scholarly journals Anticancer Potential of L-Asparaginase: An Overview

2021 ◽  
Vol 12 (1) ◽  
pp. 125-129
Author(s):  
Kamesh Kumar Keshri ◽  
Mrunali Nandanwar ◽  
Eesha Shukla ◽  
Aswatha Ram H N ◽  
Aravinda Pai ◽  
...  

Asparaginase, derived from microbial origin hydrolyses L-asparagine to L-aspartic acid. The enzyme finds principal use in the treatment of Acute Lymphoblastic Leukemia during childhood that primarily occurs between two to ten years of age. L-Asparaginase finds its use in management of haemopoietic disorders especially in pediatrics that is caused due to proliferation and enlargement of lymphoblast in bone marrow and in blood as well as other part of the body. L- Asparaginase from bacterial sources exhibit quaternary and tertiary structural forms. However for using it in therapeutic and clinical application it should not generate any fatal allergic reaction to the patient. Such effects can occur due to the enzyme associated L-Glutaminase activity and also due to the endotoxins from bacteria in enzyme preparations. Therefore, with the recent development in biotechnology with respect to production and purification techniques it is possible to get pure L- asparaginase from microbial origin. The present article provides an insight into the mechanism of action of L-Asparaginase as an anticancer agent and its industrial applications. 

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4774-4774
Author(s):  
Masanori Tsuji ◽  
Hideki Akiyama ◽  
Takeshi Kobayashi ◽  
Miwa Sakai ◽  
Takuya Yamashita ◽  
...  

Abstract [Introduction] Blastic mantle cell leukemia is defined as CD5-positive, CD23-negative, cyclin D1-positive mature B-lymphoid tumor characterized by leukemic presentation, blastic blood and bone marrow features with aggressive clinical behavior. Its prognosis is usually dismal and overall survival was reported to be 3 months. We present the case of blastic mantle cell leukemia treated with rituximab, enjoying complete remission for 3 years. [Case presentation] A 68 year-old man was admitted because of leukocytosis. His CBC revealed WBC 31.0 x 10E9/L with 64% of blast. Hemoglobin level was 5.3 g/dl, and 78% of medium-sized blasts that were positive for CD5, CD19, CD20, and HLA-DR. Chromosomal study revealed normal karyotype. He was treated with adriamycin, vincristine, cyclophosphamide, and predonisone as for acute lymphoblastic leukemia, and then, with another two cycles of intensive chemotherapy including hyper-CVAD without any significant response. He was transferred to our hospital for further treatment. The blastic cells showed bcl1/IgH re-arrangement on FISH analysis and bone marrow biopsy revealed CD23-negative and cyclin D-positive that confirmed the diagnosis of mantle cell lymphoma/leukemia. CT scan of the body showed no significant lymphadenopathy. He was treated with fludarabine and idarubicin without any effect and then was treated with rituximab 375 mg/m2. After the initiation of rituximab treatment, blasts disappeared from peripheral blood within 24 hours completely and after 4 times of rituximab once per every week, CBC returned to normal and bone marrow examination revealed complete remission. He was treated with another 2 injection of rituximab and then followed without any further treatment. He has been in complete-remission status for 3 years since then. [Discussion] Blastic mantle cell leukemia is usually chemotherapy-resistant as our case is and its prognosis is dismal. Our case represent the possibility that even in those patients, one may enjoy prolonged complete remission after the simple treatment with rituximab. This is, of course, only a single case experience and it is necessary to proceed for further investigation.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 64-64
Author(s):  
Roel Polak ◽  
Bob De Rooij ◽  
Rob Pieters ◽  
Monique L. den Boer

Abstract Background: Acute lymphoblastic leukemia (ALL) cells reside in the bone marrow microenvironment, which nurtures and protects cells from chemotherapeutic drugs. Bidirectional signaling between leukemic cells and their niche is shown to be essential for these processes. A major gap in our knowledge is the lack of insight into the functional mechanism regulating and controlling this crosstalk. Tunneling nanotubes (TNTs) have recently been reported as a novel mode of communication between eukaryotic cells, which can facilitate the transport of several types of cellular cargo. Objectives: This study aims to investigate the presence and functional importance of TNTs in the leukemic niche. Results: Here, we show for the first time that TNT signaling occurs between primary patient-derived leukemic cells and primary mesenchymal stromal cells using flow cytometry and time-lapse confocal microscopy. TNTs form within minutes after the start of co-culture and efficiently transfer lipophilic carbocyanine dye DiI from ALL cells towards MSCs. Dye transfer was significantly reduced when TNT signaling was inhibited using three independent experimental setups: actin inhibition, mechanical disruption through gentle shaking of cell cultures, and physical separation using a 3.0 µm pore-sized transwell system (4-fold, 5-fold and 35-fold reduction, respectively). In reciprocal experiments we also observed dye transfer via TNTs from MSCs to BCP-ALL cells, but the magnitude was strikingly less (175-fold, p ≤ 0.001). In addition, we show that leukemic cells use TNTs to modulate their microenvironment by directing non-malignant stromal cells to produce pro-survival cytokines. We observed patient-specific cytokine signatures after co-culture of primary ALL cells with different primary MSCs. For example, IP10/CXCL10 levels increased more than 1000-fold when patient ALL#1 cells were co-cultured with primary MSCs, but were undetectable in co-cultures from patient ALL#2 cells. Induction of all cytokines was dependent on TNT signaling, as TNT inhibition significantly lowered cytokine production (p ≤ 0.001). Importantly, we show that TNT signaling is functionally important for leukemic cell survival and stroma-driven drug resistance. Leukemic cell viability was assessed by flow cytometry after staining with Annexin V, Propidium Iodide and CD19. Primary leukemic cell survival significantly increased in 5-day co-cultures with primary MSCs compared to mono-culture (p ≤ 0.001). When TNT formation was prevented by shaking of these co-cultures or by transwell conditions, the cell viability reduced 3.5- and 3.6-fold, respectively (p ≤ 0.001). TNT inhibition similarly reduced the survival of primary ALL cells in co-culture with MSCs during prednisolone exposure (p ≤ 0.01). Co-culture with primary MSCs also induced resistance to prednisolone 2.5-fold compared to mono-culture in a proliferative setting, using the BCP-ALL cell line NALM6. Inhibition of TNT formation by shaking or transwell conditions significantly reduced this effect: cells in co-culture were only 1.4- and 1.1-fold more resistant compared to mono-culture, respectively (p ≤ 0.01). Conclusion: The presented study identifies TNT formation as a major regulator of interaction between ALL cells and their bone marrow niche, which facilitates signaling mainly from leukemic cells towards MSCs. This signaling drives the release of cytokines within the microenvironment. Disruption of tunneling nanotubes inhibits this release, diminishes the survival benefit that MSCs provide to primary ALL cells, and sensitizes ALL cells to the important anti-leukemic drug prednisolone. This observation gives insight into the pathogenesis of BCP-ALL and opens new avenues to develop more effective therapies that interfere with the leukemic niche. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Moataz Dowaidar

Quantum dots (QDs) are nanoscale semiconductor crystals shown to be intriguing materials in several domains, including biology. Alexei Ekimov originally discovered QDs in the 1980s. The development and utilization of chemical, physical and biological disciplines and new approaches are expected to be available for clinical usage in the near future (e.g., surface functionalization techniques). These efforts should focus largely on overcoming the long-term toxicity of QDs to produce a pharmaceutical QD product for clinical and industrial applications. Other issues include repeatability in QD manufacturing and setting uniform quality standards to ensure batch-to-batch differences are minimized. Additionally, the techniques of administering produced QDs into the body and their regimens should be fully assessed and assessed to fulfill clinical criteria. It is suggested that recent improvements in our understanding of the body's molecular interactions give an insight into the prospective use of QDs in customized treatment. Non-specific QD binding to cell and tissue molecular compartments (e.g. proteins) remains a challenge and researchers worldwide are recommended to focus more on it. Another major impediment to the widespread use of QDs is the heterogeneity in the structure and content of QDs (whether bare or functional), which makes it difficult to draw conclusions about their potential in therapeutic applications and necessitates additional research to develop dependable techniques. Although the barriers to employing QDs in clinical applications have not been completely solved, emerging advances allow this class of materials to approach its therapeutic potential.


2021 ◽  
pp. 26-28
Author(s):  
Мадина Борисовна Хоконова ◽  
Ольга Константиновна Цагоева

Использование ферментных препаратов микробного происхождения в промышленности имеет устойчивую тенденцию к увеличению, при этом 2/3 текущего объема составляют ферменты для пищевой промышленности, а их основная доля приходится на спиртовую отрасль. При этом потребность спиртовой отрасли России в комплексных ферментных препаратах составляет около 7 тыс. т, доля отечественных препаратов составляет менее 15%. Объектами исследований служили ферменты микробного происхождения, плесневые грибы, затор спиртового производства. Осахаривание проводили при температуре 57…58 °С, длительность брожения при этом составляла 62 ч. Установлено, что для достижения максимального действия фермента, при других постоянных условиях, требуется сравнительно большая концентрация субстрата. У большинства ферментов вне клетки она выше, чем концентрация данного вещества в организме, то есть фермент действует менее эффективно, чем в искусственно созданных условиях, где он насыщается субстратом. В зависимости от активности расход грибной культуры может колебаться в определенных пределах. Скорость и глубина гидролиза углеводов сырья определяются активностью глубинной культуры плесневого гриба. Таким образом, свойства ферментов определяются главным образом особыми свойствами белков. При этом в молекуле белка изменяется укладка пептидных цепей, что приводит к потере характерных свойств белка. Способность ферментов в благоприятных условиях пережить материнские клетки и проявлять свое действие вне клетки позволяет широко использовать биологические катализаторы в различных отраслях пищевой промышленности. The use of enzyme preparations of microbial origin in industry has a steady tendency to increase, with 2/3 of the current volume being enzymes for the food industry, and their main share is in the alcohol industry. At the same time, the need of the alcohol industry in Russia for complex enzyme preparations is about 7 thousand tons, the share of domestic preparations is less than 15%. The objects of research were enzymes of microbial origin, mold fungi, mash of alcohol production. Saccharification was carried out at a temperature of 57…58 °C, the duration of fermentation was 62 hours. It was found that to achieve the maximum effect of the enzyme, under other constant conditions, a relatively high concentration of the substrate is required. For most enzymes outside the cell, it is higher than the concentration of a given substance in the body, so the enzyme acts less efficiently than in artificially created conditions, where it is saturated with a substrate. Depending on the activity, the consumption of the mushroom culture can fluctuate within certain limits. The rate and depth of hydrolysis of raw carbohydrates are determined by the activity of the deep culture of the mold. Thus, the properties of enzymes are determined mainly by the special properties of proteins. In this case, the folding of peptide chains in the protein molecule changes, which leads to the loss of the characteristic properties of the protein. The ability of enzymes to survive mother cells under favorable conditions and to exert their action outside the cell makes it possible to widely use biological catalysts in various branches of the food industry.


Author(s):  
Zoran Vrucinic

The future of medicine belongs to immunology and alergology. I tried to not be too wide in description, but on the other hand to mention the most important concepts of alergology to make access to these diseases more understandable, logical and more useful for our patients, that without complex pathophysiology and mechanism of immune reaction,we gain some basic insight into immunological principles. The name allergy to medicine was introduced by Pirquet in 1906, and is of Greek origin (allos-other + ergon-act; different reaction), essentially representing the reaction of an organism to a substance that has already been in contact with it, and manifested as a specific response thatmanifests as either a heightened reaction, a hypersensitivity, or as a reduced reaction immunity. Synonyms for hypersensitivity are: altered reactivity, reaction, hypersensitivity. The word sensitization comes from the Latin (sensibilitas, atis, f.), which means sensibility,sensitivity, and has retained that meaning in medical vocabulary, while in immunology and allergology this term implies the creation of hypersensitivity to an antigen. Antigen comes from the Greek words, anti-anti + genos-genus, the opposite, anti-substance substance that causes the body to produce antibodies.


Author(s):  
David Carus

This chapter explores Schopenhauer’s concept of force, which lies at the root of his philosophy. It is force in nature and thus in natural science that is inexplicable and grabs Schopenhauer’s attention. To answer the question of what this inexplicable term is at the root of all causation, Schopenhauer looks to the will within us. Through will, he maintains that we gain immediate insight into forces in nature and hence into the thing in itself at the core of everything and all things. Will is thus Schopenhauer’s attempt to answer the question of the essence of appearance. Yet will, as it turns out, cannot be known immediately as it is subject to time, and the acts of will, which we experience within us, do not correlate immediately with the actions of the body (as Schopenhauer had originally postulated). Hence, the acts of will do not lead to an explanation of force, which is at the root of causation in nature. Schopenhauer sets out to explain what is at the root of all appearances, derived from the question of an original cause, or as Schopenhauer states “the cause of causation,” but cannot determine this essence other than by stating that it is will; a will, however, that cannot be immediately known.


Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 712-718 ◽  
Author(s):  
SD Smith ◽  
EM Uyeki ◽  
JT Lowman

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanxiu Sun ◽  
Yu Yuan ◽  
Wei Wu ◽  
Le Lei ◽  
Lingli Zhang

AbstractBone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.


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