Improved Enzymatic Procedure for the Synthesis of Anandamide andN-Fatty Acylalkanolamine Analogues: A Combination Strategy to Antitumor Activity

2015 ◽  
Vol 2016 (3) ◽  
pp. 518-528 ◽  
Author(s):  
Paula G. Quintana ◽  
Guadalupe García Liñares ◽  
Santiago N. Chanquia ◽  
Roxana M. Gorojod ◽  
Mónica L. Kotler ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Combination Strategy ◽  
Enzymatic Procedure

scholarly journals Combined ALK and MDM2 inhibition increases antitumor activity and overcomes resistance in human ALK mutant neuroblastoma cell lines and xenograft models

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Hui Qin Wang ◽  
Ensar Halilovic ◽  
Xiaoyan Li ◽  
Jinsheng Liang ◽  
Yichen Cao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Wild Type ◽  
Combination Strategy ◽  
Human Neuroblastoma ◽  
Xenograft Models ◽  
Neuroblastoma Cell Lines

The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is limited, highlighting the need to improve their effectiveness in these patients. To this end, we sought to develop a combination strategy to enhance the antitumor activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and xenograft models expressing activated ALK. Herein, we report that combined inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and pro-apoptotic proteins. Consequently, this combination treatment synergistically inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK amplification or mutations in vitro, and resulted in complete and durable responses in neuroblastoma xenografts derived from these cells. We further demonstrate that concurrent inhibition of MDM2 and ALK was able to overcome ceritinib resistance conferred by MYCN upregulation in vitro and in vivo. Together, combined inhibition of ALK and MDM2 may provide an effective treatment for TP53 wild-type neuroblastoma with ALK aberrations.

710: TNF-Related Apoptosis Inducing Ligand (TRAIL/APO-2L): A Novel Mechanism for BCG-Induced Antitumor Activity

2004 ◽  
Vol 171 (4S) ◽  
pp. 188-189
Author(s):  
Aaron T. Ludwig ◽  
Jill M. Moore ◽  
Yi Luo ◽  
Xiaohong Chen ◽  
Michael A. O’Donnell ◽  
...  
Keyword(s):  
Antitumor Activity

Antitumor activity of tricin, a flavone isolated from leaves of Casearia arborea (Salicaceae)

2017 ◽  
Author(s):  
P Sartorelli ◽  
A Santos ◽  
C Figueiredo ◽  
J Lago ◽  
M Soares
Keyword(s):  
Antitumor Activity

Adaptive NK cells with decreased antitumor activity are expanded in HBV-associated HCC

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
C Rennert ◽  
C Tauber ◽  
B Zecher ◽  
A Schuch ◽  
M Hofmann ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Nk Cells

1295-P: Economic Evaluation of Drug Combination Strategy for Type 2 Diabetes in China

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1295-P
Author(s):  
SHUYAN GU ◽  
YI SHEN ◽  
LIZHENG SHI ◽  
HENGJIN DONG
Keyword(s):  
Type 2 Diabetes ◽  
Economic Evaluation ◽  
Drug Combination ◽  
Combination Strategy

Synthesis of Some New Tetracyclic Pyrimidine Derivatives Using Exocyclic α,β-Unsaturated Ketone and Evaluation of Their Antitumor Activities

2016 ◽  
Vol 12 (8) ◽  
pp. 311-317
Author(s):  
Kamelia El-Mahdy
Keyword(s):  
Antitumor Activity ◽  
Spectroscopic Data ◽  
Acid Hydrazide ◽  
Chloroacetic Acid ◽  
Equimolar Amount ◽  
Unsaturated Ketone ◽  
Cyanoacetic Acid ◽  
Antitumor Activities ◽  
Pyrimidine Derivatives ◽  
Cyanoacetic Acid Hydrazide

Thiazolopyrimidine 2 was obtained from the reaction of dihydropyrimidinone with chloroacetic acid and benzaldehyde. Thiazolopyrimidine 2 containing an α,β-unsaturated ketonic function [-CH=CH-CO-] has been used as a component of Michael addition with an equimolar amount of dinucleophiles to give a series of novel tetracyclic pyrimidine derivatives. Treatment of thiazolopyrimidine 2 with uracil, aminotriazole, cyanoacetic acid hydrazide, o-phenylenediamine or diaminopyridine afforded the corresponding pyridopyrimidine, triazolopyrimidine, pyrazolone, benzodiazepine and triazepine derivative, respectively. The detailed synthesis, spectroscopic data, and antitumor activity for synthesized compounds were reported.

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.

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