Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for...Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.展开更多
BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a r...BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a rare,serious adverse event requiring drug discontinuation.CASE SUMMARY We report a case of tamoxifen-induced thrombocytopenia in a 51-year-old preme-nopausal woman with breast cancer,occurring within 4 weeks of initiating adju-vant tamoxifen therapy.Platelet counts normalized after drug cessation,but th-rombocytopenia recurred upon rechallenge,leading to permanent disconti-nuation.CONCLUSION This case underscores the need for regular complete blood count monitoring in patients on tamoxifen to detect rare hematologic adverse events promptly.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
It was reported previously that tamoxifen （TAM） could increase the intracellular accumulation of drug-loaded liposomes, but the exact mechanism is unknown although it was supposed that TAM might enhance the cell upt...It was reported previously that tamoxifen （TAM） could increase the intracellular accumulation of drug-loaded liposomes, but the exact mechanism is unknown although it was supposed that TAM might enhance the cell uptake by inhibiting the drug efflux caused by P-glycoprotein （P-gp）. To identify the mechanism of increased cellular uptake of liposomes induced by tamoxifen, PEGgylated liposomes （SSL） ofP-gp-substrate doxorubicin （DOX） or non-P-gp-substrate coumarin （Cou） were prepared with or without TAM. The cell uptake of these liposome systems was investigated in cell lines with different P-gp-expressing levels and the interaction of TAM with lipid membrane was also studied. As the results, the co-encapsulation of TAM with DOX-SSL increased the intracellular uptake in all three tumor cell lines. In P-gp-highly-expressing MCF-7/Adr cells, the effect of TAM was the strongest and in negative control Hela cells, the impact weakened but still significant. The improvement was also observed in the cellular uptake of Cou-SSL. Surface plasmon resonance （SPR） studies demonstrated that TAM-SSL exhibited a much stronger atYmity with model biomembrane compared with empty SSL, and ft^her test with isothermal titration calorimetry （ITC） showed that free TAM had an obvious interaction with lipid membrane. In conclusion, TAM could increase the affinity of liposomes with biomembrane and enhance the intracellular accumulation of liposomes via both TAM-mediated P-gp inhibition and the increased interaction between hydrophobic TAM molecules and lipid membrane.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
文摘Objective Selective estrogen receptor modulators(SERMs)have demonstrated efficacy in the treatment of hypogonadism in males and male factor infertility.Two SERMs,clomiphene citrate and tamoxifen,are now prescribed for off-label use to treat both conditions in males.However,existing literature compares mixed protocols with active management.We aimed to conduct a meta-analysis to evaluate the effect of clomiphene and tamoxifen versus placebo on natural pregnancy rates.Methods We conducted a comprehensive systematic review of electronic databases:MEDLINE,PubMed/PMC,EMBASE,CINAHL,Cochrane Central Register of Controlled Trials(CENTRAL),Scopus,Google Scholar,and Web of Science.Articles satisfying all selection criteria were analyzed.The primary outcome was the incidence of pregnancy after receiving the treatment.Secondary outcomes included serum follicle-stimulating hormone,luteinizing hormone,and testosterone levels,and sperm count and motility.We calculated the pooled odds ratio,risk ratio,and risk difference to ascertain possible alterations in the direction of the pooled effect size.Results Ten randomized controlled trials were ultimately included and underwent data extraction.Clomiphene citrate and placebo groups had similar pregnancy rates(10.4%and 7.1%,respectively;odds ratio 1.30[95%confidence interval 0.27–6.17];p=0.74).No meta-analysis could be calculated for pregnancy rates in tamoxifen versus placebo groups.Heterogeneity among the studies of both SERMs ranged from low to high.Conclusion Although clomiphene citrate and tamoxifen are often used off-label for the treatment of male infertility secondary to hypogonadism,studies of SERMs in the treatment of idiopathic male factor infertility are limited and heterogenous,preventing this meta-analysis from investigating the efficacy of SERMs on male infertility.The effect of clomiphene citrate or tamoxifen on the pregnancy rate remains uncertain.
文摘BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a rare,serious adverse event requiring drug discontinuation.CASE SUMMARY We report a case of tamoxifen-induced thrombocytopenia in a 51-year-old preme-nopausal woman with breast cancer,occurring within 4 weeks of initiating adju-vant tamoxifen therapy.Platelet counts normalized after drug cessation,but th-rombocytopenia recurred upon rechallenge,leading to permanent disconti-nuation.CONCLUSION This case underscores the need for regular complete blood count monitoring in patients on tamoxifen to detect rare hematologic adverse events promptly.
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National Natural Science Foundation of China(Grant No.81130059)
文摘It was reported previously that tamoxifen （TAM） could increase the intracellular accumulation of drug-loaded liposomes, but the exact mechanism is unknown although it was supposed that TAM might enhance the cell uptake by inhibiting the drug efflux caused by P-glycoprotein （P-gp）. To identify the mechanism of increased cellular uptake of liposomes induced by tamoxifen, PEGgylated liposomes （SSL） ofP-gp-substrate doxorubicin （DOX） or non-P-gp-substrate coumarin （Cou） were prepared with or without TAM. The cell uptake of these liposome systems was investigated in cell lines with different P-gp-expressing levels and the interaction of TAM with lipid membrane was also studied. As the results, the co-encapsulation of TAM with DOX-SSL increased the intracellular uptake in all three tumor cell lines. In P-gp-highly-expressing MCF-7/Adr cells, the effect of TAM was the strongest and in negative control Hela cells, the impact weakened but still significant. The improvement was also observed in the cellular uptake of Cou-SSL. Surface plasmon resonance （SPR） studies demonstrated that TAM-SSL exhibited a much stronger atYmity with model biomembrane compared with empty SSL, and ft^her test with isothermal titration calorimetry （ITC） showed that free TAM had an obvious interaction with lipid membrane. In conclusion, TAM could increase the affinity of liposomes with biomembrane and enhance the intracellular accumulation of liposomes via both TAM-mediated P-gp inhibition and the increased interaction between hydrophobic TAM molecules and lipid membrane.
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.
