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L-asparaginase: An ultimate anti-neoplastic enzyme

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Prasad Talluri V. S. S. L., Bhavana M., Mahesh Kumar M. V. S., Rajagopal S. V.

International Letters of Natural Sciences

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2014

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tom 10

The objective of the study described the importance of L-asparaginase and its importance in the field of medicine. Different types of enzymes are produced based on the adaptation to the environment where the living organisms live to tune the metabolic pathways according to their adapted changes. The enzymes present in various organs are produced by many cell types in multicellular organisms. Except ribosomes all other known enzymes are proteinaceous in nature. L-asparaginase is a potential therapeutic agent for acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia which is approved by FDA & WHO. L-asparaginase catalyzes the deamination of L-asparagine to L-aspartic acid & ammonia. Unlike normal cells, malignant cells require large amount of L-asparagine for protein synthesis and cell division. From this background the present review is an effort to gather the information on the mechanism, sources, molecular details and application of L-asparaginase enzyme.

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Molecular interactions and dynamics in liposome-drug systems revealed by EPR spectroscopy

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Grof P.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.

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Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug resistance-associated protein 1: Their stability in fetal calf serum and human plasma

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Rebowski G., Wojcik M., Boczkowska M., Gendaszewska E., Soszynski M., Bartosz G., Niewiarowski W.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

Multidrug resistance-associated protein (MRP1) is a transmembrane pump protein responsible for the efflux of chemotherapeutic drugs, an important cause of anticancer treatment failure. Trying to circumvent MRP-mediated resistance we designed and synthesized hairpin loops forming antisense oligodeoxyribonucleotides (ODNs), both phosphodiesters (PO-ODNs) and their phosphorothioate analogues (PS-ODNs), to reduce the protein expression by targeting its mRNA in a sequence specific manner. Melting temperature measurements as well as polyacrylamide gel elec- trophoresis supported the preferential formation of a secondary structure, which was expected to protect ODNs against 3-exonuclease degradation. ODNs and PS-ODNs designed in this work were successfully tested as antisense inhibitors of the expression of MRP1 in the leukaemia HL60/ADR cell line. Foreseeing the necessity to perform clinical studies with such ODNs we investigated their stability against the 3 -exonuclease activity of fetal calf serum and human plasma. Under the conditions, corresponding to physiological ones, we observed high stability of hairpin loop forming ODNs, especially those containing longer (e.g. 7 base pair) stems. Comparative studies on the stability of chemically unmodified hairpin loop forming ODNs and their PS-counterparts indicated that endonuclease activity did not play any important role in the process of their nucleolytic degradation. Our studies provide strong evidence for high stability of chemically unmodified hairpin loop ODNs, making them an attractive alternative to phosphorothioate analogues commonly used in antisense strategy.

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Immunocytochemical analysis of apoptotic bone marroow cells after treatment of mice with WR-2721 and chemotherapeutic drugs

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Mazur L., Czyzewska A.

Folia Histochemica et Cytobiologica

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2001

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tom 39

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nr 2

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Low-glucose medium induces ORP150 expression and exerts inhibitory effect on apoptosis and senescence of human breast MCF7 cells

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Kretowski R., Stypulkowska A., Cechowska-Pasko M.

Acta Biochimica Polonica

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2013

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tom 60

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nr 2

Glucose deprivation is a factor evoking endoplasmic reticulum (ER) stress and induction of expression of an oxygen-regulated protein of 150 kDa (ORP150). We studied the effect of inducible overexpression of ORP150 on senescence and apoptosis of human breast carcinoma cells (MCF7) and human skin fibroblasts. We found an inhibitory effect of ORP150 on apoptosis and senescence of MCF7 cells, but not fibroblasts in ER stress conditions. An increased expression of senescence-associated β-galactosidase and acid β-galactosidase activity (biomarkers of cellular senescence) was observed. We suggest that ORP150 induction in cancer cells can promote tumour progression and may be a major cause of their resistance to chemotherapeutics.

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Signs, symptoms and the prevalence of fungi detected from the oral cavity and pharynx of radiotherapy subjects with head and neck tumors, and their susceptibility to chemotherapeutics

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Kurnatowski P., Moqbil S., Kaczmarczyk D.

Annals of Parasitology

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2014

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tom 60

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nr 3

Radio- and chemotherapy for malignant neoplasms, especially in head and neck region, is associated with a greater risk of fungal infections due to secondary alterations in the mucous membranes. The study had three aims: 1. to determine the signs and symptoms which occur among patients undergoing radiotherapy; 2. to determine the fungi prevalence in the mouth and throat of patients before, during and after radiotherapy; 3. to examine the sensitivity of strains to antimycotic drugs. The study comprised 44 patients (11 female, 33 male) with head and neck cancers, examined at the following stages: before radiotherapy (44 patients – batch 1), 3rd week of therapy (30 of the 44 patients – batch 2), last day of therapy (28 of batch 2 – batch 3) and the 6th week after completion of radiotherapy (10 of batch 3 – batch 4). Clinical examination was performed and mycological status was estimated from an oral rinse on a selected medium. The fungal strains were isolated and sensitivity to antifungal drugs was determined. The most common symptoms were pain, dysphagia, and dysgeusia. Physical examination revealed signs of mucositis mainly among patients from batches 2 and 3. The presence of fungi in the mouth and throat was noted in over 2/3 (66.2%) of the patients from batch 1, and in 4/5 (80%) of batch 2. The fungi were detected in over half (57.1%) of patients from batch 3 and also in patients from batch 4. In all cases, fungi of various Candida species were identified: 6 species in batch 1, 8 in batch 2, 6 in batch 3 and 5 in batch 4. The most frequently detected species was C. albicans, constituting 40–60%; the other species detected are known to be resistant to antimycotic drugs. The isolated strains were the most sensitive to nystatin and miconazole, and the least to ketoconazole and fluconazole. Conclusions: 1. Patients undergoing radiotherapy complain of pain, dysphagia, and dysgeusia; in most cases mucositis is diagnosed. 2. The high prevalence of fungi in the mouth and throat of patients treated by radiotherapy reinforces the need to perform mycological examinations in this group of patients to detect fungi, identify their species and determine of their sensitivity to drugs in order to prevent complications. 3. The species most frequently isolated from the patients are C. albicans and C. glabrata. The latter is characterized by resistance to the majority of antimycotic medications. 4. Most of the isolated strains are sensitive to nystatin and miconazole (applied locally) and to itraconazole (absorbed from the gastrointestinal tract).

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dUTP pyrophosphatase as a potential target for chemotherapeutic drug development

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McIntosh E. M., Haynes R. H.

Acta Biochimica Polonica

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1997

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tom 44

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nr 2

Aberrant dUTP metabolism plays a critical role in the molecular mechanism of cell killing induced by inhibitors of dihydrofolate reductase and thymidylate synthase. While considerable effort has been directed towards discovering new, more potent inhibitors of these two enzymes, little attention has been given dUTP pyrophosphatase (dUTPase)--the key modulator of cellular dUTP levels--as a potential target for chemotherapeutic drug development. Recent studies have provided evidence that dUTPase is vital for cellular and, in some cases, viral DNA replication. Furthermore, some retroviruses encode dUTPases--a fact which suggests that cellular dUTP metabolism may be more important than previously realized. Here, we briefly review current knowledge of cellular and viral dUTPases and discuss the potential of these enzymes as targets for cancer chemotherapeutic and anti-viral drug development.

Ograniczanie wyników

L-asparaginase: An ultimate anti-neoplastic enzyme

Molecular interactions and dynamics in liposome-drug systems revealed by EPR spectroscopy

Antisense hairpin loop oligonucleotides as inhibitors of expression of multidrug resistance-associated protein 1: Their stability in fetal calf serum and human plasma

Immunocytochemical analysis of apoptotic bone marroow cells after treatment of mice with WR-2721 and chemotherapeutic drugs

Low-glucose medium induces ORP150 expression and exerts inhibitory effect on apoptosis and senescence of human breast MCF7 cells

Signs, symptoms and the prevalence of fungi detected from the oral cavity and pharynx of radiotherapy subjects with head and neck tumors, and their susceptibility to chemotherapeutics

dUTP pyrophosphatase as a potential target for chemotherapeutic drug development