Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability...Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier(SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase Ⅲ trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events andit has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.展开更多
There is currently no effective treatment for the Ebola virus(EBOV)thus far.Most drugs and vaccines developed to date have not yet been approved for human trials.Two FDA-approved c-AbI1 tyrosine kinase inhibitors Glee...There is currently no effective treatment for the Ebola virus(EBOV)thus far.Most drugs and vaccines developed to date have not yet been approved for human trials.Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles;however,their clinical dosages are much lower than the dosages required for effective EBOV suppression.Anα-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion.Additionally,the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90%of treated mice survived after Clomiphene/Toremifene treatments.However,the uptake efficiency of Clomiphene by oral administration is very low.Thus,I propose a hypothetical treatment protocol to treat Ebola virus infection with a cumulative use of both Miglustat and Toremifene to inhibit the virus effectively and synergistically.EBOV infection induces massive apoptosis of peripheral lymphocytes.Also,cytolysis of endothelial cells triggers disseminated intravascular coagulation(DIC)and subsequent multiple organ failures.Therefore,blood transfusions and active treatments with FDA-approved drugs to treat DIC are also recommended.展开更多
文摘Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier(SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase Ⅲ trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events andit has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.
基金We thank LetPub for its linguistic assistance during the preparation of this manuscriptThis work was supported by the National Natural Science Foundation of China(31300207)+1 种基金the Preeminent Youth Fund of Sichuan Province(2015JQO045)the Support Program of Sichuan Agricultural University(03570305).
文摘There is currently no effective treatment for the Ebola virus(EBOV)thus far.Most drugs and vaccines developed to date have not yet been approved for human trials.Two FDA-approved c-AbI1 tyrosine kinase inhibitors Gleevec and Tasigna block the release of viral particles;however,their clinical dosages are much lower than the dosages required for effective EBOV suppression.Anα-1,2-glucosidase inhibitor Miglustat has been shown to inhibit EBOV particle assembly and secretion.Additionally,the estrogen receptor modulators Clomiphene and Toremifene prevent membrane fusion of EBOV and 50-90%of treated mice survived after Clomiphene/Toremifene treatments.However,the uptake efficiency of Clomiphene by oral administration is very low.Thus,I propose a hypothetical treatment protocol to treat Ebola virus infection with a cumulative use of both Miglustat and Toremifene to inhibit the virus effectively and synergistically.EBOV infection induces massive apoptosis of peripheral lymphocytes.Also,cytolysis of endothelial cells triggers disseminated intravascular coagulation(DIC)and subsequent multiple organ failures.Therefore,blood transfusions and active treatments with FDA-approved drugs to treat DIC are also recommended.
