Low-dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF-A-mediated angiogenesis

Albertsson P, Lennernäs B, Norrby K. Low-dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF-A-mediated angiogenesis. APMIS 2011

Elderly patients with myocardial infarction selected for conservative or invasive treatment strategy

BACKGROUND: There are limited data on patients aged >75 years with myocardial infarction (MI), especially those who are treated conservatively. HYPOTHESIS: There are important differences in the clinical characteristics and outcome between elderly MI patients selected for invasive or conservative treatment strategy. METHODS: A total of 1,413 elderly patients (>75 years old) admitted to Sahlgrenska University Hospital, Gothenburg, Sweden with a final diagnosis of acute MI in 2001 or 2007, were divided into two groups, those who underwent a conservative treatment strategy (conservative group [CG], n=1,169) and those who underwent coronary angiography and were revascularized if indicated (invasive group [IG], n=244). RESULTS: Other than higher age in the CG, there were no significant differences in traditional risk factors such as hypertension, diabetes, and smoking in the two groups. A higher proportion of patients in the CG had a history of heart failure and cerebrovascular disease. The hazard ratio (with 95% confidence interval), adjusted for potential confounders, for 5 year mortality in the IG in relation to the CG was 0.49 (0.39, 0.62), P<0.0001. Overall, in the elderly with MI, the proportion who underwent an invasive treatment strategy doubled from 12% in 2001 to 24% in 2007, despite a slightly higher mean age. CONCLUSION: Elderly patients with MI in the CG (no coronary angiography), were generally older and a higher proportion had chronic diseases such as congestive heart failure and cerebrovascular disease than those in the IG. Our data suggest that the invasive treatment strategy is associated with better outcome. However, randomized trials will be needed to determine whether revascularization procedures are beneficial in elderly patients with MI, in terms of less symptoms, better outcome, and improved quality of life

BIOTINYLATED AND CHELATED POLY-L-LYSINE AS EFFECTOR FOR PRETARGETING IN CANCER THERAPY AND IMAGING

Objective: The aim of this study was to synthesise and evaluate polylysine-based effectors for pretargeted radioimmunotherapy and imaging. These molecules can readily be size-modified and charge-modified to decrease the renal uptake of radioactivity, which is often a major problem for small radiolabeled molecules. Several chelators and biotin molecules (for antibody-streptavidin-binding in vivo) are also easily incorporated into one structure because of the polylysine.Methods: The effectors were synthesised using poly-L-lysine, NHS-LC-biotin, CHX-A''-DTPA or p-SCN-Bn-DOTA and succinic anhydride. They were characterised, labelled with 213Bi for targeted α therapy, 68Ga for PET and 111In for SPECT, and evaluated in vitro. A kidney uptake study was performed as well with two different-sized 213Bi-labeled effectors, to evaluate how the difference in size affects the renal filtration.Results: Radiochemical purities between 97.4±0.6 % and 99.6±0.1 % and decay-corrected yields of 80.2±2.4 % after purification were achieved with the radiolabeled molecules, as well as a specific activity of 7.6 × 103GBq/µmol. The avidin binding capacity was 94.4±1.9%. The kidney uptake study demonstrated a reduction of renal absorbed dose by 80% when modifying the molecular size and charge.Conclusion: The synthesised polylysine-based effectors show potential for further in vivo evaluation in pretargeted radioimmunotherapy and imaging

Astatine-211 based radionuclide therapy: Current clinical trial landscape

Astatine-211 (211At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects

Acute coronary syndrome in octogenarians: association between percutaneous coronary intervention and long-term mortality

AIM: Evidence of improved survival after use of percutaneous coronary intervention (PCI) in elderly patients with acute coronary syndrome (ACS) is limited. We assessed the association between PCI and long-term mortality in octogenarians with ACS. METHODS AND RESULTS: We followed 353 consecutive patients aged ≥80 years hospitalized with ACS during 2006–2007. Among them, 182 were treated with PCI, whereas 171 were not. PCI-treated patients were younger and more often male, and had less stroke and dependency in activities of daily living, but there were no significant differences in occurrence of diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and uncured malignancies between the two groups. The association between PCI and all-cause mortality was assessed in the overall cohort and a 1:1 matched cohort based on propensity score (PS). In overall cohort, 5-year all-cause mortality was 46.2% and 89.5% in the PCI and non-PCI groups, respectively. Cox regression analysis in overall cohort by adjustment for ten baseline variables showed statistically significant association between PCI and reduced long-term mortality (P<0.001, hazard ratio 0.4, 95% confidence interval [CI] 0.2–0.5). In propensity-matched cohort, 5-year all-cause mortality was 54.9% and 83.1% in the PCI and non-PCI groups, respectively. Kaplan–Meier survival curves and log rank test showed significantly improved mean survival rates (P=0.001): 48 months (95% CI 41–54) for PCI-treated patients versus 35 months (95% CI 29–42) for non-PCI-treated patients. Furthermore, by performing Cox regression analysis, PCI was still associated with reduced long-term mortality (P=0.029, hazard ratio 0.5, 95% CI 0.3–0.9) after adjustment for PS and confounders: age, male sex, cognitive deterioration, uncured malignancies, left ventricular ejection fraction ≤45%, estimated glomerular filtration rate ≤35 mL/min, ST-segment elevation myocardial infarction, mitral regurgitation, and medication at discharge with clopidogrel and statins. CONCLUSION: In octogenarians with ACS, PCI was associated with improved survival from all-cause death over 5 years of follow-up

Matrix Metalloproteinases in Cytotoxic Lymphocytes Impact on Tumour Infiltration and Immunomodulation

To efficiently combat solid tumours, endogenously or adoptively transferred cytotoxic T cells and natural killer (NK) cells, need to leave the vasculature, traverse the interstitium and ultimately infiltrate the tumour mass. During this locomotion and migration in the three dimensional environment many obstacles need to be overcome, one of which is the possible impediment of the extracellular matrix. The first and obvious one is the sub-endothelial basement membrane but the infiltrating cells will also meet other, both loose and tight, matrix structures that need to be overridden. Matrix metalloproteinases (MMPs) are believed to be one of the most important endoprotease families, with more than 25 members, which together have function on all known matrix components. This review summarizes what is known on synthesis, expression patterns and regulation of MMPs in cytotoxic lymphocytes and their possible role in the process of tumour infiltration. We also discuss different functions of MMPs as well as the possible use of other lymphocyte proteases for matrix degradation

Nordic anal cancer (NOAC) group consensus guidelines for risk-adapted delineation of the elective clinical target volume in anal cancer

Background: To date, anal cancer patients are treated with radiotherapy to similar volumes despite a marked difference in risk profile based on tumor location and stage. A more individualized approach to delineation of the elective clinical target volume (CTVe) could potentially provide better oncological outcomes as well as improved quality of life. The aim of the present work was to establish Nordic Anal Cancer (NOAC) group guidelines for delineation of the CTVe in anal cancer.Methods: First, 12 radiation oncologists reviewed the literature in one of the following four areas: (1) previous delineation guidelines; (2) patterns of recurrence; (3) anatomical studies; (4) common iliac and para-aortic recurrences and delineation guidelines. Second, areas of controversy were identified and discussed with the aim of reaching consensus.Results: We present consensus-based recommendations for CTVe delineation in anal cancer regarding (a) which regions to include, and (b) how the regions should be delineated. Some of our recommendations deviate from current international guidelines. For instance, the posterolateral part of the inguinal region is excluded, decreasing the volume of irradiated normal tissue. For the external iliac region and the cranial border of the CTVe, we agreed on specifying two different recommendations, both considered acceptable. One of these recommendations is novel and risk-adapted; the external iliac region is omitted for low-risk patients, and several different cranial borders are used depending on the individual level of risk.Conclusion: We present NOAC consensus guidelines for delineation of the CTVe in anal cancer, including a risk-adapted strategy.Peer reviewe

Eggs of the copepod Acartia tonsa Dana require hypoxic conditions to tolerate prolonged embryonic development arrest

Additional file 1. Raw data and calculations for all experiments as well as an overview of experiments in this study

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen