Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

Purpose: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder.

Methods: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured.

GEP-NET radiomics: a systematic review and radiomics quality score assessment.

Objective: The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence.

Methods: PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed.

Circulating CD8 mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.

Objectives: While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are an abundant population of innate-like T cells expressing a semi-invariant T-cell receptor restricted to the MHC class I-like molecule, MR1, presenting vitamin B metabolites derived from bacteria. We sought to characterise MAIT cells in melanoma patients and determined their association with treatment responses and clinical outcomes.

Efficacy of Physical Exercise to Offset Anthracycline-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis of Clinical and Preclinical Studies.

Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases.

SUV values at FDG PET-CT to predict malignancy in lymph nodes aspirated by real time image fused USgFNAC in head and neck squamous cell carcinoma.

F-fluordeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET-CT) and ultrasound guided fine-needle aspiration cytology (USgFNAC) are commonly used to detect nodal metastases in head and neck squamous cell carcinoma (HNSCC). FDG PET-CT helps to guide selection of borderline suspicious nodes to aspirate using USgFNAC. Real time image fusion of FDG PET-CT with US is a new available technique and can improve this selection.

MRI predicts increased eligibility for sphincter preservation after CRT in low rectal cancer.

Unlabelled: Chemoradiation increases the eligibility for sphincter preservation in low rectal cancer, as assessed by MRI.

Introduction: We evaluated whether MRI can predict sphincter preservation after chemoradiation (CRT), and whether the feasibility of sphincter preservation increases after CRT, when compared with MRI before neoadjuvant treatment.

Methods: 85 patients with low rectal tumour (≤5 cm from anorectal junction (ARJ)) were included.

Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models.

Currently, patients with extremity soft tissue sarcoma (eSTS) who have undergone curative resection are followed up by a heuristic approach, not covering individual patient risks. The aim of this study was to develop two flexible parametric competing risk regression models (FPCRRMs) for local recurrence (LR) and distant metastasis (DM), aiming at providing guidance on how to individually follow-up patients. Three thousand sixteen patients (1931 test, 1085 validation cohort) with high-grade eSTS were included in this retrospective, multicenter study.

Factors influencing long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei originating from appendiceal neoplasms.

Background: Pseudomyxoma peritonei (PMP) is a rare disease, most commonly of appendiceal origin. Treatment consists of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The aim of this study was to identify prognostic factors for recurrence and survival.

"I am busy surviving" - Views about physical exercise in older adults scheduled for colorectal cancer surgery.

Objective: Seventy percent of patients with colorectal cancer (CRC) are aged 65 years or older. Netherlands Comprehensive Cancer Organization (n.d.

The G2 checkpoint-a node-based molecular switch.

Tight regulation of the eukaryotic cell cycle is paramount to ensure genomic integrity throughout life. Cell cycle checkpoints are present in each phase of the cell cycle and prevent cell cycle progression when genomic integrity is compromised. The G2 checkpoint is an intricate signaling network that regulates the progression of G2 to mitosis (M).

The added value of hysterectomy in the management of gestational trophoblastic neoplasia.

Background: Despite the undoubted effectiveness of chemotherapeutic treatment in gestational trophoblastic neoplasia (GTN), problems related to toxicity of chemotherapy and chemo-resistant disease have led to reconsideration of the use of hysterectomy. Aim of the present study was to evaluate indications for and outcome of hysterectomy in patients with GTN in a nation-wide cohort.

Methods: Between 1977 and 2012, we identified all patients diagnosed with GTN and treated with hysterectomy from the Dutch national databases.

FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer.

This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of translocation and amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3.

ATP Released by Injured Neurons Activates Schwann Cells.

Injured nerve terminals of neuromuscular junctions (NMJs) can regenerate. This remarkable and complex response is governed by molecular signals that are exchanged among the cellular components of this synapse: motor axon nerve terminal (MAT), perisynaptic Schwann cells (PSCs), and muscle fiber. The nature of signals that govern MAT regeneration is ill-known.

Baseline tumor volume in assessing prognosis of patients with intermediate-risk synchronous metastatic renal cell carcinoma.

Objective: To analyze if prediction of survival for patients with synchronous metastatic renal cell cancer (mRCC) could be further refined by baseline volume of the primary tumor, the metastases, or the remaining volume after surgery; this study was performed because survival expectancies of patients with intermediate-risk mRCC vary substantially.

Material And Methods: The predictive value of the different volumes on overall survival (OS) was analyzed retrospectively in patients with intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk profile and ≤3 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) factors, who received sunitinib in our institute. Tumor volumes were calculated on segmented computed tomography using in-house developed software.

Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis.

Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to correlate OATP1B expression with hyperbilirubinemia in common liver diseases.

Incorporation of concentration data below the limit of quantification in population pharmacokinetic analyses.

Handling of data below the lower limit of quantification (LLOQ), below the limit of quantification (BLOQ) in population pharmacokinetic (PopPK) analyses is important for reducing bias and imprecision in parameter estimation. We aimed to evaluate whether using the concentration data below the LLOQ has superior performance over several established methods. The performance of this approach ("All data") was evaluated and compared to other methods: "Discard," "LLOQ/2," and "LIKE" (likelihood-based).

Unnatural amino acid incorporation in E. coli: current and future applications in the design of therapeutic proteins.

Unnatural amino acid (UAA) incorporation by amber codon suppression offers scientists a powerful tool to modify the properties of proteins at will. UAA incorporation has been used for a plethora of fundamental research applications and, more recently, also for the selective modification of therapeutic proteins. In this review most recent developments in Escherichia coli codon expansion and, unnatural amino acid incorporation are discussed together with some remarkable recent developments in improved efficient UAA incorporation.

Penile sparing surgery for penile cancer-does it affect survival?

Purpose: Management of squamous cell carcinoma of the penis changed in recent decades in favor of penile sparing surgery. We assessed whether penile sparing therapies were increasingly applied in our penile squamous cell carcinoma cohort with time and whether penile sparing affected 5-year cancer specific survival.

Materials And Methods: We reviewed the records of 1,000 patients treated between 1956 and 2012, of whom 859 with invasive tumors were eligible for analysis.

A high-throughput functional complementation assay for classification of BRCA1 missense variants.

Unlabelled: Mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers, and therefore sequence analysis of both genes is routinely conducted in patients with early-onset breast cancer. Besides mutations that clearly abolish protein function or are known to increase cancer risk, a large number of sequence variants of uncertain significance (VUS) have been identified. Although several functional assays for BRCA1 VUSs have been described, thus far it has not been possible to conduct a high-throughput analysis in the context of the full-length protein.

Loss of telomere protection: consequences and opportunities.

Telomeres are repetitive sequences at the natural ends of linear eukaryotic chromosomes that protect these from recognition as chromosome breaks. Their ability to do so critically depends on the binding of sufficient quantities of functional shelterin, a six-unit protein complex with specific and crucial roles in telomere maintenance and function. Insufficient telomere length, leading to insufficient concentration of shelterin at chromosome ends, or otherwise crippled shelterin function, causes telomere deprotection.

Into the intracellular logistics of cross-presentation.

The induction of cytotoxic CD8(+) T cell responses requires the presentation of antigenic peptides by MHC class I molecules (MHC I). MHC I usually present peptides derived from endogenous proteins. However, some subtypes of dendritic cells have developed the ability to efficiently present peptides derived from exogenous antigens on MHC I via a process called cross-presentation.