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PDF file - 5906K, Supplemental Table I - Inhibition of mammary carcinogenesis in Wistar-Furth rats by mda-7/IL-24 Supplemental Table II - Microarray analysis of differential gene expression in FE1.2 + IL-24S compared to FE1.2 + IL-24AS cells. Supplemental Figure 1: Serum starvation induces GAS3 expression in both FE1.2 and FE1.3 cells. Supplemental Figure 2: GAS3 downregulation decreases the growth of cells in soft agar. Supplemental Figure 3: STAT3 inhibition reduced attachment of attaches cells to culture plates. Supplemental Figure 4: GAS3 expression reduced attachment of confluent cells to culture plates. Supplemental Figure 5: Binding of GAS3 to β1 integrin using immunoprecipitation assay. Supplemental Figure 6: GAS3 expression inhibits attachment to and proliferation on fibronectin coated culture plates. Supplemental Figure 7: GAS3 expression increases attachment to laminin coated culture plates. Supplemental Figure 8: GAS3 expression by immunohistochemistry.

Melanoma differentiation-associated gene (MDA)-7)/interleukin (IL)-24, a member of the IL-10 family of cytokines, inhibits growth of various human cancer cells, yet the underlying mechanism is largely unknown. Here, we report that mda-7/IL-24 efficiently suppresses the development of rat mammary tumors in vivo. Microarray analysis for genes differentially expressed in rat mammary tumor cells overexpressing MDA-7/IL-24 compared with those that do not express this cytokine identified growth arrest-specific gene-3 (gas3) as a target for mda-7/IL-24. Upregulation of gas3 by mda-7/IL-24 was STAT3 dependent. Induction of gas3 inhibited attachment and proliferation of tumor cells in vitro and in vivo by inhibiting the interaction of β1 integrin with fibronectin. A mutated GAS3, which is unable to bind β1 integrin, was also unable to inhibit fibronectin-mediated attachment and cell growth both in adherent and suspension cultures, suggesting that GAS3 exerts its effects through interaction with and regulation of β1 integrin. Thus, mda-7/IL-24 inhibits breast cancer growth, at least in part, through upregulation of GAS3 and disruption of β1 integrin function. Importantly, the expression of the mda-7/IL-24 receptor, IL-20R1, is highly correlated with GAS3 expression in human breast cancer (P = 1.02 × 10−9), and the incidence of metastases is significantly reduced in patients with HER2+ breast cancer expressing high-levels of IL-20R1. Together, our results identify a novel MDA-7/IL-24-GAS3-β1integrin–fibronectin signaling pathway that suppresses breast cancer growth and can be targeted for therapy. Mol Cancer Res; 11(6); 593–603. ©2013 AACR.

List of the Tumor types having mutations in both MYH9 and RHOA genes in the cBioPortal for Cancer Genomics database

List of the tumor specific mutations identified by whole-genome sequencing and validated in the 10 pairs of MPM tumor and germline DNA samples

Expression levels of candidate genes in 151 patients by gender and histology

List of SNVs identified in the analyzed genes

Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. Cancer Res; 76(2); 319–28. ©2015 AACR.

List of the 51 canonical pathways significantly enriched (p

Schematic representation of the SNVs and/or chromosomal aberrations identified in BAP1, NF2, TP53, MYH9, RHOA, MYH6, MYH10, PIK3C2A, TNFRSF1A, and 22q and 9p in a panel of 147 MPM tumors.

Expression levels for BAP1, NF2, TP53, MYH9, MYH6, MYH10, PIK3C2A, RHOA, and TNFRSF1A detected by Affymetrix® Human Gene 1.1 ST Array in 151 MPM

Whole genome sequencing data analysis of 10 MPM tumor and matched DNA generated by Complete Genomics platform

The Thoracic Surgery Social Media Network (TSSMN) is a collaborative effort of leading journals in cardiothoracic surgery to highlight publications via social media. This study aims to evaluate the 1-year results of a prospective randomized social media trial to determine the effect of tweeting on subsequent citations and nontraditional bibliometrics.A total of 112 representative original articles were randomized 1:1 to be tweeted via TSSMN or a control (non-tweeted) group. Measured endpoints included citations at 1 year compared with baseline, as well as article-level metrics (Altmetric score) and Twitter analytics. Independent predictors of citations were identified through univariable and multivariable regression analyses.When compared with control articles, tweeted articles achieved significantly greater increase in Altmetric scores (Tweeted 9.4 ± 5.8 vs Non-tweeted 1.0 ± 1.8, P.001), Altmetric score percentiles relative to articles of similar age from each respective journal (Tweeted 76.0 ± 9.1 percentile vs Non-tweeted 13.8 ± 22.7 percentile, P.001), with greater change in citations at 1 year (Tweeted +3.1 ± 2.4 vs Non-Tweeted +0.7 ± 1.3, P.001). Multivariable analysis showed that independent predictors of citations were randomization to tweeting (odds ratio [OR] 9.50; 95% confidence interval [CI] 3.30-27.35, P .001), Altmetric score (OR 1.32; 95% CI 1.15-1.50, P.001), open-access status (OR 1.56; 95% CI 1.21-1.78, P.001), and exposure to a larger number of Twitter followers as quantified by impressions (OR 1.30, 95% CI 1.10-1.49, P.001).One-year follow-up of this TSSMN prospective randomized trial importantly demonstrates that tweeting results in significantly more article citations over time, highlighting the durable scholarly impact of social media activity.

Graphical abstract

The Grand Bay estuary is in the north-central Gulf of Mexico and lacks riverine sediment input for marsh elevation maintenance. This study quantified trends in surface elevation change and accretion along an elevation gradient within the estuary. Elevation change rates were compared to short (13.71 mm/yr; 95% CI: -2.38 – 29.81), medium (6.97 mm/yr; 95% CI: 3.31 – 10.64), and long-range (3.50 mm/yr; 95% CI: 2.88 – 4.11) water level rise (WLR) rates for the region. Elevation change rates ranged from 0.54 mm/yr (95% CI: -0.63 – 1.72) to 5.45 mm/yr (95% CI: 4.27 – 6.62) and accretion rates ranged from 0.82 mm/yr (95% CI: -0.16 – 1.80) to 3.89 mm/yr (95% CI: 2.90 – 4.89) among marsh zones. Only the elevation change rate at a Juncus roemerianus marsh located high in the tidal frame was lower than long- ( P

Background Virtual journal clubs on Twitter (TweetChats) provide a platform to globally discuss publications. The Thoracic Surgery Social Media Network (TSSMN) is an organization that focuses on bringing social media attention to key publications in cardiothoracic surgery. TSSMN recently formed a Trainee Group with the goal of conducting chats covering key topics in cardiothoracic surgical training. The aim of this study was to characterize the pilot experience of this group. Methods The TSSMN trainee group held 3 TweetChats during the study period between 2017 and 2018. Each TweetChat was a structured discussion of 2 to 4 publications. The number of tweets, participants, most popular tweets, and impressions was assessed for each of the TweetChats. Results The 3 TweetChats had a mean of 40 participants (range, 36-45), generating an average of 497 tweets (range, 451-526) with a mean of 809,746 impressions (range, 591,814-1,140,000). Fruitful discussions on the topics of simulation in surgery, assessment of resident autonomy, and development of optimal organizational cultures to maximize team performance were held. Conclusions Twitter is a useful tool to collaborate and disseminate information. The 3 TweetChats organized by TSSMN trainee delegates generated approximately 1500 tweets with 2 million impressions. By these metrics, the feasibility of a trainee-led TSSMN TweetChat was confirmed.

The potential total number of solitary aculeate wasp and bee species on 34 research sites was estimated using non-parametric Chao and Jackknife tests of presence/absence. Successful estimates of the maximum number of species were achieved for some but not for other sites. Making further visits to a site or removing 'tourist' species data led to further success in estimating the potential number of species. The optimum number of visits required to successfully evaluate the aculeate fauna at a site was determined.

1. Yearly records of worker Vespula germanica (Fabricius) taken in suction traps at Silwood Park (28 years) and at Rothamsted Research (39 years) are examined. 2. Using the autocorrelation function (ACF), a significant negative 1-year lag followed by a lesser non-significant positive 2-year lag was found in all, or parts of, each data set, indicating an underlying population dynamic of a 2-year cycle with a damped waveform. 3. The minimum number of years before the 2-year cycle with damped waveform was shown varied between 17 and 26, or was not found in some data sets. 4. Ecological factors delaying or preventing the occurrence of the 2-year cycle are considered.

The Thoracic Surgery Social Media Network (TSSMN) represents a collaborative effort of leading journals in cardiothoracic surgery to highlight publications via social media, specifically Twitter. We conducted a prospective randomized trial to determine the effect of scheduled tweeting on nontraditional bibliometrics of dissemination.A total of 112 representative original articles (2017-2018) were selected and randomized 1:1 to an intervention group to be tweeted via TSSMN or a control (non-tweeted) group. Four articles per day were tweeted by TSSMN delegates for 14 days. Primary endpoints included change in article-level metrics (Altmetric) score pre-tweet and post-tweet compared with the control group. Secondary endpoints included change in Twitter analytics day 1 post-tweet and day 7 post-tweet for each article compared with baseline.Tweeting via TSSMN significantly improved article Altmetric scores (pre-tweet 1 vs post-tweet 8; P.001), Mendeley reads (pre-tweet 1 vs post-tweet 3; P.001), and Twitter impressions (day 1 post-tweet 1599 vs day 7 post-tweet 2296; P.001). Subgroup analysis demonstrates that incorporating photos into the tweets trended toward increased link clicks to the full-text article (P = .08) whereas tweeting at 1 pm Eastern Standard Time and 9 pm Eastern Standard Time generated the highest and lowest audience reach (P = .022), respectively. Articles published in adult cardiac surgery achieved the highest change in Altmetric score (P = .028) and Mendeley reads (P = .028), and were more likely to be retweeted (P = .042) than were those published on education, general thoracic surgery, and congenital surgery.Social media highlights of scholarly literature via TSSMN Twitter activity improves article Altmetric scores, Mendeley reads, and Twitter analytics, with dissemination to a greater audience.

The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the activity and/or the expression of MVA pathway enzymes. This Review summarizes recent advances and discusses unique opportunities for immediately targeting this metabolic vulnerability in cancer with agents that have been approved for other therapeutic uses, such as the statin family of drugs, to improve outcomes for cancer patients.

Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer, but the mechanisms responsible for these associations are not known. An animal model could facilitate such an understanding. Both genotoxic and nongenotoxic carcinogens induce aberrant crypt foci (ACF) in the colons of F344 rats. F344 rats were provided with diets that contained putative risk factors for CRC: low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure or a control diet for 14 wk. The rats were then assessed with biochemical measures and by topological examination for evidence of colon abnormalities. Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and ACF were increased from 0.7 to 13.6 lesions/colon (both P < 0.001). Rats exposed to the multiple environmental conditions associated with colon cancer, developed ACF similar to the heterogeneous or ill-defined ACF in the human colon. Heterogeneous ACF are the most frequently seen in humans and are also seen in rats shortly after exposure to the non-genotoxic colon carcinogen, dextransulfate sodium. The rodent model could be used to assess the pathways from diet and environment to colon cancer and to provide guidance for clinical studies.

Melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) is a novel member of the IL-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues. The ability to investigate the critical events underlying cancer initiation and progression, as well as the capacity to test the efficacy of novel therapeutics, has been significantly advanced by the development of genetically engineered mice (GEMs) that accurately recapitulate specific human cancers. We utilized three transgenic mouse models to better comprehend the in vivo role of MDA-7/IL-24 in breast cancer. Using the MMTV-PyMT spontaneous mammary tumor model, we confirmed that exogenously introducing MDA-7/IL-24 using a Cancer Terminator Virus caused a reduction in tumor burden and also produced an antitumor "bystander" effect. Next we performed xenograft studies in a newly created MMTV-MDA-7 transgenic model that over-expresses MDA-7/IL-24 in the mammary glands during pregnancy and lactation, and found that MDA-7/IL-24 overexpression delayed tumor growth following orthotopic injection of a murine PDX tumor cell line (mPDX) derived from a tumor formed in an MMTV-PyMT mouse. We also crossed the MMTV-MDA-7 line to MMTV-Erbb2 transgenic mice and found that MDA-7/IL-24 overexpression delayed the onset of mammary tumor development in this model of spontaneous mammary tumorigenesis as well. Finally, we assessed the role of MDA-7/IL-24 in immune regulation, which can potentially contribute to tumor suppression in vivo. Our findings provide further direct in vivo evidence for the role of MDA-7/IL-24 in tumor suppression in breast cancer in immune-competent transgenic mice.

// You-Jun Li 1,* , Guodong Liu 2,* , Lei Xia 4 , Xiao Xiao 4 , Jeff C. Liu 5 , Mitchell E. Menezes 6 , Swadesh K. Das 6 , Luni Emdad 6 , Devanand Sarkar 6 , Paul B. Fisher 6 , Michael C. Archer 2,3 , Eldad Zacksenhaus 3,5 and Yaacov Ben-David 3,4 1 Department of Anatomy, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, China 2 Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada 3 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada 4 Division of Biology, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, China 5 Toronto General Research Institute - University Health Network, Toronto, Ontario, Canada 6 Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA * These authors have contributed equally to this work Correspondence to: Yaacov Ben-David, email: // Eldad Zacksenhaus, email: // Keywords : mda-7/IL-24, HER2, breast cancer, prevention, mouse model Received : July 06, 2015 Accepted : September 23, 2015 Published : October 09, 2015 Abstract Melanoma differentiation associated gene-7/interleukin-24 ( mda-7/IL-24 ) encodes a tumor suppressor gene implicated in the growth of various tumor types including breast cancer. We previously demonstrated that recombinant adenovirus-mediated mda-7/IL-24 expression in the mammary glands of carcinogen-treated (methylnitrosourea, MNU) rats suppressed mammary tumor development. Since most MNU-induced tumors in rats contain activating mutations in Ha-ras, which arenot frequently detected in humans, we presently examined the effect of MDA-7/IL-24 on Her2/Neu - induced mammary tumors, in which the RAS pathway is induced. We generated tet-inducible MDA-7/IL-24 transgenic mice and crossed them with Her2/Neu transgenic mice. Triple compound transgenic mice treated with doxycycline exhibited a strong inhibition of tumor development, demonstrating tumor suppressor activity by MDA-7/IL-24 in immune-competent mice. MDA-7/IL-24 induction also inhibited growth of tumors generated following injection of Her2/Neu tumor cells isolated from triple compound transgenic mice that had not been treated with doxycycline, into the mammary fat pads of isogenic FVB mice. Despite initial growth suppression, tumors in triple compound transgenic mice lost mda-7/IL-24 expression and grew, albeit after longer latency, indicating that continuous presence of this cytokine within tumor microenvironment is crucial to sustain tumor inhibitory activity. Mechanistically, MDA-7/IL-24 exerted its tumor suppression effect on HER2 + breast cancer cells, at least in part, through PERP, a member of PMP-22 family with growth arrest and apoptosis-inducing capacity. Overall, our results establish mda-7/IL-24 as a suppressor of mammary tumor development and provide a rationale for using this cytokine in the prevention/treatment of human breast cancer.

Malignant pleural mesothelioma is a locally aggressive asbestos-related cancer that has a worldwide distribution and an overall poor prognosis. The average median survival for patients receiving the current best nonsurgical therapy, cisplatin/pemetrexed chemotherapy, is between 7 and 13 months. In selected patients with early stage disease and favorable tumor characteristics, aggressive surgical management in combination with adjuvant or neoadjuvant therapy extends survival in up to 20% of patients. Despite the benefits of surgery for mesothelioma, many patients are not suitable for operative intervention due to advanced stage disease at presentation or the inability to tolerate aggressive surgical resection. The frontiers of mesothelioma research and treatment include an urgent search for biomarkers that can reliably detect early stage cancer in at-risk populations, clinical tests or indices that can reliably predict prognosis among surgical candidates and the development of efficacious drugs and targeted therapies that offer more durable local disease control.

Introduction The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. Publisher PDF

Tracheobronchial injuries can be difficult to diagnose and manage, especially in the presence of polytrauma. A 50-year-old woman presented as a Level I trauma activation after being struck by a motor vehicle. Initial evaluation demonstrated intracranial hemorrhage and multiple chest injuries, including multilevel bilateral rib fractures, pneumomediastinum, and concern for tracheobronchial injury. After initial stabilization, bronchoscopy was performed and demonstrated an injury to the carina. We report a novel airway and ventilation strategy in the setting of concomitant tracheobronchial injury after severe blunt chest trauma in which extracorporeal support is contraindicated.

Aim: Understanding the role of enemy release in biological invasions requires an assessment of the invader's home range, the number of invasion events and enemy prevalence. The common wasp (Vespula vulgaris) is a widespread invader. We sought to determine the Eurasian origin of this wasp and examined world-wide populations for microsporidian pathogen infections to investigate enemy release. Location: Argentina, Eurasia, New Zealand. Methods: A haplotype network and phylogenetic tree were constructed from combined wasp COI and cytb mitochondrial markers. A morphometric study using canonical discriminant analysis was conducted on wing venation patterns. Microsporidian pathogens prevalence was also examined using small subunit rRNA microsporidia-specific primers. Results: Our spatially structured haplotype network from the native range suggested a longitudinal cline of wasp haplotypes along an east to west gradient. Six haplotypes were detected from New Zealand, and two from Argentina. The populations from the introduced range were genetically similar to the western European, United Kingdom and Ireland. The morphometric analysis showed significant morphological variation between countries and supported the Western European origin for New Zealand populations, although not for Argentine samples. Microsporidian infection rates were highest in New Zealand samples (54%), but no significant differences in infection rates were observed between the invaded and native range. Nosema species included matches to N. apis (a pathogen from honey bees) and N. bombi (from bumble bees). Main conclusions: Multiple introductions of the common wasp have occurred in the invaded range. A high microsporidian infection rate within the native range, combined with multiple introductions and a reservoir of pathogens in other social insects such as bees, likely contributes to the high microsporidian infection rates in the invaded range. Enemy release is likely to be more frequent when pathogens are rare in the home range, or are host specific and rare in reservoir populations of the introduced range. Fil: Lester, P. J.. Victoria University of Wellington; Nueva Zelanda Fil: Gruber, M. A. M.. Victoria University of Wellington; Nueva Zelanda Fil: Brenton Rule, E. C.. Victoria University of Wellington; Nueva Zelanda Fil: Archer, M.. York St. John University; Reino Unido Fil: Corley, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Dvorak, L.. Mestske muzeum Marianske Lazne; República Checa Fil: Masciocchi, Maité. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Oystaeyen, A. Van. Katholikie Universiteit Leuven; Bélgica

Cancer cells exhibit altered metabolism characterized by the generation of adenosine triphosphate by glycolysis and generation of fatty acids by de novo synthesis. The majority of genes involved in these pathways have binding sites for specificity protein (Sp) transcription factors in their promoters. Studies showing that Sp transcription factors, particularly Sp1, are involved in the regulation in cancer cells of hexokinase, pyruvate kinase, lactate dehydrogenase, fatty acid synthase, and hypoxia-inducible factor-1α are reviewed. Glycolysis and lipogenesis in cancers are also known to be stimulated by the constitutive activation of the PI3K/Akt signaling pathway. Evidence is presented for the notion that Sp transcription factors may act in concert with Akt to regulate the abnormal metabolism of cancer cells.

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.

Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.

Obesity, particularly visceral adiposity, is an established risk factor for colorectal cancer (CRC) and this is thought to result, at least in part, from insulin resistance and chronic hyperinsulinemia that may be mediated by adipokines. Serum levels of adiponectin, the most abundant protein secreted from adipocytes, are decreased in obesity and are inversely associated with insulin resistance and hyperinsulinemia. The objective of this study was to determine whether elevated circulating adiponectin plays a role in colon carcinogenesis using adiponectin transgenic (AdTg) mice that have 2–3-fold elevated circulating adiponectin but similar body weights as wildtype (WT) littermates used as controls. Eight-week old male and female AdTg and WT mice were treated with 4 weekly injections of the colon-specific carcinogen azoxymethane (AOM). One week following the last dose of AOM, all mice were placed on a high-fat diet and killed 24 weeks later, at 36 weeks of age, for the analysis of colon tumors. Glucose tolerance tests (GTT) were performed by injecting 2g/kg dextrose or 1.25–1.5 g/kg dextrose into all 12-week and 32–35-week-old mice respectively, and measuring blood from the tail vein 15, 30, 60 and 120 min following glucose administration. There were no significant differences in colon tumor incidence, number or size between AdTg and WT mice of either sex. AdTg mice of both sexes displayed resistance to diet-induced decreases in insulin sensitivity. Our results show that constitutively elevated levels of circulating adiponectin in AdTg mice do not confer protection against the development of colon tumors. © 2008 Wiley-Liss, Inc.

SYNOPSIS An account is given of worker characteristics, worker activities and brood characteristics in nests of Vespula vulgaris. Variations in queen productivity and efficiency of reproduction are discussed.

Wistar-Furth rats develop multiple mammary adenocarcinomas following initiation with methylnitrosourea, whereas Copenhagen rats are resistant to the development of mammary tumors. We have previously isolated cell lines from tumors induced in resistant Copenhagen × Wistar-Furth F1 rats by infusion of a retrovirus harboring v-Ha-ras directly into the main mammary ducts. Some of the cell lines were able to grow in soft agar, but a significant number did not display anchorage-independent growth. Here, we compared by microarray analysis genes that are differentially expressed in these cell lines. The expression of interleukin-24 (IL-24) and β4 integrin was highly correlated with the inability of cells to grow in soft agar. Ectopic expression of IL-24 in anchorage-independent cells inhibited their growth in monolayer culture, in soft agar, and in nude mice in vivo and inhibited their ability to migrate and invade in in vitro assays. Furthermore, growth suppression by IL-24 was associated with the transcriptional up-regulation of p27Kip1 via the activation of Stat3. We showed, for the first time, that β4 integrin is a downstream target of IL-24. However, β4 does not play a direct role in regulating the proliferative capacity of rat mammary tumor cells. Our results show that IL-24 suppresses the growth of rat mammary carcinoma cells and may play a role in the resistance of Copenhagen rats to mammary carcinogenesis. (Mol Cancer Res 2009;7(3):433–42)