Efficiency of colorectal carcinoma treatment by chemotherapy is diminished as the resistance develops over time in patients. The same holds true for 5-fluorouracil, the drug used in first line chemotherapy of colorectal carcinoma. Chemoresistant derivative of HT-29 cells was prepared by long-term culturing in increasing concentration of 5-fluorouracil. Cells were characterized by viability assays, flow cytometry, gene expression arrays and kinetic imaging. Immunomagnetic separation was used for isolation of subpopulations positive for cancer stem cells-related surface markers. Aldehyde dehydrogenase expression was attenuated by siRNA. In vivo studies were performed on SCID/bg mice. The prepared chemoresistant cell line labeled as HT-29/EGFP/FUR is assigned with different morphology, decreased proliferation rate and 135-fold increased IC50 value for 5-fluorouracil in comparison to parental counterparts HT-29/EGFP. The capability of chemoresistant cells to form tumor xenografts, when injected subcutaneously into SCID/bg mice, was strongly compromised, however, they formed distant metastases in mouse lungs spontaneously. Derived cells preserved their resistance in vitro and in vivo even without the 5-fluorouracil selection pressure. More importantly, they were resistant to cisplatin, oxaliplatin and cyclophosphamide exhibiting high cross-resistance along with alterations in expression of cancer-stem cell markers such as CD133, CD166, CD24, CD26, CXCR4, CD271 and CD274. We also detected increased aldehyde dehydrogenase (ALDH) activity associated with overexpression of specific ALDH isoform 1A3. Its inhibition by siRNA approach partially sensitized cells to various agents, thus linking for the first time the ALDH1A3 and chemoresistance in colorectal cancer. Our study demonstrated that acquired chemoresistance goes along with metastatic and migratory phenotype and can be accompanied with increased activity of aldehyde dehydrogenase. We describe here the valuable model to study molecular link between resistance to chemotherapy and metastatic dissemination.

Nowadays, a wide range of materials is used for car body structures in order to improve both the passengers’ safety and fuel consumption. These are joined by laser welding and solid state fiber lasers being used more and more in present. The article is focused on the research of laser welding influence on the mechanical and deformation properties, microstructure and microhardness of advanced high-strength steels: high-strength low-alloyed steel HC340LA, dual phase steel HCT600X and multi-phase residual austenite steel RAK40/70. The proper welding parameters have been found based on weld quality evaluation. The specimens for tensile test with longitudinal laser weld were used to measure mechanical and deformation properties. Microstructure and microhardness of laser welds were evaluated in the base metal, heat affected zone and fusion zone. The higher values of strength and lower ones for deformation properties of laser-welded materials have been found for dual and multi-phase steel. The microhardness strongly depends on the carbon equivalent of steel. Deformation properties are more sensitive than strength properties to the change of microstructure in the fusion zone and heat affected zone.

The decrease of emissions from vehicle operation is connected mainly to the reduction of the car’s body weight. The high strength and good formability of the dual phase steel grades predetermine these to be used in the structural parts of the car’s body safety zones. The plastic properties of dual phase steel grades are determined by the ferrite matrix while the strength properties are improved by the volume and distribution of martensite. The aim of this paper is to describe the relationship between the mechanical properties and the parameters of structure and substructure. The heat treatment of low carbon steel X60, low alloyed steel S460MC, and dual phase steel DP600 allowed for them to reach states with a wide range of volume fractions of secondary phases and grain size. The mechanical properties were identified by a tensile test, volume fraction of secondary phases, and grain size were measured by image analysis. It was found that by increasing the annealing temperature, the volume fraction of the secondary phase increased, and the ferrite grains were refined. Regression analysis was used to find out the equations for predicting mechanical properties based on the volume fraction of the secondary phase and grain size, following the annealing temperature. The hardening mechanism of the dual phase steel grades for the states they reached was described by the relationship between the strain-hardening exponent and the density of dislocations. This allows for the designing of dual phase steel grades that are “tailored” to the needs of the automotive industry customers.

The friction coefficient in the simulation of stamping processes should be defined. Modern simulation software allows its definition as constant or its dependence on pressure or temperature. It is also useful in stamping processes to define different values in different regions, as it often reflects the nature of deformation process. This article deals with the regression and analytical models commonly used to determine the friction coefficients in specified areas of the stamping process. Analytical models were verified by an experimental strip drawing test under the same contact conditions. Steel sheets for the automotive industry were used in experiments and simulations—extra deep drawing quality DC 05 and austenitic stainless steel AISI 304. Friction coefficients were also evaluated when the cup test was performed. A regression model of drawing to the blankholding force was applied to the results. Conformity of friction coefficients when measured by cup tests and strip tests was confirmed. The values of the friction coefficient reached from the experiment were applied in FEM simulation software.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field.