The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
Background： An examination of the distribution of ancient charcoal kiln sites in the forest landscape seems to be worthwhile, since general trends in the selection of suitable kiln site locations in the past might be...Background： An examination of the distribution of ancient charcoal kiln sites in the forest landscape seems to be worthwhile, since general trends in the selection of suitable kiln site locations in the past might become obvious. In this way forest landscape elements with a more intense usage by charcoal burning can be identified. By doing this, we can expect to gain information on the former condition and tree species composition of woodland. Investigations on the spatial distribution of charcoal kiln sites in relation to landscape attributes are sparse, however, probably due to the high on-site mapping effort. The outstanding suitability of LiDAR-derived digital terrain models （DTMs） for the detection of charcoal kiln sites has been recently proved. Hence, DTM-based surveys of charcoal kiln sites represent a promising attempt to fill this research gap. Methods： Based on DTM-based surveys, we analyzed the spatial distribution of charcoal kiln sites in two forest landscapes in the German federal state of Hesse： Reinhardswald and Kellerwald-Edersee National Park. In doing so, we considered the landscape attibutes ＂tree species composition＂, ＂water supply status＂, ＂nutrient supply status＂, ＂soil complex classes＂, ＂altitude＂, ＂exposition＂, and ＂inclination＂. Results： We found that charcoal kiln sites were established preferably on hillside locations that provided optimal growing and regeneration conditions for European beech （Fagus sylvatico） due to their acidic brown soils and sufficient water supply. These results are in line with instructions for the selection of appropriate kiln site locations, found in literature from the 18th to the 19th century. Conclusions： We conclude that there were well-stocked, beech-dominated deciduous forest stands in northern Hesse before 1800, particularly at poorly accessible hillside locations. These large stocks of beech wood were utilized by the governments of the different Hessian territories through the establishment of ironworks and hammer mills. Our argumentation is well in line with findings which underline that not all Hessian forests were overexploited in the 18th century. Frequently repeated complaints about ＂wood shortage＂ seemed to be more a political instrument than reality, not only in Hesse, but all over Europe. Consequently, a differentiated assessment of woodland conditions in proto-industrial times is strictly advised, even if contemporary sources draw a dark picture of the historic situation.展开更多
For increase in hardness (durability) and fire resistance (stability to melts metals) corundum ceramics on the basis of Al2O3 authors of the present work have suggested to protect for the first time its surface strong...For increase in hardness (durability) and fire resistance (stability to melts metals) corundum ceramics on the basis of Al2O3 authors of the present work have suggested to protect for the first time its surface stronger and fire-resistant coverings, for example, from TiB2. In work results of high-temperature diffusion TiB2 in a surface of plates from Al 2O3 are shown. For the first time the method cathodeluminescencium (KL) for identification and a condition of atom Ti after diffusion is used, in for an establishment of its quantity used method X-ray spectrum the microanalysis (RSMA). Durability increase defined a method microindentification by means of a pyramid of Knoop and strength at a bend. Researches have shown perspectivity of hardening of a surface corundum ceramics and use of the above-stated methods for studying of results of diffusion.展开更多
Advanced hormone receptor-positive breast cancer is one of the women’s most common malignant diseases and remains incurable despite recent therapeutic innovations.The dependence of hormone receptor-positive breast ca...Advanced hormone receptor-positive breast cancer is one of the women’s most common malignant diseases and remains incurable despite recent therapeutic innovations.The dependence of hormone receptor-positive breast cancer on hormonal growth signals offers the possibility of inhibiting this signaling pathway using anti-hormonal therapy.Nevertheless,the development of resistance to antitumoral drugs remains a challenge.Molecularly-targeted substances significantly improve survival rates and(as in the case of cyclin-dependent kinase 4 and 6 inhibitors)are widely used in clinical practice and enhance endocrine therapy’s efficacy.Agents such as everolimus,alpelisib,and capivasertib target the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway,which is a promising approach to overcoming endocrine resistance.Novel therapies are being studied in numerous trials,and some already show significant benefits in survival rates.The development of new therapies to avert endocrine resistance is an urgent challenge in modern medicine.The following review will examine some promising therapeutic approaches.展开更多
The immune system plays an important role in breast cancer.Triple-negative breast cancer(TNBC)has a higher mutational load compared to other subtypes.In addition,higher levels of tumor-associated antigens suggests tha...The immune system plays an important role in breast cancer.Triple-negative breast cancer(TNBC)has a higher mutational load compared to other subtypes.In addition,higher levels of tumor-associated antigens suggests that immunotherapies are a promising treatment option especially for TNBC.Our review discusses both the complexity of the immune system and the cancer immune-cell cycle.In fact,a higher level of tumor-infiltrating lymphocytes is associated with an improved prognosis as well as a better response to chemotherapy in TNBC.Important target structures within the cancer immune-cell cycle are the so-called“immune checkpoints”.Immune checkpoint inhibitors(ICPi)block the interaction of certain cell surface proteins that serve as“brakes”of immune reactions.Recent studies have shown ICPi improved survival in early as well as advanced TNBC.However,this has the price of increasing,mainly,immune-mediated toxicity.ICPi strengthen tumor-specific T cell-mediated immunity by“releasing the brake”of the immune system.In combination with chemotherapy,ICPi are already approved for TNBC.As a further step,individualized vaccination strategies against tumor-associated neoantigens represent another promising approach.A liposome-formulated intravenous RNA vaccine encoding different tumor-associated antigens is currently being studied in TNBC and leads to neoantigen-specific immune responses.These novel strategies will improve the prognosis of patients with triple-negative breast cancer.展开更多
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
文摘Background： An examination of the distribution of ancient charcoal kiln sites in the forest landscape seems to be worthwhile, since general trends in the selection of suitable kiln site locations in the past might become obvious. In this way forest landscape elements with a more intense usage by charcoal burning can be identified. By doing this, we can expect to gain information on the former condition and tree species composition of woodland. Investigations on the spatial distribution of charcoal kiln sites in relation to landscape attributes are sparse, however, probably due to the high on-site mapping effort. The outstanding suitability of LiDAR-derived digital terrain models （DTMs） for the detection of charcoal kiln sites has been recently proved. Hence, DTM-based surveys of charcoal kiln sites represent a promising attempt to fill this research gap. Methods： Based on DTM-based surveys, we analyzed the spatial distribution of charcoal kiln sites in two forest landscapes in the German federal state of Hesse： Reinhardswald and Kellerwald-Edersee National Park. In doing so, we considered the landscape attibutes ＂tree species composition＂, ＂water supply status＂, ＂nutrient supply status＂, ＂soil complex classes＂, ＂altitude＂, ＂exposition＂, and ＂inclination＂. Results： We found that charcoal kiln sites were established preferably on hillside locations that provided optimal growing and regeneration conditions for European beech （Fagus sylvatico） due to their acidic brown soils and sufficient water supply. These results are in line with instructions for the selection of appropriate kiln site locations, found in literature from the 18th to the 19th century. Conclusions： We conclude that there were well-stocked, beech-dominated deciduous forest stands in northern Hesse before 1800, particularly at poorly accessible hillside locations. These large stocks of beech wood were utilized by the governments of the different Hessian territories through the establishment of ironworks and hammer mills. Our argumentation is well in line with findings which underline that not all Hessian forests were overexploited in the 18th century. Frequently repeated complaints about ＂wood shortage＂ seemed to be more a political instrument than reality, not only in Hesse, but all over Europe. Consequently, a differentiated assessment of woodland conditions in proto-industrial times is strictly advised, even if contemporary sources draw a dark picture of the historic situation.
文摘For increase in hardness (durability) and fire resistance (stability to melts metals) corundum ceramics on the basis of Al2O3 authors of the present work have suggested to protect for the first time its surface stronger and fire-resistant coverings, for example, from TiB2. In work results of high-temperature diffusion TiB2 in a surface of plates from Al 2O3 are shown. For the first time the method cathodeluminescencium (KL) for identification and a condition of atom Ti after diffusion is used, in for an establishment of its quantity used method X-ray spectrum the microanalysis (RSMA). Durability increase defined a method microindentification by means of a pyramid of Knoop and strength at a bend. Researches have shown perspectivity of hardening of a surface corundum ceramics and use of the above-stated methods for studying of results of diffusion.
文摘Advanced hormone receptor-positive breast cancer is one of the women’s most common malignant diseases and remains incurable despite recent therapeutic innovations.The dependence of hormone receptor-positive breast cancer on hormonal growth signals offers the possibility of inhibiting this signaling pathway using anti-hormonal therapy.Nevertheless,the development of resistance to antitumoral drugs remains a challenge.Molecularly-targeted substances significantly improve survival rates and(as in the case of cyclin-dependent kinase 4 and 6 inhibitors)are widely used in clinical practice and enhance endocrine therapy’s efficacy.Agents such as everolimus,alpelisib,and capivasertib target the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway,which is a promising approach to overcoming endocrine resistance.Novel therapies are being studied in numerous trials,and some already show significant benefits in survival rates.The development of new therapies to avert endocrine resistance is an urgent challenge in modern medicine.The following review will examine some promising therapeutic approaches.
文摘The immune system plays an important role in breast cancer.Triple-negative breast cancer(TNBC)has a higher mutational load compared to other subtypes.In addition,higher levels of tumor-associated antigens suggests that immunotherapies are a promising treatment option especially for TNBC.Our review discusses both the complexity of the immune system and the cancer immune-cell cycle.In fact,a higher level of tumor-infiltrating lymphocytes is associated with an improved prognosis as well as a better response to chemotherapy in TNBC.Important target structures within the cancer immune-cell cycle are the so-called“immune checkpoints”.Immune checkpoint inhibitors(ICPi)block the interaction of certain cell surface proteins that serve as“brakes”of immune reactions.Recent studies have shown ICPi improved survival in early as well as advanced TNBC.However,this has the price of increasing,mainly,immune-mediated toxicity.ICPi strengthen tumor-specific T cell-mediated immunity by“releasing the brake”of the immune system.In combination with chemotherapy,ICPi are already approved for TNBC.As a further step,individualized vaccination strategies against tumor-associated neoantigens represent another promising approach.A liposome-formulated intravenous RNA vaccine encoding different tumor-associated antigens is currently being studied in TNBC and leads to neoantigen-specific immune responses.These novel strategies will improve the prognosis of patients with triple-negative breast cancer.
