We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumo...We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.展开更多
Ongoing progress in nanotechnologies has led to their implementation for in vivo diagnostic and therapy. Thus, the main applications of inorganic nanoparticles are imaging for diagnosis and cell tracking, photothermal...Ongoing progress in nanotechnologies has led to their implementation for in vivo diagnostic and therapy. Thus, the main applications of inorganic nanoparticles are imaging for diagnosis and cell tracking, photothermal and drug-delivery therapies. Following nanoparticles in vivo administration, the systemic circulation can distribute them to every body organ and tissue. Precise characterization of nanoparticles distribution and accumulation in the different body parts in preclinical models is required before any application in humans. The biodistribution of inorganic nanoparticles has been analysed in different preclinical models, particularly mouse, rat and rabbit. This review covers the in vivo biodistribution of different inorganic nanoparticles in preclinical models: gold nanoparticles, silica nanoparticles, iron oxide magnetic nanoparticles, quantum dots and carbon nanotubes.展开更多
In fifty years, laser technology has made great progress, and its many applications make it essential in everyday life. However, this technology is still open to numerous developments. Across multiple applications, th...In fifty years, laser technology has made great progress, and its many applications make it essential in everyday life. However, this technology is still open to numerous developments. Across multiple applications, there is particular focus in the field of medicine, for diagnosis for tailored therapies, and as a research tool in biology. Whereas its use is now well-demonstrated in ophthalmologic and dermatologic treatments, and surgery, one of the most fascinating aspects of laser technology in the field of biology emerged in the late 1990s with the development of devices able to perform fine dissections of biological tissues using a laser beam. The so-called laser-associated microdissection offers a rapid, precise method of isolating and removing targeted cells or groups of cells from complex biological tissues. It represents the missing link between clinical observations and the intrinsic physiological mechanisms of biological tissues. The molecular examination of pathologically altered cells and tissues for DNA, RNA, and protein expression has revolutionized research and diagnosis in pathology, enabling assessment of the role of the cell type in the normal physiological or disease process. Alongside conventional diagnostic and therapeutic approaches, another field of application contribute to the development of targeted treatments at the nanoscale level of laser technology, mainly in the field of cancer, leading to design new and innovative strategies in drug delivery and image-guided surgery. Most of these approaches, but although not exhaustively, will be presented here.展开更多
Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of cancers.We assume that most cancers are the result of germline mutations...Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of cancers.We assume that most cancers are the result of germline mutations of low to moderate penetrance,combined with acquired mutations due to external carcinogenic stressors.With their accumulation over time,aging is associated with an increased risk of multiple cancer development in a given individual.For decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be identified.More recently,population-wide studies have led to the identification of considerable numbers of polymorphisms associated with cancer risk.However,most of them are of unknown functional value,thus limiting their translational application.展开更多
The incidence of lymphoma has gradually increased over previous decades,and it ranks among the ten most prevalent cancers worldwide.With the development of targeted therapeutic strategies,though a subset of lymphoma p...The incidence of lymphoma has gradually increased over previous decades,and it ranks among the ten most prevalent cancers worldwide.With the development of targeted therapeutic strategies,though a subset of lymphoma patients has become curable,the treatment of refractory and relapsed diseases remains challenging.Many efforts have been made to explore new targets and to develop corresponding therapies.In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors,immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment.Although these targeted agents have shown great success in treating lymphoma patients,adverse events should be noted.The selection of the most suitable candidates,optimal dosage,and effective combinations warrant further investigation.In this review,we systematically outlined the advances in targeted therapy for malignant lymphoma,providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.展开更多
文摘We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.
文摘Ongoing progress in nanotechnologies has led to their implementation for in vivo diagnostic and therapy. Thus, the main applications of inorganic nanoparticles are imaging for diagnosis and cell tracking, photothermal and drug-delivery therapies. Following nanoparticles in vivo administration, the systemic circulation can distribute them to every body organ and tissue. Precise characterization of nanoparticles distribution and accumulation in the different body parts in preclinical models is required before any application in humans. The biodistribution of inorganic nanoparticles has been analysed in different preclinical models, particularly mouse, rat and rabbit. This review covers the in vivo biodistribution of different inorganic nanoparticles in preclinical models: gold nanoparticles, silica nanoparticles, iron oxide magnetic nanoparticles, quantum dots and carbon nanotubes.
文摘In fifty years, laser technology has made great progress, and its many applications make it essential in everyday life. However, this technology is still open to numerous developments. Across multiple applications, there is particular focus in the field of medicine, for diagnosis for tailored therapies, and as a research tool in biology. Whereas its use is now well-demonstrated in ophthalmologic and dermatologic treatments, and surgery, one of the most fascinating aspects of laser technology in the field of biology emerged in the late 1990s with the development of devices able to perform fine dissections of biological tissues using a laser beam. The so-called laser-associated microdissection offers a rapid, precise method of isolating and removing targeted cells or groups of cells from complex biological tissues. It represents the missing link between clinical observations and the intrinsic physiological mechanisms of biological tissues. The molecular examination of pathologically altered cells and tissues for DNA, RNA, and protein expression has revolutionized research and diagnosis in pathology, enabling assessment of the role of the cell type in the normal physiological or disease process. Alongside conventional diagnostic and therapeutic approaches, another field of application contribute to the development of targeted treatments at the nanoscale level of laser technology, mainly in the field of cancer, leading to design new and innovative strategies in drug delivery and image-guided surgery. Most of these approaches, but although not exhaustively, will be presented here.
文摘Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of cancers.We assume that most cancers are the result of germline mutations of low to moderate penetrance,combined with acquired mutations due to external carcinogenic stressors.With their accumulation over time,aging is associated with an increased risk of multiple cancer development in a given individual.For decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be identified.More recently,population-wide studies have led to the identification of considerable numbers of polymorphisms associated with cancer risk.However,most of them are of unknown functional value,thus limiting their translational application.
基金supported,in part,by research funding from the National Natural Science Foundation of China(81520108003,81830007,and 81670176)the Chang Jiang Scholars Program,the Shanghai Commission of Science and Technology(16JC1405800)+3 种基金the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206 and 20152208)the Clinical Research Plan of Shanghai Hospital Development Center(SHDC,16CR2017A)the Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601)the Collaborative Innovation Center of Systems Biomedicine,the Samuel Waxman Cancer Research Foundation,the innovative research team of high-level local universities in Shanghai,and the shared Research Project Grants,University of Sydney and SJTU.
文摘The incidence of lymphoma has gradually increased over previous decades,and it ranks among the ten most prevalent cancers worldwide.With the development of targeted therapeutic strategies,though a subset of lymphoma patients has become curable,the treatment of refractory and relapsed diseases remains challenging.Many efforts have been made to explore new targets and to develop corresponding therapies.In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors,immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment.Although these targeted agents have shown great success in treating lymphoma patients,adverse events should be noted.The selection of the most suitable candidates,optimal dosage,and effective combinations warrant further investigation.In this review,we systematically outlined the advances in targeted therapy for malignant lymphoma,providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.
