Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped survive and quickly regrow, or acquisition mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized cell cycle arrest, epithelial-to-mesenchymal transition (EMT) reversible upregulation multidrug (MDR) efflux transporter P-glycoprotein (P-gp). The persister (DTP)...

Abstract Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, principal role of neurons emergence this essential cognitive mechanism has been questioned. To address possibility astrocytic involvement SWA, we used transgenic rat line expressing calcium sensitive fluorescent protein both astrocytes interneurons simultaneously imaged neuronal vivo . Here demonstrate, for first...

Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy target collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study, our aim was catalog various compounds that were reported elicit increased toxicity in P-glycoprotein (Pgp)-overexpressing MDR cells. We show activity most serendipitously identified cells fact cell-line specific, and not influenced significantly by function Pgp....

Mathematical models of tumor growth in response to chemotherapy are crucial for therapy optimization and outcome. We create a relatively simple model describing the antitumor effect pegylated liposomal doxorubicin (PLD) validated with real experimental data obtained genetically engineered mouse breast cancer. use formal reaction kinetics describe pathophysiological phenomena using differential equations, carry out parametric identification based on experiments mixed-effect stochastic...

Chemotherapy optimization based on mathematical models is a promising direction of personalized medicine. Personalizing, thus optimizing treatments, may have multiple advantages, from fewer side effects to lower costs. However, personalization complicated process in practice. We discuss model tumor growth and therapy algorithms that can be used personalize therapies. The generation the concept keeping drug level over specified value. A mixed-effect for parametric identification, doses are...

Intrarenal changes in cytoplasmic calcium levels have a key role determining pathologic and pharmacologic responses major kidney diseases. However, cell-specific delivery of calcium-sensitive probes vivo remains problematic. We generated transgenic rat stably expressing the green fluorescent protein-calmodulin-based genetically encoded indicator (GCaMP2) predominantly proximal tubules. The transposon-based method used allowed generation homozygous rats containing one copy transgene per...

Abstract Bioimpedance spectrum (BIS) measurements have a great future in vitro experiments, meeting all the requirements for non-destructive and label-free methods. Nevertheless, real basic research can provide necessary milestones to achieve success of method. In this paper self-developed technology-based approach assays is proposed. Authors invented special graphene-based measuring plate order assess high sensitivity reproducibility introduced technique. The design self-produced BIS plates...

We synthesized substituted benzaldehyde derived α-hydroxyphosphonates (αOHP), α-hydroxyphosphonic acids (αOHPA) and α-phosphinoyloxyphosphonates (αOPP) characterized their cytotoxicity against a panel of cancer cell lines.

Cancer therapy optimization is an issue that can be solved using the control engineering approach. An optimal generation algorithm presented and tested a tractable mouse model of breast cancer. The optimized therapeutic protocol calculated in closed‐loop manner at fixed time instants, twice week. controller consists nonlinear predictive which uses state estimation moving horizon estimator. estimator also computes parameter estimates prediction such varying nature tumor evolution captured....

Optimized therapies for the individual patient provide a more cost-effective, secure method of chemotherapy. Therapy optimization demands reliable mathematical model tumor growth, pharmacodynamics, and effect chemotherapeutic agent used during therapy. Examining these effects processes in vitro cell culture experiments maintain cheaper ethical to create growth pharmacodynamics models estimate their parameters. In this work, parameter identification was carried out by using cytotoxicity...

Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated cancer progression; however, its role oncogenesis not well defined. In this study, the function of was investigated HCT116 colon cells by knocking out using CRISPR/Cas9 system. Surprisingly, absence induced significant changes cell morphology, motility, adhesion expression,...

Breast cancer is the most commonly occurring in women and second common overall. By age of 80, estimated risk for breast with germline BRCA1 or BRCA2 mutations around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study pathogenesis therapy triple negative cancer. Here we present newly established Brca1−/−, p53−/− mammary tumor cell line, designated as CST. CST shows prominent features BRCA1-mutated triple-negative cancers including increased motility,...

Mesenchymal stem cells (MSCs) are an integral part of the tumor microenvironment (TME); however, their role is somewhat controversial: conflicting reports suggest that, depending on stage development, MSCs can either support or suppress growth and spread. Additionally, influence drug resistance also ambiguous. Previously, we showed despite proliferating significantly more slowly than cancer cells, there chemotherapeutic drugs which proved to be similarly toxic both cell types. Here...

Abstract In drug discovery, prediction of selectivity and toxicity require the evaluation cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology toxicology studies, while currently no indicator protein expressing model available. We established transgenic strain stably GCaMP2 fluorescent sensor by transposon-based methodology. Zygotes were co-injected with mRNA transposase CAG-GCaMP2 construct animals one transgene copy pre-selected measuring fluorescence in...

Background: Treatment of malignancies is still a major challenge in human and canine cancer, mostly due to the emergence multidrug resistance (MDR). One main contributors MDR overexpression P-glycoprotein (Pgp), which recognizes extrudes various chemotherapeutics from cancer cells. Methods: To study mechanisms underlying development drug resistance, we established an vitro treatment protocol rapidly induce Pgp-mediated Based on clinical observation showing that 33-day-long, unplanned holiday...

Melanoma-associated fibroblasts (MAFs) are integral parts of melanoma, providing a protective network for melanoma cells. The phenotypical and functional similarities between MAFs mesenchymal stromal cells (MSCs) prompted us to investigate if, similarly MSCs, capable modulating macrophage functions. Using immunohistochemistry, we showed that macrophages in intimate contact within the tumor stroma. We then demonstrated indeed potent inducers IL-10 production various types vitro, this process...

With the advancement of technology and medicine, personalized therapies arise which may provide a promising solution for problems chemotherapy, such as many side effects. Personalized can be applied that meet individual needs patients, this make healthcare cancer patients safer more cost-effective. However, therapy requires reliable model tumor dynamics effect drug during therapy. Examining certain drugs on in vitro cell cultures helps us to gain understanding mechanism create...

Optimizing computer-generated therapy may be one of the most promising tools for future medical treatments. In silico experiments are crucial planning and testing, this requires a reliable virtual patient model. We present noise model that can used to real measurement from mice add experiments, measurements performed with digital caliper, tumor is measured through skin, which reason why significant nonlinear expected. use data preclinical estimate transformation whiten noise. Finally, we...

Abstract Purpose Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting entry of therapeutic drugs into tumor cells. Although a higher expression these has been correlated with an unfavorable response chemotherapy, transporter does not necessarily correlate function. In this study, we characterized pharmacological properties [ 18 F]AVT-011, new PET radiotracer for imaging...

Mesenchymal stem cells (MSCs) or fibroblasts are one of the most abundant cell types in tumor microenvironment (TME) exerting various anti- and pro-apoptotic effects during tumorigenesis, invasion, drug treatment. Despite recently discovered importance MSCs progression therapy, response these to chemotherapeutics compared cancer is rarely investigated. A widely accepted view that naive have higher tolerance than due a significantly lower proliferation rate. Here, we examine differences...

Fluorescent live cell imaging is a widely used method in studying vitro cultures, thus the behavior of tumor spheroids can be examined cheaply and simply over several days. However, during days lasting experiments with many measurement points, strong laser light that excites fluorescent sample have destructive effect on living cells. This phenomenon phototoxicity, consideration which fundamental importance such long-term cytotoxicity measurements, order to filter out those cell-damaging...