Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.

Specific correlation between the major chromosome 10q26 haplotype conferring risk for age-related macular degeneration and the expression of HTRA1.

PURPOSE: A region within chromosome 10q26 has a set of single nucleotide polymorphisms (SNPs) that define a haplotype that confers high risk for age-related macular degeneration (AMD). We used a bioinformatics approach to search for genes in this region that may be responsible for risk for AMD by assessing levels of gene expression in individuals carrying different haplotypes and by searching for open chromatin regions in the retinal pigment epithelium (RPE) that might include one or more of the SNPs. METHODS: We surveyed the PubMed and the 1000 Genomes databases to find all common (minor allele frequency > 0.01) SNPs in 10q26 strongly associated with AMD. We used the HaploReg and LDlink databases to find sets of SNPs with alleles in linkage disequilibrium and used the Genotype-Tissue Expression (GTEx) database to search for correlations between genotypes at individual SNPs and the relative level of expression of the genes. We also accessed Encyclopedia of DNA Elements (ENCODE) to find segments of open chromatin in the region with the AMD-associated SNPs. Predicted transcription factor binding motifs were identified using HOMER, PROMO, and RegulomeDB software programs. RESULTS: There are 34 polymorphisms within a 30-kb region that are in strong linkage disequilibrium (r2>0.8) with the reference SNP rs10490924 previously associated with risk for AMD. The expression of three genes in this region, PLEKHA1, ARMS2, and HTRA1 varies between people who have the low-AMD-risk haplotype compared with those with the high-AMD-risk haplotype. For PLEKHA1, 44 tissues have an expression pattern with the high-AMD-risk haplotype associated with low expression (rs10490924 effect size -0.43, p = 3.8 x 10-5 in ovary). With regard to ARMS2, the variation is most pronounced in testes: homozygotes with the high-AMD-risk haplotype express ARMS2 at lower levels than homozygotes with the low-AMD-risk haplotype; expression in heterozygotes falls in between (rs10490924 effect size -0.79, p = 7.5 x 10-24). For HTRA1, the expression pattern is the opposite; the high-AMD-risk haplotype has higher levels of expression in 27 tissues (rs10490924 effect size 0.40, p = 1.5 × 10-7 in testes). None of the other 22 genes within one megabase of rs10490924, or any gene in the entire genome, have mRNA expression levels that correlate with the high-AMD-risk haplotype. More than 100 other SNPs in the 10q26 region affect the expression of PLEKHA1 and ARMS2 but not that of HTRA1; none of these SNPs affects the risk for AMD according to published genome-wide association studies (GWASs). Two of the AMD-risk SNPs (rs36212732 and rs36212733) affect transcription factor binding sites in proximity to a DNase I hypersensitive region (i.e., a region of open chromatin) in RPE cells. CONCLUSIONS: SNPs in chromosome 10q26 that influence the expression of only PLEKHA1 or ARMS2 are not associated with risk for AMD, while most SNPs that influence the expression of HTRA1 are associated with risk for AMD. Two of the AMD-risk SNPs affect transcription factor binding sites that may control expression of one of the linked genes in the RPE. These findings suggest that the variation in the risk for AMD associated with chromosome 10q26 is likely due to variation in HTRA1 expression. Modulating HTRA1 activity might be a potential therapy for AMD.

Complement Factor B Inhibition or Deletion Is Not Sufficient to Prevent Neurodegeneration in a Murine Model of Glaucoma.

Purpose: Activation of the classical complement pathway is thought to contribute to the development and progression of glaucoma. The role of alternative complement or amplification pathways in glaucoma is not well understood. We evaluated complement factor B (FB) expression in postmortem human ocular tissues with or without glaucoma and the effect of FB inhibition and deletion in a mouse ocular hypertensive model of glaucoma induced by photopolymerized hyaluronic acid glycidyl methacrylate (HAGM). Methods: Human CFB mRNA in human eyes was assessed by RNAscope and TaqMan. HAGM model was performed on C57BL6/J mice. The effect of FB in HAGM model was evaluated with an oral FB inhibitor and Cfb-/- mice. Complement mRNA and proteins in mouse eyes were assessed by TaqMan and western blot, respectively. Results: CFB mRNA in human glaucomatous macular neural retina and optic nerve head was upregulated. Cfb mRNA is also upregulated in the HAGM model. Oral FB inhibitor, ED-79-GX17, dosed daily at 200 mg/kg for 3 days after intraocular pressure (IOP) induction in wild-type mice showed complement inhibition in ocular tissues and significantly inhibited systemic complement levels. Daily dosing of ED-79-GX17 for 30 days or Cfb deletion was also unable to prevent retinal ganglion cell or axon loss 30 days after IOP induction in mice. Conclusion: The alternative complement component FB may not substantially contribute to RGC loss in the HAGM mouse glaucoma model despite upregulation of Cfb expression and activation of the alternative pathway. The relevance of these findings to human glaucoma remains to be determined.

Health status of adolescent and young adult cancer survivors.

BACKGROUND: Adolescents and young adults (AYA) ages 15 to 29 years who are diagnosed with cancer are at risk for long-term morbidity and mortality associated with treatment of their cancer and the cancer itself. In this article, the authors describe the self-reported health status of AYA cancer survivors. METHODS: The authors examined 2009 data from the Behavioral Risk Factor Surveillance System, including demographic characteristics, risk behaviors, chronic conditions, health status, and health care access, among AYA cancer survivors compared with respondents who had no history of cancer. RESULTS: The authors identified 4054 AYA cancer survivors and 345,592 respondents who had no history of cancer. AYA cancer survivors, compared with respondents who had no history of cancer, reported a significantly higher prevalence of current smoking (26% vs 18%); obesity (31% vs 27%); chronic conditions, including cardiovascular disease (14% vs 7%), hypertension (35% vs 29%), asthma (15% vs 8%), disability (36% vs 18%), and poor mental health (20% vs 10%) and physical health (24% vs 10%); and not receiving medical care because of cost (24% vs 15%). CONCLUSIONS: AYA cancer survivors commonly reported adverse behavioral, medical, and health care access characteristics that may lead to poor long-term medical and psychosocial outcomes. Increased adherence to established follow-up guidelines may lead to improved health among AYA cancer survivors.

Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues.

T cell activation by intestinal dendritic cells (DC) induces gut-tropism. We show that, reciprocally, DC from peripheral lymph nodes (PLN-DC) induce homing receptors promoting CD8 T cell accumulation in inflamed skin, particularly ligands for P- and E-selectin. Differential imprinting of tissue-tropism was independent of Th1/Th2 cytokines and not restricted to particular DC subsets. Fixed PLN-DC retained the capacity to induce selectin ligands on T cells, which was suppressed by addition of live intestinal DC. By contrast, fixed intestinal DC failed to promote gut-tropism and instead induced skin-homing receptors. Moreover, the induction of selectin ligands driven by antigen-pulsed PLN-DC could be suppressed "in trans" by adding live intestinal DC, but PLN-DC did not suppress gut-homing receptors induced by intestinal DC. Reactivation of tissue-committed memory cells modified their tissue-tropism according to the last activating DC's origin. Thus, CD8 T cells activated by DC acquire selectin ligands by default unless they encounter fixation-sensitive signal(s) for gut-tropism from intestinal DC. Memory T cells remain responsive to these signals, allowing for dynamic migratory reprogramming by skin- and gut-associated DC.

Induction of Ocular Complement Activation by Inflammatory Stimuli and Intraocular Inhibition of Complement Factor D in Animal Models.

Purpose: Genome-wide association studies suggest a role for the complement system in age-related macular degeneration (AMD). We characterized ocular complement activation and evaluated a complement factor D (FD) neutralizing antibody. Methods: Mice were treated with toll-like receptor (TLR) ligands, intravitreal injection (IVT), or corneal debridement. Levels of complement proteins and mRNA were measured. A FD neutralizing antibody was administered IVT into eyes of rabbits that were challenged with LPS (lipopolysaccharide) administered intravenously. Results: Levels of C3 and factor B (FB) mRNA and protein in the eye were increased following intraperitoneal injection of TLR4 ligand LPS. Increased levels of C3 and FB breakdown products were observed in both eye tissues and plasma. Complement activation products were markedly reduced in C3-/- and Cfb-/- mice challenged with LPS. Ocular complement levels were also elevated in mice treated systemically with TLR2 and -3 ligands, injured by IVT injection or corneal debridement, or even in normal aging. IVT administration of a complement FD neutralizing antibody in rabbits inhibited LPS-induced complement activation in the posterior segment of the eye, but not in the anterior segment of the eye or in plasma. Conclusions: Systemic TLR stimulation and eye tissue injury induced time-dependent alternative complement pathway activation in the eye. Ocular complement levels were also gradually elevated during aging. An anti-FD antibody IVT potently inhibited LPS-induced complement activation in the posterior segment of the eye. This study provides insights into the dynamic profile of ocular complement activation, which is valuable for complement research in eye diseases and for developing complement therapeutics for AMD.

Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts.

Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention's (CDC's) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice.

The Association Between Adverse Childhood Experiences and Risk of Cancer in Adulthood: A Systematic Review of the Literature.

CONTEXT: Adverse childhood experiences (ACEs) can affect health and well-being across the life course. OBJECTIVE: This systematic review summarizes the literature on associations between ACEs and risk of cancer in adulthood. DATA SOURCES: We searched PubMed to identify relevant publications published on or before May 31, 2015. STUDY SELECTION: We included original research quantifying the association between ACEs and adult cancer incidence. Case reports and reviews were excluded. DATA ABSTRACTION: Two reviewers independently abstracted and summarized key information (eg, ACE type, cancer type, risk estimates) from included studies and resolved all discrepancies. RESULTS: Twelve studies were included in the review. In studies in which ACE summary scores were calculated, significant associations were observed between the scores and an increased risk of cancer in adulthood. Of the different types of ACEs examined, physical and psychological abuse victimization were associated with risk of any cancer in 3 and 2 studies, respectively. Two studies also reported significant associations with regard to sexual abuse victimization (1 for cervical cancer and 1 for any cancer). However, 2 other studies reported no significant associations between childhood sexual or physical abuse and incidence of cervical or breast cancer. LIMITATIONS: Because of heterogeneity across studies, we were unable to compute a summary effect estimate. CONCLUSIONS: These findings suggest that childhood adversity in various forms may increase a person's cancer risk. Further research is needed to understand the mechanisms driving this relationship and to identify opportunities to prevent and mitigate the deleterious effects of early adversity on long-term health.

Public Health Action Model for Cancer Survivorship.

Long-term objectives associated with cancer survivors have been suggested by Healthy People 2020, including increasing the proportion of survivors living beyond 5 years after diagnosis and improving survivors' mental and physical health-related quality of life. Prior to reaching these objectives, several intermediate steps must be taken to improve the physical, social, emotional, and financial well-being of cancer survivors. Public health has a role in developing strategic, actionable, and measurable approaches to facilitate change at multiple levels to improve the lives of survivors and their families. The social ecological model has been used by the public health community as the foundation of multilevel intervention design and implementation, encouraging researchers and practitioners to explore methods that promote internal and external changes at the individual, interpersonal, organizational, community, and policy levels. The survivorship community, including public health professionals, providers, policymakers, survivors, advocates, and caregivers, must work collaboratively to identify, develop, and implement interventions that benefit cancer survivors. The National Action Plan for Cancer Survivorship highlights public health domains and associated strategies that can be the impetus for collaboration between and among the levels in the social ecological model and are integral to improving survivor outcomes. This paper describes the Public Health Action Model for Cancer Survivorship, an integrative framework that combines the National Action Plan for Cancer Survivorship with the social ecological model to demonstrate how interaction among the various levels may promote better outcomes for survivors.

Evaluation of a Web-Based Program for African American Young Breast Cancer Survivors.

INTRODUCTION: Among women aged <45 years, African Americans have the highest breast cancer incidence rates of any ethnic/racial group and disproportionately higher rates of mortality. Young breast cancer survivors (YBCSs) may require psychosocial and reproductive health support when navigating diagnosis, treatment, and follow-up care. To address these needs, the Young Sisters Initiative: A Guide to a Better You! Program (YSI) was developed, implemented, and evaluated. The purpose of this study was to assess implementation and fidelity; identify barriers and facilitators to implementation; and explore audience access, use, and perceived value of the YSI. METHODS: A mixed-method, process evaluation of the YSI using interviews, an online screener, and post-use survey was conducted with data collected and analyzed from February through August 2013. Thematic analysis of qualitative data was conducted without qualitative data analysis software. Survey data were analyzed using PASW Statistics, version 18. RESULTS: YSI core elements were implemented as intended. A total of 1,442 people visited the YSI website; 93% of breast cancer survivors who visited the site (and consented to be in the study) were African American; 75% of post-use survey YBCS respondents were very or somewhat satisfied with the YSI; and 70% of YBCS respondents said the YSI content was somewhat or very useful. CONCLUSIONS: Findings suggest the value of using the Internet, including social media, to provide African-American YBCSs who are newly diagnosed, in treatment, and post-treatment with reproductive and psychosocial information and support. Further implementation and evaluation of programs addressing the needs of YBCSs are needed.

Post-treatment Neurocognition and Psychosocial Care Among Breast Cancer Survivors.

INTRODUCTION: Chemotherapy for breast cancer has been associated with cognitive problems; however, the impact of adjuvant hormone therapy is less clear. No studies have explored provider discussions about cognitive concerns or factors associated with neurocognitive treatment. This study examined cognitive problems, factors associated with having a provider discussion, and receipt of neurocognitive treatment. METHODS: Female breast cancer survivors (N=2,537) from the Sister Study and the Two Sister Study who were at least 1 year post-treatment were surveyed in 2012 about their cancer therapies (confirmed by medical records); cognitive concerns; related provider discussions; and neurocognitive treatment. A total of 2,296 women were included in the current 2014 analysis. Extensive covariate information was also ascertained for predictive multivariate models. RESULTS: The prevalence of self-reported cognitive problems after treatment was 60%. Of those reporting cognitive problems, only 37% had discussed those concerns with a provider and 15% had been treated for cognitive symptoms. The odds of reported cognitive concerns that started during and after treatment were elevated for those who received only hormone therapy and no chemotherapy (OR=1.64, 95% CI=1.15, 2.33); chemotherapy and no hormone therapy (OR=5.63, 95% CI=3.52, 9.00); or both (OR=6.33, 95% CI=4.21, 9.54) compared with those reporting neither treatment. CONCLUSIONS: The high prevalence of cognitive concerns underscores the importance of monitoring breast cancer survivors for potential neurocognitive effects of hormone and chemotherapy, discussions with survivors about those concerns, and treatment referrals. Monitoring changes over time can help to evaluate both psychosocial and neurocognitive care provided for survivors.

Psychosocial barriers and facilitators to clinical trial enrollment and adherence for adolescents with cancer.

Adolescents (aged 15-19 years) have not experienced the same survival gains as children and older adults diagnosed with cancer. Poor clinical trial enrollment and adherence rates among adolescents may account for some of this disparity. Although biological, regulatory, systemic, and practice-related challenges to clinical trial enrollment and adherence have been examined, studies of psychosocial factors, which can serve as barriers or facilitators to enrollment and adherence, are limited. To bring attention to these psychological factors, we reviewed existing literature on psychosocial barriers and facilitators that can affect an adolescent's decision to enroll and adhere to a clinical trial. We also provide potential strategies to address psychosocial factors affecting clinical trial accrual and adherence.

Treatment setting, clinical trial enrollment, and subsequent outcomes among adolescents with cancer: a literature review.

BACKGROUND: There has been an overall improvement in survival rates for persons with cancer over the past 35 years. However, these gains are less prevalent among adolescents with cancer aged 15 to 19 years, which may be due to lower clinical trial enrollment among adolescents with cancer. METHODS: We conducted a literature review to assess current research regarding clinical trial enrollment and subsequent outcomes among adolescents with cancer. The search included English-language publications that reported original data from January 1985 to October 2011. RESULTS: The search identified 539 records. Of these 539 records, there were 30 relevant original research articles. Multiple studies reported that adolescents with cancer are enrolled in clinical trials at lower rates compared with younger children and older adults. Treatment setting, physician type, and institution type may all be factors in the low enrollment rate among adolescents. Few data focused solely on adolescents, with many studies combining adolescents with young adults. The number of available studies related to this topic was limited, with significant variability in study design, methods, and outcomes. CONCLUSIONS: This literature review suggests that adolescents with cancer are not treated at optimal settings and are enrolled in clinical trials at low rates. This may lead to inferior treatment and poor subsequent medical and psychosocial outcomes. The scarcity in data further validates the need for additional research focusing on this population.

Cancer incidence rates and trends among children and adolescents in the United States, 2001-2009.

OBJECTIVES: Cancer continues to be the leading disease-related cause of death among children and adolescents in the United States. More current information is needed to describe recent cancer trends and identify demographic and geographic variations. METHODS: We analyzed data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results statewide registries representing 94.2% of the US population to identify cancers diagnosed among persons aged 0 to 19 years during 2001-2009. Age-adjusted rates and annual percentage change for trends were calculated. Data were stratified by age, gender, race, ethnicity, and geography. RESULTS: We identified 120,137 childhood and adolescent cancer cases during 2001-2009 with an age-adjusted incidence rate of 171.01 per million. The overall rate of all cancers combined remained stable over time (annual percent change [APC], 0.3%; 95% confidence interval [CI], -0.1 to 0.7). There was an increase in the overall cancer trend among African American children and adolescents (APC, 1.3%; 95% CI, 0.2 to 2.5). An increasing trend for thyroid cancer was observed among both genders (APC, 4.9%; 95% CI, 3.2 to 6.6) and specifically among adolescents and those in the Northeast, South, and West regions of the United States. Renal carcinoma incidence was increasing significantly overall (APC, 5.4%; 95% CI, 2.8 to 8.1). Extracranial and extragonadal germ cell tumors and melanoma were both significantly decreasing. CONCLUSIONS: This study reports the novel finding that renal carcinoma rates are increasing among children and adolescents. This study confirms that thyroid cancer rates are increasing and further describes rising cancer rates among African Americans.

Understanding and addressing the lack of clinical trial enrollment among adolescents with cancer.

Despite overall improvement in survival, morbidity, and quality of life of US patients with cancer, this progress is less prevalent in the population of adolescent and young adult patients with cancer, including those between the ages of 15 and 19 years. Evidence suggests that participation in clinical trials is associated with better survival outcomes among children and adolescents with cancer; however, adolescents have lower clinical trial participation rates compared with younger age cohorts. To better understand the unique concerns among adolescent patients with cancer, the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention convened a workgroup of researchers and health care providers in the field of adolescent and young adult oncology and cancer survivorship to examine the barriers and challenges limiting the participation of adolescents in clinical trials and to define ways to improve upon these concerns. This article summarizes the activities of the workgroup and their suggestions for enhanced accrual.

Reliability of the mouse model of choroidal neovascularization induced by laser photocoagulation.

PURPOSE: We attempted to reproduce published studies that evaluated whether the following factors influence choroidal neovascularization (CNV) induced by laser photocoagulation in murine retinas: small interfering RNA (siRNA), cobra venom factor, complement factors C3 and C5, and complement receptor C5aR. In addition, we explored whether laser-induced CNV in mice was influenced by the vendor of origin of the animals. METHODS: Reagents or genotypes reported by others to influence CNV in this model were assessed using our standard procedures. Retrospective analyses of control or placebo mice in many experiments were done to evaluate whether the CNV area induced by laser photocoagulation varied according to vendor. RESULTS: Administration of the following agents did not have a substantial impact on the CNV induced by laser burns in mice: siRNA, low-molecular-weight inhibitor of the C5a receptor (PMX53), or cobra venom factor. Jackson Laboratory (JAX) mice lacking either C3 or C5 had increased neovascularization compared to non-littermate JAX wild-type controls. Taconic mice lacking C3 had reduced CNV compared to non-littermate Taconic wild-type control mice. A retrospective analysis of vehicle-treated wild-type C57BL/6 mice used as controls across 132 experiments conducted from 2007 to 2010 revealed that mice purchased from JAX or from Charles River produced less neovascularization than mice from Taconic. CONCLUSIONS: We present our recommended methods for conducting experiments with the mouse laser-induced CNV model to enhance reproducibility and minimize investigator bias.

Lack of involvement of CEP adducts in TLR activation and in angiogenesis.

Proteins that are post-translationally adducted with 2-(ω-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others.

Opportunities for public health communication, intervention, and future research on breast cancer in younger women.

BACKGROUND: Approximately 6% of breast cancers in the United States occur in women under the age of 40 years. Compared with women ≥40 years of age, younger women are diagnosed at later stages, have higher rates of recurrence and death, and may be predisposed to secondary breast or ovarian cancer. An informal meeting of experts discussed opportunities for research and public health communication related to breast cancer among young (<40 and/or premenopausal) women. METHODS: In September 2011, the Centers for Disease Control and Prevention hosted 18 experts in oncology, genetics, behavioral science, survivorship and advocacy, public health, communication, ethics, nutrition, physical activity, and environmental health. They (1) reviewed research and programmatic knowledge on risk and preventive factors, early detection, and survivorship; and (2) discussed ideas for research, communication, and programmatic efforts related to young women diagnosed with or at risk for early onset breast cancer. RESULTS: Levels of evidence and themes for future research regarding risk and preventive factors, including exposures, were discussed. Early detection strategies, including screening, risk assessment, and genetic counseling, as well as survivorship issues, follow-up care, fertility and reproductive health, and psychosocial care were highlighted. CONCLUSION: Community and academic researchers, providers, advocates, and the federal public health community discussed strategies and opportunities for this unique population. Although the evidence is limited, future research and communication activities may be useful to organize future public health initiatives.

Receipt of psychosocial care among cancer survivors in the United States.

PURPOSE: Given the importance of psychosocial care for cancer survivors, this study used population-based data to characterize survivors who reported a discussion with health care provider(s) about the psychosocial effects of cancer and who reported using professional counseling or support groups (PCSG) and tested associations between receipt of psychosocial care and satisfaction with care. PATIENTS AND METHODS: We examined survivors of adult cancers from the 2010 National Health Interview Survey (N = 1,777). Multivariable logistic regression models examined factors associated with receipt of and satisfaction with psychosocial care. RESULTS: Most survivors (55.1%) reported neither provider discussions nor use of PCSG; 31.4% reported provider discussion only, 4.4% reported use of PCSG only, and 8.9% reported both. Non-Hispanic blacks (v non-Hispanic whites), married survivors, survivors of breast cancer (v prostate or less prevalent cancers), those treated with chemotherapy, and survivors reporting past research study/clinical trial participation were more likely to report provider discussion(s) (P < .01). Hispanics (v non-Hispanic whites), survivors age 40 to 49 years (v ≤ 39 years), survivors of breast cancer (v melanoma or less prevalent cancers), those diagnosed ≤ 1 year ago (v > 5 years ago), survivors treated with radiation, and past research participants were more likely to report use of PCSG (P < .05). Survivors reporting any psychosocial care were more likely to be "very satisfied" with how their needs were met (P < .001). CONCLUSION: Many survivors do not report a discussion with providers about the psychosocial effects of cancer, which reflects a missed opportunity to connect survivors to psychosocial services. These data can benchmark the success of efforts to improve access to cancer-related psychosocial care.

Changes among US Cancer Survivors: Comparing Demographic, Diagnostic, and Health Care Findings from the 1992 and 2010 National Health Interview Surveys.

Background. Differences in healthcare and cancer treatment for cancer survivors in the United States (US) have not been routinely examined in nationally representative samples or studied before and after important Institute of Medicine (IOM) recommendations calling for higher quality care provision and attention to comprehensive cancer care for cancer survivors. Methods. To assess differences between survivor characteristics in 1992 and 2010, we conducted descriptive analyses of 1992 and 2010 National Health Interview Survey (NHIS) data. Our study sample consisted of 1018 self-reported cancer survivors from the 1992 NHIS and 1718 self-reported cancer survivors from the 2010 NHIS who completed the Cancer Control (CCS) and Cancer Epidemiology (CES) Supplements. Results. The prevalence of reported survivors increased from 1992 to 2010 (4.2% versus 6.3%). From 1992 to 2010, there was an increase in long-term cancer survivors and a drop in multiple malignancies, and surgery remained the most widely used treatment. Significantly fewer survivors (<10 years after diagnosis) were denied insurance coverage. Survivors continue to report low participation in counseling or support groups. Conclusions. As the prevalence of cancer survivors continues to grow, monitoring differences in survivor characteristics can be useful in evaluating the effects of policy recommendations and the quality of clinical care.