22 research outputs found

    Prognostic value of colorectal cancer biomarkers

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    Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC

    The role of wireless capsule endoscopy (WCE) in the detection of occult primary neuroendocrine tumors

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    BACKGROUND AND AIMS: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumors in patients showing liver NET metastases when first-line investigations are inconclusive. METHOD: Twenty-four patients with a histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration. RESULTS: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded. CONCLUSIONS: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary sit

    Slide preparation for single-cell-resolution imaging of fluorescent proteins in their three-dimensional near-native environment

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    In recent years, many mouse models have been developed to mark and trace the fate of adult cell populations using fluorescent proteins. High-resolution visualization of such fluorescent markers in their physiological setting is thus an important aspect of adult stem cell research. Here we describe a protocol to produce sections (150-200 mum) of near-native tissue with optimal tissue and cellular morphology by avoiding artifacts inherent in standard freezing or embedding procedures. The activity of genetically expressed fluorescent proteins is maintained, thereby enabling high-resolution three-dimensional (3D) reconstructions of fluorescent structures in virtually all types of tissues. The procedure allows immunofluorescence labeling of proteins to depths up to 50 mum, as well as a chemical 'Click-iT' reaction to detect DNA-intercalating analogs such as ethynyl deoxyuridine (EdU). Generation of near-native sections ready for imaging analysis takes approximately 2-3 h. Postsectioning processes, such as antibody labeling or EdU detection, take up to 10 h. [KEYWORDS: Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Luminescent Proteins/ analysis, Microscopy, Fluorescence/methods, Microtomy, Single-Cell Analysis/ methods

    Advanced Placement Drawing Portfolio & the Essence of Adobe Photoshop Competence for Success

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    The goal of this dissertation is to determine the impact of Adobe Photoshop when the studio art students at Williamstown High School utilize the software, as they prepare for the College Board Advanced Placement Drawing exam. The purpose of Adobe Photoshop is to assist the students in creating a successful art portfolio. The dissertation investigates the impact of Adobe Photoshop on the creative process and the realization of students' artistic vision. The plan and investigation of the research examines the extent to which the appropriation and manipulation of digital imagery can influence the art making process and foster transformation in student artwork. To conduct the research, Mrs. Jennifer Carullo, supervisor of the school's technology department, set up a digital lab with five computers and installed Adobe Photoshop on each computer. It is unprecedented in the studio art curriculum. During the research, the author observed and studied the impact of Adobe Photoshop on the artistic and creative process as it applied to the students' sustained concentration portfolio preparation (for AP Art). Prior to the 2019-2020 school year, digital manipulation and Adobe Photoshop was not part of the AP Studio Art curriculum at Williamstown High School. However, through the research in the digital lab, and the result of the survey and data, the author envisioned the possibility of implementing Adobe Photoshop & the digital lab into the Studio Art curriculum. Ultimately, the research will conform to the National Educational Leadership Preparation (NELP) PROGRAM STANDARDS for Building Level. Standard 1: Mission, Vision, and Improvement

    Advanced Placement Drawing Portfolio & the Essence of Adobe Photoshop Competence for Success

    No full text
    The goal of this dissertation is to determine the impact of Adobe Photoshop when the studio art students at Williamstown High School utilize the software, as they prepare for the College Board Advanced Placement Drawing exam. The purpose of Adobe Photoshop is to assist the students in creating a successful art portfolio. The dissertation investigates the impact of Adobe Photoshop on the creative process and the realization of students' artistic vision. The plan and investigation of the research examines the extent to which the appropriation and manipulation of digital imagery can influence the art making process and foster transformation in student artwork. To conduct the research, Mrs. Jennifer Carullo, supervisor of the school's technology department, set up a digital lab with five computers and installed Adobe Photoshop on each computer. It is unprecedented in the studio art curriculum. During the research, the author observed and studied the impact of Adobe Photoshop on the artistic and creative process as it applied to the students' sustained concentration portfolio preparation (for AP Art). Prior to the 2019-2020 school year, digital manipulation and Adobe Photoshop was not part of the AP Studio Art curriculum at Williamstown High School. However, through the research in the digital lab, and the result of the survey and data, the author envisioned the possibility of implementing Adobe Photoshop & the digital lab into the Studio Art curriculum. Ultimately, the research will conform to the National Educational Leadership Preparation (NELP) PROGRAM STANDARDS for Building Level. Standard 1: Mission, Vision, and Improvement

    MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

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    View the MathML source: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. View the MathML source: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor β receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. View the MathML source: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. View the MathML source:ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer

    Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer

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    Purpose: The outcome of patients with colorectal cancer is more favorable when the tumor exhibits high-frequency microsatellite instability (MSI). Although associated with earlier-stage tumors, MSI has been proposed as an independent predictor of survival. We tested the prognostic value of MSI in a large series of patients diagnosed with colorectal cancer in the last decade. Experimental Design: The survival of 893 consecutive patients with colorectal cancer characterized by microsatellite status was analyzed. The 89 (10%) patients with MSI cancer were classified according to tumor mismatch repair (MMR) defect, MMR germ-line mutation, hMLH1 and p16 promoter methylation, BRAF and K-ras mutations, and frameshifts of target genes. Results: The colorectal cancer - specific survival was significantly (P = 0.02) better in patients with MSI cancer than in those with stable tumor (MSS). MSI did not predict a significantly lower risk of cancer-related death if tumor stage was included in the multivariate analysis [hazard ratio, 0.72; 95% confidence interval (95% CI), 0.40-1.29; P = 0.27]. Instead, MSI was strongly associated with a decreased likelihood of lymph node (odds ratio, 0.31; 95% CI, 0.17-0.56; P < 0.001) and distant organ (odds ratio, 0.13; 95% CI, 0.05-0.33; P < 0.001) metastases at diagnosis, independently of tumor pathologic features. Molecular predictors of reduced metastatic risk, and then of more favorable prognosis, included TGFβRII mutation for all MSI tumors, hMSH2 deficiency for hereditary non-polyposis colorectal cancer, and absence of p16 methylation for sporadic hMLH1-deficient cancers. Conclusions: Tumor MSI is a stage-dependent predictor of survival in patients with colorectal cancer. The decreased likelihood of metastases in patients with MSI cancer is associated with specific genetic and epigenetic changes of the primary tumor

    Contextualizing narrative theory: reading the politics of formal innovation in contemporary women's fiction

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    To ignore the strategies and structures through which stories are told, this thesis contends, is to neglect a vital dimension of their politics. Narratology provides productive analytical tools to illuminate the complex and varied mechanics of narrative form, yet it also bears the traces of its structuralist origins. Its value is therefore contingent upon its continuing reformulation as an expansive, pluralist and contextualized critical discipline. Participating in this expansion, this thesis evidences the pertinence and vitality of some narratological models and the limitations of others. It opens up alternative critical possibilities by drawing upon insights within contemporary critical theory, from poststructuralist philosophy to transcultural feminism to sociolinguistics. Above all, my interventions proceed from close readings of innovative fiction by women writers hitherto all but unrepresented in, and therefore potentially subversive of, existing models: Nicole Brossard, Daphne Marlatt, Hiromi Goto, Ali Smith, Jackie Kay, Erna Brodber, Dionne Brand, Aritha van Herk. The first chapter formulates an in-between critical space where feminist and postmodernist theories of narrative intersect. It re-examines metafiction through the lens of auto(bio)graphical practice and feminist poststructuralist theories of self, and introduces the notions of folds and echoes to describe specific structural innovations. Chapter Two examines unconventional uses of second-person address and reconsiders existing narratological approaches in their light, focusing on the `push and pull of narrative' that the `you' form enacts. Chapter Three addresses the insufficient attention paid to multiply narrated novels, theorizing them as `narrative communities' and introducing terms to describe different internal relations between narrators, relations that can often be read as determinedly 'democratic'. The final chapter contests the hegemony of temporal models of narrativity by formulating a 'spatial poetics' that accounts both for how spatial structures can be agents of narrative change and for the complexity of textual constructions of space, which frequently exceed static definitions of 'setting'. Running throughout is a reconception of narrative as located not with the figure of the narrator, but in relations of intersubjectivity. The narratological criticism formulated here works towards a situated ethics of reading responsive to the politics of writing: it is engaged, relational, and ever in process
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