Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug re...Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.展开更多
Background: In Sudan, the common endocrine therapy tamoxifen is prescribed to HR-positive patients, which is associated with a variety of complications such as hot flashes, vaginal discharge, and vaginal dryness. Obje...Background: In Sudan, the common endocrine therapy tamoxifen is prescribed to HR-positive patients, which is associated with a variety of complications such as hot flashes, vaginal discharge, and vaginal dryness. Objective: This study aimed to determine the gynecological side effects of tamoxifen among Sudanese women who have been diagnosed with breast cancer in Khartoum, Sudan. Methods: A retrospective cross-sectional study was conducted at Alzara Hospital in Al Amal Toure Revere, Sudan. A convenience sample of individuals previously diagnosed with breast cancer attended refer clinic. From October 2020 to September 2021, all patients attending were checked for eligibility. Results: A total of 100 patients were enrolled in the study;60% of patients reported increased vaginal secretions after taking the drug, 28% reported normal vaginal secretions with no change, and 11% reported decreased secretions after taking the medication, while 22% developed vaginal bleeding, and 22% of the ultrasound results revealed endometrial masses among the study patients. Also, 54 percent of female patients experienced hot flashes after taking the medication, and 12% of women missed some doses of treatment. Conclusion: Tamoxifen results in several gynecological side effects in women with breast cancer. A high percentage of women in the study developed hot flashes, vaginal bleeding, and discharge, in addition to having ultrasound results showing endometrial masses among them.展开更多
BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP...BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.展开更多
Objective:To explore the best endometrial preparation scheme of freeze-thawed embryo transfer(FET)for patients with thin endometrium with kidney deficiency and blood stasis by comparing the clinical outcomes of three ...Objective:To explore the best endometrial preparation scheme of freeze-thawed embryo transfer(FET)for patients with thin endometrium with kidney deficiency and blood stasis by comparing the clinical outcomes of three endometrial preparation schemes of estradiol valerate tablets Hormone Replacement(HRT),Tamoxifen(TAM)and Endometrial Prescription combined with TAM(EP-TAM group).Method:Retrospective analysis of 318 patients with thin endometrium with kidney deficiency and blood stasis who underwent FET in Changle People's Hospital of Shandong Province,Shandong Maternal and Child Health Hospital,and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from September 2018 to March 2023,including 101 patients in HRT group(estradiol valerate tablets);108 patients in TAM group;109 patients in EP-TAM group.The cycle cancellation rate,intimal thickness,clinical pregnancy rate,embryo implantation rate,early abortion rate and ectopic pregnancy rate were compared among the three groups.Result:Cycle cancellation rates of TAM group and EP-TAM group were significantly lower than HRT group(8.3%,9.2%vs 17.8%,P<0.05).The intimal thickness of TAM group[(8.11±0.36)mm]and EP-TAM group[(8.21±0.40)mm]was significantly thicker than HRT group[(7.11±0.43)mm](P<0.05).The clinical pregnancy rate and implantation rate of TAM group and EP-TAM group were higher than HRT group,the early abortion rate and ectopic pregnancy rate were lower than HRT group,and EP-TAM group was more significant(P<0.05).Conclusion:Patients with thin endometrium underwent FET can try Endometrium Prescription combined with TAM(EP-TAM)to prepare the endometrium.展开更多
基金supported by the National Natural Science Foundation of China(81973839)High Level Chinese Medical Hospital Promotion Project-Special Project on Formulation R&D and New Drug Translation for Medical Institutions(HLCMHPP2023037)Upgrading the Development and Promotion of about 30 Integrated Chinese and Western Medicine Diagnosis and Treatment Programs(Guidelines for the Diagnosis and Treatment of Breast Cancer with the Combination of Traditional Chinese Medicine and Western Medicine)(ZYZB-2022-798).
文摘Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.
文摘Background: In Sudan, the common endocrine therapy tamoxifen is prescribed to HR-positive patients, which is associated with a variety of complications such as hot flashes, vaginal discharge, and vaginal dryness. Objective: This study aimed to determine the gynecological side effects of tamoxifen among Sudanese women who have been diagnosed with breast cancer in Khartoum, Sudan. Methods: A retrospective cross-sectional study was conducted at Alzara Hospital in Al Amal Toure Revere, Sudan. A convenience sample of individuals previously diagnosed with breast cancer attended refer clinic. From October 2020 to September 2021, all patients attending were checked for eligibility. Results: A total of 100 patients were enrolled in the study;60% of patients reported increased vaginal secretions after taking the drug, 28% reported normal vaginal secretions with no change, and 11% reported decreased secretions after taking the medication, while 22% developed vaginal bleeding, and 22% of the ultrasound results revealed endometrial masses among the study patients. Also, 54 percent of female patients experienced hot flashes after taking the medication, and 12% of women missed some doses of treatment. Conclusion: Tamoxifen results in several gynecological side effects in women with breast cancer. A high percentage of women in the study developed hot flashes, vaginal bleeding, and discharge, in addition to having ultrasound results showing endometrial masses among them.
文摘BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.
基金Shenzhen“Medical and Health Three Projects”Project Grant(SZZYSM 202106003)Shenzhen Bao’an District of Medical and Health Research Project(2023JD212)+1 种基金Shenzhen Bao’an District of Traditional Chinese Medicine Clinical Research Project(2023ZYYLCZX-12)Weifang Health Committee Scientific Research Project(wfwsjk-2023-140).
文摘Objective:To explore the best endometrial preparation scheme of freeze-thawed embryo transfer(FET)for patients with thin endometrium with kidney deficiency and blood stasis by comparing the clinical outcomes of three endometrial preparation schemes of estradiol valerate tablets Hormone Replacement(HRT),Tamoxifen(TAM)and Endometrial Prescription combined with TAM(EP-TAM group).Method:Retrospective analysis of 318 patients with thin endometrium with kidney deficiency and blood stasis who underwent FET in Changle People's Hospital of Shandong Province,Shandong Maternal and Child Health Hospital,and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from September 2018 to March 2023,including 101 patients in HRT group(estradiol valerate tablets);108 patients in TAM group;109 patients in EP-TAM group.The cycle cancellation rate,intimal thickness,clinical pregnancy rate,embryo implantation rate,early abortion rate and ectopic pregnancy rate were compared among the three groups.Result:Cycle cancellation rates of TAM group and EP-TAM group were significantly lower than HRT group(8.3%,9.2%vs 17.8%,P<0.05).The intimal thickness of TAM group[(8.11±0.36)mm]and EP-TAM group[(8.21±0.40)mm]was significantly thicker than HRT group[(7.11±0.43)mm](P<0.05).The clinical pregnancy rate and implantation rate of TAM group and EP-TAM group were higher than HRT group,the early abortion rate and ectopic pregnancy rate were lower than HRT group,and EP-TAM group was more significant(P<0.05).Conclusion:Patients with thin endometrium underwent FET can try Endometrium Prescription combined with TAM(EP-TAM)to prepare the endometrium.