Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions.However,their clinical use has been limited to extracellular applications due to their inability to cross plasma membra...Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions.However,their clinical use has been limited to extracellular applications due to their inability to cross plasma membranes.Overcoming this physiological barrier would unlock the potential of protein drugs for the treatment of many intractable diseases.In this review,we highlight progress made toward achieving cytosolic delivery of recombinant proteins.We start by first considering intracellular protein delivery as a drug modality compared to existing Food and Drug Administration-approved drug modalities.Then,we summarize strategies that have been reported to achieve protein internalization.These techniques can be broadly classified into 3 categories:physical methods,direct protein engineering,and nanocarrier-mediated delivery.Finally,we highlight existing challenges for cytosolic protein delivery and offer an outlook for future advances.展开更多
Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue....Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.展开更多
文摘Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions.However,their clinical use has been limited to extracellular applications due to their inability to cross plasma membranes.Overcoming this physiological barrier would unlock the potential of protein drugs for the treatment of many intractable diseases.In this review,we highlight progress made toward achieving cytosolic delivery of recombinant proteins.We start by first considering intracellular protein delivery as a drug modality compared to existing Food and Drug Administration-approved drug modalities.Then,we summarize strategies that have been reported to achieve protein internalization.These techniques can be broadly classified into 3 categories:physical methods,direct protein engineering,and nanocarrier-mediated delivery.Finally,we highlight existing challenges for cytosolic protein delivery and offer an outlook for future advances.
文摘Myeloid sarcoma, also known as granulocytic sarcoma or chloroma is an unusual accumulation of malignant myeloid precursor cells in an extramedullary site, which disrupts the normal architecture of the involved tissue. It is known to occur more commonly in patients with acute myelogenous leukemia and less commonly in those with myelodysplastic syndrome and myeloproliferative neoplasm, such as chronic myelogenous leukemia. The most common sites of involvement include bone, skin and lymph nodes. However, rare cases have been reported in the gastrointestinal tract, genitourinary tract, or breast. Most commonly, a neoplastic extramedullary proliferation of myeloid precursors in a patient would have systemic involvement of a myeloid neoplasm, including in the bone marrow and peripheral blood. Infrequently, extramedullary disease may be the only site of involvement. It may also occur as a localized antecedent to more generalized disease or as a site of recurrence. Herein, we present the first case in the English literature of a patient presenting with an isolated site of myeloid sarcoma arising in the form of a colonic polyp which, after subsequent bone marrow biopsy, was found to be a harbinger of chronic myelogenous leukemia.
