Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Unlabelled: Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab.

Preorientation of olefins toward a single photodimer: cucurbituril-mediated photodimerization of protonated azastilbenes in water.

With the view to establishing the generality of cucurbit[8]uril as a template, the photodimerization of hydrochloride salts of eight azastilbenes has been investigated in an aqueous medium. Whereas in solution upon excitation all of these olefins yield products of geometric isomerization, cyclization, and hydration, in the presence of cucurbit[8]uril the predominant product is that of dimerization. Such a change in product distribution is attributed to the localization of the olefins by the host cucurbit[8]uril.

Mutation Research: the origin.

This brief commentary reflects on the founding of the journal Mutation Research. It includes a photograph of the participants in the scientific conference held in 1962 at the University of Leiden, The Netherlands, at which Professor F.H.

Construction of di-scFv through a trivalent alkyne-azide 1,3-dipolar cycloaddition.

Heterofunctional azide and alkyne PEG-linkers have been synthesized and site specifically conjugated to scFv via a reactive thiol functionality; two scFv were coupled by copper catalyzed 1,3-dipolar cycloaddition to make divalent scFv (di-scFv) with an inter-scFv distance defined to provide divalent binding; antigen binding was maintained for the di-scFv construct and increased several times compared to that of the parent scFv; the cycloaddition reaction reported herein represents an important ligation strategy to covalently link macromolecular proteins and retain sensitive structural conformations.

Synthesis and radiolabeling of selective high-affinity ligands designed to target non-Hodgkin's lymphoma and leukemia.

Selective high-affinity ligands (SHALs) were synthesized as molecular targeting agents for HLA-DR10, a cell surface receptor upregulated on malignant B-cell lymphocytes in non-Hodgkin's lymphoma and leukemia. SHALs are designed to mimic the affinity and selectivity of Lym-1, an antibody that binds to the beta-subunit of HLA-DR10. To bind selectively to HLA-DR10, SHALs were constructed to bind to two adjacent pockets on the surface of the beta-subunit of HLA-DR10 located within an epitope recognized by the Lym-1 antibody.

Coronary artery bypass surgery in elderly people.

An increasing number of elderly individuals are now undergoing coronary artery bypass surgery. Elderly patients, compared with patients of a younger age group, present for surgery with a greater burden of risk factors and reduced functional levels. Short-term outcomes are hence poorer in them.

Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF--induced thermoablative therapy for human breast cancer in mice.

Unlabelled: Antibody (mAb)-linked iron oxide nanoparticles (bioprobes) provide the opportunity to develop tumor specific thermal therapy (Rx) for metastatic cancer when inductively heated by an externally applied alternating magnetic field (AMF). To evaluate the potential of this Rx, in vivo tumor targeting, efficacy, and predictive radionuclide-based heat dosimetry were studied using (111)In-ChL6 bioprobes (ChL6 is chimeric L6) in a human breast cancer xenograft model.

Methods: Using carbodiimide, (111)In-DOTA-ChL6 (DOTA is dodecanetetraacetic acid) was conjugated to polyethylene glycol-iron oxide-impregnated dextran 20-nm particles and purified as (111)In-bioprobes.

Micronucleus frequency in peripheral blood lymphocytes and buccal mucosa cells of copper smelter workers, with special regard to arsenic exposure.

Occupational exposure in copper smelters may produce various adverse health effects including cancer which, according to available epidemiologic data, is associated mainly with exposure to arsenic. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelters workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of micronuclei (MN) frequency in peripheral blood lymphocytes and buccal epithelial cells from copper smelter workers was undertaken.

Photolithographic patterning of C2C12 myotubes using vitronectin as growth substrate in serum-free medium.

The C2C12 cell line is frequently used as a model of skeletal muscle differentiation. In our serum-free defined culture system, differentiation of C2C12 cells into myotubes required surface-bound signals such as substrate-adsorbed vitronectin or laminin. On the basis of this substrate requirement of myotube formation, we developed a photolithography-based method to pattern C2C12 myotubes, where myotubes formed exclusively on vitronectin surface patterns.

Asymmetric induction during photocyclization of chiral and achiral alpha-oxoamides within achiral zeolites.

The photochemistry of 31 alpha-oxoamides capable of undergoing gamma-hydrogen transfer has been examined within zeolites. These molecules, upon excitation, yield two products--a beta-lactam and oxazolidinone--in solution, both resulting from gamma-hydrogen transfer. While in benzene the major product is oxazolidinone, within an MY zeolite, the main product is a beta-lactam.

Adaptive response to DNA and chromosomal damage induced by X-rays in human blood lymphocytes.

Nucleoid sedimentation, single-cell gel electrophoresis (comet assay) and premature chromosome condensation (PCC) technique were utilized to estimate the involvement of DNA strand breaks and chromosomal damage in radio-adaptive response of stimulated human lymphocytes. Conditioning of cells with 0.02 Gy X-rays rendered them more resistant to single- and double-strand DNA breaks produced by 1 Gy challenging treatment as revealed by the sedimentation behaviour of the nucleoids and the comet assay.

Development of tissue plasminogen activator specific "on demand cleavable" (odc) linkers for radioimmunotherapy by screening one-bead-one-compound combinatorial peptide libraries.

New strategies are needed to protect normal organs from radiation in cancer radioimmunotherapy (RIT). This can be achieved by rapid clearance of radiometal in the circulation after accumulation of radioimmunoconjugates (RIC) in the tumor. Our strategy is to place highly efficient and specific cleavable linkers between radiometal chelates and the tumor targeting agents.

Templating photodimerization of stilbazoles with water-soluble calixarenes.

Water soluble six and eight membered calixarenes template the dimerization of trans-stilbazoles. In the absence of calixarenes at the concentrations employed stilbazoles mainly isomerize to the corresponding cis isomers. Calixarenes help to localize the olefins and orient them in a specific geometry to yield anti-head-tail dimers.

Induced transgenerational genetic effects in rodents and humans.

Delayed appearance of induced mutations has been observed in Drosophila, plants, rodents and recently in humans. The significance of this phenomenon is now recognized especially after the pioneering work of Nomura demonstrating transgenerational tumour induction in mice following treatment with urethane or ionizing radiation. A brief review of the literature on transgenerational genetic effects, namely, chromosomal aberrations and mutations, in rodents and humans is presented here.

Regioselective photodimerization of cinnamic acids in water: Templation with cucurbiturils.

Cinnamic acids upon irradiation in solution undergo geometric isomerization while dimerizing to different dimers in the crystalline state. Controlling the nature of the dimer formed upon irradiation remains a challenging task. We have aligned a variety of cinnamic acid molecules in a head-head fashion employing cucurbit[8]uril, a weakly water soluble host as a template.

Structure and dynamics of ASC2, a pyrin domain-only protein that regulates inflammatory signaling.

Pyrin domain (PYD)-containing proteins are key components of pathways that regulate inflammation, apoptosis, and cytokine processing. Their importance is further evidenced by the consequences of mutations in these proteins that give rise to autoimmune and hyperinflammatory syndromes. PYDs, like other members of the death domain (DD) superfamily, are postulated to mediate homotypic interactions that assemble and regulate the activity of signaling complexes.

Synthesis of conformationally constrained lysine analogues.

The synthesis of two conformationally constrained lysine analogues is reported. The synthesis of the novel analogue 1 based on the 3-aza-bicyclo[3.1.

Development of tumor targeting anti-MUC-1 multimer: effects of di-scFv unpaired cysteine location on PEGylation and tumor binding.

MUC1 mucin expressed in epithelial cancer, such as prostate and breast, is aberrantly glycosylated providing unique targets for imaging and therapy. In order to create a broadly applicable construct to target these unique epitopes on metastatic cancer, we selected an antibody fragment (scFv) that binds both synthetic MUC1 core peptide and epithelial cancer cell-expressed MUC1, and developed a recombinant bivalent molecule (di-scFv). Genetically engineered modifications of the di-scFv were constructed to create five molecular versions, each having a free cysteine (di-scFv-c) at different locations for site-specific conjugation.