Chinese Medicine (CM) has been used for several thousand years, playing an important role in the prevention and treatment of diseases including cancer. In the recent four decades, a number of CM herbs have aroused extreme interest in the world-isolating anticancer components from medicinal herbs, using them as biological response modifiers, and most recently as angiogenesis inhibitors. The present review reports both the experimental and clinical results obtained in the field of clinical oncology, especially conducted by our group. The review also presents the possible future of integration of CM and modern medicine in basic research and clinical practice, especially when CM used as adjuvant and maintenance therapy.
Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; History, Ancient ; Humans ; Integrative Medicine ; Medical Oncology ; history ; Medicine, Chinese Traditional ; history

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Bibenzyls ; chemistry ; pharmacology ; therapeutic use ; Diphosphates ; chemistry ; pharmacology ; therapeutic use ; Endothelial Cells ; drug effects ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; Oligopeptides ; chemistry ; pharmacology ; therapeutic use ; Organophosphorus Compounds ; chemistry ; pharmacology ; therapeutic use ; Serine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Stilbenes ; chemistry ; pharmacology ; therapeutic use ; Tubulin Modulators ; chemistry ; pharmacology ; therapeutic use ; Xanthones ; chemistry ; pharmacology ; therapeutic use

Ursolic acid (UA) is a sort of pentacyclic triterpenoid carboxylic acid purified from natural plant. UA has a series of biological effects such as sedative, anti-inflammatory, anti-bacterial, anti-diabetic, antiulcer, etc. It is discovered that UA has a broad-spectrum anti-tumor effect in recent years, which has attracted more and more scholars' attention. This review explained anti-tumor actions of UA, including (1) the protection of cells' DNA from different damages; (2) the anti-tumor cell proliferation by the inhibition of epidermal growth factor receptor/mitogen-activated protein kinase signal or of FoxM1 transcription factors, respectively; (3) antiangiogenesis, (4) the immunological surveillance to tumors; (5) the inhibition of tumor cell migration and invasion; (6) the effect of UA on caspase, cytochromes C, nuclear factor kappa B, cyclooxygenase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or mammalian target of rapamycin signal to induce tumor cell apoptosis respectively, and etc. Moreover, UA has selective toxicity to tumor cells, basically no effect on normal cells. With further studies, UA would be one of the potential anti-tumor agents.
Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Immunologic Surveillance ; drug effects ; Neoplasms ; blood supply ; drug therapy ; immunology ; pathology ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

In this article, the literatures concerning the mechanism of TCM in anti-tumor and tumor metastasis prevention in recent years were reviewed and summarized into categories of effective components, effective portion, extraction of single drug, and TCM compound.
Adjuvants, Immunologic ; pharmacology ; therapeutic use ; Angiogenesis Inhibitors ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Neoplasm Metastasis ; prevention & control ; Neoplasms ; pathology ; prevention & control ; Phytotherapy ; methods ; trends

Zebrafish has become an important model organism in many fields of biomedical studies and been increasingly used in Chinese materia medica studies in recent years. This article summarized the achievements and prospect for zebrafish as a pharmacological and toxicological tool in the study and development of Chinese materia medica.
Angiogenesis Inducing Agents ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Disease Models, Animal ; Materia Medica ; pharmacology ; therapeutic use ; toxicity ; Medicine, Chinese Traditional ; Memory Disorders ; prevention & control ; Neovascularization, Physiologic ; drug effects ; Zebrafish

Carbon source plays an important role in the constitutive expression of foreign proteins in Pichia pastoris. In present study, glucose , glycerol , methanol and oil acid, was used respectively as the only carbon source to constitutively express hAS in Pichia pastoris GS115 (pGAP9K-AS)in shaking flask. The result shows that oleic acid is the best (163 mg/L) compared with glycerol (83mg/L), glucose (76 mg/L)and methanol (57 mg/L). Since oleic acid is insoluble in water, glycerol was used as the carbon source in the high-density cell culture of GS115 (pGAP9K-AS) in a 30 liter bioreactor and 169 mg/L of angiostatin was obtained after 48h of culture. The expressed angiostatin is immunologically active as shown by Western blotting. The recombinant hAS inhibits bFGF induced CAM angiogenesis and suppresses the growth of B16 melanoma in C57BL/6J mice. The tumor inhibition rate is 90% after 12 days of treatment. Statistics analysis revealed that the tumor volume difference of mice between the hAS group and PBS group is prominent (P < 0.01).
Angiogenesis Inhibitors ; biosynthesis ; genetics ; therapeutic use ; Angiostatins ; biosynthesis ; genetics ; therapeutic use ; Animals ; Bioreactors ; microbiology ; Culture Media ; pharmacology ; Fermentation ; Glycerol ; pharmacology ; Humans ; Melanoma, Experimental ; drug therapy ; Mice ; Mice, Inbred C57BL ; Pichia ; genetics ; growth & development ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; therapeutic use

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood supply ; pathology ; Humans ; Lung Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; drug therapy ; therapy ; Societies, Medical

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Angiogenesis Inhibitors/pharmacology* ; Bevacizumab/therapeutic use* ; Brain/metabolism* ; Consensus ; Humans ; Lung Neoplasms/drug therapy* ; Necrosis/etiology* ; Radiation Injuries/etiology* ; Vascular Endothelial Growth Factor A/metabolism*

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Antimetabolites, Antineoplastic ; therapeutic use ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Female ; Ginsenosides ; pharmacology ; therapeutic use ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation

OBJECTIVETo explore the effect and mechanism of alphastatin on tumor angiogenesis in nude mice bearing human gastric cancer xenografts.

METHODSNude mice were injected subcutaneously with matrigel matrix into matrigel plug. The effect of alphastatin on neovasculature inside Matrigel plug was observed. Human gastric cancer cells (BGC823) were injected subcutaneously in nude mice. After intraperitoneal injection of PBS or alphastatin,tumor volume, weight and microvascular density were analyzed. Sphingosine kinase(SPK) activity assay was used to evaluate the effect of alphastatin on tumor endothelial cells.

RESULTSIn vivo, alphastatin was sufficiently potent to suppress nude mice neovascularization. Daily administration of alphastatin produced significant tumor growth suppression [tumor volume:(612.65+/-23.45) microm(3),(1145.96+/-29.89) microm(3) vs(1771+/-31.05) microm(3) (P<0.05), tumor weight: (0.31+/-0.03) g, (0.12+/-0.02) g vs (0.67+/-0.02) g (P<0.05)]. Immunohistochemical studies of tumor tissues revealed decreased microvessel density in alphastatin-treated animals as compared with controls. Alphastatin significantly inhibited tumor endothelial cells SPK activity.

CONCLUSIONAlphastatin shows potent antiangiogenic properties in nude mice,which might be closely associated with down-regulation of tumor endothelial cells SPK activity.

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Cell Line, Tumor ; Fibrinogen ; pharmacology ; therapeutic use ; Humans ; Mice ; Mice, Nude ; Neovascularization, Pathologic ; prevention & control ; Stomach Neoplasms ; blood supply ; pathology ; Xenograft Model Antitumor Assays