Disease relevance of KIAA0999

• Then we performed biodistribution studies in mice bearing a subcutaneously implanted F9 murine teratocarcinoma, using a high-affinity human antibody fragment (L19) directed against the ED-B domain of fibronectin [1].
• The L19 overexpression in these breast tumor samples was not associated with the increased expression of the mRNAs for other ribosomal proteins (S16 and L26) [2].
• CONCLUSIONS: The ability of L19(scFv)(2) to target tumors in patients provides the foundations for new therapeutic applications, in which the L19 antibody is engineered to selectively deliver bioactive molecules to primary tumors as well as to metastases [3].
• RESULTS: The dimeric L19 antibody selectively localized in tumor lesions in aggressive types of lung cancer and colorectal cancer [3].
• CONCLUSION: Compared with other L19-based radioimmunoconjugates, I-131-L19-SIP is characterized by superior antitumor efficacy and toxicity profile in the F9 teratocarcinoma animal model [4].

High impact information on KIAA0999

• From this library, 2 clones, L7 and L19, were isolated by a differential hybridization procedure and shown by in situ hybridization to be Purkinje cell-specific within the cerebellum [5].
• We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis [6].
• The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells [6].
• No evidence of gene amplification for L19 was identified [2].
• The exchange of three large subunit proteins (L10, L19, L28) was detected by labeling of protein after ribosome synthesis had been inhibited with actinomycin D [7].

Biological context of KIAA0999

• When separated from the resistance mutation located in S12, the three different compensatory amino acid substitutions in L19 at position 40 (Q40H, Q40L and Q40R) caused a decrease in fitness while the G104A change had no effect on bacterial growth [8].

Anatomical context of KIAA0999

• Steady-state levels of L19 mRNA were lower in ribozyme-transfected cells compared to either vector-transfected cells or native PC12 cells, and a sequence within the L19 message was cleaved by the betaAPP hairpin ribozyme in vitro [9].
• Aortas isolated 4 hours, 24 hours, and 3 days after injection exhibited a selective and stable uptake of L19 when using radiographic or fluorescent imaging [10].

Other interactions of KIAA0999

• Of the 147 genes, 19 have no prior named Unigene cluster designation, and are designated herein as L1 to L19 [11].

Analytical, diagnostic and therapeutic context of KIAA0999

• The fact that ED-B is 100% homologous in human and mouse, thus ensuring that L19 reacts equally well with human and murine antigen, should ultimately expedite transfer of this reagent to clinical trials [12].
• Moreover, no significant differences in size were observed among the tumors from the different control groups (using the control fusion protein, a mixture of IL-2 and L19, or saline alone) [12].
• The resulting antibody, L19, bound to the ED-B domain of fibronectin with very high affinity (Kd = 54 pM), as determined by real-time interaction analysis with surface plasmon resonance detection, band shift analysis, and by competition experiments with electrochemiluminescent detection [13].
• Site-directed mutagenesis of residues in the A and B beta-strands (E9P and L19P) resulted in sawtooth patterns with all-or-none unfolding events that elongated the molecule by 19(+/-2) nm [14].
• Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e(6), after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors [15].

References