Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors....Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.展开更多
BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation...BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.展开更多
Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of do...Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.展开更多
Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The express...Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD<sub>20</sub> antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD<sub>20</sub> molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.展开更多
基金supported by the European Crohn’s and Colitis Organization(ECCO)(Grant“The Role of Galectin 3 in Acute Colitis”)Serbian Ministry of Science(Grant Nos.ON175069 and ON175103),Faculty of Medical Sciences University of Kragujevac(Grant No.MP01/18).
文摘Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.
文摘BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.
文摘Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.
文摘Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD<sub>20</sub> antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD<sub>20</sub> molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.
