Relevant bibliographies by topics / PFKFB3 inhibitor

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  2. Dissertations / Theses
  3. Conference papers

Academic literature on the topic 'PFKFB3 inhibitor'

Author: Grafiati
Published: 9 March 2023
Last updated: 11 March 2023

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Journal articles on the topic "PFKFB3 inhibitor"

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Sun, Chen-min, Da-bo Xiong, Yang Yan, Jiang Geng, Min Liu, and Xu-dong Yao. "Genetic Alteration in Phosphofructokinase Family Promotes Growth of Muscle-Invasive Bladder Cancer." International Journal of Biological Markers 31, no. 3 (July 2016): 286–93. http://dx.doi.org/10.5301/jbm.5000189.

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Aims Metabolic alterations in cancer, including bladder cancer, have been addressed in recent years. We aimed to study the role of phosphofructokinase (PFK) in muscle-invasive bladder cancer (MIBC). Method By in silico analysis of the bladder cancer data from the Cancer Genome Atlas (TCGA) database using the cBioPortal platform, we studied genetic alteration of genes within the PFK family (PFKL, PFKM, PFKP, PFKFB1, PFKFB2, PFKFB3, and PFKFB4). In vitro studies were carried out using the PFK inhibitor 2,5-anhydro-D-glucitol-6-phosphate. Results Genetic alterations of PFK family genes were observed in ~44% of MIBC cases in TCGA. The main alterations were amplification and upregulation. Patients with altered PFK gene status were more likely to have a history of noninvasive bladder cancer. Altered PFK status was not associated with survival or disease relapse. Use of the PFK inhibitor significantly decreased the level of glycolysis and inhibited the growth and invasion of bladder cancer cells. Conclusions PFKs were critical genes in charge of glycolysis and were upregulated in bladder cancer. Targeting this pathway could inhibit cell growth in bladder cancer.
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Kotowski, Krzysztof, Jakub Rosik, Filip Machaj, Stanisław Supplitt, Daniel Wiczew, Karolina Jabłońska, Emilia Wiechec, Saeid Ghavami, and Piotr Dzięgiel. "Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets." Cancers 13, no. 4 (February 22, 2021): 909. http://dx.doi.org/10.3390/cancers13040909.

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Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.
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Regueira, Mariana, Silvana Lucía Artagaveytia, María Noel Galardo, Eliana Herminia Pellizzari, Selva Beatriz Cigorraga, Silvina Beatriz Meroni, and María Fernanda Riera. "Novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells." REPRODUCTION 150, no. 4 (October 2015): 311–21. http://dx.doi.org/10.1530/rep-15-0093.

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The aim of the study was to analyze molecular mechanisms involved in FSH and basic fibroblast growth factor (bFGF) regulation of lactate production in rat Sertoli cells. The regulation of the availability of pyruvate, which is converted to lactate, could be a mechanism utilized by hormones to ensure lactate supply to germ cells. On one hand, the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) expression could result in increased glycolysis, while an increase in pyruvate availability may also result from a lower conversion to acetyl-CoA by negative regulation of pyruvate dehydrogenase complex (PDC) activity by phosphorylation. Sertoli cell cultures obtained from 20-day-old rats were used. Stimulation of the cultures with FSH or bFGF showed that FSH increases Pfkfb1 and Pfkfb3 expression while bFGF increases Pfkfb1 mRNA levels. Additionally, we observed that FSH-stimulated lactate production was inhibited in the presence of a PFKFB3 inhibitor, revealing the physiological relevance of this mechanism. As for the regulation of PDC, analysis of pyruvate dehydrogenase kinase (Pdk) expression showed that FSH increases Pdk3 and decreases Pdk4 mRNA levels while bFGF increases the expression of all Pdks. In addition, we showed that bFGF increases phosphorylated PDC levels and that bFGF-stimulated lactate production is partially inhibited in the presence of a PDK inhibitor. Altogether, these results add new information regarding novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells. Considering that lactate is essential for the production of energy in spermatocytes and spermatids, these mechanisms might be relevant in maintaining spermatogenesis and male fertility.
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Minchenko, Oleksandr H., Iryna L. Opentanova, Tsutomu Ogura, Dmytro O. Minchenko, Sergiy V. Komisarenko, Jaime Caro, and Hiroyasu Esumi. "Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines." Acta Biochimica Polonica 52, no. 4 (July 11, 2005): 881–88. http://dx.doi.org/10.18388/abp.2005_3402.

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Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in the prostate and hepatoma cancer cell lines. Here we have studied expression and hypoxic regulation of the testis isoenzyme of PFKFB4 in several malignant cell lines from a female organ--the mammary gland. Our studies clearly demonstrated that PFKFB4 mRNA is also expressed in mammary gland malignant cells (MCF-7 and T47D cell lines) in normoxic conditions and that hypoxia strongly induces it expression. To better understand the mechanism of hypoxic regulation of PFKFB4 gene expression, we used dimethyloxalylglycine, a specific inhibitor of HIF-1alpha hydroxylase enzymes, which strongly increases HIF-1alpha levels and mimics the effect of hypoxia. It was observed that PFKFB4 expression in the MCF7 and T47D cell lines was highly responsive to dimethyloxalylglycine, suggesting that the hypoxia responsiveness of PFKFB4 gene in these cell lines is regulated by HIF-1 proteins. Moreover, desferrioxamine and cobalt chloride, which mimic the effect of hypoxia by chelating or substituting for iron, had a similar stimulatory effect on the expression of PFKFB mRNA. In other mammary gland malignant cell lines (BT549, MDA-MB-468, and SKBR-3) hypoxia and hypoxia mimics also induced PFKFB4 mRNA, but to variable degrees. The hypoxic induction of PFKFB4 mRNA was equivalent to the expression of PFKFB3, Glut1, and VEGF, which are known HIF-1-dependent genes. Hypoxia and dimethyloxalylglycine increased the PFKFB4 protein levels in all cell lines studied except MDA-MB-468. Through site-specific mutagenesis in the 5'-flanking region of PFKFB4 gene the hypoxia response could be limited. Thus, this study provides evidence that PFKFB4 gene is also expressed in mammary gland cancer cells and strongly responds to hypoxia via an HIF-1alpha dependent mechanism. Moreover, the PFKFB4 and PFKFB3 gene expression in mammary gland cancer cells has also a significant role in the Warburg effect which is found in all malignant cells.
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Emini Veseli, Besa, Pieter Van Wielendaele, Mirela Delibegovic, Wim Martinet, and Guido R. Y. De Meyer. "The PFKFB3 Inhibitor AZ67 Inhibits Angiogenesis Independently of Glycolysis Inhibition." International Journal of Molecular Sciences 22, no. 11 (May 31, 2021): 5970. http://dx.doi.org/10.3390/ijms22115970.

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Angiogenesis is the process of new blood vessel formation. In this complex orchestrated growth, many factors are included. Lately, focus has shifted to endothelial cell metabolism, particularly to the PFKFB3 protein, a key regulatory enzyme of the glycolytic pathway. A variety of inhibitors of this important target have been studied, and a plethora of biological effects related to the process of angiogenesis have been reported. However, recent studies have disputed their mechanism of action, questioning whether all the effects are indeed due to PFKFB3 inhibition. Remarkably, the most well-studied inhibitor, 3PO, does not bind to PFKFB3, raising questions about this target. In our study, we aimed to elucidate the effects of PFKFB3 inhibition in angiogenesis by using the small molecule AZ67. We used isothermal titration calorimetry and confirmed binding to PFKFB3. In vitro, AZ67 did not decrease lactate production in endothelial cells (ECs), nor ATP levels, but exhibited good inhibitory efficacy in the tube-formation assay. Surprisingly, this was independent of EC migratory and proliferative abilities, as this was not diminished upon treatment. Strikingly however, even the lowest dose of AZ67 demonstrated significant inhibition of angiogenesis in vivo. To our knowledge, this is the first study to demonstrate that the process of angiogenesis can be disrupted by targeting PFKFB3 independently of glycolysis inhibition.
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Truong, Thu Ha, Elizabeth A. Benner, Kyla M. Hagen, Nuri A. Temiz, Carlos Perez Kerkvliet, Ying Wang, Emilio Cortes-Sanchez, et al. "Steroid Receptor Co-Activators Regulate Metabolic Kinases to Drive Therapy Resistant ER+ Breast Cancer." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A1031—A1032. http://dx.doi.org/10.1210/jendso/bvab048.2111.

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Abstract Recurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER+) breast cancer. Disseminated ER+ tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the maintenance and expansion of breast cancer stem cells (CSCs). Breast CSCs are poorly proliferative and frequently exist as a minority population in therapy resistant tumors. Our objective is to define novel signaling pathways that govern therapy resistance in ER+ breast cancer. In this study, we show that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, modulate breast CSC expansion through upregulation of the HIF-activated metabolic target genes PFKFB3 and PFKFB4. Seahorse metabolic assays demonstrated that cytoplasmic PELP1 influences cellular metabolism by increasing both glycolysis and mitochondrial respiration. PELP1 interacts with PFKFB3 and PFKFB4 proteins, and inhibition of PFKFB3 and PFKFB4 kinase activity blocks PELP1-induced tumorspheres and protein-protein interactions with SRC-3. PFKFB4 knockdown inhibited in vivo emergence of circulating tumor cell (CTC) populations in ER+ mammary intraductal (MIND) xenografts. Application of PFKFB inhibitors in combination with ER targeted therapies blocked tumorsphere formation in multiple models of advanced breast cancer, including tamoxifen (TamR) and paclitaxel (TaxR) resistant models and ER+ patient-derived organoids (PDxO). Together, our data suggest that PELP1, SRC-3, and PFKFBs cooperate to drive ER+ tumor cells that include CSCs and CTCs. Identifying non-ER pharmacological targets offers a useful approach to blocking metastatic escape from standard of care ER/estrogen (E2)-targeted strategies to overcome endocrine and chemotherapy resistance in ER+ breast cancer.
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Zhou, Z., L. G. Plug, E. S. M. de Jonge-Muller, A. Abou Elmagd, A. E. van der Meulen-de Jong, M. C. Barnhoorn, and L. J. A. C. Hawinkels. "P028 Inhibition of stromal glycolysis by targeting PFKFB3 decreases experimental colitis." Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i150. http://dx.doi.org/10.1093/ecco-jcc/jjab232.157.

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Abstract Background Studies in fibrotic diseases revealed that glycolysis is the preferred energy source for fibroblasts. 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) has the highest kinase activity to shunt glucose toward glycolysis. Therefore inhibition of PFKFB3 has been proposed as a potential target for several cancers and inflammatory diseases. However, the metabolic status of fibroblasts in patients with inflammatory bowel disease (IBD) and the role of PFKFB3 are currently unknown. Methods Single-sample gene set enrichment analysis (ssGSEA) of GSE16879 was performed to evaluate metabolic changes in IBD. Seahorse real-time cell metabolic analysis was performed to explore the metabolic activity of fibroblasts. Next the expression of PFKFB3 in primary patient derived intestinal fibroblast was determined by quantitative PCR (qPCR) and western blot under normal and inflammatory conditions. Proliferation and migration of fibroblasts were measured using colony formation and wound healing assays. In order to evaluate the effect of the inhibition of PFKFB3 in vivo, PFK15, a specific inhibitor of PFKFB3, was intraperitoneal injected in mice with dextran sodium sulfate (DSS)-induced colitis and in the T-cell transfer model for colitis. Next to clinical parameters, the abundance of α-smooth muscle actin (α-SMA) expressing fibroblasts, immune cells (CD45) and endothelial cells (CD105) was determined by immunohistochemistry. Results The ssGSEA analysis revealed glycolysis was significantly higher in IBD patients, compared to healthy controls. Consistently, the expression of PFKFB3 was also elevated in a cohort of inflamed intestinal tissues from IBD patients compared to non-inflamed sites from the same patient or healthy controls. On the cellular levels, this analysis showed that PFKB3 expression was higher in IBD-derived stromal cells compared to healthy or non-inflamed stromal cells. In vitro PFKFB3 expression in fibroblasts was increased after the stimulation with pro-inflammatory cytokines like TNF-α and a mix of cytokines often upregulated in IBD patients: interleukin (IL)-17A, oncostatin M (OSM) and IL-1β. As for the metabolic changes, inflamed fibroblasts had a higher extracellular acidification rate and a lower oxygen consumption rate, which could be reverted by inhibition of PFKFB3 using PFK15. Furthermore, PFK15 suppressed the proliferation and migration of fibroblasts. The in vivo experiments showed that PFK15 reduced the severity of the colitis, accompanied by a reduction of the total amount of immune cells (CD45), activated fibroblasts (α-SMA) and angiogenesis (CD105). Conclusion Increased PFKFB3 expression seems to contribute the inflammation and the pathological function of fibroblasts in IBD.
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Yu, Hongbin, Chuang Dai, Wei Zhu, Yude Jin, and Chunhui Wang. "PFKFB3 Increases IL-1β and TNF-α in Intestinal Epithelial Cells to Promote Tumorigenesis in Colitis-Associated Colorectal Cancer." Journal of Oncology 2022 (August 16, 2022): 1–8. http://dx.doi.org/10.1155/2022/6367437.

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Colorectal cancer (CRC) is significantly correlated with inflammatory bowel disease, which usually manifests as chronic relapsing-remitting colitis. Phosphofructo-2-kinase/fructose-2,6-biophosphatase 3 (PFKFB3) can catalyze to produce fructose-2,6-bisphosphate and function as an oncogene. In this study, we revealed the function of PFKFB3 in colitis-associated CRC (CAC) and the potential mechanism. RT-qPCR and Western blot were utilized to detect the level of PFKFB3 expression. Increased PFKFB3 expression was observed in the mouse CAC model and CAC patient samples. We identified that overexpression of PFKFB3 in intestinal epithelial cells (IECs) could increase the proliferation, migration, and invasion of CRC cells by the coculture system. Mechanistically, overexpression of PFKFB3 induced phospho-p65 and promoted the expression of IL-1β and tumor necrosis factor alpha (TNF-α) in the development of colitis and CAC. In addition, PFK158, the PFKFB3 inhibitor, could reduce the CRC cell viability, migration, and invasion caused by PFKFB3 overexpression. In conclusion, overexpression of PFKFB3 promoted tumorigenesis in CAC by inducing phospho-p65 and expression of IL-1β and TNF-α. Our study suggested that PFKFB3 acted as a potential treatment target for CAC.
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Grewal, Jaspreet, Jamaal Ricthie, Numan Al Rayyan, Sucheta Telang, Kavitha Yaddanapudi, and Jason Chesney. "6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is necessary for human melanoma MDSC differentiation and function." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 74.8. http://dx.doi.org/10.4049/jimmunol.196.supp.74.8.

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Abstract Myeloid derived suppressor cells (MDSCs) inhibit the expansion of tumor antigen-specific effector CD8+ T cells via arginase, transforming growth factor – β (TGF – β) and indoleamine 2,3-dioxygenase (IDO). Recently, MDSCs were found to over-express hypoxia inducible factor 1 alpha (HIF-1α) which is required for their differentiation. An essential transcriptional target of HIF-1α is 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) which synthesizes fructose 2,6-bisphosphate, an allosteric stimulator of glycolysis and of proliferation via stimulation of cyclin dependent kinase-1 (CDK1). We hypothesized that MDSCs might over-express PFKFB3 which in turn might be required for their function as T cell suppressors. We demonstrate that monocytic MDSCs (M-MDSCs) induced by co-culture with A375 melanoma cells express increased PFKFB3 and that exposure to the PFKFB3 inhibitor, PFK-158, blocks the suppressive function of these M-MDSCs on T cell activation. Furthermore, we analyzed three advanced cancer patients for circulating MDSCs before and after PFK-158 administration as part of a multi-center phase 1 clinical trial. And, we found that the MDSCs were markedly reduced in each patient. Taken together, these data indicate that selective inhibition of PFKFB3 may be a novel approach to target MDSCs and combinations of PFKFB3 inhibitors with immunotherapies may be a rational strategy to promote durable immune-mediated remissions in cancer patients.
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Reddy, Mamatha M., Margret Fernandes, James D. Griffin, and Martin Sattler. "The JAK2V617F Oncogene, Associated with Myeloproliferative Neoplasms, Requires Expression of Inducible Phosphofructokinase/Fructose Bisphosphatase 3 for Cell Growth and Increased Metabolic Activity." Blood 116, no. 21 (November 19, 2010): 793. http://dx.doi.org/10.1182/blood.v116.21.793.793.

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Abstract Abstract 793 Myeloproliferative neoplasms (MPNs) and myeloid leukemias, characterized by overproduction of myeloid lineage cells, are frequently associated with transforming oncogenic kinases, including JAK2V617F, BCR-ABL, or FLT3-ITD. The mechanisms that regulate altered energy metabolism in these diseases are poorly understood but cancer cells tend to produce energy through increased glycolysis instead of oxidative phosphorylation, even under normoxic conditions (Warburg effect). Our data in JAK2V617F-transformed HEL cells show that glucose uptake, the first step in glucose metabolism, is reduced in response to a JAK2 inhibitor (−22.29%, p<0.05, n=3). Further, introduction of JAK2V617F into murine BaF3 cells resulted in increased glucose uptake (103.72%, p<0.05, n=3), compared to parental BaF3 cells. Exposure of cells transformed by BCR/ABL or FLT3-ITD with appropriate kinase inhibitors similarly resulted in a 30 to 40% decrease in glucose uptake, and introduction of either BCR-ABL or FLT3-ITD into BaF3 cells resulted in substantial increases in glucose uptake (BCR-ABL, +122.74%, and FLT3-ITD, +142.77%; p<0.05, n=3). Consistent with an increase in glucose uptake, we also found elevated cell surface expression of the glucose transporter Glut1 in BaF3.JAK2V617F cells. Importantly, cell growth and metabolic activity were strictly dependent on the presence of glucose in the culture medium. Also, treatment with the hexokinase inhibitor, 2-deoxyglucose, led to reduced cell growth, further supporting the notion that JAK2V617F transformed cells rely on glucose for their metabolic functions. JAK2V617F increased the expression of at least two rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2) as well as 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and in particular, a JAK2 inhibitor substantially decreased the expression of PFKFB3 in HEL cells. To determine the significance of altered PFKFB3 expression, we targeted PFKFB3 in HEL cells using a lentiviral-based shRNA approach. We found that PFKFB3 knockdown reduced cell growth by 46.3 to 46.8% in HEL cells (p<0.05, n=3) compared to control shRNA. The impact on cell growth was similar under normoxic (20% O2) compared to hypoxic (0.1% O2) conditions (−58.2% to −45.5%; p<0.05, n=3), further underlining the importance of this pathway for cell growth. We also observed a reduction in oxidative metabolic activity (−32.26% to −34.14%, p<0.05, n=3) and glucose uptake (−28.58% to −22.5%, p<0.05, n=3) in response to PFKFB3 knockdown. Finally, in order to understand the role of the JAK2V617F target STAT5 in the regulation of increased PFKFB3 expression, we used BaF3 cells with a doxycycline inducible form of active STAT5. These cells, upon induction of active STAT5, showed increased growth and metabolic activity as well as elevated expression of PFKFB3, compared to controls. It is not known whether PFKFB3 is a direct transcriptional target of STAT5. Overall, these data suggest that inducible PFKFB3 is required for increased growth, metabolic activity and is regulated through the JAK2V617F/STAT5 pathway, hinting at novel targets for drug development. Small molecule drugs that target PFKFB3 would be expected to specifically inhibit this pathway and to have activity in diseases dependent on JAK2V617F or active STAT5 in related malignancies. Disclosures: No relevant conflicts of interest to declare.
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Dissertations / Theses on the topic "PFKFB3 inhibitor"

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NUKALA, SARATH BABU. "BIOANALYTICAL AND PROTEOMIC APPROACHES IN THE STUDY OF PATHOLOGIC ECS DYSFUNCTIONALITY, OXIDATIVE STRESS AND THE EFFECTS OF PFKFB3 MODULATORS." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/644236.

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Vascular dysfunction is one of the primary factors in the onset and progression of atherosclerosis and other vascular-related diseases such as acute myocardial infarction (AMI) and chronic thromboembolic pulmonary hypertension (CTEPH). Emerging evidence indicates that pathological blood vessel responses and endothelial dysfunction are associated with metabolic alterations in endothelial cells (ECs). The identification of the insights and causes resulting in dysfunctional ECs is crucial for the understanding of the disease and to the development of new therapeutic tools. Therefore, to study the characteristics of such EC dysfunction in AMI and CTEPH diseases, we aim to determine the protein profile and/or the altered redox status of patient-derived EC lines by using mass spectrometry-based label-free quantitative proteomic and/or, spectrophotometric and fluorometric approaches. Moreover, quantitative proteomic approach was used to explore the underlying mechanisms of 3PO [(3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one), PFKFB3 inhibitor] at cellular level. 3PO is a compound able to inhibit the glycolytic flux partially and transiently and to reduce pathological angiogenesis in a variety of disease models. Bioinformatic and network analyses performed on pathologic HCAEC-AMI cells revealed the alteration of a) metabolism of RNA, b) platelet activation, signaling and aggregation, c) neutrophil degranulation, d) metabolism of amino acids and derivatives, e) cellular responses to stress and, f) response to elevated platelet cytosolic Ca2+ pathways. Similarly, network analysis in pathologic CTEPH-ECs, revealed the differentially regulation of pathways related to a) neutrophil and platelet degranulation, b) metabolism of lipids, amino acids and selenoamino acids, c) response to elevated cytosolic Ca2+, d) detoxification of reactive oxygen species. In addition, the main parameters, indicators of the redox status of both HCAEC-AMI and CTEPH-ECs were significantly increased: advanced oxidation protein products (AOPPs), protein carbonyls (PCO) content, and intracellular reactive oxygen species (ROS). Interestingly, the amount of GSH/GSSG (reduced glutathione/oxidized glutathione) and NADPH/NADP (reduced/oxidized form of nicotinamide adenine dinucleotide phosphate) ratios in dysfunctional ECs were reduced, a clear indication of oxidative stress involvement in both the pathological ECs. Finally, 3PO has multiple targets in the ECs, targeting mitochondrial inner membrane and it inhibits the important cellular pathways including the tricarboxylic acid cycle, the mitochondrial respiratory chain, and vasculogenesis, that may be useful for understanding the inhibitory effect of 3PO on EC proliferation and migration. Therefore, the present data suggest a potential application of this molecule as a starting point in designing novel molecules to prevent diseases where inflammatory reactions are involved, such as in atherosclerosis, cancer or neurodegenerative diseases.
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Conference papers on the topic "PFKFB3 inhibitor"

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O'Neal, Julie, Gilles Tapolsky, Brian Clem, Sucheta Telang, and Jason Chesney. "Abstract 962: Identification of a PFKFB3 inhibitor suitable for phase I trial testing that synergizes with the B-Raf inhibitor vemurafenib." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-962.

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Zheng, Jia-Bo. "IDDF2021-ABS-0189 Metabolic inhibitor of PFKFB3 and its implication in immune evasion by upregulating pd-l1 expression via the PHOSPHOPFKFB3–HIF1Α–PD-L1 axis." In Abstracts of the International Digestive Disease Forum (IDDF), Hong Kong, 4–5 September 2021. BMJ Publishing Group Ltd and British Society of Gastroenterology, 2021. http://dx.doi.org/10.1136/gutjnl-2021-iddf.53.

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Lea, Michael A., Raymond Geherty, Rachelle David, and Charles desBordes. "Abstract 3363: Inhibition of glycolysis and proliferation of colon cancer cells by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) an inhibitor of 6-phosphofructo-2-kinase (PFKFB3)." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-3363.

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Telang, Sucheta, Kavitha Yaddanapudi, Jaspreet Grewal, Rebecca Redman, Siqing Fu, Paula Pohlmann, Devalingam Mahalingam, Michael Kurman, Gilles Tapolsky, and Jason Chesney. "Abstract B90: PFK-158 is a first-in-human inhibitor of PFKFB3 that selectively suppresses glucose metabolism of cancer cells and inhibits the immunosuppressive Th17 cells and MDSCs in advanced cancer patients." In Abstracts: AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; May 12-15, 2016; Orlando, FL. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.panca16-b90.

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Redman, Rebecca, Paula Pohlmann, Michael Kurman, Gilles H. Tapolsky, and Jason Chesney. "Abstract CT206: PFK-158, first-in-man and first-in-class inhibitor of PFKFB3/ glycolysis: A phase I, dose escalation, multi-center study in patients with advanced solid malignancies." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-ct206.

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Mondal, Susmita, Debarshi Roy, Eleftheria Kalogera, Ashwani Khurana, Gilles H. Tapolsky, Sucheta Telang, Jason Chesney, and Viji Shridhar. "Abstract 2706: Inhibition of PFKFB3/glycolysis overcomes chemoresistance in ovarian cancers." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2706.

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Lea, Michael A., Yolanda Guzman, and Charles desBordes. "Abstract 32: Inhibition of cancer cell growth by combined treatment with lactate dehydrogenase (LDHA) inhibitors and either phenformin or inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3)." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-32.

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Xiao, Yinan, Ling Jin, Sayantani Sarkar Bhattacharya, Julie Staub, Chaolin Deng, Xiaoling Fang, and Viji Shridhar. "Abstract 6222: Inhibition of 6-Phosphofructo-2-kinase (PFKFB3) induces cell death and synergistically enhances chemosensitivity in endometrial cancer." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-6222.

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Bhattacharya, Sayantani Sarkar, Ling Jin, Debarshi Roy, Deokbeom Jung, Prabhu Thirusangu, Yinan Xiao, Julie Staub, Julian Molina, and Viji Shridhar. "Abstract 2658: PFKFB3 inhibition reprograms malignant pleural mesothelioma to glycolytic stress-induced macropinocytosis and ER stress as independent binary adaptive responses." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-2658.

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Bhattacharya, Sayantani Sarkar, Ling Jin, Debarshi Roy, Deokbeom Jung, Prabhu Thirusangu, Yinan Xiao, Julie Staub, Julian Molina, and Viji Shridhar. "Abstract 2658: PFKFB3 inhibition reprograms malignant pleural mesothelioma to glycolytic stress-induced macropinocytosis and ER stress as independent binary adaptive responses." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-2658.

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