Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase Ill trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4x epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4x docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6x epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy

Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice

Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting

Cancer stem cells (CSCs) subpopulation within the tumour is responsible for metastasis and cancer relapse. Here we investigate in vitro and in vivo the effects of a pancreatic (pro)enzyme mixture composed of Chymotrypsinogen and Trypsinogen (PRP) on CSCs derived from a human pancreatic cell line, BxPC3. Exposure of pancreatic CSCs spheres to PRP resulted in a significant decrease of ALDEFLUOR and specific pancreatic CSC markers (CD 326, CD 44 and CxCR4) signal tested by flow cytometry, further CSCs markers expression was also analyzed by western and immunofluorescence assays. PRP also inhibits primary and secondary sphere formation. Three RT2 Profiler PCR Arrays were used to study gene expression regulation after PRP treatment and resulted in, (i) epithelialmesenchymal transition (EMT) inhibition; (ii) CSCs related genes suppression; (iii) enhanced expression of tumour suppressor genes; (iv) downregulation of migration and metastasis genes and (v) regulation of MAP Kinase Signalling Pathway. Finally, in vivo anti-tumor xenograft studies demonstrated high anti-tumour efficacy of PRP against tumours induced by BxPC3 human pancreatic CSCs. PRP impaired engrafting of pancreatic CSC’s tumours in nude mice and displayed an antigrowth effect toward initiated xenografts. We concluded that (pro)enzymes treatment is a valuable strategy to suppress the CSC population in solid pancreatic tumours

The biogeography of South African terrestrial plant invasions

Thousands of plant species have been introduced, intentionally and accidentally, to South Africa from many parts of the world. Alien plants are now conspicuous features of many South African landscapes and hundreds of species have naturalised (i.e. reproduce regularly without human intervention), many of which are also invasive (i.e. have spread over long distances). There is no comprehensive inventory of alien, naturalised, and invasive plants for South Africa, but 327 plant taxa, most of which are invasive, are listed in national legislation. We collated records of 759 plant taxa in 126 families and 418 genera that have naturalised in natural and semi-natural ecosystems. Over half of these naturalised taxa are trees or shrubs, just under a tenth are in the families Fabaceae (73 taxa) and Asteraceae (64); genera with the most species are Eucalyptus,Acacia, and Opuntia. The southern African Plant Invaders Atlas (SAPIA) provides the best data for assessing the extent of invasions at the national scale. SAPIA data show that naturalised plants occur in 83% of quarter-degree grid cells in the country. While SAPIA data highlight general distribution patterns (high alien plant species richness in areas with high native plant species richness and around the main human settlements), an accurate, repeatable method for estimating the area invaded by plants is lacking. Introductions and dissemination of alien plants over more than three centuries, and invasions over at least 120 years (and especially in the last 50 years) have shaped the distribution of alien plants in South Africa. Distribution patterns of naturalised and invasive plants define four ecologically-meaningful clusters or “alien plant species assemblage zones”, each with signature alien plant taxa for which trait-environment interactions can be postulated as strong determinants of success. Some widespread invasive taxa occur in high frequencies across multiple zones; these taxa occur mainly in riparian zones and other azonal habitats,or depend on human-mediated disturbance, which weakens or overcomes the factors that determine specificity to any biogeographical region

State of the world’s plants and fungi 2020

Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity

Selection of the optimal anesthesia regimen for cesarean section

Approximately one third of all children in Germany are delivered by cesarean section. Depending on the individual patient's condition and the situation, the anesthesiologist has to choose between a general or a regional anesthesia regimen. The decisive factor for the selection is the obstetric urgency (decision-delivery time) after ascertainment of the indications. Furthermore, the need for postoperative analgesia varies depending on the chosen anesthesia regimen

RECCAS - REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial

Background: On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome. Extracorporeal cytokine elimination with a novel haemoadsorption (HA) device (CytoSorb (R)) promises to attenuate inflammatory response. This study primarily assesses the efficacy of intraoperative HA during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine burden during and after on-pump cardiac surgery, and secondarily, we aim to evaluate effects on postoperative organ dysfunction and outcomes in patients at high risk. Methods/design: This will be a single-centre randomised, two-arm, patient-blinded trial of intraoperative HA in patients undergoing on-pump cardiac surgery. Subjects will be allocated to receive either CPB with intraoperative HA or standard CPB without HA. The primary outcome is the difference in mean interleukin 6 (IL-6) serum levels between the two study groups on admission to the intensive care unit. A total number of 40 subjects was calculated as necessary to detect a clinically relevant 30 % reduction in postoperative IL-6 levels. Secondary objectives evaluate effects of HA on markers of inflammation up to 48 hours postoperatively, damage to the endothelial glycocalyx and effects on clinical scores and parameters of postoperative organ dysfunction and outcomes. Discussion: In this pilot trial we try to assess whether intraoperative HA with CytoSorb (R) can relevantly reduce postoperative IL-6 levels in patients undergoing on-pump cardiac surgery. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of haemoadsorption

Tumor Characteristics and Prognostic Factors in Nodal Positive Early Stage Breast Cancer of Obese Patients - Sub Analysis of the German ADEBAR Study

Abstract Background: Obesity is often associated with an increased risk of dying from breast cancer and poor outcomes of therapy. There are several possible explanations for this phenomenon. The aim of this analysis was to examine the correlation and potential causality between overweight, obesity and breast cancer. Tumor size, tumor histology, tumor grading and tumor localisation, number of positive lymph nodes, patients age, menopausal status, hormone receptor and HER-2 status are relevant characteristics in prognosis and treatment of breast cancer and at the same time potentially strongly associated with the body mass index. Patients and Methods: The ADEBAR study is a german multicenter phase III trial (n=1502). Study-goal was to evaluate whether breast cancer (BC) pts with &amp;gt; 3 axillarylymph node metastases benefit from a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21 days followed by 4 cycles docetaxel [D] 100mg/m2 q21 days) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1-14, q4 weeks). For our evaluation at hand Adebar-Patients were grouped according the WHO global database on body mass index (BMI) into normal range (18,50 - 24,99 kg/sqm) and obese (≤30,00 kg/sqm) high risk patients. Results: There is a strong correlation between body mass index, age and menopausal status at clinical diagnosis of breast cancer. Obese patients (n=300) at diagnosis in median are 55 years old (range 27-71 year) and already postmenopausal (52%, n=209). This analysis shows no connection of tumor localisation (unilateral left or right and bilateral breast cancer) and BMI.The tumor size at clinical diagnosis was strongly associated to the patient's weight (&amp;lt;0.0001). Breast tumors in obese patients have shown a size &amp;gt;3cm in 61 % (n=184) and a size &amp;gt;5cm in 16% (n=47). In normal weight and obese patients there was no sign for a significant difference in the number of positive lymph nodes (p=0.0440), tumor histology (p=0.8028) and grading (p=0.7353). Breast Cancer positivity for ER and PR hormone receptors (ER p=0.7364, PR p=0.4405) and the expression of HER-2 at the tumor surface (p=0.1560) were not significant associated to obesity in study patients. Conclusion: Our sub analysis between normal weight and obese patients shows a highly significant coherence between body mass index and tumor size in patients with early stage node positive breast cancer.This finding is in line with current publications which show that overweight and obese woman have often been diagnosed at a more advanced stage of disease and the treatment in this patients being less effective as a consequence. Weight reduction and tumor prevention in this high risk collective might be an additional approach on breast cancer therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-06.</jats:p