Effects of triggers of senescence and senolysis in murine pancreatic cancer cells.

Background: The combination of senescence triggers with senolytic drugs is considered a promising new approach to cancer therapy. Here, we studied the efficacy of the genotoxic agent etoposide (Eto) and irradiation in inducing senescence of Panc02 pancreatic cancer cells, and the capability of the Bcl-2 inhibitor navitoclax (ABT-263; Nav) to trigger senolysis.

Methods: Panc02 cells were treated with Eto or irradiated with 5-20 Gy before exposure to Nav.

Logic-based modeling and drug repurposing for the prediction of novel therapeutic targets and combination regimens against E2F1-driven melanoma progression.

Melanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream prometastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds the potential to prevent metastasis however, these networks entail complex feedback and feedforward regulatory motifs among various regulatory layers, which make it difficult to identify druggable components.

In Silico Analysis of MicroRNA Expression Data in Liver Cancer.

Abnormal miRNA expression has been evidenced to be directly linked to HCC initiation and progression. This study was designed to detect possible prognostic, diagnostic, and/or therapeutic miRNAs for HCC using computational analysis of miRNAs expression. Methods: miRNA expression datasets meta-analysis was performed using the YM500v2 server to compare miRNA expression in normal and cancerous liver tissues.

Computational Models for Clinical Applications in Personalized Medicine-Guidelines and Recommendations for Data Integration and Model Validation.

The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes and pathways that characterize human biology, but they also lead to a more profound understanding of the mechanisms and factors that drive diseases; hence, they allow personalized treatment strategies that are guided by central clinical questions. However, despite the growing popularity of computational-modelling approaches in different stakeholder communities, there are still many hurdles to overcome for their clinical routine implementation in the future.

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression.

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently.

The Atlas of Inflammation Resolution (AIR).

Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes.

WITHDRAWN: The Atlas of Inflammation Resolution (AIR).

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.

Integrative workflows for network analysis.

Due to genetic heterogeneity across patients, the identification of effective disease signatures and therapeutic targets is challenging. Addressing this challenge, we have previously developed a network-based approach, which integrates heterogeneous sources of biological information to identify disease specific core-regulatory networks. In particular, our workflow uses a multi-objective optimization function to calculate a ranking score for network components (e.

A web platform for the network analysis of high-throughput data in melanoma and its use to investigate mechanisms of resistance to anti-PD1 immunotherapy.

Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analyses.

A Network-Based Integrative Workflow to Unravel Mechanisms Underlying Disease Progression.

Unraveling mechanisms underlying diseases has motivated the development of systems biology approaches. The key challenges for the development of mathematical models and computational tool are (1) the size of molecular networks, (2) the nonlinear nature of spatio-temporal interactions, and (3) feedback loops in the structure of interaction networks. We here propose an integrative workflow that combines structural analyses of networks, high-throughput data, and mechanistic modeling.

Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures.

Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly aggressive bladder and breast tumors, and use network analysis methods to identify the tumor type-specific core of the network.

MicroRNA and Transcription Factor Gene Regulatory Network Analysis Reveals Key Regulatory Elements Associated with Prostate Cancer Progression.

Technological and methodological advances in multi-omics data generation and integration approaches help elucidate genetic features of complex biological traits and diseases such as prostate cancer. Due to its heterogeneity, the identification of key functional components involved in the regulation and progression of prostate cancer is a methodological challenge. In this study, we identified key regulatory interactions responsible for primary to metastasis transitions in prostate cancer using network inference approaches by integrating patient derived transcriptomic and miRomics data into gene/miRNA/transcription factor regulatory networks.

Is it necessary to submit grossly normal looking gall bladder specimens for histopathological examination?

Background: The objectives of the study were to: 1) determine the frequency of incidental malignancy in unsuspected/grossly normal looking gall bladders; 2) determine the frequency of malignancy in suspected/grossly abnormal looking gall bladders.

Materials And Methods: This prospective, cross sectional study was carried out at a tertiary care hospital in Pakistan, during a four year period (Jan 2009-dec2012). All the cholecystectomy cases performed for gallstone diseases were examined initially by a surgeon and later on by a pathologist for macroscopic abnormalities and accordingly assigned to one of the three categories i.

A novel approach toward fuzzy generalized bi-ideals in ordered semigroups.

In several advanced fields like control engineering, computer science, fuzzy automata, finite state machine, and error correcting codes, the use of fuzzified algebraic structures especially ordered semigroups plays a central role. In this paper, we introduced a new and advanced generalization of fuzzy generalized bi-ideals of ordered semigroups. These new concepts are supported by suitable examples.

Monitor unit calculations for external photon and electron beams: Report of the AAPM Therapy Physics Committee Task Group No. 71.

A protocol is presented for the calculation of monitor units (MU) for photon and electron beams, delivered with and without beam modifiers, for constant source-surface distance (SSD) and source-axis distance (SAD) setups. This protocol was written by Task Group 71 of the Therapy Physics Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol defines the nomenclature for the dosimetric quantities used in these calculations, along with instructions for their determination and measurement.

Hybrid modeling of the crosstalk between signaling and transcriptional networks using ordinary differential equations and multi-valued logic.

A decade of successful results indicates that systems biology is the appropriate approach to investigate the regulation of complex biochemical networks involving transcriptional and post-transcriptional regulations. It becomes mandatory when dealing with highly interconnected biochemical networks, composed of hundreds of compounds, or when networks are enriched in non-linear motifs like feedback and feedforward loops. An emerging dilemma is to conciliate models of massive networks and the adequate description of non-linear dynamics in a suitable modeling framework.

Kinetic modeling-based detection of genetic signatures that provide chemoresistance via the E2F1-p73/DNp73-miR-205 network.

Drug resistance is a major cause of deaths from cancer. E2F1 is a transcription factor involved in cell proliferation, apoptosis. and metastasis through an intricate regulatory network, which includes other transcription factors like p73 and cancer-related microRNAs like miR-205.

Phytobezoar in a jejunal diverticulum as a cause of small bowel obstruction: a case report.

Introduction: Phytobezoars are concretions of poorly digested fruit and vegetable fibers found in the alimentary tract. Previous gastric resection, gastrojejunostomy, or pyloroplasty predispose people to bezoar formation. Small-bowel bezoars normally come from the stomach, and primary small-bowel bezoars are very rare.

Situs inversus totalis with perforated duodenal ulcer: a case report.

Introduction: Situs inversus is an uncommon anomaly. Situs inversus viscerum can be either total or partial. Total situs inversus, also termed as mirror image dextrocardia, is characterized by a heart on the right side of the midline while the liver and the gall bladder are on the left side.

Recommendations for clinical electron beam dosimetry: supplement to the recommendations of Task Group 25.

The goal of Task Group 25 (TG-25) of the Radiation Therapy Committee of the American Association of.Physicists in Medicine (AAPM) was to provide a methodology and set of procedures for a medical physicist performing clinical electron beam dosimetry in the nominal energy range of 5-25 MeV. Specifically, the task group recommended procedures for acquiring basic information required for acceptance testing and treatment planning of new accelerators with therapeutic electron beams.

Application of measured pencil beam parameters for electron beam model evaluation.

Most current electron beam models, as are used in commercial treatment planning systems, combine measured broad beam central axis depth dose data with measured or modeled functions to approximate radial scatter and heterogeneity effects. In this paper, we extend a recently developed pencil beam model to calculate doses outside the field edge and doses in heterogeneous media. We have also explored use of this model as a tool for evaluating commercial electron planning programs.