The management of cancer in the elderly: targeted therapies in oncology

Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described

Non-response in a survey of physicians on end-of-life care for the elderly

<p>Abstract</p> <p>Background</p> <p>Physicians are quite often surveyed with the aim to investigate their opinions regarding provision and improvement of health care. However, in many cases response rates tend to be rather low. The aim of the study is to reflect methodological aspects regarding survey conduction and to analyse factors that cause physicians to take part in a study on delivering end-of-life care for the elderly.</p> <p>Methods</p> <p>N = 4,727 physicians in Lower Saxony, Germany, received a standardised questionnaire on their attitudes about end-of-life care for the elderly. Non-responders were asked to state the reasons for non-participation. Comparison of the sociodemographic characteristics between responders and non-responders, and evaluation of the reasons for non-participation were made.</p> <p>Results</p> <p>The response rate to the questionnaire on end-of-life care for the elderly was 40% (n = 1,892). Of the non-responders to the questionnaire, 12.8% (n = 364) stated the reasons for non-participation. Overall, the response rate to the questionnaire varied with specialty and location of the practice: radiotherapists answered significantly more frequently than other categories of physician (e.g. general practitioners) and physicians in rural areas significantly more frequently than their colleagues in urban areas. The reasons most frequently given for non-participation were "Not concerned with the subject" and "No time".</p> <p>Conclusions</p> <p>The varying rates of response indicate that the survey was not sufficiently relevant to all groups of physicians, or that the awareness of the topic may be partly underdeveloped.</p

High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

Aeromagnetic anomalies reveal the link between magmatism and tectonics during the early formation of the Canary Islands

The 3-D inverse modelling of a magnetic anomaly measured over the NW submarine edifice of the volcanic island of Gran Canaria revealed a large, reversely-magnetized, elongated structure following an ENE-WSW direction, which we interpreted as a sill-like magmatic intrusion emplaced during the submarine growth of this volcanic island, with a volume that could represent up to about 20% of the whole island. The elongated shape of this body suggests the existence of a major crustal fracture in the central part of the Canary Archipelago which would have favoured the rapid ascent and emplacement of magmas during a time span from 0.5 to 1.9 My during a reverse polarity chron of the Earth’s magnetic field prior to 16 Ma. The agreement of our results with those of previous gravimetric, seismological and geodynamical studies strongly supports the idea that the genesis of the Canary Islands was conditioned by a strike-slip tectonic framework probably related to Atlas tectonic features in Africa. These results do not contradict the hotspot theory for the origin of the Canary magmatism, but they do introduce the essential role of regional crustal tectonics to explain where and how those magmas both reached the surface and built the volcanic edifices.Project CGL2015-63799-P of the Spanish Ministry of Economy and Competitivenes

Time in a Bottle: The Evolutionary Fate of Species Discrimination in Sibling Drosophila Species

Disadvantageous hybridization favors the evolution of prezygotic isolating behaviors, generating a geographic pattern of interspecific mate discrimination where members of different species drawn from sympatric populations exhibit stronger preference for members of their own species than do individuals drawn from allopatric populations. Geographic shifts in species' boundaries can relax local selection against hybridization; under such scenarios the fate of enhanced species preference is unknown. Lineages established from populations in the region of sympatry that have been maintained as single-species laboratory cultures represent cases where allopatry has been produced experimentally. Using such cultures dating from the 1950s, we assess how Drosophila pseudoobscura and D. persimilis mate preferences respond to relaxed natural selection against hybridization. We found that the propensity to hybridize generally declines with increasing time in experimental allopatry, suggesting that maintaining enhanced preference for conspecifics may be costly. However, our data also suggest a strong role for drift in determining mating preferences once secondary allopatry has been established. Finally, we discuss the interplay between populations in establishing the presence or absence of patterns consistent with reinforcement

Reproductive protein evolution in two cryptic species of marine chordate

<p>Abstract</p> <p>Background</p> <p>Reproductive character displacement (RCD) is a common and taxonomically widespread pattern. In marine broadcast spawning organisms, behavioral and mechanical isolation are absent and prezygotic barriers between species often operate only during the fertilization process. Such barriers are usually a consequence of differences in the way in which sperm and egg proteins interact, so RCD can be manifest as faster evolution of these proteins between species in sympatry than allopatry. Rapid evolution of these proteins often appears to be a consequence of positive (directional) selection. Here, we identify a set of candidate gamete recognition proteins (GRPs) in the ascidian <it>Ciona intestinalis </it>and showed that these GRPs evolve more rapidly than control proteins (those not involved in gamete recognition). Choosing a subset of these gamete recognition proteins that show evidence of positive selection (CIPRO37.40.1, CIPRO60.5.1, CIPRO100.7.1), we then directly test the RCD hypothesis by comparing divergence (omega) and polymorphism (McDonald-Kreitman, Tajima's D, Fu and Li's D and F, Fay and Wu's H) statistics in sympatric and allopatric populations of two distinct forms of <it>C. intestinalis </it>(Types A and B) between which there are strong post-zygotic barriers.</p> <p>Results</p> <p>Candidate gamete recognition proteins from two lineages of <it>C. intestinalis </it>(Type A and B) are evolving more rapidly than control proteins, consistent with patterns seen in insects and mammals. However, ω (d_N/d_S) is not significantly different between the sympatric and allopatric populations, and none of the polymorphism statistics show significant differences between sympatric and allopatric populations.</p> <p>Conclusions</p> <p>Enhanced prezygotic isolation in sympatry has become a well-known feature of gamete recognition proteins in marine broadcast spawners. But in most cases the evolutionary process or processes responsible for this pattern have not been identified. Although gamete recognition proteins in <it>C. intestinalis </it>do appear to evolve more rapidly, on average, than proteins with other functions, rates of evolution are not different in allopatric and sympatric populations of the two reproductively isolated forms. That sympatry is probably human-mediated, and therefore recent, may explain the absence of RCD.</p

Social disparities in exposures to bisphenol A and polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006

<p>Abstract</p> <p>Background</p> <p>Bisphenol A (BPA) and polyfluoroalkyl chemicals (PFCs) are suspected endocrine disrupting compounds known to be ubiquitous in people's bodies. Population disparities in exposure to these chemicals have not been fully characterized.</p> <p>Methods</p> <p>We analyzed data from the 2003-2006 National Health and Nutrition Examination Survey. Using multivariable linear regression we examined the association between urinary concentrations of BPA, serum concentrations of four PFCs, and multiple measures of socioeconomic position (SEP): family income, education, occupation, and food security. We also examined associations with race/ethnicity.</p> <p>Results</p> <p>All four PFCs were positively associated with family income, whereas BPA was inversely associated with family income. BPA concentrations were higher in people who reported very low food security and received emergency food assistance than in those who did not. This association was particularly strong in children: 6-11 year-olds whose families received emergency food had BPA levels 54% higher (95% CI, 13 to 112%) than children of families who did not. For BPA and PFCs we saw smaller and less consistent associations with education and occupation. Mexican Americans had the lowest concentrations of any racial/ethnic group of both types of chemicals; for PFCs, Mexican Americans not born in the U.S. had much lower levels than those born in the U.S.</p> <p>Conclusions</p> <p>People with lower incomes had higher body burdens of BPA; the reverse was true for PFCs. Family income with adjustment for family size was the strongest predictor of chemical concentrations among the different measures of SEP we studied. Income, education, occupation, and food security appear to capture different aspects of SEP that may be related to exposure to BPA and PFCs and are not necessarily interchangeable as measures of SEP in environmental epidemiology studies. Differences by race/ethnicity were independent of SEP.</p