The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND tr...The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and epirubicin/cyclophosphamide-based chemotherapy as a neoadjuvant treatment for TNBC(ChiCTR2000035262).The primary endpoint was pathological complete response(pCR),with the secondary endpoints including safety assessment and objective response rate(ORR).ScRNA-seq,bulk RNA-seq,TCR-seq,cyTOF and WES were performed on pre-treatment and post-treatment samples.Among 53 total enrolled patients,44 completed the combined neoadjuvant therapy,and 30 of 44 patients(68.18%)achieved pCR.Additionally,14 out of 44 patients had a complete response(31.82%),with an ORR of 93.18%.The most commonly observed treatment-related adverse events(TRAEs)were alopecia,nausea and liver injury with 6 cases classified as grade 3 or higher adverse events.Immune response-related pathways,including TNF signaling pathway,T cell receptor signaling pathway,were enriched in pCR group.Pre-treatment model was identified and construct to predict response to immunotherapy.CDKN1A+CD8 T lymphocytes were enriched in pCR group after neoadjuvant immunotherapy.Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment effcacy.In conclusion,neoadjuvant treatment of tislelizumab with nab-paclitaxel and anthracycline-based chemotherapy showed promising clinical activity and was well-tolerated among TNBC patients,without high incidence of TRAEs.These findings provide evidence supporting neoadjuvant tislelizumab with chemotherapy as an effective rational approach for treating TNBC.展开更多
Lack of investment for magnetic resonance(MR)fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway.We developed a coordinate-based method to support cognitiv...Lack of investment for magnetic resonance(MR)fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway.We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions.In each patient,the prostate is considered as two separate hemiprostates,and each hemiprostate is divided into 4×4×4 units.Each unit is therefore defined by a three-dimensional coordinate.We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men.Among 45(of 106;42.5%)lesions positive for cancer,27 lesions(60.0%)harbored clinically significant disease.PSA density was significantly higher in patients with proven cancer(median:0.264 ng ml^(-2))when compared to the noncancer group(median:0.145 ng ml-2;P=0.003,Wilcoxon ranksum test).Lesions with Prostate Imaging-Reporting and Data System(PIRADS)score of 5 were found to have a cancer incidence of 65.2%,while PI RADS 4 and 3 lesions have a lower risk of cancer detection,as expected,at 37.3%and 31.3%,respectively.The probability of a lesion being cancerous in our series significantly decreases as we go from the“apex-to-base”dimension(odds ratio[OR]:2.62,95%confidence interval[Cl]:1.55-4.44,P=0.00034).Our analysis also indicates that the probability of cancer decreases as the prostate volume increases(OR:1.03,95%Cl:1.01-1.05,P=0.00327).Based on this feasibility study,the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.展开更多
A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor kil...A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.展开更多
Intestinal epithelium serves as the first barrier against the infections and injuries that mediate colonic inflammation.Colorectal cancer is often accompanied with chronic inflammation.Differed from its well-known onc...Intestinal epithelium serves as the first barrier against the infections and injuries that mediate colonic inflammation.Colorectal cancer is often accompanied with chronic inflammation.Differed from its well-known oncogenic role in many malignancies,we present here that Golgi membrane protein 1(G0LM1,also referred to as GP73)suppresses colorectal tumorigenesis via maintenance of intestinal epithelial barrier.G0LM1 deficiency in mice conferred susceptibility to mucosal inflammation and colitis-induced epithelial damage,which consequently promoted colon cancer.Mechanistically,depletion of G0LM1 in intestinal epithelial cells(lECs)led to aberrant Notch activation that interfered with IEC differentiation,maturation,and lineage commitment in mice.Pharmacological inhibition of Notch pathway alleviated epithelial lesions and restrained pro-tumorigenic inflammation in G0LM1-deficient mice.Therefore,G0LM1 maintains IEC homeostasis and protects against colitis and colon tumorigenesis by modulating the equilibrium of Notch signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China(82203786,82373231)the Natural Science Foundation of Liaoning Province of China(2022-YGJC-68,2023-BS-105)Chinese Young Breast Experts Research Project(CYBER-2021-A02,CYBER-2022-001).
文摘The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and epirubicin/cyclophosphamide-based chemotherapy as a neoadjuvant treatment for TNBC(ChiCTR2000035262).The primary endpoint was pathological complete response(pCR),with the secondary endpoints including safety assessment and objective response rate(ORR).ScRNA-seq,bulk RNA-seq,TCR-seq,cyTOF and WES were performed on pre-treatment and post-treatment samples.Among 53 total enrolled patients,44 completed the combined neoadjuvant therapy,and 30 of 44 patients(68.18%)achieved pCR.Additionally,14 out of 44 patients had a complete response(31.82%),with an ORR of 93.18%.The most commonly observed treatment-related adverse events(TRAEs)were alopecia,nausea and liver injury with 6 cases classified as grade 3 or higher adverse events.Immune response-related pathways,including TNF signaling pathway,T cell receptor signaling pathway,were enriched in pCR group.Pre-treatment model was identified and construct to predict response to immunotherapy.CDKN1A+CD8 T lymphocytes were enriched in pCR group after neoadjuvant immunotherapy.Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment effcacy.In conclusion,neoadjuvant treatment of tislelizumab with nab-paclitaxel and anthracycline-based chemotherapy showed promising clinical activity and was well-tolerated among TNBC patients,without high incidence of TRAEs.These findings provide evidence supporting neoadjuvant tislelizumab with chemotherapy as an effective rational approach for treating TNBC.
文摘Lack of investment for magnetic resonance(MR)fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway.We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions.In each patient,the prostate is considered as two separate hemiprostates,and each hemiprostate is divided into 4×4×4 units.Each unit is therefore defined by a three-dimensional coordinate.We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men.Among 45(of 106;42.5%)lesions positive for cancer,27 lesions(60.0%)harbored clinically significant disease.PSA density was significantly higher in patients with proven cancer(median:0.264 ng ml^(-2))when compared to the noncancer group(median:0.145 ng ml-2;P=0.003,Wilcoxon ranksum test).Lesions with Prostate Imaging-Reporting and Data System(PIRADS)score of 5 were found to have a cancer incidence of 65.2%,while PI RADS 4 and 3 lesions have a lower risk of cancer detection,as expected,at 37.3%and 31.3%,respectively.The probability of a lesion being cancerous in our series significantly decreases as we go from the“apex-to-base”dimension(odds ratio[OR]:2.62,95%confidence interval[Cl]:1.55-4.44,P=0.00034).Our analysis also indicates that the probability of cancer decreases as the prostate volume increases(OR:1.03,95%Cl:1.01-1.05,P=0.00327).Based on this feasibility study,the use of coordinates to guide cognitive targeted prostate biopsies warrants future validation study in additional centers.
基金the Harbin Medical University Cancer Hospital(CN)Nn10 Project(Nn10py2017-01)。
文摘A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.
基金This work was supported by the National Natural Science Foundation of China(81602456,81730078,81800552,31700785)the Chinese Academy of Medical Sciences Initiative for Innovative Medicine(2016-I2M-1-001)the Liaoning Provincial Natural Science Foundation of China(2019-MS-068).
文摘Intestinal epithelium serves as the first barrier against the infections and injuries that mediate colonic inflammation.Colorectal cancer is often accompanied with chronic inflammation.Differed from its well-known oncogenic role in many malignancies,we present here that Golgi membrane protein 1(G0LM1,also referred to as GP73)suppresses colorectal tumorigenesis via maintenance of intestinal epithelial barrier.G0LM1 deficiency in mice conferred susceptibility to mucosal inflammation and colitis-induced epithelial damage,which consequently promoted colon cancer.Mechanistically,depletion of G0LM1 in intestinal epithelial cells(lECs)led to aberrant Notch activation that interfered with IEC differentiation,maturation,and lineage commitment in mice.Pharmacological inhibition of Notch pathway alleviated epithelial lesions and restrained pro-tumorigenic inflammation in G0LM1-deficient mice.Therefore,G0LM1 maintains IEC homeostasis and protects against colitis and colon tumorigenesis by modulating the equilibrium of Notch signaling pathway.
