The CDK inhibitors in cancer research and therapy

Chemical compounds that interfere with an enzymatic function of kinases are useful for gaining insight into the complicated biochemical processes in mammalian cells. Cyclin-dependent kinases (CDK) play an essential role in the control of the cell cycle and/or proliferation. These kinases as well as their regulators are frequently deregulated in different human tumors. Aberrations in CDK activity have also been observed in viral infections, Alzheimer's, Parkinson's diseases, ischemia and some proliferative disorders. This led to an intensive search for small-molecule CDK inhibitors not only for research purposes, but also for therapeutic applications. Here, we discuss seventeen CDK inhibitors and their use in cancer research or therapy. This review should help researchers to decide which inhibitor is best suited for the specific purpose of their research. For this purpose, the targets, commercial availability and IC50 values are provided for each inhibitor. The review will also provide an overview of the clinical studies performed with some of these inhibitor

Mycobacteria produce proteins involved in biofilm formation and growth-affecting processes

The aim of this study was to determine the effect of mycobacterial proteins on mycobacterial biofilm formation and growth processes. We separated growth-affecting proteins (GEPs) from wild type of Mycobacterium bovis and ATCC strain of Mycobacterium avium subsp. avium. Our results showed that these mycobacteria-secreted GEPs are involved in biofilm formation, growth stimulatory, and inhibitory processes. Our findings suggest that GEP stimulated M. avium subsp. avium growth in vitro. Stimulation process was observed in mycobacteria affected with GEP extracted from M. avium subsp. avium. We found that both GEPs inhibited the growth of the M. bovis. Optical density measurement and visual analysis confirm that GEP plays an important role in biofilm formation process. Most of M. bovis GEP are associated with the type VII secretion and general secretion pathways. Our results contribute to a better understanding of the mechanisms underlying mycobacterial biofilm formation and growth-affecting processes and better characterization of mycobacterial proteins and their functions. It is noteworthy that this finding represents the first demonstration of GEP-mediated growth effects on a solid and liquid medium

Proteomics analysis of proteins associating with Nck-a 1 Proteomic analysis of proteins associating with Nck-a

Nck proteins are a family of SH2/SH3 domain-containing adaptor proteins. Both Nck-a and Nck-b play a major role in regulating a wide variety of cellular processes, including cytoskeletal rearrangement, cell morphology, gene expression and protein translation. We have analysed proteins interacting with SH3 domains of Nck-a. The proteins were separated using two-dimensional electrophoresis, subjected to in-gel digestion with trypsin and identified by mass spectrometry using MALDI-TOF mass fingerprinting. Here we report novel potential binding partners for Nck-a such as 14-3-3g protein, eukaryotic translation initiation factor 4E and ras-related protein Rab-30. Our results provide additional information presumably confirming Nck-a role in actin cytoskeleton rearrangement regulation and the modulation of the eukaryotic translation initiation. Data also suggest that Nck-a might be involved in the control of Golgi functioning

Vienasienių nanovamzdelių ir Coprinus Cinereus peroksidazės kompleksų sintezė ir tyrimas

Carbon nanotube-peroxidase conjugates can catalyze oxidation of “Amplex Red“ into fluorescent resorufin so they may be useful as a marker. Synthesis of carbon nanotube-enzyme conjugates was carried out with different starting concentrations of Coprinus Cinereus peroxidase and polyethylenimine, also in the medium with different pH. Specific activity of conjugates was determined spectrophotometrically with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and hydrogen peroxide as substrates. The scanning electron and confocal fluorescence microscope analysis were performed on the conjugates. It was concluded that these structures have perspective to be used as fluorescent markers.Anglies nanovamzdelių-peroksidazės kompleksai gali katalizuoti „Amplex Red“ oksidaciją. Proceso metu susidaro fluoresuojantis rezorufinas. Todėl šie kompleksai gali būti naudoajami kaip nanožymenys. Nanovamzdelių fermentinių kompleksų sintezė buvo atlikta su skirtingomis pradinėmis Coprinus Cinereus peroksidazės ir polietilenimino koncentracijomis, taip pat terpėje su skirtingu pH. Gautų kompleksų specifinis aktyvumas buvo nustatytas spektrofotometriškai naudojant 2,2‘-azino-bis-3-etilbenztiazolino-6-sulfoninę rūgštį (ABTS) ir vandenilio peroksidą kaip substratus. Atliktos analizės naudojantis skanuojančiu elektroniniu ir fluoresentiniu konfokaliniu mikroskopu, parodyta, kad kompleksai turi didelį katalitinį pajekumą ir gali būti naudojami kaip fluorescentiniai markeriai. Reikšminiai žodžiai: anglies nanovamzdeliai, peroksidazė, polietileniminas, nanožymenys, specifinis aktyvumas

Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

The sharp contrast of the intracellular distribution after microinjection of quantum dots in comparison with incubation as well as the limited transfer of quantum dots from vesicles into the cytosol and vice versa support the endocytotic origin of the natural uptake of quantum dots. Quantum dots with proteins adsorbed from the culture medium had a different fate in the final stage of accumulation from that of the protein-free quantum dots, implying different internalization pathways

The perspectives of patients with type 2 diabetes mellitus on marketing mix elements in primary health care: a quantitative study from Lithuania

A competitive advantage in health care institutions can be cultivated by marketing activities and value creation for patients with chronic diseases in primary health care. Type 2 diabetes mellitus (T2DM) is a major challenge in primary health care, as managing risk factors and managing patient knowledge can help to prevent a number of major of complications. This study reveals the expectations and attitudes of patients with T2DM regarding marketing mix elements in the management of their condition. Aim of the study: To explore the perspectives of patients with T2DM on marketing mix elements in the primary health care institutions of Lithuania. Materials and methods: The design of the national study was based on a survey of patients with T2DM that was conducted after consultation with a family physician in primary health care institutions in Lithuania. The survey was conducted from October 2017 to January 2018, and involved 510 patients with T2DM. Data analysis included factor analysis and linear logistic regression. A hypothetical model was built, defining the relationships between marketing mix elements and both perceived value (emotional, functional, and social) and satisfaction with primary health care services. Results: The marketing mix element of ‘Service’ is statistically significantly dependent on the gender of the respondents, and is expressed more frequently by women (rcr = 0.118, P = 0.007). The occupation of respondents with T2DM (rcr = 0.151, P = 0.009) and affiliation to primary health care institution (rcr = 0.091, P = 0.040) statistically positively affect the marketing mix element of ‘Price’. The marketing mix elements of ‘Promotion’ and ‘People’ do not statistically significantly depend on the sociodemographic characteristics of the respondents. Only a weak correlation between the sociodemographic characteristics of the respondents and the marketing element of ‘Place’ was found. The ‘Process’ element is statistically significantly more relevant to patients with an average monthly income of €350 (rcr = 0.104, P = 0.019). The element of ‘Physical evidence’ is more statistically significantly related to respondents with an average monthly income of €350 (rcr = 0.092, P = 0.038). Conclusions: Marketing mix analysis provides information about patients’ expectations of primary health care services and identifies areas of improvement for the health services provided by primary health care institutions. The competitiveness of primary health care services is strengthened by enhancing value for patients, by using elements of the health care marketing, and by increasing patient satisfaction

CEACAM6’s role as a chemoresistance and prognostic biomarker for pancreatic cancer: a comparison of CEACAM6’s diagnostic and prognostic capabilities with those of CA19-9 and CEA

Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, 267 patients were included in the study. Surgically collected pancreatic tissue samples were analysed via high-definition mass spectrometry. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was discovered as a possible promising pancreatic cancer biomarker. The predominance of CEACAM6 to pancreatic cancer was validated using antibodies in tissue samples. CEACAM6, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) blood serum concentrations were evaluated for clinical evaluation and comparison. Kaplan–Meier survival analyses were used to evaluate disease-free survival (DFS) and overall survival (OS). Poorer overall survival was significantly dependent on increased CEACAM6 blood serum concentrations (17.0 vs. 12.6 months, p = 0.017) in pancreatic cancer patients after radical treatment and adjuvant chemotherapy. Increased CEA and CA19-9 concentrations showed no significant dependencies with survival. Thus, CEACAM6 is a promising new biomarker with significant prognostic value and prediction of chemoresistance properties, enabling the improvement of individualised approaches to patients with pancreatic cancer

The GTPase-Activating Protein of Ras Suppresses Platelet-Derived

receptor signaling by silencing phospholipase suppresses platelet-derived growth factor beta The GTPase-activating protein of Ra