Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker

Aim: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer patients. Methods: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers. We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients, either newly diagnosed with gastric cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well as follow-up patients. Findings were controlled by using plasma samples from 54 tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR. Results: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumor-free volunteers and gastric cancer patients (P < 0.001). Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage, compared to tumor-free volunteers: patients with tumors without metastasis (P = 0.005), with synchronous metastasis (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow-up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89 (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival when compared with patients demonstrating low MACC1 levels (P = 0.0015). Furthermore, gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated (P = 0.001). Conclusion: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study

Circulating MACC1 transcripts in colorectal cancer patient plasma predict metastasis and prognosis

BACKGROUND: Metastasis is the most frequent cause of treatment failure and death in colorectal cancer. Early detection of tumors and metastases is crucial for improving treatment strategies and patient outcome. Development of reliable biomarkers and simple tests routinely applicable in the clinic for detection, prognostication, and therapy monitoring is of special interest. We recently identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for colon cancer metastasis and allows identification of high-risk subjects in early stages, when determined in patients' primary tumors. To overcome the limitation of a restricted number of molecular analyses in tumor tissue, the establishment of a non-invasive blood test for early identification of high-risk cancer patients, for monitoring disease course and therapy response is strongly needed. METHODOLOGY/PRINCIPAL FINDINGS: For the first time, we describe a non-invasive assay for quantification of circulating MACC1 transcripts in blood of more than 300 colorectal cancer patients. MACC1 transcript levels are increased in all disease stages of the cancer patients compared to tumor-free volunteers. Highest MACC1 levels were determined in individuals with metastases (all P<0.05). Importantly, high MACC1 levels correlate with unfavorable survival (P<.0001). Combining MACC1 with circulating transcripts of the metastasis gene S100A4, a transcriptional target of the Wnt/beta-catenin-pathway, improves survival prediction for newly diagnosed cancer patients. CONCLUSION/SIGNIFICANCE: This blood-based assay for circulating MACC1 transcripts, which can be quantitated on a routine basis, is clinically applicable for diagnosis, prognosis, and therapeutic monitoring of cancer patients. Here we demonstrate the diagnostic and prognostic value of circulating MACC1 transcripts in patient plasma for metastasis and survival. Since MACC1 represents a promising target for anti-metastatic therapies, circulating MACC1 transcripts may prove to be an ideal read-out for monitoring therapeutic response of future interventions targeting MACC1-induced metastasis in cancer patients

3.13 Tank mixtures of insecticides and fungicides, adjuvants, additives, fertilizers and their effects on honey bees after contact exposure in a spray chamber

In agriculture honey bees may be exposed to multiple pesticides. In contrast to single applications of plant protection products (PPP), the effects of tank mixtures of two or more PPP on honey bees are not routinely assessed in the risk assessment of plant protection products. However, tank mixes are often common practice by farmers. Mixtures of practically non-toxic substances can lead to synergistic increase of toxic effects on honey bees, observed for the first time in 19921 in combinations of pyrethroids and azole fungicides. 2004 Iwasa et al. already reported that ergosterol-biosynthesis-inhibiting (EBI) fungicides strongly increase the toxicity of neonicotinoids in laboratory for the contact exposure route. Furthermore, in agricultural practice additives, adjuvants and fertilizers may be added to the spray solution. For these additives usually no informations on potential side effects on bees are available when mixed with plant protection products. Therefore, it is considered necessary to investigate possible additive or synergistic impacts and evaluate potentially critical combinations to ensure protection of bees. Here, we investigated the effects on bees of combinations of insecticides, fungicides and fertilizers under controlled laboratory conditions. A spray chamber was used to evaluate effects following contact exposure by typical field application rates. Subsequently, mortality and behaviour of bees were monitored for at least 48 h following the OECD acute contact toxicity test 2143. Dependencies of synergistic effects and the time intervals between the applications of the mixing partners were evaluated.In agriculture honey bees may be exposed to multiple pesticides. In contrast to single applications of plant protection products (PPP), the effects of tank mixtures of two or more PPP on honey bees are not routinely assessed in the risk assessment of plant protection products. However, tank mixes are often common practice by farmers. Mixtures of practically non-toxic substances can lead to synergistic increase of toxic effects on honey bees, observed for the first time in 19921 in combinations of pyrethroids and azole fungicides. 2004 Iwasa et al. already reported that ergosterol-biosynthesis-inhibiting (EBI) fungicides strongly increase the toxicity of neonicotinoids in laboratory for the contact exposure route. Furthermore, in agricultural practice additives, adjuvants and fertilizers may be added to the spray solution. For these additives usually no informations on potential side effects on bees are available when mixed with plant protection products. Therefore, it is considered necessary to investigate possible additive or synergistic impacts and evaluate potentially critical combinations to ensure protection of bees. Here, we investigated the effects on bees of combinations of insecticides, fungicides and fertilizers under controlled laboratory conditions. A spray chamber was used to evaluate effects following contact exposure by typical field application rates. Subsequently, mortality and behaviour of bees were monitored for at least 48 h following the OECD acute contact toxicity test 2143. Dependencies of synergistic effects and the time intervals between the applications of the mixing partners were evaluated

a retrospective analysis

Background Several animal studies suggest beneficial effects on kidney function upon administration of levosimendan. As recent data from clinical studies are heterogeneous, we sought to investigate whether levosimendan is associated with improved postoperative kidney function in cardiac surgery patients with respect to timing of its administration. Methods Retrospective, single centre, observational analysis at a university hospital in Berlin, Germany. All adult patients without preoperative renal dysfunction that underwent coronary artery bypass grafting and/or valve reconstruction/replacement between 01/01/2007 and 31/12/2011 were considered for analyses. Results Out of 1.095 included patients, 46 patients were treated with levosimendan due to a severely reduced left ventricular systolic function preoperatively (LVEF < 35%) and/or clinical signs of a low cardiac output syndrome. Sixty-one percent received the drug whilst in the OR, 39% after postoperative intensive care unit admission. When levosimendan was given immediately after anaesthesia induction, creatinine plasma levels (p = 0.009 for nonparametric analysis of longitudinal data in a two-factorial design) and incidence of postoperative renal dysfunction (67.9% vs. 94.4%; p = 0.033) were significantly reduced in contrast to a later start of treatment. In addition, duration of renal replacement therapy was significantly shorter (79 [35;332] vs. 272 [132;703] minutes; p = 0.046) in that group. Conclusions Postoperative kidney dysfunction is a common condition in patients under going cardiac surgery. Patients with severely reduced left ventricular function and/or clinical signs of a low cardiac output syndrome who preoperatively presented with a normal kidney function may benefit from an early start of levosimendan administration, i.e. immediately after anaesthesia

Quantifying potential particulate matter intake dose in a low-income community in South Africa

Understanding how exposure to particulate matter impacts human health is complex. Personal exposure is a function of the pollution concentrations measured at any given place and time. The health impacts of this exposure are, in part, determined by how high pollutant concentrations are and how much pollution can potentially enter the body. This study considered data gathered in the winter of 2013 in a low-income community on the Mpumalanga Highveld, South Africa, which is a geographical area known for its high air pollution levels. Data collected by GPS monitors worn by individuals in the community were used to understand in which microenvironments people spend most of their time. Participants spent time in five main micro-environments: (highest rank first) inside a house, directly outside a house, on a dirt road, on a tar road, and on an open field. Eight days’ worth of ambient, indoor and personal particulate matter measurements were paired with individual GPS positioning data for one study participant. We identified pollutant concentrations where the person spent time and how much particulate matter the person potentially inhaled. Highest concentrations were measured inside the dwelling and directly outside the dwelling of the individual. When comparing directly (ranging from 0.02 – 0.76 mg) - and indirectly (0.02 – 0.34 mg) derived time-weighted potential intake doses, directly derived intake doses were higher and more likely to represent how much particulate matter was potentially inhaled by the participant. This study suggests that people living in communities on the Mpumalanga Highveld are exposed to unacceptably high air pollution levels in places in which they spend most of their time. Direct exposure and intake dose assessments are an important element of environmental health studies to supplement data collected by stationary monitors in order to better understand exactly what people are breathing.https://cleanairjournal.org.zaam2022Geography, Geoinformatics and Meteorolog

Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

BACKGROUND: The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control. METHODS: Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4-6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function). DISCUSSION: Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach

GHQ increases among Scottish 15 year olds 1987–2006

BACKGROUND: Increases in a number of psychosocial disorders have been identified among Western youth in the second half of the Twentieth century. However findings are not consistent, trends are complex, and comparisons over time are hampered by methodological problems. METHODS: Data were drawn from three samples identical in respect of age (15 years), school year (final year of statutory schooling) and geographical location (the West of Scotland). Each sample was administered the 12-item General Health Questionnaire, a measure of self-report psychological distress, in 1987 (N = 505), 1999 (N = 2,196) and 2006 (N = 3,194). Analyses were conducted to examine changes in: GHQ 'caseness'; individual items; and factors, derived via confirmatory factor analysis representing (a) 'negative' and 'positive' items, and (b) 'anxiety and depression', 'loss of confidence or self-esteem' and 'anhedonia and social dysfunction'. RESULTS: Based on the standard (2/3) cut-off, 'caseness' rates in 1987, 1999 and 2006 were 12.7, 15.1 and 21.5% (males) and 18.8, 32.5 and 44.1% (females). Similar increases were observed with more stringent 'caseness' cut-offs. Examination of individual items showed some to have increased much more markedly over time than others. There were larger increases among females for all except two items and some evidence, among both genders, of steeper increases among 'negative' items compared with 'positive' ones. However, the differences in slope were very small compared with the overall increases in both types. CONCLUSIONS: Data from three samples identical in respect of age, school year and geographical location, show marked increases in GHQ-12 'caseness' among females between 1987 and 1999 and among both males and females between 1999 and 2006. Although slightly steeper increases in 'negative' items raise the possibility that endorsing such symptoms may have become more acceptable, these were small in comparison with increases in all dimensions of psychological distress. The next step is to identify causal explanations for the increases reported here