Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Ceruloplasmin, the blue protein of the plasma of vertebrates, was isolated from dolphin, a marine mammal. The protein showed overall physico-chemical parameters very similar to those of all other mammalian ceruloplasmins. The spectroscopic properties indicated a conservation of the copper binding sites. 2. Non-denaturing electrophoresis revealed a conformation similar to that of other mammalian ceruloplasmins. EPR spectroscopy and calorimetric analyses indicated a three-domain arrangement of the protein typical of "aged" ceruloplasmin. 3. Dolphin ceruloplasmin is the only mammalian ceruloplasmin insensitive to trypsin, plasmin or chymotrypsin. This property, however, does not result in a higher conformational stability of the molecule. Thus, susceptibility of ceruloplasmin to aging is not directly related to the lability to proteases, which is typical of all other mammalian ceruloplasmins so far studied.
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PMID:Dolphin ceruloplasmin: the first proteolytically stable mammalian ceruloplasmin. 133 85

Many animal experiments performed worldwide have proven EPR effects However, it is hard to say that the EPR effect works in clinical practice. In the case of hematological malignancies, the administered anticancer agents (ACA) can physically interact with the malignant cells, making it easier to reflect in vitro data. In solid tumors, however, the extravasated ACAs must diffuse evenly within the whole tumor mass. Therefore, the cancer stroma and the tumor mass itself can be obstacles to drug delivery systems (DDS) including antibody therapeutics. We have demonstrated that hypercoagulability caused by cancer forms cancer stroma. We further showed that the more aggressive the cancer, the greater the deposition of insoluble fibrin (IF) in cancer tissue. In this background, we decided to create monoclonal antibody (mAb) that specifically binds to IF. After a long effort, a new and unique IF-specific mAb was developed. Subsequently, anti-IF mAb conjugated with an ACA using a V-L-K linker which can be cut by plasmin. Because plasmin is activated only during IF formation, the ACA is released from the ADC only when the conjugate is bound to the IF. The released ACA may readily get to cancer cells through the stromal obstacle because of its small size. The ACA also damages the capillary that nourish cancer cells. We have named this strategy cancer (CA) stroma (S) targeting (T) therapy, or CAST therapy.
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PMID:Cancer stromal targeting therapy to overcome the pitfall of EPR effect. 3265 19