19 results on '"Stańczak M"'
Search Results
2. 112P_PR - Immune response and adverse events to influenza vaccine in cancer patients undergoing PD-1 blockade
- Author
-
Rothschild, S.I., Balmelli, C., Kaufmann, L., Stanczak, M., Syedbasha, M., Vogt, D., Gautschi, O., Egli, A., Zippelius, A., and Laeubli, H.
- Published
- 2017
- Full Text
- View/download PDF
3. Abstract No. 31 - Monitoring postablation renal cellular carcinoma using 3D contrast enhanced ultrasound and time intensity curve analysis: preliminary results
- Author
-
Carr, M, Shaw, C, Nam, K, Stanczak, M, Lyshchik, A, Forsberg, F, Liu, J, Lallas, C, Trabulsi, E, and Eisenbrey, J
- Published
- 2017
- Full Text
- View/download PDF
4. 12P - Lectin Galactoside-Binding Soluble 3 Binding Protein (LGALS3BP) is a Cancer-Associated Ligand for Inhibitory Siglecs
- Author
-
Läubli, H., Stanczak, M., Alisson-Silva, F., Varki, N., and Varki, A.
- Published
- 2014
- Full Text
- View/download PDF
5. Numerical and experimental study on mechanical behaviour of the AlSi10Mg aluminium structures manufactured additively and subjected to a blast wave
- Author
-
Stanczak M., Fras T., Blanc L., Pawlowski P., and Rusinek A.
- Subjects
Physics ,QC1-999 - Abstract
The paper is related to energy absorptive properties of additively manufactured metallic cellular structures. The samples of Honeycomb, Auxetic, rhomboidal Lattice and a regular Foam are subjected to a dynamic compression due to the blast tests. The cuboidal samples are manufactured by the Direct Metal Laser Sintering (DMLS) method using AlSi10Mg aluminium powder. The experimental tests are performed by means of an Explosive Driven Shock Tube (EDST). The measured results of the transmitted forces in relation to the shortening of the samples allow to analyse the deformation processes of each selected geometry. In addition, the evaluation of the structural responses leads to identification of the structure properties, such as the equivalent stress over equivalent strain or the energy absorption per a unit of mass. Moreover, the process of compression is modelled numerically using the explicit code LS-DYNA R9.0.1. The obtained simulations provide the complete analysis of the experimentally observed mechanisms.
- Published
- 2021
- Full Text
- View/download PDF
6. Possible applications of dynamic taping in women after the removal of lymph nodes because of breast cancer,Możliwości zastosowania dynamicznego plastrowania u kobiet po usunięciu węzłów chłonnych z powodu raka gruczołu piersiowego
- Author
-
Lipińska, A., Lipińska-Stańczak, M., Macek, P., Szczepaniak, R., Jandziś, S., and Zbigniew Śliwiński
7. Adsorption and dissociation equilibrium of benzoic acid on the mercury electrode
- Author
-
Dojlido, J., primary, Dmowska-Stańczak, M., additional, and Galus, Z., additional
- Published
- 1978
- Full Text
- View/download PDF
8. Tendon Cell Biology: Effect of Mechanical Loading.
- Author
-
Stańczak M, Kacprzak B, and Gawda P
- Subjects
- Humans, Animals, Stress, Mechanical, Tendinopathy pathology, Tendinopathy metabolism, Tenocytes metabolism, Tendons metabolism, Tendons pathology, Extracellular Matrix metabolism, Mechanotransduction, Cellular
- Abstract
Tendons play a crucial role in the musculoskeletal system, connecting muscles to bones and enabling efficient force transfer. However, they are prone to acute and chronic injuries, which, if not properly repaired, can significantly impair function. Tendinopathy, a prevalent condition affecting approximately 20% of musculoskeletal complaints, arises from an imbalance between micro-injury accumulation and repair processes. The extracellular matrix (ECM) of tendons is a hierarchical structure comprising collagen fibrils, proteoglycans, and glycoproteins that regulate organization, hydration, and mechanical properties. Mechanotransduction pathways, mediated by integrins and focal adhesion complexes, activate signaling cascades such as MAPK/ERK and PI3K/Akt, driving tenocyte gene expression and ECM remodeling. Adaptations to load involve region-specific remodeling, with tensile regions favoring aligned Type I collagen and compressive regions promoting proteoglycans like aggrecan. Stress shielding or reduced loading disrupts these pathways, leading to matrix disorganization and inflammation, predisposing tendons to degenerative changes. Insights into these molecular mechanisms inform rehabilitation strategies to enhance tendon repair and mitigate tendinopathy progression in both athletic and general populations., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)
- Published
- 2024
- Full Text
- View/download PDF
9. Genetic hallmarks and clinical implications of chromothripsis in childhood T-cell acute lymphoblastic leukemia.
- Author
-
Pastorczak A, Urbanska Z, Styka B, Miarka-Walczyk K, Sedek L, Wypyszczak K, Wakulinska A, Nowicka Z, Szczepański T, Stańczak M, Fendler W, Kowalczyk J, Młynarski W, and Lejman M
- Subjects
- Humans, Child, Male, Child, Preschool, Female, Prognosis, Adolescent, Infant, Genomic Instability, DNA Copy Number Variations, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma mortality, Chromothripsis
- Abstract
Chromothripsis (cth) is a form of genomic instability leading to massive de novo structural chromosome rearrangements in a one-time catastrophic event. It can cause cancer-promoting alterations, such as loss of sequences for tumor-suppressor genes, formation of oncogenic fusions, and oncogene amplifications. We investigated the genetic background and clinical significance of cth in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. For this purpose, whole-genome copy number alterations were analyzed in 173 children with newly diagnosed T-ALL using high-density microarrays. Cth was identified in 10 T-ALL samples (5.78%). In six of them, cth occurred in a constitutional background of Nijmegen breakage syndrome (n = 5) or Li-Fraumeni syndrome (n = 1). Cth generated alterations, including deletions of CDKN2A/B (n = 4) and EZH2 (n = 4), amplifications of CDK6 (n = 2), and NUP214::ABL1 and TFG::GPR128 fusions. Cth-positive leukemias exhibited deletions involving the tumor-suppressor genes RB1 (n = 3), TP53 (n = 1) and MED12 (n = 2). Cth-positive T-ALL patients had a lower probability of 5-year overall survival (OS) [0.56 vs. 0.81; hazard ratio (HR) = 4.14 (1.42-12.02) p = 0.017] as did 5-year event-free survival [0.45 vs. 0.74; HR = 3.91 (1.52-10.08); p = 0.012]. Chromothripsis is an infrequent genomic phenomenon in pediatric T-ALL but is significantly associated with cancer-predisposing syndromes and may associate with inferior prognosis., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
10. Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study.
- Author
-
Stańczak M, Wyszomirski A, Słonimska P, Kołodziej B, Jabłoński B, Stanisławska-Sachadyn A, and Karaszewski B
- Abstract
Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown., Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not., Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only., Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium., Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stańczak, Wyszomirski, Słonimska, Kołodziej, Jabłoński, Stanisławska-Sachadyn and Karaszewski.)
- Published
- 2024
- Full Text
- View/download PDF
11. Preliminary results of Polish national multicenter study on colostomy reversal - LICO (Liquidation of Colostomy) study.
- Author
-
Kisielewski M, Wojewoda T, Richter K, Wysocki M, Jankowski M, Krawczyk W, Wantulok J, Jeleńska-Bieńkowska K, Stańczak M, Grudzińska E, Molasy B, Komorowski AL, Zdrojewski M, Sachańbiński T, Franczak P, Wierdak M, Dowgiałło-Gornowicz N, and Wysocki WM
- Abstract
Introduction: Creation of colostomy is still a commonly performed procedure in emergency settings, when intestinal anastomosis cannot be performed safely. Reversing a stoma has been linked with high rates of morbidity and also mortality., Aim: The primary goal of the study was to identify the risk of postoperative complications in patients undergoing colostomy liquidation. The secondary goal was to assess perioperative care parameters., Material and Methods: The LIquidation of COlostomy (LICO) study is an open multicenter prospective cohort study that began in October 2022 and will continue until December 2023. Data from 20 Polish surgical departments were collected. Overall 45 patients were reported over the initial 3 months; based on that group we performed a preliminary analysis., Results: Mean operative time was 163 min. Patients were operated on by specialists in 93.3% of cases. Complications occurred in 15 (33.3%) patients. Wound infection was the most common complication (17.8%). In 3 (6.7%) cases anastomotic leakage was diagnosed, and in 2 of those cases reoperation was required. The overall mortality rate was 2.2%. The mean length of hospital stay was 10.1 days. Preoperative fasting was used in 53.3% of patients, and the mechanical bowel preparation rate was 75.6%. Only in 8.9% of cases was laparoscopic access used for stoma reversal, and only in 1 out of 45 cases was mesh used for incisional peristomal hernia prophylactics. The stoma site was closed by single sutures in 73.3%, and negative pressure assisted closure was performed in 6.7% of patients., Conclusions: Colostomy liquidation is associated with significant morbidity and minor mortality in the Polish population. Standardized perioperative care should be established for stoma reversal surgery., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Fundacja Videochirurgii.)
- Published
- 2024
- Full Text
- View/download PDF
12. Influence of Nutritional Interventions on Functional Outcomes in Stroke Rehabilitation: A Systematic Review.
- Author
-
Kolanu ND, Ahmed S, Kerimkulova MK, Stańczak M, Aguirre Vera GJ, Shaikh N, Addula AR, Cheran M, Chilla SP, Oliveira Souza Lima SR, Shehryar A, and Rehman A
- Abstract
Stroke, a major cause of disability worldwide, necessitates comprehensive rehabilitation, with nutrition playing a pivotal role in recovery. Our systematic review assesses the impact of nutritional interventions on stroke survivors' rehabilitation. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science, and Scopus, using keywords related to stroke rehabilitation and nutrition. Studies were selected based on criteria emphasizing dietary interventions and their effect on functional recovery in stroke patients. The review involved detailed data extraction and synthesis, covering study design, participant characteristics, interventions, and outcomes. Five studies met our inclusion criteria, encompassing longitudinal and prospective studies, retrospective cohorts, and randomized controlled trials. These studies highlighted the importance of early nutritional assessment, particularly for sarcopenic patients, and the role of energy and protein intake soon after a stroke. Findings indicated high nutritional risk correlated with poorer functional outcomes and increased inflammation. Tailored dietary support appeared beneficial for muscle mass maintenance and overall functional recovery, especially in older patients. Our review emphasizes the critical role of nutritional interventions in stroke rehabilitation. It suggests that personalized nutritional strategies can positively impact functional recovery, notably in older and nutritionally vulnerable stroke survivors. These insights underscore the necessity of integrating dietary assessments and interventions into standard stroke rehabilitation protocols, advocating a holistic approach to patient care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kolanu et al.)
- Published
- 2024
- Full Text
- View/download PDF
13. Lipopolysaccharide Primes Human Macrophages for Noncanonical Inflammasome-Induced Extracellular Vesicle Secretion.
- Author
-
Cypryk W, Czernek L, Horodecka K, Chrzanowski J, Stańczak M, Nurmi K, Bilicka M, Gadzinowski M, Walczak-Drzewiecka A, Stensland M, Eklund K, Fendler W, Nyman TA, and Matikainen S
- Subjects
- Humans, Caspases metabolism, Escherichia coli metabolism, Inflammasomes metabolism, Nerve Growth Factors metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Toll-Like Receptor 4 metabolism, Extracellular Vesicles metabolism, Lipopolysaccharides pharmacology, Macrophages metabolism
- Abstract
Human macrophages secrete extracellular vesicles (EVs) loaded with numerous immunoregulatory proteins. Vesicle-mediated protein secretion in macrophages is regulated by poorly characterized mechanisms; however, it is now known that inflammatory conditions significantly alter both the quantities and protein composition of secreted vesicles. In this study, we employed high-throughput quantitative proteomics to characterize the modulation of EV-mediated protein secretion during noncanonical caspase-4/5 inflammasome activation via LPS transfection. We show that human macrophages activate robust caspase-4-dependent EV secretion upon transfection of LPS, and this process is also partially dependent on NLRP3 and caspase-5. A similar effect occurs with delivery of the LPS with Escherichia coli-derived outer membrane vesicles. Moreover, sensitization of the macrophages through TLR4 by LPS priming prior to LPS transfection dramatically augments the EV-mediated protein secretion. Our data demonstrate that this process differs significantly from canonical inflammasome activator ATP-induced vesiculation, and it is dependent on the autocrine IFN signal associated with TLR4 activation. LPS priming preceding the noncanonical inflammasome activation significantly enhances vesicle-mediated secretion of inflammasome components caspase-1, ASC, and lytic cell death effectors GSDMD, MLKL, and NINJ1, suggesting that inflammatory EV transfer may exert paracrine effects in recipient cells. Moreover, using bioinformatics methods, we identify 15-deoxy-Δ12,14-PGJ2 and parthenolide as inhibitors of caspase-4-mediated inflammation and vesicle secretion, indicating new therapeutic potential of these anti-inflammatory drugs., (Copyright © 2023 by The American Association of Immunologists, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
14. The kinetics of blast clearance are associated with copy number alterations in childhood B-cell acute lymphoblastic leukemia.
- Author
-
Urbańska Z, Lejman M, Taha J, Madzio J, Ostrowska K, Miarka-Walczyk K, Wypyszczak K, Styka B, Jakubowska J, Sędek Ł, Szczepański T, Stańczak M, Fendler W, Młynarski W, and Pastorczak A
- Subjects
- Child, Humans, DNA Copy Number Variations, Kinetics, Neoplasm, Residual, Chromosome Aberrations, Transcription Factors genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
We analyzed the pattern of whole-genome copy number alterations (CNAs) and their association with the kinetics of blast clearance during the induction treatment among 195 pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) who displayed intermediate or high levels of minimal residual disease (MRD). Using unsupervised hierarchical clustering of CNAs > 5 Mbp, we dissected three clusters of leukemic samples with distinct kinetics of blast clearance [A - early slow responders (n=105), B - patients with persistent leukemia (n=24), C - fast responders with the low but detectable disease at the end of induction (n=66)] that corresponded with the patients' clinical features, the microdeletion profile,the presence of gene fusions and patients survival. Low incidence of large CNAs and chromosomal numerical aberrations occurred in cluster A which included ALL samples showing recurrent microdeletions within the genes encoding transcription factors (i.e., IKZF1, PAX5, ETV6, and ERG), DNA repair genes (XRCC3 and TOX), or harboring chromothriptic pattern of CNAs. Low hyperdiploid karyotype with trisomy 8 or hypodiploidy was predominantly observed in cluster B. Whereas cluster C included almost exclusively high-hyperdiploid ALL samples with concomitant mutations in RAS pathway genes. The pattern of CNAs influences the kinetics of leukemic cell clearance and selected aberrations affecting DNA repair genes may contribute to BCP-ALL chemoresistance., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2023
- Full Text
- View/download PDF
15. Body Posture Defects and Body Composition in School-Age Children.
- Author
-
Wilczyński J, Lipińska-Stańczak M, and Wilczyński I
- Abstract
The aim of the study was to assess the relationship between the shape of the anteriorposterior spinal curvature and body composition in schoolchildren. The study included 257 children, aged 11-12. Correct spinal curvature was established in 106 (41.08%) subjects. Other types included: decreased kyphosis and correct lordosis-40 participants (15.50%), correct kyphosis and decreased lordosis-24 individuals (9.30%), increased kyphosis and correct lordosis-17 subjects (6.59%), correct kyphosis and increased lordosis-22 children (8.53%), decreased kyphosis and decreased lordosis-32 people (12.40%), decreased kyphois and increased lordosis-four of the examined subjects (1.55%) increased kyphosis and lordosis-13 people (5.04%). In addition, 134 (51.94%) demonstrated scoliotic posture and eight (3.10%) scoliosis. There were significant relationships between the shape of the anteriorposterior curvatures and body composition in schoolchildren. Those with a strong body build (predominance of mesomorphs) were generally characterised by the correct formation of these curvatures. In contrast, lean subjects (with the predominance of ectomorphic factors) were more likely to experience abnormalities. No correlations with body composition were observed in the group with scoliotic posture or scoliosis. Both in the prevention and correction of postural defects, one should gradually move away from one-sided, usually one-system, therapeutic effects. An approach that takes into account both somatic and neurophysiological factors seems appropriate. With the correct body composition and structure, shaping the habit of correct posture is much easier.
- Published
- 2020
- Full Text
- View/download PDF
16. Adsorption - Membrane process for treatment of stabilized municipal landfill leachate.
- Author
-
Zielińska M, Kulikowska D, and Stańczak M
- Subjects
- Adsorption, Charcoal, Membranes, Artificial, Ultrafiltration, Water Pollutants, Chemical, Water Purification
- Abstract
The aim of this study was to investigate the efficiency of removal of difficult-to-biodegrade organic compounds from real stabilized landfill leachate with a membrane process alone and in combination with powdered-activated-carbon (PAC) adsorption. For filtration, ceramic membranes were used. The characteristics of the raw leachate were 788 mg COD/L and color of 0.4458 cm
-1 . With all combinations of PAC-adsorption and a membrane process (MF, UF, fine-UF) and with fine-UF alone, leachate treatment was highly efficient. For each membrane, treatment was more efficient when the membrane process was combined with PAC addition. This means that adsorption (PAC dose 3 g/L, adsorption time 30 min) made the largest contribution to leachate treatment (COD and color removal efficiency of 73.1% and 94.4%, respectively). In all cases, organic particles bigger than 100 kDa were removed most efficiently, whereas particles smaller than 3 kDa were removed least efficiently. The efficiency of leachate treatment with PAC + MF, PAC + UF and PAC + fine-UF did not differ significantly (>87% COD and > 97% color). With regard to membrane flux, however, these combinations can be ranked in the following order: PAC + MF > PAC + UF > PAC + fine-UF. Therefore, PAC + MF (0.3 MPa) was selected as the most effective solution (COD and color removal efficiencies of 87.8% and 97.2%, respectively; permeate flux of 167.6 L/(m2 ∙h)), as it combined efficient pollutant removal with low membrane pressure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
17. Significance of CD10 protein expression in the diagnostics of follicular lymphoma: A comparison of conventional immunohistochemistry with flow cytometry supported by the establishment of BCL2 and BCL6 rearrangements.
- Author
-
Szumera-Ciećkiewicz A, Rymkiewicz G, Sokół K, Paszkiewicz-Kozik E, Borysiuk A, Poleszczuk J, Bachnio K, Bystydzienski Z, Woroniecka R, Grygalewicz B, Kotarska M, Stańczak M, Owczarek D, Pytlak B, Prochorec-Sobieszek M, and Walewski J
- Subjects
- Female, Humans, Male, Middle Aged, Flow Cytometry, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Immunohistochemistry, Lymphoma, Follicular blood, Lymphoma, Follicular diagnosis, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology, Neprilysin blood, Neprilysin genetics, Proto-Oncogene Proteins c-bcl-2 blood, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 blood, Proto-Oncogene Proteins c-bcl-6 genetics
- Abstract
Introduction: Histopathological examination and immunohistochemistry (IHC) with a crucial role of CD10 expression remain a standard diagnostic tool in follicular lymphoma (FL). The results of IHC CD10 detection with different primary antibodies are not fully reproducible, but some reports show that flow cytometry (FCM) can be a reliable method of CD10 identification., Methods: The aim of the study was to compare results of CD10 expression in FL by IHC and FCM including immunophenotypic features in the context of the BCL2 and BCL6 alterations., Results: Out of 76 histopathologically diagnosed FL, a group of 25 cases had simultaneously FCM. Immunohistochemically 77.6% of cases were CD10-positive with comparable and reproducible results to FCM. Differences between the FCM expression of CD5/CD10/CD11c/CD25/CD43 and BCL2 overexpression (BCL2(+)
higher ) correlated with the BCL2 and BCL6 rearrangements (R) status. Lack of CD10 expression corresponded with the absence of BCL2R and higher MUM1 expression by IHC results but had no clinical impact on the long-time outcomes., Conclusions: Immunohistochemistry staining is a comparable method to FCM assessment in the evaluation of CD10 expression and diagnosis of FL. Fine-needle aspiration biopsy/FCM (FNAB/FCM) could be a useful tool for verifying FL diagnosis and CD10 detection. Despite its heterogeneity, FL has a characteristic immunophenotype. BCL2R and BCL6R FL cases differ mainly in levels of BCL2 and CD10 with CD43 co-expression; BCL2(+)higher by FCM correlates with BCL2R. Moreover, FNAB plays an important role in material provision for supportive karyotyping and BCL2R, BCL6R assessed by FISH., (© 2020 John Wiley & Sons Ltd.)- Published
- 2020
- Full Text
- View/download PDF
18. Defining and Targeting Adaptations to Oncogenic KRAS G12C Inhibition Using Quantitative Temporal Proteomics.
- Author
-
Santana-Codina N, Chandhoke AS, Yu Q, Małachowska B, Kuljanin M, Gikandi A, Stańczak M, Gableske S, Jedrychowski MP, Scott DA, Aguirre AJ, Fendler W, Gray NS, and Mancias JD
- Subjects
- Cell Line, Tumor, Cell Proliferation, Down-Regulation, Humans, Models, Biological, Neoplasms genetics, Neoplasms pathology, Proteome metabolism, Time Factors, Up-Regulation, Mutation genetics, Oncogenes, Proteomics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Covalent inhibitors of the KRAS
G12C oncoprotein have recently been developed and are being evaluated in clinical trials. Resistance to targeted therapies is common and may limit long-term efficacy of KRAS inhibitors (KRASi). To identify pathways of adaptation to KRASi and predict drug combinations that circumvent resistance, we use mass-spectrometry-based quantitative temporal proteomics to profile the proteomic response to KRASi in pancreatic and lung cancer 2D and 3D cellular models. We quantify 10,805 proteins, representing the most comprehensive KRASi proteome (https://manciaslab.shinyapps.io/KRASi/). Our data reveal common mechanisms of acute and long-term response between KRASG12C -driven tumors. Based on these proteomic data, we identify potent combinations of KRASi with phosphatidylinositol 3-kinase (PI3K), HSP90, CDK4/6, and SHP2 inhibitors, in some instances converting a cytostatic response to KRASi monotherapy to a cytotoxic response to combination treatment. Overall, using quantitative temporal proteomics, we comprehensively characterize adaptations to KRASi and identify combinatorial regimens with potential therapeutic utility., Competing Interests: Declaration of Interests J.D.M. is an inventor on a patent pertaining to the autophagic control of iron metabolism. N.S.G. reports receiving a commercial research grant from Takeda and is a consultant/advisory board member for C4, Syros, Soltego, and B2S Bio. N.S.G. is a founder, science advisory board member (SAB), and equity holder in Gatekeeper, Syros, Petra, C4, B2S, and Soltego. B.M. reports receiving research grant support from Polpharma. A.S.C. is now employed at Fog Pharma. The remaining authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
19. Alcohol reduces aversion to ambiguity.
- Author
-
Tyszka T, Macko A, and Stańczak M
- Abstract
Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.