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Biologic Drug Substance and Drug Product Manufacture
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Ajit S. Narang, Mary E. Krause, Shelly Pizarro, Joon Chong Yee
The nutritional requirements of the auxotrophs form the basis of selection of cells post-transfection for those expressing exogenous proteins and has been utilized to also increase the transgene copy number and expression levels. Commonly used auxotrophs of CHO cells are the DG44 and DUKXB-11 host cell lines that are deficient in the dihydrofolate reductase (DHFR) enzyme. This enzyme reduces dihydrofolic acid to tetrahydrofolic acid, an essential cellular biochemical product for purine and thymidylate synthesis. Cells lacking the DHFR enzyme require glycine, hypoxanthine, and thymidine to grow (and are thus called triple auxotrophs). This property is utilized for the expression of a heterologous gene by co-transfection with a functional copy of the DHFR gene, such that the transfected cells do not require exogenously supplied glycine, hypoxanthine, and thymidine in the growth medium. Hence, cell culture in a deficient growth medium allows the selection of transfected cells. Another recombinant DNA expression strategy is the glutamine synthetase (GS) system utilized in GS deficient CHO cells. GS catalyzes the production of glutamine, an essential amino acid required for cellular metabolism, from glutamate and ammonia. Upon co-transfection of the recombinant gene and GS into host cells, the cells are cultivated in glutamine-free media to select for producing clones.
Assessment of Quercetin Isolated from Enicostemma Littorale Against Few Cancer Targets: An in Silico Approach
Published in A. K. Haghi, Ana Cristina Faria Ribeiro, Lionello Pogliani, Devrim Balköse, Francisco Torrens, Omari V. Mukbaniani, Applied Chemistry and Chemical Engineering, 2017
(DHFR) is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid using NADPH as electron donor which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the DHFR gene10 found in all organisms, DHFR has a critical role in regulating the amount of tetrahydrofolate in the cell. Tetrahydrofolate and its derivatives are essential for purine and thymidylate synthesis which is important for cell proliferation and cell growth.9DHFR plays a central role in the synthesis of nucleic acid precursors, and it has been shown that mutant cells that completely lack DHFR require glycine, a purine, and thymidine to grow.23
Pneumonitis induced by non-cytotoxic agents
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Umair A Gauhar, J Allen D Cooper
Methotrexate is structurally related to the vitamin folic acid and acts as an antagonist of that vitamin by inhibiting dihydrofolate reductase, the enzyme involved in converting folic acid to its active coenzyme form, tetrahydrofolic acid. This leads to decreased biosynthesis of thymidylic acid, methionine, serine and the purines and thus eventually to decreased DNA, RNA and protein synthesis causing cell death.1 The dose of methotrexate used in RA is much smaller (15–25 mg per week administered orally, intramuscularly or subcutaneously) as compared to doses used in malignant diseases (100–1000 mg/m2).2
Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Mei Zhang, Yajun Tang, Zhenhua Zhu, He Zhao, Jihang Yao, Dahui Sun
Osteosarcoma (OS) is one malignant connective tissue tumor, the incidence of osteosarcoma takes the first position among the malignant tumor. Osteosarcoma is a common, high malignant degree and poor prognosis entity of the malignant osseous tumor. It’s spread to the lungs in a few months. The survival rate is only 5 to 20% after amputation 3 to 5 years. Local resection or resection of the tumor and chemotherapy may be used in the treatment of low grade osteosarcoma and peripheral sarcoma. If the tumor is highly malignant, preoperative chemotherapy plus amputation and postoperative chemotherapy should be adopted. The completion of the operation is not the end of the treatment, patients should adhere to the doctor's advice, insist on regular chemotherapy, in order to have a good prognosis. Significant progress have been made in the OS treatment in the preoperative chemotherapy with cisplatin (DDP), adriamycin (ADR), methotrexate-tetrahydrofolic acid (MTX-CF), bleomycin-cyclophosphamide-dactinomycin (BCD), ifosfamide (IFO) and cyclophosphamide (CTX), etc., and the distance-disease-free survival is 42–89% [1–3].
DFT studies of temperature effect on coordination chemistry of Cu(II)-trimethoprim complexes
Published in Journal of Coordination Chemistry, 2018
Malik Zaheer Ahmed, Uzma Habib
Trimethoprim {(2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine, TMP} belongs to a synthetic antibacterial agent and diaminopyrimidine (pyridine-3,4-diamine) compound group. Dihydrofolate reductase (DHFR) is the target enzyme of trimethoprim. This enzyme catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate in the presence of NADPH. Trimethoprim is a good inhibitor of bacterial dihydrofolate reductase and is used to prevent the conversion of dihydrofolic acid to tetrahydrofolic acid [1, 2] (Figure 1).