The literature on cervical embryonal rhabdomyosarcoma(RMS)is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer.Specifically,the Pub Med,Web of Sc...The literature on cervical embryonal rhabdomyosarcoma(RMS)is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer.Specifically,the Pub Med,Web of Science and Google Scholar databases,were searched to find published case series on cervical embryonal RMS reporting on four or more patients,of whom at least one was>40-year-old.Theχ^(2 )test was used to assess heterogeneity.Five articles published between 1986 and 2013 were identified,reporting on a total of 47 patients,of whom 22(46.8%)were older and 25(53.2%)younger than 40-year-old.Although the two age groups did not differ significantly by stage of disease or radiotherapy treatment,the older age groupreceived less chemotherapy(55%vs 90%,P=0.008)and had more hysterectomy(86%vs 43%,P=0.009).Follow-up data was missing for 18/47(38.3%)patients.Among the 29 patients with follow-up data,survival was shorter in the older group,with 8/12(67%)alive and3 with disease at a median follow-up of 2.6 years,as compared with the younger group that had 15/17(88%)alive and none with disease at a median follow-up of 3.5years.The longest survivals among the older women were observed in those who received radiotherapy,including one case with a resected lung metastasis.A prospective multi-institutional collaboration and better follow-up are needed to determine the optimal management of cervical embryonal RMS.Long-term survival appears feasible if management is accompanied by chemotherapy and radiotherapy.展开更多
Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of ne...Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.展开更多
Thyroid cancer(TC)is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few decades.Aggressive TCs metastasize quickly and often levy poor prognoses,as they a...Thyroid cancer(TC)is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few decades.Aggressive TCs metastasize quickly and often levy poor prognoses,as they are frequently resistant to first-line treatment options.Patients diagnosed with aggressive,dedifferentiated TC have a prognosis of under a year with the most current treatment modalities.Like many cancers,TCs also exhibit altered cell metabolism,which enhances the cell’s ability to generate energy,protect against reactive oxygen species,and synthesize macromolecules such as lipids,proteins,and nucleotides for proliferation.Genetic and enzyme profiling of TC tissues and cell lines have uncovered several dysregulated metabolic pathways such as glycolysis,the pentose phosphate pathway,glutamine metabolism,and pyrimidine synthesis.These aberrations are most often due to overexpression of rate-limiting enzymes or metabolite transporters.Metabolic pathways pose attractive therapeutic targets in aggressive TC and may serve to work in tandem with standard therapeutics such as kinase inhibitors depending on the genetic,metabolic,and signaling backgrounds of individual tumors.Further studies are needed to clearly delineate altered metabolic targets across TC subtypes for implementing therapeutic metabolic inhibitors that have shown success in other aggressive tumors.展开更多
Malignant mesothelioma(MM)is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen.Survival rates for patients with MM remain extremely low and effective treatments a...Malignant mesothelioma(MM)is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen.Survival rates for patients with MM remain extremely low and effective treatments are limited.MM tumors harbor both genotypic and phenotypic features that indicate MM tumor cells are under increased oxidative stress,similar to other aggressive cancers.This increased oxidative stress in MM cells supports aggressive growth while providing a therapeutic vulnerability exploitable by redox-modulating compounds.MM tumor cells also exhibit altered mitochondrial structure and function that contribute to the disease through perturbations in metabolism and reactive oxygen species(ROS)production and metabolism.Targeting the altered redox status in cancer through increasing cellular ROS levels directly or inhibiting cellular antioxidant pathways and disrupting ROS scavenging mechanisms has become an exciting area for therapeutic intervention.This review discusses ROS sources and signaling,mitochondrial structure and function and targeting mitochondria ROS as a therapeutic approach for the treatment of MM.展开更多
文摘The literature on cervical embryonal rhabdomyosarcoma(RMS)is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer.Specifically,the Pub Med,Web of Science and Google Scholar databases,were searched to find published case series on cervical embryonal RMS reporting on four or more patients,of whom at least one was>40-year-old.Theχ^(2 )test was used to assess heterogeneity.Five articles published between 1986 and 2013 were identified,reporting on a total of 47 patients,of whom 22(46.8%)were older and 25(53.2%)younger than 40-year-old.Although the two age groups did not differ significantly by stage of disease or radiotherapy treatment,the older age groupreceived less chemotherapy(55%vs 90%,P=0.008)and had more hysterectomy(86%vs 43%,P=0.009).Follow-up data was missing for 18/47(38.3%)patients.Among the 29 patients with follow-up data,survival was shorter in the older group,with 8/12(67%)alive and3 with disease at a median follow-up of 2.6 years,as compared with the younger group that had 15/17(88%)alive and none with disease at a median follow-up of 3.5years.The longest survivals among the older women were observed in those who received radiotherapy,including one case with a resected lung metastasis.A prospective multi-institutional collaboration and better follow-up are needed to determine the optimal management of cervical embryonal RMS.Long-term survival appears feasible if management is accompanied by chemotherapy and radiotherapy.
文摘Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.
基金supported in part by the University of Vermont Cancer Center.
文摘Thyroid cancer(TC)is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few decades.Aggressive TCs metastasize quickly and often levy poor prognoses,as they are frequently resistant to first-line treatment options.Patients diagnosed with aggressive,dedifferentiated TC have a prognosis of under a year with the most current treatment modalities.Like many cancers,TCs also exhibit altered cell metabolism,which enhances the cell’s ability to generate energy,protect against reactive oxygen species,and synthesize macromolecules such as lipids,proteins,and nucleotides for proliferation.Genetic and enzyme profiling of TC tissues and cell lines have uncovered several dysregulated metabolic pathways such as glycolysis,the pentose phosphate pathway,glutamine metabolism,and pyrimidine synthesis.These aberrations are most often due to overexpression of rate-limiting enzymes or metabolite transporters.Metabolic pathways pose attractive therapeutic targets in aggressive TC and may serve to work in tandem with standard therapeutics such as kinase inhibitors depending on the genetic,metabolic,and signaling backgrounds of individual tumors.Further studies are needed to clearly delineate altered metabolic targets across TC subtypes for implementing therapeutic metabolic inhibitors that have shown success in other aggressive tumors.
基金Brian Cunniff receives funding from RS Oncology,LLC through a Sponsored Research Agreement between the University of Vermont and RS Oncology,LLC.
文摘Malignant mesothelioma(MM)is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen.Survival rates for patients with MM remain extremely low and effective treatments are limited.MM tumors harbor both genotypic and phenotypic features that indicate MM tumor cells are under increased oxidative stress,similar to other aggressive cancers.This increased oxidative stress in MM cells supports aggressive growth while providing a therapeutic vulnerability exploitable by redox-modulating compounds.MM tumor cells also exhibit altered mitochondrial structure and function that contribute to the disease through perturbations in metabolism and reactive oxygen species(ROS)production and metabolism.Targeting the altered redox status in cancer through increasing cellular ROS levels directly or inhibiting cellular antioxidant pathways and disrupting ROS scavenging mechanisms has become an exciting area for therapeutic intervention.This review discusses ROS sources and signaling,mitochondrial structure and function and targeting mitochondria ROS as a therapeutic approach for the treatment of MM.
