Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion

Descriptive statistics.

<p>Descriptive statistics.</p

The relationship between biomarkers (1980) and happiness (2001).

<p>The relationship between biomarkers (1980) and happiness (2001).</p

Pairwise correlations between biomarkers and happiness.

<p>Pairwise correlations between biomarkers and happiness.</p

Pairwise correlations for the triglyceride measures between 1980, 1983, 1986 and 2001.

<p>Pairwise correlations for the triglyceride measures between 1980, 1983, 1986 and 2001.</p

Characteristics of the study population.

*<p>Median values and interquartile range (IQR), Mann-Whitney test for between-group differences.</p>†<p>Chi-squared test for differences between groups.</p><p>Abbreviations: BMI,body mass index; cf-DNA, cell-free DNA; COCs, combined oral contraceptives; CRP, C-reactive protein; N.S., not significant.</p

The UGT1A1 interaction network generated using the Ingenuity Pathway Analysis.

<p>The molecular relationships connecting UGT1A1 to DNA metabolism synthesis, fragmentation and quantity of DNA are indicated with Fx symbols, and the associated Canonical Pathways are indicated with CP symbols. Abbreviations: AHR, aryl hydrocarbon receptor; HMGB1, high-mobility group box protein 1; IL1B, interleukin-1 beta; MYC, v-myc myelocytomatosis viral oncogene homolog; NR1I3, nuclear receptor subfamily 1, group I, member 3; PPARGC1A, peroxisome proliferator –activated receptor gamma coactivator 1 alpha; RELA, v-rel reticuloendotheliosis viral oncogene homolog A (avian); TLR4, Toll-like receptor 4.</p

The top SNPs in each of the 9 sub-blocks in the <i>UGT1A</i> gene region (see Figure 2).

<p>The four SNPs that are associated most significantly with serum cf-DNA levels are in sub-block 8.</p>†<p>For each SNP, the ancestral allele was modelled, and the β coefficient represents the change in cf-DNA level (µg/ml) with one additional copy of the ancestral allele.</p>*<p>Adjusted for age, sex, BMI and genetic East-West stratification in the Finnish population.</p><p>Abbreviations: SNP, single nucleotide polymorphism; Chr, chromosome; bp, base pairs; MAF, minor allele frequency; S.E., standard error.</p

El Diario de Pontevedra : periódico liberal: Ano XXIV Número 7068 - 1907 novembro 9

Results of mixed models with age as a categorical predictor and log-insulin as a continuous predictor: LS means contrasts (No adult T2DM vs. adult T2DM) and significance at each age averaged over- (Table S1.) or adjusted for the levels of sex (Table S2.) and pairwise comparisons of Least-square means of BMI and 95% CIs at each age in each T2DM status group averaged over levels of sex (Figure S1.) at each age in each T2DM status group and sex group combination (M = males, F-females, 1 = No adult T2DM, 2 = adult T2DM) (Figure S2.) and adjusted for log(insulin). (DOCX 549 kb

Individual changes in hyperemia to baseline ratio of flow velocity in cold pressor test (CPT)

before cognac [before], after a moderate dose (ethanol 0.5 g/kg) [dose1] and a high dose (ethanol 1.0 g/kg) [dose2]. Control 1 corresponds to the first measurement on a control day. Control 2 corresponds to the measurement carried out 2 h after Control 1.<p><b>Copyright information:</b></p><p>Taken from "Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men"</p><p>http://www.cardiovascularultrasound.com/content/6/1/25</p><p>Cardiovascular Ultrasound 2008;6():25-25.</p><p>Published online 3 Jun 2008</p><p>PMCID:PMC2427009.</p><p></p