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Sample records for repair proficient colorectal

  1. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Science.gov (United States)

    2010-07-01

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a... killing or growth inhibition of repair deficient bacteria in a set of repair proficient and deficient...

  2. Mismatch repair proficiency is not required for radioenhancement by gemcitabine

    International Nuclear Information System (INIS)

    Bree, Chris van; Rodermond, Hans M.; Vos, Judith de; Haveman, Jaap; Franken, Nicolaas

    2005-01-01

    Purpose: Mismatch repair (MMR) proficiency has been reported to either increase or decrease radioenhancement by 24-h incubations with gemcitabine. This study aimed to establish the importance of MMR for radioenhancement by gemcitabine after short-exposure, high-dose treatment and long-exposure, low-dose treatment. Methods and Materials: Survival of MMR-deficient HCT116 and MMR-proficient HCT116 + 3 cells was analyzed by clonogenic assays. Mild, equitoxic gemcitabine treatments (4 h, 0.1 μM vs. 24 h, 6 nM) were combined with γ-irradiation to determine the radioenhancement with or without recovery. Gemcitabine metabolism and cell-cycle effects were evaluated by high-performance liquid chromatography analysis and bivariate flow cytometry. Results: Radioenhancement after 4 h of 0.1 μM of gemcitabine was similar in both cell lines, but the radioenhancement after 24 h of 6 nM of gemcitabine was reduced in MMR-proficient cells. No significant differences between both cell lines were observed in the gemcitabine metabolism or cell-cycle effects after these treatments. Gemcitabine radioenhancement after recovery was also lower in MMR-proficient cells than in MMR-deficient cells. Conclusion: Mismatch repair proficiency decreases radioenhancement by long incubations of gemcitabine but does not affect radioenhancement by short exposures to a clinically relevant gemcitabine dose. Our data suggest that MMR contributes to the recovery from gemcitabine treatment

  3. Recombinant methods for screening human DNA excision repair proficiency

    International Nuclear Information System (INIS)

    Athas, W.F.

    1988-01-01

    A method for measuring DNA excision repair in response to ultraviolet radiation (UV)-induced DNA damage has been developed, validated, and field-tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiologic studies seeking to investigate associations between excision repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the belief that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum (XP) primarily is a result of the reduced capacity of patients cells to repair UV-induced DNA damage. For assay, UV-irradiated non-replicating recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (CAT) indicator gene is introduced into lymphocytes using DEAE-dextran short-term transfection conditions. Exposure to UV induces transcriptionally-inactivating DNA photoproducts in the plasmid DNA which inactivate CAT gene expression. Excision repair of the damaged CAT gene is monitored indirectly as a function of reactivated CAT enzyme activity following a 40 hour repair/expression incubation period

  4. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne

    2014-01-01

    BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

  5. Mismatch repair deficiency in colorectal cancer patients in a low ...

    African Journals Online (AJOL)

    2013-02-06

    Feb 6, 2013 ... This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. Objectives. The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the. Northern Cape.

  6. Differential effect of ionizing radiation on transcription in repair-deficient and repair-proficient mice

    International Nuclear Information System (INIS)

    Munson, G.P.; Woloschak, G.E.

    1990-01-01

    Experiments were designed to examine in vivo changes in total transcription and in the expression of the c-fos gene following whole-body exposure of mice to JANUS fission-spectrum neutrons. Radiation repair-deficient (wst/wst) and -proficient (wst/., C57BL/6 x C3H F1) mice were exposed to JANUS fission-spectrum neutrons calibrated to deliver a gut dose of 50 cGy. Animals were sacrificed less than 10 or at 60 min postirradiation, and gut tissues were removed for study. Our results revealed that, in repair-proficient mice, an immediate depression (relative to untreated control) in total transcription was evident that continued through 1 h postirradiation. Conversely, radiation-sensitive wst/wst mice displayed doubled transcription levels postirradiation. Expression of c-fos was consistently depressed following radiation exposure in control and wst/wst mice. However, the depression of c-fos mRNA was delayed in wst/wst mice relative to controls. These results demonstrate abnormal regulation of transcription and of c-fos mRNA accumulation in repair-deficient wasted mice following exposure to ionizing radiation. In addition, this work documents rapid total transcriptional depression in normal mice following radiation exposure

  7. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

    Science.gov (United States)

    Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

    2017-08-01

    Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

  8. Surgical management of colorectal injuries: colostomy or primary repair?

    Science.gov (United States)

    Papadopoulos, V N; Michalopoulos, A; Apostolidis, S; Paramythiotis, D; Ioannidis, A; Mekras, A; Panidis, S; Stavrou, G; Basdanis, G

    2011-10-01

    Several factors have been considered important for the decision between diversion and primary repair in the surgical management of colorectal injuries. The aim of this study is to clarify whether patients with colorectal injuries need diversion or not. From 2008 to 2010, ten patients with colorectal injuries were surgically treated by primary repair or by a staged repair. The patients were five men and five women, with median age 40 years (20-55). Two men and two women had rectal injuries, while 6 patients had colon injuries. The mechanism of trauma in two patients was firearm injuries, in two patients was a stab injury, in four patients was a motor vehicle accident, in one woman was iatrogenic injury during vaginal delivery, and one case was the transanal foreign body insertion. Primary repair was possible in six patients, while diversion was necessary in four patients. Primary repair should be attempted in the initial surgical management of all penetrating colon and intraperitoneal rectal injuries. Diversion of colonic injuries should only be considered if the colon tissue itself is inappropriate for repair due to severe edema or ischemia. The role of diversion in the management of unrepaired extraperitoneal rectal injuries and in cases with anal sphincter injuries is mandatory.

  9. Sporadic colorectal polyps and mismatch repair proteins

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    Mahsa Molaei

    2011-01-01

    Full Text Available Background: Colorectal cancers often arise from benign polyps. Adenomatous polyps and serrated polyps progress step by step to adenocarcinoma and change into malignant cancers. Genetic and epigenetic changes have correlation with specific stages of polyp-adenocarcinoma progression and colorectal cancer histopathological changes. Aims: In this study we used immunohistochemistry (IHC staining in sporadic colorectal polyps to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins, to track genetic/epigenetic roles of this issue in our patients. Materials and Methods: In this cross-sectional study we assessed all patients who were admitted with sporadic colorectal polyps and underwent polypectomy in endoscopy department during 2004-2008. Result: IHC results were abnormal in 6.8% cases for MLH1, in 4.5% cases for MSH2, in 3% for MSH6, and in 4.8% for PMS2. In all cases with abnormal PMS2, MLH1 was also reported as abnormal. Same results were reported for abnormal MSH2, which is accompanied with abnormal MSH6 in all cases (P values < 0.001. There is no significant difference between IHC staining results, gender, dysplasia grade, adenomatous type, and invasion. On the other hand, there was significant difference between IHC staining results, polyp location, and mean age of patients. The same significant difference was between adenomatous polyps and serrated adenoma polyps by MLH1 and PMS2 (P values < 0.05. Conclusion: According to our findings, maybe MMR dysfunction is the cause of sporadic colorectal polyps in younger age and its increasing risk of dysplasia progression and malignancy progression is only in serrated adenoma. Sporadic polyps in left colon had a higher risk to progress to malignancies, and abnormal IHC staining for MLH1 and PMS2 in serrated polyps is much more than in other adenomatous polyps.

  10. Mismatch repair status and synchronous metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...

  11. Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry

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    Jiyoon Jung

    2017-03-01

    Full Text Available Background Colorectal cancer (CRC is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2 has emerged as a useful technique to complement polymerase chain reaction (PCR analyses. Methods In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results Based on IHC, 7/61 primary tumors (11.4% showed deficient MMR systems, while 13/61 secondary tumors (21.3% showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61. These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

  12. Lethality in repair-proficient Escherichia coli after 365nm ultraviolet light irradiation is dependent on fluence rate

    International Nuclear Information System (INIS)

    Peak, J.G.; Peak, M.J.

    1982-01-01

    Reciprocity (total applied fluence produces the same response, regardless of the fluence rate) for the lethal effects caused by 365 and 254 nm ultraviolet light (UV) was studied for repair-proficient and -deficient Escherichia coli strains. In the repair-proficient strain, E. coli WP2 uvr A + recA + , reciprocity after 365 nm UV was only observed at fluence rates of about 750 Wm -2 and above. Below this rate, the cells became increasingly sensitive as the fluence rate was decreased. Similar lack of reciprocity was obtained whether the cells were exposed at 0 or 25 0 C. The double repair-defective mutant, E. coli WP100 uvr A recA, showed complete reciprocity after 365 nm UV over the same range of fluence rates measured for the repair-proficient strain. For 254 nm UV, complete reciprocity occurred in both strains over a range of fluence rates differing by an order of magnitude. (author)

  13. DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis.

    Science.gov (United States)

    Fahrer, Jörg; Frisch, Janina; Nagel, Georg; Kraus, Alexander; Dörsam, Bastian; Thomas, Adam D; Reißig, Sonja; Waisman, Ari; Kaina, Bernd

    2015-10-01

    Epidemiological studies indicate that N-nitroso compounds (NOC) are causally linked to colorectal cancer (CRC). NOC induce DNA alkylations, including O (6)-methylguanine (O (6)-MeG) and N-methylated purines, which are repaired by O (6)-MeG-DNA methyltransferase (MGMT) and N-alkyladenine-DNA glycosylase (AAG)-initiated base excision repair, respectively. In view of recent evidence of nonlinear mutagenicity for NOC-like compounds, the question arises as to the existence of threshold doses in CRC formation. Here, we set out to determine the impact of DNA repair on the dose-response of alkylation-induced CRC. DNA repair proficient (WT) and deficient (Mgmt (-/-), Aag (-/-) and Mgmt (-/-)/Aag (-/-)) mice were treated with azoxymethane (AOM) and dextran sodium sulfate to trigger CRC. Tumors were quantified by non-invasive mini-endoscopy. A non-linear increase in CRC formation was observed in WT and Aag (-/-) mice. In contrast, a linear dose-dependent increase in tumor frequency was found in Mgmt (-/-) and Mgmt (-/-)/Aag (-/-) mice. The data were corroborated by hockey stick modeling, yielding similar carcinogenic thresholds for WT and Aag (-/-) and no threshold for MGMT lacking mice. O (6)-MeG levels and depletion of MGMT correlated well with the observed dose-response in CRC formation. AOM induced dose-dependently DNA double-strand breaks in colon crypts including Lgr5-positive colon stem cells, which coincided with ATR-Chk1-p53 signaling. Intriguingly, Mgmt (-/-) mice displayed significantly enhanced levels of γ-H2AX, suggesting the usefulness of γ-H2AX as an early genotoxicity marker in the colorectum. This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. The Relationship between Neighborhood Immigrant Composition, Limited English Proficiency, and Late-Stage Colorectal Cancer Diagnosis in California

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    Cynthia M. Mojica

    2015-01-01

    Full Text Available Despite the availability of effective early detection technologies, more than half (61% of colorectal cancers in the United States and 55% in California are identified at an advanced stage. Data on colorectal cancer patients (N=35,030 diagnosed from 2005 to 2007 were obtained from the California Cancer Registry. Multivariate analyses found a relationship among neighborhood concentration of recent immigrants, neighborhood rates of limited English proficiency, and late-stage colorectal cancer diagnosis. Hispanics living in neighborhoods with a greater percentage of recent immigrants (compared to the lowest percentage had greater odds (OR 1.57, 95% CI 1.22, 2.02 of late-stage diagnosis whereas Hispanics living in neighborhoods with the highest percentage of limited English proficiency (compared to the lowest percentage had lower odds (OR .71, 95% CI .51, .99 of late-stage diagnosis. These relationships were not observed for other ethnic groups. Results highlight the complex relationship among race/ethnicity, neighborhood characteristics, and colorectal cancer stage at diagnosis.

  15. Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

    Science.gov (United States)

    Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

    2016-01-01

    The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

  16. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

    International Nuclear Information System (INIS)

    Sousa Neto, A. de.

    1980-01-01

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

  17. Prospective evaluation of fluorouracil chemotherapy based on the genetic makeup of colorectal cancer

    OpenAIRE

    Carethers, J M

    2006-01-01

    Evaluation of 5‐fluorouracil chemotherapy and survival, based on mismatch repair (MMR) status, indicates that patients with MMR proficient colorectal tumours benefit from 5‐fluorouracil treatment while patients with MMR deficient tumours do not

  18. Distinct Clinicopathological Patterns of Mismatch Repair Status in Colorectal Cancer Stratified by KRAS Mutations.

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    Wenbin Li

    Full Text Available In sporadic colorectal cancer (CRC, the BRAFV600E mutation is associated with deficient mismatch repair (MMR status and inversely associated with to KRAS mutations. In contrast to deficient MMR (dMMR CRC, data on the presence of KRAS oncogenic mutations in proficient MMR (pMMR CRC and their relationship with tumor progression are scarce. We therefore examined the MMR status in combination with KRAS mutations in 913 Chinese patients and correlated the findings obtained with clinical and pathological features. The MMR status was determined based on detection of MLH1, MSH2, MSH6 and PMS2 expression. KRAS mutation and dMMR status were detected in 36.9% and 7.5% of cases, respectively. Four subtypes were determined by MMR and KRAS mutation status: KRAS (+/pMMR (34.0%, KRAS (+/dMMR (2.9%, KRAS (-/pMMR (58.5% and KRAS (-/dMMR (4.6%. A higher percentage of pMMR tumors with KRAS mutation were most likely to be female (49.0%, proximal located (45.5%, a mucinous histology (38.4%, and to have increased lymph node metastasis (60.3%, compared with pMMR tumors without BRAFV600E and KRAS mutations (36.0%, 29.3%, 29.4% and 50.7%, respectively; all P < 0.01. To the contrary, compared with those with KRAS(-/dMMR tumors, patients with KRAS(+/dMMR tumors demonstrated no statistically significant differences in gender, tumor location, pT depth of invasion, lymph node metastasis, pTNM stage, and histologic grade. This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with MMR status stratified by KRAS mutation. Knowledge of MMR and KRAS mutation status may enhance molecular pathologic staging of CRC patients and metastatic progression in CRC can be estimated based on the combination of these biomarkers.

  19. An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers.

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    Ajay Goel

    2010-02-01

    Full Text Available Microsatellite instability (MSI is used to screen colorectal cancers (CRC for Lynch Syndrome, and to predict outcome and response to treatment. The current technique for measuring MSI requires DNA from normal and neoplastic tissues, and fails to identify tumors with specific DNA mismatch repair (MMR defects. We tested a panel of five quasi-monomorphic mononucleotide repeat markers amplified in a single multiplex PCR reaction (pentaplex PCR to detect MSI.We investigated a cohort of 213 CRC patients, comprised of 114 MMR-deficient and 99 MMR-proficient tumors. Immunohistochemical (IHC analysis evaluated the expression of MLH1, MSH2, PMS2 and MSH6. MSI status was defined by differences in the quasi-monomorphic variation range (QMVR from a pool of normal DNA samples, and measuring differences in allele lengths in tumor DNA.Amplification of 426 normal alleles allowed optimization of the QMVR at each marker, and eliminated the requirement for matched reference DNA to define MSI in each sample. Using > or = 2/5 unstable markers as the criteria for MSI resulted in a sensitivity of 95.6% (95% CI = 90.1-98.1% and a positive predictive value of 100% (95% CI = 96.6%-100%. Detection of MSH6-deficiency was limited using all techniques. Data analysis with a three-marker panel (BAT26, NR21 and NR27 was comparable in sensitivity (97.4% and positive predictive value (96.5% to the five marker panel. Both approaches were superior to the standard approach to measuring MSI.An optimized pentaplex (or triplex PCR offers a facile, robust, very inexpensive, highly sensitive, and specific assay for the identification of MSI in CRC.

  20. Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions

    DEFF Research Database (Denmark)

    Wilding, Jennifer L; McGowan, Simon; Liu, Ying

    2010-01-01

    , and have distinct pathologies. Regulatory sequences controlling all aspects of mRNA processing, especially including message stability, are found in the 3'UTR sequence of most genes. The relevant sequences are typically A/U-rich elements or U repeats. Microarray analysis of 14 RER+ (deficient) and 16 RER......- (proficient) colorectal cancer cell lines confirms a striking difference in expression profiles. Analysis of the incidence of mononucleotide repeat sequences in the 3'UTRs, 5'UTRs, and coding sequences of those genes most differentially expressed in RER+ versus RER- cell lines has shown that much...... of this differential expression can be explained by the occurrence of a massive enrichment of genes with 3'UTR T repeats longer than 11 base pairs in the most differentially expressed genes. This enrichment was confirmed by analysis of two published consensus sets of RER differentially expressed probesets for a large...

  1. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

    OpenAIRE

    Poulogiannis , George; Frayling , Ian; Arends , Mark

    2009-01-01

    Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

  2. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

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    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  3. Metformin enhances radiosensitivity via inhibition of DNA repair pathway in colorectal cancer

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    Jeong, Youn Kyoung; Kim, Mi Sook; Lee, Ji Young; Song, Kyung Hee; Choi, Kyul; Kim, Eun Ho; Ha, Hun Joo [Ewha Womans University, Seoul (Korea, Republic of)

    2014-04-15

    In this study, we provide a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer. Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Currently, it is one of the commonest chemoradiotherapy worked better than the radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, it is to use potential anticancer agents that act as radiosensitizers. Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. Our data shows that metformin combined with radiation enhances the efficacy of radiotherapy and down-regulates DNA repair proteins. Therefore, we provides a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer.

  4. Metformin enhances radiosensitivity via inhibition of DNA repair pathway in colorectal cancer

    International Nuclear Information System (INIS)

    Jeong, Youn Kyoung; Kim, Mi Sook; Lee, Ji Young; Song, Kyung Hee; Choi, Kyul; Kim, Eun Ho; Ha, Hun Joo

    2014-01-01

    In this study, we provide a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer. Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Currently, it is one of the commonest chemoradiotherapy worked better than the radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, it is to use potential anticancer agents that act as radiosensitizers. Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. Our data shows that metformin combined with radiation enhances the efficacy of radiotherapy and down-regulates DNA repair proteins. Therefore, we provides a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer

  5. Mismatch repair deficiency in colorectal cancer patients in a low ...

    African Journals Online (AJOL)

    Background. In a previous study we identified 206 patients with colorectal adenocarcinoma in the Northern Cape province of South Africa, diagnosed between January 2002 and February 2009. The age-standardised incidence was 4.2/100 000 per year world standard population. This is 10% of the rate reported in ...

  6. Genetic variation in the base excision repair pathway, environmental risk factors, and colorectal adenoma risk.

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    Roman Corral

    Full Text Available Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER. We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013; FEN1 interaction p = 0.013, one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024 and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08 on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation.

  7. Selecting patients with young-onset colorectal cancer for mismatch repair gene analysis

    DEFF Research Database (Denmark)

    Walker, M; O'Sullivan, B; Perakath, B

    2007-01-01

    BACKGROUND: Young patients with colorectal cancer are at increased risk of carrying a germline mutation in mismatch repair (MMR) genes. This study investigated the role of clinical criteria and immunohistochemistry for MMR proteins in selecting young patients for mutation testing. METHODS: A cohort...... of 56 consecutive patients with colorectal cancer aged less than 45 years were stratified into three groups based on clinical criteria: 'Amsterdam criteria', 'high risk' and 'young onset only'. Immunohistochemistry for four MMR proteins was carried out and the rate of compliance with clinical guidelines...

  8. Folate and Colorectal Cancer in Rodents: A Model of DNA Repair Deficiency

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    Rita Rosati

    2012-01-01

    Full Text Available Fortification of grains has resulted in a positive public health outcome vis-a-vis reduced incidence of neural tube defects. Whether folate has a correspondingly beneficial effect on other disease outcomes is less clear. A role for dietary folate in the prevention of colorectal cancer has been established through epidemiological data. Experimental data aiming to further elucidate this relationship has been somewhat equivocal. Studies report that folate depletion increases DNA damage, mutagenesis, and chromosomal instability, all suggesting inhibited DNA repair. While these data connecting folate depletion and inhibition of DNA repair are convincing, we also present data demonstrating that genetic inhibition of DNA repair is protective in the development of preneoplastic colon lesions, both when folate is depleted and when it is not. The purpose of this paper is to (1 give an overview of the data demonstrating a DNA repair defect in response to folate depletion, and (2 critically compare and contrast the experimental designs utilized in folate/colorectal cancer research and the corresponding impact on tissue folate status and critical colorectal cancer endpoints. Our analysis suggests that there is still an important need for a comprehensive evaluation of the impact of differential dietary prescriptions on blood and tissue folate status.

  9. Quantitative assessment of the dose-response of alkylating agents in DNA repair proficient and deficient ames tester strains.

    Science.gov (United States)

    Tang, Leilei; Guérard, Melanie; Zeller, Andreas

    2014-01-01

    Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.

  10. DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Pardini, Barbara; Naccarati, Alessio; Novotný, J.; Šmerhovský, Z.; Vodičková, Ludmila; Poláková, Veronika; Hánová, Monika; Slyšková, Jana; Tulupová, Elena; Kumar, R.; Bortlík, M.; Barale, R.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 638, 1-2 (2008), s. 146-153 ISSN 0027-5107 R&D Projects: GA ČR GA310/05/2626; GA MZd NR8563 Grant - others:EU(SE) 505609 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK Keywords : Colorectal cancer * Individual susceptibility * DNA repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  11. Variations in mismatch repair genes and colorectal cancer risk and clinical outcome

    Czech Academy of Sciences Publication Activity Database

    Vymetálková, Veronika; Pardini, B.; Rosa, F.; Di Gaetano, C.; Novotný, J.; Levý, M.; Buchler, T.; Slyšková, Jana; Vodičková, Ludmila; Naccarati, Alessio; Vodička, Pavel

    2014-01-01

    Roč. 29, č. 4 (2014), s. 259-265 ISSN 0267-8357 R&D Projects: GA ČR GPP304/11/P715; GA ČR GAP304/10/1286; GA MZd NT12025 Institutional support: RVO:68378041 Keywords : colorectal cancer , , * mismatch repair genes * miRNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.793, year: 2014

  12. Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients

    Czech Academy of Sciences Publication Activity Database

    Vymetálková, Veronika; Slyšková, Jana; Korenková, Vlasta; Bielik, Ludovít; Langerová, Lucie; Procházka, Pavel; Rejhová, Alexandra; Schwarzová, L.; Pardini, B.; Naccarati, Alessio; Vodička, Pavel

    2014-01-01

    Roč. 15, č. 1 (2014), s. 17 ISSN 1471-2350 R&D Projects: GA AV ČR IAA500200917; GA ČR(CZ) GPP304/11/P715 Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : colorectal cancer * mismatch repair genes * expression levels Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.083, year: 2014

  13. Ultraviolet light-resistant primary transfectants of xeroderma pigmentosum cells are also DNA repair-proficient

    International Nuclear Information System (INIS)

    Stark, M.; Naiman, T.; Canaani, D.

    1989-01-01

    In a previous work, an immortal xeroderma pigmentosum cell line belonging to complementation group C was complemented to a UV-resistant phenotype by transfection with a human cDNA clone library. We now report that the primary transformants selected for UV-resistance also acquired normal levels of DNA repair. This was assessed both by measurement of UV-induced [ 3 H]thymidine incorporation and by equilibrium sedimentation analysis of repair-DNA synthesis. Therefore, the transduced DNA element which confers normal UV-resistance also corrects the excision repair defect of the xeroderma pigmentosum group C cell line

  14. Alcohol Consumption and the Risk of Colorectal Cancer for Mismatch Repair Gene Mutation Carriers.

    Science.gov (United States)

    Dashti, S Ghazaleh; Buchanan, Daniel D; Jayasekara, Harindra; Ait Ouakrim, Driss; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M; Macrae, Finlay A; Giles, Graham G; Parry, Susan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Thibodeau, Stephen N; Lindor, Noralane M; Newcomb, Polly A; Potter, John D; Baron, John A; Hopper, John L; Jenkins, Mark A; Win, Aung Ko

    2017-03-01

    Background: People with germline mutation in one of the DNA mismatch repair (MMR) genes have increased colorectal cancer risk. For these high-risk people, study findings of the relationship between alcohol consumption and colorectal cancer risk have been inconclusive. Methods: 1,925 MMR gene mutations carriers recruited into the Colon Cancer Family Registry who had completed a questionnaire on lifestyle factors were included. Weighted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between alcohol consumption and colorectal cancer. Results: Colorectal cancer was diagnosed in 769 carriers (40%) at a mean (SD) age of 42.6 (10.3) years. Compared with abstention, ethanol consumption from any alcoholic beverage up to 14 g/day and >28 g/day was associated with increased colorectal cancer risk (HR, 1.50; 95% CI, 1.09-2.07 and 1.69; 95% CI, 1.07-2.65, respectively; P trend = 0.05), and colon cancer risk (HR, 1.78; 95% CI, 1.27-2.49 and 1.94; 95% CI, 1.19-3.18, respectively; P trend = 0.02). However, there was no clear evidence for an association with rectal cancer risk. Also, there was no evidence for associations between consumption of individual alcoholic beverage types (beer, wine, spirits) and colorectal, colon, or rectal cancer risk. Conclusions: Our data suggest that alcohol consumption, particularly more than 28 g/day of ethanol (∼2 standard drinks of alcohol in the United States), is associated with increased colorectal cancer risk for MMR gene mutation carriers. Impact: Although these data suggested that alcohol consumption in MMR carriers was associated with increased colorectal cancer risk, there was no evidence of a dose-response, and not all types of alcohol consumption were associated with increased risk. Cancer Epidemiol Biomarkers Prev; 26(3); 366-75. ©2016 AACR . ©2016 American Association for Cancer Research.

  15. A mycobacterial smc null mutant is proficient in DNA repair and long-term survival.

    Science.gov (United States)

    Güthlein, Carolin; Wanner, Roger M; Sander, Peter; Böttger, Erik C; Springer, Burkhard

    2008-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  16. A Mycobacterial smc Null Mutant Is Proficient in DNA Repair and Long-Term Survival▿

    OpenAIRE

    Güthlein, Carolin; Wanner, Roger M.; Sander, Peter; Böttger, Erik C.; Springer, Burkhard

    2007-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  17. The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.

    Science.gov (United States)

    Esteban-Jurado, Clara; Franch-Expósito, Sebastià; Muñoz, Jenifer; Ocaña, Teresa; Carballal, Sabela; López-Cerón, Maria; Cuatrecasas, Miriam; Vila-Casadesús, Maria; Lozano, Juan José; Serra, Enric; Beltran, Sergi; Brea-Fernández, Alejandro; Ruiz-Ponte, Clara; Castells, Antoni; Bujanda, Luis; Garre, Pilar; Caldés, Trinidad; Cubiella, Joaquín; Balaguer, Francesc; Castellví-Bel, Sergi

    2016-10-01

    Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC.

  18. Inhibition of topoisomerase II activity in repair-proficient CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

    International Nuclear Information System (INIS)

    Grdina, D.J.; Constantinou, A.; Shigematsu, N.

    1992-09-01

    The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation protector under in vitro conditions when it is administered 30 min prior to radiation exposure at a concentration of 4 mM to repair-proficient Chinese hamster ovary Kl cells (i.e., a dose modification factor of 1.4). In contrast, the DNA double-strand break, repair-deficient Chinese hamster ovary xrs-5 cell line is not protected under these conditions (i.e., a dose modification factor of 1.0). Topoisomerase (topo) I and II activities and protein contents were measured in both Kl and xrs-5 cell lines and were found to be similar in magnitude. Neither exposure to radiation, to WR-1065, or to both affected these variables in xrs-5 cells. WR 1065 was effective, however, in reducing topo 11 activity by a factor of 2 in the repair-proficient Kl cell line. Topo II protein content, however, was not affected by these exposure conditions. One of several mechanisms of radiation protection attributed to aminothiol compounds has been their ability to affect enzymatic reactions involved in DNA synthesis, repair, and cell cycle progression. These results demonstrate a modifying effect by 2-[(aminopropyl)amino]ethanethiol on a specific nuclear enzyme (i.e., type H topoisomerase), which is involved in DNA synthesis. These results also suggest that differences do exist between the topo 11 enzymes isolated from the parent repair-proficient Kl and the DNA double-strand break, repair-deficient xrs-5 mutant cell lines

  19. Inhibition of topoisomerase II activity in repair-proficient CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J.; Constantinou, A.; Shigematsu, N.

    1992-09-01

    The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation protector under in vitro conditions when it is administered 30 min prior to radiation exposure at a concentration of 4 mM to repair-proficient Chinese hamster ovary Kl cells (i.e., a dose modification factor of 1.4). In contrast, the DNA double-strand break, repair-deficient Chinese hamster ovary xrs-5 cell line is not protected under these conditions (i.e., a dose modification factor of 1.0). Topoisomerase (topo) I and II activities and protein contents were measured in both Kl and xrs-5 cell lines and were found to be similar in magnitude. Neither exposure to radiation, to WR-1065, or to both affected these variables in xrs-5 cells. WR 1065 was effective, however, in reducing topo 11 activity by a factor of 2 in the repair-proficient Kl cell line. Topo II protein content, however, was not affected by these exposure conditions. One of several mechanisms of radiation protection attributed to aminothiol compounds has been their ability to affect enzymatic reactions involved in DNA synthesis, repair, and cell cycle progression. These results demonstrate a modifying effect by 2-[(aminopropyl)amino]ethanethiol on a specific nuclear enzyme (i.e., type H topoisomerase), which is involved in DNA synthesis. These results also suggest that differences do exist between the topo 11 enzymes isolated from the parent repair-proficient Kl and the DNA double-strand break, repair-deficient xrs-5 mutant cell lines.

  20. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer

    International Nuclear Information System (INIS)

    Jin, Hei-Ying; Zhao, Ronghua; Liu, Xiufang; Li, Vicky Ka Ming; Ding, Yijiang; Yang, Bolin; Geng, Jianxiang; Lai, Rensheng; Ding, Shuqing; Ni, Min

    2008-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC. There has been a great deal of research on the value of these tests in other countries. However, literature about the Chinese population is scarce. Our objective is to detect and study microsatellite instability (MSI) and mismatch repair (MMR) gene germline mutation carriers among a Chinese population with colorectal cancer. In 146 prospectively recruited consecutive patients with clinically proven colorectal cancer, MSI carriers were identified by analysis of tumor tissue using multiplex fluorescence polymerase chain reaction (PCR) using the NCI recommended panel and classified into microsatellite instability-low (MSI-L), microsatellite instability-high (MSI-H) and microsatellite stable (MSS) groups. Immunohistochemical staining for MSH2, MSH6 and MLH1 on tissue microarrays (TMAs) was performed, and methylation of the MLH1 promoter was analyzed by quantitative methylation specific PCR (MSP). Germline mutation analysis of blood samples was performed for MSH2, MSH6 and MLH1 genes. Thirty-four out of the 146 colorectal cancers (CRCs, 23.2%) were MSI, including 19 MSI-H CRCs and 15 MSI-L CRCS. Negative staining for MSH2 was found in 8 CRCs, negative staining for MSH6 was found in 6 CRCs. One MSI-H CRC was negative for both MSH6 and MSH2. Seventeen CRCs stained negatively for MLH1. MLH1 promoter methylation was determined in 34 MSI CRCs. Hypermethylation of the MLH1 promoter occurred in 14 (73.7%) out of 19 MSI-H CRCs and 5 (33.3%) out of 15 MSI-L CRCs. Among the 34 MSI carriers and one MSS CRC with MLH1 negative staining, 8 had a MMR gene germline mutation, which accounted for 23.5% of all MSI colorectal cancers and 5.5% of all the colorectal cancers. Five patients harbored MSH2 germline mutations, and three patients harbored MSH6 germline mutations. None of the patients had an MLH

  1. Sporadic colorectal cancer and individual susceptibility: A review of the association studies investigating the role of DNA repair genetic polymorphisms

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Pardini, B.; Hemminki, K.; Vodička, Pavel

    2007-01-01

    Roč. 635, 2-3(2007), s.118-145 ISSN 1383-5742 R&D Projects: GA MZd NR8563; GA ČR GA310/05/2626 Institutional research plan: CEZ:AV0Z50390512 Keywords : Sporadic colorectal cancer * Individual susceptibility * DNA repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.353, year: 2007

  2. Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel.

    Science.gov (United States)

    Abu Freha, Naim; Leibovici Weissman, Yaara; Fich, Alexander; Barnes Kedar, Inbal; Halpern, Marisa; Sztarkier, Ignacio; Behar, Doron M; Arbib Sneh, Orly; Vilkin, Alex; Baris, Hagit N; Gingold, Rachel; Lejbkowicz, Flavio; Niv, Yaron; Goldberg, Yael; Levi, Zohar

    2018-01-01

    We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type /normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

  3. Impact of DNA repair on the dose-response of colorectal cancer formation induced by dietary carcinogens.

    Science.gov (United States)

    Fahrer, Jörg; Kaina, Bernd

    2017-08-01

    Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is causally linked to dietary habits, notably the intake of processed and red meat. Processed and red meat contain dietary carcinogens, including heterocyclic aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce various N-methylated DNA adducts and O 6 -methylguanine (O 6 -MeG), which are removed by base excision repair (BER) and O 6 -methylguanine-DNA methyltransferase (MGMT), respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed from DNA by nucleotide excision repair (NER). Both O 6 -MeG and HCA-induced DNA adducts are linked to the occurrence of KRAS and APC mutations in colorectal tumors of rodents and humans, thereby driving CRC initiation and progression. In this review, we focus on DNA repair pathways removing DNA lesions induced by NOC and HCA and assess their role in protecting against mutagenicity and carcinogenicity in the large intestine. We further discuss the impact of DNA repair on the dose-response relationship in colorectal carcinogenesis in view of recent studies, demonstrating the existence of 'no effect' point of departures (PoDs), i.e. thresholds for genotoxicity and carcinogenicity. The available data support the threshold concept for NOC with DNA repair being causally involved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Designing a proficiency-based, content validated virtual reality curriculum for laparoscopic colorectal surgery: A Delphi approach

    NARCIS (Netherlands)

    Palter, Vanessa N.; Graafland, Maurits; Schijven, Marlies P.; Grantcharov, Teodor P.

    2012-01-01

    Background. Although task training on virtual reality (VR) simulators has been shown to transfer to the operating room, to date no VR curricula have been described for advanced laparoscopic procedures. The purpose of this study was to develop a proficiency-based VR technical skills curriculum for

  5. Individual sensitivity to radiations and DNA repair proficiency: the comet assay contribution; Sensibilite individuelle aux radiations et reparation de l`ADN: apport du test des cometes

    Energy Technology Data Exchange (ETDEWEB)

    Alapetite, C. [Institut Curie, 75 - Paris (France)

    1998-09-01

    Some are hereditary syndromes demonstrate high cancer risk and hypersensitivity in response to exposures to agents such as ultraviolet or ionising radiation, and are characterized by a defective processing of DNA damage. They highlight the importance of the individual risk associated to exposures. The comet assay, a simple technique that detects DNA strand breaks, requires few cells and allows examination of DNA repair capacities in established cell lines, in blood samples or biopsies. The assay has been validated on cellular systems with known repair defects such as xeroderma pigmentosum defective in nucleotide excision repair, on mutant rodent cell lines defective in DNA single strand breaks rejoining (XRCC5/Ku80 and XRCC7/DNAPKcs) (neutral conditions). This assay does not allow to distinguish a defective phenotype in ataxia telangiectasia cells. It shows in homozygous mouse embryo fibroblasts Brca2-/- an impaired DNA double strand break rejoining. Simplicity, rapidity and sensitivity of the alkaline comet assay allow to examine the response of lymphocytes. It has been applied to the analysis of the role of DNA repair in the pathogenesis of collagen diseases, and the involvement of individual DNA repair proficiency in the thyroid tumorigenesis induced in some patients after therapeutic irradiation at childhood has been questioned. Preliminary results of these studies suggest that this type of approach could help for adapting treatment modalities and surveillance in subgroups of patients defective in DNA repair process. It could also have some incidence in the radioprotection field. (author)

  6. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Heather eDawson

    2013-10-01

    Full Text Available Background: Approximately 20% of all colorectal cancers are hypothesized to arise from the serrated pathway characterized by mutation in BRAF, high-level CpG Island Methylator Phenotype (CIMP and microsatellite instability/mismatch repair (MMR-deficiency. MMR-deficient cancers show frequent losses of Cdx2, a homeodomain transcription factor. Here, we determine the predictive value of Cdx2 expression for MMR-deficiency and investigate changes in expression between primary cancers and matched lymph node metastases. Methods: Immunohistochemistry for Cdx2, Mlh1, Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients with primary colorectal cancer and 59 cases of matched lymph node metastases. Receiver operating characteristic (ROC curve analysis and Area under the Curve (AUC were investigated; association of Cdx2 with clinicopathological features and patient survival was carried out.Results Loss of Cdx2 expression was associated with higher tumor grade (p=0.0002, advanced pT (p=0.0166, and perineural invasion (p=0.0228. Cdx2 loss was an unfavorable prognostic factor in univariate (p=0.0145 and multivariate (p=0.0427; HR (95%CI: 0.58 (0.34-0.98 analysis. The accuracy (AUC for discriminating MMR-proficient and –deficient cancers was 87% (OR (95%CI:0.96 (0.95-0.98; p<0.0001. Specificity and negative predictive value for MMR-deficiency was 99.1% and 96.3%. 174 patients had MMR-proficient cancers, of which 60 (34.5% showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency (p<0.0001. There was no difference in expression between primary tumors and matched metastases.Conclusion: Loss of Cdx2 is a sensitive and specific predictor of MMR-deficiency, but is not limited to these tumors, suggesting that events upstream of the development of MSI may impact Cdx2 expression.

  7. Inhibition of colorectal cancer genomic copy number alterations and chromosomal fragile site tumor suppressor FHIT and WWOX deletions by DNA mismatch repair

    Science.gov (United States)

    Gelincik, Ozkan; Blecua, Pedro; Edelmann, Winfried; Kucherlapati, Raju; Zhou, Kathy; Jasin, Maria; Gümüş, Zeynep H.; Lipkin, Steven M.

    2017-01-01

    Homologous recombination (HR) enables precise DNA repair after DNA double strand breaks (DSBs) using identical sequence templates, whereas homeologous recombination (HeR) uses only partially homologous sequences. Homeologous recombination introduces mutations through gene conversion and genomic deletions through single-strand annealing (SSA). DNA mismatch repair (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in HeR suppression are poorly characterized. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) carrying Mlh1, Pms2, and Mlh3 mutations have higher HeR rates, by using 7,863 uniquely mapping paired direct repeat sequences (DRs) in the mouse genome as endogenous gene conversion and SSA reporters. Additionally, when DSBs are induced by gamma-radiation, Mlh1, Pms2 and Mlh3 mutant MEFs have higher DR copy number alterations (CNAs), including DR CNA hotspots previously identified in mouse MMR-deficient colorectal cancer (dMMR CRC). Analysis of The Cancer Genome Atlas CRC data revealed that dMMR CRCs have higher genome-wide DR HeR rates than MMR proficient CRCs, and that dMMR CRCs have deletion hotspots in tumor suppressors FHIT/WWOX at chromosomal fragile sites FRA3B and FRA16D (which have elevated DSB rates) flanked by paired homologous DRs and inverted repeats (IR). Overall, these data provide novel insights into the MMR-dependent HeR inhibition mechanism and its role in tumor suppression. PMID:29069730

  8. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

    Science.gov (United States)

    Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-10-01

    The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of

  9. Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan.

    Science.gov (United States)

    Sugano, Kokichi; Nakajima, Takeshi; Sekine, Shigeki; Taniguchi, Hirokazu; Saito, Shinya; Takahashi, Masahiro; Ushiama, Mineko; Sakamoto, Hiromi; Yoshida, Teruhiko

    2016-11-01

    Germline PMS2 gene mutations were detected by RT-PCR/direct sequencing of total RNA extracted from puromycin-treated peripheral blood lymphocytes (PBL) and multiplex ligation-dependent probe amplification (MLPA) analyses of Japanese patients with colorectal cancer (CRC) fulfilling either the revised Bethesda Guidelines or being an age at disease onset of younger than 70 years, and screened by mismatch repair protein immunohistochemistry of formalin-fixed paraffin embedded sections. Of the 501 subjects examined, 7 (1.40%) showed the downregulated expression of the PMS2 protein alone and were referred to the genetic counseling clinic. Germline PMS2 mutations were detected in 6 (85.7%), including 3 nonsense and 1 frameshift mutations by RT-PCR/direct sequencing and 2 genomic deletions by MLPA. No mutations were identified in the other MMR genes (i.e. MSH2, MLH1 and MSH6). The prevalence of the downregulated expression of the PMS2 protein alone was 1.40% among the subjects examined and IHC results predicted the presence of PMS2 germline mutations. RT-PCR from puromycin-treated PBL and MLPA may be employed as the first screening step to detect PMS2 mutations without pseudogene interference, followed by the long-range PCR/nested PCR validation using genomic DNA. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis

    Directory of Open Access Journals (Sweden)

    Jingwei Liu

    2018-01-01

    Full Text Available Background. Nucleotide excision repair (NER plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC development. Method. Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results. ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS in colon cancer (HR=1.53, P=0.043. Colon cancer patients with high ERCC4 expression showed favorable OS in males (HR=0.54, P=0.035. High XPC expression demonstrated decreased death hazards in rectal cancer (HR=0.40, P=0.026. Conclusion. ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

  11. Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene

    Science.gov (United States)

    Win, Aung Ko; Reece, Jeanette C.; Buchanan, Daniel D.; Clendenning, Mark; Young, Joanne P.; Cleary, Sean P.; Kim, Hyeja; Cotterchio, Michelle; Dowty, James G.; MacInnis, Robert J.; Tucker, Katherine M.; Winship, Ingrid M.; Macrae, Finlay A.; Burnett, Terrilea; Le Marchand, Loïc; Casey, Graham; Haile, Robert W.; Newcomb, Polly A.; Thibodeau, Stephen N.; Lindor, Noralane M.; Hopper, John L.; Gallinger, Steven; Jenkins, Mark A.

    2015-01-01

    The base excision repair protein, MUTYH, functionally interacts with the DNA mismatch repair (MMR) system. As genetic testing moves from testing one gene at a time, to gene panel and whole exome next generation sequencing approaches, understanding the risk associated with co-existence of germline mutations in these genes will be important for clinical interpretation and management. From the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1 with c.536A>G p.(Tyr179Cys)) and a MMR gene mutation (3 in MLH1, 6 in MSH2, and 1 in PMS2), 375 carriers of a single (monoallelic) MUTYH mutation alone, and 469 carriers of a MMR gene mutation alone. Of the 10 carriers of both gene mutations, 8 were diagnosed with colorectal cancer. Using a weighted cohort analysis, we estimated that risk of colorectal cancer for carriers of both a MUTYH and a MMR gene mutation was substantially higher than that for carriers of a MUTYH mutation alone [hazard ratio (HR) 21.5, 95 % confidence interval (CI) 9.19–50.1; p colorectal cancer for carriers of a MMR gene mutation alone. Our finding suggests MUTYH mutation testing in MMR gene mutation carriers is not clinically informative. PMID:26202870

  12. Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra

    International Nuclear Information System (INIS)

    Vreeswijk, Maaike P.G.; Meijers, Caro M.; Giphart-Gassler, Micheline; Vrieling, Harry; Zeeland, Albert A. van; Mullenders, Leon H.F.; Loenen, Wil A.M.

    2009-01-01

    Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C > T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

  13. Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

    Science.gov (United States)

    Yan, Tao; Seo, Yuji; Kinsella, Timothy J

    2009-11-15

    MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

  14. 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.

  15. Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Cordero, F.; Pardini, B.; Korenková, Vlasta; Vymetálková, Veronika; Bielik, Ludovít; Vodičková, Ludmila; Pitule, P.; Liška, V.; Matejka, V. M.; Levý, M.; Buchler, T.; Kubista, Mikael; Naccarati, Alessio; Vodička, Pavel

    2015-01-01

    Roč. 54, č. 9 (2015), s. 769-778 ISSN 0899-1987 R&D Projects: GA ČR GAP304/10/1286; GA ČR GPP304/11/P715; GA MZd NT14329; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : colorectal cancer * DNA instability * DNA repair Subject RIV: EB - Genetics ; Molecular Biology; EI - Biotechnology ; Bionics (BTO-N) Impact factor: 4.722, year: 2015

  16. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems; Efeitos letais da luz solar em bacterias proficientes e deficientes em reparos: acoes e interacoes

    Energy Technology Data Exchange (ETDEWEB)

    Sousa Neto, A de

    1981-12-31

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author).

  17. Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair-proficient colorectal cancers

    DEFF Research Database (Denmark)

    Sønderstrup, Ida Marie Heeholm; Nygård, Sune Boris; Poulsen, Tim Svenstrup

    2015-01-01

    to MMR status by immunohistochemical analysis using validated antibodies for MLH1, MLH2, MSH6 and PMS2, and information on TOP1, CEN20, TOP2A and CEN17 status was previously published for this cohort. RESULTS: The observed TOP1 gene copy numbers in the 36 CRC test cohort were significantly greater (p

  18. Gene expression signatures for colorectal cancer microsatellite status and HNPCC

    DEFF Research Database (Denmark)

    Kruhøffer, M; Jensen, J L; Laiho, P

    2005-01-01

    The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI...... of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated...... is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression...

  19. Variation within 3' UTRs of base excision repair genes and response to therapy in colorectal cancer patients: a potential modulation of microRNAs binding.

    Czech Academy of Sciences Publication Activity Database

    Pardini, B.; Rosa, F.; Barone, E.; Di Gaetano, C.; Slyšková, Jana; Novotný, J.; Levý, M.; Garritano, S.; Vodičková, Ludmila; Buchler, T.; Gemignani, F.; Landi, S.; Vodička, Pavel; Naccarati, Alessio

    2013-01-01

    Roč. 19, č. 21 (2013), s. 6044-6056 ISSN 1078-0432 R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal cancer * base excision repair * survival Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.193, year: 2013

  20. Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition

    NARCIS (Netherlands)

    Roepman, P.; Schlicker, A.; Tabernero, J.; Majewski, I.; Tian, S.; Moreno, V.; Snel, M.H.; Chresta, C.M.; Rosenberg, R.; Nitsche, U.; Macarulla, T.; Capella, G.; Salazar, R.; Orphanides, G.; Wessels, L.F.A.; Bernards, R.; Simon, I.M.

    2013-01-01

    In most colorectal cancer (CRC) patients, outcome cannot be predicted because tumors with similar clinicopathological features can have differences in disease progression and treatment response. Therefore, a better understanding of the CRC biology is required to identify those patients who will

  1. Prevalence of adenomas and hyperplastic polyps in mismatch repair mutation carriers among CAPP2 participants: report by the colorectal adenoma/carcinoma prevention programme 2

    DEFF Research Database (Denmark)

    Liljegren, Annelie; Barker, Gail; Elliott, Faye

    2008-01-01

    PURPOSE: To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously...... in smaller studies, and the results have been found to be variable. PATIENTS AND METHODS: Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before...

  2. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  3. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).

    Science.gov (United States)

    Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

    2014-01-01

    Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

  4. BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

    Science.gov (United States)

    Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

    2017-06-20

    Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

  5. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

    DEFF Research Database (Denmark)

    Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

    2006-01-01

    PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

  6. Double-strand break repair and colorectal cancer: gene variants within 3' UTRs and microRNAs binding as modulators of cancer risk and clinical outcome.

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Rosa, F.; Vymetálková, Veronika; Barone, E.; Jirásková, Kateřina; Gaetano, C.; Novotný, J.; Levý, M.; Vodičková, Ludmila; Gemignani, F.; Buchler, T.; Landi, S.; Vodička, Pavel; Pardini, B.

    2016-01-01

    Roč. 7, č. 17 (2016), s. 23156-23169 ISSN 1949-2553 R&D Projects: GA MZd(CZ) NV15-26535A; GA ČR(CZ) GAP304/12/1585; GA ČR(CZ) GA15-14789S Institutional support: RVO:68378041 Keywords : 3'UTR polymorphisms * colorectal cancer risk and clinical outcomes * double-strand break repair (DSBR) genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.168, year: 2016

  7. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes

    Czech Academy of Sciences Publication Activity Database

    Farkas, S. A.; Vymetálková, Veronika; Vodičková, Ludmila; Vodička, Pavel; Torbjörn, K. N.

    2014-01-01

    Roč. 6, č. 2 (2014), s. 179-191 ISSN 1750-1911 R&D Projects: GA ČR GPP304/11/P715; GA ČR(CZ) GAP304/12/1585; GA MZd NT14329 Institutional support: RVO:68378041 Keywords : CpG * DNA repair genes * sporadic colorectal cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.649, year: 2014

  8. Functional, genetic and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Korenková, Vlasta; Collins, A. R.; Procházka, Pavel; Vodičková, Ludmila; Švec, Jiří; Lipská, L.; Levý, M.; Schneiderová, M.; Liška, V.; Holubec, L.; Kumar, R.; Souček, P.; Naccarati, Alessio; Vodička, Pavel

    2012-01-01

    Roč. 18, č. 21 (2012), s. 5878-5887 ISSN 1078-0432 R&D Projects: GA ČR GAP304/12/1585; GA ČR(CZ) GAP304/10/1286; GA MZd NT12025 Grant - others:UICC(XE) ICR/11/068/2011; EEA-research fund:(NO) B/CZ0046/40031 Institutional research plan: CEZ:AV0Z50390512 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : DNA repair capacity * DNA repair gene expression * methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.837, year: 2012

  9. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.

    Science.gov (United States)

    Choi, Young Eun; Battelli, Chiara; Watson, Jacqueline; Liu, Joyce; Curtis, Jennifer; Morse, Alexander N; Matulonis, Ursula A; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A

    2014-05-15

    The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.

  10. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

    Czech Academy of Sciences Publication Activity Database

    Tulupová, Elena; Kumar, R.; Hánová, Monika; Slyšková, Jana; Pardini, Barbara; Poláková, Veronika; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Halamková, J.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 648, 1-2 (2008), s. 40-45 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA mismatch repair * Genetic polymorphism * Haplotype analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  11. Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patients and healthy controls

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Naccarati, Alessio; Pardini, Barbara; Poláková, Veronika; Vodičková, Ludmila; Šmerhovský, Z.; Levý, M.; Lipská, L.; Liška, V.; Vodička, Pavel (ed.)

    2012-01-01

    Roč. 27, č. 2 (2012), s. 225-232 ISSN 0267-8357 R&D Projects: GA ČR GAP304/10/1286; GA MZd NS10230 Grant - others:EEA-research fund:(NO) A/CZ0046/2/0012 Institutional research plan: CEZ:AV0Z50390512 Keywords : biomarkers * DNA damage * DNA repair capacity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  12. Polymorphisms in miRNA binding sites of nucleotide excision repair genes and colorectal cancer risk

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Pardini, Barbara; Landi, S.; Landi, D.; Slyšková, Jana; Novotný, J.; Levý, M.; Poláková, Veronika; Lipská, L.; Vodička, Pavel

    2012-01-01

    Roč. 33, č. 7 (2012), s. 1346-1351 ISSN 0143-3334 R&D Projects: GA ČR GAP304/10/1286; GA ČR GP305/09/P194 Institutional research plan: CEZ:AV0Z50390703 Keywords : DNA repair * polymorphisms * miRNA binding sites Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.635, year: 2012

  13. Meta-analysis of mismatch repair polymorphisms within the cogent consortium for colorectal cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Simone Picelli

    Full Text Available In the last four years, Genome-Wide Association Studies (GWAS have identified sixteen low-penetrance polymorphisms on fourteen different loci associated with colorectal cancer (CRC. Due to the low risks conferred by known common variants, most of the 35% broad-sense heritability estimated by twin studies remains unexplained. Recently our group performed a case-control study for eight Single Nucleotide Polymorphisms (SNPs in 4 CRC genes. The present investigation is a follow-up of that study. We have genotyped six SNPs that showed a positive association and carried out a meta-analysis based on eight additional studies comprising in total more than 8000 cases and 6000 controls. The estimated recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H, decreased from 1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to 1.08 in the initial meta-analysis. Since the corresponding summary probability value was 0.06, we decided to retrieve additional information for this polymorphism. The incorporation of six further studies resulted in around 13000 cases and 13000 controls. The newly updated OR was 1.03. The results from the present large, multicenter study illustrate the possibility of decreasing effect sizes with increasing samples sizes. Phenotypic heterogeneity, differential environmental exposures, and population specific linkage disequilibrium patterns may explain the observed difference of genetic effects between Sweden and the other investigated cohorts.

  14. Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study.

    Science.gov (United States)

    Ismael, Nour El Hoda S; El Sheikh, Samar A; Talaat, Suzan M; Salem, Eman M

    2017-03-15

    Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters. There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status. Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

  15. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma.

    Science.gov (United States)

    Hall, Geoffrey; Clarkson, Adele; Shi, Amanda; Langford, Eileen; Leung, Helen; Eckstein, Robert P; Gill, Anthony J

    2010-01-01

    Currently, testing for mismatch repair deficiency in colorectal cancers is initiated by performing immunohistochemistry with four antibodies (MLH1, PMS2, MSH2 and MSH6). If any one of these stains is negative the tumour is considered microsatellite unstable and, if clinical circumstances warrant it, the patient is offered genetic testing for Lynch's syndrome. Due to the binding properties of the mismatch repair heterodimer complexes, gene mutation and loss of MLH1 and MSH2 invariably result in the degradation of PMS2 and MSH6, respectively, but the converse is not true. We propose that staining for PMS2 and MSH6 alone will be sufficient to detect all cases of mismatch repair deficiency and should replace routine screening with all four antibodies. The electronic database of the department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia, was searched for all colorectal carcinomas on which a four panel immunohistochemical microsatellite instability screen was performed. An audit of the slides for concordant loss of MLH1-PMS2 and MSH2-MSH6 was then undertaken. Unusual or discordant cases were reviewed and, in some cases, re-stained to confirm the staining pattern. Of 344 cases of colorectal cancer which underwent four antibody immunohistochemistry, 104 displayed loss of at least one mismatch repair protein. Of these, 100 showed concordant mismatch repair loss (i.e., loss of MLH1 and PMS2 or loss of MSH2 and MSH6). The four discordant cases comprised two single negative cases (1 MSH6 negative/MSH2 positive case, 1 PMS2 negative/MLH1 positive) and two triple negative (both MLH1/PMS2/MSH6 negative). The microsatellite instability (MSI) group showed a relatively high median age (69.3 years) due to the departmental policy of testing all cases with possible MSI morphology regardless of age. The sensitivity and specificity of a two panel test comprised of PMS2 and MSH6, compared to a four panel test, is 100%. No false negatives or positives were

  16. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  17. Mismatch Repair Deficiency Testing in Patients With Colorectal Cancer and Nonadherence to Testing Guidelines in Young Adults.

    Science.gov (United States)

    Shaikh, Talha; Handorf, Elizabeth A; Meyer, Joshua E; Hall, Michael J; Esnaola, Nestor F

    2018-02-08

    Mismatch repair (MMR) deficiency of DNA has been observed in up to 15% of sporadic colorectal cancers (CRCs) and is a characteristic feature of Lynch syndrome, which has a higher incidence in young adults (age, testing in adults with CRC and analyze nonadherence to long-standing testing guidelines in younger adults using a contemporary national data set to help identify potential risk factors for nonadherence to newly implemented universal testing guidelines. Adult (age, testing status were identified using the National Cancer Database. The study was conducted from March 16, 2016, to March 1, 2017. Patient sociodemographic, facility, tumor, and treatment characteristics. The primary outcome of interest was receipt of MMR deficiency testing. Multivariable logistic regression was used to identify independent predictors of testing in adult and/or young adult patients. A total of 152 993 adults with CRC were included in the study (78 579 [51.4%] men; mean [SD] age, 66.9 [13.9] years). Of these patients, only 43 143 (28.2%) underwent MMR deficiency testing; the proportion of patients tested increased between 2010 and 2012 (22.3% vs 33.1%; Ptesting; the proportion tested increased between 2010 and 2012 (36.1% vs 48.0%; P testing, whereas older age (OR, 0.31; 95% CI, 0.26-0.37); Medicare (OR, 0.89; 95% CI, 0.84-0.95), Medicaid (OR, 0.83; 95% CI, 0.73-0.93), or uninsured (OR, 0.78; 95% CI, 0.66-0.92) status; nonacademic vs academic/research facility type (OR, 0.44; 95% CI, 0.34-0.56); rectosigmoid or rectal tumor location (OR, 0.76; 95% CI, 0.68-0.86); unknown grade (OR, 0.61; 95% CI, 0.53-0.69); and nonreceipt of definitive surgery (OR, 0.33; 95% CI, 0.30-0.37) were associated with underuse of MMR deficiency testing. Despite recent endorsement of universal use of MMR deficiency testing in patients with CRC and well-established guidelines aimed at high-risk populations, overall utilization of testing is poor and significant underuse of testing among young adults

  18. The use of synthetic mesh in patients undergoing ventral hernia repair during colorectal resection: Risk of infection and recurrence

    Directory of Open Access Journals (Sweden)

    Galal H. El-Gazzaz

    2012-10-01

    Conclusions: Use of non-absorbable mesh during colorectal resection should be very selective. Comorbidity, duration of follow-up, emergency operations, size of area covered and infection are independent factors associated with recurrence.

  19. 5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency

    DEFF Research Database (Denmark)

    Bracht, K; Nicholls, A M; Liu, Ying

    2010-01-01

    Colorectal cancer is (CRC) one of the commonest cancers and its therapy is still based on few drugs. Currently, no biological criteria are used to choose the most effective of the established drugs for treatment.......Colorectal cancer is (CRC) one of the commonest cancers and its therapy is still based on few drugs. Currently, no biological criteria are used to choose the most effective of the established drugs for treatment....

  20. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Kazuya Shinmura

    2014-01-01

    Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

  1. Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al.

    Science.gov (United States)

    Deming, Dustin A

    2016-01-01

    Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to target cancers have evolved expediently over the last 5 years, especially the use of checkpoint inhibitors. Recently, a subset of patients whose colorectal cancers harbor a deficiency in mismatch repair proteins have demonstrated dramatic and durable response to checkpoint blockade. Unfortunately, the vast majority of colorectal cancers are mismatch repair proficient and resistant to these inhibitors. The tumor microenvironment has been implicated in the resistance to checkpoint block and ways to overcome these resistance mechanisms would be a major advance for the treatment of colorectal cancer. Here we provide commentary on a manuscript from Halama et al. examining CCL5/CCR5 as an immune biomarker and the potential role of anti-CCR5 agents for the treatment of patients with colorectal cancer.

  2. Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Montazer Haghighi, Mahdi; Radpour, Ramin; Aghajani, Katayoun; Zali, Narges; Molaei, Mahsa; Zali, Mohammad Reza

    2009-08-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations.

  3. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

    Science.gov (United States)

    Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

    2010-12-01

    A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

  4. Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer

    OpenAIRE

    Mrkonjic, M; Chappell, E; Pethe, V V; Manno, M; Daftary, D; Greenwood, C M; Gallinger, S; Zanke, B W; Knight, J A; Bapat, B

    2009-01-01

    ApoE single nucleotide polymorphisms (SNPs) Cys112Arg (Epsilon-4), and Arg158Cys (Epsilon-2) have been implicated in cardiovascular and Alzheimer's disease, but their role in colorectal cancer (CRC) has not been extensively studied. We investigated whether ApoE polymorphisms alone or in combination with dietary factors selectively contribute to mismatch-repair (MMR) proficient (microsatellite stable/low or MSS/L) vs deficient (microsatellite unstable or MSI-H) CRCs. We carried out a case?cont...

  5. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

    Science.gov (United States)

    Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

    2018-06-08

    Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

  6. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  7. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

    1996-01-01

    Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

  8. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

    Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

  9. Mutation avoidance and DNA repair proficiency in Ustilago maydis are differentially lost with progressive truncation of the REC1 gene product

    Energy Technology Data Exchange (ETDEWEB)

    Onel, K.; Thelen, M.P.; Ferguson, D.O.; Bennett, R.L.; Holloman, W.K. [Cornell Univ. Medical College, NY, NY (United States)

    1995-10-01

    The REC1 gene of Ustilago maydis has an uninterrupted open reading frame, predicted from the genomic sequence to encode a protein of 522 amino acid residues. Nevertheless, an intron is present, and functional activity of the gene in mitotic cells requires an RNA processing event to remove the intron. This results in a change in reading frame and production of a protein of 463 amino acid residues. The 3{prime}{r_arrow}5{prime} exonuclease activity of proteins derived form the REC1 genomic open reading frame, the intronless open reading frame, and several mutants was investigated. The mutants included a series of deletions constructed by removing restriction fragments at the 3{prime} end of the cloned REC1 gene and a set of mutant alleles previously isolated in screens for radiation sensitivity. The results indicated that elimination of the C-terminal third of the protein did not result in a serious reduction in 3{prime}{r_arrow}5{prime} exonuclease activity, but deletion into the midsection caused a severe loss of activity. The biological activity of the rec1-1 allele, which encodes a truncated polypeptide with full 3{prime}{r_arrow}5{prime} exonuclease activity, and the rec1-5 allele, which encodes a more severely truncated polypeptide with no exonuclease activity, was investigated. The two mutants were equally sensitive to the lethal effect of UV light, but the spontaneous mutation rate was elevated 10-fold over the wild-type rate in the rec1-1 mutant and 100-fold in the rec1-5 mutant. The elevated spontaneous mutation rate correlated with the ablation of exonuclease activity, but the radiation sensitivity did not. These results indicate that the C-terminal portion of the Rec1 protein is not essential for exonuclease activity but is crucial in the role of REC1 in DNA damage repair. 49 refs., 3 figs., 1 tab.

  10. Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

    DEFF Research Database (Denmark)

    Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas

    2013-01-01

    Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....

  11. Proficiency tests, Evaluating

    NARCIS (Netherlands)

    Cofino, W.P.; Molenaar, J.; Torfs, P.J.J.F.

    2017-01-01

    Marine monitoring programs provide data that are essential for marine management. The reliability of such data is underpinned by proficiency tests. In the context of Quasimeme, a proficiency testing program for the marine environment, a statistical model has been developed in 2000 to evaluate data

  12. Management of Colorectal Trauma

    Science.gov (United States)

    2011-01-01

    Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

  13. A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico DNA repair gene expression in synchronic tumors of sporadic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Igor Proscurshim

    2007-03-01

    Full Text Available RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colorretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico.BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6 mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.

  14. Colorectal polyps

    Science.gov (United States)

    Intestinal polyps; Polyps - colorectal; Adenomatous polyps; Hyperplastic polyps; Villous adenomas; Serrated polyp; Serrated adenoma; Precancerous polyps; Colon cancer - polyps; Bleeding - colorectal polyps

  15. Excess Polθ functions in response to replicative stress in homologous recombination-proficient cancer cells

    Directory of Open Access Journals (Sweden)

    T. Goullet de Rugy

    2016-10-01

    Full Text Available DNA polymerase theta (Polθ is a specialized A-family DNA polymerase that functions in processes such as translesion synthesis (TLS, DNA double-strand break repair and DNA replication timing. Overexpression of POLQ, the gene encoding Polθ, is a prognostic marker for an adverse outcome in a wide range of human cancers. While increased Polθ dosage was recently suggested to promote survival of homologous recombination (HR-deficient cancer cells, it remains unclear whether POLQ overexpression could be also beneficial to HR-proficient cancer cells. By performing a short interfering (siRNA screen in which genes encoding druggable proteins were knocked down in Polθ-overexpressing cells as a means to uncover genetic vulnerabilities associated with POLQ overexpression, we could not identify genes that were essential for viability in Polθ-overexpressing cells in normal growth conditions. We also showed that, upon external DNA replication stress, Polθ expression promotes cell survival and limits genetic instability. Finally, we report that POLQ expression correlates with the expression of a set of HR genes in breast, lung and colorectal cancers. Collectively, our data suggest that Polθ upregulation, besides its importance for survival of HR-deficient cancer cells, may be crucial also for HR-proficient cells to better tolerate DNA replication stress, as part of a global gene deregulation response, including HR genes.

  16. A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

    Science.gov (United States)

    Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S; Brhane, Yonathan; Amos, Christopher I; Kraft, Peter; Hung, Rayjean J; Sellers, Thomas A; Witte, John S; Pharoah, Paul; Henderson, Brian E; Gruber, Stephen B; Hunter, David J; Garber, Judy E; Joshi, Amit D; McDonnell, Kevin; Easton, Doug F; Eeles, Ros; Kote-Jarai, Zsofia; Muir, Kenneth; Doherty, Jennifer A; Schildkraut, Joellen M

    2016-01-01

    DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. We identified three susceptibility DNA repair genes, RAD51B (P cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. ©2015 American Association for Cancer Research.

  17. Summary of microsatellite instability test results from laboratories participating in proficiency surveys: proficiency survey results from 2005 to 2012.

    Science.gov (United States)

    Boyle, Theresa A; Bridge, Julia A; Sabatini, Linda M; Nowak, Jan A; Vasalos, Patricia; Jennings, Lawrence J; Halling, Kevin C

    2014-03-01

    The College of American Pathologists surveys are the largest laboratory peer comparison programs in the world. These programs allow laboratories to regularly evaluate their performance and improve the accuracy of the patient test results they provide. Proficiency testing is offered twice a year to laboratories performing microsatellite instability testing. These surveys are designed to emulate clinical practice, and some surveys have more challenging cases to encourage the refinement of laboratory practices. This report summarizes the results and trends in microsatellite instability proficiency testing from participating laboratories from the inception of the program in 2005 through 2012. We compiled and analyzed data for 16 surveys of microsatellite instability proficiency testing during 2005 to 2012. The number of laboratories participating in the microsatellite instability survey has more than doubled from 42 to 104 during the 8 years analyzed. An average of 95.4% of the laboratories correctly classified each of the survey test samples from the 2005A through 2012B proficiency challenges. In the 2011B survey, a lower percentage of laboratories (78.4%) correctly classified the specimen, possibly because of overlooking subtle changes of microsatellite instability and/or failing to enrich the tumor content of the specimen to meet the limit of detection of their assay. In general, laboratories performed well in microsatellite instability testing. This testing will continue to be important in screening patients with colorectal and other cancers for Lynch syndrome and guiding the management of patients with sporadic colorectal cancer.

  18. Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis.

    Science.gov (United States)

    Esteller, M; Risques, R A; Toyota, M; Capella, G; Moreno, V; Peinado, M A; Baylin, S B; Herman, J G

    2001-06-15

    Defects in DNA repair may be responsible for the genesis of mutations in key genes in cancer cells. The tumor suppressor gene p53 is commonly mutated in human cancer by missense point mutations, most of them G:C to A:T transitions. A recognized cause for this type of change is spontaneous deamination of the methylcytosine. However, the persistence of a premutagenic O(6)-methylguanine can also be invoked. This last lesion is removed in the normal cell by the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). In many tumor types, epigenetic silencing of MGMT by promoter hypermethylation has been demonstrated and linked to the appearance of G to A mutations in the K-ras oncogene in colorectal tumors. To study the relevance of defective MGMT function by aberrant methylation in relation to the presence of p53 mutations, we studied 314 colorectal tumors for MGMT promoter hypermethylation and p53 mutational spectrum. Inactivation of MGMT by aberrant methylation was associated with the appearance of G:C to A:T transition mutations at p53 (Fischer's exact test, two-tailed; P = 0.01). Overall, MGMT methylated tumors displayed p53 transition mutations in 43 of 126 (34%) cases, whereas MGMT unmethylated tumors only showed G:C to A:T changes in 37 of 188 (19%) tumors. A more striking association was found in G:C to A:T transitions in non-CpG dinucleotides; 71% (12 of 17) of the total non-CpG transition mutations in p53 were observed in MGMT aberrantly methylated tumors (Fischer's exact test, two-tailed; P = 0.008). Our data suggest that epigenetic silencing of MGMT by promoter hypermethylation may lead to G:C to A:T transition mutations in p53.

  19. Colorectal Cancer

    Science.gov (United States)

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  20. Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2011-01-01

    with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly...... differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite...

  1. Challenges in the Identification of MSH6-Associated Colorectal Cancer: Rectal Location, Less Typical Histology, and a Subset With Retained Mismatch Repair Function

    DEFF Research Database (Denmark)

    Klarskov, Louise Laurberg; Holck, Susanne; Bernstein, Inge Thomsen

    2011-01-01

    with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly...... differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite...

  2. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

    International Nuclear Information System (INIS)

    Stubbert, Lawton J; Smith, Jennifer M; McKay, Bruce C

    2010-01-01

    One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

  3. Correlation between cell survival and DNA single-strand break repair proficiency in the Chinese hamster ovary cell lines AA8 and EM9 irradiated with 365-nm ultraviolet-A radiation

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Peak, J.G.; Peak, M.J. (Argonne National Lab., IL (USA))

    1991-02-01

    Cell survival parameters and the induction and repair of DNA single-strand breaks were measured in two Chinese hamster ovary cell lines after irradiation with monochromatic UVA radiation of wavelength 365 nm. The radiosensitive mutant cell line EM9 is known to repair ionizing-radiation-induced single-strand breaks (SSB) more slowly than the parent line AA8. EM9 was determined to be 1.7-fold more sensitive to killing by 365-nm radiation than AA8 at the 10% survival level, and EM9 had a smaller shoulder region on the survival curve ({alpha} = 1.76) than AA8 ({alpha} = 0.62). No significant differences were found between the cell lines in the initial yields of SSB induced either by {gamma}-radiation (as determined by alkaline sucrose gradient sedimentation) or by 365-nm UVA (as determined by alkaline elution). For measurement of initial SSB, cells were irradiated at 0.5{sup o}C to minimize DNA repair processes. Rejoining of 365-nm induced SSB was measured by irradiating cells at 0.5{sup o}C, allowing them to repair at 37{sup o}C in full culture medium, and then quantitating the remaining SSB by alkaline elution. The repair of these breaks followed biphasic kinetics in both cell lines. EM9 repaired the breaks more slowly (T{sub 1/2} values of 1.3 and 61.3 min) than did AA8 (T{sub 1/2} values of 0.9 and 53.3 min), and EM9 also left more breaks unrepaired 90 min after irradiation (24% vs 8% for AA8). Thus, the sensitivity of EM9 to 365-nm radiation correlated with its deficiency in repairing DNA lesions revealed as SSB in alkaline elution. These results suggest that DNA may be a critical target in 365-nm induced cellular lethality and that the ability of AA8 and EM9 cells to repair DNA strand breaks may be related to their ability to survive 365-nm radiation. (author).

  4. Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  5. Colorectal Cancer Prevention

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  6. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.

    Science.gov (United States)

    Esteller, M; Toyota, M; Sanchez-Cespedes, M; Capella, G; Peinado, M A; Watkins, D N; Issa, J P; Sidransky, D; Baylin, S B; Herman, J G

    2000-05-01

    O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from the O6 position of guanine. O6-methylguanine mispairs with thymine during replication, and if the adduct is not removed, this results in conversion from a guanine-cytosine pair to an adenine-thymine pair. In vitro assays show that MGMT expression avoids G to A mutations and MGMT transgenic mice are protected against G to A transitions at ras genes. We have recently demonstrated that the MGMT gene is silenced by promoter methylation in many human tumors, including colorectal carcinomas. To study the relevance of defective MGMT function by aberrant methylation in relation to the presence of K-ras mutations, we studied 244 colorectal tumor samples for MGMT promoter hypermethylation and K-ras mutational status. Our results show a clear association between the inactivation of MGMT by promoter hypermethylation and the appearance of G to A mutations at K-ras: 71% (36 of 51) of the tumors displaying this particular type of mutation had abnormal MGMT methylation, whereas only 32% (12 of 37) of those with other K-ras mutations not involving G to A transitions and 35% (55 of 156) of the tumors without K-ras mutations demonstrated MGMT methylation (P = 0.002). In addition, MGMT loss associated with hypermethylation was observed in the small adenomas, including those that do not yet contain K-ras mutations. Hypermethylation of other genes such as p16INK4a and p14ARF was not associated with either MGMT hypermethylation or K-ras mutation. Our data suggest that epigenetic silencing of MGMT by promoter hypermethylation may lead to a particular genetic change in human cancer, specifically G to A transitions in the K-ras oncogene.

  7. Southeast Asian Languages Proficiency Examinations.

    Science.gov (United States)

    Brown, James Dean; And Others

    The design, administration, revision, and validation of the Southeast Asian Summer Studies Institute proficiency examinations are reported. The examinations were created as parallel language proficiency tests in each of five languages: Indonesian, Khmer, Tagalog, Thai, and Vietnamese. Four tests were developed in each language: multiple-choice…

  8. Clinical Wisdom among Proficient Nurses

    DEFF Research Database (Denmark)

    Uhrenfeldt, Lisbeth; Hall, Elisabeth

    2007-01-01

    This paperexamines clinical wisdom which has emerged from a broader study anout nurse managers´influence on proficient registered nurse turnover and retention. The purpose of the study was to increase understanding of proficient nurses´experience and clinical practice by giving voice to the nurses...

  9. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study

    NARCIS (Netherlands)

    Botma, A.; Vasen, H.F.; Duijnhoven, F.J.B. van; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  10. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome: The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, A.; Vasen, H.F.; Duijnhoven, van F.J.B.; Kleibeuker, J.H.; Nagengast, F.M.; Kampman, E.

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  11. Dietary Patterns and Colorectal Adenomas in Lynch Syndrome The GEOLynch Cohort Study

    NARCIS (Netherlands)

    Botma, Akke; Vasen, Hans F. A.; van Duijnhoven, Franzel J. B.; Kleibeuker, Jan H.; Nagengast, Fokko M.; Kampman, Ellen

    2013-01-01

    BACKGROUND: Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in

  12. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.

    NARCIS (Netherlands)

    Vos tot Nederveen Cappel, W.H. de; Nagengast, F.M.; Griffioen, G.; Menko, F.H.; Taal, B.G.; Kleibeuker, J.H.; Vasen, H.F.

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  13. Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

    NARCIS (Netherlands)

    Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  14. Management of colorectal trauma: a review.

    Science.gov (United States)

    Cheong, Ju Yong; Keshava, Anil

    2017-07-01

    Traumatic colorectal injuries are common during times of military conflict, and major improvements in their care have arisen in such periods. Since World War II, many classification systems for colorectal trauma have been proposed, including (i) Flint Grading System; (ii) Penetrating Abdominal Trauma Index; (iii) Colonic/Rectal Injury Scale; and (iv) destructive/non-destructive colonic injuries. The primary goal of these classifications was to aid surgical management and, more particularly, to determine whether a primary repair or faecal diversion should be performed. Primary repair is now the preferred surgical option. Patients who have been identified as having destructive injuries have been found to have higher anastomotic leak rates after a primary repair. Damage control principles need to be adhered to in surgical decision-making. In this review, we discuss the mechanisms of injury, classifications, clinical presentation and current recommendations for the management of colorectal trauma. © 2017 Royal Australasian College of Surgeons.

  15. National radon measurement-proficiency program: Individual proficiency report

    International Nuclear Information System (INIS)

    1992-05-01

    In February 1986, the U.S. Environmental Protection Agency (EPA) established the Radon Measurement Proficiency (RMP) Program to assist the public in identifying organizations capable of providing reliable radon measurement services. In December 1991, EPA announced the new individual proficiency listing category in the RMP Program. Individuals applying for this new listing status must demonstrate knowledge of radon measurement fundamentals by passing a written proficiency examination, maintain affiliation with an RMP listed organization, and meet other program requirements. This report lists those individuals who have met the requirements of the RMP Program as of April 30, 1992. These requirements are designed to provide minimum proficiency criteria for individuals who provide radon measurement services on-site in a residential environment

  16. National Radon Contractor Proficiency Program. Proficiency report: Supplement

    International Nuclear Information System (INIS)

    1991-02-01

    The report, a supplement to the RCP Proficiency Report, will further assist governmental officials in providing advice to the public on the selection of proficient radon mitigation contractors. These reports list 1,123 contractors who have met the requirements of the RCP Program as of December 15, 1990. The Proficiency Report provides information on each contractor's name, RCP identification number, company name, address, phone number, and geographic service area. The report provides two additional tables, indexed by company name and by RCP identification number. The report is intended to help users quickly identify a proficient contractor if only the company name is known, or to verify which contractor is associated with a particular ID number

  17. National Radon Contractor Proficiency (RCP) Program. Proficiency report, June 1991

    International Nuclear Information System (INIS)

    1991-06-01

    The primary objective of the U.S. Environmental Protection Agency's (EPA) efforts to address the indoor radon problem is to reduce radon levels in buildings throughout the country. Achieving the objective requires a nationwide supply of capable radon mitigation contractors. In the Indoor Radon Abatement Act of 1988, Congress authorized EPA to establish a program to evaluate radon mitigation contractors and to provide the information to the public in cooperation with the States. The Radon Contractor Proficiency (RCP) Program was developed to assist States, EPA Regions, local government officials, and the public in selecting contractors who have demonstrated their proficiency in reducing indoor radon levels. The program is managed by the EPA Office of Radiation Programs' Radon Division. Under the voluntary program, radon contractors demonstrate their proficiency by meeting specific Program requirements. Individual contractors who meet these requirements are then listed in periodic RCP Proficiency Reports

  18. Decreased UV light resistance of spores of Bacillus subtilis strains deficient in pyrimidine dimer repair and small, acid-soluble spore proteins

    International Nuclear Information System (INIS)

    Setlow, B.; Setlow, P.

    1988-01-01

    Loss of small, acid-soluble spore protein alpha reduced spore UV resistance 30- to 50-fold in Bacillus subtilis strains deficient in pyrimidine dimer repair, but gave only a 5- to 8-fold reduction in UV resistance in repair-proficient strains. However, both repair-proficient and -deficient spores lacking this protein had identical heat and gamma-radiation resistance

  19. Testing Proficiency in Interpersonal Communication

    Science.gov (United States)

    Byers, Burton H.

    1973-01-01

    Discusses several hypotheses about the measurement of speech-communication proficiency which are being tested at the University of Hawaii and a testing instrument entitled Dy Comm'' (dyadic communication) which emerged from this research. (DD)

  20. Proficiency testing for radionuclides

    International Nuclear Information System (INIS)

    Faanhof, A.; Kotze, O.; Louw, I.

    2010-01-01

    Proficiency testing in general is only useful when it suites a certain purpose. With regards to radionuclides basically three fields of interest can be identified: (I)Foodstuffs-Introduced in the early 1960's to monitor the fall-out of nuclear tests and eventually the pathway to foodstuffs fit for human consumption. The demand for analysis increased substantially after the Chernobyl accident. (II) Natural radioactivity-Associated with mining and mineral processing of uranium and thorium baring mineral resources throughout the world where the radionuclides from the natural uranium and thorium decay series are found to pose concern for professional and public exposure. (III) Artificial radioactivity-This category covers mostly the long-lived nuclides generated by nuclear fission of the fuel used in nuclear power plants, research reactors and nuclear bomb tests. All three categories require a specific approach for laboratories to test their ability to analyze specific radio nuclides of interest in a variety of matrices. In this lecture I will give a compiled overview of the required radioanalytical skills, analysis sensitivity needed and radionuclides of interest, with more specific emphasis on QAQC of water sources and the recommended monitoring approach. And provide information on available reference materials and organizations/institutes that provide regular exercises for participating laboratories. I will also briefly communicate on the advantages and disadvantages of ISO/IEC 17025 accreditation for test laboratories, which is these days a prerequisite in national and international trade especially where foodstuffs and mineral products are concerned.

  1. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry.

    Science.gov (United States)

    Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

    2015-06-01

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P(trend) carcinogens relevant for CRC risk. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

    International Nuclear Information System (INIS)

    Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

    2015-01-01

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P trend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (P trend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (P trend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk

  3. Colorectal tuberculosis

    International Nuclear Information System (INIS)

    Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

    2003-01-01

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  4. Colorectal Cancer

    Science.gov (United States)

    ... possible. Research will help us better understand whether chemotherapy can benefit elderly colorectal cancer patients. Such patients often do not receive chemotherapy due to concerns about side effects. We will ...

  5. Computer proficiency questionnaire: assessing low and high computer proficient seniors.

    Science.gov (United States)

    Boot, Walter R; Charness, Neil; Czaja, Sara J; Sharit, Joseph; Rogers, Wendy A; Fisk, Arthur D; Mitzner, Tracy; Lee, Chin Chin; Nair, Sankaran

    2015-06-01

    Computers and the Internet have the potential to enrich the lives of seniors and aid in the performance of important tasks required for independent living. A prerequisite for reaping these benefits is having the skills needed to use these systems, which is highly dependent on proper training. One prerequisite for efficient and effective training is being able to gauge current levels of proficiency. We developed a new measure (the Computer Proficiency Questionnaire, or CPQ) to measure computer proficiency in the domains of computer basics, printing, communication, Internet, calendaring software, and multimedia use. Our aim was to develop a measure appropriate for individuals with a wide range of proficiencies from noncomputer users to extremely skilled users. To assess the reliability and validity of the CPQ, a diverse sample of older adults, including 276 older adults with no or minimal computer experience, was recruited and asked to complete the CPQ. The CPQ demonstrated excellent reliability (Cronbach's α = .98), with subscale reliabilities ranging from .86 to .97. Age, computer use, and general technology use all predicted CPQ scores. Factor analysis revealed three main factors of proficiency related to Internet and e-mail use; communication and calendaring; and computer basics. Based on our findings, we also developed a short-form CPQ (CPQ-12) with similar properties but 21 fewer questions. The CPQ and CPQ-12 are useful tools to gauge computer proficiency for training and research purposes, even among low computer proficient older adults. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Fruits, vegetables and hMLH1 protein-deficient and-proficient colon cancer: the Netherlands Cohort Study

    NARCIS (Netherlands)

    Wark, P.A.; Weijenberg, M.P.; Veer, van 't P.; Wijhe, van G.; Luchtenborg, M.; Muijen, van G.N.P.; Goeij, de A.F.P.M.; Goldbohm, R.A.; Brandt, van den P.A.

    2005-01-01

    Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.METHODS:

  7. National Radon Contractor Proficiency (RCP) program. Proficiency report, September 1991

    International Nuclear Information System (INIS)

    1991-09-01

    The primary objective of the U.S. Environmental Protection Agency's (EPA) efforts to address the indoor radon problem is to reduce radon levels in buildings throughout the country. Achieving this objective requires a nationwide supply of capable radon mitigation contractors. In the Indoor Radon Abatement Act of 1988, Congress authorized EPA to establish a program to evaluate radon mitigation contractors and to provide this information to the public in cooperation with the States. The Radon Contractor Proficiency (RCP) Program was developed to assist States, EPA Regions, local government officials, and the public in selecting contractors who have demonstrated their proficiency in reducing indoor radon levels. The program is managed by the EPA Office of Radiation Programs' Radon Division. Under this voluntary program, radon contractors demonstrate their proficiency by meeting specific Program requirements. Individual contractors who meet these requirements are then listed in the Report

  8. National Radon Contractor Proficiency (RCP) Program. Proficiency report, January 1992

    International Nuclear Information System (INIS)

    1992-01-01

    The primary objective of the U.S. Environmental Protection Agency's (EPA) efforts to address the indoor radon problem is to reduce radon levels in buildings throughout the country. Achieving the objective requires a nationwide supply of capable radon mitigation contractors. In the Indoor Radon Abatement Act of 1988, Congress authorized EPA to establish a program to evaluate radon mitigation contractors and to provide the information to the public in cooperation with the States. The Radon Contractor Proficiency (RCP) Program was developed to assist States, EPA Regions, local government officials, and the public in selecting contractors who have demonstrated their proficiency in reducing indoor radon levels. The program is managed by the EPA Office of Radiation Programs' Radon Division. Under the voluntary program, radon contractors demonstrate their proficiency by meeting specific Program requirements. Individual contractors who meet these requirements are then listed in the Report

  9. Language proficiency and nursing registration.

    Science.gov (United States)

    Müller, Amanda

    2016-02-01

    This discussion paper focuses on English proficiency standards for nursing registration in Australia, how Australia has dealt with the issue of language proficiency, and the factors which have led to the establishment of the current language standards. Also, this paper will provide a comparison of the two language tests that are currently accepted in Australia (OET and IELTS), including the appropriateness of these tests and the minimum standards used. The paper will also examine the use of educational background as an indicator of language proficiency. Finally, communication-based complaints in the post-registration environment will be explored, and some discussion will be provided about why pre-registration measures might have failed to prevent such problematic situations from occurring. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. National Radon Contractor Proficiency Program. Proficiency report, October 1990

    International Nuclear Information System (INIS)

    1990-10-01

    The report lists those individual contractors in the United States who have met the requirements of the Radon Contractor Proficiency (RCP) Program as of August 18, 1990. These requirements are designed to provide minimum proficiency criteria for individuals who design and supervise the installation of radon mitigation systems in buildings. (Some States have more stringent requirements as part of their radon certification programs. The States should be consulted directly for details on their programs; see Section 5 for a list of State radon contacts). The RCP Program measures the proficiency of an individual contractor, not their company. Therefore, users of the report who select a mitigation firm should ensure that the services are provided by the listed contractor. The National RCP Program does not accredit mitigation contractors, nor does it certify, recommend, or endorse participating companies. Only the listed contractor, not their company of affilation, are deemed proficient. The inclusion of a contractor in the report should not be interpreted as a certification or accreditation of the individual or affiliated company

  11. Learning Strategies in Proficient and Less Proficient Readers in Medicine

    Science.gov (United States)

    Nemati, Majid; Nodoushan, Mohammad Ali Salmani; Ashrafzadeh, Anis

    2010-01-01

    The current study aimed to diagnose the probable significant differences in the use of language learning strategies among medical-text readers of opposite sex from different levels of proficiency. 120 (N = 120) participants were randomly selected from Azad Medical University of Mashhad: 60 medical students (age range 23-25; 30 = male and 30 =…

  12. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  13. Discrepancies between perceptions of English proficiency and ...

    African Journals Online (AJOL)

    multilingual awareness pedagogy” embedded in Dörnyei's (2009) L2 Motivational Self System theory. Key words: self-reported perceptions, language proficiency, English proficiency, multilingualism, pedagogy, resilience, L2 Motivational Self System ...

  14. An Accounting Writing Proficiency Survey

    Science.gov (United States)

    Firch, Tim; Campbell, Annhenrie; Filling, Steven; Lindsay, David H.

    2011-01-01

    Although there has been much discussion about improving college student writing with college-level courses, little is known about how accounting programs, in particular, are addressing the writing proficiency challenge. This study surveys the 852 accounting programs in the United States to identify the frequency and types of accounting writing…

  15. THE SCANDCLEFT RANDOMISED CONTROLLED TRIALS: SPEECH OUTCOMES IN 5-YEAR-OLDS WITH UCLP – consonant proficiency and errors

    DEFF Research Database (Denmark)

    Willadsen, Elisabeth; Persson, Christina; Lohmander, Anette

    2017-01-01

    Background and aim: Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocol...... in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed. Trial registration: ISRCTN29932826. Keywords: Primary palatal repair, unilateral cleft lip and palate, consonant proficiency, cleft speech characteristics, randomised clinical trial...

  16. MSH3 mismatch repair protein regulates sensitivity to cytotoxic drugs and a histone deacetylase inhibitor in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available MSH3 is a DNA mismatch repair (MMR gene that undergoes frequent somatic mutation in colorectal cancers (CRCs with MMR deficiency. MSH3, together with MSH2, forms the MutSβ heteroduplex that interacts with interstrand cross-links induced by drugs such as cisplatin. To date, the impact of MSH3 on chemosensitivity is unknown.We utilized isogenic HCT116 (MLH1-/MSH3- cells where MLH1 is restored by transfer of chromosome 3 (HCT116+ch3 and also MSH3 by chromosome 5 (HCT116+3+5. We generated HCT116+3+5, SW480 (MLH1+/MSH3+ and SW48 (MLH1-/MSH3+ cells with shRNA knockdown of MSH3. Cells were treated with 5-fluorouracil (5-FU, SN-38, oxaliplatin, or the histone deacetylase (HDAC inhibitor PCI-24781 and cell viability, clonogenic survival, DNA damage and apoptosis were analyzed.MSH3-deficient vs proficient CRC cells showed increased sensitivity to the irinotecan metabolite SN-38 and to oxaliplatin, but not 5-FU, as shown in assays for apoptosis and clonogenic survival. In contrast, suppression of MLH1 attenuated the cytotoxic effect of 5-FU, but did not alter sensitivity to SN-38 or oxaliplatin. The impact of MSH3 knockdown on chemosensitivity to SN-38 and oxaliplatin was maintained independent of MLH1 status. In MSH3-deficient vs proficient cells, SN-38 and oxaliplatin induced higher levels of phosphorylated histone H2AX and Chk2, and similar results were found in MLH1-proficient SW480 cells. MSH3-deficient vs proficient cells showed increased 53BP1 nuclear foci after irradiation, suggesting that MSH3 can regulate DNA double strand break (DSB repair. We then utilized PCI-24781 that interferes with homologous recombination (HR indicated by a reduction in Rad51 expression. The addition of PCI-24781 to oxaliplatin enhanced cytotoxicity to a greater extent compared to either drug alone.MSH3 status can regulate the DNA damage response and extent of apoptosis induced by chemotherapy. The ability of MSH3 to regulate chemosensitivity was independent of MLH1

  17. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

    Directory of Open Access Journals (Sweden)

    Smith Jennifer M

    2010-05-01

    Full Text Available Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi was used to reduce the transcription-coupled nucleotide excision repair (TC-NER capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic.

  18. Colorectal cancer

    International Nuclear Information System (INIS)

    Akiba, Suminori

    1992-01-01

    This paper describes colorectal cancer risk in relation to A-bomb radiation. The RERF Life Span Study has revealed the incidence of colorectal cancer to be significantly high in the group of A-bomb survivors than the control group. With regard to relative risk or excess relative risk, there is no definitive difference among sites in the colon. Risk for colon cancer is found to be linearly increased with increasing radiation doses, and in younger A-bomb survivors at the time of exposure. Risk associated with one Gy is estimated to be increased by double. There is no definitive variation between sex and between Hiroshima and Nagasaki. Excess relative risk would be increased rapidly with aging in the whole group of A-bomb survivors and with the cancer-prone age in younger A-bomb survivors at the time of exposure. (N.K.)

  19. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  20. Knowledge Management and Organizational Proficiency with NPP

    International Nuclear Information System (INIS)

    Marler, M.

    2016-01-01

    Full text: The pace of new NPP construction, startup, and operation is straining the supply of proficient operators, technicians, and engineers. This technical brief explains an approach implemented by a US nuclear utility to capture and transfer knowledge possessed by proficient workers to new workers using the VISION learning content management system. This approach could also be used to accelerate worker proficiency in new NPP organizations. (author

  1. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview What to Expect ... section Overview 2 of 6 sections The Basics: Colorectal Cancer What is colorectal cancer? Colorectal cancer is a ...

  2. Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

    OpenAIRE

    Wang, Xu-Lin; Yuan, Ying; Zhang, Su-Zhan; Cai, Shan-Rong; Huang, Yan-Qin; Jiang, Qiang; Zheng, Shu

    2006-01-01

    AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.

  3. Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    de Jong, Andrea E.; van Puijenbroek, Marjo; Hendriks, Yvonne; Tops, Carli; Wijnen, Juul; Ausems, Margreet G. E. M.; Meijers-Heijboer, Hanne; Wagner, Anja; van Os, Theo A. M.; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans F. A.; Morreau, Hans

    2004-01-01

    Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis can be used to identify patients with a possible DNA mismatch repair defect [hereditary nonpolyposis colorectal carcinoma (HNPCC)]. The Bethesda criteria have been proposed to select families for determination of MSI. The aims

  4. DNA repair and cancer

    International Nuclear Information System (INIS)

    Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha

    2012-01-01

    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)

  5. Maintenance proficiency evaluation test bank

    International Nuclear Information System (INIS)

    Maier, Loran

    2003-01-01

    The Maintenance Proficiency Evaluation Test Bank (MPETB) is an Electric Power Research Institute- (EPRJ-) operated, utility-sponsored means of developing, maintaining, and disseminating secure, high-quality written and performance maintenance proficiency tests. EPRTs charter is to ensure that all tests and test items that go into the Test Bank have been validated, screened for reliability, and evaluated to high standards of psychometric excellence. Proficiency tests of maintenance personnel.(mechanics, electricians, and instrumentation and control [I and C] technicians) are most often used to determine if an experienced employee is capable of performing maintenance tasks without further training. Such tests provide objective evidence for decisions to exempt an employee from what, for the employee, is unnecessary training. This leads to considerable savings in training costs and increased productivity because supervisors can assign personnel to tasks at which their competence is proven. The ultimate objective of proficiency evaluation is to ensure that qualified maintenance personnel are available to meet the maintenance requirements of the plant Numerous task-specific MPE tests (both written and performance) have been developed and validated using the EPRI MPE methodology by the utilities participating in the MPETB project A task-specific MPE consists of a multiple-choice written examination and a multi-step performance evaluation that can be used to assess an individual's present knowledge and skill level for a given maintenance task. The MPETB contains MPEs and test items for the mechanical, electrical, and I and C classifications that are readily available to participating utilities. Presently, utilities are placing emphasis on developing MPEs to evaluate outage-related maintenance tasks that demonstrate the competency and qualifications of plant and contractor personnel before the start of outage work. Utilities are also using the MPE methodology and process to

  6. Clinical definition of hereditary non-polyposis colorectal cancer : A search for the impossible?

    NARCIS (Netherlands)

    Berends, MJW; Wu, Y; Sijmons, RH; Hofstra, RMW; van der Zee, AGJ; Buys, CHCM; Kleibeuker, JH

    2001-01-01

    Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system. are responsible

  7. Enhancement of ultraviolet-DNA repair in denV gene transfectants and T4 endonuclease V-liposome recipients

    International Nuclear Information System (INIS)

    Kibitel, J.T.; Yee, V.; Yarosh, D.B.

    1991-01-01

    The phage T4 denV gene, coding for the pyrimidine-dimer specific T4 endonuclease V, was transfected into human repair-proficient fibroblasts, repair-deficient xeroderma pigmentosum fibroblasts, and wild type CHO hamster cells. Transfectants maintained denV DNA and expressed denV mRNA. Purified T4 endonuclease V encapsulated in liposomes was also used to treat repair-proficient and -deficient human cells. The denV transfected clones and liposome-treated cells showed increased unscheduled DNA synthesis and enhanced removal of pyrimidine dimers compared to controls. Both denV gene transfection and endonuclease V liposome treatment enhanced post-UV survival in xeroderma pigmentosum cells but had no effect on survival in repair-proficient human or hamster cells. The results demonstrate that an exogenous DNA repair enzyme can correct the DNA repair defect in xeroderma pigmentosum cells and enhance DNA repair in normal cells. (author)

  8. Interobserver variability in the evaluation of mismatch repair protein immunostaining

    DEFF Research Database (Denmark)

    Klarskov, Louise Laurberg; Ladelund, Steen; Holck, Susanne

    2010-01-01

    Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliabi......Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data...... on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein...... variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance...

  9. National proficiency-gain curves for minimally invasive gastrointestinal cancer surgery.

    Science.gov (United States)

    Mackenzie, H; Markar, S R; Askari, A; Ni, M; Faiz, O; Hanna, G B

    2016-01-01

    Minimal access surgery for gastrointestinal cancer has short-term benefits but is associated with a proficiency-gain curve. The aim of this study was to define national proficiency-gain curves for minimal access colorectal and oesophagogastric surgery, and to determine the impact on clinical outcomes. All adult patients undergoing minimal access oesophageal, colonic and rectal surgery between 2002 and 2012 were identified from the Hospital Episode Statistics database. Proficiency-gain curves were created using risk-adjusted cumulative sum analysis. Change points were identified, and bootstrapping was performed with 1000 iterations to identify a confidence level. The primary outcome was 30-day mortality; secondary outcomes were 90-day mortality, reintervention, conversion and length of hospital stay. Some 1696, 15 008 and 16 701 minimal access oesophageal, rectal and colonic cancer resections were performed during the study period. The change point in the proficiency-gain curve for 30-day mortality for oesophageal, rectal and colonic surgery was 19 (confidence level 98·4 per cent), 20 (99·2 per cent) and three (99·5 per cent) procedures; the mortality rate fell from 4·0 to 2·0 per cent (relative risk reduction (RRR) 0·50, P = 0·033), from 2·1 to 1·2 per cent (RRR 0·43, P curve for reintervention in oesophageal, rectal and colonic resection was 19 (98·1 per cent), 32 (99·5 per cent) and 26 (99·2 per cent) procedures respectively. There were also significant proficiency-gain curves for 90-day mortality, conversion and length of stay. The introduction of minimal access gastrointestinal cancer surgery has been associated with a proficiency-gain curve for mortality and major morbidity at a national level. Unnecessary patient harm should be avoided by appropriate training and monitoring of new surgical techniques. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  10. [Laboratory accreditation and proficiency testing].

    Science.gov (United States)

    Kuwa, Katsuhiko

    2003-05-01

    ISO/TC 212 covering clinical laboratory testing and in vitro diagnostic test systems will issue the international standard for medical laboratory quality and competence requirements, ISO 15189. This standard is based on the ISO/IEC 17025, general requirements for competence of testing and calibration laboratories and ISO 9001, quality management systems-requirements. Clinical laboratory services are essential to patient care and therefore should be available to meet the needs of all patients and clinical personnel responsible for human health care. If a laboratory seeks accreditation, it should select an accreditation body that operates according to this international standard and in a manner which takes into account the particular requirements of clinical laboratories. Proficiency testing should be available to evaluate the calibration laboratories and reference measurement laboratories in clinical medicine. Reference measurement procedures should be of precise and the analytical principle of measurement applied should ensure reliability. We should be prepared to establish a quality management system and proficiency testing in clinical laboratories.

  11. Motor Proficiency in Young Children

    Directory of Open Access Journals (Sweden)

    Fotini Venetsanou

    2016-01-01

    Full Text Available This study aimed to examine motor proficiency in young children, focusing on potential gender differences. For that purpose, the Bruininks-Oseretsky Test of Motor Proficiency–Long Form (BOTMP-LF was administered to 540 children (272 boys, 4½ to 6 years old. First, the 2 (sex × 4 (age groups ANOVA computed on children’s total BOTMP-LF scores showed that age had a statistically significant effect, whereas gender did not. Second, the one-way MANCOVA applied on subtest scores, with age as covariate, revealed statistical significant gender differences; however, η2 values were found to be small or moderate. Finally, the MANCOVA applied on items where significant gender differences have been reported showed a significant effect of gender. Nonetheless, η2 values exceeded the limit of practical significance only on two items (“standing on preferred leg on floor”, “throwing a ball at a target with preferred hand” that are associated with gender-stereotyped activities. It can be concluded that (a besides statistical significance, effect sizes should be examined for the results of a study to be adequately interpreted; (b young boys’ and girls’ motor proficiency is similar rather than different. Gender differences in specific skills should be used for movement programs to be individualized.

  12. Proficiency test for aflatoxin in pig feed

    NARCIS (Netherlands)

    Elbers, I.J.W.; Nijs, de W.C.M.

    2015-01-01

    Proficiency testing is conducted to provide laboratories with a powerful tool to evaluate and demonstrate the reliability of the data that are produced. Next to validation and accreditation, proficiency testing is an important requirement of the EU Additional Measures Directive 93/99/EEC [1] and is

  13. Proficiency study for quinolones in egg

    NARCIS (Netherlands)

    Berendsen, B.J.A.; Stolker, A.A.M.

    2008-01-01

    The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of quinolones in egg. Furthermore the specificity of the applied methods is evaluated by including possibly interfering compounds in the proficiency study. This

  14. Measuring receptive collocational competence across proficiency ...

    African Journals Online (AJOL)

    The present study investigates (i) English as Foreign Language (EFL) learners' receptive collocational knowledge growth in relation to their linguistic proficiency level; (ii) how much receptive collocational knowledge is acquired as linguistic proficiency develops; and (iii) the extent to which receptive knowledge of ...

  15. Proficiency test for allergens in food 2014

    NARCIS (Netherlands)

    Bremer, M.G.E.G.; Alamenou, P.; Elbers, I.J.W.

    2015-01-01

    In the autumn of 2014 a proficiency test for allergens in baby cereal was organized by RIKILT, Wageningen UR. This PT-test enabled laboratories to evaluate their competence for the analysis of allergens in baby cereal. Both quantitative and qualitative methods were accepted. The proficiency test was

  16. Language proficiency: Current strategies, future remedies ...

    African Journals Online (AJOL)

    Language proficiency among young South Africans is low. This is true not only of mother tongue speakers of English and Afrikaans, but also, and especially, of non-mother tongue speakers of English, among whom language proficiency levels raise serious concern. Some examples are given to illustrate the importance of ...

  17. A Contextualized Approach to Describing Oral Proficiency.

    Science.gov (United States)

    Chalhoub-Deville, Micheline

    1995-01-01

    Studies learners' second-language (L2) oral proficiency, incorporating an interview, a narration, and a read-aloud. Results show that the nature of the L2 oral construct is not constant. The article concludes that proficiency researchers should use dimensions empirically derived according to the specific elicitation task and audience. (53…

  18. Language Learning Strategy Use across Proficiency Levels

    Science.gov (United States)

    Zarei, Abbas, Ali; Baharestani, Nooshin

    2014-01-01

    To investigate the use of language learning strategies (LLS) by Iranian EFL learners across proficiency levels, a total of 180 Iranian adult female EFL learners were selected and divided into three different proficiency level groups. To collect data, Oxford's (1990) Strategy Inventory for Language Learning (SILL) was used. One-way ANOVA procedures…

  19. Avaliação da expressão tecidual do gene de reparo MLH1 e dos níveis de dano oxidativo ao DNA em doentes com câncer colorretal Evaluation of expression of mismatch repair gene MLH1 and levels of oxidative DNA damage in normal and neoplastic tissues of patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez

    2009-09-01

    form the DNA, allowing mutations in controlling genes of the cell cycle. The cells have a defense system represented by the DNA mismatch repair genes that correct the errors of matching prevent the development of DNA mutations. Few studies have evaluated the relationship between oxidative DNA damage and the tissue expression of mismatch repair genes. AIM: The aim of the present study was evaluate the levels of oxidative DNA and the tissue expression of MLH1 mismatch repair gene in the cells of normal and neoplastic colonic mucosa of patients with colorectal cancer. MATERIAL AND METHODS: Were studied 44 patients with diagnosis of colorectal adenocarcinoma. Were excluded patients with hereditary colorectal cancer, with colorectal cancer associate with inflammatory bowel diseases and those undergoing neoadjuvant radioquimiotherapy. To evaluate the levels of oxidative DNA damage was used the single cell gel electrophoresis (comet assay evaluating 100 cells obtained from normal and neoplastic tissues. For the evaluation of the tissue expression of MLH1 gene was employed the technique of polymerase chain reaction in real time (RT-PCR with primer specifically designed for MLH1 gene. The comparison among the levels of DNA oxidative stress and expression of MLH1 mismatch repair gene in normal and neoplastic tissues was done by Student t test adopting a significance level of 5% (p< 0.05. RESULTS: The levels of oxidative DNA damage in tumor tissue were significantly higher when compared to the level of the normal tissue (p = 0.0001. The tissue expression of MLH1 mismatch repair gene in tumor tissue was significantly lower when compared to normal tissue (p=0.02. CONCLUSION: The mismatch repair gene MLH1 are less expressed in tumor tissue and inversely related to levels of oxidative DNA damage.

  20. Measuring receptive collocational competence across proficiency levels

    Directory of Open Access Journals (Sweden)

    Déogratias Nizonkiza

    2015-12-01

    Full Text Available The present study investigates, (i English as Foreign Language (EFL learners’ receptive collocational knowledge growth in relation to their linguistic proficiency level; (ii how much receptive collocational knowledge is acquired as proficiency develops; and (iii the extent to which receptive knowledge of collocations of EFL learners varies across word frequency bands. A proficiency measure and a collocation test were administered to English majors at the University of Burundi. Results of the study suggest that receptive collocational competence develops alongside EFL learners’ linguistic proficiency; which lends empirical support to Gyllstad (2007, 2009 and Author (2011 among others, who reported similar findings. Furthermore, EFL learners’ collocations growth seems to be quantifiable wherein both linguistic proficiency level and word frequency occupy a crucial role. While more gains in terms of collocations that EFL learners could potentially add as a result of change in proficiency are found at lower levels of proficiency; collocations of words from more frequent word bands seem to be mastered first, and more gains are found at more frequent word bands. These results confirm earlier findings on the non-linearity nature of vocabulary growth (cf. Meara 1996 and the fundamental role played by frequency in word knowledge for vocabulary in general (Nation 1983, 1990, Nation and Beglar 2007, which are extended here to collocations knowledge.

  1. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  2. A New Tool for Assessing Mobile Device Proficiency in Older Adults: The Mobile Device Proficiency Questionnaire.

    Science.gov (United States)

    Roque, Nelson A; Boot, Walter R

    2018-02-01

    Mobile device proficiency is increasingly required to participate in society. Unfortunately, there still exists a digital divide between younger and older adults, especially with respect to mobile devices (i.e., tablet computers and smartphones). Training is an important goal to ensure that older adults can reap the benefits of these devices. However, efficient/effective training depends on the ability to gauge current proficiency levels. We developed a new scale to accurately assess the mobile device proficiency of older adults: the Mobile Device Proficiency Questionnaire (MDPQ). We present and validate the MDPQ and a short 16-question version of the MDPQ (MDPQ-16). The MDPQ, its subscales, and the MDPQ-16 were found to be highly reliable and valid measures of mobile device proficiency in a large sample. We conclude that the MDPQ and MDPQ-16 may serve as useful tools for facilitating mobile device training of older adults and measuring mobile device proficiency for research purposes.

  3. A role for MLH3 in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

    2001-01-01

    We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,

  4. ORIGINAL ARTICLES Colorectal cancer in South Africa: A heritable ...

    African Journals Online (AJOL)

    in the DNA mismatch repair genes hMLH1 and hMSH2, and less frequently hMSH6 and PMS2, leading to the rapid development of neoplasms ..... nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer.

  5. Candidate driver genes in microsatellite-unstable colorectal cancer

    DEFF Research Database (Denmark)

    Alhopuro, Pia; Sammalkorpi, Heli; Niittymäki, Iina

    2012-01-01

    Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers...

  6. Loss of heterozygosity in colorectal cancer | Ozaslan | African ...

    African Journals Online (AJOL)

    Colorectal cancer (CRC) is one of the most common malignancies in the world. The development and progression of CRC is a multistep process, which involves many dietary and environmental factors. A great number of oncogenes, tumour suppressor genes and DNA repair genes contribute to molecular and biological ...

  7. A Database to Support the Interpretation of Human Mismatch Repair Gene Variants

    NARCIS (Netherlands)

    Ou, Jianghua; Niessen, Renee C.; Vonk, Jan; Westers, Helga; Hofstra, Robert M. W.; Sijmons, Rolf H.

    Germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 can cause Lynch syndrome. This syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominantly-inherited disorder predominantly characterized by colorectal and endometrial cancer.

  8. Genetic etiology of hereditary colorectal cancer: new mechanisms and advanced mutation detection techniques

    NARCIS (Netherlands)

    Gazzoli, I.

    2006-01-01

    The human DNA mismatch repair (MMR) system functions to repair mispaired bases in DNA that result from DNA replication errors and thereby prevents the accumulation of mutations due to such replication errors. Hereditary nonpolyposis colorectal cancer (HNPCC), the most common form of inherited colon

  9. Developing Adaptive Proficiency in Special Forces Officers

    National Research Council Canada - National Science Library

    White, Susan S; Mueller-Hanson, Rose A; Dorsey, David W; Pulakos, Elaine D; Wisecarver, Michelle M; Deagle, Edwin A., III; Mendini, Kip G

    2005-01-01

    Adaptive proficiency is critical for operating in the dynamic Special Forces (SF) mission environment and a recent focus on this requirement has resulted in a greater emphasis on adaptability in current training for SF...

  10. Repair of near-UV (365nm or 313 nm) induced DNA strand breaks

    International Nuclear Information System (INIS)

    Miguel, A.G.

    1981-01-01

    The action of near-UV (365 nm or 313 nm) radiation in cellular inactivaton (biological measurements) and induction and repair of breaks (physical measurements) is studied in repair proficient strain and in pol A, rec A and uvr A deficient strains of Escherichia coli K-12. (M.A.C.) [pt

  11. Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Petersen, Sanne M; Dandanell, Mette; Rasmussen, Lene J

    2013-01-01

    Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomi...

  12. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Colorectal Cancer: A Personal Journey Past Issues / Summer 2016 Table ... Carmen Marc Valvo is an outspoken voice for colorectal cancer screening. Photo Courtesy of: Phil Fisch Photography Designer ...

  13. Constitutional mismatch repair deficiency syndrome: Do we know it?

    Science.gov (United States)

    Ramachandra, C; Challa, Vasu Reddy; Shetty, Rachan

    2014-04-01

    Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis-1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

  14. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  15. Unique Contributions of Maternal Reading Proficiency to Predicting Children's Preschool Receptive Vocabulary and Reading Proficiency

    Science.gov (United States)

    Phillips, Linda M.; Norris, Stephen P.; Hayward, Denyse V.; Lovell, Meridith A.

    2017-01-01

    This study investigated whether mothers' measured reading proficiency and their educational level predict, over and above each other, their children's receptive vocabulary and reading proficiency when confounding factors of speaking a minority language, ethnicity, number of children in the family, and marital and employment status are controlled.…

  16. Assessment of Preschoolers' Gross Motor Proficiency: Revisiting Bruininks-Oseretsky Test of Motor Proficiency

    Science.gov (United States)

    Lam, Hazel Mei Yung

    2011-01-01

    Literature reveals that there are very few validated motor proficiency tests for young children. According to Gallahue and Ozmun, the Bruininks-Oseretsky Test of Motor Proficiency is a valid test. However, manipulative skills, which are classified as gross motor skills by most motor development specialists, are only tested in the Upper Limb…

  17. Epigenetics and Colorectal Cancer

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

  18. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  19. Meningocele repair

    Science.gov (United States)

    ... is surgery to repair birth defects of the spine and spinal membranes. Meningocele and myelomeningocele ... is covered by a sterile dressing. Your child may then be transferred to a neonatal intensive ...

  20. Beyond English Proficiency: Rethinking Immigrant Integration

    Science.gov (United States)

    Akresh, Ilana Redstone; Massey, Douglas S.; Frank, Reanne

    2014-01-01

    We develop and test a conceptual model of English language acquisition and the strength of the latter in predicting social and cultural assimilation. We present evidence that the path to English proficiency begins with exposure to English in the home country and on prior U.S. trips. English proficiency, then, has direct links to the intermediate migration outcomes of occupational status in the U.S., the amount of time in the U.S. since the most recent trip, and the co-ethnic residential context in the U.S. In turn, pre-migration characteristics and the intermediate characteristics work in tandem with English proficiency to determine social assimilation in the U.S., while cultural assimilation is primarily determined by pre-migration habits. A shift in focus to English use is desirable in studies of immigrant integration. PMID:24576636

  1. Gamma-ray induced inhibition of DNA synthesis in ataxia telangiectasia fibroblasts is a function of excision repair capacity

    International Nuclear Information System (INIS)

    Smith, P.J.; Paterson, M.C.

    1980-01-01

    The extent of the deficiency in γ-ray induced DNA repair synthesis in an ataxia telangiectasia (AT) human fibroblast strain was found to show no oxygen enhancement, consistent with a defect in the repair of base damage. Repair deficiency, but not repair proficiency, in AT cells was accompanied by a lack of inhibition of DNA synthesis by either γ-rays or the radiomimetic drug bleomycin. Experiments with 4-nitroquinoline 1-oxide indicated that lack of inhibition was specific for radiogenic-type damage. Thus excision repair, perhaps by DNA strand incision or chromatin modification, appears to halt replicon initiation in irradiated repair proficient cells whereas in repair defective AT strains this putatively important biological function is inoperative

  2. Synchronous colorectal liver metastases

    NARCIS (Netherlands)

    A.E.M. van der Pool (Anne)

    2011-01-01

    textabstractColorectal cancer is one of the most common malignancies worldwide and ranks second in cancer-related deaths in many parts of the Western world. Once in the lymph or blood vessels, colorectal cancer can quickly spread and the liver is known to be a favourable site for metastases. The

  3. [Obesity and colorectal cancer].

    Science.gov (United States)

    Na, Soo-Young; Myung, Seung-Jae

    2012-01-01

    Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

  4. Diagnosing lynch syndrome in absence of colorectal cancer.

    Science.gov (United States)

    Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

    2012-11-01

    There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

  5. Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach

    Directory of Open Access Journals (Sweden)

    Timothy A. Rockall

    2011-03-01

    Full Text Available It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-β.

  6. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome

    NARCIS (Netherlands)

    Westdorp, Harm; Kolders, Sigrid; Hoogerbrugge, Nicoline; de Vries, I Jolanda M; Jongmans, Marjolijn C.J.; Schreibelt, Gerty

    2017-01-01

    Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations

  7. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

    In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin

  8. The correlation between motor proficiency and physical activity in ...

    African Journals Online (AJOL)

    Lizl-Louise van Niekerk

    eOseretsky Test of Motor Proficiency 2 (BOT-2) for motor proficiency, and the International. Physical Activity ... Pienaar, 2007; Malina, 2012). ..... sults of Hardy, Reinten-Reynolds, Espinel, Zask, and Okely .... Journal of Psychiatric and Mental.

  9. A 30-Year-Old Man with Three Primary Malignancies: A Case of Constitutional Mismatch Repair Deficiency

    OpenAIRE

    Rengifo-Cam, William; Jasperson, Kory; Garrido-Laguna, Ignacio; Colman, Howard; Scaife, Courtney; Samowitz, Wade; Samadder, N. Jewel

    2017-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which clinical manifestations, genetic screening, and cancer prevention strategies are limited. We report a case of CMMRD presenting with metachronous colorectal cancer and brain cancer. Oncologists and gastroenterologists should be aware of the CMMRD syndrome as a rare cause of very early-onset colorectal cancer.

  10. A 30-Year-Old Man with Three Primary Malignancies: A Case of Constitutional Mismatch Repair Deficiency.

    Science.gov (United States)

    Rengifo-Cam, William; Jasperson, Kory; Garrido-Laguna, Ignacio; Colman, Howard; Scaife, Courtney; Samowitz, Wade; Samadder, N Jewel

    2017-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which clinical manifestations, genetic screening, and cancer prevention strategies are limited. We report a case of CMMRD presenting with metachronous colorectal cancer and brain cancer. Oncologists and gastroenterologists should be aware of the CMMRD syndrome as a rare cause of very early-onset colorectal cancer.

  11. Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

    Science.gov (United States)

    Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

    2008-02-15

    Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

  12. From Universal Access to Universal Proficiency.

    Science.gov (United States)

    Lewis, Anne C.

    2003-01-01

    Panel of five education experts--Elliot Eisner, John Goodlad, Patricia Graham, Phillip Schlechty, and Warren Simons--answer questions related to recent school reform efforts, such as the No Child Left Behind Act, aimed at achieving universal educational proficiency. (PKP)

  13. Measuring receptive collocational competence across proficiency ...

    African Journals Online (AJOL)

    Kate H

    frequency bands. A proficiency measure and a collocation test were administered to English ... battery may negatively impact the test-takers' performance. ..... examples. The major finding is that raising learners' awareness constitutes the best way forward ..... Amsterdam: John Benjamins Publishing Company. Green, R.

  14. Foreign language proficiency and working memory capacity

    NARCIS (Netherlands)

    Noort, M.W.M.L. van den; Bosch, M.P.C.; Hugdahl, K.

    2006-01-01

    In this study, the hypothesis that working memory capacity interacts with (foreign) language proficiency was tested on multilinguals, who were native (L1) Dutch speakers, were fluent in their second (L2) language, German, and had recently started the acquisition of their third (L3) language,

  15. Proficiency test for paracitides in salmon muscle

    NARCIS (Netherlands)

    Elbers, I.J.W.

    2012-01-01

    The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of parasiticides in salmon muscle. This study also provided an evaluation of the methods applied for the quantitative analysis of parasiticides in salmon muscle.

  16. Proficiency Testing in Nondestructive Testing (NDT)

    International Nuclear Information System (INIS)

    Amry Amin Abbas; Suhairy Sani; Mohamad Pauzi Ismail; Abd Nassir Ibrahim

    2014-01-01

    Department of Standard Malaysia (DSM) launched myPTP programme on 31 December 2013 in accordance to ISO/IC 17043. The standard states the requirements for Proficiency Testing. The provider of these services is called Proficiency Testing Provider (PTP). The role of PTP is to compare the proficiency level between inspection bodies or laboratories. With the assistance of expert panel, the PTP will determine the assigned value as reference to be compared to the values obtained from the inspection bodies or laboratories. Quality wise, this services is important as participation will improve wuality of the inspection quality continuously and increase confidence level of client and improve safety level. Requirement of PT in NDT is mentioned in SC1.5- Specific Criteria for Accreditation of Mechanical Testing and Non-Destructive Testing (NDT) for MS ISO/IEC17025 and MTR2- MIBAS Technical Requirements for Accreditation of NDT. This paper explains and discusses the result of this proficiency test done on a number of NDT companies that participated. (author)

  17. It Really Works: Cultural Communication Proficiency.

    Science.gov (United States)

    Bennett, Ruth, Ed.

    This paper describes the cultural communication proficiency method of indigenous language instruction, developed at Humboldt State University's Center for Indian Community Development (California), and demonstrates the method with five Hupa lesson plans. The method is based on three principles: that Native American students learn by doing, learn…

  18. The Oral Proficiency Interview: A Research Agenda

    Science.gov (United States)

    Chalhoub-Deville, Micheline; Fulcher, Glenn

    2003-01-01

    Many researchers and practitioners maintain that ACTFL's efforts to improve instructional practices and promote proficiency assessments tied to descriptors of what learners can do in real life have contributed significantly to second language teaching and testing. Similar endeavors in the area of research, however, are critically needed. Focusing…

  19. 14 CFR 61.98 - Flight proficiency.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight proficiency. 61.98 Section 61.98 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN...) Navigation; (viii) Slow flight and stalls; (ix) Emergency operations; and (x) Postflight procedures. (2) For...

  20. 14 CFR 61.107 - Flight proficiency.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight proficiency. 61.107 Section 61.107 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN... reference maneuvers; (vii) Navigation; (viii) Slow flight and stalls; (ix) Basic instrument maneuvers; (x...

  1. 14 CFR 61.127 - Flight proficiency.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight proficiency. 61.127 Section 61.127 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN...; (x) High-altitude operations; and (xi) Postflight procedures. (2) For an airplane category rating...

  2. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  3. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

    2012-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

  4. 34 CFR 300.27 - Limited English proficient.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Limited English proficient. 300.27 Section 300.27... CHILDREN WITH DISABILITIES General Definitions Used in This Part § 300.27 Limited English proficient. Limited English proficient has the meaning given the term in section 9101(25) of the ESEA. (Authority: 20...

  5. A Validation Study of the Student Oral Proficiency Assessment (SOPA).

    Science.gov (United States)

    Thompson, Lynn E.; Kenyon, Dorry M.; Rhodes, Nancy C.

    This study validated the Student Oral Proficiency Assessment (SOPA), an oral proficiency instrument designed for students in elementary foreign language programs. Elementary students who were tested with the SOPA were also administered other instruments designed to measure proficiency. These instruments included the Stanford Foreign Language Oral…

  6. Proverb Comprehension as a Function of Reading Proficiency in Preadolescents.

    Science.gov (United States)

    Nippold, Marilyn A.; Allen, Melissa M.; Kirsch, Dixon I.

    2001-01-01

    Proverb comprehension through reading was examined in 42 preadolescent students, 24 of whom were identified as "proficient readers," and 18 as "less proficient readers." Comprehension on both unfamiliar concrete and abstract proverbs was associated with reading proficiency, word knowledge, and analogical reasoning. (Contains references.)…

  7. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  8. Screening for colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  9. Repair process and a repaired component

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, III, Herbert Chidsey; Simpson, Stanley F.

    2018-02-20

    Matrix composite component repair processes are disclosed. The matrix composite repair process includes applying a repair material to a matrix composite component, securing the repair material to the matrix composite component with an external securing mechanism and curing the repair material to bond the repair material to the matrix composite component during the securing by the external securing mechanism. The matrix composite component is selected from the group consisting of a ceramic matrix composite, a polymer matrix composite, and a metal matrix composite. In another embodiment, the repair process includes applying a partially-cured repair material to a matrix composite component, and curing the repair material to bond the repair material to the matrix composite component, an external securing mechanism securing the repair material throughout a curing period, In another embodiment, the external securing mechanism is consumed or decomposed during the repair process.

  10. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers : A study of hereditary nonpolyposis colorectal cancer families

    NARCIS (Netherlands)

    Vasen, HFA; Stormorken, A; Menko, FH; Nagengast, FM; Kleibeuker, JH; Griffioen, G; Taal, BG; Moller, P; Wijnen, JT

    2001-01-01

    Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

  11. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

    NARCIS (Netherlands)

    Vasen, H.F.; Stormorken, A.; Menko, F.H.; Nagengast, F.M.; Kleibeuker, J.H.; Griffioen, G.; Taal, B.G.; Moller, P.; Wijnen, J.T.

    2001-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

  12. Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

    Science.gov (United States)

    Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

    2013-11-01

    CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

  13. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  14. Colorectal cancer associated with abdominal aortic aneurysm: results of EVAR followed by colectomy.

    Science.gov (United States)

    Illuminati, Giulio; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

    2013-01-01

    The association of colorectal cancer and abdominal aortic aneurysm (AAA) is infrequent but poses special problems of priority of treatment under elective circumstances. The purpose of this study was to retrospectively evaluate the outcome of 16 consecutive patients undergoing endovascular aneurysm repair (EVAR) followed by colectomy. Operative mortality was nil. Operative morbidity included two transient rise of serum creatinine level and one extraperitoneal anastomotic leakage which evolved favourably with conservative treatment. EVAR allowed a very short delay of treatment of colorectal cancer after aneurysm repair, minimizing operative complications.

  15. Turbine repair process, repaired coating, and repaired turbine component

    Science.gov (United States)

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  16. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship........59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...

  17. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  18. Colorectal cancer screening

    OpenAIRE

    Plumb, A. A.; Halligan, S.

    2015-01-01

    Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...

  19. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.

  20. Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

    Directory of Open Access Journals (Sweden)

    Giulia Magnani

    2015-01-01

    Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

  1. Evaluation of Mycology Laboratory Proficiency Testing

    OpenAIRE

    Reilly, Andrew A.; Salkin, Ira F.; McGinnis, Michael R.; Gromadzki, Sally; Pasarell, Lester; Kemna, Maggi; Higgins, Nancy; Salfinger, Max

    1999-01-01

    Changes over the last decade in overt proficiency testing (OPT) regulations have been ostensibly directed at improving laboratory performance on patient samples. However, the overt (unblinded) format of the tests and regulatory penalties associated with incorrect values allow and encourage laboratorians to take extra precautions with OPT analytes. As a result OPT may measure optimal laboratory performance instead of the intended target of typical performance attained during routine patient te...

  2. More Proficient vs. Less Proficient EFL Learners’ Perceptions of Teachers ‘Motivation Raising Strategies

    Directory of Open Access Journals (Sweden)

    Nasrin Yousefi

    2022-09-01

    Full Text Available Motivation raising strategies are frequently used in English as a Foreign Language (EFL classes; nevertheless, learners’ perceptions of such strategies used by language teachers have not sufficiently been explored. Also, there are not enough studies on differences and similarities between more and less proficient EFL learners regarding this issue. To scrutinize this topic, a groups of more (No=50 and less proficient EFL learners (No=50 participated in this study by completing to a validated, researcher-made questionnaire with a five-point Likert type format. Non-parametric Mann-Whiteny U test was run in the SPSS ver. 23 to check the differences between the two groups. The results of the study verified that, regardless of each individual scale in the utilized questionnaire, overall, the more proficient ones manifested significantly less perceptions on teachers’ motivation raising strategies based on the total estimated mean ranks compared with the less proficient learners.  However, within the surveyed scales, only in the classroom atmosphere scale, the results showed that the less proficient learners were more mindful of teacher strategies for motivation raising. The findings from this study have implications for motivation raising strategy instructions for a language classroom.

  3. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  4. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...

  5. RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.

    Science.gov (United States)

    Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J

    2018-01-01

    The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers

  6. Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

    Science.gov (United States)

    Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

    2015-02-01

    The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of ... at the National Cancer Institute, shared developments in colorectal cancer screening methods with NIH MedlinePlus magazine. What ...

  8. Improving Quality in Colorectal Surgery

    NARCIS (Netherlands)

    J.C. Slieker (Juliette)

    2014-01-01

    markdownabstract__Abstract__ Colorectal surgery is an important aspect of our current health system, due to the high incidence of colorectal cancer combined with an ageing population, improved long-term outcomes after colorectal surgery, and the perfectioning of the operative and postoperative

  9. Transfer of Chinese hamster DNA repair gene(s) into repair-deficient human cells (Xeroderma pigmentosum)

    International Nuclear Information System (INIS)

    Karentz, D.; Cleaver, J.E.

    1985-01-01

    Transfer of repair genes by DNA transfection into repair-deficient Xeroderma pigmentosum (XP) cells has thus far been unsuccessful, presenting an obstacle to cloning XP genes. The authors chose an indirect route to transfer repair genes in chromosome fragments. DNA repair-competent (UV resistant) hybrid cell lines were established by PEG-mediated fusions of DNA repair-deficient (UV sensitive) human fibroblasts (XP12RO) with wild type Chinese hamster (CHO) cells (AA8). CHO cells were exposed to 5 Krad X-rays prior to fusions, predisposing hybrid cells to lose CHO chromosome fragments preferentially. Repair-competent hybrids were selected by periodic exposures to UV light. Secondary and tertiary hybrid cell lines were developed by fusion of X-irradiated hybrids to XP12RO. The hybrid cell lines exhibit resistance to UV that is comparable to that of CHO cells and they are proficient at repair replication after UV exposure. Whole cell DNA-DNA hybridizations indicate that the hybrids have greater homology to CHO DNA than is evident between XP12RO and CHO. These observations indicate that CHO DNA sequences which can function in repair of UV-damaged DNA in human cells have been transferred into the genome of the repair-deficient XP12RO cells

  10. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a w......Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  11. Proficiency and sentence constraint effects on second language word learning.

    Science.gov (United States)

    Ma, Tengfei; Chen, Baoguo; Lu, Chunming; Dunlap, Susan

    2015-07-01

    This paper presents an experiment that investigated the effects of L2 proficiency and sentence constraint on semantic processing of unknown L2 words (pseudowords). All participants were Chinese native speakers who learned English as a second language. In the experiment, we used a whole sentence presentation paradigm with a delayed semantic relatedness judgment task. Both higher and lower-proficiency L2 learners could make use of the high-constraint sentence context to judge the meaning of novel pseudowords, and higher-proficiency L2 learners outperformed lower-proficiency L2 learners in all conditions. These results demonstrate that both L2 proficiency and sentence constraint affect subsequent word learning among second language learners. We extended L2 word learning into a sentence context, replicated the sentence constraint effects previously found among native speakers, and found proficiency effects in L2 word learning. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

    Science.gov (United States)

    Win, Aung Ko; Jenkins, Mark A.; Dowty, James G.; Antoniou, Antonis C.; Lee, Andrew; Giles, Graham G.; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Ahnen, Dennis J.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Haile, Robert W.; Potter, John D.; Zheng, Yingye; Lindor, Noralane M.; Newcomb, Polly A.; Hopper, John L.; MacInnis, Robert J.

    2016-01-01

    Background While high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. Methods We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the USA, Canada and Australia and screened probands for mutations in mismatch repair genes and MUTYH. We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband’s age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of and hazard ratio for unidentified major gene mutations, and the variance of the residual polygenic component. Results We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1= 1 in 1946, MSH2= 1 in 2841, MSH6= 1 in 758, PMS2= 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30–50% after allowing for unidentified major genes and decreased from 3.3 for age colorectal cancer. Impact Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. PMID:27799157

  13. Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells

    DEFF Research Database (Denmark)

    Akbari, Mansour; Otterlei, Marit; Pena Diaz, Javier

    2004-01-01

    Nuclear uracil-DNA glycosylase UNG2 has an established role in repair of U/A pairs resulting from misincorporation of dUMP during replication. In antigen-stimulated B-lymphocytes UNG2 removes uracil from U/G mispairs as part of somatic hypermutation and class switch recombination processes. Using......, PCNA and DNA ligase, the latter detected as activity. Short-patch repair was the predominant mechanism both in extracts and UNG2-ARC from proliferating and less BER-proficient growth-arrested cells. Repair of U/G mispairs and U/A pairs was completely inhibited by neutralizing UNG...

  14. What Is Lexical Proficiency? Some Answers from Computational Models of Speech Data

    Science.gov (United States)

    Crossley, Scott A.; Salsbury, Tom; McNamara, Danielle S.; Jarvis, Scott

    2011-01-01

    Lexical proficiency, as a cognitive construct, is poorly understood. However, lexical proficiency is an important element of language proficiency and fluency, especially for second language (L2) learners. Lexical proficiency is also an important attribute of L2 academic achievement. Generally speaking, lexical proficiency comprises breadth of…

  15. Differences in Less Proficient and More Proficient ESL College Writing in the Philippine Setting

    Science.gov (United States)

    Gustilo, Leah E.

    2016-01-01

    The present study aimed at characterizing what skilled or more proficient ESL college writing is in the Philippine setting through a contrastive analysis of three groups of variables identified from previous studies: resources, processes, and performance of ESL writers. Based on Chenoweth and Hayes' (2001; 2003) framework, the resource level…

  16. Developing English Writing Proficiency in Limited English Proficient College Students through Cooperative Learning Strategies.

    Science.gov (United States)

    Gooden-Jones, Epsey M.; Carrasquillo, Angela L.

    A study followed ten limited-English-proficient (LEP) community college students who were taught English largely using a cooperative learning approach. For four months, the students worked together using brainstorming techniques and collaborative reading and writing tasks. Task emphasis was on development of thinking skills through collaboration…

  17. MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

    Science.gov (United States)

    Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2016-10-01

    Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (PMLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

  18. Colorectal cancer screening

    OpenAIRE

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  19. Frequency of intrachromosomal homologous recombination induced by UV radiation in normally repairing and excision repair-deficient human cells

    International Nuclear Information System (INIS)

    Tsujimura, T.; Maher, V.M.; McCormick, J.J.; Godwin, A.R.; Liskay, R.M.

    1990-01-01

    To investigate the role of DNA damage and nucleotide excision repair in intrachromosomal homologous recombination, a plasmid containing duplicated copies of the gene coding for hygromycin resistance was introduced into the genome of a repair-proficient human cell line, KMST-6, and two repair-deficient lines, XP2OS(SV) from xeroderma pigmentosum complementation group A and XP2YO(SV) from complementation group F. Neither hygromycin-resistance gene codes for a functional enzyme because each contains an insertion/deletion mutation at a unique site, but recombination between the two defective genes can yield hygromycin-resistant cells. The rates of spontaneous recombination in normal and xeroderma pigmentosum cell strains containing the recombination substrate were found to be similar. The frequency of UV-induced recombination was determined for three of these cell strains. At low doses, the group A cell strain and the group F cell strain showed a significant increase in frequency of recombinants. The repair-proficient cell strain required 10-to 20-fold higher doses of UV to exhibit comparable increases in frequency of recombinants. These results suggest that unexcised DNA damage, rather than the excision repair process per se, stimulates such recombination

  20. Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

    NARCIS (Netherlands)

    Brouwer, Jesca G.M.; Makama, Maureen; Woudenbergh, Van Geertruida J.; Vasen, Hans F.A.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Kampman, Ellen; Duijnhoven, Van Fränzel J.B.

    2017-01-01

    Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.

  1. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome : a cohort study

    NARCIS (Netherlands)

    Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.

    Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of

  2. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  3. Dietary patterns and colorectal adenomas in Lynch syndrome: the GEOLynch cohort study.

    Science.gov (United States)

    Botma, Akke; Vasen, Hans F A; van Duijnhoven, Fränzel J B; Kleibeuker, Jan H; Nagengast, Fokko M; Kampman, Ellen

    2013-02-01

    Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in LS patients was assessed. In the GEOLynch cohort of 486 persons with LS, dietary information was collected, using a food frequency questionnaire. Dietary pattern scores were obtained by principal components analysis. Hazard ratios (HR) between dietary patterns and colorectal adenomas were calculated using Cox regression models. Robust sandwich variance estimates were used to control for dependency within families. Final models were adjusted for age, sex, smoking habits, colorectal adenoma history, and extent of colon resection. During a median follow-up of 20 months, colorectal adenomas were detected in 58 persons. Four dietary patterns were identified: a "Prudent," "Meat," "Snack," and "Cosmopolitan" pattern. Individuals within the highest tertile of the "Prudent" pattern had a HR of 0.73 (95% confidence interval [CI], 0.32-1.66) for colorectal adenomas, compared with the lowest tertile. Those with high "Meat" pattern scores had a HR of 1.70 (95% CI, 0.83-3.52). A high "Snack" pattern was associated with an increased risk of colorectal adenomas (HR, 2.16; 95% CI, 1.03-4.49). A HR of 1.25 (95% CI, 0.61-2.55) was observed for persons in the highest tertile of the "Cosmopolitan" pattern. These findings suggest that dietary patterns may be associated with development of colorectal adenoma in patients with Lynch syndrome. The directions of these findings are corroborative with those observed in studies investigating sporadic colorectal cancer. Copyright © 2012 American Cancer Society.

  4. Evaluation of Mycology Laboratory Proficiency Testing

    Science.gov (United States)

    Reilly, Andrew A.; Salkin, Ira F.; McGinnis, Michael R.; Gromadzki, Sally; Pasarell, Lester; Kemna, Maggi; Higgins, Nancy; Salfinger, Max

    1999-01-01

    Changes over the last decade in overt proficiency testing (OPT) regulations have been ostensibly directed at improving laboratory performance on patient samples. However, the overt (unblinded) format of the tests and regulatory penalties associated with incorrect values allow and encourage laboratorians to take extra precautions with OPT analytes. As a result OPT may measure optimal laboratory performance instead of the intended target of typical performance attained during routine patient testing. This study addresses this issue by evaluating medical mycology OPT and comparing its fungal specimen identification error rates to those obtained in a covert (blinded) proficiency testing (CPT) program. Identifications from 188 laboratories participating in the New York State mycology OPT from 1982 to 1994 were compared with the identifications of the same fungi recovered from patient specimens in 1989 and 1994 as part of the routine procedures of 88 of these laboratories. The consistency in the identification of OPT specimens was sufficient to make accurate predictions of OPT error rates. However, while the error rates in OPT and CPT were similar for Candida albicans, significantly higher error rates were found in CPT for Candida tropicalis, Candida glabrata, and other common pathogenic fungi. These differences may, in part, be due to OPT’s use of ideal organism representatives cultured under optimum growth conditions. This difference, as well as the organism-dependent error rate differences, reflects the limitations of OPT as a means of assessing the quality of routine laboratory performance in medical mycology. PMID:10364601

  5. Proficiency test in the accreditation system

    International Nuclear Information System (INIS)

    Legarda, F.; Herranz, M.; Idoeta, R.

    2008-01-01

    In the accreditation process of a radioactivity measurements laboratory, according to ISO standard 17025, proficiency tests play a fundamental role. These PTs constitute an irreplaceable tool for the validation of measuring methods. In the case of Spain, ENAC, which is the Spanish accreditation national body, requires that the laboratory has to take part in a PT for each one of the accredited measuring methods in the period of time between two reassessments of the accreditation, what happens every 4-5 years. In specific areas of determination procedures, among which radioactive measurements could be included, the number of methods which can be accredited is very large. The purpose of the present work is to establish a classification into families of the different radioactivity measurement procedures, as well as to establish complementary actions that guarantee that carrying out periodically proficiency-tests on any of the included procedures in each family, every measurement procedure include in that family is controlled, complying with the criteria established by ENAC

  6. DNA repair , cell repair and radiosensitivity

    International Nuclear Information System (INIS)

    Zhestyanikov, V.D.

    1983-01-01

    Data obtained in laboratory of radiation cytology and literature data testifying to a considerable role of DNA repair in cell sensitivity to radiation and chemical DNA-tropic agents have been considered. Data pointing to the probability of contribution of inducible repair of DNA into plant cells sensitivity to X-rays are obtained. Certain violations of DNA repair do not result in the increase of radiosensitivity. It is assumed that in the cases unknown mechanisms of DNA repair operate

  7. 76 FR 81958 - Notice of Submission of Proposed Information Collection to OMB; Limited English Proficiency...

    Science.gov (United States)

    2011-12-29

    ... Proposed Information Collection to OMB; Limited English Proficiency Initiative (LEPI) Program AGENCY... that support the assistance of persons with limited English proficiency in utilizing the services...: Limited English Proficiency Initiative (LEPI) Program. OMB Approval Number: 2529-0051. Form Numbers...

  8. Does sex of the patient play a role in survival for MSI colorectal cancer?

    Directory of Open Access Journals (Sweden)

    Adrian Tulin

    2018-04-01

    Full Text Available Microsatellite instability (MSI is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center study which included 122 colorectal cancer patients who were tested for MSI using immunohistochemistry. The trial included patients with stage II to IV colorectal cancer, treated in the Prof. Dr. Agrippa Ionescu Emergency Hospital, Bucharest, Romania. Follow-up data were collected during a 24-month period. The study attempted to determine whether differences exist in overall survival for MSI (microsatellite instability vs. MSS (microsatellite stable colorectal cancer and to ascertain whether sex of the patient influences prognosis in MSI patients, irrespective of stage or treatment. Results demonstrated no significant differences in survival for MSI vs MSS colorectal patients, and patients’ gender proved not to influence the outcome in MSI patients.

  9. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  10. Teaching English through English: Proficiency, Pedagogy and Performance

    Science.gov (United States)

    Richards, Jack C.

    2017-01-01

    Most of the world's English language teachers speak English as a second or third language rather than as their first language. For many, their level of proficiency in English may not reach benchmarks established by their employers, raising the issue that is the focus of this article, namely, what kind of proficiency in English is necessary to be…

  11. The Nevada Proficiency Examination Program: Evaluating the Writing Samples.

    Science.gov (United States)

    Howard, Edward H.

    Writing tests are part of the mandated statewide proficiency examination in Nevada. The ninth-grade screening test and the eleventh-grade diploma-certifying test require that a student write a paragraph and a business letter, each on an assigned topic and each at an acceptable level of proficiency. Pilot tests, extended discussion, and statistical…

  12. Reconnecting Proficiency, Literacy, and Culture: From Theory to Practice

    Science.gov (United States)

    Warford, Mark K.; White, William L.

    2012-01-01

    What does it mean to capably communicate across languages? This article introduces two theoretical models and a lesson plan format designed to facilitate the integration of proficiency, literacy, and culture teaching in foreign language teaching. The Second Symbolic Competencies Model configures proficiency and literacy as subordinate clusters of…

  13. 5 CFR 9901.364 - Foreign language proficiency pay.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Foreign language proficiency pay. 9901... NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Pay and Pay Administration Premium Pay § 9901.364 Foreign language proficiency pay. (a) General provisions. (1) This section applies to employees who may be paid...

  14. Proficiency testing for sensory profile panels : measuring panel performance

    NARCIS (Netherlands)

    Mcewan, J.A.; Hunter, E.A.; Gemert, L.J. van; Lea, P.

    2002-01-01

    Proficiency testing in sensory analysis is an important step towards demonstrating that results from one sensory panel are consistent with the results of other sensory panels. The uniqueness of sensory analysis poses some specific problems for measuring the proficiency of the human instrument

  15. English Proficiency and Participation in Online Discussion for Learning

    Science.gov (United States)

    Leung, Steve

    2013-01-01

    Does English proficiency affect participation in online discussion? This study polled 14 students from a postgraduate online course that require online discussion. The students are divided into groups according to their home language spoken and self-assessed English proficiency, and measure against their participation level in the required…

  16. Proficiency test for tropane alkaloids in food en feed

    NARCIS (Netherlands)

    Pereboom-de Fauw, D.P.K.H.; Elbers, I.J.W.; Mulder, P.P.J.; Nijs, de W.C.M.

    2014-01-01

    Proficiency testing is conducted to provide laboratories with a powerful tool to evaluate and demonstrate the reliability of the data that are produced. Next to validation and accreditation, proficiency testing is an important requirement of the EU Additional Measures Directive 93/99/EEC [1] and is

  17. The correlation between motor proficiency and physical activity in ...

    African Journals Online (AJOL)

    Background: One of the risks associated with low physical activity levels is the insufficient development of motor proficiency, which in turn has an impact on participation in physical activity and sport during adolescence. Objectives: To determine the relationship between motor proficiency and physical activity levels in ...

  18. Proficiency test for heavy metals in compound feed

    NARCIS (Netherlands)

    Pereboom, D.P.K.H.; Elbers, I.J.W.; Jong, de J.; Lee, van der M.K.; Nijs, de W.C.M.

    2016-01-01

    The here described proficiency test for heavy metals in compound feed was organised by RIKILT, Wageningen UR in accordance with ISO 17043. RIKILT Wageningen UR has an ISO/IEC 17043 accreditation for proficiency tests of residues in products of animal origin. However, this specific test is not part

  19. Radioimmunodetection of colorectal cancer

    International Nuclear Information System (INIS)

    Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

    1980-01-01

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131 I at a total dose of at least 1.0 μCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131 I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131 I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures

  20. Effects of post-treatment incubation on recombinogenesis in incision-proficient and incision-deficient strains of saccharomyces cerevisiae, 2

    International Nuclear Information System (INIS)

    Saeki, Tetsuya; Machida, Isamu

    1991-01-01

    After the photoaddition of mono- and bifunctional furocoumarins to G1 phase cells, most gene conversion and crossing-over occurred without post-irradiation incubation of these cells in incision-proficient strains. In contrast, incision-deficient cells showed marked induction of both recombinational events only after treated cells had been incubated for several hours before selection. These results indicate that when furocoumarins are photoadded to G1 cells, initiation of recombinational events occurs during the same G1 phase in the incision-proficient cells; whereas, it occurs only after post-irradiation DNA replication in incision-deficient cells. The action of the PSO2 gene product specific for the repair of DNA crosslinks in recombination induction is discussed and compared to the actions of the excision repair genes RAD1 and RAD2. (author)

  1. The Rating of Direct and Semi-Direct Oral Proficiency Interviews: Comparing Performance at Lower Proficiency Levels.

    Science.gov (United States)

    Kenyon, Dorry M.; Tschirner, Erwin

    2000-01-01

    Reports on a study comparing student performances and test reliabilities for the German Speaking Test, a semi-direct tape-mediated oral proficiency test (GST) developed by the Center for Applied Linguistics, and the American Council on the Teaching of Foreign Languages Oral Proficiency Interviews. (Author/VWL)

  2. Microbiota, Inflammation and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cécily Lucas

    2017-06-01

    Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.

  3. Intrabilary obstruction by colorectal metastases

    OpenAIRE

    Traeger, Luke; Kiroff, George

    2018-01-01

    Abstract Intrabiliary colorectal metastases are rare. We present a case of an 84-year-old man who developed obstructive jaundice secondary to intrabiliary growth of colorectal metastases. The patient presented with three weeks of jaundice and significant weight loss in the preceding months. The patient’s background included metastatic colorectal carcinoma, with a previous right hemicolectomy and left hepatectomy for liver metastases. A MRCP showed an obstruction of the biliary tract transitio...

  4. Proficiency-based cervical cancer brachytherapy training.

    Science.gov (United States)

    Zhao, Sherry; Francis, Louise; Todor, Dorin; Fields, Emma C

    2018-04-25

    Although brachytherapy increases the local control rate for cervical cancer, there has been a progressive decline in its use. Furthermore, the training among residency programs for gynecologic brachytherapy varies considerably, with some residents receiving little to no training. This trend is especially concerning given the association between poor applicator placement and decline in local control. Considering the success of proficiency-based training in other procedural specialties, we developed and implemented a proficiency-based cervical brachytherapy training curriculum for our residents. Each resident placed tandem and ovoid applicators with attending guidance and again alone 2 weeks later using a pelvic model that was modified to allow for cervical brachytherapy. Plain films were taken of the pelvic model, and applicator placement quality was evaluated. Other evaluated metrics included retention of key procedural details, the time taken for each procedure and presession and postsession surveys to assess confidence. During the initial session, residents on average met 4.5 of 5 placement criteria, which improved to 5 the second session. On average, residents were able to remember 7.6 of the 8 key procedural steps. Execution time decreased by an average of 10.5%. Resident confidence with the procedure improved dramatically, from 2.6 to 4.6 of 5. Residents who had previously never performed a tandem and ovoid procedure showed greater improvements in these criteria than those who had. All residents strongly agreed that the training was helpful and wanted to participate again the following year. Residents participating in this simulation training had measurable improvements in the time to perform the procedure, applicator placement quality, and confidence. This curriculum is easy to implement and is of great value for training residents, and would be particularly beneficial in programs with low volume of cervical brachytherapy cases. Simulation programs could

  5. Aberrant PO2 values in proficiency testing.

    Science.gov (United States)

    Fonzi, C E; Clausen, J L; Mahoney, J

    1993-03-01

    We prospectively determined the frequency of aberrant vials of fluorocarbon/buffer used for proficiency testing of measurements of pH, PCO2, and PO2, using 20 duplicate vials from 12 lots of fluorocarbon/buffer and two arterial blood gas analyzers in eight reference laboratories. We defined aberrant vials as vials for which both duplicate measurements differed from the mean value of repeated measurements for the specific instrument (for each lot of testing materials) by > 0.04 for pH, > 10% of the mean or 3.0 mm Hg, whichever was greater, for PCO2; or > 10% of the mean or 6 mm Hg, whichever was greater, for PO2. Four of 1620 vials (0.25%) were aberrant, all based on PO2 measurements (range of mean values: pH, 7.181-7.631; PCO2, 12.7-65.9; PO2, 32.5-150.1) were 0.0055 for pH, 0.67 mm Hg for PCO2, and 1.65 mm Hg for PO2. Deliberate contamination of the fluorocarbon emulsion with room air, as might occur during sampling from the vial, indicated that only minor increases in PO2 (e.g., 1.0 mm Hg at PO2 of 56 mm Hg) occur when samples are aspirated. Larger increases in PO2 (mean 7.1 mm Hg at a PO2 of 66 mm Hg) occurred when the syringe samples were contaminated with room air. We conclude that isolated aberrant measurements of PO2 in blood gas proficiency testing attributable to vial contents can occur, but the frequency is very low.

  6. Lysyl oxidase in colorectal cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine T

    2013-01-01

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... advancements in the field of colorectal cancer....

  7. Endoscopic management of colorectal adenomas.

    Science.gov (United States)

    Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

    2017-01-01

    Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy.

  8. What is the optimal management of an intra-operative air leak in a colorectal anastomosis?

    Science.gov (United States)

    Mitchem, J B; Stafford, C; Francone, T D; Roberts, P L; Schoetz, D J; Marcello, P W; Ricciardi, R

    2018-02-01

    An airtight anastomosis on intra-operative leak testing has been previously demonstrated to be associated with a lower risk of clinically significant postoperative anastomotic leak following left-sided colorectal anastomosis. However, to date, there is no consistently agreed upon method for management of an intra-operative anastomotic leak. Therefore, we powered a noninferiority study to determine whether suture repair alone was an appropriate strategy for the management of an intra-operative air leak. This is a retrospective cohort analysis of prospectively collected data from a tertiary care referral centre. We included all consecutive patients with left-sided colorectal or ileorectal anastomoses and evidence of air leak during intra-operative leak testing. Patients were excluded if proximal diversion was planned preoperatively, a pre-existing proximal diversion was present at the time of surgery or an anastomosis was ultimately unable to be completed. The primary outcome measure was clinically significant anastomotic leak, as defined by the Surgical Infection Study Group at 30 days. From a sample of 2360 patients, 119 had an intra-operative air leak during leak testing. Sixty-eight patients underwent suture repair alone and 51 underwent proximal diversion or anastomotic reconstruction. The clinically significant leak rate was 9% (6/68; 95% CI: 2-15%) in the suture repair alone arm and 0% (0/51) in the diversion or reconstruction arm. Suture repair alone does not meet the criteria for noninferiority for the management of intra-operative air leak during left-sided colorectal anastomosis. Further repair of intra-operative air leak by suture repair alone should be reconsidered given these findings. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  9. Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018.

    Science.gov (United States)

    Bhalla, Amarpreet; Zulfiqar, Muhammad; Bluth, Martin H

    2018-06-01

    The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

    Science.gov (United States)

    Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

    2017-09-01

    One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Colorectal anastomotic leakage: aspects of prevention, detection and treatment.

    Science.gov (United States)

    Daams, Freek; Luyer, Misha; Lange, Johan F

    2013-04-21

    All colorectal surgeons are faced from time to time with anastomotic leakage after colorectal surgery. This complication has been studied extensively without a significant reduction of incidence over the last 30 years. New techniques of prevention, by innovative anastomotic techniques should improve results in the future, but standardization and "teachability" should be guaranteed. Risk scoring enables intra-operative decision-making whether to restore continuity or deviate. Early detection can lead to reduction in delay of diagnosis as long as a standard system is used. For treatment options, no firm evidence is available, but future studies could focus on repair and saving of the anastomosis on the one hand or anastomotical breakdown and definitive colostomy on the other hand.

  12. Mismatch repair deficiency in colorectal cancer patients in a low ...

    African Journals Online (AJOL)

    2013-02-06

    Feb 6, 2013 ... products of the hMLH1 and hMSH2 genes) in the tumours using heat-induced antigen retrieval and .... Tumour IHC is a highly sensitive and specific strategy .... The grade of differentiation was identified in 67 cases: 59.

  13. Colorectal Cancer Screening

    OpenAIRE

    Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo

    2012-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...

  14. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.

    Science.gov (United States)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier; Collura, Ada; Tinat, Julie; Lavoine, Noémie; Guilloux, Agathe; Chalastanis, Alexandra; Lafitte, Philippe; Coulet, Florence; Buisine, Marie-Pierre; Ilencikova, Denisa; Ruiz-Ponte, Clara; Kinzel, Miriam; Grandjouan, Sophie; Brems, Hilde; Lejeune, Sophie; Blanché, Hélène; Wang, Qing; Caron, Olivier; Cabaret, Odile; Svrcek, Magali; Vidaud, Dominique; Parfait, Béatrice; Verloes, Alain; Knappe, Ulrich J; Soubrier, Florent; Mortemousque, Isabelle; Leis, Alexander; Auclair-Perrossier, Jessie; Frébourg, Thierry; Fléjou, Jean-François; Entz-Werle, Natacha; Leclerc, Julie; Malka, David; Cohen-Haguenauer, Odile; Goldberg, Yael; Gerdes, Anne-Marie; Fedhila, Faten; Mathieu-Dramard, Michèle; Hamelin, Richard; Wafaa, Badre; Gauthier-Villars, Marion; Bourdeaut, Franck; Sheridan, Eamonn; Vasen, Hans; Brugières, Laurence; Wimmer, Katharina; Muleris, Martine; Duval, Alex

    2015-10-01

    Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are noninformative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors in repetitive DNA sequences. We investigated whether these features could be used to identify patients with CMMRD. We examined MSI by PCR analysis and tolerance to methylating or thiopurine agents (functional characteristics of MMR-deficient tumor cells) in lymphoblastoid cells (LCs) from 3 patients with CMMRD and 5 individuals with MMR-proficient LCs (controls). Using these assays, we defined experimental parameters that allowed discrimination of a series of 14 patients with CMMRD from 52 controls (training set). We then used the same parameters to assess 23 patients with clinical but not genetic features of CMMRD. In the training set, we identified parameters, based on MSI and LC tolerance to methylation, that detected patients with CMMRD vs controls with 100% sensitivity and 100% specificity. Among 23 patients suspected of having CMMRD, 6 had MSI and LC tolerance to methylation (CMMRD highly probable), 15 had neither MSI nor LC tolerance to methylation (unlikely to have CMMRD), and 2 were considered doubtful for CMMRD based on having only 1 of the 2 features. The presence of MSI and tolerance to methylation in LCs identified patients with CMMRD with 100% sensitivity and specificity. These features could be used in diagnosis of patients. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  16. The dutch surgical colorectal audit

    NARCIS (Netherlands)

    Leersum, N.J. van; Snijders, H.S.; Henneman, D.; Kolfschoten, N.E.; Gooiker, G.A.; Berge, M.G. Ten; Eddes, E.H.; Wouters, M.W.; Tollenaar, R.A.E.M.; Bemelman, W.A.; Dam, R.M. van; Elferink, M.A.; Karsten, T.M.; Krieken, J.H. van; Lemmens, V.E.; Rutten, H.J.; Manusama, E.R.; Velde, C.J. van de; Meijerink, W.J.H.J.; Wiggers, T.; Harst, E. van der; Dekker, J.W.T.; Boerma, D.

    2013-01-01

    INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated

  17. Colorectal Cancer—Patient Version

    Science.gov (United States)

    Colorectal cancer often begins as a growth called a polyp inside the colon or rectum. Finding and removing polyps can prevent colorectal cancer. Start here to find information on colon and rectal cancer treatment, causes and prevention, screening, research, and statistics.

  18. The Dutch surgical colorectal audit

    NARCIS (Netherlands)

    van Leersum, N. J.; Snijders, H. S.; Henneman, D.; Kolfschoten, N. E.; Gooiker, G. A.; ten Berge, M. G.; Eddes, E. H.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.; Bemelman, W. A.; van Dam, R. M.; Elferink, M. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Lemmens, V. E. P. P.; Rutten, H. J. T.; Manusama, E. R.; van de Velde, C. J. H.; Meijerink, W. J. H. J.; Wiggers, Th; van der Harst, E.; Dekker, J. W. T.; Boerma, D.

    2013-01-01

    In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch

  19. Exercise and Low-Dose Ibuprofen for Cognitive Impairment in Colorectal Cancer Patients Receiving Chemotherapy

    Science.gov (United States)

    2018-03-13

    Cognitive Impairment; Stage 0 Colorectal Cancer; Stage I Colorectal Cancer; Stage II Colorectal Cancer; Stage IIA Colorectal Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage III Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer

  20. Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2018-07-01

    Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

  1. THE BANGLADESHI EMPLOYMENT SECTOR: EMPLOYER PERSPECTIVES CONCERNING ENGLISH PROFICIENCY

    Directory of Open Access Journals (Sweden)

    Rubina Khan

    2012-07-01

    Full Text Available Abstract: This paper presents a brief summary of a study which was carried out to investigate how employers representing major employment sectors in the Bangladeshi Industry view the skills and English proficiency level of the current employees. Opinions were also solicited on what skills are required for fresh recruits. Semi-structured interviews were conducted with 30 employers representing the major employment sectors in Bangladeshi Industry. Results revealed the importance of English as an indispensible means of communication in the Bangladeshi corporate sector and showed that the business enterprises use extensive amounts of English. It also highlighted that the existent English proficiency of the employees was far below the required proficiency level. Recommendations were made to address the gap and prepare the youth to meet the demands of the global market. Keywords: English proficiency, competency, employability skills, global literacy skills

  2. Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients.

    Science.gov (United States)

    Du, Feng; Shi, Su-Sheng; Sun, Yong-Kun; Wang, Jin-Wan; Chi, Yihebali

    2015-12-05

    Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair (MMR) status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type (7/19). Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor (P = 0.02). Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.

  3. Physical activity and the risk of colorectal cancer in Lynch syndrome.

    Science.gov (United States)

    Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

    2018-06-14

    Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

  4. Reduced repair of potentially lethal radiation damage in glutathione synthetase-deficient human fibroblasts after X-irradiation

    International Nuclear Information System (INIS)

    Midander, J.; Revesz, L.; Deschavanne, P.J.; Debieu, D.; Malaise, E.P.

    1986-01-01

    Using a human fibroblast strain deficient in glutathione synthetase and a related proficient control strain, the role of glutathione (GSH) in repair of potentially lethal damage (PLD) has been investigated in determining survival by plating cells immediately or 24 h after irradiation. After oxic or hypoxic irradiation, both cell strains repair radiation-induced damage. However, under hypoxic conditions, the proficient cells repair PLD as well as under oxic conditions while the deficient cells repair less PLD after irradiation under hypoxic than under oxic conditions. Therefore, the oxygen enhancement ratio (o.e.r.) for proficient cells is similar whether the cells are plated immediately or 24 h later (2.0 and 2.13, respectively). In contrast, the o.e.r. for deficient cells is lower when the cells are plated 24 h after irradiation than when they are plated immediately thereafter (1.16 as compared to 1.55). The results indicate that GSH is involved in PLD repair and, in particular, in the repair of damage induced by radiation delivered under hypoxic conditions. (author)

  5. PROFICIENT CLASSROOM MANAGEMENT THROUGH FOCUSED MATHEMATIC TEACHING

    Directory of Open Access Journals (Sweden)

    Marcus Samuelsson

    2017-12-01

    Full Text Available A not entirely unusual position among teachers is that they believe that they must first establish a peaceful classroom before they can begin to teach the subject. This research, shows how a proficient mathematics teacher teaches his subject and thereby creates a quiet and focused classroom and exerts effective leadership, just by teaching mathematics. The researchers observed a male mathematics teacher for almost half a year, i.e. one semester. The results of research present several patterns that the researchers saw during the observations of his teaching. The teacher showed an interest in each student’s mathematical thinking and expressed explicitly how students were expected to learn mathematics. He also directed students’ attention to mathematics and established a culture where all solutions were important in the teaching process. In the teaching process, he used multiple representations to motivate students and a lot of supportive expressions that made them feel that they were able to learn mathematics. He worked patiently to establish structures, and there was almost no disruptive behaviour. Students simply did not have time to interfere because they were so engaged in learning mathematics.

  6. Trainee-Associated Factors and Proficiency at Percutaneous Nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Kazem Aghamir

    2017-09-01

    Full Text Available Percutaneous nephrolithotomy (PNL is a complicated procedure for urology trainees. This study was designed to investigate the effect of trainees’ ages and previous experience, as well as the number of operated cases, on proficiency at PNL by using patient outcomes. A cross sectional observational study was designed during a five-year period. Trainees in PNL fellowship programs were included. At the end of the program, the trainees’ performance in PNL was assessed regarding five competencies and scored 1-5. If the overall score was 4 or above, the trainee was considered as proficient. The trainees’ age at the beginning of the program and the years passed from their residency graduation were asked and recorded. Also, the number of PNL cases operated by each trainee was obtained via their logbooks. The age, years passed from graduation, and number of operated cases were compared between two groups of proficient and non-proficient trainees. Univariate and multivariate binary logistic regression analysis was applied to estimate the effect of aforementioned variables on the occurrence of the proficiency. Forty-two trainees were included in the study. The mean and standard deviation for the overall score were 3.40 (out of 5 and 0.67, respectively. Eleven trainees (26.2% recognized as proficient in performing PNL. Univariate regression analysis indicated that each of three variables (age, years passed from graduation and number of operated cases had statistically significant effect on proficiency. However, the multivariate regression analysis revealed that just the number of cases had significant effect on achieving proficiency. Although it might be assumed that trainees’ age negatively correlates with their scores, in fact, it is their amount of practice that makes a difference. A certain number of cases is required to be operated by a trainee in order to reach the desired competency in PNL.

  7. Trainee-Associated Factors and Proficiency at Percutaneous Nephrolithotomy.

    Science.gov (United States)

    Aghamir, Seyed Mohammad Kazem; Behtash, Negar; Hamidi, Morteza; Farahmand, Hasan; Salavati, Alborz; Mortaz Hejri, Sara

    2017-07-01

    Percutaneous nephrolithotomy (PNL) is a complicated procedure for urology trainees. This study was designed to investigate the effect of trainees' ages and previous experience, as well as the number of operated cases, on proficiency at PNL by using patient outcomes. A cross sectional observational study was designed during a five-year period. Trainees in PNL fellowship programs were included. At the end of the program, the trainees' performance in PNL was assessed regarding five competencies and scored 1-5. If the overall score was 4 or above, the trainee was considered as proficient. The trainees' age at the beginning of the program and the years passed from their residency graduation were asked and recorded. Also, the number of PNL cases operated by each trainee was obtained via their logbooks. The age, years passed from graduation, and number of operated cases were compared between two groups of proficient and non-proficient trainees. Univariate and multivariate binary logistic regression analysis was applied to estimate the effect of aforementioned variables on the occurrence of the proficiency. Forty-two trainees were included in the study. The mean and standard deviation for the overall score were 3.40 (out of 5) and 0.67, respectively. Eleven trainees (26.2%) recognized as proficient in performing PNL. Univariate regression analysis indicated that each of three variables (age, years passed from graduation and number of operated cases) had statistically significant effect on proficiency. However, the multivariate regression analysis revealed that just the number of cases had significant effect on achieving proficiency. Although it might be assumed that trainees' age negatively correlates with their scores, in fact, it is their amount of practice that makes a difference. A certain number of cases is required to be operated by a trainee in order to reach the desired competency in PNL.

  8. Language proficiency and the international postgraduate student experience

    OpenAIRE

    Weaver, M

    2016-01-01

    In an increasingly competitive environment, with reduced government funding, full fee-paying international students are an important source of revenue for higher education institutions (HEIs). Although many previous studies have focused on the role of English language proficiency on academic success, there is little known about the extent to which levels of English language proficiency affect these non-native English speaking students’ overall course experience. There have been a wealth of st...

  9. STRATEGIES OF MAINTAINING PROFICIENCY BY TEACHERS OF ENGLISH IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Junaidi Mistar, Alfan Zuhairini

    2011-10-01

    Full Text Available The objectives of the present study are four-fold: (1 to identify the types of strategies to maintain proficiency used by teachers of English in Indonesia, (2 to know the intensity of use of the obtained strategy types, (3 to measure the inter-correlation in the use of the obtained strategy types, and (4 to investigate the effect of proficiency level on the use of maintaining strategies. The subjects were 93 teachers applying for S2 degree in 2010/2011 at the postgraduate program of the Islamic University of Malang. They were given two sets of instrument, a Likert-scale questionnaire of English proficiency maintaining strategies and a TOEFL test. Then, a factor analysis identified nine strategy categories, including language focusing, metacognitive and affective developing, reading and writing activating, language resource utilizing, cognitive processing, culture learning, social communicating, text analyzing, and radio listening strategies. These strategy types explained 63.84% of variances of maintaining strategies and they were used at high level of intensity. Moreover, the use of the nine strategy types were found to be inter-correlated with one another. Finally, no significant effect of proficiency level on strategy use was found, indicating that teachers with different level of proficiency reported using the same strategies of maintaining their proficiency.

  10. Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours

    NARCIS (Netherlands)

    von Bueren, A. O.; Bacolod, M. D.; Hagel, C.; Heinimann, K.; Fedier, A.; Kordes, U.; Pietsch, T.; Koster, J.; Grotzer, M. A.; Friedman, H. S.; Marra, G.; Kool, M.; Rutkowski, S.

    2012-01-01

    BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in O-6-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA

  11. Cell cycle phase dependent role of DNA polymerase beta in DNA repair and survival after ionizing radiation.

    NARCIS (Netherlands)

    Vermeulen, C.; Verwijs-Janssen, M.; Begg, A.C.; Vens, C.

    2008-01-01

    PURPOSE: The purpose of the present study was to determine the role of DNA polymerase beta in repair and response after ionizing radiation in different phases of the cell cycle. METHODS AND MATERIALS: Synchronized cells deficient and proficient in DNA polymerase beta were irradiated in different

  12. Repair of ultraviolet-light-induced DNA damage in Vibrio cholerae

    International Nuclear Information System (INIS)

    Das, G.; Sil, K.; Das, J.

    1981-01-01

    Repair of ultraviolet-light-induced DNA damage in a highly pathogenic Gram-negative bacterium, Vibrio cholerae, has been examined. All three strains of V. cholerae belonging to two serotypes, Inaba and Ogawa, are very sensitive to ultraviolet irradiation, having inactivation cross-sections ranging from 0.18 to 0.24 m 2 /J. Although these cells are proficient in repairing the DNA damage by a photoreactivation mechanism, they do not possess efficient dark repair systems. The mild toxinogenic strain 154 of classical Vibrios presumably lacks any excision repair mechanism and studies of irradiated cell DNA indicate that the ultraviolet-induced pyrimidine dimers may not be excised. Ultraviolet-irradiated cells after saturation of dark repair can be further photoreactivated. (Auth.)

  13. Effect of 8-MOP plus treatment on survival and repair of plasmid pBR322

    International Nuclear Information System (INIS)

    Bauluz, C.; Vidania, R.

    1992-01-01

    We have studied the lethality produced in pBR322 DNA after PUVA treatment (8-MOP+UVA). As recipients, we used a collection of E. coli strains differing in their repair capacities and analysed the involvement of several DNA repair pathways in the removal of plasmid lesions. We have also studied the effect of UVA radiation alone, in order to determine more precisely the effect attributable only to psoralen molecules. Results showed a strong lethal effect derived from PUVA treatment; however, some plasmid recovery was achieved in bacterial hosts proficient in Excision repair and SOS repair. another repair pathway, only detectable at high density of lesions, appeared to be relevant for the removal of 8-MOP:DNA adducts. (author)

  14. Cell-free assay measuring repair DNA synthesis in human fibroblasts

    International Nuclear Information System (INIS)

    Ciarrocchi, G.; Linn, S.

    1978-01-01

    Osmotic disruption of confluent cultured human fibroblasts that have been irradiated or exposed to chemical carcinogens allows the specific measurement of repair DNA synthesis using dTTP as a precursor. Fibroblasts similarly prepared from various xeroderma pigmentosum cell lines show the deficiencies of uv-induced DNA synthesis predicted from in vivo studies, while giving normal responses to methylmethanesulfonate. A pyrimidine-dimer-specific enzyme, T4 endonuclease V, stimulated the rate of uv-induced repair synthesis with normal and xeroderma pigmentosum cell lines. This system should prove useful for identifying agents that induce DNA repair, and cells that respond abnormally to such induction. It should also be applicable to an in vitro complementation assay with repair-defective cells and proteins obtained from repair-proficient cells. Finally, by using actively growing fibroblasts and thymidine in the system, DNA replication can be measured and studied in vitro

  15. Collision Repair Campaign

    Science.gov (United States)

    The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.

  16. Retinal detachment repair

    Science.gov (United States)

    ... medicines Problems breathing You may not recover full vision. ... detachments can be repaired. Failure to repair the retina always results in loss of vision to some degree. After surgery, the quality of ...

  17. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance

    NARCIS (Netherlands)

    Hendriks, Yvonne M. C.; Wagner, Anja; Morreau, Hans; Menko, Fred; Stormorken, Astrid; Quehenberger, Franz; Sandkuijl, Lodewijk; Møller, Pal; Genuardi, Maurizio; van Houwelingen, Hans; Tops, Carli; van Puijenbroek, Marjo; Verkuijlen, Paul; Kenter, Gemma; van Mil, Anneke; Meijers-Heijboer, Hanne; Tan, Gita B.; Breuning, Martijn H.; Fodde, Riccardo; Wijnen, Juul Th; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans

    2004-01-01

    BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20

  18. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...

  19. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  20. Diagnosis of colorectal tumors

    International Nuclear Information System (INIS)

    Vogl, T.J.; Pegios, W.; Jacobi, V.; Schaefer, S.; Abolmaali, N.; Luboldt, W.

    2003-01-01

    With the introduction of multislice CT extensive volumetric data sets can be quickly acquired in high spatial resolution. The high spatial resolution reduces partial volume effects and enables multiplanar reconstructions. Regarding the colorectum this means that the colon can be assessed if the colon is sufficiently cleaned and distended, and that transmural infiltration of colorectal carcinoma and liver metastases can be better detected. T-staging of colon cancer is less important than T-staging of rectal cancer. Based on the higher contrast MRI is superior to CT in T-staging of rectal cancer and in the differentiation between scarring tissue and recurrence of carcinoma. (orig.) [de

  1. Mutagenesis and repair of DNA

    International Nuclear Information System (INIS)

    Janion, C.; Grzesiuk, E.; Fabisiewicz, A.; Tudek, B.; Ciesla, J.; Graziewicz, M.; Wojcik, A.; Speina, E.

    1998-01-01

    Full text. The discovery that the mfd gene codes for a transcription-coupling repair factor (TRCF) prompted us to re-investigate the MFD (mutation frequency decline) phenomenon in E.coli K-12 strain when mutations were induced by ultraviolet light, halogen light or MMS-treatment. These studies revealed that: (i) the process of MFD involves the proofreading activity of DNA pol III and the mismatch repair system, as well as, TRCF and the UvrABC-excinuclease (ii) a semi-rich plate test may be replaced by a rich liquid medium, (iii) the T-T pyrimidine dimers are the lesions excised with the highest activity, and (iv) overproduction of UmuD(D'C) proteins leads to a great increase in mutant frequency in irradiated and MMS-treated cells. The role of mismatch repair (MR) in MMS-induced mutagenesis is obscured by the fact that the spectra of mutational specificity are different in bacteria proficient and deficient in MR. It has been found that transposons Tn10 (and Tn5) when inserted into chromosomal DNA of E. coli influence the phenotype lowering the survival and frequency of mutations induced by UV or halogen light irradiation. This is connected with a deficiency of UmuD(D') and UmuC proteins. Transformation of bacteria with plasmids bearing the umuD(D')C genes, suppresses the effects of the transposon insertion, a phenomenon which has not been described before. Single-stranded DNA of M13mp18 phage was oxidized in vitro by a hydroxyl radical generating system including hypoxanthine/xanthine oxidase/Fe3+/EDTA, and it was found that Fapy-Ade, Fapy-Gua, 8-oxyAde and thymine glycol were the main products formed. Replication of the oxidized template by T7 phage DNA polymerase, Klenow fragment of polymerase I, or polymerase beta from bovine thymus has revealed that oxidized pyrimidines are stronger blockers than oxidized purines for T7 phage and Klenow fragment polymerases and the blocking potency depends on the neighboring bases and on the type of polymerase. Studies of

  2. Primary prevention of colorectal cancer.

    Science.gov (United States)

    Chan, Andrew T; Giovannucci, Edward L

    2010-06-01

    Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.

  3. Commutability of food microbiology proficiency testing samples.

    Science.gov (United States)

    Abdelmassih, M; Polet, M; Goffaux, M-J; Planchon, V; Dierick, K; Mahillon, J

    2014-03-01

    Food microbiology proficiency testing (PT) is a useful tool to assess the analytical performances among laboratories. PT items should be close to routine samples to accurately evaluate the acceptability of the methods. However, most PT providers distribute exclusively artificial samples such as reference materials or irradiated foods. This raises the issue of the suitability of these samples because the equivalence-or 'commutability'-between results obtained on artificial vs. authentic food samples has not been demonstrated. In the clinical field, the use of noncommutable PT samples has led to erroneous evaluation of the performances when different analytical methods were used. This study aimed to provide a first assessment of the commutability of samples distributed in food microbiology PT. REQUASUD and IPH organized 13 food microbiology PTs including 10-28 participants. Three types of PT items were used: genuine food samples, sterile food samples and reference materials. The commutability of the artificial samples (reference material or sterile samples) was assessed by plotting the distribution of the results on natural and artificial PT samples. This comparison highlighted matrix-correlated issues when nonfood matrices, such as reference materials, were used. Artificially inoculated food samples, on the other hand, raised only isolated commutability issues. In the organization of a PT-scheme, authentic or artificially inoculated food samples are necessary to accurately evaluate the analytical performances. Reference materials, used as PT items because of their convenience, may present commutability issues leading to inaccurate penalizing conclusions for methods that would have provided accurate results on food samples. For the first time, the commutability of food microbiology PT samples was investigated. The nature of the samples provided by the organizer turned out to be an important factor because matrix effects can impact on the analytical results. © 2013

  4. Social media in colorectal surgery.

    Science.gov (United States)

    Wexner, S D; Petrucci, A M; Brady, R R; Ennis-O'Connor, M; Fitzgerald, J E; Mayol, J

    2017-02-01

    The engagement of social media in healthcare continues to expand. For members of the colorectal community, social media has already made a significant impact on practice, education and patient care. The applications are unique such that they provide a platform for instant communication and information sharing with other users worldwide. The purpose of this article is to provide an overview of how social media has the potential to change clinical practice, training, research and patient care in colorectal surgery. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  5. Reporting colorectal cancer.

    Science.gov (United States)

    Quirke, P; Morris, E

    2007-01-01

    The management of colorectal cancer is a team process. High-quality reporting of colorectal cancer is very important as the whole team relies upon the skill of the pathologist. Failure to report key features can lead to undertreatment of this disease. The use of a proforma has been demonstrated to be beneficial and we recommend staying with TNM5 due to scientific and reproducibility issues with TNM6. Important features in stage II/Dukes' B cases are extramural vascular invasion, peritoneal involvement, extent of extramural spread, incomplete resection and perforation. All of these may lead to adjuvant therapy being administered. The surgically created circumferential resection margin (CRM) and the mode of its creation are important features and the CRM retains its value after preoperative therapy. Regression grading should be applied only to fully resected tumours and the dissection and sampling must be standardized to allow comparison of results between trials and centres. When reporting local resections of early-stage cancers we need to look for features that predict spread to local lymph nodes to allow a full resection to be considered.

  6. Verb-Noun Collocation Proficiency and Academic Years

    Directory of Open Access Journals (Sweden)

    Fatemeh Ebrahimi-Bazzaz

    2014-01-01

    Full Text Available Generally vocabulary and collocations in particular have significant roles in language proficiency. A collocation includes two words that are frequently joined concurrently in the memory of native speakers. There have been many linguistic studies trying to define, to describe, and to categorise English collocations. It contains grammatical collocations and lexical collocations which include nouns, adjectives, verbs, and adverb. In the context of a foreign language environment such as Iran, collocational proficiency can be useful because it helps the students improve their language proficiency. This paper investigates the possible relationship between verb-noun collocation proficiency among students from one academic year to the next. To reach this goal, a test of verb-noun collocations was administered to Iranian learners. The participants in the study were 212 Iranian students in an Iranian university. They were selected from the second term of freshman, sophomore, junior, and senior years. The students’ age ranged from 18 to 35.The results of ANOVA showed there was variability in the verb-noun collocations proficiency within each academic year and between the four academic years. The results of a post hoc multiple comparison tests demonstrated that the means are significantly different between the first year and the third and fourth years, and between the third and the fourth academic year; however, students require at least two years to show significant development in verb-noun collocation proficiency. These findings provided a vital implication that lexical collocations are learnt and developed through four academic years of university, but requires at least two years showing significant development in the language proficiency.

  7. English language proficiency and smoking prevalence among California's Asian Americans.

    Science.gov (United States)

    Tang, Hao; Shimizu, Robin; Chen, Moon S

    2005-12-15

    The authors documented California's tobacco control initiatives for Asian Americans and the current tobacco use status among Asian subgroups and provide a discussion of the challenges ahead. The California Tobacco Control Program has employed a comprehensive approach to decrease tobacco use in Asian Americans, including ethnic-specific media campaigns, culturally competent interventions, and technical assistance and training networks. Surveillance of tobacco use among Asian Americans and the interpretation of the results have always been a challenge. Data from the 2001 The California Health Interview Survey (CHIS) were analyzed to provide smoking prevalence estimates for all Asian Americans and Asian-American subgroups, including Korean, Filipino, Japanese, South Asian, Chinese, and Vietnamese. Current smoking prevalence was analyzed by gender and by English proficiency level. Cigarette smoking prevalence among Asian males in general was almost three times of that among Asian females. Korean and Vietnamese males had higher cigarette smoking prevalence rates than males in other subgroups. Although Asian females in general had low smoking prevalence rates, significant differences were found among Asian subgroups, from 1.1% (Vietnamese) to 12.7% (Japanese). Asian men who had high English proficiency were less likely to be smokers than men with lower English proficiency. Asian women with high English proficiency were more likely to be smokers than women with lower English proficiency. Smoking prevalence rates among Asian Americans in California differed significantly on the basis of ethnicity, gender, and English proficiency. English proficiency seemed to have the effect of reducing smoking prevalence rates among Asian males but had just the opposite effect among Asian females. Cancer 2005. (c) 2005 American Cancer Society.

  8. Differential radioprotective effects of misoprostol in DNA repair-proficient and -deficient or radiosensitive cell systems

    NARCIS (Netherlands)

    van Buul, P. P.; van Duyn-Goedhart, A.; de rooij, D. G.; Sankaranarayanan, K.

    1997-01-01

    The protective effects of misoprostol (MP), an analogue of prostaglandin E1, on X-ray-induced chromosomal aberrations, were studied in normal or mutant Chinese hamster cell lines grown as spheroids in vitro and on cell-killing in stem-cell spermatogonia of a mutant (acid) mouse strain or its

  9. The CpG island methylator phenotype (CIMP) in colorectal cancer.

    Science.gov (United States)

    Nazemalhosseini Mojarad, Ehsan; Kuppen, Peter Jk; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

    2013-01-01

    It is clear that colorectal cancer (CRC) develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: (i) mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability (MSI) phenotype, (ii) mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability (CIN) phenotype, and (iii) global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype (CIMP). Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer.

  10. Colorectal choriocarcinoma in a patient with probable Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Viktor Hendrik Koelzer

    2016-11-01

    Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

  11. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription*

    Science.gov (United States)

    Nadkarni, Aditi; Burns, John A.; Gandolfi, Alberto; Chowdhury, Moinuddin A.; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E.; Scicchitano, David A.

    2016-01-01

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N6-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N6-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N6-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N6-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N6-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID:26559971

  12. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...... of 295 patients with primary colorectal cancer we found a sensitivity of preoperative ultrasound, surgical exploration, and intraoperative ultrasound of 70%, 84%, and 97%, respectively, based on a patient-by-patient comparison (p

  13. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long...

  14. Colorectal Anastomotic Leakage: New perspectives

    NARCIS (Netherlands)

    F. Daams (Freek)

    2014-01-01

    markdownabstract__Abstract__ This thesis provides new perspectives on colorectal anastomotic leakages. In both experimental and clinical studies, aspects of prevention, early identification, treatment and consequences of anastomotic leakage are discussed.

  15. Obesity and colorectal cancer risk

    International Nuclear Information System (INIS)

    Hano Garcia, Olga Marina; Wood Rodriguez, Lisette; Villa Jimenez, Oscar Manuel

    2011-01-01

    Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes

  16. Post-irradiation replication and repair in UV-irradiated cells of Proteus mirabilis depends on protein synthesis and a functioning rec+ gene

    International Nuclear Information System (INIS)

    Hofemeister, J.

    1977-01-01

    The amount of and the molecular weight of newly synthesized DNA (piDNA) as well as its repair after UV irradiation in excision-proficient strains of P.mirabilis and E.coli K12 have been compared. A fraction of post-replication repair (PRR) in P.mirabilis is found to be dependent on de novo protein synthesis after UV irradiation. Pre-irradiation by UV and pre-treatment with nalidixic acid increase the efficiency of post-irradiation replication and PRR even in the presence of chloramphenicol. An inducible repair function in P.mirabilis is supposed to stimulate post-irradiation replication and repair. (author)

  17. Post-irradiation replication and repair in uv-irradiated cells of Proteus mirabilis depends on protein synthesis and a functioning rec/sup +/ gene

    Energy Technology Data Exchange (ETDEWEB)

    Hofemeister, J [Akademie der Wissenschaften der DDR, Gatersleben. Zentralinstitut fuer Genetik und Kulturpflanzenforschung

    1977-02-28

    The amount of and the molecular weight of newly synthesized DNA (piDNA) as well as its repair after uv irradiation in excision-proficient strains of P.mirabilis and E.coli K12 have been compared. A fraction of post-replication repair (PRR) in P.mirabilis is found to be dependent on de novo protein synthesis after uv irradiation. Pre-irradiation by uv and pre-treatment with nalidixic acid increase the efficiency of post-irradiation replication and PRR even in the presence of chloramphenicol. An inducible repair function in P.mirabilis is supposed to stimulate post-irradiation replication and repair.

  18. The proficiency testing of determination of dioxins in food

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, R.; Tsutsumi, T.; Maitani, T. [National Institute of Health Sciences, Tokyo (Japan); Toyoda, M. [Jissen Womens Univ., Hino (Japan)

    2004-09-15

    Food intake is the main route of human dioxin exposure, making the determination of dioxins in food indispensable for risk assessment and risk management of dioxins. The uncertainty of analytical results, however, can be very great because of the low concentration of the analytes and complicated cleanup procedures. The risk assessment of dioxins based on analytical results also suffers from a similar degree of uncertainty. The Ministry of Health, Labor and Welfare of Japan has published ''Guideline for the Determination of Dioxins in Food'' to standardize the analytical procedures. The guideline contains the quality assurance procedures to obtain reliable analytical results and recommends participation in the relevant proficiency testing scheme. The proficiency testing provides the fair evaluation of the analytical results. The central science laboratory in England and the food and drug safety center in Japan offer the proficiency testing on food. The National Institute of Health Sciences of Japan (NIHS) also has carried out proficiency testing of dioxins in food since 1998 to assure the quality of analytical results for dioxins. In this presentation we will show the results of 5 rounds of proficiency testing.

  19. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  20. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention....

  1. EPIDEMIOLOGICAL EVALUATION OF COLORECTAL CANCER

    OpenAIRE

    B. Shafayan M. Keyhani

    2003-01-01

    This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC): From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56), 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most com...

  2. Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Garry N. Hannan

    2013-09-01

    Full Text Available Hereditary non-polyposis colorectal cancer (HNPCC is the commonest form of inherited colorectal cancer (CRC predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.

  3. Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.

    Science.gov (United States)

    Funck, Alexandre; Santos, Juliana C; Silva-Fernandes, Isabelle J L; Rabenhorst, Silvia H B; Martinez, Carlos A R; Ribeiro, Marcelo L

    2014-09-01

    The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR-RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner.

  4. Robotics in Colorectal Surgery

    Science.gov (United States)

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  5. Colorectal Cancer: Prognostic Values

    Directory of Open Access Journals (Sweden)

    Suzana Manxhuka-Kerliu

    2009-02-01

    Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.

  6. First year evaluation of EPA's radon contractor proficiency (RCP) program

    International Nuclear Information System (INIS)

    Salmon, G.L.

    1990-01-01

    This paper reports that the Environmental Protection Agency (EPA) has developed a voluntary program to evaluate radon reduction contractors and provide this information to the public, as part of activities mandated by the Indoor Radon Abatement Act (IRAA) of 1988. The Radon Contractor Proficiency Program consists of several elements that collectively help to ensure the proficiency of radon mitigators and give the public greater confidence in their capability. Contractors who participate in the program must pass a written examination, adhere to mitigation guidelines, keep records of work, meet continuing education requirements and pass a re-examination every two years. Upon meeting the program's requirements, mitigators are listed in EPA's National RCP Proficiency Report. The first Report released on May 15, 1990 listed 636 contractors. The second Report, to be release in August, will list 895 contractors, representing an increase of 40 per cent

  7. Physical activity and movement skills proficiency of young Filipino children.

    Science.gov (United States)

    Capio, Catherine M; Sit, Cindy H P; Eguia, Kathlynne F; Abernethy, Bruce

    2014-08-01

    Recent reports indicate an increasing prevalence of overweight among Filipino children. Considering the known association of physical activity (PA) with obesity, this study reports the findings of an objective monitoring of PA in a sample of Filipino children. The study also explores the relationship of PA with fundamental movement skills (FMS) proficiency. Thirty-two children (6.54 ± 2.45 years old) wore an accelerometer for 7 days of PA monitoring and were assessed on five FMS (throw, catch, kick, run, jump). The children met the World Health Organization's recommendation of 60 min of PA per day, with more active time being accrued during weekdays than weekends. Children with greater FMS proficiency were found to spend more time in PA than those who were less skillful during weekends. Further research is recommended to examine PA and FMS proficiency associations, exploring the role of social interactions on weekends and weekdays. © 2014 Japan Pediatric Society.

  8. Hereditary non-polyposis colorectal cancer is predicted to contribute towards colorectal cancer in young South African blacks

    Directory of Open Access Journals (Sweden)

    M. Ramsay

    2009-12-01

    Full Text Available A disproportionately large number of young (<50 years black patients present with colorectal cancer (CRC in South Africa. Although a phenomenon previously described elsewhere in Africa, its specificmolecular basis,whether sporadic or hereditary, has not been established. Molecular analysis of these tumours could link them to the features known to be associated with specific types of hereditary colorectal cancer, specifically through examination of levels of microsatellite instability, promoter methylation and the presence or absence of KRAS and BRAF mutations. The molecular features of cancer tissue samples from 44 CRC cases of black and white patients in South Africa were accordingly retrospectively analysed without knowledge of family history. Compared with samples from older blacks (>50 years, those from young black patients presented more often with a low methylation phenotype (CIMP-L and high levels of microsatellite instability (MSI-H. Furthermore, as determined by real-time PCR using probe technology, the tissues from35%of young blacks showed mutations within exon 1 of the KRAS gene. The BRAF-V600E mutation was only evident in the case of a single young black patient. Based on these results it seems likely that a proportion of CRC cases in young black patients from South Africa develop through the accumulation of mutations resulting in a mismatch repair deficiency linked to MSI-H and, possibly, germline mutations in the mismatch repair genes. The features in these patients are consistent with a diagnosis of the Hereditary Non-Polyposis Colorectal Cancer (HNPCC syndrome. This finding has important implications for patient management and suggests that family members may be at high risk for CRC.

  9. Colorectal Cancer: The Importance of Early Detection

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

  10. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... before 50). Dave has Lynch syndrome and had colorectal cancer at 28. Amy found out she has Lynch syndrome when she was diagnosed with colorectal cancer days after turning 47. Why is it Important ...

  11. Colorectal Cancer—Health Professional Version

    Science.gov (United States)

    Colorectal cancer studies often consider colon and rectal cancer together. Worldwide, colorectal cancer is the third most common form of cancer. Find evidence-based information on colon and rectal cancer treatment, causes and prevention, screening, research, genetics, and statistics.

  12. Colorectal Cancer: What You Should Know

    Science.gov (United States)

    ... Products For Consumers Home For Consumers Consumer Updates Colorectal Cancer: What You Should Know Share Tweet Linkedin Pin ... with—and more than 50,000 died from—colorectal cancer, according to the National Cancer Institute. It is ...

  13. DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kuehne, Martin; Fleckenstein, Jochen; Graeber, Stefan; Graf, Norbert; Ruebe, Christian

    2010-01-01

    Purpose: To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

  14. Human Postmeiotic Segregation 2 Exhibits Biased Repair at Tetranucleotide Microsatellite Sequences

    OpenAIRE

    Shah, Sandeep N.; Eckert, Kristin A.

    2009-01-01

    The mismatch repair (MMR) system plays a major role in removing DNA polymerization errors, and loss of this pathway results in hereditary cancers characterized by microsatellite instability. We investigated microsatellite stability during DNA replication within human postmeiotic segregation 2 (hPMS2)–deficient and proficient human lymphoblastoid cell lines. Using a shuttle vector assay, we measured mutation rates at reporter cassettes containing defined mononucleotide, dinucleotide, and tetra...

  15. 'Regular' and 'emergency' repair

    International Nuclear Information System (INIS)

    Luchnik, N.V.

    1975-01-01

    Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)

  16. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ... Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal

  17. Repair kinetics in tissues

    International Nuclear Information System (INIS)

    Thames, H.D.

    1989-01-01

    Monoexponential repair kinetics is based on the assumption of a single, dose-independent rate of repair of sublethal injury in the target cells for tissue injury after exposure to ionizing radiation. Descriptions of the available data based on this assumption have proved fairly successful for both acutely responding (skin, lip mucosa, gut) and late-responding (lung, spinal cord) normal tissues. There are indications of biphasic exponential repair in both categories, however. Unfortunately, the data usually lack sufficient resolution to permit unambiguous determination of the repair rates. There are also indications that repair kinetics may depend on the size of the dose. The data are conflicting on this account, however, with suggestions of both faster and slower repair after larger doses. Indeed, experiments that have been explicitly designed to test this hypothesis show either no effect (gut, spinal cord), faster repair after higher doses (lung, kidney), or slower repair after higher doses (skin). Monoexponential repair appears to be a fairly accurate description that provides an approximation to a more complicated picture, the elucidation of whose details will, however, require very careful and extensive experimental study. (author). 30 refs.; 1 fig

  18. Colorectal cancer with venous tumor thrombosis

    OpenAIRE

    Kensuke Otani; Soichiro Ishihara; Keisuke Hata; Koji Murono; Kazuhito Sasaki; Koji Yasuda; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Kazushige Kawai; Hiroaki Nozawa; Hironori Yamaguchi; Toshiaki Watanabe

    2018-01-01

    Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological ...

  19. Colorectal cancer complicating Crohn's disease.

    Science.gov (United States)

    Freeman, H J

    2001-04-01

    Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  20. Colorectal Cancer Complicating Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2001-01-01

    Full Text Available Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%. All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%, no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  1. Relevance of DNA repair pathways on ascorbic acid effects on Echerichia Coli K-12 cells

    International Nuclear Information System (INIS)

    Slyus, M.A. van; Oliveira, R.L.B. da C.; Felzenszwalb, I.; Gomes, R.A.; Menck, C.F.

    1985-01-01

    Inactivation kinetics were performed with repair proficient and deficient Escherichia coli K-12 cells treated with oxidized solutions of ascorbic acid. The repair pathways controlled by the recA and uvrA gene products are essential for cell survival to the treatment. However, SOS chromotest result indicates that the SOS functions are only induced at high and toxic concentrations of the drug. Moreover, single strand breaks in DNA from treated cells are detected, demonstrating genome damage promoted by oxidized solutions of ascorbate. (M.A.C.) [pt

  2. Molecular Classification and Correlates in Colorectal Cancer

    OpenAIRE

    Ogino, Shuji; Goel, Ajay

    2008-01-01

    Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

  3. Cost-effectiveness of colorectal cancer screening

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2011-01-01

    textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to

  4. Bone morphogenetic protein signalling in colorectal cancer

    NARCIS (Netherlands)

    Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

    2008-01-01

    Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The

  5. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines

    International Nuclear Information System (INIS)

    Bedford, P.; Fichtinger-Schepman, A.M.; Shellard, S.A.; Walker, M.C.; Masters, J.R.; Hill, B.T.

    1988-01-01

    The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin

  6. Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells.

    Science.gov (United States)

    Gong, Shu; Xu, Dongsheng; Zhu, Jialin; Zou, Fangdong; Peng, Rui

    2018-05-22

    Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity

  7. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  8. Online Assessment of Oral Proficiency for Intercultural Professional Communication

    NARCIS (Netherlands)

    Rusman, Ellen; Stoyanov, Slavi

    2012-01-01

    Rusman, E., & Stoyanov, S. (2011, 18 May). Online Assessment of Oral Proficiency for Intercultural Professional Communication. Presentation about the CEFcult project (www.cefcult.eu) at the workshop ‘Crossing borders’ organised by the Talenacademie, Heerlen, The Netherlands: Open University in the

  9. Cultutal Factors Affecting English Proficiency in Rural Areas

    Science.gov (United States)

    Ler, Ee Chop

    2012-01-01

    The purpose of this study is to investigate the rural "cultural" problems and to determine their effect on the learning of English. Twenty students from different ethnic backgrounds and English language proficiency in six rural schools in Terengganu, Malaysia were interviewed. In addition the teachers also from different rural schools…

  10. Predicting the Proficiency Level of Language Learners Using Lexical Indices

    Science.gov (United States)

    Crossley, Scott A.; Salsbury, Tom; McNamara, Danielle S.

    2012-01-01

    This study explores how second language (L2) texts written by learners at various proficiency levels can be classified using computational indices that characterize lexical competence. For this study, 100 writing samples taken from 100 L2 learners were analyzed using lexical indices reported by the computational tool Coh-Metrix. The L2 writing…

  11. Pathways from Toddler Information Processing to Adolescent Lexical Proficiency

    Science.gov (United States)

    Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.

    2015-01-01

    This study examined the relation of 3-year core information-processing abilities to lexical growth and development. The core abilities covered four domains--memory, representational competence (cross-modal transfer), processing speed, and attention. Lexical proficiency was assessed at 3 and 13 years with the Peabody Picture Vocabulary Test (PPVT)…

  12. Determinants of Second Language Proficiency among Refugees in the Netherlands

    Science.gov (United States)

    van Tubergen, Frank

    2010-01-01

    Little is known about the language acquisition of refugees in Western countries. This study examines how pre- and post-migration characteristics of refugees are related to their second language proficiency. Data are from a survey of 3,500 refugees, who were born in Afghanistan, Iran, Iraq, former Yugoslavia and Somalia, and who resided in the…

  13. Proficiency test on incurred and spiked pesticide residues in cereals

    DEFF Research Database (Denmark)

    Poulsen, Mette Erecius; Christensen, Hanne Bjerre; Herrmann, Susan Strange

    2009-01-01

    A proficiency test on incurred and spiked pesticide residues in wheat was organised in 2008. The test material was grown in 2007 and treated in the field with 14 pesticides formulations containing the active substances, alpha-cypermethrin, bifentrin, carbendazim, chlormequat, chlorpyrifos...

  14. Reading Processing Skills among EFL Learners in Different Proficiency Levels

    Science.gov (United States)

    Dhanapala, Kusumi Vasantha; Yamada, Jun

    2015-01-01

    This study aims to understand how EFL learners in different reading proficiency levels comprehend L2 texts, using five-component skills involving measures of (1) vocabulary knowledge, (2) drawing inferences and predictions, (3) knowledge of text structure and discourse organization, (4) identifying the main idea and summarizing skills, and (5)…

  15. Determinants of second language proficiency among refugees in the Netherlands

    NARCIS (Netherlands)

    Tubergen, F.A. van

    2010-01-01

    Little is known about the language acquisition of refugees in Western countries. This study examines how pre- and post-migration characteristics of refugees are related to their second language proficiency. Data are from a survey of 3,500 refugees, who were born in Afghanistan, Iran, Iraq, former

  16. A new role of proficiency testing in nuclear analytical work

    DEFF Research Database (Denmark)

    Heydorn, Kaj

    2008-01-01

    The most recent definition of measurement result requires a statement of uncertainty whenever results obtained by nuclear or other quantitative methods of analysis are reported. Proficiency testing (PT) therefore must include the ability of laboratories to present not only unbiased quantity values...

  17. The Effects of Elementary Departmentalization on Mathematics Proficiency

    Science.gov (United States)

    Taylor-Buckner, Nicole C.

    2014-01-01

    Mathematics education in the elementary schools has experienced many changes in recent decades. With the curriculum becoming more complex as a result of each modification, immense pressure has been put on schools to increase student proficiency. The Common Core State Standards is the latest example of this. These revisions to the mathematics…

  18. Motor proficiency and physical fitness in active and inactive girls ...

    African Journals Online (AJOL)

    In modern day society physical activity levels diminish rapidly among girls and may be a direct consequence of girls experiencing motor difficulties. Therefore the aim of the study was to compare motor proficiency levels and physical fitness levels among active and inactive girls (N=97), aged 12 to 13 years. The BOTMP ...

  19. Beyond Host Language Proficiency: Coping Resources Predicting International Students' Satisfaction

    Science.gov (United States)

    Mak, Anita S.; Bodycott, Peter; Ramburuth, Prem

    2015-01-01

    As international students navigate in a foreign educational environment, having higher levels of coping or stress-resistance resources--both internal and external--could be related to increased satisfaction with personal and university life. The internal coping resources examined in this study were host language proficiency, self-esteem,…

  20. Developing Autonomous Learning for Oral Proficiency Using Digital Storytelling

    Science.gov (United States)

    Kim, SoHee

    2014-01-01

    Since online educational technology can support a ubiquitous language learning environment, there are many ways to develop English learners' autonomy through self-access learning. This study investigates whether English as a second language (ESL) learners can improve their oral proficiency through independent study by using online self-study…

  1. Advisory Working Alliance, Perceived English Proficiency, and Acculturative Stress

    Science.gov (United States)

    Wei, Meifen; Tsai, Pei-Chun; Chao, Ruth Chu-Lien; Du, Yi; Lin, Shu-Ping

    2012-01-01

    The aim of this study was to examine the moderators of (a) general or cross-cultural advisory working alliances and (b) perceived English proficiency on the association between acculturative stress and psychological distress. A total of 143 East Asian international students completed an online survey. Results from a hierarchical regression…

  2. The Education Consequences of Language Proficiency for Young Children

    NARCIS (Netherlands)

    Yao, Yuxin; Ohinata, Asako; van Ours, Jan

    2016-01-01

    This paper studies the educational consequences of language proficiency by investigating the relationship between dialect-speaking and academic performance of 5-6 year old children in the Netherlands. We find that dialect-speaking has a modestly negative effect on boys' language test scores. In

  3. The educational consequences of language proficiency for young children

    NARCIS (Netherlands)

    Yao, Yuxin; Ohinata, Asako; van Ours, Jan

    2016-01-01

    Our paper studies the educational consequences of language proficiency by investigating the relationship between dialect-speaking and academic performance of 5–6 year old children in the Netherlands. We find that dialect-speaking has a modestly negative effect on boys’ language test scores. In

  4. Teaching Mathematical Problem Solving to Students with Limited English Proficiency.

    Science.gov (United States)

    Kaplan, Rochelle G.; Patino, Rodrigo A.

    Many mainstreamed students with limited English proficiency continue to face the difficulty of learning English as a second language (ESL) while studying mathematics and other content areas framed in the language of native speakers. The difficulty these students often encounter in mathematics classes and their poor performance on subsequent…

  5. Naming Abilities in Low-Proficiency Second Language Learners

    Science.gov (United States)

    Borodkin, Katy; Faust, Miriam

    2014-01-01

    Difficulties in second language (L2) learning are often associated with recognizable learning difficulties in native language (L1), such as in dyslexia. However, some individuals have low L2 proficiency but intact L1 reading skills. These L2 learners experience frequent tip-of-the-tongue states while naming in L1, which indicates that they have a…

  6. Differential Effects of Learning Games on Mathematics Proficiency

    Science.gov (United States)

    Chang, Mido; Evans, Michael A.; Kim, Sunha; Norton, Anderson; Samur, Yavuz

    2015-01-01

    This study examined the effects of a learning game, [The Math App] on the mathematics proficiency of middle school students. For the study, researchers recruited 306 students, Grades 6-8, from two schools in rural southwest Virginia. Over a nine-week period, [The Math App] was deployed as an intervention for investigation. Students were assigned…

  7. Listening and Reading Proficiency Levels of College Students

    Science.gov (United States)

    Tschirner, Erwin

    2016-01-01

    This article examines listening and reading proficiency levels of U.S. college foreign language students at major milestones throughout their undergraduate career. Data were collected from more than 3,000 participants studying seven languages at 21 universities and colleges across the United States. The results show that while listening…

  8. Impact of English Proficiency on Academic Performance of International Students

    Science.gov (United States)

    Martirosyan, Nara M.; Hwang, Eunjin; Wanjohi, Reubenson

    2015-01-01

    Using an ex-post facto, non-experimental approach, this research examined the impact of English language proficiency and multilingualism on the academic performance of international students enrolled in a four-year university located in north central Louisiana in the United States. Data were collected through a self-reported questionnaire from 59…

  9. Linguistic Proficiency and Strategies on Reading Performance in English

    Science.gov (United States)

    Talebi, Seyed Hassan

    2015-01-01

    General English (L2) proficiency and reading strategies are believed to be highly effective in successful reading performance. However, available studies rarely investigated the combined effects of these two variables on successful reading. To fill this gap, 78 university students were divided into four groups of different degrees of these two…

  10. Music Teachers in Turkey: Their Proficiency, Working Environments and Problems

    Science.gov (United States)

    Otacioglu, Sena Gursen

    2008-01-01

    The aim of this study was the collection of data concerning Turkish music teachers' proficiency and their place in the primary and secondary education system. In addition, information was collected regarding the teachers' working environment and professional complications. A total of 200 music teachers' opinions were compiled for the determination…

  11. Planes, Politics and Oral Proficiency: Testing International Air Traffic Controllers

    Science.gov (United States)

    Moder, Carol Lynn; Halleck, Gene B.

    2009-01-01

    This study investigates the variation in oral proficiency demonstrated by 14 Air Traffic Controllers across two types of testing tasks: work-related radio telephony-based tasks and non-specific English tasks on aviation topics. Their performance was compared statistically in terms of level ratings on the International Civil Aviation Organization…

  12. Foreign Language Teachers' Language Proficiency and Their Language Teaching Practice

    Science.gov (United States)

    Richards, Heather; Conway, Clare; Roskvist, Annelies; Harvey, Sharon

    2013-01-01

    Teachers' subject knowledge is recognized as an essential component of effective teaching. In the foreign language context, teachers' subject knowledge includes language proficiency. In New Zealand high schools, foreign languages (e.g. Chinese, French, German, Japanese and Spanish) have recently been offered to learners earlier in their schooling,…

  13. Rater Judgment and English Language Speaking Proficiency. Research Report

    Science.gov (United States)

    Chalhoub-Deville, Micheline; Wigglesworth, Gillian

    2005-01-01

    The paper investigates whether there is a shared perception of speaking proficiency among raters from different English speaking countries. More specifically, this study examines whether there is a significant difference among English language learning (ELL) teachers, residing in Australia, Canada, the UK, and the USA when rating speech samples of…

  14. The Minnesota Articulation Project and Its Proficiency-Based Assessments.

    Science.gov (United States)

    Chalhoub-Deville, Micheline

    1997-01-01

    Reports on the Minnesota Articulation Project, providing an overview of the projects' three principal working groups: political action, curriculum, and assessment. The article then outlines the theoretical underpinnings of the proficiency-based assessment instruments developed in French, German, and Spanish and describes in detail the content and…

  15. P-2 Years Targeted to Achieve Grade 3 Reading Proficiency

    Science.gov (United States)

    Gewertz, Catherine

    2011-01-01

    In a bid to help more students read proficiently in 3rd grade--a skill considered critical to their future educational success--new laws and initiatives springing up around the country require educators to step up their efforts to identify and help struggling readers even before they enter kindergarten. It's not unusual for states or school…

  16. Trends in Teacher Certification: Equipping Teachers to Prepare Proficient Readers

    Science.gov (United States)

    Rowland, Julie

    2015-01-01

    Ensuring that students are reading proficiently by third grade is a key component of keeping students on track to graduate high school and pursue college and careers. Because of the magnitude of this academic milestone, states typically pursue policies that promote early identification and intervention for struggling readers. However, teachers are…

  17. Statistical analysis of nematode counts from interlaboratory proficiency tests

    NARCIS (Netherlands)

    Berg, van den W.; Hartsema, O.; Nijs, Den J.M.F.

    2014-01-01

    A series of proficiency tests on potato cyst nematode (PCN; n=29) and free-living stages of Meloidogyne and Pratylenchus (n=23) were investigated to determine the accuracy and precision of the nematode counts and to gain insights into possible trends and potential improvements. In each test, each

  18. A retrospective evaluation of proficiency testing, and rapid HIV test ...

    African Journals Online (AJOL)

    Background: Proficiency testing (PT) has been implemented as a form of External Quality Assurance (EQA) by the National HIV Reference Laboratory in Kenya since 2007 in order to monitor and improve on the quality of HIV testing and counselling HTC services. Objective: To compare concordance between National HIV ...

  19. Predicting Lexical Proficiency in Language Learner Texts Using Computational Indices

    Science.gov (United States)

    Crossley, Scott A.; Salsbury, Tom; McNamara, Danielle S.; Jarvis, Scott

    2011-01-01

    The authors present a model of lexical proficiency based on lexical indices related to vocabulary size, depth of lexical knowledge, and accessibility to core lexical items. The lexical indices used in this study come from the computational tool Coh-Metrix and include word length scores, lexical diversity values, word frequency counts, hypernymy…

  20. 76 FR 66318 - Announcement of Funding Awards; Limited English Proficiency Initiative Program (LEPI), Fiscal...

    Science.gov (United States)

    2011-10-26

    ... limited English proficiency (LEP), and develop and implement a system to provide those services so LEP... Awards; Limited English Proficiency Initiative Program (LEPI), Fiscal Year 2010/2011 AGENCY: Office of... (NOFA) for the Limited English Proficiency Initiative (LEPI) Program for Fiscal Year (FY) 2010/2011...

  1. Comparing Examinee Attitudes Toward Computer-Assisted and Other Oral Proficiency Assessments.

    Science.gov (United States)

    Kenyon, Dorry M.; Malabonga, Valerie

    2001-01-01

    Examined attitudes toward taking different formats of oral proficiency assessments across three languages: Spanish, Arabic, and Chinese. Students were administered both the tape-mediated Simulated Oral Proficiency Interview (SOPI) and a new Computerized Oral Proficiency Instrument (COPI). Questionnaire responses showed examinees, particularly…

  2. Measures for Determining English Language Proficiency and the Resulting Implications for Instructional Provision and Intervention

    Science.gov (United States)

    Albers, Craig A.; Kenyon, Dorry M.; Boals, Timothy J.

    2009-01-01

    Although numerous English language proficiency (ELP) measures currently exist, many were developed prior to the No Child Left Behind Act of 2001 (NCLB). These pre-NCLB measures typically focused on social language proficiency, whereas post-NCLB measures are linked to ELP standards and focus on academic language proficiency (ALP). ELP measures are…

  3. Snowmobile Repair. Teacher Edition.

    Science.gov (United States)

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  4. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

    Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)

  5. Investigating Executive Working Memory and Phonological Short-Term Memory in Relation to Fluency and Self-Repair Behavior in L2 Speech

    Science.gov (United States)

    Georgiadou, Effrosyni; Roehr-Brackin, Karen

    2017-01-01

    This paper reports the findings of a study investigating the relationship of executive working memory (WM) and phonological short-term memory (PSTM) to fluency and self-repair behavior during an unrehearsed oral task performed by second language (L2) speakers of English at two levels of proficiency, elementary and lower intermediate. Correlational…

  6. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  7. Proficiency training on a virtual reality robotic surgical skills curriculum.

    Science.gov (United States)

    Bric, Justin; Connolly, Michael; Kastenmeier, Andrew; Goldblatt, Matthew; Gould, Jon C

    2014-12-01

    The clinical application of robotic surgery is increasing. The skills necessary to perform robotic surgery are unique from those required in open and laparoscopic surgery. A validated laparoscopic surgical skills curriculum (Fundamentals of Laparoscopic Surgery or FLS™) has transformed the way surgeons acquire laparoscopic skills. There is a need for a similar skills training and assessment tool for robotic surgery. Our research group previously developed and validated a robotic training curriculum in a virtual reality (VR) simulator. We hypothesized that novice robotic surgeons could achieve proficiency levels defined by more experienced robotic surgeons on the VR robotic curriculum, and that this would result in improved performance on the actual daVinci Surgical System™. 25 medical students with no prior robotic surgery experience were recruited. Prior to VR training, subjects performed 2 FLS tasks 3 times each (Peg Transfer, Intracorporeal Knot Tying) using the daVinci Surgical System™ docked to a video trainer box. Task performance for the FLS tasks was scored objectively. Subjects then practiced on the VR simulator (daVinci Skills Simulator) until proficiency levels on all 5 tasks were achieved before completing a post-training assessment of the 2 FLS tasks on the daVinci Surgical System™ in the video trainer box. All subjects to complete the study (1 dropped out) reached proficiency levels on all VR tasks in an average of 71 (± 21.7) attempts, accumulating 164.3 (± 55.7) minutes of console training time. There was a significant improvement in performance on the robotic FLS tasks following completion of the VR training curriculum. Novice robotic surgeons are able to attain proficiency levels on a VR simulator. This leads to improved performance in the daVinci surgical platform on simulated tasks. Training to proficiency on a VR robotic surgery simulator is an efficient and viable method for acquiring robotic surgical skills.

  8. Effect of 8-MOP plus UVA treatment on survival and repair of plasmid pBR322

    International Nuclear Information System (INIS)

    Bauluz, C.; Vidania, R. de

    1991-01-01

    We have studied the lethality produced in pBR322 DNA after PUVA treatment (8-MOP+UVA). As recipients, we used a collection of E. coli strains differing in their repair capacities and analysed the involvement of several DNA repair pathways in the removal of plasmid lesions. We have also studied the effect of UVA radiation alone, in order to determine more precisely the effect attributable only to psoralen molecules. Results showed a strong lethal effect derived from PUVA treatment; however, some plasmid recovery was achieved in bacterial hosts proficient in Excision repair and SOS repair. Another repair pathway, only detectable at high density of lesions, appeared to be relevant for the removal of 8-MOP:DNA adducts.(Author) 11 refs

  9. Undefined familial colorectal cancer.

    Science.gov (United States)

    Zambirinis, Constantinos Pantelis; Theodoropoulos, George; Gazouli, Maria

    2009-10-15

    Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.

  10. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R

    2010-01-01

    for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we......Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology...

  11. EPIDEMIOLOGICAL EVALUATION OF COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    B. Shafayan M. Keyhani

    2003-07-01

    Full Text Available This study was carried out to analyze certain epidemiological variations in Iranian patients with colorectal cancer. (CRC: From March 1981 up to March 1993, 103 patients were analyzed retrospectively for age, gender, marital state, job, nutritional habits, presenting symptoms and histopathological features. Most of the patients with colorectal cancer were male, age range 20-75 (mean 56, 25.4 percent were long-term smokers and bleeding was the most common symptom. The rectum was the most common site and moderately differentiated carcinoma was considered as the main common histopathological variety. In conclusion, increasing incidence of colorectal cancer in younger Iranian population, below 30 and late admission and diagnosis were the main findings in the present study necessitating screening programs with annual fecal occult blood tests in high risk families.

  12. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  13. [Oligometastasized colorectal cancer-modern treatment strategies].

    Science.gov (United States)

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  14. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  15. Mutations in APC, CTNNBI en K-ras genes and expression of hMLHI in sporadic colorectal carcinomas from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Wark, P.A.; Merdan Saritas, M.

    2005-01-01

    Background - The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of

  16. Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

    Science.gov (United States)

    Kravochuck, Sara E; Church, James M

    2017-12-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

  17. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%; inherited (5% and familial (25%. The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN, microsatellite instability (MSI and CpG island methylator phenotype (CIMP. Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53, and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined

  18. Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage

    International Nuclear Information System (INIS)

    Noda, Taichi; Takahashi, Akihisa; Kondo, Natsuko; Mori, Eiichiro; Okamoto, Noritomo; Nakagawa, Yosuke; Ohnishi, Ken; Zdzienicka, Malgorzata Z.; Thompson, Larry H.; Helleday, Thomas; Asada, Hideo

    2011-01-01

    The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA -/- , FANCC -/- , FANCA -/- C -/- , FANCD2 -/- and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical γH2AX-staining assay. Although the sensitivity of FANCA -/- , FANCC -/- and FANCA -/- C -/- cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2 -/- cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, γH2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. -- Research highlights: → We examined to clarify the repair pathways of formaldehyde-induced DNA damage. Formaldehyde induces DNA double strand breaks (DSBs). → DSBs are repaired through the Fanconi anemia (FA) repair pathway. → This pathway is independent of the FA nuclear core complex. → We also found that homologous recombination repair was induced by formaldehyde.

  19. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Krukshenk, A.

    1986-01-01

    Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)

  20. Robotic colorectal surgery: previous laparoscopic colorectal experience is not essential.

    Science.gov (United States)

    Sian, Tanvir Singh; Tierney, G M; Park, H; Lund, J N; Speake, W J; Hurst, N G; Al Chalabi, H; Smith, K J; Tou, S

    2018-06-01

    A background in minimally invasive colorectal surgery (MICS) has been thought to be essential prior to robotic-assisted colorectal surgery (RACS). Our aim was to determine whether MICS is essential prior to starting RACS training based on results from our initial experience with RACS. Two surgeons from our centre received robotic training through the European Academy of Robotic Colorectal Surgery (EARCS). One surgeon had no prior formal MICS training. We reviewed the first 30 consecutive robotic colorectal procedures from a prospectively maintained database between November 2014 and January 2016 at our institution. Fourteen patients were male. Median age was 64.5 years (range 36-82) and BMI was 27.5 (range 20-32.5). Twelve procedures (40%) were performed by the non-MICS-trained surgeon: ten high anterior resections (one conversion), one low anterior resection and one abdomino-perineal resection of rectum (APER). The MICS-trained surgeon performed nine high and four low anterior resections, one APER and in addition three right hemicolectomies and one abdominal suture rectopexy. There were no intra-operative complications and two patients required re-operation. Median post-operative stay was five days (range 1-26). There were two 30-day re-admissions. All oncological resections had clear margins and median node harvest was 18 (range 9-39). Our case series demonstrates that a background in MICS is not essential prior to starting RACS training. Not having prior MICS training should not discourage surgeons from considering applying for a robotic training programme. Safe and successful robotic colorectal services can be established after completing a formal structured robotic training programme.

  1. Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD).

    Science.gov (United States)

    Ramchander, N C; Ryan, N A J; Crosbie, E J; Evans, D G

    2017-04-05

    Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Constitutional mismatch repair

  2. The English Proficiency of the Academics of the Teacher Training and Education Institutions

    Directory of Open Access Journals (Sweden)

    Ali Saukah

    2016-02-01

    Full Text Available The study is aimed at describing the general English proficiency level of the academics of Teacher Training and Education Institutions (LPTK's as indicated by their TOEFL scores. Specifically, the study is focused on finding out whether there is any difference among the academics' English proficiencies when they are grouped in terms of the geographic regions of their institutions and their fields of study. This study is also intended to reveal any possible relationship between the academics' English proficiency and their age. The results indicate that the English proficiency of the academics on the average is far below the average of that of the international students. The academics in West Java are the highest in their English proficiency, and the English group, as expected, has the best English proficiency. In addition, there is a negative correlation between English proficiency and age

  3. Minilaparoscopic Colorectal Resections: Technical Note

    Directory of Open Access Journals (Sweden)

    S. Bona

    2012-01-01

    Full Text Available Laparoscopic colorectal resections have been shown to provide short-term advantages in terms of postoperative pain, general morbidity, recovery, and quality of life. To date, long-term results have been proved to be comparable to open surgery irrefutably only for colon cancer. Recently, new trends keep arising in the direction of minimal invasiveness to reduce surgical trauma after colorectal surgery in order to improve morbidity and cosmetic results. The few reports available in the literature on single-port technique show promising results. Natural orifices endoscopic techniques still have very limited application. We focused our efforts in standardising a minilaparoscopic technique (using 3 to 5 mm instruments for colorectal resections since it can provide excellent cosmetic results without changing the laparoscopic approach significantly. Thus, there is no need for a new learning curve as minilaparoscopy maintains the principle of instrument triangulation. This determines an undoubted advantage in terms of feasibility and reproducibility of the procedure without increasing operative time. Some preliminary experiences confirm that minilaparoscopic colorectal surgery provides acceptable results, comparable to those reported for laparoscopic surgery with regard to operative time, morbidity, and hospital stay. Randomized controlled studies should be conducted to confirm these early encouraging results.

  4. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  5. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Colorectal Cancer Awareness and Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-06

    An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer.  Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2017.

  7. Costs of Colorectal Cancer Screening

    Centers for Disease Control (CDC) Podcasts

    2017-04-04

    A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening.  Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/4/2017.

  8. Optimisation of colorectal cancer treatment

    NARCIS (Netherlands)

    Broek, Colette Bernadine Maria-Theresia van den

    2014-01-01

    Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with

  9. Wound Disruption Following Colorectal Operations.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

    2015-12-01

    Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

  10. HISTOMORPHOLOGICAL STUDY OF COLORECTAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Sarvesh

    2015-07-01

    Full Text Available BACKGROUND: Colorectal cancer is the most common cancer in men and in women worldwide. Incidence rates of colorectal cancer vary 10 - fold in both sexes worldwide, Within Asia, the incidence rates vary widely and are uniformly low in all south Asian countries and high i n all developed Asian countries. Fortunately, the age adjusted incidence rates of colorectal cancer in all the Indian cancer registries are very close to the lowest rates in the world. The present study is under taken to study the prevalence and types of c olorectal cancer among the patients in the rural population in and around Chidambaram. OBJECTIVES: To study the prevalence of malignant colorectal neoplasms among the speci mens received in the Department of Pathology and the gross and histomorphological pa ttern of the lesions and finally to correlate the findings with clinical data. METHOD: The materials consisted of 68 specimens who were submitted to the Department of Pathology, during the period of Jan 2008 - Dec 2012. Data collected and entered in MS - Excel and were analyzed using SPSS - 16. RESULTS : Out of 8454 colonoscopic specimens, 68(0.8% showed colorectal malignancy. A higher frequency of colorectal was seen in 6 th decade. Out of 68 specimens of malignant neoplasms majority were Carcinoma of the Rectum (79.41% followed in decreasing order of frequency by malignant lesions of descending colon(8.82%, ascending and Sigmoid colon (4.41% each, recto - sigmoid (2.94% and cecum (2.63%, and transverse colon (2.63%. Youngest patient was 19 years old and the o ldest patient was 80 years old with a mean age of 49.5 years and median age of 50 years. CONCLUSION: Colorectal cancer is a common and lethal disease. The adenoma carcinoma. S equence offers a window of opportunity in which the precursor lesion or early car cinoma can be removed endoscopically to prevent systematic disease. The result of a careful and systematic examination of surgical specimens from patients with

  11. First Language Proficiency and Successful Foreign Language Learning: The Case of High School Students Learning French as a Foreign Language

    Science.gov (United States)

    Gnintedem, Antoine

    2014-01-01

    This study investigated whether there was a correlation between first language proficiency as measured by the Mississippi Curriculum Test (MCT II) Reading and Language Arts and foreign language proficiency as measured by the French Language Proficiency Test. Data for the independent variable, first language proficiency, was collected from the…

  12. Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

    NARCIS (Netherlands)

    Diergaarde, B.

    2004-01-01

    Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

  13. DNA Repair Systems

    Indian Academy of Sciences (India)

    DNA molecule which makes it ideal for storage and propagation of genetic information. ... of these errors are broadly referred to as DNA repair. DNA can ... changes occur in the human genome per day. ..... nails, frequent physical and mental.

  14. Brain aneurysm repair - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000123.htm Brain aneurysm repair - discharge To use the sharing features ... this page, please enable JavaScript. You had a brain aneurysm . An aneurysm is a weak area in ...

  15. Ventral hernia repair

    Science.gov (United States)

    ... incarcerated) in the hernia and become impossible to push back in. This is usually painful. The blood supply ... you are lying down or that you cannot push back in. Risks The risks of ventral hernia repair ...

  16. Omphalocele repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100033.htm Omphalocele repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Omphalocele is an abdominal wall defect at the base ...

  17. Nordic proficiency test for whole body counting facilities

    Energy Technology Data Exchange (ETDEWEB)

    del Risco Norrlid, L. (Swedish Radiation Safety Authority (Sweden)); Halldorsson, O. (Icelandic Radiation Safety Authority, GR (Iceland)); Holm, S. (Copenhagen Univ. Hospital. NM and PET (Denmark)); Huikari, J. (Radiation and Nuclear Safety Authority (Finland)); Isaksson, M. (Goeteborg Univ., Dep. Radiation Physics Sahlgren Academy (Sweden)); Lind, B. (Norwegian Radiation Protection Authority (Norway))

    2012-01-15

    The PIANOLIB activity aims to harmonize the calibrations of the measurement equipment in the region and to evaluate the quality of this kind of measurement by means of a proficiency test exercise. In this report the results of the proficiency test are presented. The exercise consisted in determining the activity of a phantom filled with two sets of certified radioactive materials, K-40 and Cs-137, in radioactive rods, uniformly spaced inside of the phantom. Most of the participants were able to quantify correctly the activities of K-40 and Cs-137 and by comparison with the results of a previous exercise of this kind, the overall performance is equally good. The problems experienced by laboratories which submitted non-acceptable results could generally be attributed to the calibration of their systems. It is important to keep the practice of intercomparison and NKS continues to be the best framework for supporting this kind of activity. (Author)

  18. Language proficiency and health status: are bilingual immigrants healthier?

    Science.gov (United States)

    Schachter, Ariela; Kimbro, Rachel T; Gorman, Bridget K

    2012-03-01

    Bilingual immigrants appear to have a health advantage, and identifying the mechanisms responsible for this is of increasing interest to scholars and policy makers in the United States. Utilizing the National Latino and Asian American Study (NLAAS; n = 3,264), we investigate the associations between English and native-language proficiency and usage and self-rated health for Asian and Latino U.S. immigrants from China, the Philippines, Vietnam, Mexico, Cuba, and Puerto Rico. The findings demonstrate that across immigrant ethnic groups, being bilingual is associated with better self-rated physical and mental health relative to being proficient in only English or only a native language, and moreover, these associations are partially mediated by socioeconomic status and family support but not by acculturation, stress and discrimination, or health access and behaviors.

  19. Linguistic Proficiency and Strategies on Reading Performance in English

    Directory of Open Access Journals (Sweden)

    Seyed Hassan Talebi

    2015-01-01

    Full Text Available General English (L2 proficiency and reading strategies are believed to be highly effective in successful reading performance. However, available studies rarely investigated the combined effects of these two variables on successful reading. To fill this gap, 78 university students were divided into four groups of different degrees of these two variables in L2 and given a reading test in English and an interview for assessing how much of the problems in L2 reading among the four groups were rooted in linguistic competence and/or strategic competence. Findings evinced that the high general proficiency level coupled with high awareness and use of reading strategies would result in best performance and that the pattern of answers to different components of reading question is different in different groups. It is concluded that both of the variables should be emphasized simultaneously for the best performance in reading comprehension.

  20. Fluctuation analysis of proficient and dysgraphic handwriting in children

    Science.gov (United States)

    Rosenblum, S.; Roman, H. E.

    2009-03-01

    We analyze handwriting records from several school children with the aim of characterizing the fluctuating behavior of the writing speed. It will be concluded that remarkable differences exist between proficient and dysgraphic handwritings which were unknown so far. It is shown that in the case of proficient handwriting, the variations in handwriting speed are strongly autocorrelated within times corresponding to the completion of a single character or letter, while become uncorrelated at longer times. In the case of dysgraphia, such correlations persist on longer time scales and the autocorrelation function seems to display algebraic time decay, indicating the presence of strong anomalies in the handwriting process. Applications of the results in educational/clinical programs are envisaged.

  1. Radon Measurement Proficiency (RMP) Program methods and devices

    International Nuclear Information System (INIS)

    Harrison, J.; Hoornbeek, J.; Jalbert, P.; Sensintaffar, E.; Hopper, R.

    1991-01-01

    The US EPA developed the voluntary Radon Measurement Proficiency Program in 1986 in response to a Federal and State need for measurement services firms to demonstrate their proficiency with radon measurement methods and devices. Since that time, the program has set basic standards for the radon measurement industry. The program has grown dramatically since its inception. In 1986, fewer than 50 companies participated in the program. By 1989, more than 5,000 companies were participating. Participants represent firms with an analytical capability as well as firms that rely upon another firm for analysis service. Since the beginning of the RMP Program, the Agency has learned a great deal about radon measurement methods and devices. This paper reviews the measurement devices used in the program and what the EPA has learned about them since the program's inception. Performance data from the RMP Program are used to highlight relevant findings

  2. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    International Nuclear Information System (INIS)

    NONE

    1999-01-01

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair

  3. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-02-12

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

  4. Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Y; Kano, Y; Paul, P; Goto, K; Yamamoto, K [Kobe Univ. (Japan). School of Medicine

    1981-01-01

    Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD/sup +/, suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation.

  5. Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

    International Nuclear Information System (INIS)

    Fujiwara, Yoshisada; Kano, Yoshio; Paul, P.; Goto, Kaoru; Yamamoto, Kazuo

    1981-01-01

    Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD + , suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation. (J.P.N.)

  6. Excision and crosslink repair of DNA and sister chromatid exchanges in cultured human fibroblasts with different repair capacities

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Y.; Kano, Y.; Paul, P.; Goto, K.; Yamamoto, K. (Kobe Univ. (Japan). School of Medicine)

    1981-01-01

    Xeroderma pigmentosum (XP) groups A to G lacked the initial stage of ultraviolet (UV) excision repair in the order of A = G > C > D > E asymptotically equals F, while the XP variant was weakly defective in the later repair steps. Killing sensitivities were in the orders of A >= G > D > C > E asymptotically equals F asymptotically equals variant > normal to UV, A = G > D > F > C = E > variant > normal to 4-nitroquinoline-1-oxide (4NQO), and A > C > D = E = F = variant > G = normal to decarbamoyl mitomycin-C(DCMC). The induced sister chromatid exchange (SCE) frequency was unrelated to the extent of repair deficiency. The SCE induction rate was consistently 3 - 6 fold higher by these UV-like mutagens in XP group A cells than in normal cells. However, repair-proficient Cockayne's syndrome (CS) cells showed a higher SCE induction by UV, which was normalized by NAD/sup +/, suggesting that chromatin lesions as well as DNA damage contribute to SCE. Two-step crosslink repair involves a first rapid half-excision and a second slow nucleotide-excision repair. Fanconi's anemia (FA) cells had an impaired first half-excision and were supersensitive to MC, but not to UV and DCMC. The SCE frequency induced by MC (1 hr) was higher in FA cells than in normal cells despite their normal response to DCMC, and vice versa in XP cells. FA cells lacked the first rapid decline and showed higher remaining SCEs. Thus, part of the crosslink seems to lead to SCE formation. Caffeine synergistically elevated UV-induced SCEs, but not UV induced mutations in V79 cells, implying that SCE may not necessarily involve mutation.

  7. Modifiable risk factors and colorectal adenomas among those at high risk of colorectal cancer

    NARCIS (Netherlands)

    Botma, A.

    2011-01-01

    Epidemiological studies have identified several modifiable risk factors for colorectal neoplasms in the general population. However, associations between modifiable risk factors, including body mass index (BMI), smoking, alcohol consumption and dietary patterns, and colorectal neoplasms in two

  8. Celebrating DNA's Repair Crew.

    Science.gov (United States)

    Kunkel, Thomas A

    2015-12-03

    This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Proficiency Testing Activities of Frequency Calibration Laboratories in Taiwan, 2009

    Science.gov (United States)

    2009-11-01

    cht.com.tw Abstract In order to meet the requirements of ISO 17025 and the demand of TAF (Taiwan Accreditation Foundation) for calibration inter... IEC 17025 General requirements for the competence of testing and calibration laboratories. The proficiency testing results are then important...on-site evaluation, an assessment team is organized to examine the technical competence of the labs and their compliance with the requirements of ISO

  10. Does childhood motor skill proficiency predict adolescent fitness?

    Science.gov (United States)

    Barnett, Lisa M; Van Beurden, Eric; Morgan, Philip J; Brooks, Lyndon O; Beard, John R

    2008-12-01

    To determine whether childhood fundamental motor skill proficiency predicts subsequent adolescent cardiorespiratory fitness. In 2000, children's proficiency in a battery of skills was assessed as part of an elementary school-based intervention. Participants were followed up during 2006/2007 as part of the Physical Activity and Skills Study, and cardiorespiratory fitness was measured using the Multistage Fitness Test. Linear regression was used to examine the relationship between childhood fundamental motor skill proficiency and adolescent cardiorespiratory fitness controlling for gender. Composite object control (kick, catch, throw) and locomotor skill (hop, side gallop, vertical jump) were constructed for analysis. A separate linear regression examined the ability of the sprint run to predict cardiorespiratory fitness. Of the 928 original intervention participants, 481 were in 28 schools, 276 (57%) of whom were assessed. Two hundred and forty-four students (88.4%) completed the fitness test. One hundred and twenty-seven were females (52.1%), 60.1% of whom were in grade 10 and 39.0% were in grade 11. As children, almost all 244 completed each motor assessments, except for the sprint run (n = 154, 55.8%). The mean composite skill score in 2000 was 17.7 (SD 5.1). In 2006/2007, the mean number of laps on the Multistage Fitness Test was 50.5 (SD 24.4). Object control proficiency in childhood, adjusting for gender (P = 0.000), was associated with adolescent cardiorespiratory fitness (P = 0.012), accounting for 26% of fitness variation. Children with good object control skills are more likely to become fit adolescents. Fundamental motor skill development in childhood may be an important component of interventions aiming to promote long-term fitness.

  11. GE Fanuc推出Proficy Historian 3.0

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    GE基础设施旗下的GE Fanuc自动化美洲公司推出了全新的ProficyTM Historian版本3.0个全新的厂级数据历史库版本。ProficyTM Historian 3.0能采集、归档并发布所有的实时现场生产数据,使用起来非常方便,可用性很高。凭藉Proficy Historian,制造商可以有效地从多个数据源采集并聚合实时工厂数据。对于诸如因设备故障和产品质量存在问题而造成的非满意事件,它能快速找出根本原因以实现最佳绩效。

  12. Cell Phone Use and Child and Adolescent Reading Proficiency

    Science.gov (United States)

    Hofferth, Sandra L.; Moon, Ui Jeong

    2016-01-01

    This study examined the association between cell phone use, including minutes spent talking and number of text messages sent, and two measures of children’s reading proficiency — tests of word decoding and reading comprehension — in the United States. Data were drawn from the Child Development Supplement to the Panel Study of Income Dynamics, a nationally representative survey of 1,147 children 10–18 in 2009. Children whose parents were better educated, who had higher family incomes, who had fewer siblings, and who lived in urban areas were more likely to own or share a cell phone. Among those with access to a phone, children who spent more time talking on the phone were less proficient at word decoding, whereas children who spent more time sending text messages had greater reading comprehension. Although girls spent more time texting than did boys, there were no gender differences in the association between time spent talking or number of text messages sent with achievement. In spite of racial/ethnic differences in cell phone use levels, there were no racial/ethnic differences in the association between cell phone use and reading proficiency. PMID:27683624

  13. Effect of gyrB-mediated changes in chromosome structure on killing of Escherichia coli by ultraviolet light: experiments with strains differing in deoxyribonucleic acid repair capacity

    International Nuclear Information System (INIS)

    von Wright, A.; Bridges, B.A.

    1981-01-01

    Mutations at the gyrB locus were found to decrease the degree of supercoiling of the Escherichia coli chromosome. The effect of a gyrB mutation on the repair of ultraviolet-induced deoxyribonucleic acid damage was studied by following the killing of strains of E. coli K-12 proficient and deficient in deoxyribonucleic acid repair. The effectiveness of both excision and postreplication types of deoxyribonucleic acid repair was found to be altered by this mutation, the former being apparently enhanced and the latter impaired

  14. Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiae by cell-free nuclear extracts.

    Science.gov (United States)

    Yuan, Fenghua; Lai, Fangfang; Gu, Liya; Zhou, Wen; El Hokayem, Jimmy; Zhang, Yanbin

    2009-05-01

    Mismatch repair corrects biosynthetic errors generated during DNA replication, whose deficiency causes a mutator phenotype and directly underlies hereditary non-polyposis colorectal cancer and sporadic cancers. Because of remarkably high conservation of the mismatch repair machinery between the budding yeast (Saccharomyces cerevisiae) and humans, the study of mismatch repair in yeast has provided tremendous insights into the mechanisms of this repair pathway in humans. In addition, yeast cells possess an unbeatable advantage over human cells in terms of the easy genetic manipulation, the availability of whole genome deletion strains, and the relatively low cost for setting up the system. Although many components of eukaryotic mismatch repair have been identified, it remains unclear if additional factors, such as DNA helicase(s) and redundant nuclease(s) besides EXO1, participate in eukaryotic mismatch repair. To facilitate the discovery of novel mismatch repair factors, we developed a straightforward in vitro cell-free repair system. Here, we describe the practical protocols for preparation of yeast cell-free nuclear extracts and DNA mismatch substrates, and the in vitro mismatch repair assay. The validity of the cell-free system was confirmed by the mismatch repair deficient yeast strain (Deltamsh2) and the complementation assay with purified yeast MSH2-MSH6.

  15. Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

    Science.gov (United States)

    Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam

    2018-01-01

    Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. PMID:29488881

  16. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2011-05-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  17. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  18. Complex pattern of immune evasion in MSI colorectal cancer.

    Science.gov (United States)

    Ozcan, Mine; Janikovits, Jonas; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2018-01-01

    Mismatch repair (MMR)-deficient cancers accumulate multiple insertion/deletion mutations at coding microsatellites (cMS), which give rise to frameshift peptide neoantigens. The high mutational neoantigen load of MMR-deficient cancers is reflected by pronounced anti-tumoral immune responses of the host and high responsiveness towards immune checkpoint blockade. However, immune evasion mechanisms can interfere with the immune response against MMR-deficient tumors. We here performed a comprehensive analysis of immune evasion in MMR-deficient colorectal cancers, focusing on HLA class I-mediated antigen presentation. 72% of MMR-deficient colorectal cancers of the DFCI database harbored alterations affecting genes involved in HLA class I-mediated antigen presentation, and 54% of these mutations were predicted to abrogate function. Mutations affecting the HLA class I transactivator NLRC5 were observed as a potential new immune evasion mechanism in 26% (6% abrogating) of the analyzed tumors. NLRC5 mutations in MMR-deficient cancers were associated with decreased levels of HLA class I antigen expression. In summary, the majority of MMR-deficient cancers display mutations interfering with HLA class I antigen presentation that reflect active immune surveillance and immunoselection during tumor development. Clinical studies focusing on immune checkpoint blockade in MSI cancer should account for the broad variety of immune evasion mechanisms as potential biomarkers of therapy success.

  19. Does a peer model's task proficiency influence children's solution choice and innovation?

    Science.gov (United States)

    Wood, Lara A; Kendal, Rachel L; Flynn, Emma G

    2015-11-01

    The current study investigated whether 4- to 6-year-old children's task solution choice was influenced by the past proficiency of familiar peer models and the children's personal prior task experience. Peer past proficiency was established through behavioral assessments of interactions with novel tasks alongside peer and teacher predictions of each child's proficiency. Based on these assessments, one peer model with high past proficiency and one age-, sex-, dominance-, and popularity-matched peer model with lower past proficiency were trained to remove a capsule using alternative solutions from a three-solution artificial fruit task. Video demonstrations of the models were shown to children after they had either a personal successful interaction or no interaction with the task. In general, there was not a strong bias toward the high past-proficiency model, perhaps due to a motivation to acquire multiple methods and the salience of other transmission biases. However, there was some evidence of a model-based past-proficiency bias; when the high past-proficiency peer matched the participants' original solution, there was increased use of that solution, whereas if the high past-proficiency peer demonstrated an alternative solution, there was increased use of the alternative social solution and novel solutions. Thus, model proficiency influenced innovation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Mismatch repair genes in Lynch syndrome: a review

    Directory of Open Access Journals (Sweden)

    Felipe Cavalcanti Carneiro da Silva

    Full Text Available Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2; mutL homolog 1 (MLH1; mutS homolog 6 (MSH6; postmeiotic segregation increased 2 (PMS2; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

  1. Nutrients, Foods, and Colorectal Cancer Prevention

    OpenAIRE

    Song, Mingyang; Garrett, Wendy S.; Chan, Andrew T.

    2015-01-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, fo...

  2. Attributable causes of colorectal cancer in China

    OpenAIRE

    Gu, Meng-Jia; Huang, Qiu-Chi; Bao, Cheng-Zhen; Li, Ying-Jun; Li, Xiao-Qin; Ye, Ding; Ye, Zhen-Hua; Chen, Kun; Wang, Jian-Bing

    2018-01-01

    Background Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the burden of colorectal cancer incidence and mortality attributable to the known risk factors in China. Methods We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies a...

  3. Nutritional status assessment in colorectal cancer patients

    OpenAIRE

    Joana Pedro Lopes; Paula Manuela de Castro Cardoso Pereira; Ana Filipa dos Reis Baltazar Vicente; Alexandra Bernardo; María Fernanda de Mesquita

    2013-01-01

    The present study intended to evaluate the nutritional status of Portuguese colorectal patients and associated it with surgery type as well as quality of life outcomes. Malnutrition can affect up to 85% of cancer patients and specifically 30-60% in colorectal cancer and can significantly influence health outcomes. A sample of 50 colorectal cancer patients was evaluated in what refers to several anthropometric measures, food intake, clinical history, complications rate before and after surgery...

  4. Management of colorectal cancer and diabetes

    OpenAIRE

    Yao, Caroline; Nash, Guy F; Hickish, Tamas

    2014-01-01

    Colorectal cancer is associated with diabetes mellitus and both of these common conditions are often managed together by a surgeon. The surgical focus is usually upon cancer treatment rather than diabetes management. The relationship between colorectal cancer and diabetes is a complex one and can raise problems in both diagnosis and the management of patients with both conditions. This literature review explores the relationship between diabetes, diabetic treatment and colorectal cancer and a...

  5. Effects of radiation on levels of DNA damage in normal non-adjacent mucosa from colorectal cancer cases.

    LENUS (Irish Health Repository)

    Sheridan, Juliette

    2013-03-01

    Defects in DNA repair pathways have been linked with colorectal cancer (CRC). Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation. It is known that radiation results in DNA damage directly or indirectly by radiation-induced bystander effect (RIBE) by causing double-strand breaks (DSBs). The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivo.

  6. Predictors of advanced colorectal neoplasia for colorectal cancer screening.

    Science.gov (United States)

    Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

    2014-05-01

    The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, pstatistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

  7. Self-Repair and Language Selection in Bilingual Speech Processing

    Directory of Open Access Journals (Sweden)

    Inga Hennecke

    2013-07-01

    Full Text Available In psycholinguistic research the exact level of language selection in bilingual lexical access is still controversial and current models of bilingual speech production offer conflicting statements about the mechanisms and location of language selection. This paper aims to provide a corpus analysis of self-repair mechanisms in code-switching contexts of highly fluent bilingual speakers in order to gain further insights into bilingual speech production. The present paper follows the assumptions of the Selection by Proficiency model, which claims that language proficiency and lexical robustness determine the mechanism and level of language selection. In accordance with this hypothesis, highly fluent bilinguals select languages at a prelexical level, which should influence the occurrence of self-repairs in bilingual speech. A corpus of natural speech data of highly fluent and balanced bilingual French-English speakers of the Canadian French variety Franco-Manitoban serves as the basis for a detailed analysis of different self-repair mechanisms in code-switching environments. Although the speech data contain a large amount of code-switching, results reveal that only a few speech errors and self-repairs occur in direct code-switching environments. A detailed analysis of the respective starting point of code-switching and the different repair mechanisms supports the hypothesis that highly proficient bilinguals do not select languages at the lexical level.Le niveau exact de la sélection des langues lors de l’accès lexical chez le bilingue reste une question controversée dans la recherche psycholinguistique. Les modèles actuels de la production verbale bilingue proposent des arguments contradictoires concernant le mécanisme et le lieu de la sélection des langues. La présente recherche vise à fournir une analyse de corpus mettant l’accent sur les mécanismes d’autoréparation dans le contexte d’alternance codique dans la production verbale

  8. [An experimental proficiency test for ability to screen 104 residual pesticides in agricultural products].

    Science.gov (United States)

    Tsumura, Yukari; Ishimitsu, Susumu; Otaki, Kayo; Uchimi, Hiroyuki; Matsumoto, Nobuyuki; Daba, Masaki; Tsuchiya, Tetsu; Ukyo, Masaho; Tonogai, Yasuhide

    2003-10-01

    An experimental proficiency test program for ability to screen 104 residual pesticides in agricultural products has been conducted. Eight Japanese laboratories joined the program. Items tested in the present study were limit of detection, internal proficiency test (self spike) and external proficiency test (blind spike). All 104 pesticides were well detected and recovered from agricultural foods in the internal proficiency test. However, the results of the external proficiency test did not completely agree with those of the internal proficiency tests. After 5 rounds of the blind spike test, the ratio of the number of correctly detected pesticides to that of actually contained ones (49 total) ranged from 65% to 100% among laboratories. The numbers of mistakenly detected pesticides by a laboratory were 0 to 15. Thus, there was a great difference among the laboratories in the ability to screen multiresidual pesticides.

  9. Abnormal recovery of DNA replication in ultraviolet-irradiated cell cultures of Drosophila melanogaster which are defective in DNA repair

    International Nuclear Information System (INIS)

    Brown, T.C.; Boyd, J.B.

    1981-01-01

    Cell cultures prepared from embryos of a control stock of Drosophila melanogaster respond to ultraviolet light with a decline and subsequent recovery both of thymidine incorporation and in the ability to synthesize nascent DNA in long segments. Recovery of one or both capacities is absent or diminished in irradiated cells from ten nonallelic mutants that are defective in DNA repair and from four of five nonallelic mutagen-sensitive mutants that exhibit normal repair capabilities. Recovery of thymidine incorporation is not observed in nine of ten DNA repair-defective mutants. On the other hand, partial or complete recovery of incorporation is observed in all but one repair-proficient mutagen-sensitive mutant. (orig./AJ) [de

  10. Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-03-22

    Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  11. Dietary patterns and colorectal cancer

    OpenAIRE

    Tayyem, Reema F.; Bawadi, Hiba A.; Shehadah, Ihab; Agraib, Lana M.; AbuMweis, Suhad S.; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E.; Heath, Dennis D.

    2016-01-01

    Summary Background & aimsDietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. MethodsDietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, g...

  12. Tumor markers in colorectal cancer

    OpenAIRE

    Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

    2002-01-01

    Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

  13. Syncytin immunoreactivity in colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2009-01-01

    monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method...... and the Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....

  14. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie

    2012-01-01

    Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...

  15. Radiologic evaluation of colorectal cancer

    International Nuclear Information System (INIS)

    Lee, Young Joong; Kang, Hee Tae; Kim, Jong Deok; Rhee, Hak Song

    1984-01-01

    The incidence of colorectal cancer of Korea is much lower than that of Western countries, but has shown a tendency to a slight increase recently. Barium enema is the most valuable, noninvasive and inexpensive method available to evaluate the size, shape and site of colorectal cancer. The authors reviewed and radiologically classified barium enema studies of 232 cases of colorectal cancer from Aug. 1967 to July 1982 at Presbyterian Medical Center, Jeonju, Confirmed clinically, operatively and pathologically. The results were as follows; 1. The ratio of male and female was 1.3:1, and youngest was 13 year-old and the oldest 86 year-old. 2. The peak incidence occurred from 5th to 7th decades, accounting for 78% of all cases (181/232), and there was a relatively high incidence of the disease in patients below 30 years of age at 7.8% (18/232). 3. Rectum and rectosigmoid region are the most frequently involved regions (127/232:54.8%). 4. The positivity of barium enema examination was 4.0% (232/5807), and its accuracy was 96.5% (224/232). 5. The radiologic findings were classified into 4 groups, and they were annular encircling 62.9% (146/232). polypoid fungating 26.8% (62/232), infiltrating 8.6% (20/232), and primary ulcerating 1.7% (4/232) in order of frequency. 6. The linear length of the cancer ranged from 1.5 Cm to 15 Cm, and the average length was 5.5 Cm. 7. There was no statistical correlation between the length of lesion, the site, and the radiologic findings, and stages of the lesion (P:0.750-0.250). 8. The majority of colorectal cancers was adenocarcinoma (217/232:93.6%)

  16. Danish Colorectal Cancer Group Database.

    Science.gov (United States)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long

  17. Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

    NARCIS (Netherlands)

    Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

    2008-01-01

    In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

  18. Radiobiological significance of DNA repair

    International Nuclear Information System (INIS)

    Kuzin, A.M.

    1978-01-01

    A short outline is given on the history of the problem relating to the repair of radiation injuries, specifically its molecular mechanisms. The most urgent problems which currently confront the researchers are noted. This is a further study on the role of DNA repair in post-radiation recovery, search for ways to activate and suppress DNA repair, investigations into the activity balance of various repair enzymes as well as the problem of errors in the structure of repairing DNA. An important role is attached to the investigations of DNA repair in solving a number of practical problems

  19. Short Hospital Stay after Laparoscopic Colorectal Surgery without Fast Track

    Directory of Open Access Journals (Sweden)

    Stefan K. Burgdorf

    2012-01-01

    Full Text Available Purpose. Short hospital stay and equal or reduced complication rates have been demonstrated after fast track open colonic surgery. However, fast track principles of perioperative care can be difficult to implement and often require increased nursing staff because of more concentrated nursing tasks during the shorter hospital stay. Specific data on nursing requirements after laparoscopic surgery are lacking. The purpose of the study was to evaluate the effect of operative technique (open versus laparoscopic operation, but without changing nurse staffing or principles for peri- or postoperative care, that is, without implementing fast track principles, on length of stay after colorectal resection for cancer. Methods. Records of all patients operated for colorectal cancer from November 2004 to December 2008 in our department were reviewed. No specific patients were selected for laparoscopic repair, which was solely dependent on the presence of two specific surgeons at the same time. Thus, the patients were not selected for laparoscopic repair based on patient-related factors, but only on the simultaneous presence of two specific surgeons on the day of the operation. Results. Of a total of 540 included patients, 213 (39% were operated by a laparoscopic approach. The median hospital stay for patients with a primary anastomosis was significantly shorter after laparoscopic than after conventional open surgery (5 versus 8 days, while there was no difference in patients receiving a stoma (10 versus 10 days, ns, with no changes in the perioperative care regimens. Furthermore there were significant lower blood loss (50 versus 200 mL, and lower complication rate (21% versus 32%, in the laparoscopic group. Conclusion. Implementing laparoscopic colorectal surgery in our department resulted in shorter hospital stay without using fast track principles for peri- and postoperative care in patients not receiving a stoma during the operation. Consequently, we

  20. Recombinational repair: workshop summary

    International Nuclear Information System (INIS)

    Howard-Flanders, P.

    1983-01-01

    Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

  1. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  2. Treatment of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Colorectal cancer (CRC is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin or FOLFIRI (5FU/LV and irinotecan, should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.

  3. Proficiency Test SYKE 8/2012. Volatile organic compounds in water and soil

    OpenAIRE

    Korhonen-Ylönen, Kaija; Nuutinen, Jari; Leivuori, Mirja; Ilmakunnas, Markku

    2013-01-01

    Proftest SYKE carried out the proficiency test for analysis of volatile organic compounds from water and soil in October 2012. One artificial sample and one river water sample and one soil sample were distributed. In total, 15 laboratories participated in the proficiency test. Either the calculated concentration or the robust mean value was chosen to be the assigned value for the measurement. The performance of the participants was evaluated by using z scores. In this proficiency test 72 % of...

  4. Meniscal repair devices.

    Science.gov (United States)

    Barber, F A; Herbert, M A

    2000-09-01

    Meniscal repair devices not requiring accessory incisions are attractive. Many factors contribute to their clinical effectiveness including their biomechanical characteristics. This study compared several new meniscal repair devices with standard meniscal suture techniques. Using a porcine model, axis-of-insertion loads were applied to various meniscal sutures and repair devices. A single device or stitch was placed in a created meniscal tear and a load applied. Both loads and modes of failure were recorded. The load-to-failure data show stratification into 4 distinct statistical groups. Group A, 113 N for a double vertical stitch; group B, 80 N for a single vertical stitch; group C, 57 N for the BioStinger, 56 N for a horizontal mattress stitch, and 50 N for the T-Fix stitch; and group D, 33 N for the Meniscus Arrow (inserted by hand or gun), 32 N for the Clearfix screw, 31 N for the SDsorb staple, 30 N for the Mitek meniscal repair system, and 27 N for the Biomet staple. The failure mechanism varied. Sutures broke away from the knot. The Meniscus Arrow and BioStinger pulled through the inner rim with the crossbar intact. The Clearfix screw failed by multiple mechanisms, whereas 1 leg of the SDsorb staple always pulled out of the outer rim. The Mitek device usually failed by pullout from the inner rim. The Biomet staple always broke at the crosshead or just below it. Although the surgeon should be aware of the material properties of the repair technique chosen for a meniscal repair, this information is only an indication of device performance and may not correlate with clinical healing results.

  5. Systems Support Mapping in Guiding Self-Management in Stage I-III Colorectal Cancer Survivors

    Science.gov (United States)

    2018-04-26

    Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

  6. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.

    Science.gov (United States)

    Nadkarni, Aditi; Burns, John A; Gandolfi, Alberto; Chowdhury, Moinuddin A; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E; Scicchitano, David A

    2016-01-08

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

    International Nuclear Information System (INIS)

    Jensen, Søren A; Vainer, Ben; Kruhøffer, Mogens; Sørensen, Jens B

    2009-01-01

    Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated. MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy. MSI was found in 43 (13.8%) tumors. Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2–0.7; P = 0.0007) and death (HR = 0.4; 95% CI: 0.2–0.9; P = 0.02) independently of the TS and DPD expressions. A direct relationship between MSI and TS intensity (P = 0.001) was found, while there was no significant association with DPD intensity (P = 0.1). The favourable outcome of MSI colorectal carcinomas is ascribed mainly to the tumor biology and to a lesser extent to antitumor response to 5-fluorouracil therapy. There is no evidence that differential TS or DPD expression may account for these outcome characteristics

  8. Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry.

    Science.gov (United States)

    Alpert, Lindsay; Pai, Reetesh K; Srivastava, Amitabh; McKinnon, Wendy; Wilcox, Rebecca; Yantiss, Rhonda K; Arcega, Ramir; Wang, Hanlin L; Robert, Marie E; Liu, Xiuli; Pai, Rish K; Zhao, Lei; Westerhoff, Maria; Hampel, Heather; Kupfer, Sonia; Setia, Namrata; Xiao, Shu-Yuan; Hart, John; Frankel, Wendy L

    2018-04-01

    - Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry to those with other forms of mismatch repair deficiency. - Ninety-three colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193 with other forms of mismatch repair deficiency were identified. Forty (43%) of the isolated PMS2 loss cases and 35 control cases (18%) had a known germline mutation or a clinical diagnosis of Lynch syndrome. - Overall, isolated PMS2-loss tumors occurred in significantly younger patients ( P PMS2-loss group also exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95% CI, 1.41-6.85; P = .007). When the analysis was restricted to germline mutation/Lynch syndrome cases and controls, no significant differences were detected for age, sex, tumor location, tumor grade, histologic features, or distant metastases, although a trend toward increased odds of disease-specific death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04; P = .10). - Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.

  9. Management of colorectal injuries during operation iraqi freedom: patterns of stoma usage.

    Science.gov (United States)

    Duncan, James E; Corwin, Christian H; Sweeney, W Brian; Dunne, James R; Denobile, John W; Perdue, Philip W; Galarneau, Michael R; Pearl, Jonathan P

    2008-04-01

    Management of penetrating colorectal injuries in the civilian trauma population has evolved away from diversionary stoma into primary repair or resection and primary anastomosis. With this in mind, we evaluated how injuries to the colon and rectum were managed in the ongoing war in Iraq. The records of Operation Iraqi Freedom patients evacuated to National Naval Medical Center (NNMC) from March 2004 until November 2005 were retrospectively reviewed. Patients with colorectal injuries were identified and characterized by the following: (1) injury type; (2) mechanism; (3) associated injuries; (4) Injury Severity Score; (5) levels of medical care involved in patient treatment; (6) time interval(s) between levels of care; (7) management; and (8) outcomes. Twenty-three patients were identified as having either colon or rectal injury. The average ISS was 24.4 (range, 9-54; median 24). On average, patients were evaluated and treated at 2.5 levels of surgically capable medical care (range, 2-3; median 2) between time of injury and arrival at NNMC, with a median of 6 days from initial injury until presentation at NNMC (range, 3-11). Management of colorectal injuries included 7 primary repairs (30.4%), 3 resections with anastomoses (13.0%), and 13 colostomies (56.6%). There was one death (4.3%) and three anastomotic leaks (30%). Total complication rate was 48%. Based upon injury severity, the complex nature of triage and medical evacuation, and the multiple levels of care involved for injured military personnel, temporary stoma usage should play a greater role in military casualties than in the civilian environment for penetrating colorectal injuries.

  10. Biological radiolesions and repair

    International Nuclear Information System (INIS)

    Laskowski, W.

    1981-01-01

    In 7 chapters, the book answers the following questions: 1) What reactions are induced in biological matter by absorption of radiation energy. 2) In what parts of the cell do the radiation-induced reactions with detectable biological effects occur. 3) In which way are these cell components changed by different qualities of radiation. 4) What are the cell mechanisms by which radiation-induced changes can be repaired. 5) What is the importance of these repair processes for man, his life and evolution. At the end of each chapter, there is a bibliography of relevant publications in this field. (orig./MG) [de

  11. Motivational interviewing and colorectal cancer screening: a peek from the inside out.

    Science.gov (United States)

    Wahab, Stéphanie; Menon, Usha; Szalacha, Laura

    2008-08-01

    This article focuses on design, training, and delivery of motivational interview (MI) in a longitudinal randomized controlled trial intended to assess the efficacy of two separate interventions designed to increase colorectal screening when compared to a usual care, control group. One intervention was a single-session, telephone-based MI, created to increase colorectal cancer screening within primary care populations. The other was tailored health counseling. We present the rationale, design, and process discussions of the one-time motivational interviewing telephone intervention. We discuss in this paper the training and supervision of study interventionists, in order to enhance practice and research knowledge concerned with fidelity issues in motivational interview interventions. To improve motivational interviewing proficiency and effectiveness, we developed a prescribed training program adapting MI to a telephone counseling session. The three interventionists trained in MI demonstrate some MI proficiency assessed by the motivational interviewing treatment integrity scale. In the post-intervention interview, 20.5% of the MI participants reported having had a CRC screening test, and another 19.75% (n=16) had scheduled a screening test. Almost half of the participants (43%) indicated that the phone conversation helped them to overcome the reasons why they had not had a screening test. Ongoing supervision and training (post-MI workshop) are crucial to supporting MI fidelity. The trajectory of learning MI demonstrated by the interventionists is consistent with the eight stages of learning MI. The MI road map created for the interventionists has shown to be more of a distraction than a facilitator in the delivery of the telephone intervention. MI can, however, be considered a useful tool for health education and warrants further study. MI training should include consistent training and process evaluation. MI can, however, be considered a useful tool for health

  12. Sensitivity of strains of Escherichia coli differing in repair capability to far UV, near UV and visible radiations

    International Nuclear Information System (INIS)

    Webb, R.B.; Brown, M.S.

    1976-01-01

    In stationary phase, strains of Escherichia coli deficient in excision (B/r Hcr) or recombination repair (K12 AB2463) were more sensitive than a repair proficient strain (B/r) to monochromatic near-ultraviolet (365nm) and visible (460 nm) radiations. The relative increase in sensitivity of mutants deficient in excision or recombination repair in comparison to the wildtype, was less at 365 nm than at 254 nm. However, a strain deficient in both excision and recombination repair (K12 AB2480) showed a large, almost equal, increase in sensitivity over mutants deficient in either excision or recombination repair at 365 nm and 254 nm. All strains tested were highly resistant to 650 nm radiation. Action spectra for lethality of strains B/r and B/r Hcr in stationary phase reveal small peaks or shoulders in the 330 to 340, 400 to 410 and 490 to 510 nm wavelength ranges. The presence of 5 micro g/ml acriflavine (an inhibitor of repair) in the plating medium greatly increased the sensitivity of strain B/r to radiation at 254, 365 and 460 nm, while strains E.coli B/r Hcr and K12 AB2463 were sensitized by small amounts. At each of the wavelengths tested, acriflavine in the plating medium had at most a small effect on E.coli K12 AB2480. Acriflavine failed to sensitize any strain tested at 650 nm. Evidence supports the interpretation that lesions induced in DNA by 365 nm and 460 nm radiations play the major role in the inactivation of E.coli by these wavelengths. Single-strand breaks (or alkali-labile bonds), but not pyrimidine dimers are candidates for the lethal DNA lesions in uvrA and repair proficient strains. At high fluences lethality may be enhanced by damage to the excision and recombination repair systems. (author)

  13. Sensitivity of strains of Escherichia coli differing in repair capability to far uv, near uv and visible radiations

    Energy Technology Data Exchange (ETDEWEB)

    Webb, R B; Brown, M S [Argonne National Lab., Ill. (USA)

    1976-11-01

    In stationary phase, strains of Escherichia coli deficient in excision (B/r Hcr) or recombination repair (K12 AB2463) were more sensitive than a repair proficient strain (B/r) to monochromatic near-ultraviolet (365nm) and visible (460 nm) radiations. The relative increase in sensitivity of mutants deficient in excision or recombination repair in comparison to the wildtype, was less at 365 nm than at 254 nm. However, a strain deficient in both excision and recombination repair (K12 AB2480) showed a large, almost equal, increase in sensitivity over mutants deficient in either excision or recombination repair at 365 nm and 254 nm. All strains tested were highly resistant to 650 nm radiation. Action spectra for lethality of strains B/r and B/r Hcr in stationary phase reveal small peaks or shoulders in the 330 to 340, 400 to 410 and 490 to 510 nm wavelength ranges. The presence of 5 micro g/ml acriflavine (an inhibitor of repair) in the plating medium greatly increased the sensitivity of strain B/r to radiation at 254, 365 and 460 nm, while strains E.coli B/r Hcr and K12 AB2463 were sensitized by small amounts. At each of the wavelengths tested, acriflavine in the plating medium had at most a small effect on E.coli K12 AB2480. Acriflavine failed to sensitize any strain tested at 650 nm. Evidence supports the interpretation that lesions induced in DNA by 365 nm and 460 nm radiations play the major role in the inactivation of E.coli by these wavelengths. Single-strand breaks (or alkali-labile bonds), but not pyrimidine dimers are candidates for the lethal DNA lesions in uvrA and repair proficient strains. At high fluences lethality may be enhanced by damage to the excision and recombination repair systems.

  14. Students' proficiency scores within multitrait item response theory

    Science.gov (United States)

    Scott, Terry F.; Schumayer, Daniel

    2015-12-01

    In this paper we present a series of item response models of data collected using the Force Concept Inventory. The Force Concept Inventory (FCI) was designed to poll the Newtonian conception of force viewed as a multidimensional concept, that is, as a complex of distinguishable conceptual dimensions. Several previous studies have developed single-trait item response models of FCI data; however, we feel that multidimensional models are also appropriate given the explicitly multidimensional design of the inventory. The models employed in the research reported here vary in both the number of fitting parameters and the number of underlying latent traits assumed. We calculate several model information statistics to ensure adequate model fit and to determine which of the models provides the optimal balance of information and parsimony. Our analysis indicates that all item response models tested, from the single-trait Rasch model through to a model with ten latent traits, satisfy the standard requirements of fit. However, analysis of model information criteria indicates that the five-trait model is optimal. We note that an earlier factor analysis of the same FCI data also led to a five-factor model. Furthermore the factors in our previous study and the traits identified in the current work match each other well. The optimal five-trait model assigns proficiency scores to all respondents for each of the five traits. We construct a correlation matrix between the proficiencies in each of these traits. This correlation matrix shows strong correlations between some proficiencies, and strong anticorrelations between others. We present an interpretation of this correlation matrix.

  15. Scientific issues related to the cytology proficiency testing regulations

    Directory of Open Access Journals (Sweden)

    Prey Marianne

    2006-01-01

    Full Text Available Abstract The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law.

  16. Inter-laboratory proficiency tests to detect viral fish diseases

    DEFF Research Database (Denmark)

    Kahns, Søren; Nicolajsen, Nicole; Skall, Helle Frank

    An inter-laboratory proficiency test has ben provided by the European Community Laboratory (CRL) for Fish Diseases every year since 1996. The test is provided to all European National Reference Laboratories (NRLs) that are obliged to participate and to a limited number of non-European NRLs, making......) but also to assess their ability to differentiate other fish viruses as spring viraemia of carp virus, infectious pancreatic necrosis virus, perch rhabdovirus etc. Five coded ampoules are provided to participants containing lyophilised supernatant from infected cell cultures. The CRL collect the data...

  17. Culture, identity and difference relationship and the proficiency exam EPPLE

    Directory of Open Access Journals (Sweden)

    Priscila Petian Anchieta

    2017-11-01

    Full Text Available The present work discusses how aspects such as identity, culture and difference are important aspects in for language teaching and learning environments. Using Woodward's (2011 definition that identity is marked by difference, we considered these aspects in foreign language teaching and learning contexts when we learn the laguage of others. In addition, we present a proficiency exam called EPPLE, aimed at language teachers, and we suggest the implementation of a task that addresses cultural issues, because we need to prepare language teachers that search not only for their linguistic and pedagogical knowledge construction, but also for their understanding about culture, identity and difference.

  18. Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan

    International Nuclear Information System (INIS)

    Yeh, Chih-Ching; Sung, Fung-Chang; Tang, Reiping; Chang-Chieh, Chung Rong; Hsieh, Ling-Ling

    2005-01-01

    Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer. We conducted a case-control study including 727 cases of cancer and 736 hospital-based age- and sex-matched healthy controls to examine the role of genetic polymorphisms of three DNA-repair genes (XRCC1, XRCC3 and XPD) in the context of colorectal cancer risk for the Taiwanese population. Genomic DNA isolated from 10 ml whole blood was used to genotype XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96–1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88–1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90–1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI = 1.21–4.90), particularly for individuals suffering tumors located in the rectum (OR = 3.18, 95% CI = 1.29–7.82) and diagnosed prior to the age of 60 years (OR = 4.90, 95% CI = 1.72–14.0). Our results suggest that DNA-repair pathways may simultaneously modulate the risk of colorectal cancer for the Taiwanese population, and, particularly

  19. Indeterminate Pulmonary Nodules at Colorectal Cancer Staging

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Wille-Jørgensen, Peer A; Jorgensen, Lars N

    2013-01-01

    This study aimed to estimate the prevalence of indeterminate pulmonary nodules and specific radiological and clinical characteristics that predict malignancy of these at initial staging chest computed tomography (CT) in patients with colorectal cancer. A considerable number of indeterminate...... pulmonary nodules, which cannot readily be classified as either benign or malignant, are detected at initial staging chest CT in colorectal cancer patients....

  20. Clinical Outcomes of Colorectal Cancer in Kenya

    African Journals Online (AJOL)

    treatment and follow up were included. Patient ... and recurrence and the associated patient and disease ... The incidence of colorectal cancer (CRC) in the devel- ... therapy, disease stage and curative intent (table 3). ... through genetic and family analyses (4,6). ... Polite BN, Dignam JJ: A colorectal cancer model of health.

  1. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

    African Journals Online (AJOL)

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

  2. Vitamin D, inflammation, and colorectal cancer progression

    NARCIS (Netherlands)

    Harten-Gerritsen, van Suzanne; Balvers, Michiel G.J.; Witkamp, Renger F.; Kampman, Ellen; Duijnhoven, van F.J.B.

    2015-01-01

    Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a

  3. Optimizing Outcomes of Colorectal Cancer Screening

    NARCIS (Netherlands)

    R.G.S. Meester (Reinier)

    2017-01-01

    markdownabstractColorectal cancer is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify areas for

  4. Pitfalls and Opportunities in Colorectal Cancer Screening

    NARCIS (Netherlands)

    P.G. van Putten (Paul)

    2013-01-01

    textabstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer in the Western world. Screening has been shown to reduce CRC incidence and mortality. The first evidence that colorectal cancer screening could effectively reduce mortality dates

  5. Excision repair in ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome, and Bloom's syndrome after treatment with ultraviolet radiation and N-acetoxy-2-acetylaminofluorene

    International Nuclear Information System (INIS)

    Ahmed, F.E.; Setlow, R.B.

    1978-01-01

    Excision repair of damage due to ultraviolet radiation, N-acetoxy-2-acetylaminofluorene and a combination of both agents was studied in normal human fibroblasts and various cells from cancer prone patients (ataxia telangiectasia, Fanconi's anemia, Cockayne syndrome and Bloom's syndrome). Three methods giving similar results were used: unscheduled DNA synthesis by radioautography, photolysis of bromodeoxyuridine incorporated into parental DNA during repair, and loss of sites sensitive to an ultraviolet endonuclease. All cell lines were proficient in repair of ultraviolet and acetoxy acetylaminofluorene damage and at saturation doses of both agents repair was additive. We interpret these data as indicating that the rate limiting step in excision repair of ultraviolet and acetoxy acetylaminofluorene is different and that there are different enzyme(s) working on incision of both types of damages. (Auth.)

  6. Colorectal Cancer Awareness for Women via Facebook: A Pilot Study.

    Science.gov (United States)

    Brittain, Kelly; Pennings Kamp, Kendra J; Salaysay, Zachary

    Colorectal cancer is the third leading cause of cancer death among U.S. women. Women report being screened for colorectal cancer less often than men, and if colorectal cancer screening guidelines were routinely followed, approximately 60% of colorectal cancer deaths could be prevented. Many colorectal cancer screening interventions have not used Facebook, which is the most popular social media site among women. Little is known about engaging women in colorectal cancer screening and risk reduction information using Facebook. The "Colorectal Cancer Screening Awareness for Women" Facebook page was created to promote colorectal cancer screening and risk reduction awareness among women. Facebook posts targeted women aged 45-64 years and highlighted colorectal cancer screening methods, guidelines, and colorectal cancer risk reduction strategies. Demographics and data about the women's interactions with the page were collected using Facebook analytics and analyzed. The majority of the 391 users of the Colorectal Cancer Screening Awareness for Women Facebook page were women aged 45-54 years (56.5%). The most "liked" posts were related to colorectal cancer risk reduction behaviors. In an effort to increase routine colorectal cancer screening and colorectal cancer risk reduction behaviors, gastroenterology nurses and practices should consider Facebook as a good method to regularly engage women in colorectal cancer screening and colorectal cancer risk reduction information.

  7. Composite Repair System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — GTL has developed an innovative composite repair methodology known as the Composite Repair System (CRS). In this phase I effort, CRS is being developed for the...

  8. About the Collision Repair Campaign

    Science.gov (United States)

    EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

  9. Vesicovaginal Fistula Repair During Pregnancy

    African Journals Online (AJOL)

    Vesicovaginal Fistula Repair During Pregnancy: A Case Report ... Abstract. We report a repair of Vesicovaginal fistula during pregnancy that was aimed at preventing another spontaneous ... practices that encourage teenage marriage and girl.

  10. Ship Repair Workflow Cost Model

    National Research Council Canada - National Science Library

    McDevitt, Mike

    2003-01-01

    The effects of intermittent work patterns and funding on the costs of ship repair and maintenance were modeled for the San Diego region in 2002 for Supervisor of Shipbuilding and Repair (SUPSHIP) San Diego...

  11. DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light

    International Nuclear Information System (INIS)

    Ben-Ishai, R.; Sharon, R.; Rothman, M.; Miskin, R.

    1984-01-01

    We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s)

  12. Social repair of relationships

    DEFF Research Database (Denmark)

    Fahnøe, Kristian Relsted

    2017-01-01

    organisations, friends and family, and communities. These social relations are viewed as the foundation of citizenship as experienced and practised. Focusing on how two dimensions of lived citizenship, namely rights-responsibilities and belonging, are affected by the social repairs, the chapter shows how...

  13. Comprehensive Small Engine Repair.

    Science.gov (United States)

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  14. Patent urachus repair - slideshow

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair - series—Normal anatomy URL of this ...

  15. Patent urachus repair

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair URL of this page: //medlineplus.gov/ ...

  16. DNA Repair Systems

    Indian Academy of Sciences (India)

    Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial ...

  17. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R [ORNL; Peter, William H [ORNL

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  18. Role of DNA repair in repair of cytogenetic damages. Slowly repaired DNA injuries involved in cytogenetic damages repair

    International Nuclear Information System (INIS)

    Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification

  19. Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

    Directory of Open Access Journals (Sweden)

    Metka Ravnik-Glavač

    2005-07-01

    Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

  20. Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

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    H. F. A. Vasen

    2004-01-01

    Full Text Available Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR protein detected by immunohistochemistry (IHC of colorectal cancer (CRC and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable