Search results for "Protein"
showing 10 items of 21431 documents
Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib
2019
Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…
Generation of multifunctional murine monoclonal antibodies specifically directed to the VP1unique region protein of human parvovirus B19.
2007
Little is known about the VP1unique region (VP1u), a part of one major capsid protein of human parvovirus B19 (B19), concerning its involvement in viral replication and infection cycle. Showing a phospholipase A2 (PLA2)-like activity, which is discussed to be necessary for viral release from host cell, its precise function remains unclear. The purpose of this study was to generate multifunctional monoclonal antibodies (mabs) for different applications that may be useful in investigating VP1u's relevance. To establish antiVP1u antibodies, spleen cells from Balb/c mice immunized with purified recombinant viral protein were used for generating antibody-producing hybridoma cell lines. Usability…
Humoral immunotherapy of multiple myeloma: perspectives and perplexities
2010
IMPORTANCE OF THE FIELDS Multiple myeloma (MM) is a hematological malignancy still remaining incurable despite the various therapies available, mainly because of the high fraction of refractory/relapsing cases. Therefore, the development of novel therapeutic approaches is urgently needed to overcome conventional treatment resistance. AREAS COVERED IN THIS REVIEW: In the era of targeted therapies, treatments combining a high specificity for neoplastic cells and the capability to interfere with environmental signals should be regarded as the weapons of choice. Monoclonal antibody (mAb)-based humoral immunotherapy could satisfy both these requirements when applied to MM. Indeed, many of the mo…
Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy
2003
Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approxi…
BCR-ABL as a target for novel therapeutic interventions.
2002
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of…
Screening for inhibitors of HIV gp120-CD4 binding using an enzyme-linked immunoabsorbent assay.
1993
Binding of the HIV-1 major viral surface glycoprotein, gp120, to the major cell receptor, CD4, is essential for HIV infection of the target cell and syncytium formation. An enzyme-linked immunoassay using solid phase CD4 was used to quantitate the binding of HIV-1 gp120 to CD4, and to assess the activity and mechanism of action of putative inhibitors of that reaction. Monoclonal antibodies to the gp120 binding site on CD4 (e.g., Leu3a) blocked gp120 binding, while monoclonal antibodies to other portions of CD4 (e.g. OKT4) did not. Both aurintricarboxylic acid and sulfonated polysaccharides (e.g., dextran sulfate) blocked CD4-gp120 interactions by binding to the CD4 component. Human polyclon…
Short synthetic CDR-peptides forming the antibody combining site of the monoclonal antibody against RNA bacteriophage fr neutralize the phage activit…
1996
The construction of a mouse hybridoma FRS2 secreting neutralizing monoclonal antibody specific for RNA bacteriophages fr, MS2 and GA is reported. The genes encoding the variable domains of the monoclonal antibody FRS2 heavy and light chains were cloned and sequenced and the corresponding complementarity determining region (CDR) peptides were chemically synthesized. The CDR-peptides were tested for their ability to neutralize the activity of RNA phage fr and related RNA phages MS2 and GA. The CDR-derived peptides H2, L2 and L3 interacted with the fr phage particles and neutralized fr phage activity. Two of these peptides-H2 and L3 also had the ability to neutralize partly the activity of rel…
Conformational and linear epitopes on virus-like particles of human papillomavirus type 33 identified by monoclonal antibodies to the minor capsid pr…
1995
The organization of epitopes on the minor capsid protein L2 of human papillomavirus (HPV) type 33 has been analysed using three monoclonal antibodies (MAbs) generated against a large fragment of the L2 protein (amino acids 82-259) expressed as a glutathione S-transferase fusion protein. The topology of the L2 epitopes has been investigated with respect to the structure of HPV-33 virus-like particles (VLPs). Two of the MAbs reacted with linear epitopes which were mapped to amino acids 153-160 and 163-170, respectively. These epitopes were accessible in denatured but not in native VLPs consisting of L1 and L2, suggesting an internal location. The third antibody was unable to detect denatured …
0135 : New regulators of iron metabolism, hepcidin and erythroferrone, in acute myocardial infarction
2016
Background Dysfunctional iron storage and transport are common in patients with chronic heart failure and associated with poor prognosis. Body iron could contribute to the pathogenesis of coronary artery disease (CAD) through its ability to induce oxidative stress. However, studies on the relationship between iron metabolism and CAD have yielded conflicting results. Patients and methods from the obseRvatoire des Infarctus de Cote d’Or (RICO) survey, 31 consecutive patients admitted in Intensive Care Unit for a first AMI were included. Serum concentrations of iron, transferrin, ferritin, the iron-regulatory hormone hepcidin and erythroferrone (a new hepcidinregulating hormone), transferrin s…
Does the renin-angiotensin system also regulate intra-ocular pressure?
2009
The renin-angiotensin-aldosterone system is known to play an essential role in controlling sodium balance and body fluid volumes, and thus blood pressure. In addition to the circulating system which regulates urgent cardiovascular responses, a tissue-localized renin-angiotensin system (RAS) regulates long-term changes in various organs. Many recognized RAS components have also been identified in the human eye. The highly vasoconstrictive angiotensin II (Ang II) is considered the key peptide in the circulatory RAS. However, the ultimate effect of RAS activation at tissue level is more complex, being based not only on the biological activity of Ang II but also on the activities of other produ…