1.Blocking Adenosine/A2AR Pathway for Cancer Therapy.
Jia LIU ; Yuequan SHI ; Xiaoyan LIU ; Dongming ZHANG ; Yu BAI ; Yan XU ; Mengzhao WANG
Chinese Journal of Lung Cancer 2022;25(7):460-467
Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.
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Adenosine/therapeutic use*
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Adenosine A2 Receptor Antagonists/therapeutic use*
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Humans
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Lung Neoplasms
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Receptor, Adenosine A2A/metabolism*
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Tumor Microenvironment
3.Progress in the research of therapeutic enzyme.
Hanmei XU ; Changlin ZHOU ; Heng ZHEN ; Wutong WU
Chinese Journal of Biotechnology 2009;25(12):1852-1862
With the development of the research on biotechnology and modern pharmacy, the application of enzyme drugs have grown rapidly and enzyme drugs have become an important branch of biopharmaceutics. In this article, some new varieties of therapeutic enzymes, enzyme targets, mechanisms and new technologies of application in therapeutic enzymes were reviewed, and the direction of development of therapeutic enzymes were discussed.
Adenosine Deaminase
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genetics
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therapeutic use
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Antineoplastic Agents
;
therapeutic use
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Enzyme Replacement Therapy
;
methods
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Fibrinolytic Agents
;
therapeutic use
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Protein C
;
genetics
;
therapeutic use
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RNA, Catalytic
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genetics
;
therapeutic use
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Streptokinase
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genetics
;
therapeutic use
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Urokinase-Type Plasminogen Activator
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genetics
;
therapeutic use
4.Advances in the study of A2B adenosine receptor antagonists.
Jing WEI ; Wen-Quan YU ; Qing-Zhi GAO
Acta Pharmaceutica Sinica 2008;43(3):241-246
A2B adenosine receptor is involved in the control of mast cell degranulation, interleukin-8 synthesis and cell growth. A2B adenosine receptor antagonists may serve as novel drugs for asthma, Alzheimer' s disease, cystic fibrosis and type-II diabetes. Therefore, seeking for the highly selective A2B adenosine receptor antagonists has been one of great interest. The molecular basis, structure-activity relationship of selective A2B adenosine receptor antagonists and their interactions with A2B adenosine receptor were reviewed.
Adenosine
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pharmacology
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Adenosine A2 Receptor Antagonists
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Adenosine A3 Receptor Antagonists
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Adenosine-5'-(N-ethylcarboxamide)
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pharmacology
;
therapeutic use
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Animals
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Anti-Asthmatic Agents
;
therapeutic use
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Asthma
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drug therapy
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Humans
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Pulmonary Artery
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drug effects
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Structure-Activity Relationship
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Xanthines
;
pharmacology
5.Treatment of periventricular leukomalacia in preterm infants.
Chinese Journal of Contemporary Pediatrics 2007;9(4):327-329
Adenosine
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therapeutic use
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Brain-Derived Neurotrophic Factor
;
therapeutic use
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Erythropoietin
;
therapeutic use
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Glucocorticoids
;
therapeutic use
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Humans
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Infant, Newborn
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Infant, Premature
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Interleukin-10
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therapeutic use
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Leukomalacia, Periventricular
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drug therapy
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Nitric Oxide
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therapeutic use
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Receptors, N-Methyl-D-Aspartate
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antagonists & inhibitors
6.Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116).
Qiuyu CAO ; Yi DING ; Yu XU ; Mian LI ; Ruizhi ZHENG ; Zhujun CAO ; Weiqing WANG ; Yufang BI ; Guang NING ; Yiping XU ; Ren ZHAO
Frontiers of Medicine 2023;17(6):1068-1079
The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans
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Ritonavir/therapeutic use*
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COVID-19
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Antiviral Agents/therapeutic use*
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China
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Nitriles
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Lactams
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Proline
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Adenosine/analogs & derivatives*
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Leucine
7.Efficacy comparison of combined intracoronary administration of high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention in patients with acute myocardial infarction.
Zi-chuan TONG ; Qiang LI ; Ming CHEN ; Guo-bin MIAO ; Yu WEI ; Fei-ou LI ; Hua ZHAO ; Jian-jun ZHANG
Chinese Journal of Cardiology 2013;41(10):839-844
OBJECTIVETo compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.
METHODSConsecutive 258 patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI, treated with thrombus aspiration and then intracoronary tirofiban, were randomly divided into adenosine group (n = 130) and control group (n = 128). Adenosine group received 2 times intracoronary adenosine (2 mg) after thrombus aspiration and after stenting of the infarct-related artery through the aspiration catheter. Control group received placebo. The primary end point was myocardial blush grade (MBG) after PCI. Secondary end points were thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI, ST-segment elevation resolution (STR), and major adverse cardiac events (MACE) at 30 days and 12 months.
RESULTSTIMI flow grade post PCI did not differ between the 2 groups, while CTFC favored the adenosine-treated patients [(21.6 ± 6.5) frames] compared with the placebo-treated patients [(25.1 ± 7.8) frames, P = 0.001]. MBG 3 was more frequently observed in the adenosine compared to the control group [45.1% (55/122) vs.32.0% (39/122), P = 0.035]. Patients in the adenosine group had a trend of higher rate of compete STR after the procedure compared patients in the control group [53.6% (67/125) vs. 41.9% (52/124), P = 0.065]. The incidence of MACE was comparable between patients randomized to adenosine and placebo at 30 days [12.3% (16/130) vs. 17.2% (22/128), P = 0.295] and at 12 months [12.3% (16/130) vs. 18.0% (23/128), P = 0.227].
CONCLUSIONIntracoronary administration of high-dose adenosine combined with tirofiban provides further improvement on myocardial perfusion after primary PCI but does not affect the clinical outcomes in patients with STEMI.
Adenosine ; therapeutic use ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; therapeutic use ; Tyrosine ; analogs & derivatives ; therapeutic use
8.A comprehensive review of natural products with anti-hypoxic activity.
Juncai LIU ; Zhen GE ; Xiao JIANG ; Jingjing ZHANG ; Jianan SUN ; Xiangzhao MAO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(7):499-515
Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.
Humans
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Biological Products/therapeutic use*
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Hypoxia/metabolism*
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Reactive Oxygen Species/metabolism*
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Adenosine Triphosphate/metabolism*
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Alkaloids
9.The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction.
Qian WANG ; Ying KONG ; Song LIN ; Ding-Yu WU ; Jian HU ; Lang HUANG ; Wen-Si ZANG ; Xiao-Wen LI ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2021;37(9):1303-1313
Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca
Adenosine Triphosphate
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Animals
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Antidepressive Agents/therapeutic use*
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Caloric Restriction
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Mice
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Mice, Knockout
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Prefrontal Cortex
10.Innovative In Vitro Chemo-Hormonal Drug Therapy for Refractory Thyroid Carcinomas.
Tae Yon SUNG ; Sung Ho CHOI ; Jung Min LEE ; Jong Ju JEONG ; Sang Wook KANG ; Woong Youn CHUNG
Journal of Korean Medical Science 2012;27(7):729-735
More than 95% of the thyroid carcinomas are well differentiated types showing favorable prognosis. However, only a few therapeutic options are available to treat the patients with undifferentiated thyroid carcinomas, especially with refractory thyroid carcinomas that are not amenable to surgery or radioiodine ablation. We investigated the anticancer effects of 20 chemotherapy and hormonal therapy drugs on 8 thyroid carcinoma cell lines. In vitro chemosensitivity was tested using the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). The tumor inhibition rate (TIR; or cell death rate) or half maximal inhibitory concentration (IC50) was analyzed to interpret the results. Of the 12 chemotherapy drugs, etoposide (178.9 index value in follicular carcinoma cell line) and vincristine (211.7 in Hurthle cell carcinoma cell line) were the most active drugs showing the highest chemosensitivity, and of the 8 additional drugs, trichostatin A (0.03 microg/mL IC50 in follicular carcinoma cell line) showed favorable outcome having the anticancer effect. In our study, the result of etoposide and vincristine show evidence as active anticancer drugs in thyroid carcinoma cell lines and trichostatin A seems be the next promising drug. These drugs may become an innovative therapy for refractory thyroid carcinomas in near future.
Adenosine Triphosphate/chemistry/pharmacology/therapeutic use
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Antineoplastic Agents/chemistry/*pharmacology/therapeutic use
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Apoptosis/drug effects
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Cell Line, Tumor
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Etoposide/chemistry/pharmacology/therapeutic use
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Humans
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Hydroxamic Acids/chemistry/pharmacology/therapeutic use
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Thyroid Neoplasms/drug therapy
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Vincristine/chemistry/pharmacology/therapeutic use