Down-regulation of SKP2 induces apoptosis in lung-cancer cells

S-Phase kinase associated protein 2 (SKP2), an F-box protein constituting the substrate-recognition subunit of the SCF^SKP2 ubiquitin ligase complex, targets cell-cycle regulators, such as the cyclin-de-pendent kinase inhibitor p27^KIP1, for ubiquitin-mediated degradation. Our earlier studies indicated frequent amplification and over-expression of the SKP2 gene in primary small-cell lung cancers (SCLCs) and cell lines derived from this type of tumor, and showed that down-regulation of SKP2 expression by means of an antisense oligonucleotide inhibited the growth of SCLC cells in culture (Yokoi et al. Am J Pathol, 161, 207-216, 2002). The anti-sense effect was confirmed in two cell lines of non-small cell lung cancer (NSCLC) that also exhibited over-expression of the gene. In the work reported here, we examined the mechanism(s) responsible for antisense-mediated growth inhibition of SCLC- and NSCLC-derived cultures. SKP2 -antisense treatment not only suppressed DNA synthesis, as determined by [³H]thymidine incorporation, but also induced spontaneous apoptosis characterized by an increase in the sub-G1 population, fragmentation of nuclei, and activation of caspase-3. Our results suggest that since down-regulation of SKP2 appears to induce apoptosis in lung-cancer cells directly, targeting this molecule could represent a promising new therapeutic approach for this type of cancer, and possibly other tumors that over-express SKP2. (Cancer Sci 2003; 94: 344–349)     

Microvessel density and vascular endothelial growth factor expression in infiltrating lobular mammary carcinoma

Angiogenesis is an important prognostic factor in infiltrating ductal carcinoma (IDC). Vascular endothelial growth factor (VEGF) stimulates angiogenesis in vivo. VEGF expression has been correlated with high vascularity in IDC. However, little is known about the prognostic significance of microvessel density (MVD) and its correlation with the expression of VEGF in infiltrating lobular carcinoma (ILC). We analyzed tumor samples from 51 patients with primary classic ILC to determine the relationship between tumoral MVD and VEGF expression. Cases of pleomorphic lobular carcinoma and tubulolobular carcinoma were excluded. Five-micron thick sections obtained from formalin-fixed, paraffin-embedded tissue blocks were immunostained with antibodies to factor VIII-related antigen (Dako, Carpenteria, CA) and VEGF (Calbiochem, Boston, MA). The former was used for MVD analysis. The vessel counts from the three most vascular fields (x200 magnification) were recorded and the highest of the vessel counts of the three fields was designated as the MVD. The intensity of VEGF staining and the proportion of cells staining were scored. Both the vessel counts and the scoring of VEGF staining were evaluated by two independent pathologists. The Student's t-test and Wilcoxon rank sum test were used to compare mean MVD and VEGF scores according to various clinical and pathologic features. All significance tests were two-sided with an alpha-level of 0.05. There was good correlation between the MVD of each observer (correlation coefficient 0.775, p < 0.001). There was no correlation of MVD or VEGF score with the size or stage of the tumor. In addition, the MVD or VEGF score was not significantly different between axillary lymph node-positive cases and node-negative cases, between patients with recurrence and those without, and between patients who survived and those who died of disease. There was, however, a weak negative correlation between the MVD and VEGF expression (Spearman correlation coefficient -0.08). Neither MVD or VEGF immunoscore were associated with tumor recurrence or vital status in patients with ILC. The absence of a statistically significant positive correlation between MVD and VEGF expression suggests that other factors may play a more important role in the angiogenesis of ILC.     

Seamless Interworking Architecture for WBAN in Heterogeneous Wireless Networks with QoS Guarantees

The IEEE 802.15.6 standard is a communication standard optimized for low-power and short-range in-body/on-body nodes to serve a variety of medical, consumer electronics and entertainment applications. Providing high mobility with guaranteed Quality of Service (QoS) to a WBAN user in heterogeneous wireless networks is a challenging task. A WBAN uses a Personal Digital Assistant (PDA) to gather data from body sensors and forwards it to a remote server through wide range wireless networks. In this paper, we present a coexistence study of WBAN with Wireless Local Area Networks (WLAN) and Wireless Wide Area Networks (WWANs). The main issue is interworking of WBAN in heterogenous wireless networks including seamless handover, QoS, emergency services, cooperation and security. We propose a Seamless Interworking Architecture (SIA) for WBAN in heterogenous wireless networks based on a cost function. The cost function is based on power consumption and data throughput costs. Our simulation results show that the proposed scheme outperforms typical approaches in terms of throughput, delay and packet loss rate.     

Comparing Two Approaches to Acquiring HIV-Risk Data from Puerto Rican Women with Severe Mental Illness

Renewed interest has been expressed by researchers in mixed-method assessment that employs both quantitative and qualitative techniques in an expansive style that utilizes a variety of tactics to address research questions. Participants consisted of Puerto Rican women with severe mental illness living in Cuyahoga County, Ohio. The women were shadowed over a 2-year period to observe and verify behaviors that were self-reported using standardized instruments in semi-structured interviews. Concurrent criterion-related validity was employed to determine the extent of the correlation between responses obtained from the two approaches. Forty-four percent of the women were diagnosed with major depression and the mean overall GAF score was 58.5 ± 14.5. A comparison of the data collected using the different methodologies revealed that inconsistent and contradictory responses are not uncommon. The mixed-method design provided a more complete way of obtaining HIV-risk behavior data. Researchers and clinicians could benefit from mixed methods research that can provide greater opportunities to obtain data of a sensitive nature.