In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of ...Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of imatinib to ensure the efficacy and safety of imatinib therapy. In the present study, an HPLC-UV method was developed and validated for quantitating imatinib in the plasma of Chinese GIST patients. The samples were processed by protein precipitation and then mixed with a neutralizing agent(1.4 gK2CO3 and 0.65g KCl dissolved in 5mL ultrapure water). The chromatographic separation was performed on an Inert Sustain C18 column(250 mm×4.6 mm, 5 μM) maintained at 40 ℃ utilizing the mobile phase consisted of 25 m MNH4H2PO4(pH 8.0)–acetonitrile(61:39, v/v) at a flow rate of 1 m L/min, with an ultraviolet detector set at 265 nm. The method was fully validated according to the published guidelines. The plotted calibration curves were all linear within the range of 50 to 10 000 ng/m L. The validation results of the intra-day and inter-day accuracies and precisions ranged from –5.81% to 6.33%. The extraction recoveries were within the range of 92.38% to 97.86%. All the results of stability studies were all consistent with the acceptance criteria of within ±15%. Finally, the method was successfully applied to trough plasma concentration monitoring of imatinib in 150 Chinese GIST patients orally administrated with imatinib. Incurred sample reanalysis was conducted, results of which were also in accordance with the acceptance criteria of within ±20%.展开更多
Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the princ...Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term(3 h)or long term(72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the m RNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin(50μM)reversed the resistance of MCF-7/DOX cells to doxorubicin(DOX)with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR1 at the m RNA level after long-term(72 h)incubation.After short-term(3 h)incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.展开更多
The multidisciplinary approach is beneficial to the treatment of gastrointestinal stromal tumors(GISTs).However,pharmacists are seldom incorporated into a multidisciplinary team(MDT)of GIST.In the present study,we eva...The multidisciplinary approach is beneficial to the treatment of gastrointestinal stromal tumors(GISTs).However,pharmacists are seldom incorporated into a multidisciplinary team(MDT)of GIST.In the present study,we evaluated the clinical and economic benefits of a pharmacist in an MDT of GIST.This was a retrospective study that included 240 GIST patients receiving imatinib therapy.The GIST MDT pharmacist developed and validated an HPLC method to monitor the trough concentrations of imatinib in GIST patients.Besides,the pharmacist also provided patient education and pharmaceutical care services and collected the data for analysis.The 240 GIST patients received the services provided by the pharmacist.The trough concentrations in 25.42%of the 240 patients were less than 1100 ng/m L.The main genotypes of 121 in the 240 patients were KIT exon 11 mutations,wild type,and KIT exon 9 mutations.Moreover,13 GIST patients with trough concentrations less than 1100 ng/m L were confirmed to have low compliance.The adverse reactions were primarily mild and tolerable,except that 13 GIST patients were adjusted to lower doses because of the intolerable adverse reactions.The daily cost could be lowered by monitoring the trough concentrations and dose reductions.Collectively,a pharmacist included in a GIST MDT could increase the compliance of Chinese GIST patients to imatinib therapy and improve the efficacy,safety,and economy of imatinib therapy.展开更多
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
文摘Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of imatinib to ensure the efficacy and safety of imatinib therapy. In the present study, an HPLC-UV method was developed and validated for quantitating imatinib in the plasma of Chinese GIST patients. The samples were processed by protein precipitation and then mixed with a neutralizing agent(1.4 gK2CO3 and 0.65g KCl dissolved in 5mL ultrapure water). The chromatographic separation was performed on an Inert Sustain C18 column(250 mm×4.6 mm, 5 μM) maintained at 40 ℃ utilizing the mobile phase consisted of 25 m MNH4H2PO4(pH 8.0)–acetonitrile(61:39, v/v) at a flow rate of 1 m L/min, with an ultraviolet detector set at 265 nm. The method was fully validated according to the published guidelines. The plotted calibration curves were all linear within the range of 50 to 10 000 ng/m L. The validation results of the intra-day and inter-day accuracies and precisions ranged from –5.81% to 6.33%. The extraction recoveries were within the range of 92.38% to 97.86%. All the results of stability studies were all consistent with the acceptance criteria of within ±15%. Finally, the method was successfully applied to trough plasma concentration monitoring of imatinib in 150 Chinese GIST patients orally administrated with imatinib. Incurred sample reanalysis was conducted, results of which were also in accordance with the acceptance criteria of within ±20%.
文摘Overexpression of P-glycoprotein(P-gp),encoded by the MDR1 gene,in tumor cells curtails the efficacy of chemotherapy,leading to multidrug resistance(MDR),which can be reversed by the P-gp inhibitor.Capsaicin,the principal pungent component of hot chili,is a reported P-gp inhibitor with anti-cancer properties.In the present study,we aimed to evaluate the MDR reversal effect of capsaicin.The MCF-7/DOX cells were treated with capsaicin for a short term(3 h)or long term(72 h).The cytotoxicity studies were completed by using the SRB method.RT-PCR method was utilized to evaluate the effect of capsaicin on the expression of MDR1 at the m RNA level.The accumulation and subcellular distribution studies were implemented to further investigate the reversal effect of capsaicin.The effect of capsaicin on the ATP production of mitochondria was also evaluated.The results of the cytotoxicity study indicated that capsaicin(50μM)reversed the resistance of MCF-7/DOX cells to doxorubicin(DOX)with the reversal fold of 4.68,and concentration-dependently down-regulated the expression of MDR1 at the m RNA level after long-term(72 h)incubation.After short-term(3 h)incubation,capsaicin reversibly and concentration-dependently increased the accumulation of DOX into MCF-7/DOX cells and induced a different subcellular distribution of DOX compared with verapamil as a positive control.The ATP production of mitochondria was also concentration-dependently inhibited by capsaicin.In conclusion,capsaicin was capable of reversing the resistance of MCF-7/DOX cells to DOX,making it a promising lead compound for MDR reversal.
基金Chongqing Science and Technology Bureau and Chongqing Health Commission(Grant No.2021-MSXM335 and 2020GDRC009)。
文摘The multidisciplinary approach is beneficial to the treatment of gastrointestinal stromal tumors(GISTs).However,pharmacists are seldom incorporated into a multidisciplinary team(MDT)of GIST.In the present study,we evaluated the clinical and economic benefits of a pharmacist in an MDT of GIST.This was a retrospective study that included 240 GIST patients receiving imatinib therapy.The GIST MDT pharmacist developed and validated an HPLC method to monitor the trough concentrations of imatinib in GIST patients.Besides,the pharmacist also provided patient education and pharmaceutical care services and collected the data for analysis.The 240 GIST patients received the services provided by the pharmacist.The trough concentrations in 25.42%of the 240 patients were less than 1100 ng/m L.The main genotypes of 121 in the 240 patients were KIT exon 11 mutations,wild type,and KIT exon 9 mutations.Moreover,13 GIST patients with trough concentrations less than 1100 ng/m L were confirmed to have low compliance.The adverse reactions were primarily mild and tolerable,except that 13 GIST patients were adjusted to lower doses because of the intolerable adverse reactions.The daily cost could be lowered by monitoring the trough concentrations and dose reductions.Collectively,a pharmacist included in a GIST MDT could increase the compliance of Chinese GIST patients to imatinib therapy and improve the efficacy,safety,and economy of imatinib therapy.
