SummaryBackground In fast-paced dermatology clinics, the process of obtaining informed consents for biopsies and providing postprocedure instructions may be incomplete and inconsistent. Objectives To compare effectiveness of video-based education with that of verbal education for giving informed consent and providing postprocedure wound care instructions in patients undergoing skin biopsies. Methods In this randomized controlled trial, participants were randomized to receive either video education on portable video devices or conventional verbal instructions regarding skin biopsies. Participants completed a skin-biopsy knowledge assessment, patient satisfaction assessment and evaluation of educational medium. Main outcome measures were differences in the changes in the prestudy and poststudy knowledge assessment scores, patient satisfaction and evaluation of the educational medium. Results Eight-four patients undergoing skin biopsies at the University of California Davis dermatology clinic participated in the study. Participants in the control group had a nonstatistically significant increase in knowledge score (mean ± SD 1AE12 ± 1AE74), whereas those in the video group had a statistically significant increase in knowledge score (mean ± SD 1AE55 ± 1AE71). The difference in knowledge scores between the video and verbal groups was not statistically significant. Participants in both groups were highly satisfied with the biopsy education. On a 10-point scale, the mean ± SD usefulness and appeal of the videos were 9AE01 ± 1AE5 and 9AE01 ± 1AE66, respectively. Conclusions Our study demonstrated a significant increase in knowledge score following video education, but not following oral education. Although betweengroup comparisons did not achieve statistical significance, portable video media for presenting informed consent and wound care instructions for skin biopsies appear to be more effective and result in higher satisfaction than traditional oral education.

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Anti-ErbB2 antibodies targeting distinct epitopes can have different biological functions on cancer cells. A21 prepared by surface epitope masking (SEM) method is a tumor-inhibitory anti-ErbB2 monoclonal antibody. Previously we engineered a single chain chimeric antibody chA21 with potential for therapy of ErbB2-overexpressing tumors. Here, we mapped the A21 epitope on ErbB2 extracellular domain (ECD) by screening a combinatorial phage display peptide library, serial subdomain deletion, and mutagenesis scanning. X-ray crystal structure of the A21 scFv fragment at 2.1 A resolution was also determined. A molecular model of Ag-Ab complex was then constructed based on the crystal structures of the A21 scFv and ErbB2 ECD. Some of biological functions of the A21 mAb and its derivative antibodies including their tumor cell growth inhibition and effects on the expression, internalization, and phosphorylation of ErbB2 receptor were also investigated. The results showed that A21 recognized a conformational epitope comprising a large region mostly from ErbB2 extracellular subdomain I with several surface-exposed residues important for the binding affinity. These data provide unique functional properties of A21 that are quite different from two broadly used anti-ErbB2 mAbs, Herceptin and 2C4. It suggested that the A21 epitope may be another valuable target for designing new anti-ErbB2 therapeutics.

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Post-translational modifications (PTMs) play important roles in mediating protein functions in a wide variety of cellular events in vivo. HEMK2-TRMT112 heterodimer has been reported to be responsible for both histone lysine methylation and eukaryotic release factor 1 (eRF1) glutamine methylation. However, how HEMK2-TRMT112 complex recognizes and catalyzes eRF1 glutamine methylation is largely unknown. Here, we present two structures of HEMK2-TRMT112, with one bound to SAM and the other bound with SAH and methylglutamine (Qme). Structural analysis, complemented by mass spectrometry experiments, indicate that the HEMK2 utilizes a specific pocket to accommodate the substrate glutamine and catalyzes the subsequent methylation. Therefore, our work not only throws light on the protein glutamine methylation mechanism, but also reveals the dual activity of HEMK2 by catalyzing the methylation of both Lys and Gln.

p185her2/neu belongs to the ErbB receptor tyrosine kinase family, which has been associated with human breast, ovarian, and lung cancers. Targeted therapies employing ectodomain-specific p185 her2/neu monoclonal antibodies (mAbs) have demonstrated clinical efficacy for breast cancer. Our previous studies have shown that p185 her2/neu mAbs are able to disable the kinase activity of homomeric and heteromeric kinase complexes and induce the conversion of the malignant to normal phenotype. We previously developed a chimeric antibody chA21 that specifically inhibits the growth of p185 her2/neu -overexpressing cancer cells in vitro and in vivo. Herein, we report the crystal structure of the single-chain Fv of chA21 in complex with an N-terminal fragment of p185 her2/neu , which reveals that chA21 binds a region opposite to the dimerization interface, indicating that chA21 does not directly disrupt the dimerization. In contrast, the bivalent chA21 leads to internalization and down-regulation of p185 her2/neu . We propose a structure-based model in which chA21 cross-links two p185 her2/neu molecules on separate homo-or heterodimers to form a large oligomer in the cell membrane. This model reveals a mechanism for mAbs to drive the receptors into the internalization/degradation path from the inactive hypophosphorylated tetramers formed dynamically by active dimers during a "physiologic process." p185 her2/neu is one of the four receptor tyrosine kinases of the ErbB family. We initially found that both homodimerization and heterodimerization with other ErbB receptors will induce transphosphorylation of the intracellular domains and result in the downstream signaling for cell proliferation and transformation. Moreover our studies have established that heterodimerization leads to increased signaling and transforming activity (1, 2). Significant overexpression of p185 her2/neu results in abnormalities in cell signaling and can cause cell transformation. Early studies from several laboratories found that her2/neu gene was amplified and overexpressed in 20 -30% of breast and ovarian cancers. Breast cancers that have p185 her2/neu overexpressed have a more aggressive course associated with higher relapse rates (3). p185her2/neu represents the first oncoprotein target amenable for drug intervention and immunotherapy in which disabling the kinase reverses the malignant properties of the transformed cell and renders the tumor sensitive to chemotherapy and radiation therapy (4 -8).The p185 her2/neu protein possesses a similar architecture to the other three ErbB members of this family. These kinases are type 1 transmembrane proteins and comprise an extracellular domain (ECD) 4 with four subdomains (I/L1, II/S1, III/L2, IV/S2), a single transmembrane helix, an intracellular tyrosine kinase domain, and a C-terminal tail (9). Recent crystallographic studies revealed that the subdomains II and IV contribute to dimerization events of the ErbB receptors (10, 11). Monoclonal antibodies that bind the ectodomains of these ErbB proteins hav...

The aim of the current study was to evaluate a novel tumor marker, neuropeptide Y receptor Y1 (NPY1R), for the detection of circulating cancer cells and to investigate its clinical significance in breast cancer patients. The Digital Gene Expression Displayer tool of the Cancer Genome Anatomy Project was used to identify the marker gene NPY1R, which is able to detect circulating cancer cells. Nested quantitative polymerase chain reaction was performed to correlate the NPY1R expression levels with the clinicopathological features of 142 breast cancer patients. A follow-up study of 131 of the breast cancer patients was conducted for 38 months. Compared with the 60 normal control individuals, NPY1R was highly expressed in the cancer patients (P<0.01). These high levels of NPY1R expression were positively correlated with the clinical stage and lymph node metastasis status of the disease, as well as with the status of the estrogen and progesterone receptors (P<0.05). Breast cancer patients with circulating cancer cells that expressed NPY1R exhibited shorter tumor-specific survival when compared with those with no NPY1R expression (P<0.01). Additionally, the mortality rate was associated with HER2 expression in the NPY1R positive and negative groups. These results indicate that NPY1R may serve as a useful marker to predict breast cancer metastasis and to evaluate the prognosis of breast cancer patients.