Resveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil.

Background And Aim: Standard rectal cancer treatment includes neoadjuvant radiotherapy sensitized by 5-fluorouracil (5-FU) chemotherapy. However, 5-FU increased chemoradiotherapy response rate comes with significant toxicity, especially in older, frail patients. The development of alternatives to chemotherapy enabling radiosensitization with limited systemic toxicity is therefore needed to improve patient management.

Integrating allele-specific PCR with CRISPR-Cas13a for sensitive KRAS mutation detection in pancreatic cancer.

Background: The clustered regulatory interspaced short palindromic repeats (CRISPR)-Cas13a system has strong potential for highly sensitive detection of exogenous sequences. The detection of KRAS point mutations with low allele frequencies may prove powerful for the formal diagnosis of pancreatic ductal adenocarcinoma (PDAC).

Results: We implemented preamplification of KRAS alleles (wild-type and mutant) to reveal the presence of mutant KRAS with CRISPR-Cas13a.

Omentoplasty versus cecal mobilization after abdominoperineal resection: A propensity score matching analysis.

Background: Despite the minimally invasive approach and early rehabilitation, abdominal-perineal resection (APR) remains a procedure with high morbidity, notably due to postoperative trapped bowel ileus and perineal healing complications. Several surgical techniques have been described for filling the pelvic void to prevent abscess formation and ileus by trapped bowel loop.

Objective: The aim of our study was to compare the post APR complications for cancer of two of these techniques, omentoplasty and cecal mobilization, in a single-center study from an expert colorectal surgery center.

Glucuronide metabolites of trans-ε-viniferin decrease triglycerides accumulation in an in vitro model of hepatic steatosis.

Trans-ε-viniferin, a resveratrol dimer found mainly in grapevine wood, has shown protective capacities against hepatic steatosis in vivo. Nevertheless, this compound is very poorly bioavailable. Thus, the aim of the present study is to determine the potential anti-steatotic properties of 1 and 10 µM of trans-ε-viniferin and its four glucuronide metabolites in AML-12 cells treated with palmitic acid as an in vitro model of hepatic steatosis.

CRISPR editing to mimic porphyria combined with light: A new preclinical approach for prostate cancer.

Thanks to its very high genome-editing efficiency, CRISPR-Cas9 technology could be a promising anticancer weapon. Clinical trials using CRISPR-Cas9 nuclease to edit and alter immune cells are ongoing. However, to date, this strategy still has not been applied in clinical practice to directly target cancer cells.

Droplet digital polymerase chain reaction detection of KRAS mutations in pancreatic FNA samples: Technical and practical aspects for routine clinical implementation.

Background: Pancreatic adenocarcinoma (PDAC) is associated with a 5-year survival rate of less than 6%, and current treatments have limited efficacy. The diagnosis of PDAC is mainly based on a cytologic analysis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples. However, the collected specimens may prove noncontributory in a significant number of cases, delaying patient management and treatment.

The Crying Need for a Better Response Assessment in Rectal Cancer.

Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a watch and wait strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment.

Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR-Cas9.

The CRISPR-Cas9 system has revolutionized our ability to precisely modify the genome and has led to gene editing in clinical applications. Comprehensive analysis of gene editing products at the targeted cut-site has revealed a complex spectrum of outcomes. ON-target genotoxicity is underestimated with standard PCR-based methods and necessitates appropriate and more sensitive detection methods.

Specific High-Sensitivity Enzymatic Reporter UnLOCKing-Mediated Detection of Oncogenic and Rearrangements.

Advances in molecular medicine have placed nucleic acid detection methods at the center of an increasing number of clinical applications. Polymerase chain reaction (PCR)-based diagnostics have been widely adopted for their versatility, specificity, and sensitivity. However, recently reported clustered regularly interspaced short palindromic repeats-based methods have demonstrated equivalent to superior performance, with increased portability and reduced processing time and cost.

Combined Reverse-Transcriptase Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing Analyses to Assign Unclassified BCL2/BCL6 Nonrearranged Small B-Cell Lymphoid Neoplasms as Follicular or Nodal Marginal Zone Lymphoma.

Distinguishing between follicular lymphoma (FL) and nodal marginal zone lymphoma (NMZL) can be difficult when morphologic and phenotypic features are unusual and characteristic cytogenetic rearrangements are absent. We evaluated the diagnostic contribution of ancillary techniques-including fluorescence in situ hybridization (FISH)-detected 1p36 deletion; reverse-transcriptase, multiplex, ligation-dependent probe amplification (RT-MLPA); and next-generation sequencing (NGS)-for tumors that remain unclassified according to standard criteria. After review, 50 CD5-negative small B-cell lymphoid neoplasms without BCL2 and BCL6 FISH rearrangements were diagnosed as FLs (n = 27), NMZLs (n = 5), or unclassified (n = 18) based on the 2016 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues.

Clinical impact of STK11 mutation in advanced-stage non-small cell lung cancer.

Background: Mutations in STK11/LKB1 gene present a negative impact on tumour immune microenvironment, especially with concomitant activating KRAS mutation. These recent data may explain a decreased response to immunotherapy treatment in STK11 mutant non-small cell lung cancer (NSCLC).

Objective: The primary objective is to evaluate, in a real-life setting, overall survival (OS) in patients with NSCLC according to the presence of STK11 mutation.

A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma.

Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome.

KRAS gene mutation quantification in the resection or venous margins of pancreatic ductal adenocarcinoma is not predictive of disease recurrence.

Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Even patients with a good pathological response after neoadjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with a worse prognosis.

Bioactive food components for colorectal cancer prevention and treatment: A good match.

Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC.

ON-Target Adverse Events of CRISPR-Cas9 Nuclease: More Chaotic than Expected.

CRISPR-Cas9 is a highly promising technology for clinical development. However, this powerful tool can induce adverse genomic events. The off-target genotoxicity is well described, predictable, detectable, and resolved by the use of new generations of Cas9 nucleases with high fidelity.

CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells.

CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.

Spleen route accelerates engraftment of human hematopoietic stem cells.

Intravenous injections of human hematopoietic stem cells (hHSCs) is routinely used in clinic and for modeling hematopoiesis in mice. However, unspecific dilution in vascular system and non-hematopoietic organs challenges engraftment efficiency. Although spleen is capable of extra medullar hematopoiesis, its ability to support human HSC transplantation has never been evaluated.

Next-Generation Cancer Biomarkers: Extracellular Vesicle DNA as a Circulating Surrogate of Tumor DNA.

Extracellular vesicles (EVs) are produced by healthy tissues and tumor cells and are released in various bodily fluids, including blood. They are limited by bilayer phospholipidic membranes, and they carry a rich content in biomolecules. Their release cleanses the cells of their waste or serves as functional local and distant cell-cell communication and molecular exchange particles.

Pigments test strips: A rapid companion test to exclude sub-arachnoid haemorrhage.

Objectives: Subarachnoid haemorrhage (SAH) is characterised by 25% of mortality or induces long-term care. It needs immediate diagnosis with computed tomography (CT) scan. For the inconclusive CT scans, the detection of haem pigments can be performed in the cerebrospinal fluid (CSF).

Circulating Tumor Cell Clusters: United We Stand Divided We Fall.

The presence of circulating tumor cells (CTCs) and CTC clusters, also known as tumor microemboli, in biological fluids has long been described. Intensive research on single CTCs has made a significant contribution in understanding tumor invasion, metastasis tropism, and intra-tumor heterogeneity. Moreover, their being minimally invasive biomarkers has positioned them for diagnosis, prognosis, and recurrence monitoring tools.

Combination treatment of resveratrol and capsaicin radiosensitizes pancreatic tumor cells by unbalancing DNA repair response to radiotherapy towards cell death.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers because it is highly resistant to every available therapeutic strategy, in particular conventional chemotherapy or radiotherapy (RT). Sensitizing tumor cells to existing treatments remains a good option to obtain fast and applicable results. Considering that ionizing radiations induce radiolysis-derived reactive oxygen species (ROS), we hypothesized that ROS-inducing bioactive food components (BFCs) could exacerbate ROS-related cell damages, including DNA double stranded breaks (DSBs), leaving the cellular ROS scavenging systems overwhelmed, and precipitating tumor cell death.