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Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes' high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits., (© 2024. The Author(s).)

Competing Interests: None. The authors declared no conflicts of interest.

Importance: People with a history of incarceration may experience barriers in access to and receipt of health care in the US., Objective: To examine the associations of incarceration history and access to and receipt of care and the contribution of modifiable factors (educational attainment and health insurance coverage) to these associations., Design, Setting, and Participants: Individuals with and without incarceration history were identified from the 2008 to 2018 National Longitudinal Survey of Youth 1979 cohort. Analyses were conducted from October 2022 to December 2023., Main Measures and Outcomes: Access to and receipt of health care were measured as self-reported having usual source of care and preventive service use, including physical examination, influenza shot, blood pressure check, blood cholesterol level check, blood glucose level check, dental check, and colorectal, breast, and cervical cancer screenings across multiple panels. To account for the longitudinal study design, we used the inverse probability weighting method with generalized estimating equations to evaluate associations of incarceration history and access to care. Separate multivariable models examining associations between incarceration history and receipt of each preventive service adjusted for sociodemographic factors; sequential models further adjusted for educational attainment and health insurance coverage to examine their contribution to the associations of incarceration history and access to and receipt of health care., Results: A total of 7963 adults with 41 614 person-years of observation were included in this study; of these, 586 individuals (5.4%) had been incarcerated, with 2800 person-years of observation (4.9%). Compared with people without incarceration history, people with incarceration history had lower percentages of having a usual source of care or receiving preventive services, including physical examinations (69.6% vs 74.1%), blood pressure test (85.6% vs 91.6%), blood cholesterol level test (59.5% vs 72.2%), blood glucose level test (61.4% vs 69.4%), dental check up (51.1% vs 66.0%), and breast (55.0% vs 68.2%) and colorectal cancer screening (65.6% vs 70.3%). With additional adjustment for educational attainment and health insurance, the associations of incarceration history and access to care were attenuated for most measures and remained statistically significant for measures of having a usual source of care, blood cholesterol level test, and dental check up only., Conclusions and Relevance: The results of this survey study suggest that incarceration history was associated with worse access to and receipt of health care. Educational attainment and health insurance may contribute to these associations. Efforts to improve access to education and health insurance coverage for people with an incarceration history might mitigate disparities in care.

Importance: Medicaid expansion under the Patient Protection and Affordable Care Act is associated with gains in health insurance coverage, earlier stage diagnosis, and improved survival among patients with cancer., Objective: To examine the association of Medicaid expansion with changes in early mortality among adults undergoing surgical resection of non-small cell lung cancer (NSCLC), a setting in which access to care is a major determinant of survival., Design, Setting, and Participants: This cohort study used the National Cancer Database to identify 14 984 adults 45 to 64 years of age who underwent surgical resection of NSCLC between 2008 and 2019. Analysis was conducted between March 28, 2021, and September 1, 2023., Exposure: State of residence Medicaid expansion status., Main Outcomes and Measures: Descriptive statistics were used to compare study population characteristics by Medicaid expansion status of patients' state of residence. Difference-in-differences analyses were used to evaluate the association between Medicaid expansion and postoperative mortality before implementation of the ACA (2008-2013) vs after (2014-2019)., Results: Among 14 984 adults included, the mean (SD) age was 56.3 (5.1) years, 54.6% were women, and 62.1% lived in Medicaid expansion states. Both 30-day (from 0.97% to 0.26%) and 90-day (from 2.63% to 1.32%) postoperative mortality decreased from before the ACA to after among patients residing in Medicaid expansion states (both P < .001) but not in nonexpansion states (30-day mortality before the ACA, 0.75% vs after the ACA, 0.68%; P = .74; and 90-day mortality before the ACA, 2.43% vs after the ACA, 2.20%; P = .57), leading to a difference-in-differences of -0.64 percentage points (95% CI, -1.19 to -0.08; P = .03) for 30-day mortality and -1.08 percentage points (95% CI, -2.08 to -0.08; P = .03) for 90-day mortality. The difference-in-differences for in-hospital mortality was not significant (P = .34) between expansion states (1.41% before the ACA to 0.77% after the ACA; 0.63 percentage point decrease; P = .004) and nonexpansion states (1.49% before the ACA to 1.20% after the ACA; 0.30 percentage point decrease; P = .29)., Conclusions and Relevance: In this cohort study of patients with NSCLC, Medicaid expansion was associated with declines in 30- and 90-day postoperative mortality following hospital discharge. These findings suggest that Medicaid expansion may be an effective strategy for improving access to care and cancer outcomes in this population.

Purpose: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients., Methods and Materials: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearson's χ 2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations., Results: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire., Conclusions: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters., Competing Interests: James Bates reports being on advisory boards for Galera Therapeutics and Castle Biosciences. Sue Yom reports grants/contracts with EMD Serono and Bristol-Myers Squibb), and payment/honoraria from Up To Date, Springer, Elsevier, and ASTRO., (© 2023 The Authors.)

Background: Advanced glycation end products (AGEs) are reactive metabolites intrinsically linked with modern dietary patterns. Processed foods, and those high in sugar, protein and fat, often contain high levels of AGEs. Increased AGE levels are associated with increased breast cancer risk, however their significance has been largely overlooked due to a lack of direct cause-and-effect relationship., Methods: To address this knowledge gap, FVB/n mice were fed regular, low AGE, and high AGE diets from 3 weeks of age and mammary glands harvested during puberty (7 weeks) or adulthood (12 weeks and 7 months) to determine the effects upon mammary gland development. At endpoint mammary glands were harvested and assessed histologically (n ≥ 4). Immunohistochemistry and immunofluorescence were used to assess cellular proliferation and stromal fibroblast and macrophage recruitment. The Kruskal-Wallis test were used to compare continuous outcomes among groups. Mammary epithelial cell migration and invasion in response to AGE-mediated fibroblast activation was determined in two-compartment co-culture models. In vitro experiments were performed in triplicate. The nonparametric Wilcoxon rank sum test was used to compare differences between groups., Results: Histological analysis revealed the high AGE diet delayed ductal elongation, increased primary branching, as well as increased terminal end bud number and size. The high AGE diet also led to increased recruitment and proliferation of stromal cells to abnormal structures that persisted into adulthood. Atypical hyperplasia was observed in the high AGE fed mice. Ex vivo fibroblasts from mice fed dietary-AGEs retain an activated phenotype and promoted epithelial migration and invasion of non-transformed immortalized and tumor-derived mammary epithelial cells. Mechanistically, we found that the receptor for AGE (RAGE) is required for AGE-mediated increases in epithelial cell migration and invasion., Conclusions: We observed a disruption in mammary gland development when mice were fed a diet high in AGEs. Further, both epithelial and stromal cell populations were impacted by the high AGE diet in the mammary gland. Educational, interventional, and pharmacological strategies to reduce AGEs associated with diet may be viewed as novel disease preventive and/or therapeutic initiatives during puberty., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: In the US, despite the recent decline in breast cancer deaths, a persistent mortality disparity exists between black and white women with breast cancer, with black women having a 41% higher death rate. Several studies are now reporting that racial disparities can exist independent of socioeconomic and standard of care issues, suggesting that biological factors may be involved. Caveolin-1 (Cav1) loss in the tumor stromal compartment is a novel clinical biomarker for predicting poor outcome in breast cancer including triple negative subtype, however the mechanism of Cav1 loss is unknown. We previously identified miR-510-5p as a novel oncomir and propose here that the high levels observed in patients is a novel mechanism leading to stromal Cav1 loss and worse outcomes., Methods: Cav1 was identified as a direct target of miR-510-5p through luciferase, western blot and qPCR assays. Stromal cross talk between epithelial cells and fibroblasts was assessed in vitro using transwell co-culture assays and in vivo using xenograft assays., Results: We found that Cav1 is a direct target of miR-510-5p and that expression in fibroblasts results in an 'activated' phenotype. We propose that this could be important in the context of cancer disparities as we also observed increased levels of circulating miR-510-5p and reduced levels of stromal Cav1 in black women compared to white women with breast cancer. Finally, we observed a significant increase in tumor growth when tumor cells were co-injected with miR-510-5p expressing cancer associated fibroblasts in vivo ., Conclusion: We propose that miR-510-5p mediated negative regulation of Cav1 in fibroblasts is a novel mechanism of aggressive tumor growth and may be a driver of breast cancer disparity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 King, Krisanits, Guo, Blake, Nogueira, Jolly, Satterwhite, Turner, Hoffman, Evans-Knowell and Findlay.)

Climate change, the greatest threat to human health of our time, has implications for cancer control efforts throughout the cancer care continuum. The direct and indirect impacts of climate change on cancer risk, access to care, and outcomes are numerous and compounding, yet many oncology professionals might not be familiar with the strong connection between climate change and cancer. Thus, to increase awareness of this topic among cancer researchers, practitioners, and other professionals, this commentary discusses the links between climate change and cancer prevention and control, provides examples of adaptation and mitigation efforts, and describes opportunities and resources for future research., (©2023 American Association for Cancer Research.)

Chagas disease remains a neglected disease that is considered to be a public health problem. The early diagnosis of cases is important to improve the prognosis of infected patients and prevent transmission. Serological tests are the method of choice for diagnosis. However, two serological tests are currently recommended to confirm positive cases. In this sense, more sensitive and specific serological tests need to be developed to overcome these current diagnosis problems. This study aimed to develop a new recombinant multiepitope protein for the diagnosis of Chagas disease, hereafter named rTC. The rTC was constructed based on amino acid sequences from different combinations of Trypanosoma cruzi antigens in the same polypeptide and tested using an enzyme-linked immunosorbent assay (ELISA) to detect different types of Chagas disease. rTC was able to discriminate between indeterminate (IND) and cardiac (CARD) cases and cross-reactive diseases, as well as healthy samples, with 98.28% sensitivity and 96.67% specificity, respectively. These data suggest that rTC has the potential to be tested in future studies against a larger serological panel for the diagnosis of Chagas disease.

Background: visceral leishmaniasis (VL) is a critical public health problem in over ninety countries. The control measures adopted in Brazil have been insufficient when it comes to preventing the spread of this overlooked disease. In this context, a precise diagnosis of VL in dogs and humans could help to reduce the number of cases of this disease. Distinct studies for the diagnosis of VL have used single recombinant proteins in serological assays; however, the results have been variable, mainly in relation to the sensitivity of the antigens. In this context, the development of multiepitope-based proteins could be relevant to solving such problem., Methods: a chimeric protein (rMELEISH) was constructed based on amino acid sequences from kinesin 39 (k39), alpha-tubulin, and heat-shock proteins HSP70 and HSP 83.1, and tested in enzyme-linked immunosorbent (ELISA) for the detection of L. infantum infection using canine ( n = 140) and human ( n = 145) sera samples., Results: in the trials, rMELEISH was able to discriminate between VL cases and cross-reactive diseases and healthy samples, with sensitivity and specificity values of 100%, as compared to the use of a soluble Leishmania antigenic extract (SLA)., Conclusions: the preliminary data suggest that rMELEISH has the potential to be tested in future studies against a larger serological panel and in field conditions for the diagnosis of canine and human VL.

Background: There are approximately 25.6 million individuals with limited English proficiency (LEP) in the USA, and this number is increasing., Objective: Investigate associations between LEP and access to care in adults., Design: Cross-sectional nationally representative survey., Participants: Adults with (n = 18,908) and without (n = 98,060) LEP aged ≥ 18 years identified from the 2014-2018 Medical Expenditure Panel Survey MAIN MEASURES: Associations between LEP and access to healthcare and preventive services were evaluated with multivariable logistic regression models, stratified by age group (18-64 and ≥ 65 years). The official government definition of LEP (answers "not at all/not well/well" to the question "How well do you speak English?") was used. Access to care included having a usual source of care (and if so, distance from usual source of care, difficulty contacting usual source of care, and provision of extended hours), visiting a medical provider in the past 12 months, having to forego or delay care, and having trouble paying for medical bills. Preventive services included blood pressure and cholesterol check, flu vaccination, and cancer screening., Key Results: Adults aged 18-64 years with LEP were significantly more likely to lack a usual source of care (adjusted odds ratios [aOR] = 2.48; 95% confidence interval [CI] = 2.27-2.70), not have visited a medical provider (aOR = 2.02; CI = 1.89-2.16), and to be overdue for receipt of preventive services, including blood pressure check (aOR = 2.00; CI = 1.79-2.23), cholesterol check (aOR = 1.22; CI = 1.03-1.44), and colorectal cancer screening (aOR = 1.58; CI = 1.37-1.83) than adults without LEP. Results were similar among adults aged ≥ 65 years., Conclusions: Adults with LEP had consistently worse access to care than adults without LEP. System-level interventions, such as expanding access to health insurance coverage, providing language services, improving provider training in cultural competence, and increasing diversity in the medical workforce may minimize barriers and improve equity in access to care., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Bacteria halo blight (BHB), a coffee plant disease caused by Pseudomonas syringae pv. garcae , has been gaining importance in producing mountain regions and mild temperatures areas as well as in coffee nurseries. Most Coffea arabica cultivars are susceptible to this disease. In contrast, a great source of genetic diversity and resistance to BHB are found in C. arabica Ethiopian accessions. Aiming to identify quantitative trait nucleotides (QTNs) associated with resistance to BHB and the influence of these genomic regions during the domestication of C. arabica , we conducted an analysis of population structure and a Genome-Wide Association Study (GWAS). For this, we used genotyping by sequencing (GBS) and phenotyping for resistance to BHB of a panel with 120 C . arabica Ethiopian accessions from a historical FAO collection, 11 C . arabica cultivars, and the BA-10 genotype. Population structure analysis based on single-nucleotide polymorphisms (SNPs) markers showed that the 132 accessions are divided into 3 clusters: most wild Ethiopian accessions, domesticated Ethiopian accessions, and cultivars. GWAS, using the single-locus model MLM and the multi-locus models mrMLM, FASTmrMLM, FASTmrEMMA, and ISIS EM-BLASSO, identified 11 QTNs associated with resistance to BHB. Among these QTNs, the four with the highest values of association for resistance to BHB are linked to g000 (Chr&#95;0&#95;434&#95;435) and g010741 genes, which are predicted to encode a serine/threonine-kinase protein and a nucleotide binding site leucine-rich repeat (NBS-LRR), respectively. These genes displayed a similar transcriptional downregulation profile in a C. arabica susceptible cultivar and in a C. arabica cultivar with quantitative resistance, when infected with P. syringae pv. garcae . However, peaks of upregulation were observed in a C. arabica cultivar with qualitative resistance, for both genes. Our results provide SNPs that have potential for application in Marker Assisted Selection (MAS) and expand our understanding about the complex genetic control of the resistance to BHB in C. arabica . In addition, the findings contribute to increasing understanding of the C. arabica domestication history., Competing Interests: GCS was employed by company Tropical Melhoramento & Genética (TMG). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ariyoshi, Sant’ana, Felicio, Sera, Nogueira, Rodrigues, Ferreira, da Silva, Resende, Destéfano, Domingues and Pereira.)

Importance: Black patients are less likely than White patients to receive guideline-concordant cancer care in the US. Proton beam therapy (PBT) is a potentially superior technology to photon radiotherapy for tumors with complex anatomy, tumors surrounded by sensitive tissues, and childhood cancers., Objective: To evaluate whether there are racial disparities in the receipt of PBT among Black and White individuals diagnosed with all PBT-eligible cancers in the US., Design, Setting, and Participants: This cross-sectional study evaluated Black and White individuals diagnosed with PBT-eligible cancers between January 1, 2004, and December 31, 2018, in the National Cancer Database, a nationwide hospital-based cancer registry that collects data on radiation treatment, even when it is received outside the reporting facility. American Society of Radiation Oncology model policies were used to classify patients into those for whom PBT is the recommended radiation therapy modality (group 1) and those for whom evidence of PBT efficacy is still under investigation (group 2). Propensity score matching was used to ensure comparability of Black and White patients' clinical characteristics and regional availability of PBT according to the National Academy of Medicine's definition of disparities. Data analysis was performed from October 4, 2021, to February 22, 2022., Exposure: Patients' self-identified race was ascertained from medical records., Main Outcomes and Measures: The main outcome was receipt of PBT, with disparities in this therapy's use evaluated with logistic regression analysis., Results: Of the 5 225 929 patients who were eligible to receive PBT and included in the study, 13.6% were Black, 86.4% were White, and 54.3% were female. The mean (SD) age at diagnosis was 63.2 (12.4) years. Black patients were less likely to be treated with PBT than their White counterparts (0.3% vs 0.5%; odds ratio [OR], 0.67; 95% CI, 0.64-0.71). Racial disparities were greater for group 1 cancers (0.4% vs 0.8%; OR, 0.49; 95% CI, 0.44-0.55) than group 2 cancers (0.3% vs 0.4%; OR, 0.75; 95% CI, 0.70-0.80). Racial disparities in PBT receipt among group 1 cancers increased over time (annual percent change = 0.09, P < .001) and were greatest in 2018, the most recent year of available data., Conclusions and Relevance: In this cross-sectional study, Black patients were less likely to receive PBT than their White counterparts, and disparities were greatest for cancers for which PBT was the recommended radiation therapy modality. These findings suggest that efforts other than increasing the number of facilities that provide PBT will be needed to eliminate disparities.

Importance: Proton beam therapy (PBT) is a potentially superior technology to photon radiotherapy for tumors with complex anatomy, those surrounded by sensitive tissues, and childhood cancers., Objective: To assess patterns of use of PBT according to the present American Society of Radiation Oncology (ASTRO) clinical indications in the US., Design, Setting, and Participants: Individuals newly diagnosed with cancer between 2004 and 2018 were selected from the National Cancer Database. Data analysis was performed from October 4, 2021, to February 22, 2022. ASTRO's Model Policies (2017) were used to classify patients into group 1, for which health insurance coverage for PBT treatment is recommended, and group 2, for which coverage is recommended only if additional requirements are met., Main Outcomes and Measures: Use of PBT., Results: Of the 5 919 368 patients eligible to receive PBT included in the study, 3 206 902 were female (54.2%), and mean (SD) age at diagnosis was 62.6 (12.3) years. Use of PBT in the US increased from 0.4% in 2004 to 1.2% in 2018 (annual percent change [APC], 8.12%; P < .001) due to increases in group 1 from 0.4% in 2010 to 2.2% in 2018 (APC, 21.97; P < .001) and increases in group 2 from 0.03% in 2014 to 0.1% in 2018 (APC, 30.57; P < .001). From 2010 to 2018, among patients in group 2, PBT targeted to the breast increased from 0.0% to 0.9% (APC, 51.95%), and PBT targeted to the lung increased from 0.1% to 0.7% (APC, 28.06%) (P < .001 for both). Use of PBT targeted to the prostate decreased from 1.4% in 2011 to 0.8% in 2014 (APC, -16.48%; P = .03) then increased to 1.3% in 2018 (APC, 12.45; P < .001). Most patients in group 1 treated with PBT had private insurance coverage in 2018 (1039 [55.4%]); Medicare was the most common insurance type among those in group 2 (1973 [52.5%])., Conclusions and Relevance: The findings of this study show an increase in the use of PBT in the US between 2004 to 2018; prostate was the only cancer site for which PBT use decreased temporarily between 2011 and 2014, increasing again between 2014 and 2018. These findings may be especially relevant for Medicare radiation oncology coverage policies.

The molecular implications of food consumption on cancer etiology are poorly defined. The rate of nutrition associated non-enzymatic glycoxidation, a reaction that occurs between reactive carbonyl groups on linear sugars and nucleophilic amino, lysyl and arginyl groups on fats and proteins, is rapidly increased by food cooking and manufacturing processes. In this study, we assign nutrition-associated glycoxidation with significant oncogenic potential, promoting prostate tumor growth, progression, and metastasis in vivo. Advanced glycation end products (AGEs) are the final irreversible product of non-enzymatic glycoxidation. Exogenous treatment of prostate tumor cells with a single AGE peptide replicated glycoxidation induced tumor growth in vivo. Mechanistically, receptor for AGE (RAGE) deficiency in the stroma inhibited AGE mediated tumor growth. Functionally, AGE treatment induced RAGE dimerization in activated fibroblasts which sustained and increased the migratory potential of tumor epithelial cells. These data identify a novel nutrition associated pathway that can promote a tissue microenvironment conducive for aggressive tumor growth. Targeted and/or interventional strategies aimed at reducing AGE bioavailability as a consequence of nutrition may be viewed as novel chemoprevention initiatives., (Copyright © 2022. Published by Elsevier Inc.)

Background: Osteoma is a benign tumor of the bones, which can be classified as central or peripheral. The occurrence in the jawbones is uncommon, but when it occurs, there is a greater prevalence of the mandible. The etiology is still unknown, and the hypothesis of its development is debated., Case Presentation: A 35-year-old Caucasian man presenting a tumor lesion in the right jawbone that had been growing for 8 years sought medical service complaining of speaking impairment. According to the patient, the tumor appeared shortly after a minor trauma caused by tooth extraction. The diagnosis of the lesion was made through clinical, radiographic, and histological methods, and the surgical treatment was successful and satisfactory for the patient as well as the surgical team, despite a short follow-up., Conclusion: Etiopathogenesis of osteoma is not determined in the majority of cases. In the present report, it was possible to hypothesize the association between a minor trauma and the development of the tumor, reinforcing the reactive theory of tumor development. The uncommon location of the osteoma, as well the possibility of identifying the possible cause of the lesion, makes this case particularly interesting., (© 2021. The Author(s).)

Despite innovations in surgical technology and advancements in radiation therapy, radical treatments for clinically localized prostate cancer are associated with significant patient morbidity, including both urinary and sexual dysfunction. This has created a vital need for therapies and management strategies that provide an acceptable degree of oncologic efficacy while mitigating these undesirable side effects. Successful developments in screening approaches and advances in prostate imaging have allowed clinicians to identify, localize, and more precisely target early cancers. This has afforded urologists with an important opportunity to develop and employ focal ablation techniques that selectively destroy tumors while preserving the remainder of the gland, thus avoiding detrimental treatment effects to surrounding sensitive structures. A lack of high-level evidence supporting such an approach had previously hindered widespread adoption of focal treatments, but there are now numerous published clinical trials which have sought to establish benchmarks for safety and efficacy. As the clinical evidence supporting a potential role in prostate cancer treatment begins to accumulate, there has been a growing acceptance of focal therapy in the urologic oncology community. In this narrative review article, we describe the techniques, advantages, and side effect profiles of the most commonly utilized focal ablative techniques and analyze published clinical trial data supporting their evolving role in the prostate cancer treatment paradigm., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tau-20-1212). The series “Current and Future Topics on Prostate Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Purpose: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed., Methods: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript., Results: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time., Conclusion: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease., Competing Interests: Murilo de Almeida LuzConsulting or Advisory Role: Bayer, Janssen, Astellas PharmaSpeakers' Bureau: Bayer, Janssen, Astellas PharmaResearch Funding: Janssen, Bayer, Pfizer, Medivation, Myovant SciencesTravel, Accommodations, Expenses: Janssen, Astellas Pharma, Bayer, Roche Álvaro Sadek SarkisEmployment: Roche (I)Leadership: FerringHonoraria: Ferring, MSD, Genomic Health, Astellas PharmaConsulting or Advisory Role: FerringSpeakers' Bureau: FerringResearch Funding: FerringTravel, Accommodations, Expenses: Ferring Amr NowierResearch Funding: Astellas Pharma Ari Adamy JrSpeakers' Bureau: Janssen-Cilag, Astellas Pharma, Bayer, PfizerTravel, Accommodations, Expenses: Janssen-Cilag, Astellas Pharma Bruno Santos BenignoSpeakers' Bureau: Janssen-Cilag Eduardo Franco CarvalhalHonoraria: Janssen Leopoldo Alves Ribeiro FilhoConsulting or Advisory Role: FerringSpeakers' Bureau: Zodiac Pharma Lucas Mendes NogueiraConsulting or Advisory Role: BayerSpeakers' Bureau: Bayer, Astellas Pharma Marcelo Roberto Pereira FreitasConsulting or Advisory Role: Janssen Oncology, Zodiac PharmaSpeakers' Bureau: Astellas Pharma, Janssen Oncology Raja B. KhauliHonoraria: Astellas Pharma, Janssen, Algorithm, Hikma, LillyConsulting or Advisory Role: Astellas Pharma, HikmaSpeakers' Bureau: Algorithm, LillyResearch Funding: Astellas Pharma (Inst) Rodolfo Borges dos ReisConsulting or Advisory Role: JanssenSpeakers' Bureau: Janssen Rodrigo Antônio Ledezma RojasHonoraria: Ferring, Quanta SystemsConsulting or Advisory Role: Quanta Systems, FerringTravel, Accommodations, Expenses: Quanta SystemsNo other potential conflicts of interest were reported.

Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided., Objective: To present survey results on management of M0 CRPC in Brazil., Design, Setting, and Participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time., Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

The dependent coverage expansion (DCE) and Medicaid expansions (ME) under the Affordable Care Act (ACA) may differentially affect eligibility for health insurance coverage in young adult cancer patients. Studies examining temporal patterns of coverage changes in young adults following these policies are lacking. We used data from the National Cancer Database 2003-2015 to conduct a quasi-experimental study of cancer patients ages 19-34 years, grouped as DCE-eligible (19- to 25-year-olds) and DCE-ineligible (27- to 34-year-olds). Although private insurance coverage in DCE-eligible cancer patients increased incrementally following DCE implementation (0.5 per quarter; P < .001), an immediate effect on Medicaid coverage gains was observed after ME in all young adult cancer patients (3.01 for DCE-eligible and 1.62 for DCE-ineligible, both P < .001). Therefore, DCE and ME each had statistically significant and distinct effects on insurance coverage gains. Distinct temporal patterns of ACA policies' impact on insurance coverage gains likely affect patterns of receipt of cancer care. Temporal patterns should be considered when evaluating the impact of health policies.

Phosphine is a highly toxic gas that forms when aluminum phosphide, a restricted-use pesticide* typically used in agricultural settings, reacts with water. Acute exposure can lead to a wide range of respiratory, cardiovascular, and gastrointestinal symptoms, and can be fatal (1). On January 2, 2017, the Texas Department of State Health Services (DSHS) was notified by the Texas Panhandle Poison Center of an acute phosphine exposure incident in Amarillo, Texas. DSHS investigated potential occupational phosphine exposures among the 51 on-scene emergency responders; 40 (78.4%) did not use respiratory protection during response operations. Fifteen (37.5%) of these 40 responders received medical care for symptoms or as a precaution after the incident, and seven (17.5%) reported new or worsening symptoms consistent with phosphine exposure within 24 hours of the incident. Emergency response organizations should ensure that appropriate personal protective equipment (PPE) is used during all incidents when an unknown hazardous substance is suspected. Additional evaluation is needed to identify targeted interventions that increase emergency responder PPE use during this type of incident., Competing Interests: No conflicts of interest were reported.

Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells. Using a miR-145 luciferase reporter assay, we determined that ectopic SNAI1 expression significantly repressed the miR-145 promoter. DLD1-SNAI1 and HCT116-SNAI1 cells demonstrated decreased RT sensitivity and, conversely, miR-145 replacement significantly enhanced RT sensitivity. Of the five parental colon cancer cell lines, SW620 cells demonstrated relatively high endogenous SNAI1 and low miR-145 levels. In the SW620 cells, miR-145 replacement decreased CSC-related transcription factor expression, spheroid formation, and radiation resistance. In rectal cancer patient-derived xenografts, CSC identified by EpCAM+/aldehyde dehydrogenase (ALDH)+ demonstrated high expression of SNAI1, c-Myc, and Nanog compared with non-CSCs (EpCAM+/ALDH-). Conversely, patient-derived CSCs demonstrated low miR-145 expression levels relative to non-CSCs. These results suggest that the SNAI1:miR-145 pathway represents a novel therapeutic target in colorectal cancer to overcome RT resistance., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Lipids, including the diterpenes cafestol and kahweol, are key compounds that contribute to the quality of coffee beverages. We determined total lipid content and cafestol and kahweol concentrations in green beans and genotyped 107 Coffea arabica accessions, including wild genotypes from the historical FAO collection from Ethiopia. A genome-wide association study was performed to identify genomic regions associated with lipid, cafestol and kahweol contents and cafestol/kahweol ratio. Using the diploid Coffea canephora genome as a reference, we identified 6,696 SNPs. Population structure analyses suggested the presence of two to three groups (K = 2 and K = 3) corresponding to the east and west sides of the Great Rift Valley and an additional group formed by wild accessions collected in western forests. We identified 5 SNPs associated with lipid content, 4 with cafestol, 3 with kahweol and 9 with cafestol/kahweol ratio. Most of these SNPs are located inside or near candidate genes related to metabolic pathways of these chemical compounds in coffee beans. In addition, three trait-associated SNPs showed evidence of directional selection among cultivated and wild coffee accessions. Our results also confirm a great allelic richness in wild accessions from Ethiopia, especially in accessions originating from forests in the west side of the Great Rift Valley.

Background: Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers. Methods: We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate ORs and 95% confidence intervals (CI). Results: Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54-0.84; P interaction = 0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23-0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04-1.45; P interaction = 0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers. Conclusions: Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers. Impact: Future studies of these biomarkers and PDA should examine results by smoking status. Cancer Epidemiol Biomarkers Prev; 26(6); 914-22. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Trends in biliary tract cancer incidence rates have increased in Shanghai, China. These trends have coincided with economic and developmental growth, as well as a shift in dietary patterns to a more Westernized diet. To examine the effect of dietary changes on incident disease, we evaluated associations between diet and biliary tract cancers amongst men and women from a population-based case-control study in Shanghai, China. Biliary tract cancer cases were recruited from 42 collaborating hospitals in urban Shanghai, and population-based controls were randomly selected from the Shanghai Household Registry. Food frequency questionnaire data were available for 225 gallbladder, 190 extrahepatic bile duct, and 68 ampulla of Vater cancer cases. A total of 39 food groups were created and examined for associations with biliary tract cancer. Interestingly, only four food groups demonstrated a suggested association with gallbladder, extrahepatic bile duct, or ampulla of Vater cancers. The allium food group, consisting of onions, garlic, and shallots showed an inverse association with gallbladder cancer (OR: 0.81, 95% CI: 0.68-0.97). Similar trends were seen in the food group containing seaweed and kelp (OR: 0.79, 95% CI: 0.67-0.96). In contrast, both preserved vegetables and salted meats food groups showed positive associations with gallbladder cancer (OR:1.27, 95% CI: 1.06-1.52; OR: 1.18, 95% CI: 1.02-1.37, respectively). Each of these four food groups showed similar trends for extrahepatic bile duct and ampulla of Vater cancers. The results of our analysis suggest intake of foods with greater anti-inflammatory properties may play a role in decreasing the risk of biliary tract cancers. Future studies should be done to better understand effects of cultural changes on diet, and to further examine the impact diet and inflammation have on biliary tract cancer incidence.

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We evaluated the expression of the PCA3 gene in urine from patients with nodular hyperplasia/benign prostatic hyperplasia (PNH) or adenocarcinoma type prostate cancer (PCa).The study included 59 men: 22 with PCa, 26 with PNH, and 11 with no alterations (controls). Patients' urine was collected following prostatic massage and quantified by quantitative real-time PCR for prostate cancer antigen 3 gene (PCA3) and prostate-specific antigen gene (PSA) expression with the ACTB gene for normalization. PCA3 gene expression was detected in 16 patients with PCa and 4 with PNH; in the control group, there was no expression of the gene. No significant difference was observed in the mean levels of PCA3 and PSA expression, the PCA3/PSA ratio, and the total PSA levels when the groups of patients with PCa and PNH were compared. The area under the receiver operating characteristic (ROC) curve was 0.625, 0.596, 0.559, and 0.503 for PCA3 and PSA expression, the PCA3/PSA ratio, and total PSA levels, respectively. The sensitivity and specificity of the PCA3 test were 73 and 85%, respectively. Considering the estimated cutoff values (0.2219 and 0.5007 for PCA3 and PCA3/PSA, respectively), we observed a significant difference between the frequency of individuals with values above in the PCa group compared with the PNH group (P < 0.001). We conclude that the qualitative PCA3 test could be applied to initial screening for differentiation between individuals with PCa or PNH and those without prostate changes.

Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density-selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

In the treatment of extrusive luxation cases, it is important that the repositioning of extruded tooth in the socket is done as soon as possible. If this does not occur, periapical clot becomes organized and makes replantation difficult reposition. In this article the patient referred to the Clinics for dental trauma sustaining extrusive luxation of the maxillary right central incisor. The patient reported having suffered a bicycle accident 12 days before, which caused traumatic tooth injuries. The repositioning was attempted without success and an alternative form of treatment was necessary to solve the case. Intentional tooth replantation, which is the deliberate extraction of the tooth and its replantation, was indicated. This technique allows clot removal and correct repositioning of the extruded tooth. Care should be taken as endodontic treatment is required for the prevention of subsequent infection-related resorption. Intracanal dressing with calcium hydroxide was used for 30 days before final root filling. Splint, systemic antibiotics and avoidance of further damage to the root surface is also important. After 49 months, showed clinical and radiographic characteristics of normality and demonstrates the availability of this technique to adversity in trauma.

Objective: To analyze explanations for tuberculosis and therapeutic itineraries of Brazilian indigenous people., Methods: Case study with a qualitative-descriptive approach. We conducted semi-structured interviews with 11 Munduruku indigenous, including direct observation of treatment for tuberculosis in the municipality of Jacareacanga, south-western region of the state of Para, Brazil. To identify explanations for tuberculosis and therapeutic itineraries, we performed thematic content analysis., Results: Traditional medicine was the first therapeutic option chosen by the indigenous. However, biomedicine was also employed, which indicates a circulation between different therapeutic contexts and health concepts among the Munduruku. The explanations provided ranged from recognition of the signs and symptoms specific to tuberculosis to the attribution of the disease to a spirit that leaves the body and wanders in the woods, returning ill into the body. Unlike the biomedical model, which links tuberculosis transmission strictly to interpersonal contact, in closed spaces without natural lighting and ventilation (preferably domestic environments), the Munduruku associate the disease to an indirect contact between people socially distant (enemies or adversaries) in public and open places., Conclusions: The explanations made by the indigenous are unique and deserve the attention of those who are responsible for developing health public policies, as well as of the teams who work on the villages. To guarantee an efficient control of tuberculosis in these regions, it is necessary that the developed actions integrate biomedicine knowledge and the traditional medicine of the indigenous people, in addition to respecting and welcoming local culture manifestations.

Epithelial-to-mesenchymal transition (EMT) has been associated with poor treatment outcomes in various malignancies and is inversely associated with miRNA145 expression. Therefore, we hypothesized that SNAI2 (Slug) may mediate 5-fluorouracil (5FU) chemotherapy resistance through inhibition of miR145 in colorectal cancer and thus represents a novel therapeutic target to enhance current colorectal cancer treatment strategies. Compared with parental DLD1 colon cancer cells, 5FU-resistant (5FUr) DLD1 cells demonstrated features of EMT, including >2-fold enhanced invasion (P < 0.001) and migration, suppressed E-cadherin expression, and 2-fold increased SNAI2 expression. DLD1 and HCT116 cells with stable expression of SNAI2 (DLD1/SNAI2; HCT116/SNAI2) also demonstrated EMT features such as the decreased E-cadherin as well as significantly decreased miR145 expression, as compared with control empty vector cells. On the basis of an miR145 luciferase promoter assay, we demonstrated that SNAI2 repressed activity of the miR145 promoter in the DLD1 and HCT116 cells. In addition, the ectopic expressing SNAI2 cell lines demonstrated decreased 5FU sensitivity, and, conversely, miR145 replacement significantly enhanced 5FU sensitivity. In the parental SW620 colon cancer cell line with high SNAI2 and low miR145 levels, inhibition of SNAI2 directly with short hairpin sequence for SNAI2 and miR145 replacement therapy both decreased vimentin expression and increased in vitro 5FU sensitivity. In pretreatment rectal cancer patient biopsy samples, low miR145 expression levels correlated with poor response to neoadjuvant 5FU-based chemoradiation. These results suggested that the SNAI2:miR145 pathway may represent a novel clinical therapeutic target in colorectal cancer and may serve as a response predictor to chemoradiation therapy., (©2014 American Association for Cancer Research.)

Socioeconomic and environmental influences are established factors promoting cancer disparity, but the contribution of biologic factors is not clear. We report a mechanistic link between carbohydrate-derived metabolites and cancer that may provide a biologic consequence of established factors of cancer disparity. Glycation is the nonenzymatic glycosylation of carbohydrates to macromolecules, which produces reactive metabolites called advanced glycation end products (AGE). A sedentary lifestyle and poor diet all promote disease and the AGE accumulation pool in our bodies and also increase cancer risk. We examined AGE metabolites in clinical specimens of African American and European American patients with prostate cancer and found a higher AGE concentration in these specimens among African American patients when compared with European American patients. Elevated AGE levels corresponded with expression of the receptor for AGE (RAGE or AGER). We show that AGE-mediated increases in cancer-associated processes are dependent upon RAGE. Aberrant AGE accumulation may represent a metabolic susceptibility difference that contributes to cancer disparity., (©2014 American Association for Cancer Research.)

Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.

Introduction: MicroRNAs are small non-coding RNAs that are involved in the post-transcriptional negative regulation of mRNAs. MicroRNA 510 (miR-510) was initially shown to have a potential oncogenic role in breast cancer by the observation of its elevated levels in human breast tumor samples when compared to matched non-tumor samples. Few targets have been identified for miR-510. However, as microRNAs function through the negative regulation of their direct targets, the identification of those targets is critical for the understanding of their functional role in breast cancer., Methods: Breast cancer cell lines were transfected with pre-miR-510 or antisense miR-510 and western blotting and quantitative real time PCR were performed. Functional assays performed included cell growth, migration, invasion, colony formation, cytotoxicity and in vivo tumor growth. We performed a PCR assay to identify novel direct targets of miR-510. The study focused on peroxiredoxin 1 (PRDX1) as it was identified through our screen and was bioinformatically predicted to contain a miR-510 seed site in its 3' untranslated region (3'UTR). Luciferase reporter assays and site-directed mutagenesis were performed to confirm PRDX1 as a direct target. The Student's two-sided, paired t-test was used and a P-value less than 0.05 was considered significant., Results: We show that miR-510 overexpression in non-transformed and breast cancer cells can increase their cell growth, migration, invasion and colony formation in vitro. We also observed increased tumor growth when miR-510 was overexpressed in vivo. We identified PRDX1 through a novel PCR screen and confirmed it as a direct target using luciferase reporter assays. The reintroduction of PRDX1 into breast cancer cell lines without its regulatory 3'UTR confirmed that miR-510 was mediating its migratory phenotype at least in part through the negative regulation of PRDX1. Furthermore, the PI3K/Akt pathway was identified as a positive regulator of miR-510 both in vitro and in vivo., Conclusions: In this study, we provide evidence to support a role for miR-510 as a novel oncomir. We show that miR-510 directly binds to the 3'UTR of PRDX1 and blocks its protein expression, thereby suppressing migration of human breast cancer cells. Taken together, these data support a pivotal role for miR-510 in breast cancer progression and suggest it as a potential therapeutic target in breast cancer patients.

The prevalence of obesity, an established risk and progression factor for breast and many other cancer types, remains very high in the United States and throughout the world. Calorie restriction (CR), a reduced-calorie dietary regimen typically involving a 20-40% reduction in calorie consumption, prevents or reverses obesity, and inhibits mammary and other types of cancer in multiple tumor model systems. Unfortunately, the mechanisms underlying the tumor inhibitory effects of CR are poorly understood, and a better understanding of these mechanisms may lead to new intervention targets and strategies for preventing or controlling cancer. We have previously shown that the anticancer effects of CR are associated with decreased systemic levels of insulin-like growth factor-1 (IGF-1), the primary source of which is liver. We have also reported that CR strongly suppresses tumor development and growth in multiple mammary cancer models. To identify CR-responsive genes and pathways, and to further characterize the role of IGF-1 as a mediator of the anticancer effects of CR, we assessed hepatic and mammary gland gene expression, hormone levels and growth of orthotopically transplanted mammary tumors in control and CR mice with and without exogenous IGF-1. C57BL/6 mice were fed either control AIN-76A diet ad libitum (AL), subjected to 20%, 30%, or 40% CR plus placebo timed-release pellets, or subjected to 30% or 40% CR plus timed-release pellets delivering murine IGF-1 (mIGF-1, 20 μg/day). Compared with AL-fed controls, body weights were decreased 14.3% in the 20% CR group, 18.5% in the 30% CR group, and 38% in the 40% CR group; IGF-1 infusion had no effect on body weight. Hepatic transcriptome analyses indicated that compared with 20% CR, 30% CR significantly modulated more than twice the number of genes and 40% CR more than seven times the number of genes. Many of the genes specific to the 40% CR regimen were hepatic stress-related and/or DNA damage-related genes. Exogenous IGF-1 rescued the hepatic expression of several metabolic genes and pathways affected by CR. Exogenous IGF-1 also rescued the expression of several metabolism- and cancer-related genes affected by CR in the mammary gland. Furthermore, exogenous IGF-1 partially reversed the mammary tumor inhibitory effects of 30% CR. We conclude that several genes and pathways, particularly those associated with macronutrient and steroid hormone metabolism, are associated with the anticancer effects of CR, and that reduced IGF-1 levels can account, at least in part, for many of the effects of CR on gene expression and mammary tumor burden.

Obesity is an established risk and progression factor for postmenopausal breast cancer. Interventions to decrease caloric intake and/or increase energy expenditure beneficially impact tumor progression in normoweight humans and animal models. However, despite the increasingly high global prevalence of obesity, the effects and underlying mechanisms of these energy balance modulating interventions are poorly characterized in obese individuals. The goal of this study was to better characterize the mechanism(s) responsible for the link between energy balance and breast cancer progression in the postmenopausal obesity context. We compared the effects of calorie restriction (CR), treadmill exercise (EX), and mammalian target of rapamycin (mTOR inhibitor) treatment on body composition, serum biomarkers, cellular signaling, and mammary tumor growth in obese mice. Ovariectomized C57BL/6 mice were administered a diet-induced obesity regimen for 8 weeks, then randomized into three treatment groups: control (semipurified diet fed ad libitum, maintained the obese state); 30% CR (isonutrient relative to control except 30% reduction in carbohydrate calories); and EX (control diet fed ad libitum plus treadmill exercise). Mice were implanted with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Rapamycin treatment (5  mg/kg every 48  h) started at week 14. Tumors were excised at week 18. CR and rapamycin (but not EX) significantly reduced final tumor weight compared to control. In follow-up analysis, constitutive activation of mTOR ablated the inhibitory effects of CR on Wnt-1 mammary tumor growth. We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity-breast cancer progression link.

We describe a case of a patient presenting with HIV and paracoccidioidomycosis co-infection. At the time of diagnosis total CD4+ T-cell count was 4 cells/mm3. Histopathology revealed tuberculoid granulomas, scarce CD4+ T cells, a moderate number of CD8+ cells and the absence of Foxp3+ cells. Most of the cutaneous lesions healed after two weeks of treatment with amphotericin B. After 14 months the patient is still under antiretroviral therapy and no clinical evidence of recurrence of the mycosis has been observed.

We tested the hypothesis that obesity reversal by calorie restriction (CR) versus treadmill exercise (EX) differentially modulates adipose gene expression using 48 female C57BL/6 mice administered a diet-induced obesity (DIO) regimen for 8 weeks, then randomized to receive for 8 weeks either: (1) a control (AIN-76A) diet, fed ad libitum (DIO control); (2) a 30% CR regimen; (3) a treadmill EX regimen (with AIN-76A diet fed ad libitum); or (4) continuation of the DIO diet. Relative to the DIO controls, both CR and EX reduced adiposity by 35-40% and serum leptin levels by 80%, but only CR increased adiponectin and insulin sensitivity. Gene expression microarray analysis of visceral white adipose tissue revealed 209 genes responsive to both CR and EX, relative to the DIO group. However, CR uniquely altered expression of an additional 496 genes, whereas only 20 were uniquely affected by EX. Of the genes distinctly responsive to CR, 17 related to carbohydrate metabolism and glucose transport, including glucose transporter (GLUT) 4. Chromatin immunoprecipitation assays of the Glut4 promoter revealed that, relative to the DIO controls, CR significantly increased histone 4 acetylation, suggesting epigenetic regulation may underlie some of the differential effects of CR versus EX on the adipose transcriptome.