Background: Chemotherapy induced mucositis is one of the deterring factors influencing adherence to cancer treatment. Sodium bicarbonate mouth wash was recently shown to increase patients’ compliance. However, the co...Background: Chemotherapy induced mucositis is one of the deterring factors influencing adherence to cancer treatment. Sodium bicarbonate mouth wash was recently shown to increase patients’ compliance. However, the cost implication of this strategy was never explored. Aim: This study is designed to explore the compounding of sodium bicarbonate 2% mouth wash from sodium bicarbonate powder USP and commercially procured intravenous solution, and to determine the estimated cost implication for patients using this strategy. Materials and Methods: Sodium bicarbonate 2% were compounded using commercially procured sterile intravenous 8.4% solution and powder USP, diluted and dissolved in sterile water for irrigation respectively. The estimated cost savings between the 2 methods were compared to each other as well as to savings from when used in preventing or in adjuvant therapy for chemotherapy induced mucositis. Ethical approval not required by UVA Institutional Review Board. Study conducted according to the International Standards of Good Practice. Result: We came up with a new recipe, sodium bicarbonate 2% mouth wash using commercially procured sterile liquid formulation. Due to shortage, we compounded with sodium bicarbonate powder USP. Using USP 795 regulation, we assigned 14 days beyond use date with refrigeration to these formulations. These formulations resulted in estimated cost savings of $3597.52 and $3686.56 respectively if patients were to be treated for chemotherapy induced mucositis for 21 days. When compared to commercially procured sterile liquid formulation, the use of powder USP, will lead to additional estimated 60 to 66.67% savings for patients. Conclusion: By using sodium bicarbonate powder or solution to compound a 2% mouth wash, we came up with a cheap product that could be used by patients in the moment in the hospital. We were also able to suggest ways that an estimated cost savings for patients undergoing cancer treatment that use this product can be computed.展开更多
Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and inde...Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal propeptide were fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site was presented in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 were shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) which induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 Nterminal fragments inhibited TGF-β signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. Although, only non-secreted form of IGFBP-3 is involved in inducing apoptosis in PC-3 cells via caspase 8 and caspase 9 activation pathways but both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Non-secreted intact IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9 pathways. Modulation in STAT-1 and TGF-β pathways may also be important for IGFBP-3 induced apoptosis in PC-3 cells in general. These studies clearly demonstrate that secreted and non-secreted FL and 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.展开更多
文摘Background: Chemotherapy induced mucositis is one of the deterring factors influencing adherence to cancer treatment. Sodium bicarbonate mouth wash was recently shown to increase patients’ compliance. However, the cost implication of this strategy was never explored. Aim: This study is designed to explore the compounding of sodium bicarbonate 2% mouth wash from sodium bicarbonate powder USP and commercially procured intravenous solution, and to determine the estimated cost implication for patients using this strategy. Materials and Methods: Sodium bicarbonate 2% were compounded using commercially procured sterile intravenous 8.4% solution and powder USP, diluted and dissolved in sterile water for irrigation respectively. The estimated cost savings between the 2 methods were compared to each other as well as to savings from when used in preventing or in adjuvant therapy for chemotherapy induced mucositis. Ethical approval not required by UVA Institutional Review Board. Study conducted according to the International Standards of Good Practice. Result: We came up with a new recipe, sodium bicarbonate 2% mouth wash using commercially procured sterile liquid formulation. Due to shortage, we compounded with sodium bicarbonate powder USP. Using USP 795 regulation, we assigned 14 days beyond use date with refrigeration to these formulations. These formulations resulted in estimated cost savings of $3597.52 and $3686.56 respectively if patients were to be treated for chemotherapy induced mucositis for 21 days. When compared to commercially procured sterile liquid formulation, the use of powder USP, will lead to additional estimated 60 to 66.67% savings for patients. Conclusion: By using sodium bicarbonate powder or solution to compound a 2% mouth wash, we came up with a cheap product that could be used by patients in the moment in the hospital. We were also able to suggest ways that an estimated cost savings for patients undergoing cancer treatment that use this product can be computed.
文摘Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induce apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal propeptide were fused to YFP and expressed in PC-3 human prostate cancer cells. In some cases, the putative IGF-binding site was presented in full length IGFBP-3 and its N-terminal fragment was also mutated. Extent of apoptosis was quantified using FACS. Up-regulation of total Stat-1 and activation of phospho-Stat-1 were shown by western blot. TGF-β signal was measured by luciferase reporter assay. Results from inhibitor studies indicated that both the Caspase 8 and caspase 9 pathways are involved in IGFBP-3 (non-secreted form) which induced apoptosis in PC-3 cells. Exogenous addition of IGFBP-3 to PC-3 cells increased Stat-1 protein expression/tyrosine phosphorylation. Interestingly, results also showed that knockdown of Stat-1 by siRNA potentiated the IGFBP-3 induced apoptosis in PC-3 cells. In addition, both full-length IGFBP-3 and its 1-97 Nterminal fragments inhibited TGF-β signaling in these cells. This is the first report that compares the signal transduction pathways involved in apoptotic pathways mediated by IGFBP-3 in PC-3 human prostate cancer cells. Non-secreted form of full length IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9. Although, only non-secreted form of IGFBP-3 is involved in inducing apoptosis in PC-3 cells via caspase 8 and caspase 9 activation pathways but both secreted and non-secreted forms of IGFBP-3 are involved in modulating Stat-1 and TGF-β pathways to induce apoptotic actions in PC-3 cells. Non-secreted intact IGFBP-3 and its N-terminal fragments induced apoptosis in PC-3 cells via activation of caspase 8 and caspase 9 pathways. Modulation in STAT-1 and TGF-β pathways may also be important for IGFBP-3 induced apoptosis in PC-3 cells in general. These studies clearly demonstrate that secreted and non-secreted FL and 1-97 N-terminal fragments induce apoptosis in PC-3 cells by regulating different mechanistic pathways.
