Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.

Motivation: Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. To evaluate the mutational signatures operative in a cancer genome, one first needs to quantify their activities by estimating the number of mutations imprinted by each signature.

Results: Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples.

Topography of mutational signatures in human cancer.

The somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored.

Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.

Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations.

Importance of circulating tumor cells in newly diagnosed colorectal cancer.

Presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The present study was conducted to determine if the presence of CTC prior to surgery and during follow‑up in patients with newly diagnosed non-metastatic CRC can identify patients at risk for disease recurrence. In a prospective single center study 183 patients with newly diagnosed non-disseminated CRC, scheduled for surgery, were enrolled and followed-up for a median of 5.

Circulating tumor cells before and during follow-up after breast cancer surgery.

The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free and overall survival for patients with metastatic and newly diagnosed breast cancer. The present study was undertaken to explore whether the presence of CTC before and during follow-up after surgery is associated with recurrence free survival (RFS) and overall survival (OS). In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 403 stage I-III patients before undergoing surgery for breast cancer (A) and if available 1 week after surgery (B), after adjuvant chemo- and/or radiotherapy or before start of long-term hormonal therapy (C), one (D), two (E) and three (F) years after surgery.

"Platelet-associated regulatory system (PARS)" with particular reference to female reproduction.

Background: Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface.

Label-free, high-throughput, electrical detection of cells in droplets.

Today, droplet based microfluidics has become a standard platform for high-throughput single cell experimentation and analysis. However, until now no label-free, integrated single cell detection and discrimination method in droplets is available. We present here a microfluidic chip for fast (>100 Hz) and label-free electrical impedance based detection of cells in droplets.

Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer.

Introduction: The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD.

Methods: In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer.

Future Prospects in Breast Cancer Research - Cancer Stem Cells.

Breast cancer is one of the leading causes of cancer deaths among women. Although significant advances in the prevention, diagnosis and management are made, still every year half a million women die of breast cancer. Personalised treatment has the potential to increase treatment efficacy, and hence decrease mortality rates.

Microfluidic Chips for Semen Analysis.

The gold standard of semen analysis is still an manual method, which is time-consuming, labour intensive and needs thorough quality control. Microfluidics can also offer advantages for this application. Therefore a first step in the development of a microfluidic chip has been made, which enables the man the semen analysis at home.

BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function.

The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential.

Microparticles and acute renal dysfunction in septic patients.

Purpose: The role of microparticles (MPs) in the pathogenesis of sepsis is not completely elucidated. We aimed to assess changes in the number of MPs during severe sepsis to follow the effect of sepsis-related organ failures, particularly renal impairment, an independent mortality factor of sepsis.

Materials And Methods: Thirty-seven severe septic patients and 20 controls were enrolled.

Activated platelet-derived microparticle numbers are elevated in patients with severe fungal (Candida albicans) sepsis.

Background: The treatment of severe sepsis highly depends on the identification of bacteria or fungi from blood and/or other body materials. Although widely available blood culturing and risk assessment scores are not completely reliable, current guidelines do not recommend the wide empirical use of antifungal medications based on questionable benefit or possible side-effects. We aimed to test whether platelet-derived microparticle (MP) measurements can improve the early detection of the infective agent behind sepsis.

Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate.

Introduction: This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account.

Method: This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI.

High-yield cell ordering and deterministic cell-in-droplet encapsulation using Dean flow in a curved microchannel.

In this article high-yield (77%) and high-speed (2700 cells s(-1)) single cell droplet encapsulation is described using a Dean-coupled inertial ordering of cells in a simple curved continuous microchannel. By introducing the Dean force, the particles will order to one equilibrium position after travelling less than 1 cm. We use a planar curved microchannel structure in PDMS to spatially order two types of myeloid leukemic cells (HL60 and K562 cells), enabling deterministic single cell encapsulation in picolitre drops.

On chip electrofusion of single human B cells and mouse myeloma cells for efficient hybridoma generation.

This article describes the development and full characterization of a microfluidic chip for electrofusion of human peripheral blood B-cells and mouse myeloma (NS-1) cells to generate hybridomas. The chip consists of an array of 783 traps, with dimensions that were optimized to obtain a final cell pairing efficiency of 33±6%. B cells were stained with a cytoplasmic stain CFDA to assess the different stages of cell fusion, i.

Evaluation of tubular poly(trimethylene carbonate) tissue engineering scaffolds in a circulating pulsatile flow system.

Tubular scaffolds (internal diameter approximately 3 mm and wall thickness approximately 0.8 mm) with a porosity of approximately 83% and an average pore size of 116 µm were prepared from flexible poly(trimethylene carbonate) (PTMC) polymer by dip-coating and particulate leaching methods. PTMC is a flexible and biocompatible polymer that crosslinks upon irradiation; porous network structures were obtained by irradiating the specimens in vacuum at 25 kGy before leaching soluble salt particles.

Flow cytometric analysis of the uptake of low-density lipoprotein by endothelial cells in microfluidic channels.

Acceptance of microfluidic technology in everyday laboratory practice by biologists is still low. One of the reasons for this is that the technology combines poorly with standard cell biological and biochemical analysis tools. Flow cytometry is an example of a conventional analytical tool that is considered to be incompatible with microfluidic technology and its inherent small sample sizes.

A new floating electrode structure for generating homogeneous electrical fields in microfluidic channels.

In this article a new parallel electrode structure in a microfluidic channel is described that makes use of a floating electrode to get a homogeneous electrical field. Compared to existing parallel electrode structures, the new structure has an easier production process and there is no need for an electrical connection to both sides of the microfluidic chip. With the new chip design, polystyrene beads suspended in background electrolyte have been detected using electrical impedance measurements.

Cancer prevalence in osteoporotic women with low serum vitamin D levels.

Objective: The aim of this study was to assess the role of vitamin D in cancer development in postmenopausal osteoporotic women.

Methods: A cross-sectional and in vitro study was carried out, with statistical analysis with odds ratios and 95% CIs presented. Human estrogen receptor-positive breast cancer cells (MCF-7) were studied in vitro.

Shear stress induces a transient and VEGFR-2-dependent decrease in the motion of injected particles in endothelial cells.

Vascular endothelial cells form the inner lining of all blood vessels and play a central role in vessel physiology and disease. Endothelial cells are highly responsive to the mechanical stimulus of fluid shear stress that is exerted by blood flowing over their surface. In this study, the immediate micromechanical response of endothelial cells to physiological shear stress was characterized by tracking of ballistically injected, sub-micron, fluorescent particles.

Dynamic culturing of smooth muscle cells in tubular poly(trimethylene carbonate) scaffolds for vascular tissue engineering.

Porous, tubular, flexible, and elastic poly(trimethylene carbonate) (PTMC) scaffolds (length 8 cm and inner diameter 3 mm) for vascular tissue engineering were prepared by means of a dip-coating and particulate leaching procedure. Using NaCl as porogen, scaffolds with an average pore size of 110 μm and a porosity of 85% were obtained. Before leaching the salt, the structures were made creep-resistant by means of crosslinking at 25 kGy gamma irradiation.