Growth inhibition by ammonia and use of a pH-controlled feeding strategy for the effective cultivation of Mycobacterium chlorophenolicum

1995 ◽  
Vol 44 (3-4) ◽  
pp. 519-525 ◽  
Author(s):  
C. Wittmann ◽  
A.-P. Zeng ◽  
W.-D. Deckwer
Keyword(s):  
Growth Inhibition ◽  
Feeding Strategy ◽  
Mycobacterium Chlorophenolicum ◽  
Ph Controlled

scholarly journals Using Metabolomics to Identify Cell Line-Independent Indicators of Growth Inhibition for Chinese Hamster Ovary Cell-Based Bioprocesses

Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 199 ◽  
Author(s):  
Nicholas Alden ◽  
Ravali Raju ◽  
Kyle McElearney ◽  
James Lambropoulos ◽  
Rashmi Kshirsagar ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Cell Lines ◽  
Chinese Hamster Ovary ◽  
Cho Cells ◽  
Feeding Strategy ◽  
Chinese Hamster ◽  
Ovary Cell ◽  
Growth Stages ◽  
Cho Cell

Chinese hamster ovary (CHO) cells are widely used for the production of biopharmaceuticals. Efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. In addition to ammonia and lactate, many other metabolites accumulate in CHO cell cultures, although their effects remain largely unknown. Elucidating these effects has the potential to further improve the productivity of CHO cell-based bioprocesses. This study used untargeted metabolomics to identify metabolites that accumulate in fed-batch cultures of monoclonal antibody (mAb) producing CHO cells. The metabolomics experiments profiled six cell lines that are derived from two different hosts, produce different mAbs, and exhibit different growth profiles. Comparing the cell lines’ metabolite profiles at different growth stages, we found a strong negative correlation between peak viable cell density (VCD) and a tryptophan metabolite, putatively identified as 5-hydroxyindoleacetaldehyde (5-HIAAld). Amino acid supplementation experiments showed strong growth inhibition of all cell lines by excess tryptophan, which correlated with the accumulation of 5-HIAAld in the culture medium. Prospectively, the approach presented in this study could be used to identify cell line- and host-independent metabolite markers for clone selection and bioprocess development.

Light-induced increase in the contents of ferulic and diferulic acids in cell walls of Avena coleoptiles: its relationship to growth inhibition by light

1994 ◽  
Vol 92 (2) ◽  
pp. 350-355 ◽  
Author(s):  
Kensuke Miyamoto ◽  
Junichi Ueda ◽  
Satomi Takeda ◽  
Kazuko Ida ◽  
Takayuki Hoson ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cell Walls

COMPARATIVE STUDY OF THE EFFECTS OF NOS INHIBITOR T1023 AND BEVACIZUMABUM ON GROWTH AND MORPHOLOGY OF LEWIS LUNG CARCINOMA

2019 ◽  
pp. 89-98
Author(s):  
М.В. Филимонова ◽  
В.В. Южаков ◽  
А.С. Филимонов ◽  
В.М. Макарчук ◽  
Л.Н. Бандурко ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Lung Carcinoma ◽  
Comparative Studies ◽  
Lewis Lung Carcinoma ◽  
Lewis Lung ◽  
Vegf Inhibitor ◽  
Nos Inhibitor ◽  
Experimental Group

Цель исследования - изучение механизмов противоопухолевой активности ингибитора NOS Т1023 и оценка перспективности его дальнейшей разработки. Методика. В качестве опухолевой модели использована эпидермоидная КЛЛ, штамм которой получен из банка опухолевых материалов ФГБУ РОНЦ им. Н.Н. Блохина и поддерживался на самцах мышей C57BL6j. КЛЛ трансплантировали самцам мышей F1 (CBA´C57BL6j) путем подкожного введения 1,5×106 клеток карциномы в 0,1 мл суспензии на основе среды 199 в область латеральной поверхности правого бедра. Для сравнительной оценки противоопухолевой эффективности использовали ингибитор NOS под шифром Т1023, синтезированный в лаборатории радиационной фармакологии МРНЦ им. А.Ф. Цыба, и VEGF-ингибитор бевацизумаб (БВЗ). Животным первой опытной группы ежедневно, со 2 по 20 сутки вводили соединение Т1023 (60 мг/кг, в/б); второй опытной группы - трижды, на 2, 5 и 10 сут вводили БВЗ (12 мг/кг, в/б); третьей опытной группы - по этим схемам и в таких же дозах вводили и Т1023, и БВЗ (при комбинированном применении Т1023 вводили через 4 ч после введения БВЗ). Контрольным животным в качестве плацебо со 2 по 20 сутки вводили 0,9% раствор натрия хлорида (0,2 мл, в/б). Противоопухолевые эффекты оценивали, сравнивая размеры опухолевых узлов, длительность задержки роста и индекс торможения роста опухоли у контрольных и опытных животных. Гистологические методы исследования включали иммуноокрашивание на PCNA, CD31, пимонидазол и морфометрический анализ микроскопических изображений. Результаты сравнительных исследований показали, что соединение Т1023 и VEGF-ингибитор бевацизумаб (БВЗ) оказывают однонаправленное влияние на карциному легких Льюис (КЛЛ), сопровождающееся торможением роста и подавлением метастазирования неоплазии. Воздействие и Т1023, и БВЗ вызывало снижение содержания сосудов в перитуморальных зонах и в «горячих точках» ангиогенеза, усиливало гипоксию паренхимы КЛЛ и стимулировало апоптоз опухолевых клеток. При комбинированном применении Т1023 и БВЗ их антинеопластическая эффективность в отношении ингибирования ангиогенеза и девитализации опухолевых клеток соответствовала аддитивному действию. Заключение. Результаты позволяют предполагать, что основой противоопухолевой активности Т1023 является антиангиогенное действие и свидетельствуют о перспективности применения ингибиторов NOS в ангиостатической терапии солидных злокачественных новообразований в сочетании с имеющимися антинеоваскулярными средствами. The aim. Study of mechanisms of NOS inhibitor T1023 antitumor activity and estimation of its prospects for further development. Methods. Epidermoid Lewis lung carcinoma (LLC) from N.N. Blokhin NMRCO bank of tumor materials was used as a tumor model. Maintenance of tumor cell culture was provided by intramuscular injection of tumor cells suspension to C57BL6j mice every 14 days. Then LLC cells were transplanted to male F1 mice (CBA´C57BL6j) by subcutaneous injection of 1,5×106 cells in 0,1 ml of 199 medium into the lateral surface of the right hip. Comparative studies of antitumor efficacy were carried out using NOS inhibitor T1023, synthesized in the laboratory of radiation pharmacology of A.F. Tsyb MRRC, and VEGF inhibitor Bevacizumab (BVZ). Mice from the first experimental group were injected intraperitoneally (ip) with compound T1023 at dose 60 mg / kg from day 2 to 20; animals from the second experimental group were treated with BVZ at dose 12 mg / kg ip at days 2, 5 and 10; the third experimental group received T1023 in combination with BVZ according to these schemes and at the same doses (T1023 was administered 4 hours after administration of BVZ). Mice from the control group received 0,9% sodium chloride solution (0,2 ml, ip) as a placebo daily from 2 to 20 days. Antitumor effects were assessed by comparing the tumor size, duration of tumor growth delay and the index of tumor growth inhibition in control and experimental groups. Histological examination methods included immunostaining on PCNA, CD31, pimonidazole and morphometric analysis of microscopic images. Results. Comparative studies have shown that compound T1023 and VEGF inhibitor Bevacizumab (BVZ) have unidirectional effects on Lewis lung carcinoma (LLC), accompanied by growth inhibition and suppression of metastasis of neoplasia. The effect of both T1023 and BVZ caused a decrease in vascular content in the peritumoral zones and in the “hot spots” of angiogenesis, increased the hypoxia in the LLC parenchyma, and stimulated apoptosis of tumor cells. The combined use of T1023 and BVZ, caused the antineoplastic efficacy against inhibition of angiogenesis and devitalization of tumor cells which was estimated as additive effect. Conclusion. The results suggest that the basis of antitumor activity of T1023 is the anti-angiogenic effect and indicate the prospects of using NOS inhibitors in the angiostatic therapy of solid malignant neoplasms in combination with available anti-neovascular agents.

The natural compound podophyllotoxin induces growth inhibition and microtubule condensation on arabidopsis roots

2018 ◽  
Vol 45 (2) ◽  
pp. 255-262
Author(s):  
A. Costas-Gil ◽  
M.J. Reigosa ◽  
A.M. Sánchez-Moreiras
Keyword(s):  
Growth Inhibition ◽  
Natural Compound
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