Despite the significant resources dedicated to the development of monoclonal antibody(m Ab)therapies for solid tumors,the clinical success,thus far,has been modest.Limited efficacy of m Ab in solid tumors likely relat...Despite the significant resources dedicated to the development of monoclonal antibody(m Ab)therapies for solid tumors,the clinical success,thus far,has been modest.Limited efficacy of m Ab in solid tumors likely relates to unique aspects of tumor physiology.Solid tumors have an aberrant vasculature and a dense extracellular matrix that slow both the convective and diffusive transport of m Abs into and within tumors.For m Abs that are directed against cellular antigens,high antigen expression and rapid antigen turnover can result in perivascular cells binding to and eliminating a significant amount of extravasated m Ab,limiting m Ab distribution to portions of the tumor that are distant from functional vessels.Many preclinical investigations have reported strategies to improve m Ab uptake and distribution;however,to our knowledge,none have translated into the clinic.Here,we provide an overview of several barriers in solid tumors that limit m Ab uptake and distribution and discuss approaches that have been utilized to overcome these barriers in preclinical studies.展开更多
Background Potassium(K)is an essential nutrient for plant growth and development.However,plant fertilization ignoring the soil K level is very likely to cause excessive fertilizer use,and further arouse a series of si...Background Potassium(K)is an essential nutrient for plant growth and development.However,plant fertilization ignoring the soil K level is very likely to cause excessive fertilizer use,and further arouse a series of side effects.This study investigated the response of cotton growth to different soil K levels and the uptake of major nutrients,aiming to evaluate the appropriate K supply level for cotton growth.Using a random block design with 6 soil K levels,we conducted 18 micro-zones field experiments over two continuous years.The soil available K concentration of each treatment was K1(99.77-100.90 mg·kg^(-1)),K2(110.90-111.26 mg·kg^(-1)),K3(123.48-128.88 mg·kg^(-1)),K4(140.13-145.10 mg·kg^(-1)),K5(154.43-155.38 mg·kg^(-1)),and K6(165.77-168.75 mg·kg^(-1)).Cotton nutrient contents,soil nutrient contents,accumulation and distribution of dry matter in cotton were determined,and the relationships between K content in soil and plants and dry matter accumulation were analyzed.Results The soil K content had a significantly positive relationship with dry matter and K accumulation in cotton plants.There were significant differences in dry matter accumulation,single-plant seed cotton yield,mineral nutrient uptake and the proportion of K accumulation in reproductive organs among different soil K levels.The results showed that there was significant difference between K4 and lower K level treatments(K1 and K2),but no significant difference between K4 and higher K level treatments(K5 and K6)in dry matter,single-plant seed cotton yield,or accumulation,distribution and seed cotton production efficiency of N,P and K.Conclusion The soil K level of K4 was able to provide sufficient K for cotton growth in our experiment.Therefore,when the soil K level reached 140.13 mg·kg^(-1),further increasing the soil K concentration no longer had a significant positive effect on cotton growth.展开更多
基金funded by the National Institutes of Health/National Cancer Institute(Grant Nos.CA204192 and CA246785)。
文摘Despite the significant resources dedicated to the development of monoclonal antibody(m Ab)therapies for solid tumors,the clinical success,thus far,has been modest.Limited efficacy of m Ab in solid tumors likely relates to unique aspects of tumor physiology.Solid tumors have an aberrant vasculature and a dense extracellular matrix that slow both the convective and diffusive transport of m Abs into and within tumors.For m Abs that are directed against cellular antigens,high antigen expression and rapid antigen turnover can result in perivascular cells binding to and eliminating a significant amount of extravasated m Ab,limiting m Ab distribution to portions of the tumor that are distant from functional vessels.Many preclinical investigations have reported strategies to improve m Ab uptake and distribution;however,to our knowledge,none have translated into the clinic.Here,we provide an overview of several barriers in solid tumors that limit m Ab uptake and distribution and discuss approaches that have been utilized to overcome these barriers in preclinical studies.
基金supported by Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciencesthe earmarked fund of China Agricultural Research System of China(CARS-15-11).
文摘Background Potassium(K)is an essential nutrient for plant growth and development.However,plant fertilization ignoring the soil K level is very likely to cause excessive fertilizer use,and further arouse a series of side effects.This study investigated the response of cotton growth to different soil K levels and the uptake of major nutrients,aiming to evaluate the appropriate K supply level for cotton growth.Using a random block design with 6 soil K levels,we conducted 18 micro-zones field experiments over two continuous years.The soil available K concentration of each treatment was K1(99.77-100.90 mg·kg^(-1)),K2(110.90-111.26 mg·kg^(-1)),K3(123.48-128.88 mg·kg^(-1)),K4(140.13-145.10 mg·kg^(-1)),K5(154.43-155.38 mg·kg^(-1)),and K6(165.77-168.75 mg·kg^(-1)).Cotton nutrient contents,soil nutrient contents,accumulation and distribution of dry matter in cotton were determined,and the relationships between K content in soil and plants and dry matter accumulation were analyzed.Results The soil K content had a significantly positive relationship with dry matter and K accumulation in cotton plants.There were significant differences in dry matter accumulation,single-plant seed cotton yield,mineral nutrient uptake and the proportion of K accumulation in reproductive organs among different soil K levels.The results showed that there was significant difference between K4 and lower K level treatments(K1 and K2),but no significant difference between K4 and higher K level treatments(K5 and K6)in dry matter,single-plant seed cotton yield,or accumulation,distribution and seed cotton production efficiency of N,P and K.Conclusion The soil K level of K4 was able to provide sufficient K for cotton growth in our experiment.Therefore,when the soil K level reached 140.13 mg·kg^(-1),further increasing the soil K concentration no longer had a significant positive effect on cotton growth.
