53 research outputs found

    Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia

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    High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia

    The Dual Consequences of Politicization of Ethnicity in Romania

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    The first two centuries of colonial agriculture in the cape colony: A historiographical review∗

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    Determination of Total Flavonoid Levels of Ethanol Extract of Sweet Potato Leaves (Ipomoea batatas L.)

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    Introduction: Dengue hemorrhagic fever (DHF) caused by the dengue virus carried by Aedes aegypti and Aedes albopictus mosquitoes as a vector to the human body through the bite of the mosquito. Method: Sweet potato leaves taken were made into the dried material and extracted using the percolation method using 70% ethanol until a thick extract is obtained. Tests are carried out microscopically on the dried material. The qualitative identification, testing extracts specific gravity and measurement of total flavonoid levels on the extract. Results: Testing of Specific Parameters observed is organoleptic identity of the extract produced is Color: blackish green, Smell: No smell and Shape: Thick. Qualitative Test with Thin Layer Chromatography, the sample contained flavonoid compounds in flavone and flavonol groups. Total flavonoid levels were measured as equivalent to standard quercetin based on the standard quercetin curve. The result of total flavonoid content from ethanol extract of sweet potato leaves was 31630 mg QE / 100 g extract. Suggestion: Total flavonoid content of 3163mg QE / 100g or 31.63% b / b
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