Markers of Field Cancerization: Proposed Clinical Applications in Prostate Biopsies

Field cancerization denotes the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. This paper tabulates markers of prostate field cancerization known to date and discusses their potential clinical value in the analysis of prostate biopsies, including diagnosis, monitoring progression during active surveillance, and assessing efficacy of presurgical neoadjuvant and focal therapeutic interventions

Treatment of human muscle cells with popular dietary supplements increase mitochondrial function and metabolic rate

BACKGROUND: Obesity is a common pathology with increasing incidence, and is associated with increased mortality and healthcare costs. Several treatment options for obesity are currently available ranging from behavioral modifications to pharmaceutical agents. Many popular dietary supplements claim to enhance weight loss by acting as metabolic stimulators, however direct tests of their effect on metabolism have not been performed. PURPOSE: This work identified the effects popular dietary supplements on metabolic rate and mitochondrial biosynthesis in human skeletal muscle cells. METHODS: Human rhabdomyosarcoma cells were treated with popular dietary supplements at varied doses for 24 hours. Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α), an important stimulator of mitochondrial biosynthesis, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was measured using flow cytometry confirmed with confocal microscopy. Glycolytic metabolism was quantified by measuring extracellular acidification rate (ECAR) and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR). Total relative metabolism was quantified using WST-1 end point assay. RESULTS: Treatment of human rhabdomyosarcoma cells with dietary supplements OxyElite Pro (OEP) or Cellucore HD (CHD) induced PGC-1α leading to significantly increased mitochondrial content. Glycolytic and oxidative capacities were also significantly increased following treatment with OEP or CHD. CONCLUSION: This is the first work to identify metabolic adaptations in muscle cells following treatment with popular dietary supplements including enhanced mitochondrial biosynthesis, and glycolytic, oxidative and total metabolism

Beta-Alanine Suppresses Malignant Breast Epithelial Cell Aggressiveness Through Alterations In Metabolism and Cellular Acidity In Vitro

Background: Deregulated energetics is a property of most cancer cells. This phenomenon, known as the Warburg Effect or aerobic glycolysis, is characterized by increased glucose uptake, lactate export and extracellular acidification, even in the presence of oxygen. beta-alanine is a non-essential amino acid that has previously been shown to be metabolized into carnosine, which functions as an intracellular buffer. Because of this buffering capacity, we investigated the effects of beta-alanine on the metabolic cancerous phenotype. Methods: Non-malignant MCF-10a and malignant MCF-7 breast epithelial cells were treated with beta-alanine at 100 mM for 24 hours. Aerobic glycolysis was quantified by measuring extracellular acidification rate (ECAR) and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR). mRNA of metabolism-related genes was quantified by qRT-PCR with corresponding protein expression quantified by immunoblotting, or by flow cytometry which was verified by confocal microscopy. Mitochondrial content was quantified using a mitochondria-specific dye and measured by flow cytometry. Results: Cells treated with beta-alanine displayed significantly suppressed basal and peak ECAR (aerobic glycolysis), with simultaneous increase in glucose transporter 1 (GLUT1). Additionally, cells treated with beta-alanine exhibited significantly reduced basal and peak OCR (oxidative metabolism), which was accompanied by reduction in mitochondrial content with subsequent suppression of genes which promote mitochondrial biosynthesis. Suppression of glycolytic and oxidative metabolism by beta-alanine resulted in the reduction of total metabolic rate, although cell viability was not affected. Because beta-alanine treatment reduces extracellular acidity, a constituent of the invasive microenvironment that promotes progression, we investigated the effect of beta-alanine on breast cell viability and migration. beta-alanine was shown to reduce both cell migration and proliferation without acting in a cytotoxic fashion. Moreover, beta-alanine significantly increased malignant cell sensitivity to doxorubicin, suggesting a potential role as a co-therapeutic agent. Conclusion: Taken together, our results suggest that beta-alanine may elicit several anti-tumor effects. Our observations support the need for further investigation into the mechanism(s) of action and specificity of beta-alanine as a co-therapeutic agent in the treatment of breast tumors

Autochthonous human and canine strongyloides stercoralis infection in europe: Report of a human case in an italian teen and systematic review of the literature

Autochthonous human and canine strongyloidiasis is reported in Europe but is unclear whether the transmission of infection still occurs. We report a previously unpublished human case in an Italian teen and perform a systematic review of literature on autochthonous human and canine strongyloidiasis in Europe to investigate the current dynamic of transmission. Overall, 109 papers published after 1987 were included and one previously unpublished Italian case was added. Eighty case reports were retrieved and 42 of them (52.5%) had severe strongyloidiasis. Most cases were diagnosed in Spain, Italy and France. The median age was 58, the most represented age group was 61–70 years, 11 patients were under 30, and 7 of them were diagnosed after 2000. Epidemiological studies on human strongyloidiasis showed prevalence ranging from 0.56% to 28%. Overall, agriculture work, mine work and walking barefoot were the most commonly reported risk factors for infection. Canine strongyloidiasis was reported mainly in Italy (68 cases), but a few cases occurred also in Iceland, Finland, England, Germany, France, Switzerland, Russia, Slovakia, Romania and Greece. Autochthonous strongyloidiasis is still reported in Europe and sporadic transmission still occurs. Health care professionals should be aware of this issue to identify infected subjects and avoid adverse outcomes, especially in immunosuppressed patients. Further investigations are needed to clarify the zoonotic transmission of this nematode

European expert network on rare communicable diseases and other rare diseases linked to mobility and globalisation focused on health care provision (EURaDMoG) : a feasibility study

Introduction: In the current mobility and globalization context, there is a growing need to identify potential changes on the pattern of diseases in the European Union (EU)/European Economic Area (EEA) and provide accurate diagnosis and treatment for the population. The pattern of rare communicable diseases that can affect people returning to EU/EEA from travel abroad, visiting EU/EEA or establishing in the EU/EEA is of special relevance. The objective of this manuscript is to give an overview about the EURaDMoG study and discuss the feasibility of establishing a European network on rare communicable diseases and other rare conditions linked to mobility and globalization. Methods: We undertook a three-steps process where we first conducted a narrative review to estimate the prevalence and incidence and to list rare communicable and non-communicable diseases linked to mobility and globalization in the EU/EEA; second, we organized an international consultation workshop with experts in the diseases previously selected; and finally, the feasibility study analysed how successful a European expert network on rare diseases linked to mobility and globalization focused on health care provision would be, accounting for different operational and also sustainability criteria. Results: First, considering the areas or topics that the network should cover, it was concluded that communicable and non-communicable rare diseases linked to mobility and globalization should be differentiated. Second, since all non-communicable rare diseases linked to mobility and globalization identified are already covered by different European Reference Networks (ERNs), there is no need for them to be included in a new European network. Three scenarios were considered for establishing a potential European network for rare communicable diseases linked to Mobility and Globalisation with a focus on Health Care provision: 1) To maintain the current situation "Status Quo" scenario; 2) to create a specific European expert network (EEN) on rare communicable diseases linked to mobility and globalisation; 3) to develop a new ERN on communicable rare diseases linked to mobility and globalisation. Conclusions: Since the focus is the provision of health care, an ERN could have the potential to better boost the quality of care being facilitated by technological tools and online platforms that permit the safe and ethically acceptable exchange of data. However, this potential new network should not eclipse current existing networks and they should be complementary

EDB-FN Targeted Peptide–Drug Conjugates for Use against Prostate Cancer

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 h. Confocal microscopy studies demonstrated increased binding of ligand 8 to EDB-FN compared to ligand 1. Therefore, we hypothesized that the EDB-FN targeted peptides (1 and 8) conjugated with an anticancer drug via a hydrolyzable linker would provide selective cytotoxicity to the cancer cells. To test our hypothesis, we selected both the normal prostate cell line, RWPE-1, and the cancerous prostate cell lines, PC3, DU-145, LNCaP, and C4-2, to evaluate the anticancer activity of synthesized peptide–drug conjugates. Docetaxel (Doce) and doxorubicin (Dox) were used as anticancer drugs. Dox conjugate 13 containing disulfide linkage showed comparable cytotoxicity versus Dox after 72 h incubation in all the cancer cell lines, whereas it was found to be less cytotoxic on RWPE-1, suggesting that it can act as a Dox prodrug. Doce conjugate 14 was found to be less cytotoxic in all the cell lines as compared to drug alone

Malaria prophylaxis policy for travellers from Europe to the Indian Sub Continent

Analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%–4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999–2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped

Profile of Trypanosoma cruzi Infection in a Tropical Medicine Reference Center, Northern Italy

Chagas disease (CD) is endemic in Central and South America, Mexico and even in some areas of the United States. However, cases have been increasingly recorded also in non-endemic countries. The estimated number of infected people in Europe is in a wide range of 14000 to 181000 subjects, mostly resident in Spain, Italy and the United Kingdom

Global results on reset-induced periodic trajectories of planar systems

We study the existence of asymptotically stable periodic trajectories induced by reset feedback. The analysis is developed for a planar system. Casting the problem into the hybrid setting, we show that a periodic orbit arises from the balance between the energy dissipated during flows and the energy restored by resets, at jumps. The stability of the periodic orbit is studied with hybrid Lyapunov tools. The satisfaction of the so-called hybrid basic conditions ensures the robustness of the asymptotic stability. Extensions of the approach to more general mechanical systems are discussed.Work supported in part by ANR under project LimICoS, contract number 12 BS03 005 01, by the iCODE institute, research project of the Idex ParisSaclay, and by the University of Trento, grant OptHySYS.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by IEEE