Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial.

Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer.

CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young.

Lipids in Extracellular Vesicles: What Can Be Learned about Membrane Structure and Function?

Extracellular vesicles, such as exosomes, can be used as interesting models to study the structure and function of biological membranes as these vesicles contain only one membrane (i.e., one lipid bilayer).

Increased Radiation Sensitivity in Patients with Phelan-McDermid Syndrome.

Phelan-McDermid syndrome is an inherited global developmental disorder commonly associated with autism spectrum disorder. Due to a significantly increased radiosensitivity, measured before the start of radiotherapy of a rhabdoid tumor in a child with Phelan-McDermid syndrome, the question arose whether other patients with this syndrome also have increased radiosensitivity. For this purpose, the radiation sensitivity of blood lymphocytes after irradiation with 2Gray was examined using the G0 three-color fluorescence in situ hybridization assay in a cohort of 20 patients with Phelan-McDermid syndrome from blood samples.

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma.

Background: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus.

Need for more focus on lipid species in studies of biological and model membranes.

The lipid composition of cellular membranes can impact a number of physiological processes such as signaling, cell migration, endocytosis and intracellular transport. In this article we focus on some aspects concerning analysis of lipids and research on lipid structure and function in mammalian cells that in our opinion have not obtained sufficient attention. This includes interleaflet coupling between the two layers of the membrane, and the role of lipid species, i.

Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors.

Background: Genetic alterations are common in non-small cell lung cancer (NSCLC), and DNA mutations and translocations are targets for therapy. Copy number aberrations occur frequently in NSCLC tumors and may influence gene expression and further alter signaling pathways. In this study we aimed to characterize the genomic architecture of NSCLC tumors and to identify genomic differences between tumors stratified by histology and mutation status.

"Built-in" PD-1 blocker to rescue NK-92 activity from PD-L1-mediated tumor escape mechanisms.

Success of adoptive cell therapy mainly depends on the ability of immune cells to persist and function optimally in the immunosuppressive tumor microenvironment. Although present at the cancer site, immune cells become exhausted and/or inhibited, due to the presence of inhibitory receptors such as PD-L1 on malignant cells. Novel genetic strategies to manipulate the PD1/PD-L1 axis comprise (i) PD-1 reversion where the receptor intracellular domain is replaced with an activating unit, (ii) the use of anti-PD-L1 CAR or (iii) the disruption of the PD-1 gene.

Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer.

Unlabelled: Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials.

Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.

T cell receptor (TCR)-engineered T cell therapy is a promising cancer treatment approach. Human telomerase reverse transcriptase (hTERT) is overexpressed in the majority of tumors and a potential target for adoptive cell therapy. We isolated a novel hTERT-specific TCR sequence, named Radium-4, from a clinically responding pancreatic cancer patient vaccinated with a long hTERT peptide.

Mass spectrometry-based measurements of cyclic adenosine monophosphate in cells, simplified using reversed phase liquid chromatography with a polar characterized stationary phase.

3', 5' - Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that is involved in many cellular functions and biological processes. In several cell types, cholera toxin will increase the level of cAMP, which mediates toxic effects on cells. In this context, we have developed a fast and simple method based on extraction with 5% trichloroacetic acid (TCA) and quantitation with liquid chromatography-mass tandem spectrometry (LC-MS/MS) for measuring cAMP in cells.

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular.

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis.

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment.

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles.

Sympathetic improvement of cancer vaccine efficacy.

The link between stress, other psychological factors and response to cancer, or even the cancer incidence and metastasis, is well established. The inhibition of β-Adrenergic receptors (β-AR) using β-blockers was demonstrated to have an inhibitory effect on cancer recurrence. Direct effects on the stress-induced suppression of anti-tumor immune responses were also shown.

Distribution of allele frequencies for genes associated with physical activity and/or physical capacity in a homogenous Norwegian cohort- a cross-sectional study.

Background: There are large individual differences in physical activity (PA) behavior as well as trainability of physical capacity. Heritability studies have shown that genes may have as much impact on exercise participation behavior as environmental factors. Genes that favor both trainability and participation may increase the levels of PA.

Biological response and cytotoxicity induced by lipid nanocapsules.

Background: Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac™ Lipophile WL1349, Lipoid S75 and Solutol HS15.

DNA Methylation of : A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients.

Background: Previous studies support a tumor-suppressor role for across various types of cancers. We aimed to investigate the association between DNA methylation of and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC).

Methods: This study included 1,230 patients with early-stage NSCLC.

Serum cytokine profiles and metabolic tumor burden in patients with non-small cell lung cancer undergoing palliative thoracic radiation therapy.

Purpose: Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (F-FDG) positron emission tomography (PET).

Methods And Materials: Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor.

Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.

Background: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs.

Material And Methods: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment.

SIOPE - Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy.

Objective: To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy.

Methods And Materials: During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution.

Results: The CTV should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa.

Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages.

Background: Macrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer.

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination.

Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound.

Detection and proteomic characterization of extracellular vesicles in human pancreatic juice.

Aims: The prognosis of patients with pancreatic cancer has remained virtually unchanged with a high mortality rate compared to other types of cancers. An earlier detection would provide a time window of opportunity for treatment and prevention of deaths. In the present study we investigated extracellular vesicle (EV)-associated potential biomarkers for pancreatic cancer by directly assessing EV size-based subpopulations in pancreatic juice samples of patients with chronic pancreatitis or pancreatic cancer.