scholarly journals Biological Roles and Therapeutic Applications of IDH2 Mutations in Human Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinxiu Guo ◽  
Ruyue Zhang ◽  
Zhe Yang ◽  
Zhenfeng Duan ◽  
Detao Yin ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Enzymatic Activity ◽  
Human Cancer ◽  
Clinical Development ◽  
Metabolic Enzyme ◽  
Idh Mutation ◽  
Small Molecular Inhibitors ◽  
Idh2 Mutation ◽  
Proof Of Principle ◽  
Made In

Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to α-ketoglutarate (α-KG). Mutations in IDH lead to loss of normal enzymatic activity and gain of neomorphic activity that irreversibly converts α-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. Encouragingly, this phenomenon can be reversed by specific small molecule inhibitors of IDH mutation. At present, small molecular inhibitors of IDH1 and IDH2 mutant have been developed, and promising progress has been made in preclinical and clinical development, showing encouraging results in patients with IDH2 mutant cancers. This review will focus on the biological roles of IDH2 mutation in tumorigenesis, and provide a proof-of-principle for the development and application of IDH2 mutant inhibitors for human cancer treatment.

scholarly journals Nucleases as molecular targets for cancer diagnosis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alien Balian ◽  
Frank J. Hernandez
Keyword(s):  
Enzymatic Activity ◽  
Cancer Diagnosis ◽  
Essential Feature ◽  
Treatment Options ◽  
Cancer Biomarkers ◽  
Diagnostic Biomarkers ◽  
Early Cancer Diagnosis ◽  
Novel Biomarkers ◽  
Made In

AbstractEarly cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

scholarly journals ASSESSMENT OF THE INFLUENCE OF ABIOTIC FACTORS ON THE ENZYMATIVE ACTIVITY OF THE SOIL

ÈKOBIOTEH ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 128-134
Author(s):  
E.V. Tovstik ◽  
◽  
A.S. Olkova ◽  
Keyword(s):  
Enzymatic Activity ◽  
Soil Solution ◽  
Ph Value ◽  
Abiotic Factors ◽  
Inverse Correlation ◽  
Invertase Activity ◽  
Soil Environment ◽  
Factors Affecting ◽  
Activity Of Enzymes ◽  
Made In

Аn attempt is made in this work to establish correlations between the level of enzymatic activity of the soil and factors of an abiotic nature. It was found that the activity of invertase and urease in the soils of more southern territories is higher than that of northern ones. In soils with a pH value of the soil environment close to neutral reaction, the level of enzymatic activity is higher than in more acidic ones. The most sensitive to soil acidity among the studied urease enzymes. In relation to zinc, an inverse correlation was established between its content in the soil and the level of invertase activity. According to the degree of resistance to salinity, the enzymes are arranged in the following order: catalase> invertase> urease. An increase in the mineralization of the soil solution leads to an increase in the activity of urease. Of the studied enzymes, the most labile are representatives of the class of hydrolases (invertase and urease), less labile are oxidoreductases (catalase). Thus, when diagnosing the state of the soil by the level of enzymatic activity, it is necessary to take into account the main abiotic factors affecting the activity of enzymes: the average annual air temperature; pH and mineralization of the soil solution; the content of substances that inhibit microorganisms and block exozymes.

Glutathione S-transferases in tracheobronchial epithelium

1995 ◽  
Vol 269 (4) ◽  
pp. L473-L481
Author(s):  
P. M. Reddy ◽  
C. P. Tu ◽  
R. Wu
Keyword(s):  
Cell Differentiation ◽  
Environmental Factors ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Mucous Cell ◽  
Collagen Gel ◽  
Bronchial Epithelium ◽  
High Level

The purpose of this study is to characterize glutathione S-transferase (GST) gene expression in airway epithelium both in vivo and in vitro. Immunohistochemical staining of nonhuman primate lungs of well-controlled healthy animals reveals the presence of alpha- and pi-class GST isoenzymes in ciliated bronchial epithelium. The stain of mu-GST antibody is either very low or absent in some of these monkey lungs. We observed that primary tracheobronchial epithelial (TBE) cells isolated from human and monkey pulmonary tissues maintain a relatively high level of GST enzymatic activity in culture, compared with various immortalized human TBE cell lines and other nonpulmonary cell lines. Northern blot analysis demonstrated the presence of mu-, pi-, and microsomal-GST messages but not the alpha-class message in cultures of primary TBE cells as well as in various human TBE cell lines. The expression of mu- and pi-class GST genes can be further regulated in culture by various environmental factors; however, most of these regulating factors are associated with TBE cell differentiation in culture. For instance, vitamin A treatment, which was shown to enhance mucous cell differentiation in vitro, stimulated the message levels of mu- and pi-class GST. Furthermore, plating cells on collagen gel substrata, which also enhanced mucous cell differentiation in culture, instead of plastic culture surface, enhanced total GST enzymatic activity by eightfold, and this enhancement is related to an increase in the expression of the pi-class GST gene. These results demonstrated that GST genes are differentially expressed and regulated by various environmental factors in primary TBE cells and various cell lines, and the regulation is correlated to the mucous cell differentiation in culture.

Myoglobin content and enzymatic activity of muscle and altitude adaptation

1962 ◽  
Vol 17 (2) ◽  
pp. 301-305 ◽  
Author(s):  
Baltazar Reynafarje
Keyword(s):  
Cytochrome C ◽  
Enzymatic Activity ◽  
High Altitude ◽  
Sea Level ◽  
Human Subjects ◽  
Reduced Form ◽  
Sartorius Muscle ◽  
Healthy Human ◽  
Altitude Adaptation ◽  
Made In

Quantitative determinations of myoglobin were made in the sartorius muscle of healthy human subjects native to sea level and high altitude. The specific activities of the reduced form of diphosphopyridine nucleotide oxidase (DPNH-oxidase), DPNH- and the reduced form of triphosphopyridine nucleotide (TPNH)-cytochrome c reductases, transhydrogenase, and isocitric and lactic dehydrogenases were also examined. There was found a significantly higher myoglobin concentration in the muscle of the high-altitude native as compared with the sea-level resident. The enzyme systems DPNH-oxidase, TPNH-cytochrome c reductase, and transhydrogenase similarly showed a significantly higher activity in the altitude resident. It was concluded that the respiratory capacity of the muscle was apparently higher in the altitude native than in the sea-level one. The enhanced enzymatic activity was probably related to the higher pigment content of the skeletal muscle. Results on myoglobin determinations in several other muscles from certain sea-level patients are discussed. Submitted on July 24, 1961

Phorbol ester–induced PKCϵ down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 3080-3087 ◽  
Author(s):  
Giuliana Gobbi ◽  
Prisco Mirandola ◽  
Cecilia Carubbi ◽  
Cristina Micheloni ◽  
Chiara Malinverno ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Surface Expression ◽  
Low Concentrations ◽  
Differentiating Agents ◽  
Receptor Surface Expression ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Made In

AbstractDespite the relevant therapeutic progresses made in these last 2 decades, the prognosis of acute myeloid leukemia (AML) remains poor. Phorbol esters are used at very low concentrations as differentiating agents in the therapy of myeloid leukemias. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), in turn, is a death ligand that spares normal cells and is therefore currently under clinical trials for cancer therapy. Emerging evidence, however, suggests that TRAIL is also involved in nonapoptotic functions, like cell differentiation. PKCϵ is differentially modulated along normal hematopoiesis, and its levels modulate the response of hematopoietic precursors to TRAIL. Here, we investigated the effects of the combination of phorbol esters (phorbol ester 4-β-phorbol-12,13-dibutyrate [PDBu]) and TRAIL in the survival/differentiation of AML cells. We demonstrate here that PDBu sensitizes primary AML cells to both the apoptogenic and the differentiative effects of TRAIL via PKCϵ down-modulation, without affecting TRAIL receptor surface expression. We believe that the use of TRAIL in combination with phorbol esters (or possibly more specific PKCϵ down-modulators) might represent a significative improvement of our therapeutic arsenal against AML.

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