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 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
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
The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk fa...The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk factor for acute pancreatitis and approximately 2% to 5% of cases of acute pancreatitis are related to drugs. We report on tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 40 years old woman with type 2 diabetes mellitus occurred by dexamethasone. She was treated with insulin infusion and fenofibrate, and goserelin acetate was started instead of tamoxifen after discharge from the hospital. Also, probable pathogenic hypotheses about the correlation between tamoxifen and dexamethasone induced type 2 diabetes mellitus on severe acute pancreatitis are provided. Clinicians should take care of risks of severe acute pancreatitis on using tamoxifen, especially for patients with dexamethasone induced diabetes mellitus. These individuals should undergo pre-post tamoxifen lipid screening and careful history taking of drugs, including dexamethasone.展开更多
Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. T...Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI： an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents （tamoxifen and a Src kinase family inhibitor known as PP2） that have been shown in our laboratory to produce neuroprotective （increase cell survival） and/or regenerative （axonal outgrowth） actions. The animal model used in our laboratory is adult female rat （N250 g） with a moderate contusion （12.5 mm） to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet （Innovative Research of America, Sarasota, FL, USA） or by intraperitoneal injections （1.5 mg/kg, every 3 days）, respectively, to produce a long-term effect （28 days）. Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regen- erative activity in vertebrates with SCI.展开更多
AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means o...AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+),mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM [15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group [(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31v1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg, (36.42±2.77) mm3, P= 0.037, P= 0.016 respectively] significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3], they were significantly less than that of control group [(634.23±119.41) mg, (507.45±93.34) mm3, P= 0.022, P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.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 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.
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The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk factor for acute pancreatitis and approximately 2% to 5% of cases of acute pancreatitis are related to drugs. We report on tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 40 years old woman with type 2 diabetes mellitus occurred by dexamethasone. She was treated with insulin infusion and fenofibrate, and goserelin acetate was started instead of tamoxifen after discharge from the hospital. Also, probable pathogenic hypotheses about the correlation between tamoxifen and dexamethasone induced type 2 diabetes mellitus on severe acute pancreatitis are provided. Clinicians should take care of risks of severe acute pancreatitis on using tamoxifen, especially for patients with dexamethasone induced diabetes mellitus. These individuals should undergo pre-post tamoxifen lipid screening and careful history taking of drugs, including dexamethasone.
基金partially supported by the MBRS-RISE Program(R25 GM061838)COBRE(5P20-GM103642)
文摘Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI： an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents （tamoxifen and a Src kinase family inhibitor known as PP2） that have been shown in our laboratory to produce neuroprotective （increase cell survival） and/or regenerative （axonal outgrowth） actions. The animal model used in our laboratory is adult female rat （N250 g） with a moderate contusion （12.5 mm） to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet （Innovative Research of America, Sarasota, FL, USA） or by intraperitoneal injections （1.5 mg/kg, every 3 days）, respectively, to produce a long-term effect （28 days）. Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regen- erative activity in vertebrates with SCI.
基金Supported by Scientific Foundation of Education Committee of Jiangsu Province. No.96039
文摘AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+),mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM [15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group [(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31v1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg, (36.42±2.77) mm3, P= 0.037, P= 0.016 respectively] significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3], they were significantly less than that of control group [(634.23±119.41) mg, (507.45±93.34) mm3, P= 0.022, P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.
