The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alteration...The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.展开更多
Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have be...Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.展开更多
Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by h...Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.展开更多
Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicit...Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.展开更多
How metastases develop is not well understood and no genetic mutations have been reported as specific metastatic drivers.Here we have addressed the idea that epigenetic reprogramming by GLI-regulated pluripotent stemn...How metastases develop is not well understood and no genetic mutations have been reported as specific metastatic drivers.Here we have addressed the idea that epigenetic reprogramming by GLI-regulated pluripotent stemness factors promotes metastases.Using primary human colon cancer cells engrafted in mice,we find that transient expression of OCT4,SOX2,KLF41/2 cMYC establishes an enhanced pro-metastatic state in the primary tumor that is stable through sequential engraftments and is transmitted through clonogenic cancer stem cells.Metastatic reprogramming alters NANOG methylation and stably boosts NANOG and NANOGP8 expression.Metastases and reprogrammed EMT-like phenotypes require endogenous NANOG,but enhanced NANOG is not sufficient to induce these phenotypes.Finally,reprogrammed tumors enhance GLI2,and we show that GLI2high and AXIN2low,which are markers of the metastatic transition of colon cancers,are prognostic of poor disease outcome in patients.We propose that metastases arise through epigenetic reprogramming of cancer stem cells within primary tumors.展开更多
Somatic, cognitive and psychiatric obstacles contribute to social impairment in 22q11.2DS and prevent adequate responses during interactions. We adapted the autism-specific SOSTA-FRA program for use during online grou...Somatic, cognitive and psychiatric obstacles contribute to social impairment in 22q11.2DS and prevent adequate responses during interactions. We adapted the autism-specific SOSTA-FRA program for use during online group sessions with geographically-isolated 22q11DS adolescents or adults. The 12 weekly sessions targeted communication, emotional awareness, and reciprocity. Twenty-two participants were evaluated on behaviour, social responsiveness, and cognition pre- and post-intervention. Parents completed a questionnaire to ascertain whether the intervention met their needs. Parents were satisfied with the format and curriculum contents and reported improved emotional awareness, well-being, and reciprocity post-intervention. Pre-post results suggest large effects on social awareness and small to medium effects on social motivation. Results indicate that online social skills training is feasible and effective for individuals with 22q11.2DS.展开更多
文摘The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.
文摘Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.
文摘Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.
基金funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,under grant no.(G-567-156-1439).
文摘Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.
基金funded by grants from the Swiss National Science Foundation,the Swiss Cancer League,the European Union grant HEALING,a James McDonnell 21st Century Brain Cancer Award,and funds from the Departement d’Instruction Publique de la Republique et Canton de Geneve,Switzerland。
文摘How metastases develop is not well understood and no genetic mutations have been reported as specific metastatic drivers.Here we have addressed the idea that epigenetic reprogramming by GLI-regulated pluripotent stemness factors promotes metastases.Using primary human colon cancer cells engrafted in mice,we find that transient expression of OCT4,SOX2,KLF41/2 cMYC establishes an enhanced pro-metastatic state in the primary tumor that is stable through sequential engraftments and is transmitted through clonogenic cancer stem cells.Metastatic reprogramming alters NANOG methylation and stably boosts NANOG and NANOGP8 expression.Metastases and reprogrammed EMT-like phenotypes require endogenous NANOG,but enhanced NANOG is not sufficient to induce these phenotypes.Finally,reprogrammed tumors enhance GLI2,and we show that GLI2high and AXIN2low,which are markers of the metastatic transition of colon cancers,are prognostic of poor disease outcome in patients.We propose that metastases arise through epigenetic reprogramming of cancer stem cells within primary tumors.
文摘Somatic, cognitive and psychiatric obstacles contribute to social impairment in 22q11.2DS and prevent adequate responses during interactions. We adapted the autism-specific SOSTA-FRA program for use during online group sessions with geographically-isolated 22q11DS adolescents or adults. The 12 weekly sessions targeted communication, emotional awareness, and reciprocity. Twenty-two participants were evaluated on behaviour, social responsiveness, and cognition pre- and post-intervention. Parents completed a questionnaire to ascertain whether the intervention met their needs. Parents were satisfied with the format and curriculum contents and reported improved emotional awareness, well-being, and reciprocity post-intervention. Pre-post results suggest large effects on social awareness and small to medium effects on social motivation. Results indicate that online social skills training is feasible and effective for individuals with 22q11.2DS.