Phase I trials of single-agent new drugs in head and neck cancer: a scoping review.

Background: The conventional method of drug development in oncology typically progresses through phase I, phase II and randomized phase III trials. Nevertheless, some recent drug approvals for head and neck cancer (HNC) relied on findings from single-arm phase II trials. This underscores the significance of disease-specific phase I trials as a crucial step in exploring new drugs for HNC patients.

Optogenetically controlled inflammasome activation demonstrates two phases of cell swelling during pyroptosis.

Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck-like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation.

Benchmarking informatics approaches for virus discovery: caution is needed when combining identification methods.

Unlabelled: Understanding the ecological impacts of viruses on natural and engineered ecosystems relies on the accurate identification of viral sequences from community sequencing data. To maximize viral recovery from metagenomes, researchers frequently combine viral identification tools. However, the effectiveness of this strategy is unknown.

Tumor acidosis-induced DNA damage response and tetraploidy enhance sensitivity to ATM and ATR inhibitors.

Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways.

3D evaluation of the extracellular matrix of hypoxic pancreatic islets using light sheet fluorescence microscopy.

Pancreatic islet transplantation is a promising treatment for type 1 diabetes, but the survival and function of transplanted islets are hindered by the loss of extracellular matrix (ECM) during islet isolation and by low oxygenation upon implantation. This study aimed to evaluate the impact of hypoxia on ECM using a cutting-edge imaging approach based on tissue clearing and 3D microscopy. Human and rat islets were cultured under normoxic (O 21%) or hypoxic (O 1%) conditions.

Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization's database.

Endocrine therapies (ETs) and inhibitors of cyclin-dependent kinases-4/6 (iCDK4/6s) are a standard treatment in breast cancer. However, data on potential neurocognitive impacts remain inconsistent for ET and are scarce for iCDK4/6s. To evaluate whether ET and iCDK4/6s are associated with neurocognitive impairment (NCI).

Does COVID-19 pandemic impact cancer outcomes in metastatic setting? A comparative cohort study among metastatic patients treated at day care hospital.

Introduction: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes.

Methods: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients.

Posttraumatic Stress Symptoms in Patients With Cancer During the COVID-19 Pandemic: A One-Year Longitudinal Study.

Background: Patients with cancer may be particularly vulnerable to psychological consequences of the COVID-19 pandemic. We studied the prevalence and evolution of posttraumatic stress symptoms (PTSS) in patients with cancer during the pandemic waves, and we investigated factors associated with high symptoms.

Methods: COVIPACT is a 1-year longitudinal prospective study of French patients with solid/hematologic malignancies receiving treatment during the first nationwide lockdown.

Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects.

Tumor acidosis promotes disease progression through a stimulation of fatty acid (FA) metabolism in cancer cells. Instead of blocking the use of FAs by acidic cancer cells, we examined whether excess uptake of specific FAs could lead to antitumor effects. We found that n-3 but also remarkably n-6 polyunsaturated FA (PUFA) selectively induced ferroptosis in cancer cells under ambient acidosis.

Therapy-induced DNA methylation inactivates MCT1 and renders tumor cells vulnerable to MCT4 inhibition.

Metabolic plasticity in cancer cells makes use of metabolism-targeting agents very challenging. Drug-induced metabolic rewiring may, however, uncover vulnerabilities that can be exploited. We report that resistance to glycolysis inhibitor 3-bromopyruvate (3-BrPA) arises from DNA methylation in treated cancer cells and subsequent silencing of the monocarboxylate transporter MCT1.

Obesity and triple-negative-breast-cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple-negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients.

Inhibition of colorectal cancer-associated fibroblasts by lipid nanocapsules loaded with acriflavine or paclitaxel.

Crosstalk between cancer-associated fibroblasts (CAFs) and colorectal cancer cells promotes tumor growth and contributes to chemoresistance. In this study, we assessed the sensitivity of a primary CAF cell line, CT5.3hTERT, to standard-of-care and alternative cytotoxic treatments.

TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells.

Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness.

Exploring the Phototoxicity of Hypoxic Active Iridium(III)-Based Sensitizers in 3D Tumor Spheroids.

Among all molecules developed for anticancer therapies, photodynamic therapeutic agents have a unique profile. Their maximal activity is specifically triggered in tumors by light, and toxicity of even systemically delivered drug is prevented in nonilluminated parts of the body. Photosensitizers exert their therapeutic effect by producing reactive oxygen species via a light-activated reaction with molecular oxygen.

Antidiabetic Biguanides Radiosensitize Hypoxic Colorectal Cancer Cells Through a Decrease in Oxygen Consumption.

The anti-diabetic biguanide drugs metformin and phenformin exhibit antitumor activity in various models. However, their radiomodulatory effect under hypoxic conditions, particularly for phenformin, is largely unknown. This study therefore examines whether metformin and phenformin as mitochondrial complex I blockades could overcome hypoxic radioresistance through inhibition of oxygen consumption.

Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions.

Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several advantages including low cost and reduced adverse effects led to consider light emitting diodes (LED) and even daylight as an alternative to use PDT to treat accessible lesions.

Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects.

Lactate exchange between glycolytic and oxidative cancer cells is proposed to optimize tumor growth. Blocking lactate uptake through monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic strategy but may stimulate glucose consumption by oxidative cancer cells. We report here that inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks of blocking lactate use while preventing glucose oxidative metabolism.

5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies.

Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA.

Inclusion complexation with β-cyclodextrin derivatives alters photodynamic activity and biodistribution of meta-tetra(hydroxyphenyl)chlorin.

Application of meta-tetra(hydroxyphenyl)chorin (mTHPC) one of the most effective photosensitizer (PS) in photodynamic therapy of solid tumors encounters several complications resulting from its insolubility in aqueous medium. To improve its solubility and pharmacokinetic properties, two modified β-cyclodextrins (β-CDs) methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) were proposed. The aim of this work was to evaluate the effect of β-CDs on mTHPC behavior at various stages of its distribution in vitro and in vivo.

Prospects of in vivo singlet oxygen luminescence monitoring: Kinetics at different locations on living mice.

Background: Singlet oxygen observation is considered a valuable tool to assess and optimize PDT treatment. In complex systems, such as tumors in vivo, only the direct, time-resolved singlet oxygen luminescence detection can give reliable information about generation and interaction of singlet oxygen. Up to now, evaluation of kinetics was not possible due to insufficient signal-to-noise ratio.

PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects.

There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic photodynamic therapy. Therefore, we aimed to develop covalent conjugates between the photosensitizer chlorin e6 (Ce6) and PAMAM G4.5 dendrimers.

[Could we trust clinical statistics from data banks of the National Health Service (NHS)?].

Can we accept the statistics provided by the Ministry of Health, which uses large computerized databases? Through MEDECHO, the Ministry provides to hospital managers, reports cards on different interventions. These reports compare different hospitals performances. Surgeons involved in the process hesitate to accept this information.