening in this insured population. Additional research should be done to determine reasons for nonadherence to screening among those with access to CRC screening services, given that over

Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H).

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Goldstein, J; Tran, B; Ensor, J; Gibbs, P; Wong, H L; Wong, S F; Vilar, E; Tie, J; Broaddus, R; Kopetz, S; Desai, J; Overman, M J

2014-05-01

The microsatellite instability-high (MSI-H) phenotype, present in 15% of early colorectal cancer (CRC), confers good prognosis. MSI-H metastatic CRC is rare and its impact on outcomes is unknown. We describe survival outcomes and the impact of chemotherapy, metastatectomy, and BRAF V600E mutation status in the largest reported cohort of MSI-H metastatic colorectal cancer (CRC). A retrospective review of 55 MSI-H metastatic CRC patients from two institutions, Royal Melbourne Hospital (Australia) and The University of Texas MD Anderson Cancer Center (United States), was conducted. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Median age was 67 years (20-90), 58% had poor differentiation, and 45% had stage IV disease at presentation. Median overall survival (OS) from metastatic disease was 15.4 months. Thirteen patients underwent R0/R1 metastatectomies, with median OS from metastatectomy 33.8 months. Thirty-one patients received first-line systemic chemotherapy for metastatic disease with median OS from the start of chemotherapy 11.5 months. No statistically significant difference in progression-free survival or OS was seen between fluoropyrimidine, oxaliplatin, or irinotecan based chemotherapy. BRAF V600E mutation was present in 14 of 47 patients (30%). BRAF V600E patients demonstrated significantly worse median OS; 10.1 versus 17.3 months, P = 0.03. In multivariate analyses, BRAF V600E mutants had worse OS (HR 4.04; P = 0.005), while patients undergoing metastatectomy (HR 0.11; P = CRC do not appear to have improved outcomes. BRAF V600E mutation is a poor prognostic factor in MSI-H metastatic CRC.

Geographic Variations of Colorectal and Breast Cancer Late-Stage Diagnosis and the Effects of Neighborhood-Level Factors.

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Lin, Yan; Wimberly, Michael C

2017-04-01

The purpose of this study was to examine the geographic variations of late-stage diagnosis in colorectal cancer (CRC) and breast cancer as well as to investigate the effects of 3 neighborhood-level factors-socioeconomic deprivation, urban/rural residence, and spatial accessibility to health care-on the late-stage risks. This study used population-based South Dakota cancer registry data from 2001 to 2012. A total of 4,878 CRC cases and 6,418 breast cancer cases were included in the analyses. Two-level logistic regression models were used to analyze the risk of late-stage CRC and breast cancer. For CRC, there was a small geographic variation across census tracts in late-stage diagnosis, and residing in isolated small rural areas was significantly associated with late-stage risk. However, this association became nonsignificant after adjusting for census-tract level socioeconomic deprivation. Socioeconomic deprivation was an independent predictor of CRC late-stage risk, and it explained the elevated risk among American Indians. No relationship was found between spatial accessibility and CRC late-stage risk. For breast cancer, no geographic variation in the late-stage diagnosis was observed across census tracts, and none of the 3 neighborhood-level factors was significantly associated with late-stage risk. Results suggested that socioeconomic deprivation, rather than spatial accessibility, contributed to CRC late-stage risks in South Dakota as a rural state. CRC intervention programs could be developed to target isolated small rural areas, socioeconomically disadvantaged areas, as well as American Indians residing in these areas. © 2016 National Rural Health Association.

Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer

International Nuclear Information System (INIS)

Pectasides, Dimitrios; Karavasilis, Vasilios; Papaxoinis, George; Gourgioti, Georgia; Makatsoris, Thomas; Raptou, Georgia; Vrettou, Eleni; Sgouros, Joseph; Samantas, Epaminontas; Basdanis, George; Papakostas, Pavlos; Bafaloukos, Dimitrios; Kotoula, Vassiliki; Kalofonos, Haralambos P.; Scopa, Chrisoula D.; Pentheroudakis, George; Fountzilas, George

2015-01-01

The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC). Patients were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A, FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status were also assessed. Between 2005 and 2008, 441 patients were enrolled, with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5–83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9–83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4–89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one–two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions. No significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size

Polar Coding with CRC-Aided List Decoding

Science.gov (United States)

2015-08-01

TECHNICAL REPORT 2087 August 2015 Polar Coding with CRC-Aided List Decoding David Wasserman Approved...list decoding . RESULTS Our simulation results show that polar coding can produce results very similar to the FEC used in the Digital Video...standard. RECOMMENDATIONS In any application for which the DVB-S2 FEC is considered, polar coding with CRC-aided list decod - ing with N = 65536

Relationship between stage II transport and number of chewing strokes as mastication progresses.

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Yamashita, Shuichiro; Sugita, Daisuke; Matsuo, Koichiro

2013-10-02

As mastication progresses, little is known about the occurrence of the stage II transport (oro-pharyngeal bolus transport). This study aimed to investigate the relationship between stage II transport and bolus aggregation in the pharynx and the number of chewing strokes. Twenty-five clinical residents with natural dentitions were recruited. The subjects were asked to chew gummy jelly with their preferred rhythm and to swallow the bolus at their preferred timing. To investigate stage II transport and bolus aggregation in the pharynx, a transnasal endoscope was used. The number of chewing strokes was measured by electromyographic activity from the masseter muscle. The mean numbers of chewing strokes of pre-stage II transport and post-stage II transport were 29.8 and 8.1, respectively; the difference was significant (pchewing strokes of pre-stage II transport to that of post-stage II transport was 4.0 to 1.0. This study showed that stage II transport started at four-fifths of the way along the progress of mastication, and that stage II transport and bolus aggregation in the pharynx are related to the number of chewing strokes. © 2013. Published by Elsevier Inc. All rights reserved.

Mining, Validation, and Clinical Significance of Colorectal Cancer (CRC)-Associated lncRNAs.

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Sun, Xiangwei; Hu, Yingying; Zhang, Liang; Hu, Changyuan; Guo, Gangqiang; Mao, Chenchen; Xu, Jianfeng; Ye, Sisi; Huang, Guanli; Xue, Xiangyang; Guo, Aizhen; Shen, Xian

2016-01-01

Colorectal cancer (CRC) is one of the deadliest tumours, but its pathogenesis remains unclear. The involvement of differentially expressed long non-coding RNAs (lncRNAs) in CRC tumorigenesis makes them suitable tumour biomarkers. Here, we screened 150 cases of CRC and 85 cases of paracancerous tissues in the GEO database for differentially expressed lncRNAs. The levels of lncRNA candidates in 84 CRC and paracancerous tissue samples were validated by qRT-PCR and their clinical significance was analyzed. We identified 15 lncRNAs with differential expression in CRC tumours; among them, AK098081 was significantly up-regulated, whereas AK025209, BC040303, BC037331, AK026659, and CR749831 were down-regulated in CRC. In a receiver operating characteristic curve analysis, the area under the curve for the six lncRNAs was 0.914. High expression of AK098081 and low expression of BC040303, CR749831, and BC037331 indicated poor CRC differentiation. CRC patients with lymph node metastasis had lower expression of BC037331. In addition, the group with high AK098081 expression presented significantly lower overall survival and disease-free survival rates than the low-expression group, confirming AK098081 as an independent risk factor for CRC patients. In conclusion, we have identified multiple CRC-associated lncRNAs from microarray expression profiles that can serve as novel biomarkers for the diagnosis and prognosis of CRC.

A Novel Least Significant Bit First Processing Parallel CRC Circuit

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Xiujie Qu

2013-01-01

Full Text Available In HDLC serial communication protocol, CRC calculation can first process the most or least significant bit of data. Nowadays most CRC calculation is based on the most significant bit (MSB first processing. An algorithm of the least significant bit (LSB first processing parallel CRC is proposed in this paper. Based on the general expression of the least significant bit first processing serial CRC, using state equation method of linear system, we derive a recursive formula by the mathematical deduction. The recursive formula is applicable to any number of bits processed in parallel and any series of generator polynomial. According to the formula, we present the parallel circuit of CRC calculation and implement it with VHDL on FPGA. The results verify the accuracy and effectiveness of this method.

Radiotherapy and chemotherapy in stages I and II non-Hodgkin's lymphomas of Waldeyer's ring

International Nuclear Information System (INIS)

Hayabuchi, Naofumi; Jingu, Kenichi; Miyoshi, Makoto; Akasi, Yuko; Masuda, Koji; Komiyama, Sotaro; Kikuchi, Masahiro.

1990-01-01

Sixty-four patients with stages I and II non-Hodgkin's lymphomas (NHL) involving Waldeyer's ring treated between 1970 and 1987 were reviewed. Patients with stage II NHL were subdivided into stage II1 (limited type) and stage II2 (advanced type) from the state of neck nodes. Stage II1 was defined as involvement of unilateral cervical nodes less than 4 cm in diameter as well as Waldeyer's ring involvement. Other stage II cases were classified as stage II2. All 17 patients with stage I HNL were treated with radiation therapy alone. Their diseases were well controlled, and none of them died of causes related to the lymphoma. Among 14 patients with stage II1 NHL, the 5-year survival rate for the 9 patients treated with radiation therapy alone was 87.5%. Until 1982, 19 of 21 patients with stage II2 NHL treated with radiation therapy alone or radiation therapy and adjuvant chemotherapy (VEMP or COPP) died within 5 years mainly of disseminated diseases. Since 1983, CHOP had been used as the main treatment as well as radiotherapy for the 12 stage II2 NHL patients. So far, only 3 of them relapsed and 2 of them died of causes related to the lymphoma. Only 1 of these 12 patients was T-cell lymphoma compared to 7 of 9 stage II2 patients before 1982. This suggests that patients with stage I and those with limited stage II can be safely treated with radiotherapy. Also aggressive chemotherapy as well as radiotherapy should be used for patients with advanced stage II HNL involving Waldeyer's ring. (author)

Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

Science.gov (United States)

2013-01-15

Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

Science.gov (United States)

Nguyen, Minh Nam; Choi, Tae Gyu; Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-10-13

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

Science.gov (United States)

Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

2017-04-01

The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

29 CFR 37.88 - Who may contact CRC about a complaint?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Who may contact CRC about a complaint? 37.88 Section 37.88... PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998 (WIA) Compliance Procedures § 37.88 Who may contact CRC... contact CRC for information about the complaint. The Director will determine what information, if any...

KRAS polymorphisms are associated with survival of CRC in Chinese population.

Science.gov (United States)

Dai, Qiong; Wei, Hui Lian; Huang, Juan; Zhou, Tie Jun; Chai, Li; Yang, Zhi-Hui

2016-04-01

rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

Detection of colorectal cancer (CRC by urinary volatile organic compound analysis.

Directory of Open Access Journals (Sweden)

Ramesh P Arasaradnam

Full Text Available Colorectal cancer (CRC is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB testing has largely been superseded by Faecal Immunochemical testing (FIT, but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs signature(s for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer. FAIMS is able to identify Inflammatory Bowel disease (IBD patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK. Data was processed using Fisher Discriminant Analysis (FDA after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS with potential as a novel screening tool.

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

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Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

2014-01-01

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

Contemporary management of stage I and II seminoma.

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Chung, Peter; Warde, Padraig

2013-10-01

Seminoma represents about 60 % of all testicular germ cell tumors. At presentation about 80 % of patients have stage I and about 15 % have stage II disease. The last three decades have seen a substantial change in the philosophy of management with the success of surveillance as a strategy to minimize unnecessary treatment, recognition of the late effects of radiation therapy, and the success of cisplatin-based chemotherapy as curative treatment either in the first-line or salvage setting. Overall, in stage I disease where 80-85 % are cured with orchiectomy alone, efforts now are directed at reducing the burden of the disease and its diagnosis on patients with increasing utilization of surveillance and decreased employment of adjuvant therapy. For stage II disease, balancing the relative toxicities of radiation and chemotherapy while avoiding the use of multimodality therapy due to the additive long-term toxicity has become the priority.

Stage II Seminoma

International Nuclear Information System (INIS)

Sagerman, R.H.; Kotlove, D.J.; Regine, W.; Chung, C.T.; King, G.A.; Dalai, P.S.

1988-01-01

Between 1966 and 1985, 32 patients with stage II (21 A,11 B) testicular seminoma were treated with postorchiectomy irradiation to the retroperitoneal and ipsilateral iliac nodes; 28 received elective mediastinal-supraclavicular irradiation. The median follow-up was 8 1/2 years; 29 patients were followed up for over 3 years and 24 for over 5 years. Twenty-eight patients remain alive and well and four have die, two of a second primary cancer. Two patients developed recurrent seminoma in the mediastinum; these patients showed a variant lymphangiographic pattern. Both remain well after further irradiation or irradiation plus chemotherapy. A third patient developed nonseminomatous ''recurrence'' in the radiation field and is well after chemotherapy

Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

International Nuclear Information System (INIS)

Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P.

1989-01-01

In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor

Systematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival.

Directory of Open Access Journals (Sweden)

Pan Li

Full Text Available We performed a systematic screening of colorectal cancer (CRC tissues to investigate whether mismatch repair (MMR status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP.The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC from cancer tissue samples of 2233 consecutive CRC patients.We observed that most CRC patients with a proficient MMR (pMMR status tended to have simultaneous ERCC1 protein expression (P< 0.001. Stage III CRC patients with deficient MMR (dMMR had higher prognoses than the same stage patients with pMMR (DFS: 74% vs 65%, P = 0.04; OS: 79% vs 69%, P = 0.04. Here, dMMR is also associated with poorer survival for stage II patients after chemotherapy (DFS: 66% vs 78%, P = 0.04. Stage II and III patients that were shown to express ERCC1 protein had higher DFS and OS than those that were deficient in expression (stage II, DFS: 83% vs 70%, P = 0.006; OS 85% vs 73%, P = 0.02. Stage III, DFS: 67% vs56%, P = 0.03; OS: 71% vs 57%, P = 0.04.Our results indicate that dMMR appeared to predictive of a survival benefit for stage III CRC patients. We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship.

MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

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Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

2015-04-01

Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

CRC concise encyclopedia of mathematics

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Weisstein, Eric W

2003-01-01

Upon publication, the first edition of the CRC Concise Encyclopedia of Mathematics received overwhelming accolades for its unparalleled scope, readability, and utility. It soon took its place among the top selling books in the history of Chapman & Hall/CRC, and its popularity continues unabated. Yet also unabated has been the dedication of author Eric Weisstein to collecting, cataloging, and referencing mathematical facts, formulas, and definitions. He has now updated most of the original entries and expanded the Encyclopedia to include 1000 additional pages of illustrated entries. The accessibility of the Encyclopedia along with its broad coverage and economical price make it attractive to the widest possible range of readers and certainly a must for libraries, from the secondary to the professional and research levels. For mathematical definitions, formulas, figures, tabulations, and references, this is simply the most impressive compendium available.

Do recent epidemiologic observations impact who and how we should screen for CRC?

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Bortniker, Ethan; Anderson, Joseph C

2015-03-01

Colorectal cancer (CRC) screening is recommended to begin at age 50 for those patients with no significant family history of CRC. However, even within this group of average-risk patients, there is data to suggest that there may be variation in CRC risk. These observations suggest that perhaps CRC screening should be tailored to target those patients at higher risk for earlier or more invasive screening as compared to those individuals at lower risk. The strategy of how to identify those higher-risk patients may not be straightforward. One method might be to use single risk factors such as smoking or elevated BMI as has been suggested in the recent American College of Gastroenterology CRC screening guidelines. Another paradigm involves the use of models which incorporate several risk factors to stratify patients by risk. This article will highlight recent large studies that examine recognized CRC risk factors as well as review recently developed CRC risk models. There will also be a discussion of the application of these factors and models in an effort to make CRC screening more efficient.

MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in colorectal cancer (CRC).

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Tong, Feng; Ying, Youhua; Pan, Haihua; Zhao, Wei; Li, Hongchen; Zhan, Xiaoli

2018-01-17

MicroRNAs (miRNAs) have an important role in the regulation of tumor development and metastasis. In this study, we investigated the clinical and prognostic value as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR-466 expression was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT-PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466 mimics or negative control miRNA. Effects of miR-466 on SW-620 cell proliferation, cell cycle and apoptosis, and invasion were investigated using CCK-8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was significantly downregulated in tumor tissues compared to matched adjacent non-tumor tissues. Low expression of miR-466 was significantly correlated with the tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant metastasis. The overall survival of CRC patients with low miR-466 expression was significantly shorter compared to high-miR-466 expression group (log-rank test: p = 0.0103). Multivariate analysis revealed that low miR-466 expression was associated with poor prognosis in CRC patients. The ectopic expression of miR-466 suppressed cell proliferation and migration/invasion, as well as induced G0/G1 arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466 decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as a suppressor miRNA in CRC and may be used as a prognostic factor in these patients.

Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

DEFF Research Database (Denmark)

Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

2011-01-01

; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

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Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle

2016-01-01

The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

2011-01-01

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

2011-11-15

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

12 CFR 617.7310 - What is the review process of the CRC?

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2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is the review process of the CRC? 617.7310... on Applications; Review of Credit Decisions § 617.7310 What is the review process of the CRC? (a) How will an applicant or borrower know when the CRC will consider the review request? The qualified lender...

The Pseudomonas aeruginosa catabolite repression control protein Crc is devoid of RNA binding activity.

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Milojevic, Tetyana; Grishkovskaya, Irina; Sonnleitner, Elisabeth; Djinovic-Carugo, Kristina; Bläsi, Udo

2013-01-01

The Crc protein has been shown to mediate catabolite repression control in Pseudomonas, leading to a preferential assimilation of carbon sources. It has been suggested that Crc acts as a translational repressor of mRNAs, encoding functions involved in uptake and breakdown of different carbon sources. Moreover, the regulatory RNA CrcZ, the level of which is increased in the presence of less preferred carbon sources, was suggested to bind to and sequester Crc, resulting in a relief of catabolite repression. Here, we determined the crystal structure of Pseudomonas aeruginosa Crc, a member of apurinic/apyrimidinic (AP) endonuclease family, at 1.8 Å. Although Crc displays high sequence similarity with its orthologs, there are amino acid alterations in the area corresponding to the active site in AP proteins. Unlike typical AP endonuclease family proteins, Crc has a reduced overall positive charge and the conserved positively charged amino-acid residues of the DNA-binding surface of AP proteins are partially substituted by negatively charged, polar and hydrophobic residues. Crc protein purified to homogeneity from P. aeruginosa did neither display DNase activity, nor did it bind to previously identified RNA substrates. Rather, the RNA chaperone Hfq was identified as a contaminant in His-tagged Crc preparations purified by one step Ni-affinity chromatography from Escherichia coli, and was shown to account for the RNA binding activity observed with the His-Crc preparations. Taken together, these data challenge a role of Crc as a direct translational repressor in carbon catabolite repression in P. aeruginosa.

Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.

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Wei, Yong; Zhang, Heng; Gao, Zeng-Qiang; Xu, Jian-Hua; Liu, Quan-Sheng; Dong, Yu-Hui

2013-01-01

The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5'-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 β strands surrounded by 13 helices, forming a four-layered α/β-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

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2017-05-03

Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

Science.gov (United States)

Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Colorectal cancer diagnosis in 2012: A new focus for CRC prevention--more serration, less inflammation

NARCIS (Netherlands)

East, James E.; Dekker, Evelien

2013-01-01

Knowledge of colorectal cancer (CRC) risks has been rebalanced in 2012. The 'serrated pathway' to CRC, exemplified by serrated polyposis syndrome, emphasizes the importance of serrated lesions. The dogma that patients with IBD are at high risk of CRC, however, might be overstated; optimizing CRC

A mid-term follow-up of Koutsogiannis’ osteotomy in adult-acquired flatfoot stage II and “early stage III”

Directory of Open Access Journals (Sweden)

Arvinius Camilla

2017-01-01

Full Text Available Introduction: Koutsogiannis’ osteotomy has been widely described to treat adult-acquired flatfoot. However, few articles describe its midterm follow-up. Our aim was to study clinical and radiological outcomes at least one year after surgery and to analyze whether a combined procedure on the medial soft tissue affected these outcomes. Methods: We performed a retrospective study of 30 feet of patients who underwent a Koutsogiannis’ osteotomy due to adult-acquired flatfoot stage II and “early stage III”: a stage III acquired flatfoot without any important structural deformities. The parameters studied were additional medial soft tissue procedures, clinical outcome through the American Orthopaedic Foot and Ankle Society (AOFAS ankle and midfoot score as well as complications and radiological measurements. Results: Sixteen cases were “early stage III” and 14 stage II. Thirteen patients underwent an associated posterior tibial tendon (PTT revision: in three cases an end-to-end suture was possible, seven cases needed a FDL transposition, and three underwent synovectomy. Statistically significant improvement was found in the AOFAS score although no significant changes were seen radiologically. No additional benefit was found with the revision of the posterior tibial tendon. As to clinical and radiological results, no differences were found between stage II and “early stage III”. Five cases presented a mild dysesthesia but only one patient needed neurolysis. Conclusions: We consider the Koutsogiannis’ osteotomy to be a safe and effective procedure to reduce pain in patients with stage II and “early stage III” adult-acquired flatfoot.

CRC-cards to support development and maintenance of product configuration systems

DEFF Research Database (Denmark)

Haug, Anders; Hvam, Lars

2009-01-01

This article presents a new definition of special Class, Responsibility and Collaboration (CRC) cards to be used for the development and maintenance of Product Configuration Systems (PCSs). CRC cards were introduced as an informal and user-friendly technique for teaching object-oriented modelling...... and maintenance of PCSs. This procedure has since been applied in several configuration projects and further developed at the Centre for Product Modelling (CPM) at the Technical University of Denmark. However, the investigations of two companies that applies CRC cards to document the knowledge base of their PCSs...

Implementation of the II. Stage decommissioning of A1 NPP

International Nuclear Information System (INIS)

Ficher, T.

2015-01-01

Presentation is focused on the implementation of the II. stage decommissioning of A1 NPP. Introductory part focuses on brief characteristics of the power plant with a history of operation, basic technical parameters and actions that were made after operation. The next section describes the basic schedule for decommissioning, structure of management and implementation of the II. stage decommissioning of the A1 NPP and objectives of the individual stages. The last and largest part of the presentation is devoted to detailed description of the II. stage decommissioning of the A1 NPP, its individual tasks and verbal and visual description of the activities that were performed. Presented is decommissioning of the technology and construction of external objects NPP A1 including storage tanks for liquid RAW, next are presented activities carried out in the Main Production Unit - decommissioning of non-operating technologies in various places/rooms, management of waste arising from these activities, treatment of case of A1 long-term spent fuel storage and long-term spent fuel storage. The subsequent section is devoted to the management and handling of contaminated soil, concrete and construction waste, including management of VLLW. (authors)

Postoperative radiotherapy for stage I/II seminoma: results for 212 patients

International Nuclear Information System (INIS)

Bauman, Glenn S.; Venkatesan, Varagur M.; Ago, C. Tetteh; Radwan, John S.; Dar, A. Rashid; Winquist, Eric W.

1998-01-01

Purpose: A retrospective review of patients with Stage I and II seminoma treated at a regional cancer center was performed to assess the long term efficacy and toxicity associated with post operative radiotherapy. Methods and Materials: Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. Results: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. No prognostic factors associated with increased risk of late toxicity or second malignancy were identified, likely a consequence of the small number of these events. Conclusion: Survival and toxicity were comparable to that reported in the literature. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma

Second Stage (S-II) Arrives at Marshall Space Flight Center For Testing

Science.gov (United States)

2004-01-01

The business end of a Second Stage (S-II) slowly emerges from the shipping container as workers prepare to transport the Saturn V component to the testing facility at MSFC. The Second Stage (S-II) underwent vibration and engine firing tests. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa

Science.gov (United States)

Pusic, Petra; Tata, Muralidhar; Wolfinger, Michael T.; Sonnleitner, Elisabeth; Häussler, Susanne; Bläsi, Udo

2016-12-01

Pseudomonas aeruginosa (PA) can thrive in anaerobic biofilms in the lungs of cystic fibrosis (CF) patients. Here, we show that CrcZ is the most abundant PA14 RNA bound to the global regulator Hfq in anoxic biofilms grown in cystic fibrosis sputum medium. Hfq was crucial for anoxic biofilm formation. This observation complied with an RNAseq based transcriptome analysis and follow up studies that implicated Hfq in regulation of a central step preceding denitrification. CrcZ is known to act as a decoy that sequesters Hfq during relief of carbon catabolite repression, which in turn alleviates Hfq-mediated translational repression of catabolic genes. We therefore inferred that CrcZ indirectly impacts on biofilm formation by competing for Hfq. This hypothesis was supported by the findings that over-production of CrcZ mirrored the biofilm phenotype of the hfq deletion mutant, and that deletion of the crcZ gene augmented biofilm formation. To our knowledge, this is the first example where competition for Hfq by CrcZ cross-regulates an Hfq-dependent physiological process unrelated to carbon metabolism.

The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development.

Science.gov (United States)

Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

2014-11-01

CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far generally accepted. © The Author 2014. Published by

B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

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Jiali Li

2018-01-01

Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

Two technicians apply insulation to S-II second stage

Science.gov (United States)

1964-01-01

Two technicians apply insulation to the outer surface of the S-II second stage booster for the Saturn V moon rocket. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

Science.gov (United States)

2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer

International Nuclear Information System (INIS)

Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.

2013-01-01

High-level evidence supports adjuvant radiotherapy for rectal cancer. We examined the influence of socio demographic factors on patterns of adjuvant radiotherapy for resected Stage II/III rectal cancer. Methods. Patients undergoing surgical resection for stage II/III rectal cancer were identified in SEER registry. Results. A total of 21,683 patients were identified. Majority of patients were male (58.8%), white (83%), and with stage III (54.9%) and received radiotherapy (66%). On univariate analysis, male gender, stage III, younger age, year of diagnosis, and higher socioeconomic status (SES) were associated with radiotherapy. Radiotherapy was delivered in 84.4% of patients <50; however, only 32.8% of those are >80 years. Logistic regression demonstrated a significant increase in the use of radiotherapy in younger patients who are 50 (OR, 10.3), with stage III (OR, 1.21), males (OR, 1.18), and with higher SES. Conclusions. There is a failure to conform to standard adjuvant radiotherapy in one-third of patients, and this is associated with older age, stage II, area-level of socioeconomic deprivation, and female sex.

Observations on Polar Coding with CRC-Aided List Decoding

Science.gov (United States)

2016-09-01

TECHNICAL REPORT 3041 September 2016 Observations on Polar Coding with CRC-Aided List Decoding David Wasserman Approved for public release. SSC...described in [2, 3]. In FY15 and FY16 we used cyclic redundancy check (CRC)-aided polar list decoding [4]. Section 2 describes the basics of polar coding ...and gives details of the encoders and decoders we used. In the course of our research, we performed simulations of polar codes in hundreds of cases

12 CFR 617.7305 - What is a CRC and who are the members?

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is a CRC and who are the members? 617.7305... on Applications; Review of Credit Decisions § 617.7305 What is a CRC and who are the members? The... decisions made by a qualified lender. The CRC may only review adverse credit decisions at the request of the...

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

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Rowe Krista L

2008-11-01

Full Text Available Abstract Background Stage at diagnosis plays a significant role in colorectal cancer (CRC survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods Two distinct healthcare populations in the United States (US were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic. Race was dichotomized (white, non-white. Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77% reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD age 67 (11, Charlson index 2.0 (1.0, and were 63% white. FFS patients were mean age 61 (13, Charlson index 1.6 (1.0, and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR 0.76, 95% confidence interval (CI 0.58–1.00; p = 0.045; no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57. In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion Higher comorbidity may lead to

A Risk Prediction Model for Sporadic CRC Based on Routine Lab Results.

Science.gov (United States)

Boursi, Ben; Mamtani, Ronac; Hwang, Wei-Ting; Haynes, Kevin; Yang, Yu-Xiao

2016-07-01

Current risk scores for colorectal cancer (CRC) are based on demographic and behavioral factors and have limited predictive values. To develop a novel risk prediction model for sporadic CRC using clinical and laboratory data in electronic medical records. We conducted a nested case-control study in a UK primary care database. Cases included those with a diagnostic code of CRC, aged 50-85. Each case was matched with four controls using incidence density sampling. CRC predictors were examined using univariate conditional logistic regression. Variables with p value CRC prediction models which included age, sex, height, obesity, ever smoking, alcohol dependence, and previous screening colonoscopy had an AUC of 0.58 (0.57-0.59) with poor goodness of fit. A laboratory-based model including hematocrit, MCV, lymphocytes, and neutrophil-lymphocyte ratio (NLR) had an AUC of 0.76 (0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6 %. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR, and oral hypoglycemic use had an AUC of 0.80 (0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7 %. Similar results were shown in an internal validation set. A laboratory-based risk model had good predictive power for sporadic CRC risk.

Brachytherapy for elderly patients with stage II tongue cancer

International Nuclear Information System (INIS)

Kimura, Tomoki; Hirokawa, Yutaka; Fujita, Minoru; Murakami, Yuji; Kenjo, Masahiro; Kaneyasu, Yuko; Ito, Katsuhide

2003-01-01

In treatment choices of stage II (T2N0M0) tongue cancer, brachytherapy is less invasive and superior in function preservation, therefore its role is more important in elderly patients. The aim of this study was to evaluate treatment results and morbidity of brachytherapy for elderly patients with stage II tongue cancer. Between 1980 and 2001, 198 patients with stage II tongue cancer were treated with brachytherapy at Hiroshima University Hospital. Patient ages ranged from 21 to 89 years old (median: 62 years old). Patients were divided into three groups as follows: 119 patients younger than 65 years old (Non-Elderly group), 53 patients between 65 and 75 years old (Junior Elderly group), and 26 patients 75 years or older (Senior Elderly group). Radiotherapy was performed in 101 patients with brachytherapy alone, and in 97 patients with brachytherapy and external radiotherapy. Chemotherapy was also performed in 77 patients. Follow-up period ranged from 4 to 243 months (median: 55 months). The 5-year local control rate was 85% in the Non-Elderly group, 85% in the Junior Elderly group and 81% in the Senior Elderly group. There was no significant difference among these groups. The 5-year cause-specific survival rate was 85%, 81% and 70% respectively. The Senior Elderly group showed poorer cause-specific survival rate than the other two groups (p=0.03). There was also a tendency of higher incidence of neck metastasis and low salvage rate by neck dissection in the Senior Elderly group. Although the Senior Elderly group showed poorer cause-specific survival rate, the local control rate was similar to those of the other two groups. Brachytherapy is an effective treatment option for elderly patients with stage II tongue cancer. (author)

Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

Science.gov (United States)

Tsoi, H; Lam, K C; Dong, Y; Zhang, X; Lee, C K; Zhang, J; Ng, S C; Ng, S S M; Zheng, S; Chen, Y; Fang, J; Yu, J

2017-11-02

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.

Radiation therapy for stage I and II testicular seminoma

International Nuclear Information System (INIS)

Latini, P.; Aristei, C.; Maranzano, E.; Checcaglini, F.; Panizza, M.B.; Perrucci, E.; Bellucci, M.C.

1988-01-01

From june 1977 through june 1987, 46 patients (36 evaluable) affected by stage I and II non-bulky testicular seminoma were treated with postoperative telecobaltotherapy (TCT). In stage I seminomas, radiotherapy was extended to the omolateral iliac and the para-aortic areas (total dose: 30 Gy over 4 weeks). In stage II seminomas, the subdiaphragmatic lymph nodes were irradiated with 40-45 Gy over 5-6 weeks; after an interval of one month the subdiaphragmatic lymph nodes were irradiated again with a total dose of 25 Gy over 3.5 weeks. Minimal follow-up lasted two years and maximum ten years (average:5.5%) recurrences occurred, but salvage radiotherapy and salvage chemotherapy respectively allowed a complete permanent remission. One patient died from a different neoplasia with no evidence of testicular involvement. The 5-year actuarial survival is 96.6±3.4. In 20% of the patients the side effects were nausea and/or vomiting, easily controlled. No late complications were observed

Second Stage (S-II) Plays Key Role in Apollo missions

Science.gov (United States)

1970-01-01

This photograph of the Saturn V Second Stage (S-II) clearly shows the cluster of five powerful J-2 engines needed to boost the Apollo spacecraft into earth orbit following first stage separation. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

29 CFR 37.38 - What information must grant applicants and recipients provide to CRC?

Science.gov (United States)

2010-07-01

... provide to CRC? 37.38 Section 37.38 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... information must grant applicants and recipients provide to CRC? In addition to the information which must be collected, maintained, and, upon request, submitted to CRC under § 37.37: (a) Each grant applicant and...

The European Dioxin Emission Inventory. Stage II. Final report

Energy Technology Data Exchange (ETDEWEB)

Quass, U.; Fermann, M.; Broeker, G.

2001-07-01

For Stage II of the European Dioxin Project the following objectives were set: - Amendment of existing emission data collected for most relevant emission sources in order to reduce uncertainties of emission estimates. Collecting first emission data from countries not yet performing dioxin emission measurement programs. Extending the inventory of dioxin emissions to ambient air produced in Stage I by a complementary study on emissions to land and water. Extending the regional scope of data collection to countries in Central Europe. The report of Stage II of the European Dioxin Project is presented in 3 Volumes. Volume 1 contains an overview on the background and approach of different activities carried out and on the results obtained. These results are put into a broader view regarding the dioxin reduction measures in Europe leading to conclusions and recommendation for future work. Volume 2 of the report contains a detailed presentation of the sub-projects carried out. The chapters of Volume 2 are structured in a similar manner and start with a short summary in order to allow for a fast cross-reading. In the case of the desk-top studies an overview of the main results or statements is given. Regarding emission measurements details on the experimental set-up and the facilities being investigated are presented. Volume 3 contains a re-evaluation of the dioxin emission inventory presented for the most relevant sources types in the Stage I report. New data gathered from the projects of Stage II as well as from independent activities in the European countries are considered for a revision of the 1995 emission estimates. Additionally, based on current trends and activities the PCDD/F emissions for the years 2000 and 2005 are estimated. Finally, an attempt is made to evaluate the PCDD/F emission reduction rates which might be possible to achieve by the year 2005 compared to 1985. (orig.)

Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC.

Science.gov (United States)

Wang, Shuwei; Zhang, Weidong

2016-05-01

Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.

Radiotherapy for stage I-II non-small cell lung cancer

International Nuclear Information System (INIS)

Okamoto, Yoshiaki; Murakami, Masao; Mizowaki, Takashi; Nakajima, Toshifumi; Kuroda, Yasumasa

1999-01-01

Surgery has been regarded as the standard treatment for patients with non-small cell lung cancer in the early stage, while radiotherapy has become an effective alternative for medically inoperable patients and those who refuse surgery. We reviewed the records of 31 patients with stage I-II non-small cell lung cancer treated by radiotherapy between 1980 and 1997. There were 15 patients in stage I and 16 in stage II. The variables analyzed for influence on cause-specific survival and loco-regional control were: age, performance status, clinical stage, tumor size, tumor site, radiation field, radiation dose, and combination with chemotherapy. The overall and cause-specific 1-, 2-, 3-, and 5-years survival rates were 71% and 77%; 63% and 73%; 34% and 48%; and 17% and 32%, respectively. Five-year survival rate for patients with peripheral tumor in the lung was 72%, with 70% loco-regional control, while the 5-year survival rate of patients whose tumor originated in the central region was 20%, with 25% loco-regional control. These differences had marginal significance on univariate analysis (P=0.07), but only tumor site (central vs peripheral) showed marginal significant influence on cause-specific survival (P=0.08) and loco-regional control (P=0.07) on multivariate analysis. There were no fatal complications, including radiation-induced myelopathy. The present series showed satisfactory results with definitive radiotherapy for patients with medically inoperable stage I-II non-small cell lung cancer, with results similar to those in recent reports of radiotherapy. The only significant variable was that patients with peripheral tumors had a better prognosis than patients with central tumors. (author)

Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Science.gov (United States)

2018-01-26

Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

Prognostic significance of Traf2- and Nck- interacting kinase (TNIK) in colorectal cancer

International Nuclear Information System (INIS)

Takahashi, Hidenori; Ishikawa, Toshiaki; Ishiguro, Megumi; Okazaki, Satoshi; Mogushi, Kaoru; Kobayashi, Hirotoshi; Iida, Satoru; Mizushima, Hiroshi; Tanaka, Hiroshi; Uetake, Hiroyuki; Sugihara, Kenichi

2015-01-01

The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. The online version of this article (doi:10.1186/s12885-015-1783-y) contains supplementary material, which is available to authorized users

78 FR 34303 - Approval and Promulgation of Implementation Plans; North Carolina; Removal of Stage II Gasoline...

Science.gov (United States)

2013-06-07

... Promulgation of Implementation Plans; North Carolina; Removal of Stage II Gasoline Vapor Recovery Program..., 2009, for the purpose of removing Stage II vapor control requirements for new and upgraded gasoline... Piping for Stage II Vapor Recovery, for all new or improved gasoline tanks. In addition, rule 15A-02D...

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

Science.gov (United States)

Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

2016-01-01

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer.

Directory of Open Access Journals (Sweden)

Lucia Perez-Carbonell

Full Text Available Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC. The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001; however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7% and IGFBP3 (83% in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%. Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28-0.85, p = 0.01. Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.

Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.

Science.gov (United States)

Sun, Rui; Liu, Jian-Ping; Gao, Chang; Xiong, Ying-Ying; Li, Min; Wang, Ya-Ping; Su, Yan-Wei; Lin, Mei; Jiang, An-Li; Xiong, Ling-Fan; Xie, Yan; Feng, Jue-Ping

2016-05-17

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (pCRC was observed in TC or TC/CC than CC individuals (pCRC risk was observed in AG, GG, and AG/GG than AA individuals (pCRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

ZEB1 Mediates Drug Resistance and EMT in p300-Deficient CRC.

Science.gov (United States)

Lazarova, Darina; Bordonaro, Michael

2017-01-01

We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis. Deregulated Wnt signaling is the major initiating event in most CRC cases. One mechanism whereby butyrate and other HDACis exert their anti-CRC effects is via Wnt signaling hyperactivation, which promotes CRC cell apoptosis. The histone acetylases (HATs) CBP and p300 are mediators of Wnt transcriptional activity, and play divergent roles in the downstream consequences of Wnt signaling. CBP-mediated Wnt signaling is associated with cell proliferation and stem cell maintenance; whereas, p300-mediated Wnt activity is associated with differentiation. We have found that CBP and p300 differentially affect the ability of butyrate to influence Wnt signaling, apoptosis, and proliferation. ZEB 1 is a Wnt signaling-targeted gene, whose product is a transcription factor expressed at the invasive front of carcinomas where it promotes malignant progression and EMT. ZEB1 is typically a transcriptional repressor; however, when associated with p300, ZEB1 enhances transcription. These changes in ZEB1 activity likely affect the cancer cell phenotype. ZEB1 has been shown to promote resistance to chemotherapeutic agents, and expression of ZEB1 is upregulated in butyrate-resistant CRC cells that lack p300 expression. Since the expression of ZEB1 correlates with poor outcomes in cancer, ZEB represents a relevant therapeutic target. Here we propose that targeting the signaling network established by ZEB1, Wnt signaling, and p300

Associations of Census-Tract Poverty with Subsite-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States

Directory of Open Access Journals (Sweden)

Kevin A. Henry

2014-01-01

Full Text Available Background. It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic subsite and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N=278,097 were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs and incidence rate ratios (IRRs were calculated. Analyses were stratified by subsite (proximal, distal, and rectum, sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12–1.17 and women (IRR = 1.06 95% CI 1.05–1.08. Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20–1.28; female IRR = 1.14 95% CI 1.10–1.18 and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in subsite-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.

Colorectal cancer staging: comparison of whole-body PET/CT and PET/MR.

Science.gov (United States)

Catalano, Onofrio A; Coutinho, Artur M; Sahani, Dushyant V; Vangel, Mark G; Gee, Michael S; Hahn, Peter F; Witzel, Thomas; Soricelli, Andrea; Salvatore, Marco; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce R; Gervais, Debra

2017-04-01

Correct staging is imperative for colorectal cancer (CRC) since it influences both prognosis and management. Several imaging methods are used for this purpose, with variable performance. Positron emission tomography-magnetic resonance (PET/MR) is an innovative imaging technique recently employed for clinical application. The present study was undertaken to compare the staging accuracy of whole-body positron emission tomography-computed tomography (PET/CT) with whole-body PET/MR in patients with both newly diagnosed and treated colorectal cancer. Twenty-six patients, who underwent same day whole-body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Correct staging was compared between methods using McNemar's Chi square test. The two methods were in agreement and correct for 18/26 (69%) patients, and in agreement and incorrect for one patient (3.8%). PET/MR and PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR staging being correct in all seven cases. PET/MR significantly outperformed PET/CT overall for accurate staging (P = 0.02). PET/MR outperformed PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of CRC patients during both at the time of diagnosis and during follow-up.

Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

Science.gov (United States)

Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

2017-07-03

Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials.

Science.gov (United States)

Richman, Susan D; Southward, Katie; Chambers, Philip; Cross, Debra; Barrett, Jennifer; Hemmings, Gemma; Taylor, Morag; Wood, Henry; Hutchins, Gordon; Foster, Joseph M; Oumie, Assa; Spink, Karen G; Brown, Sarah R; Jones, Marc; Kerr, David; Handley, Kelly; Gray, Richard; Seymour, Matthew; Quirke, Philip

2016-03-01

HER2 overexpression/amplification is linked to trastuzumab response in breast/gastric cancers. One suggested anti-EGFR resistance mechanism in colorectal cancer (CRC) is aberrant MEK-AKT pathway activation through HER2 up-regulation. We assessed HER2-amplification/overexpression in stage II-III and IV CRC patients, assessing relationships to KRAS/BRAF and outcome. Pathological material was obtained from 1914 patients in the QUASAR stage II-III trial and 1342 patients in stage IV trials (FOCUS and PICCOLO). Tissue microarrays were created for HER2 immunohistochemistry. HER2-amplification was assessed using FISH and copy number variation. KRAS/BRAF mutation status was assessed by pyrosequencing. Progression-free survival (PFS) and overall survival (OS) data were obtained for FOCUS/PICCOLO and recurrence and mortality for QUASAR; 29/1342 (2.2%) stage IV and 25/1914 (1.3%) stage II-III tumours showed HER2 protein overexpression. Of the HER2-overexpressing cases, 27/28 (96.4%) stage IV tumours and 20/24 (83.3%) stage II-III tumours demonstrated HER2 amplification by FISH; 41/47 (87.2%) also showed copy number gains. HER2-overexpression was associated with KRAS/BRAF wild-type (WT) status at all stages: in 5.2% WT versus 1.0% mutated tumours (p < 0.0001) in stage IV and 2.1% versus 0.2% in stage II-III tumours (p = 0.01), respectively. HER2 was not associated with OS or PFS. At stage II-III, there was no significant correlation between HER2 overexpression and 5FU/FA response. A higher proportion of HER2-overexpressing cases experienced recurrence, but the difference was not significant. HER2-amplification/overexpression is identifiable by immunohistochemistry, occurring infrequently in stage II-III CRC, rising in stage IV and further in KRAS/BRAF WT tumours. The value of HER2-targeted therapy in patients with HER2-amplified CRC must be tested in a clinical trial. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society

29 CFR 37.84 - What happens if CRC does not have jurisdiction over a complaint?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true What happens if CRC does not have jurisdiction over a complaint? 37.84 Section 37.84 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE... Procedures § 37.84 What happens if CRC does not have jurisdiction over a complaint? If CRC does not have...

Segmental mastectomy and radiotherapy as treatment of stage II breast cancer

International Nuclear Information System (INIS)

Faria, S.L.; Chiminazzo Junior, H.; Schlupp, W.R.; Cunha, L.S.M. da

1987-01-01

The treatment of operable breast cancer with segmental mastectomy and radiotherapy has been described since decade 30. Many recent prospective and retrospective studies have shown the efficacy of this conservative management, particularly in stage I. There are still doubts in its use in stage II. (Author) [pt

Result of Radiation Therapy for Stage I, II Non-Hodgkin Lymphoma

International Nuclear Information System (INIS)

Lee, Kyu Chan; Kim, Chul Yong; Choi, Myung Sun

1993-01-01

A retrospective analysis was done for 69 patients with Stage I and II non-Hodgkin lymphoma who were treated from May 1981 to December 1990, in the Department of Radiadtion Oncology, Korea University Hospital. We used Ann Arbor Staging system and Working Formulation for histological classification. Forty-three patients(43/69, 62.3%) were Stage I and 26 patients (26/69, 37.7%) were Stage II, and B symptom was found in 10.1%(7/69). Local control rate for all patients was 88.4%(61/69), with 80% (12/15) for nodal lymphoma and 90.7%(49/54) for extra nodal lymphoma. The total failure rate was 34.8%(24/69). Five of 24 (20.8%) patients who were failed developed local failure only, 12.5%(3/24) local failure with distant failure, and distant failure only were found in 66.7%(16/24). Between nodal lymphoma and extra nodal lymphoma, there was no significant survival difference, but extra nodal lymphoma showed higher incidence

Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC).

Science.gov (United States)

Vilkin, Alex; Niv, Yaron

2011-04-01

Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.

Evaluation of the I. Stage of decommissioning and implementation of the II. Stage of decommissioning of NPP V1

International Nuclear Information System (INIS)

Hrasnova, E.

2015-01-01

In this paper author deals with following aspects: 1. Introduction of company Nuclear and Decommissioning Company, plc; 2. Evaluation of the I. stage of decommissioning and implementation of the II. Stage of decommissioning of NPP V1; (author)

Stage I/II endometrial carcinomas: preoperative radiotherapy: results

International Nuclear Information System (INIS)

Maingon, P.; Belichard, C.; Horiot, J.C.; Barillot, I.; Fraisse, J.; Collin, F.

1996-01-01

The AIM of this retrospective study is to analyse the indications and the results of treatment of endometrial carcinomas by preoperative radiotherapy. MATERIAL: From 1976 to 1995, 183 patients FIGO stage I or II were treated by preoperative radiotherapy consisting in 95 cases of external radiotherapy (XRT) and brachytherapy (BT) followed by surgery (S) and, in 88 cases of BT alone before surgery, XRT was indicated in cases of grade 2 or 3 and/or cervical involvement. METHODS: XRT was delivered with a 4-fields technique to 40 Gy in 20 fractions with a medial shielding at 30 Gy. BT was done with low dose rate Cs137 and Fletcher-Suit-Delclos applicators with two intra-uterine tubes and vaginal ovoieds. Complications were scored using the French-Italian syllabus. RESULTS: Five-year actuarial survival rates per stage are: Ia=91%, Ib=83%, II=71%, and per grade: G1=80%, G2=79%, G3=90%. Failures were pelvic in 5/183 (2.7%), vaginal in 4 cases (2%) and nodal in 2 cases (1%). Twelve patients developed metastases (6.5%). Complications were analysed during the radiotherapy, after the surgery and with unlimited follow-up. After BT/S, 12 grade 1, 1 grade 2 and 1 grade 3 complications were observed. In the group of patients treated by RT/BT/S, 22 grade 1, 11 grade 2, 4 grade 3 occurred. There is no statistical correlation between complications and parameters of treatment (XRT, hwt, HWT, reference dose to the bladder and rectum, dose rate of brachytherapy). SUMMARY: Preoperative irradiation is an effective and safe treatment of high risk stage I/II endometrial carcinomas. Results seem independent of the pathology grade

Associations of Census-Tract Poverty with Sub site-Specific Colorectal Cancer Incidence Rates and Stage of Disease at Diagnosis in the United States

International Nuclear Information System (INIS)

Henry, K. A.; Stroup, A. M.; Sherman, R. L.

2014-01-01

It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC) incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic sub site and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N = 278,097) were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by sub site (proximal, distal, and rectum), sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12-1.17) and women (IRR = 1.06 95% CI 1.05-1.08). Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20-1.28; female IRR = 1.14 95% CI 1.10-1.18) and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in sub site-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.

RGC32 induces epithelial-mesenchymal transition by activating the Smad/Sip1 signaling pathway in CRC.

Science.gov (United States)

Wang, Xiao-Yan; Li, Sheng-Nan; Zhu, Hui-Fang; Hu, Zhi-Yan; Zhong, Yan; Gu, Chuan-Sha; Chen, Shi-You; Liu, Teng-Fei; Li, Zu-Guo

2017-05-04

Response gene to complement 32 (RGC32) is a transcription factor that regulates the expression of multiple genes involved in cell growth, viability and tissue-specific differentiation. However, the role of RGC32 in tumorigenesis and tumor progression in colorectal cancer (CRC) has not been fully elucidated. Here, we showed that the expression of RGC32 was significantly up-regulated in human CRC tissues versus adjacent normal tissues. RGC32 expression was significantly correlated with invasive and aggressive characteristics of tumor cells, as well as poor survival of CRC patients. We also demonstrated that RGC32 overexpression promoted proliferation, migration and tumorigenic growth of human CRC cells in vitro and in vivo. Functionally, RGC32 facilitated epithelial-mesenchymal transition (EMT) in CRC via the Smad/Sip1 signaling pathway, as shown by decreasing E-cadherin expression and increasing vimentin expression. In conclusion, our findings suggested that overexpression of RGC32 facilitates EMT of CRC cells by activating Smad/Sip1 signaling.

Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

Science.gov (United States)

2018-04-17

Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

12 CFR 617.7315 - What records must the qualified lender maintain on behalf of the CRC?

Science.gov (United States)

2010-01-01

... on behalf of the CRC? 617.7315 Section 617.7315 Banks and Banking FARM CREDIT ADMINISTRATION FARM... must the qualified lender maintain on behalf of the CRC? A qualified lender must maintain a complete file of all requests for CRC reviews, including participation in state mediation programs, the minutes...

Report: Cultural Research Centre (CRC)

OpenAIRE

Cross-Cultural Foundation of Uganda

2010-01-01

This report arises from research carried out in Iganga and Namutumba districts in late 2006/early 2007 by the Cultural Research Centre (CRC), based in Jinja. Our research focus was to gauge the impact of using Lusoga as a medium of instruction (since 2005 in "pilot" lower primary classes) within and outside the classroom. This initiative was in response to a new set of circumstances in the education sector in Uganda, especially the introduction by Government of teaching in local languages in ...

Influence of the Hfq and Crc global regulators on the control of iron homeostasis in Pseudomonas putida.

Science.gov (United States)

Sánchez-Hevia, Dione L; Yuste, Luis; Moreno, Renata; Rojo, Fernando

2018-04-30

Metabolically versatile bacteria use catabolite repression control to select their preferred carbon sources, thus optimizing carbon metabolism. In pseudomonads, this occurs through the combined action of the proteins Hfq and Crc, which form stable tripartite complexes at target mRNAs, inhibiting their translation. The activity of Hfq/Crc is antagonised by small RNAs of the CrcZ family, the amounts of which vary according to carbon availability. The present work examines the role of Pseudomonas putida Hfq protein under conditions of low-level catabolite repression, in which Crc protein would have a minor role since it is sequestered by CrcZ/CrcY. The results suggest that, under these conditions, Hfq remains operative and plays an important role in iron homeostasis. In this scenario, Crc appears to participate indirectly by helping CrcZ/CrcY to control the amount of free Hfq in the cell. Iron homeostasis in pseudomonads relies on regulatory elements such as the Fur protein, the PrrF1-F2 sRNAs, and several extracytoplasmic sigma factors. Our results show that the absence of Hfq is paralleled by a reduction in PrrF1-F2 small RNAs. Hfq thus provides a regulatory link between iron and carbon metabolism, coordinating the iron supply to meet the needs of the enzymes operational under particular nutritional regimes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Virulence of Pseudomonas syringae pv. tomato DC3000 Is Influenced by the Catabolite Repression Control Protein Crc.

Science.gov (United States)

Chakravarthy, Suma; Butcher, Bronwyn G; Liu, Yingyu; D'Amico, Katherine; Coster, Matthew; Filiatrault, Melanie J

2017-04-01

Pseudomonas syringae infects diverse plant species and is widely used as a model system in the study of effector function and the molecular basis of plant diseases. Although the relationship between bacterial metabolism, nutrient acquisition, and virulence has attracted increasing attention in bacterial pathology, it is largely unexplored in P. syringae. The Crc (catabolite repression control) protein is a putative RNA-binding protein that regulates carbon metabolism as well as a number of other factors in the pseudomonads. Here, we show that deletion of crc increased bacterial swarming motility and biofilm formation. The crc mutant showed reduced growth and symptoms in Arabidopsis and tomato when compared with the wild-type strain. We have evidence that the crc mutant shows delayed hypersensitive response (HR) when infiltrated into Nicotiana benthamiana and tobacco. Interestingly, the crc mutant was more susceptible to hydrogen peroxide, suggesting that, in planta, the mutant may be sensitive to reactive oxygen species generated during pathogen-associated molecular pattern-triggered immunity (PTI). Indeed, HR was further delayed when PTI-induced tissues were challenged with the crc mutant. The crc mutant did not elicit an altered PTI response in plants compared with the wild-type strain. We conclude that Crc plays an important role in growth and survival during infection.

Risk of recurrence in patients with colon cancer stage II and III

DEFF Research Database (Denmark)

Bockelman, C.; Engelmann, Bodil E.; Kaprio, T.

2015-01-01

Background. Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements...

Interplay between the catabolite repression control protein Crc, Hfq and RNA in Hfq-dependent translational regulation in Pseudomonas aeruginosa.

Science.gov (United States)

Sonnleitner, Elisabeth; Wulf, Alexander; Campagne, Sébastien; Pei, Xue-Yuan; Wolfinger, Michael T; Forlani, Giada; Prindl, Konstantin; Abdou, Laetitia; Resch, Armin; Allain, Frederic H-T; Luisi, Ben F; Urlaub, Henning; Bläsi, Udo

2018-02-16

In Pseudomonas aeruginosa the RNA chaperone Hfq and the catabolite repression control protein (Crc) act as post-transcriptional regulators during carbon catabolite repression (CCR). In this regard Crc is required for full-fledged Hfq-mediated translational repression of catabolic genes. RNAseq based transcriptome analyses revealed a significant overlap between the Crc and Hfq regulons, which in conjunction with genetic data supported a concerted action of both proteins. Biochemical and biophysical approaches further suggest that Crc and Hfq form an assembly in the presence of RNAs containing A-rich motifs, and that Crc interacts with both, Hfq and RNA. Through these interactions, Crc enhances the stability of Hfq/Crc/RNA complexes, which can explain its facilitating role in Hfq-mediated translational repression. Hence, these studies revealed for the first time insights into how an interacting protein can modulate Hfq function. Moreover, Crc is shown to interfere with binding of a regulatory RNA to Hfq, which bears implications for riboregulation. These results are discussed in terms of a working model, wherein Crc prioritizes the function of Hfq toward utilization of favored carbon sources.

Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.

Science.gov (United States)

Thomas, Michelle L; Hewett, Peter J; Ruszkiewicz, Andrew R; Moore, James W E

2015-12-01

In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC. Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing. In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI. © 2015 The Authors. Asia-Pacific Journal of Clinical Oncology Published by Wiley Publishing Asia Pty Ltd.

Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review.

Directory of Open Access Journals (Sweden)

Rebeca Sanz-Pamplona

Full Text Available INTRODUCTION: The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. METHODS: A literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. RESULTS: Five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. CONCLUSIONS: The published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic.

CRC handbook of modern telecommunications

CERN Document Server

Morreale, Patricia A

2001-01-01

This authoritative handbook, contributed to by a team of international experts, covers the most dynamic areas in the changing telecommunications landscape. Written for telecommunications specialists who implement the new technologies, The CRC Handbook of Modern Telecommunications is an excellent companion volume to the authors' The Telecommunications Handbook, but stands well on its own, as it extends the range of topics to include voice over Internet, traffic management, quality of service, and other dominant future trends. It is an indispensable reference for all professionals working in the

[Value of transcutaneous staged dynamic oximetry of stage II arteritis of the leg].

Science.gov (United States)

Grard, C; Desmytterre, J; Vinckier, L; Hatron, P Y; Roux, J P; Warembourg, H; Devulder, B

1990-03-01

The clinical and prognostic value of transcutaneous oxygen pressure measurements at rest has been established in Leriche Stage III and IV occlusive peripheral arterial disease but is controversial in Stage II because there is an overlap of transcutaneous pO2 (Tc pO2) values with those of normal subjects. The authors report the results of Tc pO2 measurements during exercise testing in a group of patients with Stage II occlusive arterial disease of the lower limbs. Seventy-eight patients with an average age of 53 years (range 40 to 65 years) whose claudication perimeter and site of pain had been carefully assessed and who had also recently undergone Doppler arterial examination and arteriography and 35 control subjects with an average age of 54 years (range 45 to 70 years) were studied. The Tc pO2 was continuously measured with a multimodular Kontron Supermon at 4 different sites simultaneously: precordium (reference probe), thigh, calf and foot in the dorsal recumbent position after 30 minutes rest, during a standardised exercise stress test at 50 watts and during the recovery phase. The results were expressed as ratio of tissue oxygenation (RTO): thigh, calf or foot Tc pO2/precordial Tc pO2 X 100 in order to take into account the patients cardiorespiratory status and adaptation to exercise. The RTO in normal subjects remained at the upper limits of the resting value throughout exercise and then returned slowly to basal values during the recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

DEFF Research Database (Denmark)

Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan

2012-01-01

To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Science.gov (United States)

Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

2018-05-01

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

Elevated tumor-to-liver uptake ratio (TLR) from 18F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

International Nuclear Information System (INIS)

Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin; Duan, Yinghua; Zhang, Zhanwen; Hu, Ping; Wang, Xiaoyan

2017-01-01

The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18 F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18 F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18 F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox

Breast carcinoma conservative treatment. Stages I and II

International Nuclear Information System (INIS)

Monti, C.R.

1990-01-01

From 1981 to 1988, 265 patients with breast cancer stages I and II (UICC-1987), were evaluated after conservative treatment with quadrantectomy plus axillectomy, radiotherapy and chemotherapy. After surgical treatment, the patients were submitted to radiation therapy in the breast. One hundred and fifty six (58,8%) patients were submitted to adjuvant chemotherapy. The median clinical follow-up period was 42.8 months with a minimum of 24 and a maximum of 99 months. Six (2,3%) patients presented local recurrence and 48 (18,1%) presented distant metastasis. After five years the total survival rate was 89,7% and the disease free survival rate was 75% in the same period. The study did not show significant differences among the clinical stages classified after surgery and the use of adjuvant chemotherapy did not influence the results of the many stages. (author). 194 refs, 33 figs, 6 tabs

Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence.

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Troiani, Teresa; Napolitano, Stefania; Della Corte, Carminia Maria; Martini, Giulia; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Fortunato

2016-01-01

Epidermal growth factor receptor (EGFR) plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). In the past 15 years, several EGFR antagonists have been approved for the treatment of NSCLC and metastatic CRC (mCRC). To optimise the use of anti-EGFR agents in clinical practice, various clinical and molecular biomarkers have been investigated, thus moving their indication from unselected to selected populations. Nowadays, anti-EGFR drugs represent a gold-standard therapy for metastatic NSCLC harbouring EGFR activating mutation and for RAS wild-type mCRC. Their clinical efficacy is limited by the presence of intrinsic resistance or the onset of acquired resistance. In this review, we provide an overview of the antitumour activity of EGFR inhibitors in NSCLC and CRC and of mechanisms of resistance, focusing on the development of a personalised approach through 15 years of preclinical and clinical research.

MEG3 is a prognostic factor for CRC and promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis.

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Li, Lixia; Shang, Jian; Zhang, Yupeng; Liu, Shi; Peng, Yanan; Zhou, Zhou; Pan, Huaqing; Wang, Xiaobing; Chen, Lipng; Zhao, Qiu

2017-09-01

A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients. Moreover, decreased serum MEG3 expression was associated with poor chemoresponse and low survival rate in CRC patients receiving oxaliplatin treatment. Subsequently, OxR cell lines were established, and MEG3 was significantly downregulated in HT29 OxR and SW480 OxR cells. In addition, overexpression of MEG3 with pMEG3 reversed oxaliplatin resistance in both CRC cell lines. Flow cytometric apoptosis analysis indicated that MEG3 promoted CRC cell apoptosis. More importantly, MEG3 enhanced oxaliplatin‑induced cell cytotoxicity in CRC. In conclusion, our integrated approach demonstrated that decreased expression of lncRNA MEG3 in CRC confers potent poor therapeutic efficacy, and that MEG3 promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis. Thus, overexpression of MEG3 may be a future direction by which to develop a novel therapeutic strategy to overcome oxaliplatin resistance of CRC patients.

Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

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Sonnleitner, Elisabeth; Valentini, Martina; Wenner, Nicolas; Haichar, Feth el Zahar; Haas, Dieter; Lapouge, Karine

2012-01-01

The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

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Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-11-22

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

Elevated tumor-to-liver uptake ratio (TLR) from {sup 18}F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

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Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin [6th Affiliated Hospital, Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, Guangdong (China); Duan, Yinghua [1st Affiliated Hospital, Sun Yat-sen University, Department of Traditional Chinese Medicine, Guangzhou (China); Zhang, Zhanwen; Hu, Ping [6th Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China); Wang, Xiaoyan [1st Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China)

2017-11-15

The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from {sup 18}F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent {sup 18}F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative {sup 18}F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with

Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

Science.gov (United States)

2011-12-07

Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

Science.gov (United States)

Brilhault, Jean; Noël, Vincent

2012-10-01

The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients.

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Tang, Jieting; Chen, Huarong; Wong, Chi-Chun; Liu, Dabin; Li, Tong; Wang, Xiaohong; Ji, Jiafu; Sung, Joseph Jy; Fang, Jing-Yuan; Yu, Jun

2018-03-14

Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.

miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

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Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

2017-08-08

Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

Postoperative radiotherapy for stage II and III rectal cancer

International Nuclear Information System (INIS)

Qian Liting; Song Yongwen; Liu Xinfan; Yu Zihao; Qian Tunan; Li Yexiong

2003-01-01

Objective: To evaluate the impact of postoperative adjuvant radiotherapy, compared with surgery alone for rectal cancer. Methods: From January 1994 to October 1997, 192 patients with stage II or III rectal cancer were treated by radical resection and postoperative radiotherapy (Group S + R) and 51 patients with the same stage lesions underwent surgery alone (Group S). The median dose of radiation was 50(32-62) Gy. Kaplan-Meier method and Log-rank test were used for analysis. Results: The 5-year overall and disease-free survival rates were 60.3% and 58.3%, respectively. The overall 5-year survival rate was 59.4% in Group S + R and 64.7% in Group S, and the 5-year disease-free survival rates were 57.0% and 66.4%, respectively. There were no significant differences between either group (P=0.601 and P=0.424). The disease-free survival was not significantly prolonged in Group S + R as compared with that of Group S. The local recurrence rate was evidently reduced in Group S + R (15.8% v 26.8%, P=0.043). Conclusion: Local recurrence is a major cause of morbidity and mortality in rectal cancer. Postoperative radiotherapy, though reduces the incidence of local recurrence, does not improve the survival in the treatment of stage II and III diseases

Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a Perspective Study Amongst Hospital Attending Eastern Indian Populations.

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Koyel, Banerjee; Priyabrata, Das; Rittwika, Bhattacharya; Swati, Dasgupta; Soma, Mukhopadhyay; Jayasri, Basak; Ashis, Mukhopadhyay

2017-12-01

Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients. The serum CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme assay was carried out following the manufacturer's instructions using auto-analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried out by PCR-SSCP. From our study, most frequently detected colorectal cancer was in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed a significant association with higher TNM staging, tumour size, smoking habit and MSI status ( p   0.05). After surgery and chemotherapy, CEA and WBCs were decreased significantly ( p   0.05). Overall, microsatellite instability was observed in approximately 40% of the populations. From our study, it was also evident that for both, MSI and abnormal CEA level predicted poor prognosis for the patient (by using Kaplan-Meier survival analysis; p  = 0.04). Thus, CEA and initial MSI status can be used as prognostic markers of CRC.

The CRC 20 years: An overview of some of the major achievements and remaining challenges.

Science.gov (United States)

Doek, Jaap E

2009-11-01

On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the international and the national level, an overview which necessarily has to be limited to some of the developments as a result of the implementation of the CRC. The first part of this paper will be devoted to the impact the CRC had and still has on the setting and development of the international agenda for the promotion and protection of the rights and welfare of children. Special attention will given to developments, achievements, and remaining challenges at the international level with regard to protection of children in armed conflict; prevention and the protection of children from sexual exploitation; and from all forms of violence. This will include some information on the impact of these international developments and actions at the national level, for example, in the area of legislation. The second part will focus on the impact at the national level. Given the wide scope of the CRC this part will be limited to some of the General Measures of Implementation (law reform, national programmes, and independent monitoring) and the General Principles (non-discrimination, best interest, right to be heard) of the CRC. This will be based on reports of States on the implementation of the CRC submitted to the CRC Committee and the Concluding Observations of this Committee and on a number of studies. The conclusion will provide remarks on poverty as one of the major remaining challenges for the implementation of children's rights.

Resistance Torque Based Variable Duty-Cycle Control Method for a Stage II Compressor

Science.gov (United States)

Zhong, Meipeng; Zheng, Shuiying

2017-07-01

The resistance torque of a piston stage II compressor generates strenuous fluctuations in a rotational period, and this can lead to negative influences on the working performance of the compressor. To restrain the strenuous fluctuations in the piston stage II compressor, a variable duty-cycle control method based on the resistance torque is proposed. A dynamic model of a stage II compressor is set up, and the resistance torque and other characteristic parameters are acquired as the control targets. Then, a variable duty-cycle control method is applied to track the resistance torque, thereby improving the working performance of the compressor. Simulated results show that the compressor, driven by the proposed method, requires lower current, while the rotating speed and the output torque remain comparable to the traditional variable-frequency control methods. A variable duty-cycle control system is developed, and the experimental results prove that the proposed method can help reduce the specific power, input power, and working noise of the compressor to 0.97 kW·m-3·min-1, 0.09 kW and 3.10 dB, respectively, under the same conditions of discharge pressure of 2.00 MPa and a discharge volume of 0.095 m3/min. The proposed variable duty-cycle control method tracks the resistance torque dynamically, and improves the working performance of a Stage II Compressor. The proposed variable duty-cycle control method can be applied to other compressors, and can provide theoretical guidance for the compressor.

78 FR 58184 - Approval and Promulgation of Implementation Plans; North Carolina; Removal of Stage II Gasoline...

Science.gov (United States)

2013-09-23

...] Approval and Promulgation of Implementation Plans; North Carolina; Removal of Stage II Gasoline Vapor... measures for new and upgraded gasoline dispensing facilities in the State. The September 18, 2009, SIP... .0953), entitled Vapor Return Piping for Stage II Vapor Recovery, for all new or improved gasoline tanks...

Low Complexity List Decoding for Polar Codes with Multiple CRC Codes

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Jong-Hwan Kim

2017-04-01

Full Text Available Polar codes are the first family of error correcting codes that provably achieve the capacity of symmetric binary-input discrete memoryless channels with low complexity. Since the development of polar codes, there have been many studies to improve their finite-length performance. As a result, polar codes are now adopted as a channel code for the control channel of 5G new radio of the 3rd generation partnership project. However, the decoder implementation is one of the big practical problems and low complexity decoding has been studied. This paper addresses a low complexity successive cancellation list decoding for polar codes utilizing multiple cyclic redundancy check (CRC codes. While some research uses multiple CRC codes to reduce memory and time complexity, we consider the operational complexity of decoding, and reduce it by optimizing CRC positions in combination with a modified decoding operation. Resultingly, the proposed scheme obtains not only complexity reduction from early stopping of decoding, but also additional reduction from the reduced number of decoding paths.

Prognostic value of stem cell quantification in stage II colon cancer.

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Maria Angeles Vaz

Full Text Available BACKGROUND: Cancer stem cells (CSCs are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. METHODS: One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. RESULTS: The average patient age was 68 years (patients were between 45-92 years of age and median follow up was 5.8 years. There was recurrent disease in 17 (17%; CD133 expression (defined by >10% positivity was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS or overall survival (OS. However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

OpenAIRE

Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

2012-01-01

Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were iden...

CEA in activated macrophages. New diagnostic possibilities for tumor markers in early colorectal cancer.

Science.gov (United States)

Japink, Dennis; Leers, Mathie P G; Sosef, Meindert N; Nap, Marius

2009-08-01

Serum tumor markers show low sensitivity, making them unsuitable for early detection of cancer. Activated macrophages (AM) from peripheral blood can accumulate tumor marker substances and facilitate early detection in prostate cancer. Here it was investigated whether carcinoembryonic antigen (CEA)-containing macrophages (CEACM) can be used to detect colorectal cancer (CRC) at earlier stages than can serum CEA. Peripheral blood was collected from patients with CRC (n=48), inflammatory colorectal disease (n=5) and from healthy controls (n=18). After separating and labeling AM with CD14-APC/CD16-FITC, AM were intracellularly labeled with anti-CEA antibody and flow cytometrically analyzed. Serum CEA and C-reactive protein (CRP) were measured. The fraction-size of CEACM discriminated between controls and CRC patients, irrespective of AJCC stage (AJCC stage I-IV, pCEA values were significantly elevated in AJCC stage II, III and IV (p=0.02, 0.006 and <0.0001, respectively). Combining CEACM with CRP levels separated CRC from inflammatory colorectal disease. CEACM combined with CRP appears to have diagnostic potential in early CRC.

Influence of the Crc regulator on the hierarchical use of carbon sources from a complete medium in Pseudomonas.

Science.gov (United States)

La Rosa, Ruggero; Behrends, Volker; Williams, Huw D; Bundy, Jacob G; Rojo, Fernando

2016-03-01

The Crc protein, together with the Hfq protein, participates in catabolite repression in pseudomonads, helping to coordinate metabolism. Little is known about how Crc affects the hierarchy of metabolite assimilation from complex mixtures. Using proton Nuclear Magnetic Resonance (NMR) spectroscopy, we carried out comprehensive metabolite profiling of culture supernatants (metabolic footprinting) over the course of growth of both Pseudomonas putida and P. aeruginosa, and compared the wild-type strains with deletion mutants for crc. A complex metabolite consumption hierarchy was observed, which was broadly similar between the two species, although with some important differences, for example in sugar utilization. The order of metabolite utilization changed upon inactivation of the crc gene, but even in the Crc-null strains some compounds were completely consumed before late metabolites were taken up. This suggests the presence of additional regulatory elements that determine the time and order of consumption of compounds. Unexpectedly, the loss of Crc led both species to excrete acetate and pyruvate as a result of unbalanced growth during exponential phase, compounds that were later consumed in stationary phase. This loss of carbon during growth helps to explain the contribution of the Crc/Hfq regulatory system to evolutionary fitness of pseudomonads. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Excisional biopsy, auxillary node dissection and definitive radiotherapy for Stages I and II breast cancer

International Nuclear Information System (INIS)

Danoff, B.F.; Pajak, T.F.; Solin, L.J.; Goodman, R.L.

1985-01-01

From 1977 to 1982, 189 patients with clinical Stage I and II breast cancer underwent excisional biopsy and auxillary node dissection followed by definitive radiotherapy at the University of Pennsylvania. One hundred and nine patients had T 1 lesions and 80 had T 2 lesions. Histologically negative nodes were found in 136 patients (72%) and histologically positive nodes in 53 patients. Median follow-up from the completion of radiotherapy was 26 months. The four year actuarial disease free survival is 82% for pathologic Stage I and 70% for pathologic Stage II. Cosmesis was judged to be good to excellent in 90% and fair in 9%. Complications included arm edema (7%), symptomatic pneumonitis (1%), rib fractures (1%), pericarditis (1%) and pleural effusion (1%). Primary radiotherapy for Stages I and II breast cancer produces a local-regional control rate of 95% and good to excellent cosmesis in 90% of the patients. While these results are preliminary, they compare favorably with other reported series

NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

Science.gov (United States)

Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

2017-08-22

The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

Saturn V Second Stage (S-II) Ready for Static Test

Science.gov (United States)

1965-01-01

Two workers are dwarfed by the five J-2 engines of the Saturn V second stage (S-II) as they make final inspections prior to a static test firing by North American Space Division. These five hydrogen -fueled engines produced one million pounds of thrust, and placed the Apollo spacecraft into earth orbit before departing for the moon. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Non-Surgical Breast-Conserving Treatment (KORTUC-BCT Using a New Radiosensitization Method (KORTUC II for Patients with Stage I or II Breast Cancer

Directory of Open Access Journals (Sweden)

Yasuhiro Ogawa

2015-11-01

Full Text Available The purpose of the present study was to establish a non-surgical breast-conserving treatment (BCT using KORTUC II radiosensitization treatment. A new radiosensitizing agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate (a CD44 ligand has been developed for intra-tumoral injection into various tumors. This new method, named KORTUC II, was approved by our local ethics committee for the treatment of breast cancer and metastatic lymph nodes. A total of 72 early-stage breast cancer patients (stage 0, 1 patient; stage I, 23; stage II, 48 were enrolled in the KORTUC II trial after providing fully informed consent. The mean age of the patients was 59.7 years. A maximum of 6 mL (usually 3 mL for tumors of less than approximately 3 cm in diameter of the agent was injected into breast tumor tissue twice a week under ultrasonographic guidance. For radiotherapy, hypofraction radiotherapy was administered using a tangential fields approach including an ipsilateral axillary region and field-in-field method; the energy level was 4 MV, and the total radiation dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added three times. Treatment was well tolerated with minimal adverse effects in all 72 patients. No patients showed any significant complications other than mild dermatitis. A total of 24 patients under 75 years old with stage II breast cancer underwent induction chemotherapy (EC and/or taxane prior to KORTUC II treatment, and 58 patients with estrogen receptor-positive tumors also received hormonal therapy following KORTUC II. The mean duration of follow-up as of the end of September 2014 was 51.1 months, at which time 68 patients were alive without any distant metastases. Only one patient had local recurrence and died of cardiac failure at 6.5 years. Another one patient had bone metastases. For two of the 72 patients, follow-up ended after several months following KORTUC II treatment. In conclusion, non

Ezrin expression combined with MSI status in prognostication of stage II colorectal cancer.

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Khadija Slik

Full Text Available Currently used factors predicting disease recurrence in stage II colorectal cancer patients are not optimal for risk stratification. Thus, new biomarkers are needed. In this study the applicability of ezrin protein expression together with MSI status and BRAF mutation status were tested in predicting disease outcome in stage II colorectal cancer. The study population consisted of 173 stage II colorectal cancer patients. Paraffin-embedded cancer tissue material from surgical specimens was used to construct tissue microarrays (TMAs with next-generation technique. The TMA-slides were subjected to following immunohistochemical stainings: MLH1, MSH2, MSH6, PMS2, ezrin and anti-BRAF V600E antibody. The staining results were correlated with clinicopathological variables and survival. In categorical analysis, high ezrin protein expression correlated with poor disease-specific survival (p = 0.038. In univariate analysis patients having microsatellite instabile / low ezrin expression tumors had a significantly longer disease-specific survival than patients having microsatellite stable / high ezrin expression tumors (p = 0.007. In multivariate survival analysis, the presence of BRAF mutation was associated to poor overall survival (p = 0.028, HR 3.29, 95% CI1.14-9.54. High ezrin protein expression in patients with microsatellite stable tumors was linked to poor disease-specific survival (p = 0.01, HR 5.68, 95% CI 1.53-21.12. Ezrin protein expression is a promising biomarker in estimating the outcome of stage II colorectal cancer patients. When combined with microsatellite status its ability in predicting disease outcome is further improved.

Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

Science.gov (United States)

2018-04-06

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

CRC Credential Attainment by State Vocational Rehabilitation Counselors

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Harpster, Anna M.; Byers, Katherine L.; Harris, LaKeisha L.

2011-01-01

This study examines 137 state vocational rehabilitation (VR) counselors' perceptions of the value of having the Certified Rehabilitation Counselor (CRC) credential. While almost 53% of this sample included persons who were certified, the majority who were not indicated that the two major reasons for not currently having this designation were: (a)…

Treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer

International Nuclear Information System (INIS)

Zhang Li; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Wang Mei; Feng Qinfu; Liang Jun; Zhou Zongmei; Ou Guangfei; Lv Jima; Yin Weibo

2008-01-01

Objective: To retrospectively analyze treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer. Methods: Between Jan. 2000 and Dec. 2005, fifty-eight such patients were enrolled into the database analysis, including 37 with clinical stage I and 21 with stage II disease. Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy. Forty- three patients were treated with 3-D conformal radiotherapy (3D-CRT) and 15 with conventional radiotherapy. Results: The 1-, 2- and 3-year overall survival rates were 85%, 54% and 30%, and the median survival time was 26.2 months for the whole group. The corresponding figures were 88%, 60%, 36% and 30.8 months for cancer-specific survival; 84%, 64%, 31% and 30.8 months for Stage I disease; 81%, 47%, 28% and 18.8 months for Stage II disease; 95%, 57%, 33% and 30.8 months for 3D-CRT group and 53%, 44%, 24% and 15.3 months for conventional radiotherapy group. By logrank test, tumor volume, pneumonitis of Grade II or higher and weight loss more than 5% showed statistically significant impact on overall survival. Tumor volume was the only independent prognostic factor in Cox multivariable regression. Pneumonitis and esophagitis of Grade II or higher were 16% and 2%, respectively. Age and lung function before treatment had a significant relationship with pneumonitis. Failure included the local recurrence (33%) and distant metastasis (21%). There was no difference between the treatment modalities and failure sites. Conclusions: For medically inoperable early stage non-small cell lung cancer patients, tumor volume is the most important prognostic factor for overall survival. The conformal radiotherapy marginally improves the survival. The age and pulmonary function are related to the incidence of treatment induced pneumonitis. (authors)

Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer

DEFF Research Database (Denmark)

Yu, Jun; Feng, Qiang; Wong, Sunny Hei

2017-01-01

known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4...... in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC. CONCLUSIONS: We present the first metagenomic profiling study of CRC faecal microbiomes...

Structural stability, electronic, mechanical and superconducting properties of CrC and MoC

Energy Technology Data Exchange (ETDEWEB)

Kavitha, M.; Sudha Priyanga, G. [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Rajeswarapalanichamy, R., E-mail: rrpalanichamy@gmail.com [Department of Physics, N.M.S.S.V.N College, Madurai 625019, Tamilnadu (India); Iyakutti, K. [Department of Physics and Nanotechnology, SRM University, Chennai 603203, Tamilnadu (India)

2016-02-01

The structural, electronic, mechanical and superconducting properties of chromium carbide (CrC) and molybdenum carbide (MoC) are investigated using first principles calculations based on density functional theory (DFT). The computed ground state properties like equilibrium lattice constants and cell volume are in good agreement with available theoretical and experimental data. A pressure induced structural phase transition from tungsten carbide phase (WC) to zinc blende phase (ZB) and then zinc blende phase (ZB) to nickel arsenide phase (NiAs) are observed in both chromium and molybdenum carbides. Electronic structure reveals that these carbides are metallic at ambient condition. All the calculated elastic constants obey the Born–Huang stability criteria, suggesting that they are mechanically stable at normal and high pressure. The super conducting transition temperatures for CrC and MoC in WC phase are found to be 31.12 K and 17.14 K respectively at normal pressure. - Highlights: • Electronic and mechanical properties of CrC and MoC are investigated. • Pressure induced structural phase transition is predicted at high pressure. • Electronic structure reveals that these materials exhibit metallic behaviour. • Debye temperature values are computed for CrC and MoC. • Superconducting transition temperature values are computed.

Evaluation of Oral Hygiene in Patients with Generalized Periodontitis of II Degree and Stage II Hypertension

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Tetiana Vivcharenko

2016-12-01

Conclusions. The level of oral hygiene in patients of both groups was low due to incorrect selection of personal hygiene products or their untimely replacement. In patients with generalized periodontitis of II degree and stage II hypertension, the level of oral hygiene was lower than in somatically healthy persons: the worse status of oral cavity hygiene – the more pronounced changes in the periodontal tissues. We can suppose that high blood pressure affects the status of the oral cavity, creates a higher risk and exacerbates the periodontal diseases.

Outcome of radiotherapy for localized stage I E and II E nasal NK/T cell lymphoma

International Nuclear Information System (INIS)

Jin Jing; Li Yexiong; Yao Bo; Fang Hui; Liu Xinfan; Zhou Liqiang; Lv Ning; Yu Zihao

2006-01-01

Objective: With the optimal therapy remains unclear for nasal NK/T cell lymphoma, the aim of this study is to analyze the outcome of radiotherapy as primary treatment for localized stage I E and II E diseases. Methods: Between January. 1983 and December 2003, 105 patients with stage I E and II E primary nasal NK/T cell lymphoma were retrospectively reviewed. According to the Ann Arbor Staging System, there were 83 stage I E and 22 stage II E. Stage I E was subdivided into limited stage I E confined to the nasal cavity (37 patients), or extensive stage I E with an extension beyond the nasal cavity (46 patients). Thirty-one patients received radiotherapy alone. Thirty-four patients were treated with radiotherapy followed by 2-4 cycles of chemotherapy. Thirty-seven patients were treated with chemotherapy followed by radiotherapy and 3 with chemotherapy alone. Of 83 patients with stage I E disease, 26 were primarily treated with radiotherapy alone, 30 with. radiotherapy followed by chemotherapy, and 27 with chemotherapy followed by radiotherapy. Results: The five-year overall survival (OS) and progression-free survival rates (PIS) for all patients was 71% and 59%, respectively. The 5-year OS for stage I E and stage II E was 78% and 46% (P<0.01), while the 5-year PFS for stage I E and stage II E was 63% and 40%, respectively (P<0.01). Patients with limited stage I E had a better OS and PFS than those with extensive stage I E, with 5-year OS and PFS of 82% and 80% versus 75% and 45%, respectively. Complete response (CR) was achieved in 91 (87%) patients after radiotherapy and/or chemotherapy. Initial radiotherapy resulted in a superior CR as compared to initial chemotherapy, with 54 of 65 (83%) patients achieving CR with initial radiotherapy, versus only 8 of 40 (20%) with initial chemotherapy. For 102 patients who received radiotherapy with or without chemotherapy, the outcome of primary, treatment with radiotherapy alone was compared to that of CMT. Five-year OS and

Treatment results of Stage I and II oral tongue cancer with interstitial brachytherapy: maximum tumor thickness is prognostic of nodal metastasis

International Nuclear Information System (INIS)

Matsuura, Kanji; Hirokawa, Yutaka; Fujita, Minoru; Akagi, Yukio; Ito, Katsuhide

1998-01-01

Purpose: To evaluate the prognostic importance of T classification and maximum tumor thickness (MTT) on the treatment results of Stage I and II oral tongue cancer treated with interstitial brachytherapy. Methods and Materials: Between January 1981 and December 1993, 173 cases were eligible for this retrospective analysis. Of 173 patients, 75 were classified as Stage I and 98 as Stage II: maximum tumor length ranged from 6 to 40 mm. MTT, which ranged from 2 to 38 mm, was measured with ultrasonography and/or palpation. Brachytherapy was performed with iridium hairpins or radium needles following external irradiation in 66 patients, or exclusively in 107 patients. Results: The 5-year local recurrence rates were Stage I, 7%; Stage II, 22%; MTT < 8 mm, 8%; and MTT ≥ 8 mm, 28%. The 5-year regional recurrence rates were Stage I, 15%; Stage II, 29%; MTT < 8 mm, 18%; and MTT ≥ 8 mm, 31%, respectively. The 5-year local recurrence rates of the patients with Stage I and MTT < 8 mm of the brachytherapy only group were significantly better than those of Stage II and MTT ≥ 8 mm (5% and 6% vs. 16% and 24%). The 5-year regional recurrence rates of the patients with Stage I and MTT < 8 mm of the brachytherapy-only group were significantly better than those of Stage II and MTT ≥ 8 mm (14% and 16% vs. 34% and 46%). There was no significant difference in the 5-year regional recurrence rates between the two groups of Stage I and Stage II, MTT < 8 mm. However, there was a significant difference in the 5-year regional recurrence rates between the two groups of MTT ≥ 8 mm (p < 0.005). Conclusions: For patients with Stage I and II oral tongue cancer, tumor thickness as well as T classification were prognostic for nodal metastasis and prognosis. Patients with MTT ≥ 8 mm are more likely to fail in the neck region. These findings suggest that MTT should be considered along with T stage in determining strategies for Stage I and II oral tongue cancer

Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

Science.gov (United States)

Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

2016-11-15

The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

Breast cancer relapse stage I and II

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Perez Braojos, Ines; Diaz Gestoso, Yadira; Franco Odio, Sonia; Samuel Gonzalez, Victor

2009-01-01

Breast cancer has always been the most common malignancy in women and is the leading cause of death in women, study relapses Stages I and II therapeutic guidelines applied in the service Mastology the 1985 - 1989, was our first objective, the database used was Clinical history, which gave us all the material necessary, treatments were: In tumors up to 3 cm node-conserving surgery plus treatment N0 with ionizing radiation on the breast tangential C0G0 in tumors greater than 3 cm or less with N1 was modified radical mastectomy according to node status for the study of the part and the receiver adjuvant treatment conducted. (Author)

Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

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Ishimaru, Shinya; Mimori, Koshi; Yamamoto, Ken; Inoue, Hiroshi; Imoto, Seiya; Kawano, Shuichi; Yamaguchi, Rui; Sato, Tetsuya; Toh, Hiroyuki; Iinuma, Hisae; Maeda, Toyoki; Ishii, Hideshi; Suzuki, Sadao; Tokudome, Shinkan; Watanabe, Masahiko; Tanaka, Jun-ichi; Kudo, Shin-ei; Sugihara, Ken-ichi; Hase, Kazuo; Mochizuki, Hidetaka; Kusunoki, Masato; Yamada, Kazutaka; Shimada, Yasuhiro; Moriya, Yoshihiro; Barnard, Graham F; Miyano, Satoru; Mori, Masaki

2012-09-01

Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

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Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

2012-05-01

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (pCRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Incidence of chemotherapy- and chemoradiotherapy-induced amenorrhea in premenopausal women with stage II/III colorectal cancer.

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Wan, Juefeng; Gai, Ya; Li, Guichao; Tao, Zhonghua; Zhang, Zhen

2015-03-01

The incidence rates of colorectal cancer (CRC) in young individuals are increasing. There has been a significant improvement in overall survival in CRC because of advances in adjuvant chemotherapy and chemoradiotherapy over the past decades. However, these procedures may compromise the function of the reproductive system, and ovarian failure and premature menopause may occur. The objective of this analysis was to determine the incidence of long-term amenorrhea (≥ 12 months) in women with CRC aged 40 years and younger after adjuvant treatment. The authors identified 162 premenopausal women with CRC aged 40 years or younger who were treated with adjuvant chemotherapy and chemoradiotherapy at Fudan University Shanghai Cancer Center from January 2008 to December 2012. One hundred twenty-three patients met all eligibility criteria and had sufficient follow-up for evaluation. The median age at diagnosis in patients with colon and rectal cancers was, respectively, 36 and 35 years (range, 17-40 and 24-40 years). All patients had regular menses before treatment; 3 patients with colon cancer (4.2%) experienced long-term amenorrhea, and 48 patients with rectal cancer (94.1%) experienced long-term amenorrhea. The incidence of amenorrhea was significantly lower in patients with colon cancer (4.2%; 3 of 72) than in patients with rectal cancer (94.1%; 48 of 51) (P amenorrhea in patients with colon and rectal cancers was 4.2% and 94.1%, respectively. We believe our data support the fact that young female patients with CRC, especially those with rectal cancer who are scheduled to undergo pelvic irradiation, should be counseled regarding fertility preservation options, including ovarian transposition and cryopreservation of ovarian tissue, embryo, or oocyte. Copyright © 2015 Elsevier Inc. All rights reserved.

Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient-derived primary and metastatic lung cancer cells.

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Sette, Giovanni; Salvati, Valentina; Giordani, Ilenia; Pilozzi, Emanuela; Quacquarini, Denise; Duranti, Enrico; De Nicola, Francesca; Pallocca, Matteo; Fanciulli, Maurizio; Falchi, Mario; Pallini, Roberto; De Maria, Ruggero; Eramo, Adriana

2018-07-01

Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells. © 2018 UICC.

Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis.

Science.gov (United States)

Li, Rui; Liu, Jianjun; Xue, Huiping; Huang, Gang

2012-10-15

The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC. Copyright © 2012 UICC.

Effect of anti-VEGF treatment on retinopathy of prematurity in Zone II Stage 3+

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Xiu-Mei Yang

2018-04-01

Full Text Available AIM: To evaluate the effect of intravitreal ranibizumab injection for retinopathy of prematurity (ROP in Zone II Stage 3+. METHODS: Data was collected for ROP patients with Zone II Stage 3+ who received intravitreal ranibizumab injections between October 2014 and Janu­ary 2017 at the Department of Ophthalmology in our hospital. No prior laser or other intravitreal treatment was done. Prior to the intervention and at each follow-up visit, fundus examination was performed. Gestational age at birth, sex, birth weight, ROP zone, ROP stage, post menstrual age (PMA at treatment, and follow-up pe­riod were recorded. The final clinical status of the retina was evaluated for each patient. The primary outcome mea­sures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization. RESULTS: Eighty-six eyes of 46 premature infants with Zone II Stage 3+ ROP were enrolled in the study. The mean gestational age at birth was 28.18±1.67 (range: 25 to 33wk and the mean birth weight was 1070.57±226.85 (range: 720.00 to 1650.00 g. The mean PMA at treatment was 38.32±2.99 (range: 32.29 to 46.00wk. Seventy-one eyes (82.56% were treated success­fully with intravitreal ranibizumab as monotherapy. Fifteen eyes (17.44% developed recurrent disease. The mean interval between the treatment and retreatment was 5.96±3.22 (range: 1.86 to 11.71wk. All eyes vascularized into zone III at the end of the study and among them 62 eyes (72.09% achieved complete vascu­larization. CONCLUSION: Intravitreal ranibizumab injection is an effective treatment in Zone II Stage 3+ ROP patients. More patients with longer follow-up duration are necessary to confirm the safety and efficacy of this treatment.

Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.

Science.gov (United States)

Han, Xinxin; Yin, Linlin; Xue, Hongwei

2012-07-01

Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

Science.gov (United States)

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

High clusterin expression correlates with a poor outcome in stage II colorectal cancers.

LENUS (Irish Health Repository)

Kevans, David

2012-02-01

The role of clusterin in tumor growth and progression remains unclear. Overexpression of cytoplasmic clusterin has been studied in aggressive colon tumors; however, no correlation between clusterin expression and survival in colorectal cancer has been identified to date. We assessed levels of clusterin expression in a group of stage II colorectal cancer patients to assess its utility as a prognostic marker. The study included 251 patients with stage II colorectal cancer. Tissue microarrays were constructed and immunohistochemistry done and correlated with clinical features and long term outcome. Dual immunofluorescence and confocal microscopy were used with terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling probes and clusterin antibody to assess the degree of co localization. Percentage epithelial cytoplasmic staining was higher in tumor compared with nonadjacent normal mucosa (P < 0.001). Within the stromal compartment, percentage cytoplamic staining and intensity was lower in tumor tissue compared with normal nonadjacent mucosa (P < or = 0.001). Survival was significantly associated with percentage epithelial cytoplasmic staining (P < 0.001), epithelial cytoplasmic staining intensity (P < 0.001), percentage stromal cytoplasmic staining (P = 0.002), and stromal cytoplasmic staining intensity (P < 0.001). Clusterin levels are associated with poor survival in stage II colorectal cancer.

Low Tumor Infiltrating Mast Cell Density Confers Prognostic Benefit and Reflects Immunoactivation in Colorectal Cancer.

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Mao, Yihao; Feng, Qingyang; Zheng, Peng; Yang, Liangliang; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; He, Guodong; Xu, Jianmin

2018-06-06

The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, this study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stage I-IV was enrolled in this study. 854 consecutive patients were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stage II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stage II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis. This article is protected by copyright. All rights reserved. © 2018 UICC.

Quality indicators for colorectal cancer surgery and care according to patient-, tumor-, and hospital-related factors

International Nuclear Information System (INIS)

Mathoulin-Pélissier, Simone; Bécouarn, Yves; Belleannée, Geneviève; Pinon, Elodie; Jaffré, Anne; Coureau, Gaëlle; Auby, Dominique; Renaud-Salis, Jean-Louis; Rullier, Eric

2012-01-01

Colorectal cancer (CRC) care has improved considerably, particularly since the implementation of a quality of care program centered on national evidence-based guidelines. Formal quality assessment is however still needed. The aim of this research was to identify factors associated with practice variation in CRC patient care. CRC patients identified from all cancer centers in South-West France were included. We investigated variations in practices (from diagnosis to surgery), and compliance with recommended guidelines for colon and rectal cancer. We identified factors associated with three colon cancer practice variations potentially linked to better survival: examination of ≥12 lymph nodes (LN), non-use and use of adjuvant chemotherapy for stage II and stage III patients, respectively. We included 1,206 patients, 825 (68%) with colon and 381 (32%) with rectal cancer, from 53 hospitals. Compliance was high for resection, pathology report, LN examination, and chemotherapy use for stage III patients. In colon cancer, 26% of stage II patients received adjuvant chemotherapy and 71% of stage III patients. 84% of stage US T3T4 rectal cancer patients received pre-operative radiotherapy. In colon cancer, factors associated with examination of ≥12 LNs were: lower ECOG score, advanced stage and larger hospital volume; factors negatively associated were: left sided tumor location and one hospital district. Use of chemotherapy in stage II patients was associated with younger age, advanced stage, emergency setting and care structure (private and location); whereas under-use in stage III patients was associated with advanced age, presence of comorbidities and private hospitals. Although some changes in practices may have occurred since this observational study, these findings represent the most recent report on practices in CRC in this region, and offer a useful methodological approach for assessing quality of care. Guideline compliance was high, although some organizational

The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

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2018-03-02

Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Economic evaluation of monoclonal antibody in the management of colorectal cancer

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Ezat SW

2013-03-01

Full Text Available Objective: This study aims to determine the cost of colorectal cancer (CRC management and compare the cost effectiveness of cetuximab and bevacizumab in the management of CRC. Method: This economic evaluation study from a societal perspective involves collecting resource utilization data based on the clinical pathway of colorectal cancer management. The cost calculated includes drugs, human resources, administrative, investigations as well as capital cost. Patient’s cost was also calculated based on an interview with colorectal cancer patients. Effectiveness estimates for monoclonal antibody (cetuximab and bevacizumab treatment were modeled from study respondents based on references from other studies. Results: Cost of treating a case of colorectal cancer in stage I is RM13,623 (RM12,467-RM14,777, stage II RM19,753 (RM16,734-RM23,520, stage III RM24,972 (RM20,291-RM29,654 and stage IV RM27, 163 (RM23, 192-RM31,133. Cost of CRC management increase with the increasing stage of the disease (Kruskal Wallis, X2=106, p<0.001. Based on estimates of 2671 new cases of CRC, the incremental cost of cetuximab is RM20, 556 480 and bevacizumab is RM7,557,953 at 50% stage III and IV as compared to the conventional chemotherapy. The incremental cost per quality adjusted life years gained for cetuximab is RM38,869 and RM14,290 for bevacizumab. Although both types of monoclonal antibody are considered cost effective (based on WHO guidelines of less than three times of GDP, bevacizumab is considered more cost effective than cetuximab. Cost effectiveness was sensitive to the percentage of late stages of CRC. Conclusions: Cost of treating late stage of CRC is high and bevacizumab are more cost effective compared to cetuximab in the management of the late stage of CRC.

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

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O'Gara Fergal

2010-11-01

Full Text Available Abstract Background Catabolite repression control (CRC is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria.

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Browne, Patrick; Barret, Matthieu; O'Gara, Fergal; Morrissey, John P

2010-11-25

Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate nutritional status cues with the regulation

Computational prediction of the Crc regulon identifies genus-wide and species-specific targets of catabolite repression control in Pseudomonas bacteria

LENUS (Irish Health Repository)

Browne, Patrick

2010-11-25

Abstract Background Catabolite repression control (CRC) is an important global control system in Pseudomonas that fine tunes metabolism in order optimise growth and metabolism in a range of different environments. The mechanism of CRC in Pseudomonas spp. centres on the binding of a protein, Crc, to an A-rich motif on the 5\\' end of an mRNA resulting in translational down-regulation of target genes. Despite the identification of several Crc targets in Pseudomonas spp. the Crc regulon has remained largely unexplored. Results In order to predict direct targets of Crc, we used a bioinformatics approach based on detection of A-rich motifs near the initiation of translation of all protein-encoding genes in twelve fully sequenced Pseudomonas genomes. As expected, our data predict that genes related to the utilisation of less preferred nutrients, such as some carbohydrates, nitrogen sources and aromatic carbon compounds are targets of Crc. A general trend in this analysis is that the regulation of transporters is conserved across species whereas regulation of specific enzymatic steps or transcriptional activators are often conserved only within a species. Interestingly, some nucleoid associated proteins (NAPs) such as HU and IHF are predicted to be regulated by Crc. This finding indicates a possible role of Crc in indirect control over a subset of genes that depend on the DNA bending properties of NAPs for expression or repression. Finally, some virulence traits such as alginate and rhamnolipid production also appear to be regulated by Crc, which links nutritional status cues with the regulation of virulence traits. Conclusions Catabolite repression control regulates a broad spectrum of genes in Pseudomonas. Some targets are genus-wide and are typically related to central metabolism, whereas other targets are species-specific, or even unique to particular strains. Further study of these novel targets will enhance our understanding of how Pseudomonas bacteria integrate

The Crc and Hfq proteins of Pseudomonas putida cooperate in catabolite repression and formation of ribonucleic acid complexes with specific target motifs.

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Moreno, Renata; Hernández-Arranz, Sofía; La Rosa, Ruggero; Yuste, Luis; Madhushani, Anjana; Shingler, Victoria; Rojo, Fernando

2015-01-01

The Crc protein is a global regulator that has a key role in catabolite repression and optimization of metabolism in Pseudomonads. Crc inhibits gene expression post-transcriptionally, preventing translation of mRNAs bearing an AAnAAnAA motif [the catabolite activity (CA) motif] close to the translation start site. Although Crc was initially believed to bind RNA by itself, this idea was recently challenged by results suggesting that a protein co-purifying with Crc, presumably the Hfq protein, could account for the detected RNA-binding activity. Hfq is an abundant protein that has a central role in post-transcriptional gene regulation. Herein, we show that the Pseudomonas putida Hfq protein can recognize the CA motifs of RNAs through its distal face and that Crc facilitates formation of a more stable complex at these targets. Crc was unable to bind RNA in the absence of Hfq. However, pull-down assays showed that Crc and Hfq can form a co-complex with RNA containing a CA motif in vitro. Inactivation of the hfq or the crc gene impaired catabolite repression to a similar extent. We propose that Crc and Hfq cooperate in catabolite repression, probably through forming a stable co-complex with RNAs containing CA motifs to result in inhibition of translation initiation. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

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Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

2015-01-01

The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials.

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Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Boer, Rob; Zauber, Ann; Habbema, J Dik F

2009-06-01

Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis. (c) 2009 American Cancer Society.

Whole Gene Capture Analysis of 15 CRC Susceptibility Genes in Suspected Lynch Syndrome Patients.

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Jansen, Anne M L; Geilenkirchen, Marije A; van Wezel, Tom; Jagmohan-Changur, Shantie C; Ruano, Dina; van der Klift, Heleen M; van den Akker, Brendy E W M; Laros, Jeroen F J; van Galen, Michiel; Wagner, Anja; Letteboer, Tom G W; Gómez-García, Encarna B; Tops, Carli M J; Vasen, Hans F; Devilee, Peter; Hes, Frederik J; Morreau, Hans; Wijnen, Juul T

2016-01-01

Lynch Syndrome (LS) is caused by pathogenic germline variants in one of the mismatch repair (MMR) genes. However, up to 60% of MMR-deficient colorectal cancer cases are categorized as suspected Lynch Syndrome (sLS) because no pathogenic MMR germline variant can be identified, which leads to difficulties in clinical management. We therefore analyzed the genomic regions of 15 CRC susceptibility genes in leukocyte DNA of 34 unrelated sLS patients and 11 patients with MLH1 hypermethylated tumors with a clear family history. Using targeted next-generation sequencing, we analyzed the entire non-repetitive genomic sequence, including intronic and regulatory sequences, of 15 CRC susceptibility genes. In addition, tumor DNA from 28 sLS patients was analyzed for somatic MMR variants. Of 1979 germline variants found in the leukocyte DNA of 34 sLS patients, one was a pathogenic variant (MLH1 c.1667+1delG). Leukocyte DNA of 11 patients with MLH1 hypermethylated tumors was negative for pathogenic germline variants in the tested CRC susceptibility genes and for germline MLH1 hypermethylation. Somatic DNA analysis of 28 sLS tumors identified eight (29%) cases with two pathogenic somatic variants, one with a VUS predicted to pathogenic and LOH, and nine cases (32%) with one pathogenic somatic variant (n = 8) or one VUS predicted to be pathogenic (n = 1). This is the first study in sLS patients to include the entire genomic sequence of CRC susceptibility genes. An underlying somatic or germline MMR gene defect was identified in ten of 34 sLS patients (29%). In the remaining sLS patients, the underlying genetic defect explaining the MMRdeficiency in their tumors might be found outside the genomic regions harboring the MMR and other known CRC susceptibility genes.

Quantitative proteomics unravels that the post-transcriptional regulator Crc modulates the generation of vesicles and secreted virulence determinants of Pseudomonas aeruginosa.

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Reales-Calderón, Jose Antonio; Corona, Fernando; Monteoliva, Lucía; Gil, Concha; Martínez, Jose Luis

2015-09-08

Recent research indicates that the post-transcriptional regulator Crc modulates susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Several P. aeruginosa virulence factors are secreted or engulfed in vesicles. To decipher the Crc modulation of P. aeruginosa virulence, we constructed a crc deficient mutant and measure the proteome associated extracellular vesicles and the vesicle-free secretome using iTRAQ. Fifty vesicle-associated proteins were more abundant and 14 less abundant in the crc-defective strain, whereas 37 were more abundant and 17 less abundant in the vesicle-free secretome. Among them, virulence determinants, such as ToxA, protease IV, azurin, chitin-binding protein, PlcB and Hcp1, were less abundant in the crc-defective mutant. Transcriptomic analysis revealed that some of the observed changes were post-transcriptional and, thus, could be attributed to a direct Crc regulatory role; whereas, for other differentially secreted proteins, the regulatory role was likely indirect. We also observed that the crc mutant presented an impaired vesicle-associated secretion of quorum sensing signal molecules and less cytotoxicity than its wild-type strain. Our results offer new insights into the mechanisms by which Crc regulates P. aeruginosa virulence, through the modulation of vesicle formation and secretion of both virulence determinants and quorum sensing signals. This article is part of a Special Issue entitled: HUPO 2014. Published by Elsevier B.V.

G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

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Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

2018-01-01

Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.

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Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H; Brun, Reto; Carballeira, Néstor M

2010-11-01

Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC(50) value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC(50) value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC(50) 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC(50) values of 0.38 and 0.58 μg/ml (IC(50) control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC(50) values 3.7-31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC(50) 20.2 μg/ml), and Leishmania donovani (IC(50) values 4.1-13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to

2-Hexadecynoic Acid Inhibits Plasmodial FAS-II Enzymes and Arrest Erythrocytic and Liver Stage Plasmodium Infections

Science.gov (United States)

Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L.; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H.; Brun, Reto; Carballeira, Néstor M.

2010-01-01

Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of P. yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC50 value 6.6. μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescense analysis (IC50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory against the PfFAS-II enzymes PfFabI and PfFabZ with IC50 values of 0.38 and 0.58 μg/ml (IC50 control drugs 14 and 30 ng/ml) respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC50 values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC50 20.2 μg/ml), and Leishmania donovani (IC50 values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature and calculated pharmacokinetic properties suggest that 2-HDA could be a useful compound to study the interaction of fatty

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

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Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-05-20

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study.

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Arakawa, K; Kawai, K; Tanaka, T; Hata, K; Sugihara, K; Nozawa, H

2018-05-12

Clinical guidelines recommend adjuvant chemotherapy for high-risk patients with Stage II-III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II-III colorectal cancer. We conducted a multicentre, retrospective study of 17 757 patients with Stage II-III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high-rate (rate > 42.8%) or low-rate (rate ≤ 42.8%), chemotherapy prescribing clinics. The 5-year overall survival (OS) of patients with Stage II-III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P colorectal cancer (both P colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

DEFF Research Database (Denmark)

Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

2016-01-01

BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate...... of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

Low Expression of TBX4 Predicts Poor Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

Directory of Open Access Journals (Sweden)

Meijuan Zong

2011-08-01

Full Text Available This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4, a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3% expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010. In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

Effect of Cu(II) coordination compounds on the activity of antioxidant enzymes catalase and superoxide dismutase in patients with colorectal cancer.

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Kubiak, Katarzyna; Malinowska, Katarzyna; Langer, Ewa; Dziki, Łukasz; Dziki, Adam; Majsterek, Ireneusz

2011-03-01

Colorectal cancer (CRC) is a serious medical and economical problem of our times. It is the most common gastrointestinal cancer in the world. In Poland, the treatment and detection of CRC are poorly developed and the pathogenesis is still unclear. One hypothesis suggests a role of reactive oxygen species (ROS) in the pathogenesis of CRC. Experimental studies in recent years confirm the participation of ROS in the initiation and promotion of CRC. The aim of the study was to examine the effect of the following coordination compounds coordination compounds: dinitrate (V) tetra(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dinitrate (V) di(1,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(1,3,4,5-tetramethyl-N1-pyrazole-κN2) copper(II) on the activity of antioxidant enzymes superoxide dismutase (SOD, ZnCu-SOD) and catalase (CAT) in a group of patients with colorectal cancer (CRC) and in the control group consisting of patients with minor gastrointestinal complaints. The study was conducted in 20 patients diagnosed with colorectal cancer at the age of 66.5±10.2 years (10 men and 10 women) versus the control group of 20 people (10 men and 10 women) aged 57.89±17.10 years without cancer lesions in the biological material - hemolysate prepared in a proportion of 1ml of water per 1 ml of blood. CAT activity was measured by the Beers method (1952), while SOD activity was measured by the Misra and Fridovich method (1972). We found that patients with CRC showed a statistically significant decrease of SOD and CAT activity (CAT - 12,75±1.97 U/g Hb, SOD - 1111.52±155.52 U/g Hb) in comparison with the control group (CAT - 19.65±2,17 U/g Hb, SOD - 2046.26±507.22 U/g Hb). Simultaneously, we observed that the investigated coordination compounds of Cu(II) significantly increased the antioxidant activity of CAT and SOD in patients with CRC (mean: CAT 25.23±4.86 U/g Hb, SOD - 3075.96±940.20 U/g Hb). Patients with

The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa.

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Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

2013-02-01

The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT-PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine-tune this virulence mechanism in response to environmental changes and nutrient sources. © 2012 The Authors. Published by Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

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Nikolouzakis, Taxiarchis Konstantinos; Vassilopoulou, Loukia; Fragkiadaki, Persefoni; Mariolis Sapsakos, Theodoros; Papadakis, Georgios Z; Spandidos, Demetrios A; Tsatsakis, Aristides M; Tsiaoussis, John

2018-06-01

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).

[Combination of NAFLD Fibrosis Score and liver stiffness measurement for identification of moderate fibrosis stages (II & III) in non-alcoholic fatty liver disease].

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Drolz, Andreas; Wehmeyer, Malte; Diedrich, Tom; Piecha, Felix; Schulze Zur Wiesch, Julian; Kluwe, Johannes

2018-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest. Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III. Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed. 134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %). Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies. © Georg Thieme Verlag KG Stuttgart · New York.

Expression of the MAP kinase phosphatase DUSP4 is associated with microsatellite instability in colorectal cancer (CRC) and causes increased cell proliferation.

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Gröschl, Benedikt; Bettstetter, Marcus; Giedl, Christian; Woenckhaus, Matthias; Edmonston, Tina; Hofstädter, Ferdinand; Dietmaier, Wolfgang

2013-04-01

DUSP4 (MKP-2), a member of the mitogen-activated protein kinase phosphatase (MKP) family and potential tumor suppressor, negatively regulates the MAPKs (mitogen-activated protein kinases) ERK, p38 and JNK. MAPKs play a crucial role in cancer development and progression. Previously, using microarray analyses we found a conspicuously frequent overexpression of DUSP4 in colorectal cancer (CRC) with high frequent microsatellite instability (MSI-H) compared to microsatellite stable (MSS) CRC. Here we studied DUSP4 expression on mRNA level in 38 CRC (19 MSI-H and 19 MSS) compared to matched normal tissue as well as in CRC cell lines by RT-qPCR. DUSP4 was overexpressed in all 19 MSI-H tumors and in 14 MSS tumors. Median expression levels in MSI-H tumors were significantly higher than in MSS-tumors (p CRC cell lines showed 6.8-fold higher DUSP4 mRNA levels than MSS cell lines. DUSP4 expression was not regulated by promoter methylation since no methylation was found by quantitative methylation analysis of DUSP4 promoter in CRC cell lines neither in tumor samples. Furthermore, no DUSP4 mutation was found on genomic DNA level in four CRC cell lines. DUSP4 overexpression in CRC cell lines through DUSP4 transfection caused upregulated expression of MAPK targets CDC25A, CCND1, EGR1, FOS, MYC and CDKN1A in HCT116 as well as downregulation of mismatch repair gene MSH2 in SW480. Furthermore, DUSP4 overexpression led to increased proliferation in CRC cell lines. Our findings suggest that DUSP4 acts as an important regulator of cell growth within the MAPK pathway and causes enhanced cell growth in MSI-H CRC. Copyright © 2012 UICC.

The Crc protein inhibits the production of polyhydroxyalkanoates in Pseudomonas putida under balanced carbon/nitrogen growth conditions.

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La Rosa, Ruggero; de la Peña, Fernando; Prieto, María Axiliadora; Rojo, Fernando

2014-01-01

Pseudomonas putida synthesizes polyhydroxyalkanoates (PHAs) as storage compounds. PHA synthesis is more active when the carbon source is in excess and the nitrogen source is limiting, but can also occur at a lower rate under balanced carbon/nitrogen ratios. This work shows that PHA synthesis is controlled by the Crc global regulator, a protein that optimizes carbon metabolism by inhibiting the expression of genes involved in the use of non-preferred carbon sources. Crc acts post-transcriptionally. The mRNAs of target genes contain characteristic catabolite activity (CA) motifs near the ribosome binding site. Sequences resembling CA motifs can be predicted for the phaC1 gene, which codes for a PHA polymerase, and for phaI and phaF, which encode proteins associated to PHA granules. Our results show that Crc inhibits the translation of phaC1 mRNA, but not that of phaI or phaF, reducing the amount of PHA accumulated in the cell. Crc inhibited PHA synthesis during exponential growth in media containing a balanced carbon/nitrogen ratio. No inhibition was seen when the carbon/nitrogen ratio was imbalanced. This extends the role of Crc beyond that of controlling the hierarchical utilization of carbon sources and provides a link between PHA synthesis and the global regulatory networks controlling carbon flow. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

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Guo, Tianhua; Krzystanek, Marcin; Szallasi, Zoltan Imre

2014-01-01

of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively...

The translational repressor Crc controls the Pseudomonas putida benzoate and alkane catabolic pathways using a multi-tier regulation strategy.

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Hernández-Arranz, Sofía; Moreno, Renata; Rojo, Fernando

2013-01-01

Metabolically versatile bacteria usually perceive aromatic compounds and hydrocarbons as non-preferred carbon sources, and their assimilation is inhibited if more preferable substrates are available. This is achieved via catabolite repression. In Pseudomonas putida, the expression of the genes allowing the assimilation of benzoate and n-alkanes is strongly inhibited by catabolite repression, a process controlled by the translational repressor Crc. Crc binds to and inhibits the translation of benR and alkS mRNAs, which encode the transcriptional activators that induce the expression of the benzoate and alkane degradation genes respectively. However, sequences similar to those recognized by Crc in benR and alkS mRNAs exist as well in the translation initiation regions of the mRNA of several structural genes of the benzoate and alkane pathways, which suggests that Crc may also regulate their translation. The present results show that some of these sites are functional, and that Crc inhibits the induction of both pathways by limiting not only the translation of their transcriptional activators, but also that of genes coding for the first enzyme in each pathway. Crc may also inhibit the translation of a gene involved in benzoate uptake. This multi-tier approach probably ensures the rapid regulation of pathway genes, minimizing the assimilation of non-preferred substrates when better options are available. A survey of possible Crc sites in the mRNAs of genes associated with other catabolic pathways suggested that targeting substrate uptake, pathway induction and/or pathway enzymes may be a common strategy to control the assimilation of non-preferred compounds. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells.

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Jumpertz, Sandra; Hennes, Thomas; Asare, Yaw; Vervoorts, Jörg; Bernhagen, Jürgen; Schütz, Anke K

2014-09-01

COP9 signalosome subunit 5 (CSN5) plays a decisive role in cellular processes such as cell cycle regulation and apoptosis via promoting protein degradation, gene transcription, and nuclear export. CSN5 regulates cullin-RING-E3 ligase (CRL) activity through its deNEDDylase function. It is overexpressed in several tumor entities, but its role in colorectal cancer (CRC) is poorly understood. Wnt/β-catenin signaling is aberrant in most CRC cells, resulting in increased levels of oncogenic β-catenin and thus tumor progression. Under physiological conditions, β-catenin levels are tightly regulated by continuous proteasomal degradation. We recently showed that knockdown of CSN5 in model and CRC cells results in decreased (phospho)-β-catenin levels. Reduced β-catenin levels were associated with an attenuated proliferation rate of different CRC cell types after CSN5 knockdown. The canonical Wnt pathway involves degradation of β-catenin by a β-TrCP1-containing E3 ligase, but is mostly non-functional in CRC cells. We thus hypothesized that alternative β-catenin degradation mediated by SIAH-1 (seven in absentia homolog-1), is responsible for the effect of CSN5 on β-catenin signaling in CRC cells. We found that SIAH-1 plays an essential role in β-catenin degradation in HCT116 CRC cells and that CSN5 affects β-catenin target gene expression in these cells. Of note, CSN5 affected SIAH-1 mRNA and SIAH-1 protein levels. Moreover, β-catenin and SIAH-1 form protein complexes with CSN5 in HCT116 cells. Lastly, we demonstrate that CSN5 promotes SIAH-1 degradation in HCT116 and SW480 cells and that this is associated with its deNEDDylase activity. In conclusion, we have identified a CSN5/β-catenin/SIAH-1 interaction network that might control β-catenin degradation in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessing Religious Orientations: Replication and Validation of the Commitment-Reflectivity Circumplex (CRC Model

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Steven L. Isaak

2017-09-01

Full Text Available The Commitment-Reflectivity Circumplex (CRC model is a structural model of religious orientation that was designed to help organize and clarify measurement of foundational aspect of religiousness. The current study successfully replicated the CRC model using multidimensional scaling, and further evaluated the reliability, structure, and validity of their measures in both a university student sample (Study 1 and a nationally representative sample (Study 2. All 10 subscales of the Circumplex Religious Orientation Inventory (CROI demonstrated good reliability across both samples. A two-week test-retest of the CROI showed that the subscales are stable over time. A confirmatory factor analysis of the CROI in the representative adult sample demonstrated good model fit. Finally, the CROI’s validity was examined in relation to the Intrinsic, Extrinsic and Quest measures. Overall, the CROI appears to clarify much of the ambiguity inherent in the established scales by breaking down what were very broad orientations into very specific suborientations. The results suggest that the CRC model is applicable for diverse populations of adults. In addition, the CROI appears to be construct valid with good structural and psychometric properties across all 10 subscales.

Long-term use of metformin and colorectal cancer risk in type II diabetics

DEFF Research Database (Denmark)

Cardel, Majken; Jensen, S. M.; Pottegård, Anton

2014-01-01

of prescriptions for a cumulative dose of 2000 g within 5 years prior to the index date. To control for potential confounders, we used unconditional logistic regression. We generated adjusted odds ratios (OR) for the association between metformin and CRC and performed subanalyses for selected subgroups...... and for the dose-response relation. We identified 2088 cases and 9060 controls during the study period. The association between long-term metformin use and CRC gave an adjusted OR at 0.83 (95% CI 0.68-1.00). A protective effect on CRC with long-term use of metformin was only evident for women (OR 0.66 vs. 0.......99 for men). There was a significant dose-response association of metformin use > 250 defined daily dose (DDD) and for the duration of metformin use > 1 year. We found an indication of a protective effect of long-term metformin use against CRC in type II diabetics, although this effect was only seen in women....

The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis.

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Han, Su-xia; Wang, Jing; Wang, Li-juan; Jin, Gui-hua; Ying, Xia; He, Chen-chen; Guo, Xi-jing; Zhang, Jian-ying; Zhang, Ying; Zhu, Qing

2014-06-01

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) plays an important role in tumor progression by helping tumor cell to escape from host immunological surveillance or modifying the characteristics of connective tissue around. RCAS1 may appropriately reflect the development and prognosis of tumor. In the study, we sought to identify the clinical significance of RCAS1 in colorectal cancer (CRC) diagnosis and tumor recurrence monitoring. Immunohistochemistry (IHC) with tissue array slides was preformed to analyze RCAS1 protein expression in CRC, colorectal polyps, and normal colon tissues. RCAS1 levels in colorectal cancer were significantly higher than those in colorectal polyps and normal colon tissues (PCRC are significantly higher than in healthy controls and polyps (PCRC was 82.1 %, which was higher than carcinoembryonic antigen (CEA). Especially in CEA-negative cases, the sensitivity of RCAS1 was 88.2 %. Finally, CRC patients who were followed up showed a serum RCAS1 level which significantly decreased after surgery (PCRC diagnosis but also useful for monitoring tumor recurrence. RCAS1 might be a supplementary serological marker for CRC.

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

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Chen Yidong; Feng Qinfu; Lu Haizhen; Mao Yousheng; Zhou Zongmei; Ou Guangfei; Wang Mei; Zhao Jun; Zhang Hongxing; Xiao Zefen; Chen Dongfu; Liang Jun; Zhai Yirui; Wang Luhua; He Jie

2010-01-01

Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

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2018-04-09

Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

[Analysis of prognostic factors after radical resection in 628 patients with stage II or III colon cancer].

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Qin, Qiong; Yang, Lin; Zhou, Ai-ping; Sun, Yong-kun; Song, Yan; DU, Feng; Wang, Jin-wan

2013-03-01

To analyze the clinicopathologic factors related to recurrence and metastasis of stage II or III colon cancer after radical resection. The clinical and pathological data of 628 patients with stage II or III colon cancer after radical resection from Jan. 2005 to Dec. 2008 in our hospital were retrospectively reviewed and analyzed. The overall recurrence and metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis showed that age, smoking intensity, depth of tumor invasion, lymph node metastasis, TNM stage, gross classification, histological differentiation, blood vessel tumor embolus, tumor gross pathology, multiple primary tumors, preoperative and postoperative serum concentration of CEA and CA19-9, and the regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of colon cancer after radical resection. Multivariate analysis showed that regional lymph node metastasis, TNM stage, the regimen of postoperative adjuvant chemotherapy, and preoperative serum concentration of CEA and CA19-9 were independent factors affecting the prognosis of colon cancer patients. Regional lymph node metastasis, TNM stage, elevated preoperative serum concentration of CEA and CA19-9, the regimen of postoperative adjuvant chemotherapy with single fluorouracil type drug are independent risk factors of recurrence and metastasis in patients with stage II-III colon cancer after radical resection.

NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.

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Wang, Hao; Nie, Lei; Wu, Lei; Liu, Qiufang; Guo, Xueyan

2017-03-25

Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC. Using comparative miRNA profiling TGF-β pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-β and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-β-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

The Crc protein participates in down-regulation of the Lon gene to promote rhamnolipid production and rhl quorum sensing in Pseudomonas aeruginosa.

Science.gov (United States)

Yang, Nana; Ding, Shuting; Chen, Feifei; Zhang, Xue; Xia, Yongjie; Di, Hongxia; Cao, Qiao; Deng, Xin; Wu, Min; Wong, Catherine C L; Tian, Xiao-Xu; Yang, Cai-Guang; Zhao, Jing; Lan, Lefu

2015-05-01

Rhamnolipid acts as a virulence factor during Pseudomonas aeruginosa infection. Here, we show that deletion of the catabolite repression control (crc) gene in P. aeruginosa leads to a rhamnolipid-negative phenotype. This effect is mediated by the down-regulation of rhl quorum sensing (QS). We discover that a disruption of the gene encoding the Lon protease entirely offsets the effect of crc deletion on the production of both rhamnolipid and rhl QS signal C4-HSL. Crc is unable to bind lon mRNA in vitro in the absence of the RNA chaperon Hfq, while Crc contributes to Hfq-mediated repression of the lon gene expression at a posttranscriptional level. Deletion of crc, which results in up-regulation of lon, significantly reduces the in vivo stability and abundance of the RhlI protein that synthesizes C4-HSL, causing the attenuation of rhl QS. Lon is also capable of degrading the RhlI protein in vitro. In addition, constitutive expression of rhlI suppresses the defects of the crc deletion mutant in rhamnolipid, C4-HSL and virulence on lettuce leaves. This study therefore uncovers a novel posttranscriptional regulatory cascade, Crc-Hfq/Lon/RhlI, for the regulation of rhamnolipid production and rhl QS in P. aeruginosa. © 2015 John Wiley & Sons Ltd.

High reflectance Cr/C multilayer at 250 eV for soft X-ray polarimetry

Energy Technology Data Exchange (ETDEWEB)

Wen, Mingwu; Jiang, Li; Zhang, Zhong; Huang, Qiushi [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Wang, Zhanshan, E-mail: wangzs@tongji.edu.cn [MOE Key Laboratory of Advanced Micro-Structured Materials, Institute of Precision Optical Engineering (IPOE), School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); She, Rui; Feng, Hua [Department of Engineering Physics, Tsinghua University, Beijing (China); Wang, Hongchang [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

2015-10-01

X-ray reflection near 45° via multilayer mirrors can be used for astronomical polarization measurements. A Cr/C multilayer mirror (designed for X-ray polarimetry at 250 eV), with a period thickness of 3.86 nm and a bi-layer number of 100, was fabricated using direct current magnetron sputtering. Grazing incidence X-ray reflectometry at 8 keV and transmission electron microscopy were used to investigate the multilayer structure. Different models were introduced to fit the hard X-ray reflectivity curve, which indicates that the layer thickness of two materials slightly drifts from the bottom to the top of the stack. Both the chromium and carbon layers are amorphous with asymmetric interfaces, while the Cr-on-C interface is slightly wider. Based on the good quality of the multilayer structure, a high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV at a grazing incidence angle of 40.7°. The fabricated Cr/C multilayer mirror exhibits high reflectivity and polarization levels in the energy region of 240 eV–260 eV. - Highlights: • We fabricated Cr/C multilayer with 3.8 nm d-spacing. • X-ray reflectometry was used to determine the exact structure of Cr/C multilayer. • A high reflectivity of 21.8% for the s-polarized light was obtained at 250 eV. • Both Cr and C were found to be amorphous with slightly asymmetric interfaces. • A 4-layer model was used to fit and explain the results.

Breast carcinoma conservative treatment. Stages I and II; Tratamento conservador do carcinoma mamario. Estadios I e II

Energy Technology Data Exchange (ETDEWEB)

Monti, C.R.

1990-12-31

From 1981 to 1988, 265 patients with breast cancer stages I and II (UICC-1987), were evaluated after conservative treatment with quadrantectomy plus axillectomy, radiotherapy and chemotherapy. After surgical treatment, the patients were submitted to radiation therapy in the breast. One hundred and fifty six (58,8%) patients were submitted to adjuvant chemotherapy. The median clinical follow-up period was 42.8 months with a minimum of 24 and a maximum of 99 months. Six (2,3%) patients presented local recurrence and 48 (18,1%) presented distant metastasis. After five years the total survival rate was 89,7% and the disease free survival rate was 75% in the same period. The study did not show significant differences among the clinical stages classified after surgery and the use of adjuvant chemotherapy did not influence the results of the many stages. (author). 194 refs, 33 figs, 6 tabs.

Breast carcinoma conservative treatment. Stages I and II; Tratamento conservador do carcinoma mamario. Estadios I e II

Energy Technology Data Exchange (ETDEWEB)

Monti, C R

1991-12-31

From 1981 to 1988, 265 patients with breast cancer stages I and II (UICC-1987), were evaluated after conservative treatment with quadrantectomy plus axillectomy, radiotherapy and chemotherapy. After surgical treatment, the patients were submitted to radiation therapy in the breast. One hundred and fifty six (58,8%) patients were submitted to adjuvant chemotherapy. The median clinical follow-up period was 42.8 months with a minimum of 24 and a maximum of 99 months. Six (2,3%) patients presented local recurrence and 48 (18,1%) presented distant metastasis. After five years the total survival rate was 89,7% and the disease free survival rate was 75% in the same period. The study did not show significant differences among the clinical stages classified after surgery and the use of adjuvant chemotherapy did not influence the results of the many stages. (author). 194 refs, 33 figs, 6 tabs.

Evaluating the impact of an educational intervention to increase CRC screening rates in the African American community: a preliminary study.

Science.gov (United States)

Philip, Errol J; DuHamel, Katherine; Jandorf, Lina

2010-10-01

Despite the acknowledged importance of colorectal cancer (CRC) screening and its proven prognostic benefit, African American men and women simultaneously possess the highest rates of CRC-related incidence and mortality (Swan et al. in Cancer 97(6):1528-1540, 2003) and lowest screening rates in the United States (Polite et al. in Med Clin N Am 89(4):771-793, 2005). Effective, targeted interventions that promote CRC screening for this community are therefore critical. The current study evaluated the impact of a print-based educational intervention on screening behavior and associated patient-based factors, including cancer-related knowledge, fatalism, worry, and decisional balance (pros-cons). One hundred and eighteen individuals (mean age = 56.08, SD = 5.58) who had not undergone screening were recruited from two health clinics in New York City. Each participant received educational print materials regarding the need for screening, the process of undergoing screening, and the benefits of regular CRC screening. One in four individuals had undergone post-intervention screening at a three-month follow-up. Whereas all participants reported a decrease in cancer-related worry (p benefits and barriers of screening may be critical in the decision to undergo CRC screening. Future interventions to increase CRC-screening rates for this community may be improved by focusing on these patient-based factors.

Ovarian Cancer Stage II

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... peritoneal cancer; the first panel (stage IIA) shows cancer inside both ovaries that has spread to the uterus and fallopian tube. The second panel (stage IIB) shows cancer inside both ovaries that has spread to the colon. The third ...

Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.

Science.gov (United States)

Fischer, Joern; Joern, Fischer; Hellmich, Gunter; Gunter, Hellmich; Jackisch, Thomas; Thomas, Jackisch; Puffer, Erik; Erik, Puffer; Zimmer, Jörg; Jörg, Zimmer; Bleyl, Dorothea; Dorothea, Bleyl; Kittner, Thomas; Thomas, Kittner; Witzigmann, Helmut; Helmut, Witzigmann; Stelzner, Sigmar; Sigmar, Stelzner

2015-06-01

This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time. This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III. Postoperative mortality and histological incomplete resection were excluded, which left 995 patients with colonic cancer and 726 patients with rectal cancer for further analysis. Five-year CSS rates improved for colonic cancer from 65.0% for patients treated between 1981 and 1986 to 88.1% for patients treated between 2007 and 2011. For rectal cancer patients, the respective 5-year CSS rates improved from 53.4% in the first observation period to 89.8% in the second one. The local recurrence rate for rectal cancer dropped from 34.2% in the years 1981-1986 to 2.1% in the years 2007-2011. In the last decade of observation, prognosis for rectal cancer was equal to that for colon cancer (CSS 88.6 vs. 86.7%, p = 0.409). Survival of patients with colon and rectal cancer has continued to improve over the last three decades. After major changes in treatment strategy including introduction of total mesorectal excision and neoadjuvant (radio)chemotherapy, prognosis for stage II and III rectal cancer is at least as good as for stage II and III colonic cancer.

Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

Science.gov (United States)

Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

2016-07-05

Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

Why Wait Until Our Community Gets Cancer?: Exploring CRC Screening Barriers and Facilitators in the Spanish-Speaking Community in North Carolina.

Science.gov (United States)

Martens, Christa E; Crutchfield, Trisha M; Laping, Jane L; Perreras, Lexie; Reuland, Daniel S; Cubillos, Laura; Pignone, Michael P; Wheeler, Stephanie B

2016-12-01

Colorectal cancer (CRC) is a leading cause of death among Hispanics in the United States. Despite the benefits of CRC screening, many Hispanics are not being screened. Using a combined methodology of focus groups and discrete choice experiment (DCE) surveys, the objectives for this research were as follows: (1) to improve understanding of preferences regarding potential CRC screening program characteristics, and (2) to improve understanding of the barriers and facilitators around CRC screening with the Hispanic, immigrant community in North Carolina. Four gender-stratified focus groups were conducted and DCE surveys were administered to 38 Spanish-speaking individuals across four counties in North Carolina. In-depth content analysis was used to examine the focus group data; descriptive analyses and mean attribute importance scores for cost of screening and follow-up care, travel time, and test options were calculated from DCE data. Data analyses showed that this population has a strong interest in CRC screening but experience barriers such as lack of access to resources, cost uncertainty, and stigma. Some of these barriers are unique to their cultural experiences in the United States, such as an expressed lack of tailored CRC information. Based on the DCE, cost variables were more important than testing options or travel time. This study suggests that Hispanics may have a general awareness of and interest in CRC screening, but multiple barriers prevent them from getting screened. Special attention should be given to designing culturally and linguistically appropriate programs to improve access to healthcare resources, insurance, and associated costs among Hispanics.

Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

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Deevi, Ravi Kiran; Javadi, Arman; McClements, Jane; Vohhodina, Jekaterina; Savage, Kienan; Loughrey, Maurice Bernard; Evergren, Emma; Campbell, Frederick Charles

2018-04-01

Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of

Family history assessment for colorectal cancer (CRC) risk analysis - comparison of diagram- and questionnaire-based web interfaces.

Science.gov (United States)

Schultz, Michael; Seo, Steven Bohwan; Holt, Alec; Regenbrecht, Holger

2015-11-18

Colorectal cancer (CRC) has a high incidence, especially in New Zealand. The reasons for this are unknown. While most cancers develop sporadically, a positive family history, determined by the number and age at diagnosis of affected first and second degree relatives with CRC is one of the major factors, which may increase an individual's lifetime risk. Before a patient can be enrolled in a surveillance program a detailed assessment and documentation of the family history is important but time consuming and often inaccurate. The documentation is usually paper-based. Our aim was therefore to develop and validate the usability and efficacy of a web-based family history assessment tool for CRC suitable for the general population. The tool was also to calculate the risk and make a recommendation for surveillance. Two versions of an electronic assessment tool, diagram-based and questionnaire-based, were developed with the risk analysis and recommendations for surveillance based on the New Zealand Guidelines Group recommendations. Accuracy of our tool was tested prior to the study by comparing risk calculations based on family history by experienced gastroenterologists with the electronic assessment. The general public, visiting a local science fair were asked to use and comment on the usability of the two interfaces. Ninety people assessed and commented on the two interfaces. Both interfaces were effective in assessing the risk to develop CRC through their familial history for CRC. However, the questionnaire-based interface performed with significantly better satisfaction (p = 0.001) than the diagram-based interface. There was no difference in efficacy though. We conclude that a web-based questionnaire tool can assist in the accurate documentation and analysis of the family history relevant to determine the individual risk of CRC based on local guidelines. The calculator is now implemented and assessable through the web-page of a local charity for colorectal cancer

Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.

Science.gov (United States)

Azad, Nilofer S; El-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J; Brown, Thomas; Medvari, Prakriti; Jones, Peter A; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

2017-05-23

Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS.

Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

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Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

2017-07-24

High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

The prognostic value of microRNA-126 and microvessel density in patients with stage II colon cancer

DEFF Research Database (Denmark)

Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Morgenthaler, Søren

2014-01-01

BACKGROUND: Angiogenesis plays a pivotal role in malignant tumour growth and the metastatic process. We analysed the prognostic value of two angiogenesis parameters, microRNA-126 (miRNA-126) and microvessel density (MVD), in a population based cohort of patients operated for stage II colon cancer...... estimate was not associated with either RF-CSS, p = 0.49, or OS, p = 0.94.CONCLUSION: The current population based study of patients operated for stage II colon cancer demonstrated correlations between several prognostic unfavourable characteristics and miRNA-126 and argues for a possible prognostic impact...

Changes of serum cortisol and plasma angiotensin-II (AT-II) levels in patients with open chest surgery during peri-operative stage

International Nuclear Information System (INIS)

Yu Yunyun; Tian Runhua; Zhao Huiyuan; Li Xiaoqin; Wang Ling

2005-01-01

Objective: To assess the systemic stress reaction in patients with open chest surgery through measurement of the changes of serum cortisol and plasma AT-II levels during peri-operative stage. Methods: Serum cortisol and plasma AT-II levels were measured with RIA in 35 patients underwent open chest surgery both before and after the operative procedure. Results: The serum level of cortisol and plasma levels of AT-II were significantly higher after operation than those before operation ( P < 0.05 ). Also, the systolic pressure and heart rate were increased significantly (P<0.05). The post-operative heart rate was significantly positively correlated with both cortisol and AT-II levels (P<0.05). Conclusion: Stress reaction is evident in patients after open chest surgery with increase of serum cortisol and plasma AT-II levels. The stress reaction, if excessive, should be properly dealt with. (authors)

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

DEFF Research Database (Denmark)

Specht, L.; Horwich, A.; Ashley, S.

1994-01-01

patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology......PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681...

Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer

Directory of Open Access Journals (Sweden)

Robert eMeier

2015-04-01

Full Text Available Abstract: Stereotactic body radiotherapy (SBRT is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I dose escalation should yield improved rates of cancer control; (II the unique radiobiology of prostate cancer favors hypofractionation and (III the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity modulated radiotherapy (IMRT. Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife. Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low dose rate (LDR brachytherapy. Patient-reported quality of life (QOL outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After five years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

A Quality Improvement Initiative to Increase Colorectal Cancer (CRC) Screening: Collaboration between a Primary Care Clinic and Research Team.

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Green, Beverly B; Fuller, Sharon; Anderson, Melissa L; Mahoney, Christine; Mendy, Peter; Powell, Susan L

2017-01-01

Multiple randomized controlled trials have demonstrated that mailed fecal testing programs are effective in increasing colorectal cancer screening participation. However, few healthcare organization in the US have Implemented such programs. Stakeholders from one clinic in an integrated healthcare system in Washington State initiated collaboration with researchers with expertise in CRC screening, aiming to increase screening rates at their clinic. Age-eligible individuals who were overdue for CRC screening and had previously completed a fecal test were randomized to receive mailed fecal immunochemical test kits (FIT) at the start of the project (Early) or 6 months later (Late). Outcomes included comparing FIT completion at 6 months by randomization group, and overall CRC screening rates at 12 months. We also assessed implementation facilitators and challenges. Overall 2,421 FIT tests were mailed at a cost of $10,739. At 6 months, FIT completion was significantly higher among the Early compared to the Late group (62% vs.47%, p CRC screening rate was 75.1% at baseline and 78.0% 12 months later. Key constructs associated with successful program implementation included strong stakeholder involvement, use of evidence-based strategies, simplicity, and low cost. Challenges included lack of a plan for maintaining the program. Collaboration between clinic stakeholders and researchers led to a successful project that rapidly increased CRC screening rates. However, institutional normalization of the program would be required to maintain it.

Barriers to CRC Screening among Latino Adults in Pennsylvania: ACCN Results

Science.gov (United States)

Garcia-Dominic, Oralia; Lengerich, Eugene J.; Wray, Linda A.; Parrott, Roxanne; Aumiller, Betsy; Kluhsman, Brenda; Renderos, Carlos; Dignan, Mark

2012-01-01

Objectives: To describe knowledge of and barriers to colorectal cancer (CRC) screening by sex and geography among Latino adults in Pennsylvania. Methods: Eighty-two Latinos greater than 50 years old engaged in one of 8 focus groups. Focus groups consisted of 4 components. Focus group data were audiotaped, transcribed, and grouped into thematic…

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

Science.gov (United States)

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with stage I supradiaphragmatic presentations vs. those in patients with stage II

International Nuclear Information System (INIS)

Fuller, Lillian M.; Mirza, Nadeem Q.; Palmer, J. Lynn; Davis, Barry R.; Ha, Chul S.; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Cabanillas, Fernando; McLaughlin, Peter; Butler, James J.; North, Luceil B.; Martin, Richard G.

1998-01-01

Purpose: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. Methods and Materials: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. Results: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated

The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

Science.gov (United States)

Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

2017-06-08

The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

CpG island methylator phenotype is an independent predictor of survival after curative resection for colorectal cancer: A prospective cohort study.

Science.gov (United States)

Kim, Chang Hyun; Huh, Jung Wook; Kim, Hyeong Rok; Kim, Young Jin

2017-08-01

The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction. CIMP-high (H) and CIMP-none/low (N/L) tumors were found in 50 cases (31.8%) and 107 cases (68.2%), respectively. CIMP-H tumors were significantly associated with female sex, colonic location, poorly/mucinous histologic type, higher T category, perineural invasion, and MSI-high status (P = 0.001). During a median of 64.5 months, tumor recurrence developed in 47 (29.9%) patients. The 5-year disease-free survival for CIMP-H and CIMP-N/L was 61.4% and 76.3% (P = 0.018). In addition, multivariate analysis showed that CIMP-H was also a significant prognostic factor (P = 0.042). When analysis was performed according to anatomical location, more marked survival differences were observed in patients with colon cancer (P = 0.026) than in patients with rectal cancer (P = 0.210). Similarly, the role of CIMP status as a prognostic indicator was more prominent in patients with stage I/II (P = 0.006) than in patients with stage III/IV CRC (P = 0.65). DNA methylation status can be considered as a useful predictor of survival after CRC surgery, particularly for patients with stage I/II disease or colon cancer. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Estimating the adjuvant chemotherapy effect in elderly stage II and III colon cancer patients in an observational study.

Science.gov (United States)

Kim, Ki-Yeol; Cha, In-Ho; Ahn, Joong Bae; Kim, Nam Kyu; Rha, Sun Young; Chung, Hyun Cheol; Roh, Jae Kyung; Shin, Sang Joon

2013-05-01

Adjuvant chemotherapy has been known as a standard treatment for patients with resected colon cancer. However, in elderly colon cancer patients, the characteristics of patients are heterogeneous with regard to life expectancy and comorbidities. Thus, with regard to the effectiveness of adjuvant chemotherapy for colon cancer, it is difficult to extrapolate data of clinical trials from the younger into the older general population. Data for 382 elderly colon cancer patients were analyzed: 217 in Stage II and 165 in Stage III. The efficacy of adjuvant chemotherapy was evaluated in elderly colon cancer patients after a match by the propensity score method. For matched patients with Stage II colon cancer, there was no significant efficacy of adjuvant chemotherapy in the risk of death during all follow-up periods (P-value, 0.06-0.37). Though there was a tendency that the adjuvant chemotherapy reduces the death rate during the follow-up periods, it was not statistically significant. In the case of Stage III, the adjuvant chemotherapy was significantly effective in matched patients for 5-year (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.30-0.90) and overall survival (HR, 0.56; 95% CI, 0.34-0.94). Adjuvant chemotherapy for elderly patients with Stage II colon cancer is not effective, whereas elderly patients with Stage III with adjuvant chemotherapy appear to have a better survival rate in the general population. Copyright © 2012 Wiley Periodicals, Inc.

29 CFR 37.64 - What procedures must the Director follow when CRC has completed a post-approval compliance review?

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true What procedures must the Director follow when CRC has completed a post-approval compliance review? 37.64 Section 37.64 Labor Office of the Secretary of Labor... (WIA) Compliance Procedures § 37.64 What procedures must the Director follow when CRC has completed a...

Early positron emission tomography response-adapted treatment in stage I and II hodgkin lymphoma

DEFF Research Database (Denmark)

André, Marc P.E.; Girinsky, Théodore; Federico, Massimo

2017-01-01

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed...

Millimeter-wave spectroscopy of CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)): Examining the chromium-carbon bond.

Science.gov (United States)

Min, J; Ziurys, L M

2016-05-14

Pure rotational spectroscopy of the CrC (X(3)Σ(-)) and CrCCH (X̃ (6)Σ(+)) radicals has been conducted using millimeter/sub-millimeter direct absorption methods in the frequency range 225-585 GHz. These species were created in an AC discharge of Cr(CO)6 and either methane or acetylene, diluted in argon. Spectra of the CrCCD were also recorded for the first time using deuterated acetylene as the carbon precursor. Seven rotational transitions of CrC were measured, each consisting of three widely spaced, fine structure components, arising from spin-spin and spin-rotation interactions. Eleven rotational transitions were recorded for CrCCH and five for CrCCD; each transition in these cases was composed of a distinct fine structure sextet. These measurements confirm the respective (3)Σ(-) and (6)Σ(+) ground electronic states of these radicals, as indicated from optical studies. The data were analyzed using a Hund's case (b) Hamiltonian, and rotational, spin-spin, and spin-rotation constants have been accurately determined for all three species. The spectroscopic parameters for CrC were significantly revised from previous optical work, while those for CrCCH are in excellent agreement; completely new constants were established for CrCCD. The chromium-carbon bond length for CrC was calculated to be 1.631 Å, while that in CrCCH was found to be rCr-C = 1.993 Å - significantly longer. This result suggests that a single Cr-C bond is present in CrCCH, preserving the acetylenic structure of the ligand, while a triple bond exists in CrC. Analysis of the spin constants suggests that CrC has a nearby excited (1)Σ(+) state lying ∼16 900 cm(-1) higher in energy, and CrCCH has a (6)Π excited state with E ∼ 4800 cm(-1).

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

Science.gov (United States)

Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

The Crc global regulator inhibits the Pseudomonas putida pWW0 toluene/xylene assimilation pathway by repressing the translation of regulatory and structural genes.

Science.gov (United States)

Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

2010-08-06

In Pseudomonas putida, the expression of the pWW0 plasmid genes for the toluene/xylene assimilation pathway (the TOL pathway) is subject to complex regulation in response to environmental and physiological signals. This includes strong inhibition via catabolite repression, elicited by the carbon sources that the cells prefer to hydrocarbons. The Crc protein, a global regulator that controls carbon flow in pseudomonads, has an important role in this inhibition. Crc is a translational repressor that regulates the TOL genes, but how it does this has remained unknown. This study reports that Crc binds to sites located at the translation initiation regions of the mRNAs coding for XylR and XylS, two specific transcription activators of the TOL genes. Unexpectedly, eight additional Crc binding sites were found overlapping the translation initiation sites of genes coding for several enzymes of the pathway, all encoded within two polycistronic mRNAs. Evidence is provided supporting the idea that these sites are functional. This implies that Crc can differentially modulate the expression of particular genes within polycistronic mRNAs. It is proposed that Crc controls TOL genes in two ways. First, Crc inhibits the translation of the XylR and XylS regulators, thereby reducing the transcription of all TOL pathway genes. Second, Crc inhibits the translation of specific structural genes of the pathway, acting mainly on proteins involved in the first steps of toluene assimilation. This ensures a rapid inhibitory response that reduces the expression of the toluene/xylene degradation proteins when preferred carbon sources become available.

Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand Up 2 cancer study

Science.gov (United States)

Azad, Nilofer S.; el-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L.; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J.; Brown, Thomas; Medvari, Prakriti; Jones, Peter A.; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C.; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W.; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

2017-01-01

Purpose Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. Experimental Design We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Results Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. Conclusion In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS. PMID:28186961

Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

LENUS (Irish Health Repository)

2012-02-01

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

Changes in soluble CEA and TIMP-1 levels during adjuvant chemotherapy for stage III colon cancer

DEFF Research Database (Denmark)

Aldulaymi, Bahir; Christensen, Ib Jarle; Sölétormos, György

2010-01-01

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antige...... (CEA) levels in patients with stage III colon cancer.......Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen...

Correlation between hindfoot joint three-dimensional kinematics and the changes of the medial arch angle in stage II posterior tibial tendon dysfunction flatfoot.

Science.gov (United States)

Zhang, Yi-Jun; Xu, Jian; Wang, Yue; Lin, Xiang-Jin; Ma, Xin

2015-02-01

The aim of this study was to explore the correlation between the kinematics of the hindfoot joint and the medial arch angle change in stage II posterior tibial tendon dysfunction flatfoot three-dimensionally under loading. Computed tomography (CT) scans of 12 healthy feet and 12 feet with stage II posterior tibial tendon dysfunction flatfoot were taken both in non- and full-body-weight-bearing condition. The CT images of the hindfoot bones were reconstructed into three-dimensional models with Mimics and Geomagic reverse engineering software. The three-dimensional changes of the hindfoot joint were calculated to determine their correlation to the medial longitudinal arch angle. The medial arch angle change was larger in stage II posterior tibial tendon dysfunction flatfoot compared to that in healthy foot under loading. The rotation and translation of the talocalcaneal joint, the talonavicular joint and the calcanocuboid joint had little influence on the change of the medial arch angle in healthy foot. However, the eversion of the talocalcaneal joint, the proximal translation of the calcaneus relative to the talus and the dorsiflexion of talonavicular joint could increase the medial arch angle in stage II posterior tibial tendon dysfunction flatfoot under loading. Joint instability occurred in patients with stage II posterior tibial tendon dysfunction flatfoot under loading. Limitation of over movement of the talocalcaneal joint and the talonavicular joint may help correct the medial longitudinal arch in stage II posterior tibial tendon dysfunction flatfoot. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gender, anthropometric factors and risk of colorectal cancer with particular reference to tumour location and TNM stage: a cohort study

Directory of Open Access Journals (Sweden)

Brändstedt Jenny

2012-10-01

Full Text Available Abstract Background It remains unclear whether the increased risk of colorectal cancer (CRC associated with obesity differs by gender, distribution of fat, tumour location and clinical (TNM stage. The primary aim of this study was to examine these associations in 584 incident colorectal cancer cases from a Swedish prospective population-based cohort including 28098 men and women. Methods Seven anthropometric factors; height, weight, bodyfat percentage, hip circumference, waist circumference, BMI and waist-hip ratio (WHR were categorized into quartiles of baseline anthropometric measurements. Relative risks of CRC, total risk as well as risk of different TNM stages, and risk of tumours located to the colon or rectum, were calculated for all cases, women and men, respectively, using multivariate Cox regression models. Results Obesity, as defined by all anthropometric variables, was significantly associated with an overall increased risk of CRC in both women and men. While none of the anthropometric measures was significantly associated with risk of tumour (T-stage 1 and 2 tumours, all anthropometric variables were significantly associated with an increased risk of T-stage 3 and 4, in particular in men. In men, increasing quartiles of weight, hip, waist, BMI and WHR were significantly associated with an increased risk of lymph node positive (N1 and N2 disease, and risk of both non-metastatic (M0 and metastatic (M1 disease. In women, there were no or weak associations between obesity and risk of node-positive disease, but statistically significant associations between increased weight, bodyfat percentage, hip, BMI and M0 disease. Interestingly, there was an increased risk of colon but not rectal cancer in men, and rectal but not colon cancer in women, by increased measures of weight, hip-, waist circumference and bodyfat percentage. Conclusions This study is the first to show a relationship between obesity, measured as several different

Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

NARCIS (Netherlands)

Eggermont, Alexander M. M.; Punt, Cornelis J. A.

2003-01-01

The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to

Adjuvant chemotherapy for stage II colon cancer: influence of care structures' characteristics on a controversial clinical practice.

Science.gov (United States)

Alter, Eléonore; Phelip, Jean-Marc; Guilhot, Jean-Noel; Matysiak, Michel; Vermorel, Michel; Roblin, Xavier

2007-11-01

Adjuvant chemotherapy for stage II colon cancer is a controversial practice and is not recommended by the French Consensus Conference outside of therapeutic trial. To assess, within a well-defined population, the influence of hospital characteristics in this practice. In the Rhône-Alpes region (10% of the French population), 534 patients presenting with colon cancer stage II were operated on in 81 hospitals in the year 2000. The influence of hospital characteristics on the use of adjuvant chemotherapy was assessed using a multivariate logistic regression. Overall, 19.5% of patients received adjuvant chemotherapy. Younger age, T4 tumour, hospital volume lower than 20 colon cancer surgeries [odds ratio (OR) 2.96; Pclinical complications at diagnosis were independently associated with higher rates of chemotherapy. On the other hand, a number of examined lymph nodes lower than recommendations did not have any influence on chemotherapy use. Hospital characteristics had independently influenced the practice of adjuvant chemotherapy in stage II colon cancer. The more important institutional factor was the hospital procedure volume. The decisions of the multidisciplinary committees appeared at times paradoxical; a more comprehensive evaluation of this practice is needed.

High NUCB2 expression level is associated with metastasis and may promote tumor progression in colorectal cancer.

Science.gov (United States)

Xie, Jun; Chen, Lina; Chen, Wenbin

2018-06-01

Nucleobindin 2 (NUCB2) is mainly expressed in the hypothalamic nuclei and has a proven role in energy homeostasis. It has also been recently reported to have a key role in tumor progression. However, the clinical significance of NUCB2 in colorectal cancer (CRC) remains unknown. In the present study, the level of NUCB2 mRNA was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in 34 paired fresh tissues from patients with CRC. RT-qPCR was followed by immunohistochemical (IHC) staining of NUCB2 protein in tissue microarrays of 251 samples to evaluate the clinical significance of NUCB2 in CRC. The RT-qPCR indicated an upregulation of NUCB2 mRNA in CRC tissues compared with normal tissues (P=0.027). IHC staining indicated a positive association between elevated NUCB2 expression and lymph node metastasis or tumor-node-metastasis (TNM) stage. Patients with CRC and lymph node metastasis demonstrated a higher expression of NUCB2 (49.5%, 50/101) compared with those without lymph node metastasis (36.7%, 55/150; P=0.043). Furthermore, NUCB2 expression was also higher in patients with CRC and TNM stage III-IV compared with those with TNM stage I-II (50.9% vs. 35.0%; P=0.011). However, Kaplan-Meier analysis indicated no significant association between NUCB2 expression and disease-free survival of patients. Additionally, multivariate analysis did not identify the upregulation of NUCB2 as an independent prognostic predictor in patients with CRC (P=0.755). In conclusion, the present study demonstrated that upregulation of NUCB2 is significantly associated with CRC metastasis, indicating that NUCB2 may be a cancer-associated oncogene associated with the aggressive progression of CRC.

Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon cancer.

Science.gov (United States)

Renouf, Daniel J; Woods, Ryan; Speers, Caroline; Hay, John; Phang, P Terry; Fitzgerald, Catherine; Kennecke, Hagen

2013-12-01

Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (Prectal cancer. DSS significantly improved for rectal (Pcolon cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). Advances in locoregional and systemic therapy significantly improved survival among patients with rectal cancer. DSS and OS are now similar between colon and rectal cancer for both stage II and III disease.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

International Nuclear Information System (INIS)

Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

2016-01-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

2016-04-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Impact of comorbidity and healthcare utilization on colorectal cancer stage at diagnosis: literature review

Science.gov (United States)

Corkum, Mark; Urquhart, Robin; Burge, Fred; Porter, Geoffrey; Johnston, Grace

2013-01-01

Purpose Individuals diagnosed with cancer close to death have low access to enrollment in palliative care programs. The purpose of this literature review was to assess the usefulness of pre-diagnostic comorbidity and healthcare utilization as indicators of late-stage colorectal cancer (CRC) diagnosis, to help with early identification of individuals who may benefit from palliative care. Methods A literature search was conducted in relevant databases using title/abstract terms which included “cancer,” “stage,” “diagnosis,” “determinants,” “predictors,” and “associated.” Included studies examined whether comorbidity and/or healthcare utilization had an impact on the stage at which CRC was diagnosed. A standardized data abstraction form was used to assess the eligibility of each study. Thirteen articles were included in the literature review. These studies were assessed and synthesized using qualitative methodology. Results We found much heterogeneity among study variables. The findings of this literature review point to the presence of comorbidity and non-emergent healthcare utilization as having no association with late-stage diagnosis. Conversely, emergency room presentation (ERP) was associated with late-stage diagnosis. Conclusions The results of this literature review did not find strong evidence to suggest that comorbidity and healthcare utilization are potential indicators of late-stage diagnosis. However, ERP may be useful as a flag for consideration of prompt referral to palliative care. Additional research is required to identify potential indicators of late-stage diagnosis that may be available in administrative databases, particularly in the area of healthcare utilization. PMID:22101505

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

DEFF Research Database (Denmark)

Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik

2011-01-01

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust...... in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The mi...... relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation...

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

Science.gov (United States)

Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

2018-02-15

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil;Ccontrole de qualidade do sistema padrao secundario NPL-CRC utilizado na calibracao de ativimetros no IPEN

Energy Technology Data Exchange (ETDEWEB)

Martins, Elaine W.; Potiens, Maria da P.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2009-07-01

The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC{sup R}-15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of {sup 133}Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

The New UN CRC General Comment 13: "The Right of the Child to Freedom from All Forms of Violence"--Changing How the World Conceptualizes Child Protection

Science.gov (United States)

Svevo-Cianci, Kimberly A.; Herczog, Maria; Krappmann, Lothar; Cook, Philip

2011-01-01

The UN Committee on the Rights of the Child established CRC General Comment 13 (April 2011) to address today's unabating high rates of violence against children globally despite CRC advances. GC13 provides clear interpretations and stronger detail to supplement the legal language of CRC Article 19, intended to establish protection of children from…

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

Science.gov (United States)

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

DEFF Research Database (Denmark)

Horwich, A.; Specht, L.; Ashley, S.

1997-01-01

relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

Intratumoral stromal morphometry predicts disease recurrence but not response to 5-fluorouracil-results from the QUASAR trial of colorectal cancer.

Science.gov (United States)

Hutchins, Gordon G A; Treanor, Darren; Wright, Alexander; Handley, Kelly; Magill, Laura; Tinkler-Hundal, Emma; Southward, Katie; Seymour, Matthew; Kerr, David; Gray, Richard; Quirke, Philip

2018-02-01

The biological importance of tumour-associated stroma is becoming increasingly apparent, but its clinical utility remains ill-defined. For stage II/Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to direct therapeutic options. We report here prognostic/predictive analyses, and molecular associations, of stromal morphometric quantification in the Quick and Simple and Reliable (QUASAR) trial of CRC. Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified on digitised haematoxylin and eosin (H&E) sections derived from 1800 patients enrolled in QUASAR, which randomised 3239 (91% stage II) CRC patients between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation. The prognostic and predictive values of PoT/PoS measurements were determined by the use of stratified log-rank analyses. A high proportion of tumour stroma (≥50%) was associated with an increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1343) for 50% higher risk of disease recurrence. This technique can reliably partition patients into subpopulations with different risks of tumour recurrence in a simple and cost-effective manner. Further prospective validation is warranted. © 2017 John Wiley & Sons Ltd.

Adherence to treatment guidelines and survival for older patients with stage II or III colon cancer in Texas from 2001 through 2011.

Science.gov (United States)

Zhao, Hui; Zhang, Ning; Ho, Vivian; Ding, Minming; He, Weiguo; Niu, Jiangong; Yang, Ming; Du, Xianglin L; Zorzi, Daria; Chavez-MacGregor, Mariana; Giordano, Sharon H

2018-02-15

Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to

Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

Science.gov (United States)

ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

2016-11-15

The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

Recovery in stages I and II of thermal and fission neutron irradiated molybdenum

International Nuclear Information System (INIS)

Coltman, R.R. Jr.; Klabunde, C.E.; Redman, J.K.

1975-01-01

The influence of initial dose and irradiation doping upon the recovery of Mo was studied for the markedly different types of damage produced by thermal and fission neutrons. The features of the Stage I recovery commonly seen for several fcc metals can be identified, including a I/sub D/ peak at 40 0 K. The typical dose-dependent behavior of a I/sub E/ subpeak was observed at approximately 47 0 K, and evidence for free interstitial migration is further supported by irradiation doping results. Stage II shows a first-order peak at 120 0 K in which the population percentage increases with increasing initial dose in opposite fashion to fcc impurity detrapping peaks. (auth)

Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials

International Nuclear Information System (INIS)

Young, R.C.; Walton, L.A.; Ellenberg, S.S.; Homesley, H.D.; Wilbanks, G.D.; Decker, D.G.; Miller, A.; Park, R.; Major, F. Jr.

1990-01-01

About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma. All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival or overall survival. In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

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Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-01-01

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

Prognostic markers for colorectal cancer: estimating ploidy and stroma.

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Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

2018-03-01

We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

The prognostic importance of miR-21 in stage II colon cancer: a population-based study

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Kjaer-Frifeldt, S.; Hansen, T. F.; Nielsen, B. S.

2012-01-01

that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited. British Journal of Cancer (2012) 107, 1169-1174. doi:10.1038/bjc.2012.365 www......BACKGROUND: Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (mi......-free cancer-specific survival (RF-CSS): HR = 1.26; 95% CI: 1.15-1.60; P importance and was found to be significantly related to poor RF-CSS: HR 1.41; 95% CI: 1.19-1.67; P

Performance of continuously reinforced concrete pavements volume 5 : maintenance and repair of CRC pavements.

Science.gov (United States)

1998-10-01

This report is one of a series of reports prepared as part of a recent study sponsored by the Federal Highway Administration (FHWA) aimed at updating the state-of-the-art of the design, construction, maintenance, and rehabiilitation of CRC pavements....

Definitive radiation therapy for medically inoperable patients with stage I and II non-small cell lung cancer

International Nuclear Information System (INIS)

Hayakawa, K.; Mitsuhashi, N.; Saito, Y.; Nakayama, Y.; Katano, S.; Furuta, M.; Sakurai, H.; Takahashi, T.; Niibe, H.

1995-01-01

Purpose: To evaluate the role of definitive radiation therapy (RT) in the treatment for medically inoperable patients with stage I-II non-small cell lung cancer (NSCLC). Materials and Methods: From 1976 through 1989, 84 patients with clinical stage I and II NSCLC were treated with definitive RT alone at Gunma University hospital. All patients were treated with 10 MV X-rays using antero-posterior parallel opposed fields. The total dose ranged from 60 Gy to 90 Gy (35 pts; 60-69 Gy, 39 pts; 70-74 Gy, 10 pts; ≥ 80 Gy) with once-daily standard fractionation. Results: The two and five-year survival rates were 74% and 31% for 28 patients with stage I disease, as compared with 40% and 19% for 56 patients with stage II respectively (p<0.05). Although there was no significant difference of survival rates by the histologic subtypes, in the patients with squamous cell carcinoma there were more long-term survivors. Fifty-three patients with tumors less than 5 cm in diameter had an infield progression rate of 14% at two years, in comparison with 38% of 31 patients with tumors greater than 5 cm (p<0.05). Overall distant failure occurred in 57% of the patients with smaller tumors and in 80% of the patients with larger tumors (p<0.05). The difference of survival rates for these two groups was statistically significant (p<0.005). Ten patients given a total dose of 80Gy or over had only 17% local progression at the time of last follow-up, however they had not been alive beyond three years because they developed pulmonary insufficiency due to severe stenosis of the proximal bronchus. For age and sex, there were no significant differences in survival, however, patients with performance status of 0-1 lived longer than those with a status of 2 or more (MST 24 versus 13 months; p=0.06). Conclusion: The tumor size was the most important factor not only for local control but also for distant failure. It was also suggested that the optimal radiation dose for medically inoperable stage I-II

Self reported awareness of child maltreatment among school professionals in Saudi Arabia: impact of CRC ratification.

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AlBuhairan, Fadia S; Inam, Sarah S; AlEissa, Majid A; Noor, Ismail K; Almuneef, Maha A

2011-12-01

The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying those in danger or at risk. The objective of this study is to identify school professional's awareness of child maltreatment and the existing national policies and procedures to examine the extent of efforts made in Saudi Arabia and to activate the roles of schools and school professionals in protecting children from violence and implementation of Article 19 of the CRC. This was a cross-sectional study, where school professionals from randomly selected schools throughout the country were invited to participate in a self-administered questionnaire. A total of 3,777 school professionals participated in the study. Fifty-five percent of professionals had at least 10 years of work experience. A low-level of awareness of child maltreatment was found in about 1/3 of school professionals. Only 1.9% of school professionals had ever attended any sort of specific training on child maltreatment, though 69.3% of those who had not, were willing to attend future training. With regards to awareness of CRC Article 19 or policies and procedures addressing child maltreatment, only 22% reported being aware of it. The majority of school professionals in Saudi Arabia have a low-intermediate level of awareness of child maltreatment, ratification of CRC, and related national policies and procedures, yet most are willing to attend training programs on this subject matter. Efforts need to be made in the country to fill this gap. Copyright © 2011 Elsevier Ltd. All rights reserved.

Validation of the 12-gene colon cancer recurrence score as a predictor of recurrence risk in stage II and III rectal cancer patients.

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Reimers, Marlies S; Kuppen, Peter J K; Lee, Mark; Lopatin, Margarita; Tezcan, Haluk; Putter, Hein; Clark-Langone, Kim; Liefers, Gerrit Jan; Shak, Steve; van de Velde, Cornelis J H

2014-11-01

The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial. RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided. Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients). The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The safety and efficacy of microwave ablation for the treatment of CRC pulmonary metastases.

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Cheng, Gui; Shi, Liangrong; Qiang, Weiguang; Wu, Jun; Ji, Mei; Lu, Qicheng; Li, Xiaodong; Xu, Bin; Jiang, Jingting; Wu, Changping

2017-11-16

Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases. From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30 d after ablation. The mean hospital stay was 3 d (range, 2-7 d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31 months (95% CI: 15.4-46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p = .007, p = .022 and p = .030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p = .017). CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases.

Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

Science.gov (United States)

2018-04-24

Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

IRRIGATION PRACTICES IN LONG-TERM SURVIVORS OF COLORECTAL CANCER (CRC) WITH COLOSTOMIES

Science.gov (United States)

Grant, Marcia; McMullen, Carmit K.; Altschuler, Andrea; Hornbrook, Mark C.; Herrinton, Lisa J.; Wendel, Christopher S.; Baldwin, Carol M.; Krouse, Robert S.

2014-01-01

Creation of a colostomy in colorectal (CRC) cancer patients results in a loss of control over bowel evacuation. The only way to re-establish some control is through irrigation, a procedure that involves instilling fluid into the bowel to allow for gas and fecal output. This article reports on irrigation practices of participants in a large, multi-site, multi-investigator study of health-related quality of life (HR-QOL) in long term CRC survivors. Questions about irrigation practices were identified in open-ended questions within a large HR-QOL survey and in focus groups of men and women with high and low HR-QOL. Descriptive data on survivors were combined with content analysis of irrigation knowledge and practices. Patient education and use of irrigation in the United States has decreased over the years, with no clear identification of why this change in practice has occurred. Those respondents who used irrigation had their surgery longer ago, and spent more time in colostomy care than those that did not irrigate. Reasons for the decrease in colostomy irrigation are unreported and present priorities for needed research. PMID:23022935

Systemic therapy for patients with colorectal cancer

DEFF Research Database (Denmark)

Pfeiffer, Per; Qvortrup, Camilla; Tabernero, Josep

2015-01-01

Recent modalities and strategies have increased the complexity of treatment choice in patients with colorectal cancer (CRC), and therefore all cases should be assessed at a multidisciplinary conference. Adjuvant chemotherapy for 6 months increases the chance of cure by absolutely 5 % in stage II...

Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma [v2; ref status: indexed, http://f1000r.es/4k6

Directory of Open Access Journals (Sweden)

Tianhua Guo

2014-10-01

Full Text Available Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female had a mean age of 69.9 years (+/- 12.7 years at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients. Although the mean platelet count increased with the depth of tumor invasion (pT, its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57 had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4% with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery. The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

Breast-conserving therapy (BCT) in stage I-II synchronous bilateral breast cancer (SBBC)

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Gollamudi, Smitha V; Gelman, Rebecca S; Peiro, Gloria; Schneider, Lindsey; Connolly, James L; Schnitt, Stuart; Silver, Barbara; Harris, Jay R

1995-07-01

PURPOSE: To determine whether patients with early-stage SBBC can be safely and effectively treated with bilateral BCT. MATERIALS and METHODS: We retrospectively reviewed records of 26 patients with clinical Stage I-II SBBC treated between 1968-1989 with bilateral BCT. SBBC was defined as tumors diagnosed no more than one month apart, with both sides demonstrating invasive cancer. Maximum (max) clinical stage was based on the more advanced breast tumor. Median age at diagnosis was 56 years (range, 32-85 years); menopausal status was 6 pre-, 16 post-, 3 peri-, and 1 unknown at diagnosis. Median follow-up for surviving pts is 95 months (range, 68-157). Outcome was compared to 1325 pts with unilateral Stage I or II breast cancer, within the same age range, treated during the same time period. There were no significant differences in median age, median total dose, tumor size, estrogen receptor (ER) status, pathologic nodal status, and use of systemic therapy between the study population and the comparison group. Local recurrence (LR) was evaluated as true recurrence (TR, i.e., in the original tumor bed), marginal miss (MM, at the edge of the boost field), or elsewhere (E). Median total dose to the primary was 6100 cGy (range, 5000-7000). Pathology was available for review in 19 cases. Cytology (nuclear and cytoplasmic features) was similar in (7(19)) evaluable cases, and architecture (growth pattern, ie, papillary, solid) was similar in (5(19)) cases. The presence of either cytologic or architectural similarity was noted in(9(19)) cases. 7 of 19 pts who had axillary lymph node evaluation on at least one side had pathological confirmation of lymph node metastasis. Stage was the same in both breasts in 13 cases (10 Stage I, 3 Stage II); ER status data was complete in 11 pts, and the same in both primaries in 9 cases. Cosmetic results and complications after BCT were scored. Statistical significance was evaluated by use of the Fisher exact test. RESULTS: The 5-yr actuarial

Biomechanical Analysis of Cuboid Osteotomy Lateral Column Lengthening for Stage II B Adult-Acquired Flatfoot Deformity: A Cadaveric Study.

Science.gov (United States)

Zhou, Haichao; Ren, Haoyang; Li, Chunguang; Xia, Jiang; Yu, Guangrong; Yang, Yunfeng

2017-01-01

Purpose . To investigate the effect of cuboid osteotomy lateral column lengthening (LCL) for the correction of stage II B adult-acquired flatfoot deformity in cadaver. Methods . Six cadaver specimens were loaded to 350 N. Flatfoot models were established and each was evaluated radiographically and pedobarographically in the following conditions: (1) intact foot, (2) flatfoot, and (3) cuboid osteotomy LCL (2, 3, 4, and 5 mm). Results . Compared with the flatfoot model, the LCLs showed significant correction of talonavicular coverage on anteroposterior radiographs and talus-first metatarsal angle on both anteroposterior and lateral radiographs ( p stage II B adult-acquired flatfoot deformity with a 3 mm lengthening in cadavers.

Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages.

Science.gov (United States)

Khoja, Aisha; Fida, Mubassar; Shaikh, Attiya

2016-06-01

To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB) in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1) were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p ≤ 0.05) . When compared with controls, there was a significant reduction in ANB angle (p cervical stages (p cervical stages (p cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and dentoalveolar structures. The favorable mandibular growth occurs during any of the cervical vertebral maturation stages, with more pronounced effect during CS-3 stage.

Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

Science.gov (United States)

Papagiorgis, Petros Christakis

2016-05-01

Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

INFLUENCE OF THE FDG-PET/CT ON THE DIAGNOSE AND STAGING OF COLORECTAL CANCER.

Directory of Open Access Journals (Sweden)

Nikola Y. Kolev

2012-06-01

Full Text Available INTRODUCTION: In patients with colorectal cancer (CRC, preoperative evaluation and staging should focus on techniques that might alter the preoperative or intraoperative surgical plan. Conventional imaging methods (CT, MRI have low accuracy for identifying the depth of tumour infiltration and have limited ability to detect regional lymph node involvement. The aim of this study was to evaluate the utility of FDG-PET in the initial staging of patients with CC in comparison with conventional staging methods and to determine its impact on therapeutic management.METHODS: In First Clinic of Surgery at University Hospital “St. Marina” one hundred and four patients with a diagnosis of CRC (53 males and 51 females; mean age 66.76± 12.36 years, selected prospectively. All patients were studied for staging using a standard procedure (CT and FDG-PET. The reference method was histology. The effect of FDG-PET on the diagnose and the operative treatment was studied.RESULTS: In 14 patients, surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14 suspected by CT. FDG-PET revealed four synchronous tumours. For N staging, both procedures showed a relatively high specificity but a low diagnostic accuracy (PET 56%, CT 60% and sensitivity (PET 21%, CT 25%. For M assessment, diagnostic accuracy was 92% for FDGPET and 87% for CT. FDG-PET results led to modification of the therapy approach in 17.85% of the patients with rectal cancer and in 14.8% of the patients with colon cancer.CONCLUSION: Compared with conventional techniques, FDGPET appears to be useful in pre-surgical staging of CC, revealing unsuspected disease and impacting on the treatment approach.

High expression of testes-specific protease 50 is associated with poor prognosis in colorectal carcinoma.

Directory of Open Access Journals (Sweden)

Lei Zheng

Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50 is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: TSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751 or CEA (P = 0.663. Abundant expression of TSP50 protein was found in CRCs (68.4% while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001. Thus, CRCs can be distinguished from them with high specificity (92.5% and positive predictive value (PPV, 95.6%. The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010, specifically in patients who had early-stage tumors (stage I and II; P = 0.004. Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio  = 2.205, 95% CI = 1.214-4.004, P = 0.009. CONCLUSION: Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

International Nuclear Information System (INIS)

Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

2009-01-01

The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.

Science.gov (United States)

Du, Changzheng; Yao, Yunfeng; Xue, Weicheng; Zhu, Wei-Guo; Peng, Yifan; Gu, Jin

2014-01-01

The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer. 145 patients with stage I/II colon cancer who underwent curative surgery alone from 2000 to 2007 were investigated. Chemokine receptor expression was assessed by immunohistochemistry. The associations between CXCR3, CXCR4 and clinicopathological variables were analysed using the χ2 test, and the relationships between chemokine receptors and a 5-year disease-free survival were analysed by univariate and multivariate analyses. The high-expression rates of CXCR3 and CXCR4 were 17.9% (26/145) and 38.6% (56/145), respectively. There were no significant associations between the expressions of CXCR3, CXCR4 and clinicopathological factors including gender, age, tumour location, histological differentiation, pathological stage, lymphovascular invasion and pretreatment serum carcinoembryonic antigen (CEA). The 5-year disease-free survival was not significantly different between low-expression groups and high-expression groups of CXCR3 and CXCR4. Multivariate analysis revealed that serum CEA and a number of retrieved lymph nodes, rather than chemokine receptors, were independent prognosticators. CXCR3 and CXCR4 are not independent prognosticators for stage I/II colon cancer after curative surgery.

Survival and Complication Rate of Radiation Therapy in Stage I and II Carcinoma of uterine Cervix

International Nuclear Information System (INIS)

Ma, Sun Young; Cho, Heung Lea; Sohn, Seung Chang

1995-01-01

Purpose : To analyze survival rate and late rectal and bladder complication for patients with stage with stage I and II carcinoma of uterine cervix treated by radiation alone or combined with chemotherapy. Materials and Methods : Between November 1984 and December 1993, 127 patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined therapy of radiation and chemotherapy. Retrospective analysis for survival rate was carried out on eligible 107 patients and review for complication was possible in 91 patients. The median follow-up was 47 months (range 3-118) and the median age of patients was 56 years (range 31-76). 26 patients were stage IB by FIGO classification. 40 were stage IIA and 41 were stage IIB. 86 cases were treated by radiation alone and 21 were treated by radiation and chemotherapy. 101 patients were treated with intracavitary radiation therapy (ICRT), of these, 80 were received low dose rate (LDR) ICRT and 21 were received high dose rate (HDR) ICRT. Of the patients who received LDR ICRT, 63 were treated by 1 intracavitary insertion and 17 were underwent 2 insertions. And we evaluated the external radiation dose and midline shield. Results : Acturial survival rate at 5 years was 92% for stage IB, 75% for stage IIA, 53% for stage IIB and 69% in all patients. Grade 1 rectal complications were developed in 20 cases(22%), grade 2 were in 22 cases (24%), 22 cases (24%) of grade 1 urinary complications and 17 cases (19%) of grade 2 urinary complications were observed But no patients had severe complications that needed surgical management or admission care. Maximum bladder dose for the group of patients with urinary complications was higher than that for the patients without urinary complications(7608cGy v 6960cGy, p<0.01). Maximum rectal dose for the group of patients with rectal complications was higher than that for the patients without urinary complications (7041cGy v 6269cGy, p<0.01). While there was no significant

Stages of Penile Cancer

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... under a microscope . Stage II In stage II , cancer has spread: to connective tissue just under the skin of the penis . Also, ... spread to one lymph node in the groin . Cancer has also spread: to connective tissue just under the skin of the penis . Also, ...

Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas

2017-01-01

Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...

Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer.

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Kleespies, Axel; Füessl, Kathrin E; Seeliger, Hendrik; Eichhorn, Martin E; Müller, Mario H; Rentsch, Markus; Thasler, Wolfgang E; Angele, Martin K; Kreis, Martin E; Jauch, Karl-Walter

2009-09-01

The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival. Using a prospective database, we analyzed potential risk factors in 233 patients, who were electively operated for non-curable stage IV CRC between 1996 and 2002. Patients with recurrent tumors, resectable metastases, emergency operations, and non-resective surgery were excluded. Risk factors for increased postoperative morbidity and limited postoperative survival were identified by multivariate analyses. Patients with colon cancer (CC = 156) and rectal cancer (RC = 77) were comparable with regard to age, sex, comorbidity, American Society of Anesthesiologists score, carcinoembryonic antigen levels, hepatic spread, tumor grade, resection margins, 30-day mortality (CC 5.1%, RC 3.9%) and postoperative chemotherapy. pT4 tumors, carcinomatosis, and non-anatomical resections were more common in colon cancer patients, whereas enterostomies (CC 1.3%, RC 67.5%, p 50%, and comorbidity >1 organ. Prognostic factors for limited postoperative survival were hepatic tumor load >50%, pT4 tumors, lymphatic spread, R1-2 resection, and lack of chemotherapy. Palliative resection is associated with a particularly unfavorable outcome in rectal cancer patients presenting with a locally advanced tumor (pT4, expected R2 resection) or an extensive comorbidity, and in all CRC patients who show a hepatic tumor load >50%. For such patients, surgery might be contraindicated unless the tumor is immediately life-threatening.

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

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Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Improved survival for rectal cancer compared to colon cancer: the four cohort study.

Science.gov (United States)

Buchwald, Pamela; Hall, Claire; Davidson, Callum; Dixon, Liane; Dobbs, Bruce; Robinson, Bridget; Frizelle, Frank

2018-03-01

Colorectal cancer (CRC) is the third most common cancer worldwide. This study was undertaken to evaluate survival outcomes and changes of disease outcomes of CRC patients over the last decades. A retrospective analysis of CRC patients in Christchurch was performed in four patient cohorts at 5 yearly intervals; 1993-94, 1998-99, 2004-05 and 2009. Data on cancer location, stage, surgical and oncological treatment and survival were collected. Univariate, multivariate and Kaplan-Meier survival analysis were performed. There were 1391 patients (355, 317, 419 and 300 per cohort), 1037 colon and 354 rectal cancers, respectively. For colon cancer, right-sided cancers appeared more common in later cohorts (P = 0.01). There was a significant decrease in the number of permanent stomas for colon cancer patients (P = 0.001). There was an analogous trend for rectal cancers (P = 0.075). More CRC patients with stage IV disease were treated surgically (P = 0.001) and colon cancer stages I and II tended to have increased survival if operated by a colorectal surgeon (P = 0.06). Oncology referrals have increased remarkably (P = 0.001). Overall 56% of patients were alive at 5 years however rectal cancer patients had significantly better 5-year survival than those with colon cancer (P rectal cancer patients have a better 5-year survival than colon cancer patients. The improved survival with early stage colon cancers operated on by specialist colorectal surgeons needs further exploration. © 2016 Royal Australasian College of Surgeons.

5-YEAR SURVIVAL OF PATIENTS WITH STAGE II UTERINE CANCER DEPENDING ON MORPHOLOGIC FEATURES OF TUMOR

Directory of Open Access Journals (Sweden)

Ye. A. Mustafina

2008-01-01

Full Text Available Retrospective data of treatment results of 109 patients with rarely observed stage II uterine cancer, admitted to N.N. Blokhin Russian Cancer Research Center from 1980 to 2000 is analyzed. Correlation of overall 5-year survival rates of stage IIA and IIB uterine can- cer patients with a number of tumor morphologic features is studied. The influence of some non-elucidated morphologic features of stage IIA and IIB uterine cancer such as the degree of cellular anaplasia, the depth of tumor invasion into the uterine neck, lymho- vascular invasion into the myometrium and uterine neck, microscopic vessels density in the area of the most extensive invasion, the presence of necrotic areas in the tumor tissue on long-term treatment results are analyzed.

Tiotropium bromide in the routine care of GOLD stage II COPD patients: a pharmaeconomic evaluation

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Orietta Zaniolo

2011-06-01

Full Text Available Background: a secondary pre-specified analysis of the UPLIFT cohort demonstrated that the inclusion of tiotropium bromide in the routine care of GOLD stage II (moderate chronic obstructive pulmonary disease (COPD patients is associated with stronger improvements of survival, quality of life, and exacerbation rate than those shown in the total cohort; in this subgroup, tiotropium furthermore induces a significant reduction in the rate of FEV1 decline.Objective: to adapt the Spiriva® model, originally built to evaluate cost-effectiveness of tiotropium inclusion in the general COPD population, to GOLD II patients.Methods: the Spiriva® model is a probabilistic Markov patient-level simulation developed over a lifetime horizon to compare outcomes associated with the inclusion of tiotropium in routine care (RC for COPD treatment with those obtained with RC alone. Patients are characterised by gender, age, height, smoking status and FEV1. Model structure and sources have been maintained unvaried, except for demographic characteristics, specific for GOLD II patients, as extrapolated from an Italian observational study, and tiotropium efficacy, based on the secondary analysis of GOLD II UPLIFT patients. As in the original model, only direct health care costs are considered.Results: patients treated with tiotropium on average (95% CI gain 0.70 (0.00/7.23 LYs or 0.77 (0.02/4.67 QALYs compared to RC. The incremental lifetime cost is € 3,520 (-6,391/26,686, meaning that the incremental cost required to gain a QALY (incremental cost-effectiveness ratio – ICER is equal to € 4,548. Sensitivity analysis shows that tiotropium has a 50% probability of being cost-effective for a willingness-to-pay (WTP around 4,600 €/QALY; 100% probability is achieved with a WTP of € 9,300.Conclusions: the adoption of a strategy based on the inclusion of tiotropium from the early COPD stages represents good value for money in Italy, as the ICER estimated for GOLD II

Efficacy of biofeedback on quality of life in stages I and II pelvic organ prolapse: A Pilot study.

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Ahadi, Tannaz; Taghvadoost, Neda; Aminimoghaddam, Soheila; Forogh, Bijan; Bazazbehbahani, Roxana; Raissi, Gholam Reza

2017-08-01

Pelvic organ prolapse (POP) is a prevalent disorder which seriously affects the sufferer's quality of life. The main goal of this study was to evaluate biofeedback impact on quality of life in women with mild to moderate POP. 40 females in stages I and II POP were allocated into 2 groups. One group received pelvic floor muscle exercise and lifestyle advice in addition to biofeedback twice a week for 4 weeks, while the other received a lifestyle advice sheet and pelvic floor muscle exercise without biofeedback. A valid Persian version of P-QOL questionnaire was applied to assess the patients̕ quality of life at baseline, 4 weeks and 12 weeks follow up. Pressure biofeedback and Physical examination were also performed in order to determine pelvic floor muscle strength and staging of the prolapse, respectively. Collected data were analyzed by mixed ANOVA test using SPSS 22. Biofeedback improved the quality of life in seven of nine P-QOL domains. However, it had no significant impact either on pelvic floor muscle strength or on the stage of the prolapse. Biofeedback could be considered as a non-invasive treatment leading to quality of life promotion in women with stages I and II POP. Copyright © 2017 Elsevier B.V. All rights reserved.

Subdiaphragmatic stage I and II Hodgkin's disease - long-term follow-up and prognostic factors

International Nuclear Information System (INIS)

Liao Zhongxing; Ha, Chul S.; Fuller, Lillian M.; Hagemeister, Fredrick B.; Cabanillas, Fernando; Tucker, Susan L.; Hess, Mark A.; Cox, James D.

1997-01-01

Purpose: To report long term follow-up results and analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic stage I and II Hodgkin's disease. Methods and Materials: From September 1962 to April 1995, 109 patients presented to the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin's disease. The medical records of these patients were retrospectively reviewed. Twenty-two patients who received no treatment at M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male:female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominence in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Thirty three (37%) patients underwent laparotomy, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen. Twenty two (25%) patients had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease which was defined as disease with largest dimension ≥ 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Sixty (69%) patients were treated with radiotherapy alone, 23 (26.4%) with chemotherapy and radiation, and 4 (4.6%) with chemotherapy alone. Results: The 10 and 20 year actuarial overall survival rates for all the patients were 74.6% and 55.3%, and the corresponding disease free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin and hemoglobin level were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and stage were

Cluster II quartet take the stage together

Science.gov (United States)

1999-11-01

This is the only occasion on which all four of ESA's Cluster II spacecraft will be on display together in Europe. Four Spacecraft, One Mission The unique event takes place near the end of the lengthy assembly and test programme, during which each individual spacecraft is being assembled in sequence, one after the other. Two have already completed their assembly and systems testing and are about to be stored in special containers at IABG prior to shipment to the Baikonur launch site in Kazakhstan next spring. In the case of the other two, flight models 5 and 8, installation of the science payloads has finished, but their exhaustive series of environmental tests at IABG have yet to begin. Following delivery to the launch site next April, the satellites will be launched in pairs in June and July 2000. Two Soyuz rockets, each with a newly designed Fregat upper stage, are being provided by the Russian-French Starsem company. This will be the first time ESA satellites have been launched from the former Soviet Union. Cluster II is a replacement for the original Cluster mission, which was lost during the maiden launch of Ariane 5 in June 1996. ESA, given the mission's importance in its overall strategy in the area of the Sun-Earth connection, decided to rebuild this unique project. ESA member states supported that proposal. On 3 April 1997, the Agency's Science Programme Committee agreed. Cluster II was born. European Teamwork Scientific institutions and industrial enterprises in almost all the 14 ESA member states and the United States are taking part in the Cluster II project. Construction of the eight Cluster / Cluster II spacecraft has been a major undertaking for European industry. Built into each 1200 kg satellite are six propellant tanks, two pressure tanks, eight thrusters, 80 metres of pipework, about 5 km of wiring, 380 connectors and more than 14 000 electrical contacts. All the spacecraft were assembled in the giant clean room at the Friedrichshafen plant of

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer

DEFF Research Database (Denmark)

Lund, C M; Nielsen, D; Dehlendorff, Christian

2016-01-01

BACKGROUND: Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. PATIENTS...... AND METHODS: A retrospective single-centre study of 529 patients with stages II-III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after......-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3-5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality...

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 8 AND 9 CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wilson, Michael L.

2001-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 8 and 9 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

CT volumetric measurement of colorectal cancer helps predict tumor staging and prognosis.

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Jin Young Park

Full Text Available To evaluate feasibility of CT colonography (CTC volumetry of colorectal cancer (CRC and its correlation with disease stage and patients' survival.CTC volumetry was performed for 126 patients who underwent preoperative CTC. Reproducibility of tumor volume (Tvol between two readers was assessed. One-way ANOVA and ROC analysis evaluated correlation between Tvol and pTNM staging. ROC analysis compared diagnostic performance to predict pTNM staging between Tvol and radiologist. Kaplan-Meier test compared overall survival.Reproducibility among readers was excellent (interclass correlation = 0.9829. Mean Tvol showed an incremental trend with T stage and Tvol of pT4b stage was significantly larger than other stages (P0.05. Smaller tumor burden (≤12.85cm3, ≤T3, N0, M0 stages, and curative surgery were significantly associated with patients' longer survival (P<0.05.CT volumetry has a limited value to predict N stage; however, it may outperform the radiologist's performance when predicting pT4b and M1b stage and can be a useful prognostic marker.

The Outcome of Postoperative Radiation Therapy for Patients with Stage II Pancreatic Cancer (T3 or N1 Disease)

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Kim, Sang Won; Chun, Misun; Kim, Myung Wook; Kim, Wook Hwan; Kang, Seok Yun; Kang, Seung Hee; Oh, Young Taek; Lee, Sunyoung; Yang, Juno [Ajou University School of Medicine, Suwon (Korea, Republic of)

2007-12-15

Purpose: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. Materials and Methods: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. Results: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1- and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2- and 3-year overall survival rates were 31.6% and 15.8%, respectively. Conclusion: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer.

The Outcome of Postoperative Radiation Therapy for Patients with Stage II Pancreatic Cancer (T3 or N1 Disease)

International Nuclear Information System (INIS)

Kim, Sang Won; Chun, Misun; Kim, Myung Wook; Kim, Wook Hwan; Kang, Seok Yun; Kang, Seung Hee; Oh, Young Taek; Lee, Sunyoung; Yang, Juno

2007-01-01

Purpose: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. Materials and Methods: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. Results: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1- and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2- and 3-year overall survival rates were 31.6% and 15.8%, respectively. Conclusion: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer

The drama of the continuous increase in end-stage renal failure in patients with type II diabetes mellitus.

Science.gov (United States)

Rychlík, I; Miltenberger-Miltenyi, G; Ritz, E

1998-01-01

Type II diabetes mellitus has become the leading cause of end-stage renal failure in many countries of Western Europe. In all European countries, even in those with a relatively low prevalence of diabetic nephropathy, the number of patients with type II diabetes mellitus admitted for renal replacement therapy has recently increased continuously. Survival and medical rehabilitation of patients with type II diabetes on renal replacement therapy is significantly worse than in non-diabetic patients. It is obvious that in order to stem the tide, intense efforts are necessary (i) to inform the medical community about the renal risk of type II diabetes and the striking effectiveness of preventive measures, (ii) to provide better care for diabetic patients, and (iii) to reduce the high prevalence of diabetes in the population by modification of the Western life style.

Colorectal cancer: intrinsic characteristics modulate cancer energy expenditure and the risk of cachexia.

Science.gov (United States)

Ravasco, Paula; Monteiro-Grillo, Isabel; Camilo, Maria

2007-08-01

To conduct a prospective longitudinal study in colorectal cancer (CRC) patients: 1) to evaluate resting energy expenditure (REE), weight/dietary intake changes, and response to treatment, taking into consideration cancer stage and histology; 2) to determine their potential interrelations; and 3) to quantify the relative contributions to REE of cancer/nutrition/treatment. 101 CRC patients proposed for neoadjuvant radiotherapy (RT) were evaluated before and after RT: REE (indirect calorimetry measurements), percentage of weight loss, usual diet (diet history), current diet (24 hour recall), and treatment response. REE was higher in Stages III/IV versus I/II, at the RT onset (p < 0.002) and end (p = 0.02), and in moderately/poorly/undifferentiated cancers vs well differentiated (onset, p < 0.001) and (RT end, p = 0.01); weight/intake reductions were also greater in Stages III/IV versus I/II (p < 0.01) and in moderately/poorly/undifferentiated cancers versus well differentiated (p < 0.02). According to patients' response to treatment, REE was increased in Stage III/IV (p < 0.005) and Grade 2/3 histology (p < 0.003). In nonresponders, REE increased 7.2 +/- 1.3 kcal/kg/day and decreased 2.8 +/- 0.4 kcal/kg/day in responders. REE changes were not-significantly influenced by weight/intake. Relative contributions to baseline REE were determined in 25 percent by stage, in 25 percent by histology, in 3 percent by intake and in 4 percent by weight loss. At the end of RT, higher REE was attributed in 26 percent to stage, in 27 percent to histology, in 30 percent to nontreatment response, in 9 percent to intake, and in 8 percent to weight loss. In this CRC patient population, higher metabolic rates were mainly determined by the tumor burden and aggressiveness in association with response to treatment clearly disclaiming the effect of weight loss and/or dietary intake reductions.

Finite element analysis and experimental verification of Polymer reinforced CRC improved for close-in detonation

DEFF Research Database (Denmark)

Riisgaard, Benjamin; Georgakis, Christos; Stang, Henrik

2007-01-01

Compact Reinforced Composite, CRC, is a high-strength cement-based composite that holds an enormous flexural and energy-absorbing capacity due to the close-spaced high strength steel reinforcement and a high-strength cement-based fiber DSP matrix. The material has been used in various constructions...

A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

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Panzone Sergio

2010-11-01

Full Text Available Abstract Background In the last years a trend towards proximalization of colorectal carcinomas (CRC has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP to establish the presence of proximalization and to assess the potential predictors. Methods We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006. Results Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001 to 30.0% (2002-2006. Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58. The proximal ADP proportion increased from 19.2% (1997-2001 to 26.0% (2002-2006 (OR: 1.43; 95% CI: 1.17-1.89. The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17. Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16. The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46. Adjusting for these factors, the difference between the two periods was no longer significant. Conclusions CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.

Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients?

Science.gov (United States)

Stojkovic Lalosevic, Milica; Stankovic, Sanja; Stojkovic, Mirjana; Markovic, Velimir; Dimitrijevic, Ivan; Lalosevic, Jovan; Petrovic, Jelena; Brankovic, Marija; Pavlovic Markovic, Aleksandra; Krivokapic, Zoran

2017-01-01

This study was designed to investigate the efficiency of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate cancer antigen (CA19-9) levels for diagnosing synchronous liver metastases and lymph node in colorectal carcinoma (CRC) patients. A total of 300 patients with histologically diagnosed CRC were included in this study between May 2014 and March 2015. The data were obtained prospectively from patient's medical records: medical history, demographics, tumor location, differentiation (grade), depth of the tumor (T), lymph node metastases (N), distant metastases (M), lymphatics, venous and perineural invasion, and disease stage. Tumor markers were measured with an electrochemiluminescent assay and the reference value was 5ng/ml for CEA and for Ca19-9, 37u/ml. There was A high statistically significant difference in the levels of serum CEA and CA19-9 between different disease stages of CRC (PCEA (stage I 3.76±8.73; II 5.68±17.27, III 7.56±14.81, and IV 70.90±253.23) and CA 19-9 levels (stage I 9.65±11.03, II 9.83±11.09; III 19.58±36.91, and IV 228.9±985.38, respectively). The mean CEA and CA19-9 serum levels were significantly higher in patients with regional lymph nodes involvement (CEA 37.21±177.85 vs 4.79±9.90, CA19-9 119.51±687.71 VS 12.24±17.69, respectively, PCEA 86.56±277.65 vs. 5.98±12.98, and CA19-9 273.27±1073.46 vs. 4.98±3142, respectively, with PCEA and CA 19-9, 3.5 ng/mL and 7.5 U/mL, respectively. While, a cut-off value for the presence of synchronous liver metastases of these two markers was 3.5ng/mL AND 5.5 U/mL. Our study showed that tumor makers, CEA and CA19-9, can be used as diagnostic factors regarding the severity of CRC specifically to suggest metastatic disease in CRC.

Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

DEFF Research Database (Denmark)

Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

2015-01-01

factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases. Methods: A total of 126 patients were included. Analyses were performed...

Comparative Analysis between preoperative Radiotherapy and postoperative Radiotherapy in Clinical Stage I and II Endometrial Carcinoma

International Nuclear Information System (INIS)

Keum, Ki Chang; Lee, Chang Geol; Chung, Eun Ji; Lee, Sang Wook; Kim, Woo Cheol; Chang, Sei Kyung; Oh, Young Taek; Suh, Chang Ok; Kim, Gwi Eon

1995-01-01

Purpose : To obtain the optical treatment method in patients with endometrial carcinoma(clinical stage FIGO I, II) by comparative analysis between preoperative radiotherapy(pre-op R) and postoperative radiotherapy(post-op RT). Materials and Methods : A retrospective review of 62 endometrial carcinoma patients referred to the Yonsei Cancer Center for radiotherapy between 1985 and 1991 was undertaken. Of 62 patients, 19 patients(Stage I; 12 patients, Stage II; 7 patients) received pre-op RT before TAH(Total Abdominal Hysterectomy) and BSO(Bilateral Salphingoophorectomy) (Group 1) and 43 patients( Stage 1; 32 patients, Stage 2; 11 patients) received post-op RT after TAH and BSO (Group 2). Pre-op irradiation was given 4-6 weeks prior to surgery and post-op RT was administered on 4-5 weeks following surgery. All patients exept 1 patient(Group2; ICR alone) received external irradiation. Seventy percent(13/19) of pre-op RT group and 54 percent(23/42) of post-op RT group received external pelvic irradiation and intracavitary radiation therapy(ICR). External radiation dose was 39.6-55Gy(median 45Gy) in 5-6 week through opposed AP/PA fields or 4-field box technique treating daily, five days per week, 180cGy per fraction. ICR doses were prescribed to point A(20-39.6 Gy, median 39Gy) in Group 1 and 0.5cm depth from vaginal surface (18-30 Gy, median 21Gy) in Group2. Results : The overall 5 year survival rate was 95%. No survival difference between pre-op and post-op RT group.(89.3% vs 97.7%, p>0.1) There was no survival difference by stage, grade and histology between two groups. The survival rate was not affected by presence of residual tumor of surgical specimen after pre-op RT in Group 1(p>0.1), but affected by presence of lymph node metastasis in post-op RT group(p<0.5). The complication rate of pre-op RT group was higher than post-op RT.(16% vs 5%) Conclusion : Post-op radiotherapy offers the advantages of accurate surgical-pathological staging and low complication rate

Carcinoma microsatellite instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for stage II rectal cancer.

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Yang, Liu; Sun, Yan; Huang, Xin-En; Yu, Dong-Sheng; Zhou, Jian-Nong; Zhou, Xin; Li, Dong-Zheng; Guan, Xin

2015-01-01

Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low- frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (pchemotherapy (pchemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; pchemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite- instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite

Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population.

Directory of Open Access Journals (Sweden)

Rupal Sinha

Full Text Available Colorectal cancer (CRC development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12 and MGMT methylation (p-value <0.049. Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044 and methylated RASSF1A (p-values 0.034, 0.044, FHIT (p-values 0.001, 0.047 and MGMT (p-values 0.018, 0.044 genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025. Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

Are stage IV vestibular schwannomas preoperatively different from other stages?

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Tringali, Stéphane; Dubreuil, Christian; Zaouche, Sandra; Ferber-Viart, Chantal

2008-01-01

The aim of this study was to focus on the clinical and paraclinical symptoms of patients suffering from Stage IV vestibular schwannomas (VSs). In this prospective study, we included 734 patients who have VS and candidates for operation. Patients were classified as having Stage I, II, III, or IV tumors according to Tos criteria as evaluated by magnetic resonance imaging. PREOPERATIVE CLINICAL EVALUATION: We recorded the occurrence of complaints (%) and duration (yr) of hearing loss, tinnitus, and balance disorder. Preoperative paraclinical evaluation included pure-tone (PTA) and speech audiometry, auditory brainstem response (ABR) patterns, and vestibular deficit at videonystamography (VNG). Continuous variables were compared between Stage IV and other stages using analysis of variance. Qualitative variables expressed as a percentage of presence were compared between Stage IV and other stages using percentage comparison. Quantitative Parameters. Patients with Stage IV VS were significantly younger as compared with patients with other stages. Stage IV hearing loss was greater compared with other stages at 250 and 500 Hz but smaller at 2,000 and 8,000 Hz. We found no difference in the loss of PTA between Stage IV and the other stages. Speech discriminancy score was smaller in Stage IV. The durations of hearing loss, tinnitus, and balance disorders were similar whatever the tumor stage. Auditory brainstem response patterns showed no difference in Wave III latency between Stage IV VS and other stages, whereas Wave V latency and V-I interval were higher in Stage IV. Both ABR threshold and VNG caloric deficit were higher in Stage IV VS compared with other stages. Qualitative Parameters. The percentage of patients with Stage IV was lower than that with Stages II and III. The percentage of men and women was similar in all stages. The occurrence of hearing loss was similar in all stages, whereas that of tinnitus was lower in Stage IV compared with Stages I and II. In

Treatment outcome, body image, and sexual functioning after orchiectomy and radiotherapy for Stage I-II testicular seminoma

International Nuclear Information System (INIS)

Incrocci, Luca; Hop, Wim C.J.; Wijnmaalen, Arendjan; Slob, A. Koos

2002-01-01

Purpose: Orchiectomy followed by infradiaphragmatic irradiation is the standard treatment for Stage I-II testicular seminoma in The Netherlands. Because body image and sexual functioning can be affected by treatment, a retrospective study was carried out to assess treatment outcome, body image, and changes in sexuality after orchiectomy and radiotherapy. Methods and Materials: The medical charts of 166 patients with Stage I-II testicular seminoma were reviewed. A questionnaire on body image and current sexual functioning regarding the frequency and quality of erections, sexual activity, significance of sex, and changes in sexuality was sent to 157 patients (at a mean of 51 months after treatment). Results: Seventy-eight percent (n=123, mean age 42 years) completed the questionnaire. During irradiation, almost half of patients experienced nausea and 19% nausea and vomiting. Only 3 patients had disease relapse. After treatment, about 20% reported less interest and pleasure in sex and less sexual activity. Interest in sex, erectile difficulties, and satisfaction with sexual life did not differ from age-matched healthy controls. At the time of the survey, 17% of patients had erectile difficulties, a figure that was significantly higher than before treatment, but which correlated also with age. Twenty percent expressed concerns about fertility, and 52% found their body had changed after treatment. Cancer treatment had negatively influenced sexual life in 32% of the patients. Conclusions: Orchiectomy with radiotherapy is an effective and well-tolerated treatment for Stage I-II testicular seminoma. Treatment-induced changes in body image and concerns about fertility were detected, but the sexual problems encountered did not seem to differ from those of healthy controls, although baseline data are lacking

ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

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Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Mendiola, Marta; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B.; Machado, Isidro; Ramos, David; Gironella, Meritxell; Espinosa-Salinas, Isabel; Ramos, Ricardo; Martín-Hernández, Roberto; Risueño, Alberto; De Las Rivas, Javier; Reglero, Guillermo; Yaya, Ricardo; Fernández-Martos, Carlos; Aparicio, Jorge; Maurel, Joan; Feliu, Jaime; de Molina, Ana Ramírez

2015-01-01

Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group. PMID:25749516

Status of the Olympus experiment at CRC

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Rogers, David V.

1992-01-01

The status of the Olympus Propagation Experiment of the Communications Research Centre in Ottawa, Canada, is briefly summarized. Path attenuation measurements at multiple frequencies correlated with concurrent dual polarized radar data provide a unique method to investigate propagation effects. An experiment of this type is being implemented by the Communications Research Centre (CRC) on the grounds of the National Research Council of Canada in Ottawa. Beacon receivers monitor signals from the Olympus satellite at 12.5, 19.77, and 29.66 GHz at a path elevation angle of 14.2 deg. Sky noise radiometers operating near the same frequencies and pointed along the same path provide additional propagation information. A colocated dual-polarized 9.6-GHz radar probes the precipitation state on the path, permitting identification of precipitation regimes that cause the observed impairments. The Olympus experiment configuration is displayed pictorially. Information on path propagation phenomena can be deduced by correlating the radar, beacon, and sky noise data. Melting layer effects and propagation losses for higher time percentages are prime interests. Data collected by Diversitel Communications during equipment verification tests are presented.

Social integration and survival after diagnosis of colorectal cancer.

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Sarma, Elizabeth A; Kawachi, Ichiro; Poole, Elizabeth M; Tworoger, Shelley S; Giovannucci, Edward L; Fuchs, Charles S; Bao, Ying

2018-02-15

Although larger social networks have been associated with lower all-cause mortality, few studies have examined whether social integration predicts survival outcomes among patients with colorectal cancer (CRC). The authors examined the association between social ties and survival after CRC diagnosis in a prospective cohort study. Participants included 896 women in the Nurses' Health Study who were diagnosed with stage I, II, or III CRC between 1992 and 2012. Stage was assigned using the American Joint Committee on Cancer criteria. Social integration was assessed every 4 years since 1992 using the Berkman-Syme Social Network Index, which included marital status, social network size, contact frequency, religious participation, and other social group participation. During follow-up, there were 380 total deaths, 167 of which were due to CRC. In multivariable analyses, women who were socially integrated before diagnosis had a subsequent reduced risk of all-cause mortality (hazard ratio [HR], 0.65; 95% confidence interval [95% CI], 0.46-0.92) and CRC mortality (HR, 0.63; 95% CI, 0.38-1.06) compared with women who were socially isolated. In particular, women with more intimate ties (family and friends) had lower all-cause mortality (HR, 0.61; 95% CI, 0.42-0.88) and CRC mortality (HR, 0.59; 95% CI, 0.34-1.03) compared with those with few intimate ties. Participation in religious or community activities was not found to be related to outcomes. The analysis of postdiagnosis social integration yielded similar results. Socially integrated women were found to have better survival after a diagnosis of CRC, possibly due to beneficial caregiving from their family and friends. Interventions aimed at strengthening social network structures to ensure access to care may be valuable programmatic tools in the management of patients with CRC. Cancer 2018;124:833-40. © 2017 American Cancer Society. © 2017 American Cancer Society.

Combined chemo-radiation therapy to adult patients with B-cell lymphoma in stage I and II

International Nuclear Information System (INIS)

Shimoyama, Masanori

1988-01-01

155 adult patients with B-lymphoma in stage I and II who were treated in National Cancer Center Hospital between 1975 and 1986 were analyzed for treatment outcome. 5-year survival rates were about 66 % in these patients and almost equal in the patients treated with radiation alone, doxorubicin-containing combination chemotherapy alone, or combined chemoradiation therapy. However, when analysis was limited to patients in stage I, patients treated with chemotherapy alone seemed to have better survival rate than those treated with radiation alone. In the patients who were in stage III or more and had bulky mass more than 10 cm in diameter, small residual tumor was sometimes detected by restaging procedure after achieving apparent remission by multi-drug chemotherapy. In these patients, additional radiation therapy was quite usefull to eradicate residual tumor cell to cure. (author)

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

International Nuclear Information System (INIS)

Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

2010-01-01

Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade

Quality control of the NPL-CRC secondary standard system used for activimeters calibration at IPEN, Sao Paulo, Brazil

International Nuclear Information System (INIS)

Martins, Elaine W.; Potiens, Maria da P.A.

2009-01-01

The objective of this study was to establish a quality control program to be applied at the NPL-CRC activimeter secondary standard system, used as reference to comparison in tests made with the work tertiary standard activimeter, Capintec basic CRC R -15BT, both belonging to the Calibration Laboratory of IPEN. The repeatability, reproducibility and the precision tests were performed using a sealed check source of 133 Ba, from Amersham. It was made 70 series of 10 measurements to each activimeter, totaling 1400 measurements. Considering the variation limit of 5% to precision and reproducibility tests in the nuclear medicine services, recommended by the Brazilian standard CNEN-NN-3.05, the results observed in the behavior of the IPEN activimeter were satisfactory. (author)

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wright, Kenneth D.

1997-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

Mantle irradiation alone for pathologic stage I and II Hodgkin's disease: long-term follow-up and patterns of failure

International Nuclear Information System (INIS)

Liao Zhongxing; Ha, Chul S.; Vlachaki, Maria T.; Hagemeister, Frederick; Cabanillas, Fernando; Hess, Mark; Tucker, Susan; Cox, James D.

2001-01-01

Purpose: We performed a retrospective study to determine the long-term outcome, patterns of failure, and prognostic factors for patients with pathologic Stage I or II Hodgkin's disease (HD) who were treated with mantle irradiation alone. Methods and Materials: The medical records of 145 patients with pathologic Stage I or II supradiaphragmatic Hodgkin's disease treated with mantle irradiation alone between June 1967 and June 1991 were reviewed. Patterns of failure, overall survival (OS) rate, and progression-free survival (PFS) rate were determined. Univariate and multivariate analyses were performed to identify adverse prognostic factors for OS and PFS. The number of adverse prognostic factors per patient was counted, and a prognostic score was assigned to each patient. The log-rank test was used to compare the OS or PFS rates among patients with prognostic scores 0, 1, and 2. Results: The median patient age was 27 years (range 10-66), with almost even male to female distribution. Every patient had splenectomy and negative laparotomy (LAP). Fifty-one patients had Stage I disease (IA-49, IB-2) and 94 Stage II (IIA-89, IIB-5). The histologic subtypes were nodular sclerosing in 110, mixed cellularity in 28, lymphocyte predominance in 5, lymphocyte depleted in 1, and unclassified in 1. Twelve patients with Stage II disease had ≥ 3 sites of nodal involvement. Fifty-four patients had a prognostic score of 0, 70 of 1, and 21 of 2. The median follow-up time for the 109 surviving patients was 146 months (range 25-381). The 10- and 20-year actuarial OS rates for the whole group were 87.6% and 65.3%, respectively. The corresponding actuarial PFS rates were 75.3% and 74.2%, respectively. Thirty-six patients (9 Stage I, 27 Stage II) had relapses in a total of 41 sites. Failures by histology were 29 patients with nodular sclerosing, 6 with mixed cellularity, and 1 with lymphocyte predominance. Failures by sites were: trans-diaphragmatic, 22 (para-aortic nodes, 15; as the only

The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses.

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Kim, Soo Young; Choi, Yoon Young; An, Ji Yeong; Shin, Hyun Beak; Jo, Ara; Choi, Hyeji; Seo, Sang Hyuk; Bang, Hui-Jae; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

2015-08-15

We previously reported that the prognosis of microsatellite instability high (MSI-H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS) gastric cancer. The reason for this seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI-H gastric cancer. Data from 1,276 patients with Stage II and III gastric cancer who underwent gastrectomy with curative intent between January 2005 and June 2010 were reviewed. The prognosis of MSI-H tumors in comparison with MSI-L/MSS tumors was analyzed, according to the administration of chemotherapy and other clinicopathologic features. A total of 361 (28.3%) patients did not receive chemotherapy (MSI-H = 47 and MSI-L/MSS = 314), whereas 915 (71.7%) patients did receive chemotherapy (MSI-H = 58 and MSI-L/MSS = 857). The hazard ratio of MSI-H versus MSI-L/MSS was 0.49 (95% confidence interval: 0.26-0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence interval: 0.78-1.71, p = 0.466) when chemotherapy was received. In subgroup analyses, the prognosis of MSI-H was better in Stage III, women, with lymph node metastasis, and undifferentiated histology subgroups when chemotherapy was not received. However, in patients treated with chemotherapy, prognosis was worse for MSI-H tumors in Stage III, undifferentiated histology, and diffuse type subgroups of gastric cancer. In conclusion, MSI-H tumors were associated with a good prognosis in Stage II and III gastric cancer when patients were treated by surgery alone, and the benefits of MSI-H status were attenuated by chemotherapy. © 2015 UICC.

Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.

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Hung, Hsin-Yuan; Yeh, Chien-Yuh; Changchien, Chung-Rong; Chen, Jinn-Shiun; Fan, Chung-Wei; Tang, Reiping; Hsieh, Pao-Shiu; Tasi, Wen-Sy; You, Yau-Tong; You, Jeng-Fu; Wang, Jeng-Yi; Chiang, Jy-Ming

2011-07-01

In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors. We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer. A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P transverse colon tumors (P = 0.21). Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience.

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Ali, Amany M; Sayd, Heba A; Hamza, Hesham M; Salem, Mohamed A

2011-03-29

Abdominal Non-Hodgkin lymphomas (NHL) are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI), Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15). Thirty patients (86%) presented with abdominal pain, 23 patients (66%) presented with abdominal mass and distention, 13 patients (34%) presented with weight loss, and intestinal obstruction occurred in six patients (17%). The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively). Burkitt's lymphoma was the most common histological type in 29 patients (83%). Ten (28.5%) stage II (group A) and 25 (71.5%) stage III (group B). Complete resections were performed in 10 (28.5%), debulking in 6 (17%) and imaging guided biopsy in 19 (54%). A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months). The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL.

Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience

Directory of Open Access Journals (Sweden)

Mohamed A. Salem

2011-03-01

Full Text Available Abdominal Non-Hodgkin lymphomas (NHL are the most common extra nodal presentation of pediatric NHL. Our aim is to assess the role of surgery as a risk factor and to evaluate the impact of risk-adjusted systemic chemotherapy on survival of patients with stages II and III disease. This study included 35 pediatric patients with abdominal NHL treated over five years at South Egypt Cancer Institute (SECI, Assiut University, between January 2005 and January 2010. The data of every patient included: Age, sex, and presentation, staging work up to determine extent of the disease and the type of resection performed, histopathological examination, details of chemotherapy, disease free survival and overall survival. The study included 25 boys and 10 girls with a median age of six years (range: 2.5:15. Thirty patients (86% presented with abdominal pain, 23 patients (66% presented with abdominal mass and distention, 13 patients (34% presented with weight loss, and intestinal obstruction occurred in six patients (17%. The ileo-cecal region and abdominal lymph nodes were the commonest sites (48.5%, 21% respectively. Burkitt's lymphoma was the most common histological type in 29 patients (83%. Ten (28.5% stage II (group A and 25 (71.5% stage III (group B. Complete resections were performed in 10 (28.5%, debulking in 6 (17% and imaging guided biopsy in 19 (54%. A11 patients received systemic chemotherapy. The median follow up duration was 63 months (range 51-78 months. The parameters that significantly affect the overall survival were stage at presentation complete resection for localized disease. In conclusion, the extent of disease at presentation is the most important prognostic factor in pediatric abdominal NHL. Surgery is restricted to defined situations such as; abdominal emergencies, diagnostic biopsy and total tumor extirpation in localized disease. Chemotherapy is the cornerstone in the management of pediatric abdominal NHL.

Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

LENUS (Irish Health Repository)

Kennedy, Richard D

2011-12-10

Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.

EpiGeNet: A Graph Database of Interdependencies Between Genetic and Epigenetic Events in Colorectal Cancer.

Science.gov (United States)

Balaur, Irina; Saqi, Mansoor; Barat, Ana; Lysenko, Artem; Mazein, Alexander; Rawlings, Christopher J; Ruskin, Heather J; Auffray, Charles

2017-10-01

The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

Science.gov (United States)

Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

2015-01-01

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

Long term results of mantle irradiation(MRT) alone in 261 patients with clinical stage I-II supradiaphragmatic Hodgkin's disease

International Nuclear Information System (INIS)

Wirth, A.; Byram, D.; Chao, M.; Corry, J.; Davis, S.; Kiffer, J.; Laidlaw, C.; Quong, G.; Ryan, G.; Liew, K.

1997-01-01

Purpose: We report our results using MRT for clinical stage I-II HD and assess the value of published prognostic criteria in our study population. Pts and Methods: Between 1969 and 1994, 261 pts were treated with MRT alone for clinical stage I-II supradiaphragmatic HD. Pt characteristics: median age-30; M-54%/F-46%; stage IA-52%, IB-2%, IIA-37%, IIB-8%; histology LP-21%, NS-51%, MC-23%, other 5%; median ESR 18. CT abdomen and LAG were performed in 61% and 60% respectively. No pt had prior staging laparotomy. No pt received infradiaphragmatic RT. Central axis dose was 32 Gy-36 Gy. Univariate analysis was performed for prognostic factors for progression-free (PFS) and overall survival(OS). Outcome was assessed in favourable subsets as defined by: EORTC (v. favourable: CSIA, LP or NS histology, age < 40, female, no bulk, ESR < 50; favourable: CSI-II, age < 50, < 4 sites, no bulky mediastinal mass, ESR < 50 with no B symptoms or ESR < 30 with B symptoms); Princess Margaret Hospital (PMH) (IA-IIA, LP or NS histology, ESR < 40, age < 50, no large mediastinal mass, no E lesion). Results: 261 pts completed RT, with 5% requiring treatment interruption for toxicity. Significant factors (P<0.05) for PFS were stage, performance status, histology, B symptoms, number of sites, ESR and bulk. Significant factors (P<0.05) for OS were age, performance status, histology and B symptoms. (The results of a multivariate analysis will be presented.) Results in our study population using published prognostic criteria (in %): Thirty-six percent progressed following RT: 8% in-field; 24% out of field only (including 10% in the paraaortic/splenic region alone); 4% marginal; Fifty-seven percent of relapsed pts remain progression free after subsequent salvage treatment. Two cases of acute leukaemia, 8 cases of non-Hodgkin's lymphoma and 14 (non-skin) carcinomas occurred, of which 11 were in-field. Seventy pts have died. The cause was: HD 41%; other malignancy 20%; cardiovascular 17%; other 15

Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

Science.gov (United States)

Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

2013-10-25

Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC. Copyright © 2013 Elsevier Inc. All rights reserved.

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 4 AND 5 OF CRYSTAL RIVER UNIT 3

Energy Technology Data Exchange (ETDEWEB)

Kenneth D. Wright

1997-07-30

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 4 and 5 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies.

Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer.

Science.gov (United States)

Overman, M J; Adam, L; Raghav, K; Wang, J; Kee, B; Fogelman, D; Eng, C; Vilar, E; Shroff, R; Dasari, A; Wolff, R; Morris, J; Karunasena, E; Pisanic, R; Azad, N; Kopetz, S

2018-01-01

Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to 220 mg/m2 owing to toxicity. A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type. Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel

Staging of Lung Cancer

Science.gov (United States)

... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

Mechanisms of topoisomerase I (TOP1) gene copy number increase in a stage III colorectal cancer patient cohort

DEFF Research Database (Denmark)

Smith, David Hersi; Christensen, Ib Jarle; Jensen, Niels Frank

2013-01-01

Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III C...

Contribution of screening and survival differences to racial disparities in colorectal cancer rates

Science.gov (United States)

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

Prognostic implication of serum hepatocyte growth factor in stage II/III breast cancer patients who received neoadjuvant chemotherapy.

Science.gov (United States)

Kim, Hyori; Youk, Jeonghwan; Yang, Yaewon; Kim, Tae-Yong; Min, Ahrum; Ham, Hye-Seon; Cho, Seongcheol; Lee, Kyung-Hun; Keam, Bhumsuk; Han, Sae-Won; Oh, Do-Youn; Ryu, Han Suk; Han, Wonshik; Park, In Ae; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

2016-03-01

In stage II/III breast cancer, neoadjuvant chemotherapy (NAC) is a standard treatment. Although several biomarkers are used to predict prognosis in breast cancer, there is no reliable predictive biomarker for NAC success. Recently, the hepatocyte growth factor (HGF) and cMet signaling pathway demonstrated to be involved in breast cancer tumor progression, and its potential as a biomarker is under active investigation. In this study, we assessed the potential of serum HGF as a prognostic biomarker for NAC efficacy. Venous blood samples were drawn from patients diagnosed with stage II/III breast cancer and treated with NAC in Seoul National University Hospital from August 2004 to November 2009. Serum HGF level was determined using an ELISA system. We reviewed the medical records of the patients and investigated the association of HGF level with patients' clinicopathologic characteristics. A total of 121 female patients (median age = 45 years old) were included. Median level of HGF was 934 pg/ml (lower quartile: 772, upper quartile: 1145 pg/ml). Patients with higher HGF level than median value were significantly more likely to have clinically detectable regional node metastasis (p = 0.017, Fisher's exact test). Patients with complete and partial response according to the American Joint Committee on Cancer 7th Edition criteria tended to have higher HGF level (p = 0.105 by t test). Patients with an HGF level higher than the upper quartile value had longer relapse-free survival than the other patients (106 vs. 85 months, p = 0.008). High serum HGF levels in breast cancer patients are associated with clinically detectable regional node metastasis and, paradoxically, with longer relapse-free survival in stage II/III breast cancer.

Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting.

Science.gov (United States)

Obrocea, F L; Sajin, Maria; Marinescu, Elena Cristina; Stoica, D

2011-01-01

Colorectal cancer (CRC) is a neoplastic disease with a continuously growing incidence in Romania and throughout the world. Although the surgery remains the first line treatment for most of the cases, newly discovered targeted molecular therapies - effective for some patients, but with various side effects and significant financial burden for the national health systems - requires not only stratification of patients in prognostic groups but also evaluation of some non-anatomic factors with major impact on the prognosis and therapeutic strategy. The AJCC/UICC TNM staging system, in his 7th revision, effective for cases diagnosed on or after January 1, 2010, responds to these needs. On the other hand, the role of the pathologist is increasing in terms of workload and amount of information to be included in the pathology report in order to deliver a personalized diagnosis. There are concerns worldwide regarding relevance, validity and completeness of pathologic reporting of CRC in the absence of a uniform reporting format. Therefore, suggestions for a standardized pathology report of CRC are made, based on TNM 7 and recent, up-to-date conclusive published data.

Analysis of RET promoter CpG island methylation using methylation-specific PCR (MSP), pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM): impact on stage II colon cancer patient outcome.

Science.gov (United States)

Draht, Muriel X G; Smits, Kim M; Jooste, Valérie; Tournier, Benjamin; Vervoort, Martijn; Ramaekers, Chantal; Chapusot, Caroline; Weijenberg, Matty P; van Engeland, Manon; Melotte, Veerle

2016-01-01

Already since the 1990s, promoter CpG island methylation markers have been considered promising diagnostic, prognostic, and predictive cancer biomarkers. However, so far, only a limited number of DNA methylation markers have been introduced into clinical practice. One reason why the vast majority of methylation markers do not translate into clinical applications is lack of independent validation of methylation markers, often caused by differences in methylation analysis techniques. We recently described RET promoter CpG island methylation as a potential prognostic marker in stage II colorectal cancer (CRC) patients of two independent series. In the current study, we analyzed the RET promoter CpG island methylation of 241 stage II colon cancer patients by direct methylation-specific PCR (MSP), nested-MSP, pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM). All primers were designed as close as possible to the same genomic region. In order to investigate the effect of different DNA methylation assays on patient outcome, we assessed the clinical sensitivity and specificity as well as the association of RET methylation with overall survival for three and five years of follow-up. Using direct-MSP and nested-MSP, 12.0 % (25/209) and 29.6 % (71/240) of the patients showed RET promoter CpG island methylation. Methylation frequencies detected by pyrosequencing were related to the threshold for positivity that defined RET methylation. Methylation frequencies obtained by pyrosequencing (threshold for positivity at 20 %) and MS-HRM were 13.3 % (32/240) and 13.8 % (33/239), respectively. The pyrosequencing threshold for positivity of 20 % showed the best correlation with MS-HRM and direct-MSP results. Nested-MSP detected RET promoter CpG island methylation in deceased patients with a higher sensitivity (33.1 %) compared to direct-MSP (10.7 %), pyrosequencing (14.4 %), and MS-HRM (15.4 %). While RET methylation frequencies detected by nested

Mapping the extent of disease by multislice computed tomography, magnetic resonance imaging and sentinel node evaluation in stage I and II cervical carcinoma

Directory of Open Access Journals (Sweden)

Rajaram S

2010-01-01

Full Text Available Aims: (1 To map the extent of disease in women with stage I and II carcinoma cervix by multislice spiral computed tomography (CT, magnetic resonance imaging (MRI and sentinel nodes. (2 To assess accuracy of each modality individually and in conjunction with FIGO clinical staging. Design and Setting: Prospective, single-blind study. Departments of Obstetrics and Gynaecology, Radiodiagnosis, and Pathology, UCMS and GTBH and Division of Radiological Imaging and Bioinformatics, INMAS, Delhi. Material and Method: The study was conducted on 25 women with cervical cancer FIGO stage I and II. Each woman underwent clinical staging, multislice spiral CT and MRI which was compared to the gold-standard histopathology/cytology. The overall accuracy of each modality and improvement of clinical staging by CT/MRI were noted. Sentinel nodes were evaluated by intracervical Patent Blue V dye injection. Statistical Analysis: Sensitivity, specificity, positive and negative predictive values were calculated by 2Χ2 contingency tables. Results: The accuracy of staging by FIGO, CT and MRI was 68%, 52% and 80%, respectively. MRI and CT improved the overall accuracy of FIGO staging to 96% and 80%, respectively. Sentinel nodes were identified in 89% of patients with 91% accuracy. Conclusion: MRI emerges as the most valuable stand-alone modality improving accuracy of FIGO staging to 96%. Sentinel lymph-node evaluation appears promising in evaluating spread beyond cervix.

Organ preservation in stage II and III head and neck cancer utilizing alternate week concomitant chemoradiotherapy

International Nuclear Information System (INIS)

Mansur, David B.; Vokes, Everett; Mittal, Bharat B.; Stenson, Kerstin; Kies, M.; Pelzer, H.; Nautiyal, Jaishanker; Kozloff, Mark; Weichselbaum, Ralph R.; Haraf, Daniel J.

1996-01-01

Purpose: A prospective phase II trial was conducted to determine the efficacy and rate of organ preservation of alternate week concomitant chemoradiotherapy in stage II and III head and neck cancer. Methods: Forty-nine patients (10 stage II and 39 stage III) with squamous cell carcinoma of the head and neck region have been entered into a prospective phase II trial. Pretreatment evaluation included history and physical examination, computed tomography of the neck, bone scan, chest x-ray, panendoscopy and biopsy confirmation of malignancy. Therapy is given in 2 week cycles consisting of 5 days of concomitant chemoradiotherapy followed by a nine day break during which no treatment is given. Each cycle of treatment consists of 1.0 gm hydroxyurea P.O. every 12 hours for 6 days (11 doses per cycle) and 800mg/m 2 /d continuous infusion 5-fluorouracil along with concomitant radiation therapy (RT) administered in 1.8-2.0 Gy daily fractions for five days. This alternate week (week on/week off) schedule is continued for a total of 7 cycles resulting in an overall treatment time of 13 weeks and a total RT dose of 70 Gy. Extent of initial surgery included biopsy only (59.2%), minimal laser debulking (12.2%), and resection with or without neck dissection (28.6%). Results: The majority of patients are male (71.4%), with a median age of 61.3 years. Primary sites included oral cavity (16.3%), oropharynx (12.2%), larynx (57.1%), hypopharynx (8.1%), and nasopharynx (4.1%). T stage included T3 (32 patients, 65.3%), T2 (16 patients, 32.7%), and T1 (1 patient). N stage included N1 (17 patients, 34.7%), and N0 (32 patients, 65.3%). With a median follow-up of 27 months, the overall response rate is 100% (91.7 complete response, and 8.3% partial response). The 5 year actuarial local control, disease free survival, and overall survival is 90.1%, 88.3%, and 65.0%, respectively. One patient has failed with distant disease alone. Four patients had isolated local failures and (3(4)) were

Prognostic significance of the PC10 index for patients with stage II and III oesophageal cancer treated with radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Sugahara, Shinji; Irie, Toshiyuki; Nozawa, Kumiko; Nakajima, Kotaro [Hitachi General Hospital, Ibaraki (Japan). Dept. of Radiology; Ohara, Kiyoshi; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Dept. of Radiology; Takahashi, Atsushi [Hitachi General Hospital, Ibaraki (Japan). Dept. of Pathology; Watanabe, Teruo [Tsukuba Univ., Ibaraki (Japan). Dept. of Pathology; Tanaka, Naomi [Tsukuba Univ., Ibaraki (Japan). Dept. of Internal Medicine

1999-07-01

The monoclonal antibody PC10 is used for immunohistochemical staining of the proliferating cell nuclear antigen (PCNA). The percentage of PC10-positive cancer cells is defined as the PC10 index. We evaluated the relationship between the PC10 index in pretreatment endoscopic biopsies and the prognoses of 47 patients with Stage II-III oesophageal squamous cell carcinoma treated with radiotherapy. The patients with a PC10 index >40% had significantly poorer prognoses than the other patients (p=0.0007). Proportional hazards model analysis indicated that only the PC10 index was a prognostic factor (p=0.0009). The patient group of complete responders showed significantly lower PC10 indices compared to patients with a partial response or no change (p=0.049). The PC10 index can be a good predictive indicator of the prognosis in patients with Stage II-III oesophageal cancer treated with radiotherapy. (orig.)

CRC DEPLETION CALCULATIONS FOR THE NON-RODDED ASSEMBLIES IN BATCHES 1, 2, AND 3 OF CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wright, Kenneth D.

1997-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain non-rodded fuel assemblies from batches 1, 2, and 3 of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support development of the disposal criticality methodology. A non-rodded assembly is one which never contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) during its irradiation history. The objective of this analysis is to provide SAS2H generated isotopic compositions for each fuel assembly's depleted fuel and depleted burnable poison materials. These SAS2H generated isotopic compositions are acceptable for use in CRC benchmark reactivity calculations containing the various fuel assemblies

The CRC 20 Years: An Overview of Some of the Major Achievements and Remaining Challenges

Science.gov (United States)

Doek, Jaap E.

2009-01-01

On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the…

Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.

Science.gov (United States)

Ghanbari, Reza; Rezasoltani, Sama; Hashemi, Javad; Mohamadkhani, Ashraf; Tahmasebifar, Arash; Arefian, Ehsan; Mobarra, Naser; Asadi, Jahanbakhsh; Nazemalhosseini Mojarad, Ehsan; Yazdani, Yaghoub; Knuutila, Sakari; Malekzadeh, Reza

2017-02-01

Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC. In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups. Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer.

Science.gov (United States)

Shigeyasu, Kunitoshi; Okugawa, Yoshinaga; Toden, Shusuke; Miyoshi, Jinsei; Toiyama, Yuji; Nagasaka, Takeshi; Takahashi, Naoki; Kusunoki, Masato; Takayama, Tetsuji; Yamada, Yasuhide; Fujiwara, Toshiyoshi; Chen, Leilei; Goel, Ajay

2018-06-21

Adenosine-to-inosine (A-to-I) RNA editing, a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family, is a recently discovered epigenetic modification dysregulated in human cancers. However, the clinical significance and the functional role of RNA editing in colorectal cancer (CRC) remain unclear. We have systematically and comprehensively investigated the significance of the expression status of ADAR1 and of the RNA editing levels of antizyme inhibitor 1 (AZIN1), one of the most frequently edited genes in cancers, in 392 colorectal tissues from multiple independent CRC patient cohorts. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues when compared with corresponding normal mucosa. High levels of AZIN1 RNA editing emerged as a prognostic factor for overall survival and disease-free survival and were an independent risk factor for lymph node and distant metastasis. Furthermore, elevated AZIN1 editing identified high-risk stage II CRC patients. Mechanistically, edited AZIN1 enhances stemness and appears to drive the metastatic processes. We have demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC. Moreover, AZIN1 RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.

Science.gov (United States)

Zohar, Sarah; Chevret, Sylvie

2003-02-01

We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.

Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

Science.gov (United States)

Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

2018-01-01

The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

A systematic review and meta-analysis of the safety, feasibility and effect of exercise in women with stage II+ breast cancer.

Science.gov (United States)

Singh, Ben; Spence, Rosalind R; Steele, Megan L; Sandler, Carolina X; Peake, Jonathan M; Hayes, Sandra C

2018-05-03

To systematically evaluate the safety, feasibility and effect of exercise among women with stage II+ breast cancer. CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published prior to March 1, 2017. Randomised, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included. Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored. There were no differences in adverse events between exercise and usual care (risk difference: feasibility outcomes were similar, irrespective of exercise mode, supervision, duration, or timing. Effects of exercise for quality of life, fitness, fatigue, strength, anxiety, depression, body mass index and waist circumference compared with usual care were significant (standardised mean difference range: 0.17-0.77, pfeasibility and effects of exercise for those with stage II+ breast cancer, suggesting that national and international exercise guidelines appear generalizable to women with local, regional and distant breast cancer. Copyright © 2018. Published by Elsevier Inc.

Social Development Training Project. Stage I and Stage II. [The Granville Project].

Science.gov (United States)

Riches, Vivienne C., Ed.

The book presents a training program developed at the Granville Work Preparation Centre in Australia, to teach mildly retarded adolescents basic social skills and competencies. The program is divided into two stages, with a total of 17 different skill areas. Stage 1 covers self-awareness, social/interpersonal skills, relaxation and behavioral self…

Lateral column lengthening for acquired adult flatfoot deformity caused by posterior tibial tendon dysfunction stage II: a retrospective comparison of calcaneus osteotomy with calcaneocuboid distraction arthrodesis.

Science.gov (United States)

Haeseker, Guus A; Mureau, Marc A; Faber, Frank W M

2010-01-01

In this study, clinical and radiological results after lateral column lengthening by calcaneocuboid distraction arthrodesis and calcaneus osteotomy were compared. Thirty-three patients (35 feet) treated with lateral column lengthening by distraction arthrodesis (14 patients, 16 feet; group I) or by calcaneus osteotomy (19 patients, 19 feet; group II) for adult-acquired flatfoot deformity caused by stage II posterior tibial tendon dysfunction were compared retrospectively. Mean follow-up was 42.4 months (range, 6-78 months) for group I and 15.8 months (range, 6-32 months) for group II (P lengthening by means of calcaneus osteotomy rather than distraction arthrodesis of the calcaneocuboid joint, for correction of stage II posterior tibial tendon dysfunction. Copyright 2010 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Could semiquantitative FDG analysis add information to the prognosis in patients with stage II/III breast cancer undergoing neoadjuvant treatment?

Energy Technology Data Exchange (ETDEWEB)

Evangelista, Laura; Cervino, Anna Rita [Veneto Institute of Oncology IOV - IRCCS, Radiotherapy and Nuclear Medicine Unit, Padua (Italy); Ghiotto, Cristina; Guarneri, Valentina; Conte, Pierfranco [Veneto Institute of Oncology IOV - IRCCS, Medical Oncology 2 Unit, Padua (Italy); Saibene, Tania; Michieletto, Silvia; Fernando, Bozza [Veneto Institute of Oncology IOV - IRCCS, Breast Unit, Padua (Italy); Orvieto, Enrico [University Hospital of Padua, Department of Pathology, Padua (Italy)

2015-10-15

We investigated whether maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and whole-body (WB) SUVmax, WB MTV and WB TLG measured by {sup 18}F-FDG PET/CT could improve prognostic stratification in patients with stage II/III breast cancer (BC). We prospectively enrolled 99 consecutive women (median age 50 years, range 27 - 77 years) with pathologically proven stage II/III BC who underwent pretreatment FDG PET/CT. WB SUVmax, WB MTV and WB TLG were measured in all malignant lesions. Survival was analysed using the Kaplan-Meier method. Cox proportional hazards models were constructed to test for relationships among WB SUVmax, WB MTV, WB TLG, and overall survival (OS) and disease-free survival (DFS), after adjustment for age, and histopathological and immunohistochemical features (oestrogen/progesterone and HER2 expression, proliferation index and grade). The median values of WB SUVmax, WB MTV and WB TLG were 16.2 (range 1.5 - 33.1), 14 cm{sup 3} (range 0.03 - 708.6 cm{sup 3}) and 62.5 (0.06 - 3869.4), respectively. All WB semiquantitative values were higher in patients with higher TNM stage, although not significantly (all p > 0.05). The median follow-up for surviving patients was 30 months, with a range of 13 - 45 months. Both PFS and OS of patients with low WB SUVmax, WB MTV and WB TLG were longer than that of patients with high WB values for progression, although not statistically significant. However, stratifying the patients in accordance with the stage of disease, both PFS and OS were significantly lower in patients with high WB TLG and stage III than in patients with stage II (p < 0.05). In multivariate analyses, WB MTV and WB TLG were independent prognostic factors for PFS (hazard ratio 1.004, 95 % confidence interval 1.002 - 1.006, p < 0.001, and hazard ratio 1.001, 95 % confidence interval 1.000 - 1.001, p = 0.011, respectively). The addition of WB TLG to clinical data may provide a more detailed

Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy

International Nuclear Information System (INIS)

Cameron, Silke; Hünerbein, Diana; Mansuroglu, Tümen; Armbrust, Thomas; Scharf, Jens-Gerd; Schwörer, Harald; Füzesi, László; Ramadori, Giuliano

2009-01-01

The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease. 20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy. Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed. This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC

Colorectal cancers detected through screening are associated with lower stages and improved survival

DEFF Research Database (Denmark)

Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

2014-01-01

in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin.

Science.gov (United States)

Overman, Michael J; Morris, Van; Moinova, Helen; Manyam, Ganiraju; Ensor, Joe; Lee, Michael S; Eng, Cathy; Kee, Bryan; Fogelman, David; Shroff, Rachna T; LaFramboise, Thomas; Mazard, Thibault; Feng, Tian; Hamilton, Stanley; Broom, Bradley; Lutterbaugh, James; Issa, Jean-Pierre; Markowitz, Sanford D; Kopetz, Scott

2016-10-11

Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high. This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks. Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (PCIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker.

Gene Expression Profile in the Early Stage of Angiotensin II-induced Cardiac Remodeling: a Time Series Microarray Study in a Mouse Model

Directory of Open Access Journals (Sweden)

Meng-Qiu Dang

2015-01-01

Full Text Available Background/Aims: Angiotensin II (Ang II plays a critical role in the cardiac remodeling contributing to heart failure. However, the gene expression profiles induced by Ang II in the early stage of cardiac remodeling remain unknown. Methods: Wild-type male mice (C57BL/6 background, 10-weeek-old were infused with Ang II (1500 ng/kg/min for 7 days. Blood pressure was measured. Cardiac function and remodeling were examined by echocardiography, H&E and Masson staining. The time series microarrays were then conducted to detected gene expression profiles. Results: Microarray results identified that 1,489 genes were differentially expressed in the hearts at day 1, 3 and 7 of Ang II injection. These genes were further classified into 26 profiles by hierarchical cluster analysis. Of them, 4 profiles were significant (No. 19, 8, 21 and 22 and contained 904 genes. Gene Ontology showed that these genes mainly participate in metabolic process, oxidation-reduction process, extracellular matrix organization, apoptotic process, immune response, and others. Significant pathways included focal adhesion, ECM-receptor interaction, cytokine-cytokine receptor interaction, MAPK and insulin signaling pathways, which were known to play important roles in Ang II-induced cardiac remodeling. Moreover, gene co-expression networks analysis suggested that serine/cysteine peptidase inhibitor, member 1 (Serpine1, also known as PAI-1 localized in the core of the network. Conclusions: Our results indicate that many genes are mainly involved in metabolism, inflammation, cardiac fibrosis and hypertrophy. Serpine1 may play a central role in the development of Ang II-induced cardiac remodeling at the early stage.

Self Reported Awareness of Child Maltreatment among School Professionals in Saudi Arabia: Impact of CRC Ratification

Science.gov (United States)

AlBuhairan, Fadia S.; Inam, Sarah S.; AlEissa, Majid A.; Noor, Ismail K.; Almuneef, Maha A.

2011-01-01

Objectives: The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying…

Blood transfusion and survival after surgery for Stage I and II breast cancer

International Nuclear Information System (INIS)

Herman, K.; Kolodziejski, L.

1993-01-01

The records of 690 Stage I and II breast cancer patients (31% of them with transfusions), who underwent mastectomy with axillary dissection were examined whether perioperative blood transfusion might be detrimental to survival. The overall 5- and 1-year survival rates for 477 patients who had not received transfusions were 75% and 63% respectively, compared with 66% and 49% for those who had transfusions (p=0.005). There was no significant difference between the group in any other of the most important prognostic factors. An analysis of the subpopulation of patients with favorable prognostic factors yielded similar results. A multivariate analysis indicated that blood transfusion was one of the four variables significantly related to survival. (author)

An evaluation on time status of functional orthopedic treatment in class II skeletal patients with cervical vertebrae maturation stage (CVMS index

Directory of Open Access Journals (Sweden)

Dalili Z.

2004-08-01

Full Text Available Statement of Problem: Considerable response to functional orthopedic appliances treatment in class II skeletal patients occurs during pubertal growth spurt. Therefore, it seems necessary to investigate indices indicating mandibular growth pattern. It has been proved that analyzing cervical vertebral maturation stage is a more valid index than that of hand wrist. Purpose: The aim of this study was to evaluate the time status of functional orthopedic treatment in class II skeletal patients using CVMS index. Materials and Methods: In this descriptive-inferential study, lateral cephalometric radiographs of 153 class II skeletal patients with mandibular deficiency, before treatment, were studied by an oral and maxillofacial radiologist using the index of cervical vertebral maturation stage (CVMS and were categorized in three phases: CVMS I (desirable phase of treatment, CVMS II (ideal phase, and CVMS III (undesirable phase of treatment. Results: Statistical analysis ranked the prevalence of treatment phases as: 41.8% in desirable phase (CVMS I, 28.1% in ideal phase (CVMA II and 30% in undesirable phase (CVMS III. No significant differences were found between the three phases using Chi-square analysis. Time status of functional orthopedic treatment was also evaluated based on age and sex. The results showed significant differences between two sexes (P=0.032. Conclusion: The present study suggests the analysis of CVMS index, along with clinical criteria, in the determination of an ideal time for functional orthopedic treatment to prevent patients’ exhaustion during treatment Period.

Role of specific DNA mutations in the peripheral blood of colorectal cancer patients for the assessment of tumor stage and residual disease following tumor resection

Science.gov (United States)

Norcic, Gregor; Jelenc, Franc; Cerkovnik, Petra; Stegel, Vida; Novakovic, Srdjan

2016-01-01

In the present study, the detection of tumor-specific KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations in the peripheral blood of colorectal cancer (CRC) patients at all stages and adenomas was used for the estimation of disease stage prior to surgery and for residual disease following surgery. A total of 65 CRC patients were enrolled. The primary tumor tested positive for the specific mutations (KRAS mutations in codons 12, 13, 61, 117 or 146 and BRAF mutations in codon 600) in 35 patients. In all these patients, the specimen of normal bowel resected with the tumor was also tested for the presence of the same mutations in order to exclude the germ-line mutations. Only patients who tested positive for the specific mutation in the primary tumor were included in further analysis for the presence of tumor-specific mutation in the peripheral blood. No statistically significant differences were found between the detection rates of tumor mutations in the blood and different tumor stages (P=0.491). However, statistically significant differences in the proportions of patients with detected tumor-specific DNA mutations in the peripheral blood were found when comparing the groups of patients with R0 and R2 resections (P=0.038). Tumor-specific DNA mutations in the peripheral blood were more frequently detected in the patients with an incomplete surgical clearance of the tumor due to macroscopic residual disease (R2 resections). Therefore, the study concludes that the follow-up of somatic KRAS- and BRAF-mutated DNA in the peripheral blood of CRC patients may be useful in assessing the surgical clearance of the disease. PMID:27900004

CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

Energy Technology Data Exchange (ETDEWEB)

Kenneth D. Wright

1997-09-03

The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies.

CRC DEPLETION CALCULATIONS FOR THE RODDED ASSEMBLIES IN BATCHES 1, 2, 3, AND 1X OF CRYSTAL RIVER UNIT 3

International Nuclear Information System (INIS)

Wright, Kenneth D.

1997-01-01

The purpose of this design analysis is to document the SAS2H depletion calculations of certain rodded fuel assemblies from batches 1, 2, 3, and 1X of the Crystal River Unit 3 pressurized water reactor (PWR) that are required for Commercial Reactor Critical (CRC) evaluations to support the development of the disposal criticality methodology. A rodded assembly is one that contains a control rod assembly (CRA) or an axial power shaping rod assembly (APSRA) for some period of time during its irradiation history. The objective of this analysis is to provide SAS2H calculated isotopic compositions of depleted fuel and depleted burnable poison for each fuel assembly to be used in subsequent CRC reactivity calculations containing the fuel assemblies

Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

Energy Technology Data Exchange (ETDEWEB)

Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

2014-07-15

Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

International Nuclear Information System (INIS)

Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.

2014-01-01

Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification

Expression of PAT and NPT II proteins during the developmental stages of a genetically modified pepper developed in Korea.

Science.gov (United States)

Kim, Hyo Jin; Lee, Si Myung; Kim, Jae Kwang; Ryu, Tae Hun; Suh, Seok Cheol; Cho, Hyun Suk

2010-10-27

Estimation of the protein levels introduced in a biotechnology-derived product is conducted as part of an overall safety assessment. An enzyme-linked immunosorbent assay (ELISA) was used to analyze phosphinothricin acetyltransferase (PAT) and neomycin phosphotransferase II (NPT II) protein expression in a genetically modified (GM) pepper plant developed in Korea. PAT and NPT II expression levels, based on both dry weight and fresh weight, were variable among different plant generations and plant sections from isolated genetically modified organism (GMO) fields at four developmental stages. PAT expression was highest in leaves at anthesis (11.44 μg/gdw and 2.17 μg/gfw) and lowest in roots (0.12 μg/gdw and 0.01 μg/gfw). NPT II expression was also highest in leaves at anthesis (17.31 μg/gdw and 3.41 μg/gfw) and lowest in red pepper (0.65 μg/gdw and 0.12 μg/gfw). In pollen, PAT expression was 0.59-0.62 μg/gdw, while NPT II was not detected. Both PAT and NPT II showed a general pattern of decreased expression with progression of the growing season. As expected, PAT and NPT II protein expression was not detectable in control pepper plants.

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery

Science.gov (United States)

Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De-Sen

2016-01-01

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment. PMID:27008710

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

Science.gov (United States)

Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

2016-04-19

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.