Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.

Background: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).

A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages.

Induction of lipid-laden foamy macrophages is a cellular hallmark of tuberculosis (TB) disease, which involves the transformation of infected phagolysosomes from a site of killing into a nutrient-rich replicative niche. Here, we show that a terpenyl nucleoside shed from Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside-producing M.

Design and Synthesis of Visible-Light-Responsive Azobenzene Building Blocks for Chemical Biology.

Tetra--fluoro-azobenzenes are a class of photoswitches useful for the construction of visible-light-controlled molecular systems. They can be used to achieve spatio-temporal control over the properties of a chosen bioactive molecule. However, the introduction of different substituents to the tetra-fluoro-azobenzene core can significantly affect the photochemical properties of the switch and compromise biocompatibility.

Disease outcome and associated factors after definitive platinum based chemoradiotherapy for advanced stage HPV-negative head and neck cancer.

Background: Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques.

The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab.

Background: The optimal volumetric threshold for determining progressive disease (PD) in recurrent glioblastoma is yet to be determined. We investigated a range of thresholds in association with overall survival (OS).

Methods: First recurrent glioblastoma patients treated with bevacizumab and/or lomustine were included from the phase II BELOB and phase III EORTC26101 trials.

The EGFRvIII transcriptome in glioblastoma: A meta-omics analysis.

Background: EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being among its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signaling compared with wildtype EGFR.

Methods: To better understand the oncogenic role of EGFRvIII, we leveraged 4 large datasets into 1 large glioblastoma transcriptome dataset (n = 741) alongside 81 whole-genome samples from 2 datasets.

Pd-catalyzed sp-sp cross-coupling of benzyl bromides using lithium acetylides.

Organolithium-based cross-coupling reactions have emerged as an indispensable method to construct C-C bonds. These transformations have proven particularly useful for the direct and fast coupling of various organolithium reagents (sp, sp2, and sp3) with aromatic (pseudo) halides (sp2). Here we present an efficient method for the cross-coupling of benzyl bromides (sp3) with lithium acetylides (sp).

Chemical Synthesis of Cell Wall Constituents of .

The pathogen (), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host-pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it.

Chiral Amplification of Phosphoramidates of Amines and Amino Acids in Water.

The origin of biomolecular homochirality continues to be one of the most fascinating aspects of prebiotic chemistry. Various amplification strategies for chiral compounds to enhance a small chiral preference have been reported, but none of these involves phosphorylation, one of nature's essential chemical reactions. Here we present a simple and robust concept of phosphorylation-based chiral amplification of amines and amino acids in water.

Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis.

is an environmental nontuberculous mycobacterium that causes opportunistic tuberculosis-like disease. It is one of the most closely related species to the complex. Using as a proxy for the - common ancestor, we asked whether introducing the -specific gene pair into affects the course of experimental infection.

Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile.

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis.

In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters ("cord factor") form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester.

The course of symptoms of anxiety and depression from time of diagnosis up to 2 years follow-up in head and neck cancer patients treated with primary (chemo)radiation.

Objectives: To identify sociodemographic and clinical factors, health-related quality of life (HRQOL) and head and neck cancer (HNC) symptoms associated with the course of symptoms of anxiety and depression from pretreatment to 24-month follow-up among HNC patients after (chemo)radiation.

Materials And Methods: Patients (n = 345) completed questionnaires on anxiety and depression (HADS), HRQOL and symptoms (EORTC QLQ-C30/QLQ-H&N35) before treatment, and 6-weeks,3-,6-12-,18-, and 24-months after treatment. Mixed model analyses were used to investigate the course of anxiety and depression from pretreatment to 24-months in relation to factors assessed at baseline, and the course of anxiety and depression from 6- to 24-months, in relation to factors assessed at 6-months.

Mycobacterium tuberculosis releases an antacid that remodels phagosomes.

Mycobacterium tuberculosis (Mtb) is the world's most deadly pathogen. Unlike less virulent mycobacteria, Mtb produces 1-tuberculosinyladenosine (1-TbAd), an unusual terpene nucleoside of unknown function. In the present study 1-TbAd has been shown to be a naturally evolved phagolysosome disruptor.

Total Synthesis of an Immunogenic Trehalose Phospholipid from Salmonella Typhi and Elucidation of Its sn-Regiochemistry by Mass Spectrometry.

Diphosphatidyltrehalose (diPT) is an immunogenic glycolipid, recently isolated from Salmonella Typhi. Despite rigorous structure elucidation, the sn-position of the acyl chains on the glycerol backbone had not been unequivocally established. A stereoselective synthesis of diPT and its regioisomer is reported herein.

Discovery of trehalose phospholipids reveals functional convergence with mycobacteria.

species are among the world's most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Paratyphi and Typhi, we focused on lipids that are enriched in Typhi, because it causes typhoid fever.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

Background: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy.

Methods: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years).

The course of sexual interest and enjoyment in head and neck cancer patients treated with primary (chemo)radiotherapy.

Introduction: The aim of this prospective study was to investigate the course of sexual interest and enjoyment in relation to sociodemographic and clinical factors, health-related quality of life (HRQOL), and symptoms of psychological distress in head and neck cancer (HNC) patients treated with primary (chemo)radiotherapy.

Methods: HNC patients (n = 354) completed patient-reported outcome measures (PROMs) on HRQOL (EORTC QLQ-C30 and QLQ-H&N35, including the sexuality subscale covering less sexual interest and enjoyment), and psychological distress (HADS) pretreatment, at 6-week follow-up and at 3-, 6-, 12-, 18-, and 24-month follow-up (i.e.

Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma: A nationwide case series of 35 patients in The Netherlands.

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT).

Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]).

TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.

Background: Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy.

Methods: Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.

Comparison of 2D (RANO) and volumetric methods for assessment of recurrent glioblastoma treated with bevacizumab-a report from the BELOB trial.

Background: The current method for assessing progressive disease (PD) in glioblastoma is according to the Response Assessment in Neuro-Oncology (RANO) criteria. Bevacizumab-treated patients may show pseudo-response on postcontrast T1-weighted (T1w) MRI, and a more infiltrative non-enhancing growth pattern on T2w/fluid attenuated inversion recovery (FLAIR) images. We investigated whether the RANO criteria remain the method of choice for assessing bevacizumab-treated recurrent glioblastoma when compared with various volumetric methods.

Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: adherence and exercise performance levels of a 12-week guided home-based program.

The background and purpose of this paper is to investigate adherence, exercise performance levels and associated factors in head and neck cancer (HNC) patients participating in a guided home-based prophylactic exercise program during and after treatment [swallowing sparing intensity modulated radiation therapy (SW-IMRT)]. Fifty patients were included in the study. Adherence was defined as the percentage of patients who kept up exercising; exercise performance level was categorized as low: ≤1, moderate: 1-2, and high: ≥2 time(s) per day, on average.

Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck.

Background: We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease.

Methods: A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured.

Impact of chemotherapy on the outcome of osteosarcoma of the head and neck in adults.

Background: There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck.

Methods: All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed.

Results: We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%.