Meningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an... Show moreMeningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an increased synthesis of the metabolite methylglyoxal (MGO) or glyoxal (GO), which is known to react with amino groups of proteins. This reaction is called glycation, thereby building advanced glycation end products (AGEs). In this study, we investigated the influence of glycation on sialylation in two meningioma cell lines, representing the WHO grade I (BEN-MEN-1) and the WHO grade III (IOMM-Lee). In the benign meningioma cell line, glycation led to differences in expression of sialyltransferases (ST3GAL1/2/3/5/6, ST6GAL1/2, ST6GALNAC2/6, and ST8SIA1/2), which are known to play a role in tumor progression. We could show that glycation of BEN-MEN-1 cells led to decreased expression of ST3Gal5. This resulted in decreased synthesis of the ganglioside GM3, the product of ST3Gal5. In the malignant meningioma cell line, we observed changes in expression of sialyltransferases (ST3GAL1/2/3, ST6GALNAC5, and ST8SIA1) after glycation, which correlates with less aggressive behavior. Show less
Background. The time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic... Show moreBackground. The time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic resonance imaging (MRI) and its impact on timing of surgery, and, second, to evaluate the impact of timing of surgery after chemoradiotherapy (CRT) on short- and long-term outcomes.Methods. Patients were selected from a collaborative rectal cancer research project including 71 Dutch centres, and were subdivided into two groups according to time interval from the start of preoperative CRT to surgery (< 14 and ae14 weeks).Results. From 2095 registered patients, 475 patients received preoperative CRT. MRI restaging was performed in 79.4% of patients, with a median CRT-MRI interval of 10 weeks (interquartile range [IQR] 8-11) and a median MRI-surgery interval of 4 weeks (IQR 2-5). The CRT-surgery interval groups consisted of 224 (< 14 weeks) and 251 patients (>= 14 weeks), and the long-interval group included a higher proportion of cT4 stage and multivisceral resection patients. Pathological complete response rate (n = 34 [15.2%] vs. n = 47 [18.7%], p = 0.305) and CRM involvement (9.7% vs. 15.9%, p = 0.145) did not significantly differ. Thirty-day surgical complications were similar (20.1% vs. 23.1%, p = 0.943), however no significant differences were found for local and distant recurrence rates, disease-free survival, and overall survival.Conclusions. These real-life data, reflecting routine daily practice in The Netherlands, showed substantial variability in the use and timing of restaging MRI after preoperative CRT for rectal cancer, as well as time interval to surgery. Surgery before or after 14 weeks from the start of CRT resulted in similar short- and long-term outcomes. Show less
Borstlap, W.A.A.; Deijen, C.L.; Dulk, M. den; Bonjer, H.J.; Velde, C.J. van de; Bemelman, W.A.; ... ; Dutch Snapshot Res Grp 2017
Aim A Snapshot study design eliminates changes in treatment and outcome over time. This population based Snapshot study aimed to determine current practice and outcome of rectal cancer treatment... Show moreAim A Snapshot study design eliminates changes in treatment and outcome over time. This population based Snapshot study aimed to determine current practice and outcome of rectal cancer treatment with published landmark randomized controlled trials as a benchmark.Method In this collaborative research project, the dataset of the Dutch Surgical Colorectal Audit was extended with additional treatment and long-term outcome data. All registered patients who underwent resection for rectal cancer in 2011 were eligible. Baseline characteristics and outcome were evaluated against the results of the Dutch TME trial and the COLOR II trial from which the original datasets were obtained.Results A total of 71 hospitals participated, and data were completed for 2102 out of the potential 2633 patients (79.8%). Median follow-up was 41 (interquartile range 25-47) months. Overall circumferential resection margin (CRM) involvement was 9.3% in the Snapshot cohort and 18.5% in the Dutch TME trial. CRM positivity after laparoscopic resection was 7.8% in the Snapshot and 9.5% in the COLOR II trial. Three-year overall local recurrence rate in the Snapshot was 5.9%, with a disease-free survival of 67.1% and overall survival of 79.5%. Benchmarking with the randomized controlled trials revealed an overall favourable long-term outcome of the Snapshot cohort.Conclusion This study showed that current rectal cancer care in a large unselected Dutch population is of high quality, with less positive CRM since the TME trial and oncologically safe implementation of minimally invasive surgery after the COLOR II trial. Show less
Like other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be subdivided into six major families, each of which recognize a general class of molecular patterns. However, there... Show moreLike other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be subdivided into six major families, each of which recognize a general class of molecular patterns. However, there also are a number of Tlrs with unknown function, the presence of which seems unique to the bony fish, among which is Tlr20. We identified full-length complementary DNA (cDNA) sequences for tlr20 of zebrafish and common carp, two closely related fish species. Zebrafish have six copies of tlr20, whereas carp express only a single copy. Both zebrafish Tlr20 (at least Tlr20a–d) and carp Tlr20 have 26 leucine-rich repeats (LRRs). Three-dimensional modeling indicates a best fit to the crystal structure of TLR8. Phylogenetic analyses place Tlr20 in the TLR11 family closest to Tlr11 and Tlr12, which sense ligands from protozoan parasites in the mouse. Conservation of genes on zebrafish chromosome 9, which carries tlr20, with genes on mouse chromosome 14, which carries tlr11, indicates Tlr11 could be a possible ortholog of Tlr20. Confocal microscopy suggests a subcellular localization of Tlr20 at the endoplasmatic reticulum. Although in vitro reporter assays could not identify a ligand unique to Tlr20, in vivo infection experiments indicate a role for Tlr20 in the immune response of carp to protozoan parasites (Trypanoplasma borreli). Carp tlr20 is mainly expressed in peripheral blood leukocytes (PBL) with B lymphocytes, in particular, expressing relatively high levels of Tlr20. In vitro stimulation of PBL with T. borreli induces an upregulation of tlr20, supportive of a role for Tlr20 in the immune response to protozoan parasites. Show less