Melatonin is an established hormone supplement and has been well recognized for its effect on the circadian cycle to improve sleep, REM (rapid eye movement), and aiding in jetlag recovery. The utility of melatonin ext...Melatonin is an established hormone supplement and has been well recognized for its effect on the circadian cycle to improve sleep, REM (rapid eye movement), and aiding in jetlag recovery. The utility of melatonin extends beyond sleep aid, however. This hormone also possesses less well-known antioxidant action and even robust anticancer activity. Melatonin may be a key supplement for addressing age-related neurologic decline while serving as a valuable adjunctive cancer treatment that reduces drug resistance in tumors and downregulates angiogenesis. In immunotherapy, melatonin activates Natural Killer (NK) cells nested within tumoral tissue and does not have the side effect profile of other immunoreactive agents used for chemotherapy. Since melatonin is found in high concentrations in the brain and other hormone-linked tissues, the relevance of melatonin is increased for the treatment of estrogen-linked cancers. The immunomodulatory effect of melatonin may also help with chronic inflammation seen in patients with autoimmune disorders. All of these effects together represent a unique and versatile therapeutic agent for integrative medicine. No other commercially available drug possesses all of these therapeutic mechanisms while having a very minimal side </span><span style="font-family:Verdana;">effect profile and being considered overall to be safe to use. Currently, melatonin is underutilized in medicine, especially in the field of integrative oncology and represents a crucial supportive adjuvant to improve the lives of patients</span><span style="font-family:Verdana;">.展开更多
The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient delivery.Herein,a localized and sustained-release thermo-sensitive hydrogel was developed for the in...The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient delivery.Herein,a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL.Based on the amphiphilic structure of poly(N-isopropylacrylamide-co-acrylic acid)-g-F68 copolymer,it was able to form nano-micelles to efficiently encapsulate TPL,and then turn into a hydrogel at 37C.TPL@nano-gel exhibited a sustained drug release profile in vitro and a stronger anticancer effect caused by"two strikes".The"first strike"was its enhanced cytotoxicity compared to free TPL,due to the enhanced pro-apoptosis effect observed in both MDA-MB-231 and MCF-7 cells caused by the regulation of endogenous mitochondrial pathways.Furthermore,TPL@nano-gel exhibited a"second-strike"through its anti-angiogenesis capabilities mediated through VEGFR-2 signaling inhibition.As expected,after intra-tumoral injection at a 0.45 mg/kg TPL-equivalent dose three times over 14 days in 4 T1 tumor-bearing mice,TPL@nano-gel led to lower systemic toxicity and higher antitumor efficacy compared to multiple injections of TPL.In this regard,these findings indicate that this injectable thermo-responsive hydrogel carries great potential for TPL as a safe and effective cancer therapy.展开更多
文摘Melatonin is an established hormone supplement and has been well recognized for its effect on the circadian cycle to improve sleep, REM (rapid eye movement), and aiding in jetlag recovery. The utility of melatonin extends beyond sleep aid, however. This hormone also possesses less well-known antioxidant action and even robust anticancer activity. Melatonin may be a key supplement for addressing age-related neurologic decline while serving as a valuable adjunctive cancer treatment that reduces drug resistance in tumors and downregulates angiogenesis. In immunotherapy, melatonin activates Natural Killer (NK) cells nested within tumoral tissue and does not have the side effect profile of other immunoreactive agents used for chemotherapy. Since melatonin is found in high concentrations in the brain and other hormone-linked tissues, the relevance of melatonin is increased for the treatment of estrogen-linked cancers. The immunomodulatory effect of melatonin may also help with chronic inflammation seen in patients with autoimmune disorders. All of these effects together represent a unique and versatile therapeutic agent for integrative medicine. No other commercially available drug possesses all of these therapeutic mechanisms while having a very minimal side </span><span style="font-family:Verdana;">effect profile and being considered overall to be safe to use. Currently, melatonin is underutilized in medicine, especially in the field of integrative oncology and represents a crucial supportive adjuvant to improve the lives of patients</span><span style="font-family:Verdana;">.
基金the financial support from the National Natural Science Foundation of China(Grant Nos.81973662and 8170371)Scientific Development Program of Sichuan Province(2019JDJQ0049,China)+1 种基金China Postdoctoral Science Foundation(Grant Nos.2017M612930 and 2019T120817)Young Elite Scientists Sponsorship Program by CAST(2018QNRC1-01,China)
文摘The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient delivery.Herein,a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL.Based on the amphiphilic structure of poly(N-isopropylacrylamide-co-acrylic acid)-g-F68 copolymer,it was able to form nano-micelles to efficiently encapsulate TPL,and then turn into a hydrogel at 37C.TPL@nano-gel exhibited a sustained drug release profile in vitro and a stronger anticancer effect caused by"two strikes".The"first strike"was its enhanced cytotoxicity compared to free TPL,due to the enhanced pro-apoptosis effect observed in both MDA-MB-231 and MCF-7 cells caused by the regulation of endogenous mitochondrial pathways.Furthermore,TPL@nano-gel exhibited a"second-strike"through its anti-angiogenesis capabilities mediated through VEGFR-2 signaling inhibition.As expected,after intra-tumoral injection at a 0.45 mg/kg TPL-equivalent dose three times over 14 days in 4 T1 tumor-bearing mice,TPL@nano-gel led to lower systemic toxicity and higher antitumor efficacy compared to multiple injections of TPL.In this regard,these findings indicate that this injectable thermo-responsive hydrogel carries great potential for TPL as a safe and effective cancer therapy.
