In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefo...In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.展开更多
Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated ...Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failu...Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy,and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic.The present study aimed to develop an advanced PDX model,namely MiniPDX,for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.Methods:We developed a rapid in vivo drug sensitivity assay,OncoVee®MiniPDX,for screening clinically relevant regimens for cancer.In this model,patient-derived tumor cells were arrayed within hollow fiber capsules,implanted subcutaneously into mice and cultured for 7 days.The cellular activity morphology and pharmacokinetics were systematically evaluated.MiniPDX performance(sensitivity,specificity,positive and negative predictive values)was examined using PDX as the reference.Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively.The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.Results:Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors.Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients,including 14 gastric cancer,10 lung cancer and 2 pancreatic cancer.The positive predictive value of MiniPDX was 92%,and the negative predictive value was 81%with a sensitivity of 80%and a specificity of 93%.Through expanding to clinical tumor samples,Min-iPDX assay showed potential of wide clinical application.Conclusions:Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens.The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay,as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.展开更多
文摘In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.
文摘Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
文摘Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy,and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic.The present study aimed to develop an advanced PDX model,namely MiniPDX,for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.Methods:We developed a rapid in vivo drug sensitivity assay,OncoVee®MiniPDX,for screening clinically relevant regimens for cancer.In this model,patient-derived tumor cells were arrayed within hollow fiber capsules,implanted subcutaneously into mice and cultured for 7 days.The cellular activity morphology and pharmacokinetics were systematically evaluated.MiniPDX performance(sensitivity,specificity,positive and negative predictive values)was examined using PDX as the reference.Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively.The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.Results:Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors.Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients,including 14 gastric cancer,10 lung cancer and 2 pancreatic cancer.The positive predictive value of MiniPDX was 92%,and the negative predictive value was 81%with a sensitivity of 80%and a specificity of 93%.Through expanding to clinical tumor samples,Min-iPDX assay showed potential of wide clinical application.Conclusions:Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens.The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay,as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.
