A rice CaMBP gene, OsCaMBP (AB363406), was isolated from a chilling treated rice using the fluorescent differential display (FDD) screening method. Its cDNA sequence (2094 bp) contains an opening reading frame ...A rice CaMBP gene, OsCaMBP (AB363406), was isolated from a chilling treated rice using the fluorescent differential display (FDD) screening method. Its cDNA sequence (2094 bp) contains an opening reading frame (ORF) encoding a 569 amino acids protein (63.2 kD). OsCaMBP has the typical structural features of the CaMBP family, including the conserved IQ calmodulin-binding motif at the N-terminus. Homology analysis revealed 38.25%-47.28% identities of OsCaMBP with other CaMBPs in plants. RT-PCR analysis showed that the expression of OsCaMBP was remarkably inducible under the chilling (8℃) and heat-shock (42℃) treatments. OsCaMBP was undetectable under the normal conditions, and induced under the chilling treatment for 1 h, as well as the heat-shock treatment for 15 min, suggesting that the gene plays important roles in the signaling pathway in rice under both chilling and heat-shock stresses.展开更多
Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promis...Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,展开更多
Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known abou...Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.展开更多
Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abun...Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and translation.Accumulating evidence demonstrates that m^(6)A plays a critical role in regulating cancer metastasis.However,there is a lack of studies that review the recent advances of m^(6)A in cancer metastasis.Here,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various cancers.Moreover,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer metastasis.This review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.展开更多
Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer patients.However,cures remain infrequent,and m...Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer patients.However,cures remain infrequent,and most patients ultimately succumb to treatment-refractory metastatic disease.Recent insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors,suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy resistance.Specialized immune cells known as regulatory T cells(Tregs)are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune homeostasis.Despite the high volume of research on Tregs,the findings have failed to reconcile tissue-specific Treg functions in organs,such as tolerance,tissue repair,and regeneration,with their suppression of local and systemic tumor immunity in the context of immunotherapy resistance.To improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy,we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis,highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy,and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer immunotherapy.Improved knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.展开更多
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University of China (Grant No. IRT0453)the National Science & Technology Pillar Program of China in the Eleventh Five-Year Plan Period (Grant No. 2007BAD81B00).
文摘A rice CaMBP gene, OsCaMBP (AB363406), was isolated from a chilling treated rice using the fluorescent differential display (FDD) screening method. Its cDNA sequence (2094 bp) contains an opening reading frame (ORF) encoding a 569 amino acids protein (63.2 kD). OsCaMBP has the typical structural features of the CaMBP family, including the conserved IQ calmodulin-binding motif at the N-terminus. Homology analysis revealed 38.25%-47.28% identities of OsCaMBP with other CaMBPs in plants. RT-PCR analysis showed that the expression of OsCaMBP was remarkably inducible under the chilling (8℃) and heat-shock (42℃) treatments. OsCaMBP was undetectable under the normal conditions, and induced under the chilling treatment for 1 h, as well as the heat-shock treatment for 15 min, suggesting that the gene plays important roles in the signaling pathway in rice under both chilling and heat-shock stresses.
基金supported by the National Natural Science Foundation of China(81370938)Shanghai Municipal Commission of Health and Family Planning(XYQ2011002)+2 种基金Shanghai Science and Technology Committee(11PJ1402000)Shenkang Hospital Development Center(SHDC12012220)the ‘‘Strategic Priority Research Program” of the Chinese Academy of Science(XDB13030500)
文摘Current therapies for obesity and related complications have been shown to have limited benefits,including unsatisfactory weight loss and poor metabolic improvement.With recent developments in bariatric surgery,promising advancements have been made in clinical and scientific research,particularly in the management of obesity and diabetes.Vertical sleeve gastrectomy(VSG)has become increasingly popular due to its safety,simplicity,
文摘Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.
基金supported by the Key Program of the National Natural Science Foundation of China(81930074,2020-2024)the Major Program of National Natural Science Foundation of China(91959203,2020-2023)the Natural Science Foundation of China(81672820,2017-2020,81672378,2017-2020,82173093)。
文摘Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes.A metastatic cas-cade is a series of complicated biological processes.N6-methyladenosine(m^(6)A)is the most abundant and conserved epi-transcriptomic modification in eukaryotic cells,which has great impacts on RNA production and metabolism,including RNA splicing,processing,degradation and translation.Accumulating evidence demonstrates that m^(6)A plays a critical role in regulating cancer metastasis.However,there is a lack of studies that review the recent advances of m^(6)A in cancer metastasis.Here,we systematically retrieved the functions and mechanisms of how the m^(6)A axis regulates metastasis,and especially summarized the organ-specific liver,lung and brain metastasis mediated by m^(6)A in various cancers.Moreover,we discussed the potential application of m^(6)A modification in cancer diagnosis and therapy,as well as the present limitations and future perspectives of m^(6)A in cancer metastasis.This review provides a comprehensive knowledge on the m^(6)A-mediated regulation of gene expression,which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m^(6)A alteration.
文摘Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer patients.However,cures remain infrequent,and most patients ultimately succumb to treatment-refractory metastatic disease.Recent insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors,suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy resistance.Specialized immune cells known as regulatory T cells(Tregs)are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune homeostasis.Despite the high volume of research on Tregs,the findings have failed to reconcile tissue-specific Treg functions in organs,such as tolerance,tissue repair,and regeneration,with their suppression of local and systemic tumor immunity in the context of immunotherapy resistance.To improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy,we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis,highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy,and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer immunotherapy.Improved knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.