• Microbiology and Biotechnology Letters
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• v.6 no.4
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• pp.187-196
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• 1978

Antimetabolite N-2292 substance, an antagonist of L-aspartic acid and L-glutamic acid was isolated from the fermentation broth of Streptomyces. Taxonomical study on the producing strain made it a related species of Streptomyces albulus judged by cultural characteristics and carbon utilization. N-2292 substance was isolated as amorphous white powder with melting point at 185$^{\circ}C$. From the physicochemical characteristics of the substance, it was peptide like substance. It was active against Gram positive and Gram negative bacteria but negative against yeast and mold in its biological properties. It was reversed by L-Asp and L-Glu on the synthetic medium.

• The Korean Journal of Zoology
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• v.33 no.4
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• pp.493-498
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• 1990

The effects of an antimetabolite, 6-aminonicotinamide (6-AN) on the levels of enzymes and metabolites in rabbit serum were investigated. The intraperitoneal administration of 6-AN (multiple doses of l5mg/kg body weight) gave tise to a remarkable increase in glucose and cholesterol levels but did not exert any appreciable influence on the concentration of albumin and total protein. Alkaline phosphatase activity was significantly reduced by administration of 6-AN, whereas creatine phophokinase, serum glutamic oxaloacetate transaminase and serum glutamic pyruvate transaminase activities were matkedly enhanced. Nevettheless, the levels of Ca, P, Na, K, Cl and Co were not affeded to any extent by 6-AN.

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.120-127
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• 2010

Objective: The purpose of this study was to identify the type and frequency of chemotherapy-related prescribing errors and assess the pharmacist intervention in preventing potential harm. Methods: This study was performed in satellite pharmacy of oncology/hematology unit in tertiary teaching hospital from April to September, 2009. All chemotherapy prescribing errors detected by pharmacists were recorded. Frequency and characteristics of prescribing errors were analyzed. Pharmacists reviewed 28, 495 chemotherapy orders from 12,719 patients during 6-month periods. Results: A total of 835 prescription errors (2.93%) in 734 patients (5.77%) were detected by pharmacists. Alkylating agents (37.6%) followed by antimetabolite (23.35%), and mitotic inhibitors (21.44%) were the most prevalent classes in which errors occurs. The most common types of error detected were incorrect dose (34%), incorrect solution (33%), incorrect route (9%) and omission errors (8%). Changes in chemotherapy order due to pharmacists' intervention occurred in all error cases. Conclusion: Pharmacists' intervention in reviewing chemotherapy and drug orders intercepted potential harm due to prescribing errors. The current study provided strategies for reduction of medication errors.

• Microbiology and Biotechnology Letters
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• v.23 no.1
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• pp.47-52
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• 1995

Since the original productivity of new aminopeptidase M inhibitors MR-387A and B by Streptomyces sp. SL-387 (KCTC 0102BP) was not enough for further chemical and biological evaluation, mutation of parent strain by the treatment of N-methyl-N'-nitro-N-nitrosoguanidine was performed in order to obtain a clone with greater inhibitory activity. Mutant N-3 was selected due to a 6-fold greater productivity (40 $\mu$g/ml) than that of the wild type(6.7 $\mu$g/ml). This mutant was resistant to 3,4-dehydro-DL-proline, an antimetabolite of proline, with 25 $\mu$g/ml of minimum inhibitory concentration. Furthermore, the characteristic morphological change from spiral spore chain in wild type to straight in mutant was observed. An aminopeptidase M nhibitor different from MR-387A and B was isolated from the culture broth of the mutant. This inhibitor was composed of 2 proline, 1 valine, and an unknown amino acid which is presumably 3-amino-4-phenylbutanoic acid. IC$_{50}$ value (89.1 $\MU$g/ml) of the purified inhibitor was lower than that of other inhibitors, which may be due to the absence of 2(S)-hydroxyl group within the structure of 3-amino-4-phenyl- butanoic acid.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9291-9293
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• 2014

Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve the outcome. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In gemcitabine based regimens, 3 clinical studies which including 57 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 15.7% (9/57) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia i. No treatment related death occurred with gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with refractory or relapsed multiple myeloma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1761-1768
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• 2013

This cross-sectional and descriptive study was designed to determine symptoms emerging due to chemotherapy treatment and their effects on children's quality of life. The research was carried out between February 2008 and February 2009 at the pediatric oncology clinics in four hospitals, focusing on 93 patients receiving chemotherapy. A survey form, the Pediatric Quality of Life Inventory (PedsQL 4.0) and the Memorial Symptom Assessment Scale (MSAS) were used as data collection tools. Chi-square and Student t tests were performed for data analysis. Some 51.6% of the children were aged 13-15 years old, and 51.8% were boys and 50.5% were diagnosed as having solid tumors. There were significant relations between: antimetabolite chemotherapeutics and feeling irritable and worrying (p=0.001, p=0.030); vinkoalkaloid and numbness/tingling in hands/feet (p=0.043); antracyclines and lack of energy and skin changes (p=0.021, p=0.004); and corticosteroids and lack of appetite, nausea and sadness (p=0.008, p=0.009, p=0.009). Several symptoms such as feeling sad, worrying and feeling irritable caused a significant decrease in the total domain of quality of life scores (p=0.034, p=0.012, p=0.010, respectively). Chemotherapeutic drugs can cause symptoms that can seriously affect quality of life in children.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7159-7162
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• 2014

Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

• Journal of Oral Medicine and Pain
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• v.40 no.2
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• pp.82-87
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• 2015

Methotrexate (MTX) is a chemotherapeutic agent that is used to treat a host of malignancies. But recently, MTX has also been used as a therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, and systemic lupus erythematosus. However, MTX is an antimetabolite that affects rapidly dividing normal cells such as oral mucosal epithelial cells, gastrointestinal epithelial cells, and bone marrow cells-which explains why oral mucositis is often an initial manifestation of MTX toxicity. Because oral lesions are frequently initially presented in dental clinics, dentists should consider the possibility of adverse drug reactions in the differential diagnoses of oral lesions through a meticulous collection of patients' medical histories. In this report, we examine patients who suffered from oral ulcerative lesions upon diagnosis of MTX-induced oral mucositis. Then, we suggest approaches for the diagnosis and treatment of MTX-induced oral mucositis through a review of literature.

• Animal cells and systems
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• v.11 no.1
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• pp.17-22
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• 2007

The effects of antimetabolite 6-AN (6-amino-nicotinamide) on viability and morphology of L6 myoblast cells have been investigated. 6-AN ($100{\mu}M$) induced a time-dependent decrease in cell viability with respect to the untreated control cells. Following 6-AN administration the viability rate started to decline sharply, reaching about 23% of the untreated control cells at 48 h. Inverted phase-contrast microscopy revealed that 6-AN caused characteristic morphological changes such as irregularly elongated and stellate shape of cells, round-shaped nucleus, cytoplasmic vacuolization, irregular cell arrangements and formation of large spaces among cell clusters. The concentrations of ATP and $NAD^{+}$ in the 6-AN treated cells were significantly lower (p < 0.01) than those of the untreated control cells. In contrast, the concentration of AMP was significantly increased by the 6-AN treatment. Activities of catalase, superoxide dismutase and glutathione peroxidase in 6-AN treated cells were significantly higher (p < 0.01) than those of the untreated control cells. The activities of glyceraldehyde-3-phosphate dehydrogenase in 6-AN treated cells were significantly lower (p < 0.01) than those of the untreated control cells. The results suggest that 6-AN caused marked reduction of cell viability and alterations of some important metabolites and enzymes.

• Applied Microscopy
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• v.13 no.1
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• pp.13-30
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• 1983

[ $1-{\beta}-D-Arabinofuranosylcytosine$ ](ara-C), which is a pyrimidine nucleoside analog is cytotonic to mammalian cells in culture and is active in vitro and in vivo against a variety of DNA viruses. The precise mechanism of action of ara-C has not been determined, although ara-C is thought to act as an antimetabolite, interfering with the synthesis of deoxyribonucleic acid(DNA). Cytosine arabinoside originally seemed to act principally by inhibiting the conversion of cytidine to deoxytidine, thus inhibiting DNA synthesis. But recent data suggest that effects upon DNA polymerase and effects via incorporation into DNA and RNA may well be of equal importance. The author have demonstrated the effect of cytosine arabinoside on the hepatocytes of albino mice treated with ara-C, observing changes in the cytoplasmic organelles of the hepatocytes. A total of 120 healthy male albino mice were divided into the control and ara-C treated groups. The animals of the ara-C group were given 10mg. per kg of body weight of mouse ara-C in physiological saline solution and the animals of control group were given physiological saline solution, intraperitoneally. After an administration of ara-C or physiological saline solution, the animal were killed at. interval of 6, 12, and 24 hours. The specimens, which were obtained from the left anterier lobe of the liver, were stained with uranyl acetate and lead citrate and observed with JEM 100B electron microscope. The results were obtained as follow: A pronounced dilatation, sacculation and fragmentation of the cisterane of rough endoplasmic reticulum with dissociation of membrane bound-ribosomes, disaggregation of free ribosomes in the cytoplasm, proliferation of the smooth endoplasmic reticulum associated with depletion of glycogen paracles, atrophies of Golgi complex, production of numerous lipid droplets, and formation of antophagic vacuoles, multivesicular bodies and residual bodies are recognized in the hepatocytes of ara-C treated mice. Consequently it is suggested that cytosine arabinoside would induce a changes of the cytoplasmic organelles of the hepatocytes in albino mice.