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Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial. 

Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangioge...

A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants. 

The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two a...

The Roles of Imprinted SLC22A18 and SLC22A18AS Gene Overexpression Caused by Promoter CpG Island Hypomethylation as Diagnostic and Prognostic Biomarkers for Non-Small Cell Lung Cancer Patients. 

Genomic imprinting is a process that involves one gene copy turned-off in a parent-of-origin-dependent manner. The regulation of imprinted genes is broadly dependent on promoter methylation marks, which are frequently associated with both oncogenes and tumor suppressors. The purpose of this study w...

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. 

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organo...

The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases. 

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In t...

Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. 

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1,...

Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. 

Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predic...

EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity. 

Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as ...

Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes. 

The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence). To evaluate the association between quantitative, li...

Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. 

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. He...

Polymerization and editing modes of a high-fidelity DNA polymerase are linked by a well-defined path. 

Proofreading by replicative DNA polymerases is a fundamental mechanism ensuring DNA replication fidelity. In proofreading, mis-incorporated nucleotides are excised through the 3'-5' exonuclease activity of the DNA polymerase holoenzyme. The exonuclease site is distal from the polymerization site, i...

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. 

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-base...

A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways. 

Independent scientific achievements have led to the discovery of aberrant splicing patterns in oncogenesis, while more recent advances have uncovered novel gene fusions involving neurotrophic tyrosine receptor kinases (NTRKs) in gliomas. The exploration of NTRK splice variants in normal and neoplas...

Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells. 

Most breast cancers exhibit low immune infiltration and are unresponsive to immunotherapy. We hypothesized that inhibition of the receptor activator of nuclear factor-κB (RANK) signaling pathway may enhance immune activation. Here we report that loss of RANK signaling in mouse tumor cells increases...

PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. 

Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled ...

In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. 

Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the ...

Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis. 

Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. ...

Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses. 

There is epidemiological evidence that patients with certain Central Nervous System (CNS) disorders have a lower than expected probability of developing some types of Cancer. We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Can...

Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer: an international validation in primary tumours. 

We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who underwent a transurethral resec...