Shade avoidance: phytochrome signalling and other aboveground neighbour detection cues

Plants compete with neighbouring vegetation for limited resources. In competition for light, plants adjust their architecture to bring the leaves higher in the vegetation where more light is available than in the lower strata. These architectural responses include accelerated elongation of the hypocotyl, internodes and petioles, upward leaf movement (hyponasty), and reduced shoot branching and are collectively referred to as the shade avoidance syndrome. This review discusses various cues that plants use to detect the presence and proximity of neighbouring competitors and respond to with the shade avoidance syndrome. These cues include light quality and quantity signals, mechanical stimulation, and plant-emitted volatile chemicals. We will outline current knowledge about each of these signals individually and discuss their possible interactions. In conclusion, we will make a case for a whole-plant, ecophysiology approach to identify the relative importance of the various neighbour detection cues and their possible interactions in determining plant performance during competitio

Family ownership, innovation and other context variables as determinants of sustainable entrepreneurship in SMEs: An empirical research study

This study focuses on the prediction of sustainable entrepreneurship, that is, behavior which demonstrates a firm’s concern about the natural environment, especially among small and medium sized enterprises (SMEs). Using a random sample of 382 Dutch SMEs we examine how organizational context (firm sector, size, ownership structure) and innovativeness influence SMEs engagement in sustainable entrepreneurship. Results show that firms from more “tangible” sectors (manufacturing, construction and agriculture), larger firms, family-owned firms, and firms with a more innovative orientation are more likely to report positive activity related to the natural environment. The paper discusses implications of the obtained results.

Beyond Size: Predicting engagement in environmental management practices of Dutch SMEs

This study focuses on the prediction of the engagement of small and medium sized enterprises (SMEs) in environmental management practices, based on a random sample of 689 SMEs. The study finds that several endogenous factors, including tangibility of sector, firm size, innovative orientation, family influence and perceived financial benefits from energy conservation, predict an SME’s level of engagement in selected environmental management practices. For family influence, this effect is found only in interaction with the number of owners. In addition to empirical research on SMEs’ environmental behavior, the article draws on the ecological modernization literature as well as the theory of planned behavior.

Immunotherapy in Urothelial Cancer:Stop When Achieving a Response, Restart upon Disease Progression

Background: Since there is no clear consensus on optimal treatment duration of PD-(L)1 targeting checkpoint inhibitors in the setting of urothelial cancer (UC) patients, even patients with durable responses are often treated up to 2 years. It is questionable whether this is necessary and whether quality of life improves when treatment is discontinued earlier and restarted when necessary. Methods: We collected available data from locally advanced or metastatic UC patients within the Netherlands between September 2017 and December 2019 treated with first or second-line pembrolizumab, to evaluate treatment duration, reasons for discontinuation, subsequent treatments and survival outcomes. Results: Data were available from 74 patients: 85% (63/74) of patients had a treatment duration of 12 months or shorter, and in seven out of them, treatment was discontinued for another reason than progressive disease. Two patients (3%) had a treatment duration between 12 and 24 months, and eight patients (11%) completed 24 months of treatment. Survival at data cut-off (1 July 2020) with a median follow-up of 35 months was 100% in patients with partial or complete response (6/7 patients) and treatment duration ≤ 12 months, and 100% in patients treated for 24 months. In total, three patients were re-treated with pembrolizumab upon progressive disease during follow-up. Conclusions: In patients who reach partial or complete response during treatment with a PD-(L)1 targeting checkpoint inhibitor, early discontinuation of treatment with pembrolizumab and restart if necessary seems to be reasonable with preserved favorable outcomes. This article should drive further efforts to optimize the treatment duration for patients who respond to treatment with pembrolizumab.</p

Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: Results from the STAMPEDE and CHAARTED trials

Androgen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-naïve (hormone-sensitive) metastatic prostate cancer (mHSPC) yielded a remarkable overall survival benefit of 13.6 months as compared with ADT alone. In the current issue of The Lancet, James et al. report results of the STAMPEDE trial in men with high-risk locally advanced or metastatic prostate cancer initiating long-term hormone therapy. The combination of six cycles of docetaxel with ADT in men commencing long-term ADT demonstrated a similar OS benefit compared with standard of care (SOC) by a median of 10 months. Based on the consistency of the data and the firmness of the benefit provided, docetaxel in addition to ADT should be considered SOC for men with newly diagnosed mHSPC

Urogenitale Oncologie: inspirerende decennia, uitdagende toekomst

Oratie handelt over het urogenitale stelsel, in het bijzonder maligne tumoren. Dit betreft onder andere kanker van de nier, de blaas, prostaat en testis. Komen maligne tumoren van deze organen vaak voor? Inderdaad, het prostaatcarcinoom is bij de man de meest voorkomende invasieve kanker en ook het blaascarcinoom staat in de top tien op de vijfde plaats. Bij vrouwen komt blaascarcinoom minder vaak voor en staat daarmee niet in de top tien. Het niercarcinoom is bij beide seksen een betrekkelijk weinig voorkomende tumor met ongeveer 1.200 nieuwe gevallen per jaar. Ook het testiscarcinoom is een betrekkelijk zeldzame kankersoort met ongeveer 1.000 nieuwe gevallen per jaar. Het is echter wel de meest voorkomende kanker bij jonge mannen en om onbekende redenen neemt de incidentie toe en is deze in de afgelopen 20 jaar verdubbeld. In de afgelopen 2 decennia zijn er bij het testiscarcinoom, blaascarcinoom, prostaatcarcinoom en het niercelcarcinoom grote sprongen voorwaarts gemaakt. Deze ontwikkelingen zullen beschreven worden. Hierbij zal de focus liggen op de rol van het Erasmus MC en de tot stand gebrachte samenwerkingsverbanden. Tenslotte zal bij elk voor deze tumortypes een blik op de toekomst gegeven worden

Possible lack of full cross-resistance of 5HT3 antagonists; a pilot study

We investigated the potential of cross-over to the serotonin receptor (5HT3) antagonist ondansetron after protection failure with tropisetron. Several cases of complete protection were observed. These limited data suggest that there is an indication for retreatment with a different 5HT3 antagonist after an initial failure to another and also stress the need and relevance for comparative studies between 5HT3 antagonists

A Compendium of AR Splice Variants in Metastatic Castration-Resistant Prostate Cancer

Treatment-induced AR alterations, including AR alternative splice variants (AR-Vs), have been extensively linked to harboring roles in primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer and therefore have gained momentum. Our aim was to uniformly determine recurrent AR-Vs in metastatic castration-resistant prostate cancer (mCRPC) using whole transcriptome sequencing in order to assess which AR-Vs might hold potential diagnostic or prognostic relevance in future research. This study reports that in addition to the promising AR-V7 as a biomarker, AR45 and AR-V3 were also seen as recurrent AR-Vs and that the presence of any AR-V could be associated with higher AR expression. With future research, these AR-Vs may therefore harbor similar or complementary roles to AR-V7 as predictive and prognostic biomarkers in mCRPC or as proxies for abundant AR expression.</p

The usefulness of CA15.3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in determining the clinical course in patients with metastatic breast cancer

Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40 women with metastatic breast cancer. A change in antigen level of more than 25%, either an increase or a decrease, was considered to predict progressive or responsive disease respectively. A change of less than 25% was considered to predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%, 76% and 48% of the patients respectively (P<0.05). The overall prediction of clinical course was similar for all three markers. A more than 25% increase of MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The predictive value of a more than 25% increase was high for all three markers: 94%, 94%, 83%. Changes in marker levels were correlated with each other. Logistic regression analysis showed that combining MCA and CA15.3 did not improve the prediction further. In conclusion, these tumour markers may help in evaluating the disease course and there is no advantage in combining MCA and CA15.3