Targeted drugs and Psycho-oncological intervention for breast cancer patients

Personalized medicine is a new field based on molecular biology and genomics in which targeted tumor therapies are administered to patients. Psycho- oncology is a complementary approach that considers social and psychological aspects of patients as part of the treatments for cancer patients. The aim of this mini-review is to weigh clinical benefits for breast cancer patients of both treatments and possibily enhance benefits by modulating the use of both interventions. We have compared and evaluated on the one hand the use of anti Vascular Endothelial Growth Factor and, on the other hand, psycho-oncological interventions in metastatic and non-metastatic breast cancer patients. Both treatments did not increase survival of metastatic breast cancer patients, while in a selected study psycho-oncological interventions extended lifespan of non-metastatic breast cancer patients and ameliorate psychological and social factors of metastatic breast cancer patients. Because the two approaches address completely different aspects of cancer patients, if the comparison is limited to the extension of survival, the value of these two treatments cannot be assessed and compared. It is likely that by comparing patients reported outcomes, possibly by using standardized Quality of Life questionnaires, both patients and health care providers can weigh the benefits of the two treatments. It is therefore important to evaluate the use of cancer patients’ quality of life measures as a mean to improve their experiences about life and treatment, and possibly to extend their survival

Determinants of the Proinflammatory Action of Ambient Particulate Matter in Immortalized Murine Macrophages

Background: Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children. Objectives: We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation. Methods: We examined the inflammatory potential of coarse [2.5–10 μm in aerodynamic diameter (PM2.5–10)] and fine [0.1–2.5 μm in aerodynamic diameter (PM0.1–2.5)] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 μg/cm2) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals, hydrocarbons, anions/cations, and endotoxin content. Results: Inflammatory responses to ambient PM varied markedly on an equal mass basis, with PM2.5–10 displaying the largest signals and contrasts among sites. Notably, we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM2.5–10. Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release, whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production, demonstrating that different PM components triggered inflammatory responses through separate pathways. Conclusions: We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells. Key words: copper, endotoxin, inflammation, iron, macrophages, metals, particulate matter, polyaromatic hydrocarbons. Environ Health Perspect 118:1728–1734 (2010). doi:10.1289/ehp.1002105 [Online 27 July 2010

Gene amplification as double minutes or homogeneously staining regions in solid tumors:Origin and structure

Double minutes (dmin) and homogeneously staining regions (hsr) are the cytogenetic hallmarks of genomic amplification in cancer. Different mechanisms have been proposed to explain their genesis. Recently, our group showed that the MYC-containing dmin in leukemia cases arise by excision and amplification (episome model). In the present paper we investigated 10 cell lines from solid tumors showing MYCN amplification as dmin or hsr. Particularly revealing results were provided by the two subclones of the neuroblastoma cell line STA-NB-10, one showing dmin-only and the second hsr-only amplification. Both subclones showed a deletion, at 2p24.3, whose extension matched the amplicon extension. Additionally, the amplicon structure of the dmin and hsr forms was identical. This strongly argues that the episome model, already demonstrated in leukemias, applies to solid tumors as well, and that dmin and hsr are two faces of the same coin. The organization of the duplicated segments varied from very simple (no apparent changes from the normal sequence) to very complex. MYCN was always overexpressed (significantly overexpressed in three cases). The fusion junctions, always mediated by nonhomologous end joining, occasionally juxtaposed truncated genes in the same transcriptional orientation. Fusion transcripts involving NBAS (also known as NAG), FAM49A, BC035112 (also known as NCRNA00276), and SMC6 genes were indeed detected, although their role in the context of the tumor is not clear

Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Background and methods: We have reviewed and pooled data from published studies to evaluate the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Thirty-one eligible studies reporting survival in 12782 patients characterised for MSI were pooled using a fixed- or random-effects model. Results: The summary odds ratio (OR) estimate for overall survival (OS) associated with MSI was 0.6 (95%CI 0.53-0.69, p < 0.0001), with no evidence of heterogeneity. The effect was similar for disease-free survival (DFS) (OR = 0.58, 95%CI 0.47-0.72, p < 0.0001). In a subset of patients treated with 5-fluorouracil (5-FU)-based chemotherapy a significant improved prognosis was found for microsatellite stable (MSS) tumours (OR = 0.52, 95%CI 0.4-0.6, p < 0.0001) with no heterogeneity (p = 0.53; I-2 = 0%). By contrast a large heterogeneity characterised the data relative to 396 patients with MSI tumours (OR = 0.69, 95%CI 0.3-1.5, p = 0.1; heterogeneity: p = 0.03; I-2 = 58%). Conclusions: This study confirmed the association between MSI and favourable prognosis as determined by both OS and DFS of CRC patients. A significant beneficial effect of 5-FU therapy was found for MSS tumours whilst no clear conclusion was reached for MSI tumours due to the high inter-study heterogeneity. We propose that this inconclusive result is due to the use of a single marker, such as MSI, that cannot account alone for the complexity of the mechanisms underlying 5-FU cytotoxicity. Future studies to predict response to 5-FU chemotherapy should include additional genome stability markers. (C) 2010 Elsevier Ltd. All rights reserved

Nutrients Intake in Individuals with Hypertension, Dyslipidemia, and Diabetes: An Italian Survey

The aim of this study is to evaluate whether nutrients intake in an Italian adult population receiving pharmacological treatment for hypertension, dyslipidemia, and diabetes are within the recommended values proposed by dietary guidelines. Cross-sectional data from the Cardiovascular Epidemiology Observatory/Health Examination Survey in 8462 individuals 35&ndash;79 years were used. Food consumption was assessed with a self-administered semi-quantitative food frequency questionnaire. Dietary sodium and potassium intakes were measured in 24-hour urine collection. Recommendations from WHO were used for salt and potassium intakes, those from the Diabetes and Nutrition Study Group for diabetes, and those from the European Society of Cardiology for hypertension and dyslipidemia. Salt intake in urine collection of participants receiving treatment for hypertension was 11.1 &plusmn; 4.0 g/day for men and 8.6 &plusmn; 3.3 g/day for women, higher than recommended. In participants treated for dyslipidemia, mean saturated fat intake was 11.4% and 11.6% total Kcal in men and women respectively, higher than recommended, while cholesterol intake was higher only in men (365.9 &plusmn; 149.6 mg/day). In both men and women receiving treatment for diabetes, mean intake of saturated fats (12.3% and 12.2% of total Kcal), simple carbohydrates (17.5% and 19.8% of total Kcal) and cholesterol (411.0 &plusmn; 150.4 and 322.7 &plusmn; 111.1 mg/day) were above the recommendations, while fiber intake was below (19.5 &plusmn; 6.3 and 17.5 &plusmn; 6.2 mg/day). Overall, 70% to 80% of participants treated for these conditions received advice from family doctors on dietary management; however, nutrition is far from being optimal

Microbiologically confirmed infections and antibiotic-resistance in a national surveillance study of hospitalised patients who died with COVID-19, Italy 2020-2021

Background: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. Methods: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. Results: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48&nbsp;h from admission) and 138 (87.9%) had secondary infections (&gt; 48&nbsp;h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. Conclusions: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance