Increasing Colonoscopy Compliance Using a Blood-Based Risk Assessment Test for Colorectal Cancer

ColonSentry® is a minimally invasive, blood-based risk assessment test for colorectal cancer. The test is used to increase patient compliance with colonoscopy. Many physicians have inquired about the incidence of non-malignant lesions found in patients after colonoscopy prompted by an increased risk score on the ColonSentry test. Here we report on the colonoscopy results of five patients with increased ColonSentry risk scores. Of those five patients, three were determined to have polyps, one of which was pre-malignant

Blood-Based Biomarkers of Aggressive Prostate Cancer

Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an “active surveillance” strategy

An Association Rule Based Algorithmic Approach to Mine Frequent Pattern in Spatial Database System

ABSTRACT Emergence of data mining methods in data representation has resulted in discovering knowledge from large database systems. Efficient algorithms to mine frequent patterns are crucial to many tasks in spatial association rule mining. A promising approach for mining such spatial frequent pattern is mining frequent sub-patterns which are closed and maximal patterns. In this paper, we make use of numerical representations and its arithmetic operations to considerably reduce the size of the transaction dataset. The proposed approach generates a TFP-tree that simplifies the generations of frequent patterns. Further analysis shows that this approach generates maximal frequent patterns and performs only minimal generalizations of frequent candidate sets. Experimental results validate the compactness and efficiency for low minimum support against existing methods in spatial domain

Unsteady solute dispersion in the presence of reversible and irreversible reactions

In an unsteady pulsatile non-Newtonian fluid past a tube with a thin wall layer, the dispersion of a narrow uniform slug of injected solute over a cross-section is examined. At the interface between the mobile fluid phase and the immobile wall phase, both irreversible and reversible reactions have been adopted. The Carreau-Yasuda model is used to describe the fluid's rheology. The impacts of fluid rheology and reaction parameters on the concentration profiles in the fluid- and wall-phases and the three transport coefficients, viz, the depletion coefficient (K-0), the convection coefficient (K-1), the dispersion coefficient (K-2) in the fluid phase are predicted numerically. A considerable shift in the behaviour of K-1 and K(2 )with a higher reaction rate may be observed in the transient stage. The axial dispersion of mobile-phase concentration in the unsteady Carreau-Yasuda II fluid model is significantly larger than in Poiseuille and steady Carreau-Yasuda II fluid models, and flow pulsatility on the immobile-phase concentration is prominent upstream at a longer time. In addition, the peak value of the mobile-phase section-mean concentration is consistently lower than in other fluid models. This study could help researchers to understand the drug delivery in blood vessels and pulmonary mechanical ventilation. (C) 2022 The Author(s) Published by the Royal Society. All rights reserved

Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death

Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis. Further, inhibiting apoptosis by Z-DEVD-FMK and N-acetyl cysteine (NAC) increased autophagic cell death after AGG treatment, suggesting that AGG simultaneously induced autophagic and apoptotic death in HeLa cells. Additionally, it observed that AGG-induced autophagic cell death in Bax knock down (Bax-KD) and 5-FU resistant HeLa cells, confirming as an alternate cell killing pathway to apoptosis. At the molecular level, AGG-induced ER stress in PERK dependent pathway and inhibition of ER stress by salubrinal, eIF2 phosphatase inhibitor as well as siPERK reduced autophagic death in the presence of AGG. Further, our in silico and colocalization study showed that AGG interacted with pleckstrin homology (PH) domain of Akt to suppress its phosphorylation and consequent downstream mTOR dephosphorylation in HeLa cells. We showed that Akt overexpression could not augment GRP78 expression and reduced autophagic cell death by AGG as compared to pcDNA control, indicating Akt modulation was the upstream signal during AGG's ER stress mediated autophagic cell death. In conclusion, we established that AGG stimulated cell death by autophagy might be used as an alternative tumor suppressor mechanism in human cervical cancer. (c) 2016 Wiley Periodicals, Inc

Autophagy: cancer’s friend or foe?

The functional relevance of autophagy in tumor formation and progression remains controversial. Autophagy can promote tumor suppression during cancer initiation and protect tumors during progression. Autophagy-associated cell death may act as a tumor suppressor, with several autophagy-related genes deleted in cancers. Loss of autophagy induces genomic instability and necrosis with inflammation in mouse tumor models. Conversely, autophagy enhances survival of tumor cells subjected to metabolic stress and may promote metastasis by enhancing tumor cell survival under environmental stress. Unraveling the complex molecular regulation and multiple diverse roles of autophagy is pivotal in guiding development of rational and novel cancer therapies

Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer

Abrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki‐67 and CD‐31, respectively. In addition, TUNEL positive cells increased in breast tumors treated with AGG suggesting that AGG mediates anti‐tumorigenic activity through induction of apoptosis and inhibition of angiogenesis. On a molecular level, AGG caused extrinsic apoptosis through ROS generation that was AKT‐dependent in breast cancer cells, without affecting primary mammary epithelial cells, suggesting potential cancer specificity of this natural compound. In addition, using HUVECs, AGG inhibited expression of the pro‐angiogenic factor IGFBP‐2 in an AKT‐dependent manner, reducing angiogenic phenotypes both in vitro and in vivo. Overall, the present results establish that AGG promotes both apoptosis and anti‐angiogenic activities in human breast tumor cells, which might be exploited for treatment of breast and other cancers

Sovereign Words : Indigenous Art, Curation and Criticism

"Sixteen Indigenous voices convene to consider some of the most burning questions surrounding this field. How will novel methodologies of word/voice-crafting be constituted to empower the Indigenous discourses of the future? Is it sufficient to expand the Modernist art-historical canon through the politics of inclusion? Is this expansion a new form of colonisation, or does it foster the cosmopolitan thought that Indigenous communities have always inhabited? To whom does the much talked-of ‘Indigenous Turn’ belong? Does it represent a hegemonic project of introspection and revision in the face of today’s ecocidal, genocidal and existential crises? A first of its kind reader of Indigenous voices, Sovereign Words charts perspectives across art and film, ethics and history, theory and the museological field. With the canonical power systems of the international art world increasingly under fire today, the book makes a strong bid for knowledge building and intellectual alliances that will inform the cultural and artistic processes of Indigenous and non-Indigenous futures." -- Publisher's web site