Ssociated with cancer tissue, depth of invasion and lymph node metastasis in AFPGC. Clinically, patients with AFPGC have poor prognosis [1,9,10]. We confirmed that the prognosis was worse for patients with than without AFP who were matched by cancer stage. Furthermore, the survival of patients with both AFP and STAT3 positivity was significantly worse than those with AFP or STAT3 positivity alone. Thus, in this specific type of gastric cancer, STAT3 appears to have an important role in cell survival and proliferation. STAT3 expression in AFPGC may explain the clinically aggressive behavior of AFPGC, and STAT3 expression may be a useful progression indicator, if validated by extensive prospective studies in larger cohorts. Downregulation of AFP and STAT3 expression may represent a relevant therapeutic strategy in AFPGC. Regarding the relationship between AFP production and STAT3 expression, there is no Met-Enkephalin available report describing the underlying mechanisms to date.It has been reported that the AFP expression in gastric cancer is due to the lack of the transcription factor ATBF1 [47]. In addition,ATBF1,as a tumor suppressor gene, enhancesthe suppression of STAT3 signaling by interaction with PIAS3 [48].Therefore, it is reasonable to consider that inactivation of the ATBF1 gene in AFPGC,through mutation or reduced expression, may be allow AFPGC cells to produce AFP protein and overexpres STAT3. To clarify which factors are involved in AFP production and STAT3 expression,further study is needed. In conclusion, As2O3 can inhibit AFPGC cell line FU97 growth and induce apoptosis. The possible mechanisms were related to downregulation of AFP and STAT3 and STAT3 targeting antiapoptotic gene Bcl-2 and upregulating the tumor suppressor gene Bax (Fig. 7). The expression of STAT3 in AFPGC plays an important role in tumour invasion and prognosis. As2O3 may be a possible new adjuvant drug in treatment of AFPGC. The present study provides some theoretical basis for its clinical use worthy of further study.Author ContributionsConceived and designed the experiments: Y-SW Y-FJ. Performed the experiments: Y-FJ X-LM S-YH YZ S-HS M-XZ H-MG XC. Analyzed the data: Y-SW Y-FJ D-JX. Contributed reagents/materials/analysis tools: YFJ. Wrote the paper: Y-FJ D-ZL Y-SW X-LM.
D -Tetrahydrocannabinol (THC), the main active component of the hemp plant Cannabis sativa [1], exerts a wide variety of biological effects by mimicking endogenous substances ?the endocannabinoids ?that bind to and activate specific cannabinoid receptors [2]. So far, two G protein oupled cannabinoid-specific receptors have been cloned and characterized from MedChemExpress Fruquintinib mammalian tissues: CB1, abundantly expressed in the brain and at many peripheral sites, and CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells [2,3]. One of the most active areas of research in the cannabinoid field is the study of the potential application of cannabinoids in the treatment of different pathologies [4,5]. Among these therapeuticapplications, cannabinoids are being investigated as anti-tumoral agents [6,7]. Thus, cannabinoid administration curbs the growth of several types of tumor xenografts in rats and mice [6,7] including gliomas [8?0]. Based on this preclinical evidence, a pilot clinical trial has been recently run to investigate the antitumor action of THC on recurrent gliomas [11]. The mechanism of THC anti-tumoral action relies on the ability of this compound to: (i) promote.Ssociated with cancer tissue, depth of invasion and lymph node metastasis in AFPGC. Clinically, patients with AFPGC have poor prognosis [1,9,10]. We confirmed that the prognosis was worse for patients with than without AFP who were matched by cancer stage. Furthermore, the survival of patients with both AFP and STAT3 positivity was significantly worse than those with AFP or STAT3 positivity alone. Thus, in this specific type of gastric cancer, STAT3 appears to have an important role in cell survival and proliferation. STAT3 expression in AFPGC may explain the clinically aggressive behavior of AFPGC, and STAT3 expression may be a useful progression indicator, if validated by extensive prospective studies in larger cohorts. Downregulation of AFP and STAT3 expression may represent a relevant therapeutic strategy in AFPGC. Regarding the relationship between AFP production and STAT3 expression, there is no available report describing the underlying mechanisms to date.It has been reported that the AFP expression in gastric cancer is due to the lack of the transcription factor ATBF1 [47]. In addition,ATBF1,as a tumor suppressor gene, enhancesthe suppression of STAT3 signaling by interaction with PIAS3 [48].Therefore, it is reasonable to consider that inactivation of the ATBF1 gene in AFPGC,through mutation or reduced expression, may be allow AFPGC cells to produce AFP protein and overexpres STAT3. To clarify which factors are involved in AFP production and STAT3 expression,further study is needed. In conclusion, As2O3 can inhibit AFPGC cell line FU97 growth and induce apoptosis. The possible mechanisms were related to downregulation of AFP and STAT3 and STAT3 targeting antiapoptotic gene Bcl-2 and upregulating the tumor suppressor gene Bax (Fig. 7). The expression of STAT3 in AFPGC plays an important role in tumour invasion and prognosis. As2O3 may be a possible new adjuvant drug in treatment of AFPGC. The present study provides some theoretical basis for its clinical use worthy of further study.Author ContributionsConceived and designed the experiments: Y-SW Y-FJ. Performed the experiments: Y-FJ X-LM S-YH YZ S-HS M-XZ H-MG XC. Analyzed the data: Y-SW Y-FJ D-JX. Contributed reagents/materials/analysis tools: YFJ. Wrote the paper: Y-FJ D-ZL Y-SW X-LM.
D -Tetrahydrocannabinol (THC), the main active component of the hemp plant Cannabis sativa [1], exerts a wide variety of biological effects by mimicking endogenous substances ?the endocannabinoids ?that bind to and activate specific cannabinoid receptors [2]. So far, two G protein oupled cannabinoid-specific receptors have been cloned and characterized from mammalian tissues: CB1, abundantly expressed in the brain and at many peripheral sites, and CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells [2,3]. One of the most active areas of research in the cannabinoid field is the study of the potential application of cannabinoids in the treatment of different pathologies [4,5]. Among these therapeuticapplications, cannabinoids are being investigated as anti-tumoral agents [6,7]. Thus, cannabinoid administration curbs the growth of several types of tumor xenografts in rats and mice [6,7] including gliomas [8?0]. Based on this preclinical evidence, a pilot clinical trial has been recently run to investigate the antitumor action of THC on recurrent gliomas [11]. The mechanism of THC anti-tumoral action relies on the ability of this compound to: (i) promote.
