Phytochemical screening, antimicrobial, antioxidant, anticancer activities on cervical cancer cell lines and aero-digestive extract of .

The phytochemical screening showed that the (MO) extract contained many compounds such as polyphenols, polyterpenes, sterols, reducing sugars, and hydrolysates tannins. The MICs of MO extract for microbial strains is 0.73 mg/ml for , , 7.

Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling.

The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling.

Differential Formation of Stress Granules in Radiosensitive and Radioresistant Head and Neck Squamous Cell Carcinoma Cells.

Purpose: Stress granules (SGs) are cytoplasmic aggregates in which mRNAs and specific proteins are trapped in response to a variety of damaging agents. They participate in the cellular defense mechanisms. Currently, their mechanism of formation in response to ionizing radiation and their role in tumor-cell radiosensitivity remain elusive.

Paired Comparison of Routine Molecular Screening of Patient Samples with Advanced Non-Small Cell Lung Cancer in Circulating Cell-Free DNA Using Three Targeted Assays.

Introduction: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80-85% of all lung cancers. Approximately 10-50% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of . Currently, for patients with advanced NSCLC, testing for sensitizing mutations in is mandatory prior to the administration of tyrosine kinase inhibitors.

Challenges in radiobiology - technology duality as a key for a risk-free α/β ratio.

Since radiotherapy discovery, prediction of biological response to ionizing radiation remains a major challenge. Indeed, several radiobiological models appeared through radiotherapy history. Nominal single dose so popular in the 1970s, was tragically linked to the dark years in radiobiology by underestimating the late toxicity of the high-dose fractions.

Non-linearity in lipase assays: A multicentric comparison on different analysers.

Objectives: Non-linearity in lipase assays and the ensuing gaps in results distribution have been described on Roche analysers, but have yet to be studied on other analysers.

Design And Methods: Eighteen lithium-heparinized plasma pools of lipase activities decreasing from 1700 to <4 U/L were prepared for multicentric evaluation on several analysers. Non-linearity was modelled as the difference between the polynomial regression of lipase activities depending on relative dilutions over the primary measuring range, and the linear regression of the same variables above the manufacturer's limit of linearity (MLL).

The 'stealth-bomber' paradigm for deciphering the tumour response to carbon-ion irradiation.

Numerous studies have demonstrated the higher biological efficacy of carbon-ion irradiation (C-ions) and their ballistic precision compared with photons. At the nanometre scale, the reactive oxygen species (ROS) produced by radiation and responsible for the indirect effects are differentially distributed according to the type of radiation. Photon irradiation induces a homogeneous ROS distribution, whereas ROS remain condensed in clusters in the C-ions tracks.

Proof of Concept of the Radiosensitizing Effect of Gadolinium Oxide Nanoparticles in Cell Spheroids and a Tumor-Implanted Murine Model of Chondrosarcoma.

Purpose: Chondrosarcomas (CHSs), which represent 20% of primary bone tumors in adults, are mostly resistant to radio- and chemotherapy. It is therefore essential that new therapeutic approaches, targeted to the tumour, be developed to improve the prognosis of patients. The effectiveness, as a radiosensitizing agent, of gadolinium oxide nanoparticles (GdoNP, AGuIX) nanoparticles in CHS was evaluated in vitro, in spheroid CHS models allowing to reproduce cell-cell extracellular matrix interactions, and, in vivo, in a nude mouse model with heterotopic tumour xenograft.

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers.

An emerging target to overcome cancer resistance to treatments is copper, which is upregulated in a wide variety of tumors and may be associated with cancer progression and metastases. The aim of this study was to develop a multimodal ultrasmall nanoparticle, CuPRiX, based on the clinical AGuIX nanoparticle made of the polysiloxane matrix on which gadolinium chelates are grafted. Such hybrid nanoparticles allow: (i) a localized depletion of copper in tumors to prevent tumor cell dissemination and metastasis formation and (ii) an increased sensitivity of the tumor to radiotherapy (RT) due to the presence of high Z gadolinium (Gd) atoms.

Circulating Tumor Cell Detection during Neoadjuvant Chemotherapy to Predict Early Response in Locally Advanced Oropharyngeal Cancers: A Prospective Pilot Study.

Patients with locally advanced oropharyngeal carcinoma treated with neoadjuvant chemotherapy are reassessed both radiologically and clinically to adapt their treatment after the first cycle. However, some responders show early tumor progression after adjuvant radiotherapy. This cohort study evaluated circulating tumor cells (CTCs) from a population of locally advanced oropharyngeal carcinoma patients treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) induction chemotherapy or DCF with a modified dose and fractioned administration.

CD44, γ-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma.

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies.

Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After Irradiation.

Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations.

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts.

Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses.

Involvement of HIF-1α in the Detection, Signaling, and Repair of DNA Double-Strand Breaks after Photon and Carbon-Ion Irradiation.

Hypoxia-Inducible Factor 1α (HIF-1α), which promotes cancer cell survival, is the main regulator of oxygen homeostasis. Hypoxia combined with photon and carbon ion irradiation (C-ions) stabilizes HIF-1α. Silencing HIF-1α under hypoxia leads to substantial radiosensitization of Head-and-Neck Squamous Cell Carcinoma (HNSCC) cells after both photons and C-ions.

Mechanisms of PhotoBioModulation (PBM) focused on oral mucositis prevention and treatment: a scoping review.

Background: Oral mucositis (OM) is a severe complication cancer patients undergo when treated with chemoradiotherapy. Photobiomodulation (PBM) therapy also known as low-level laser therapy has been increasingly used for the treatment of such oral toxicity. The aim of this review is to discuss the mechanisms of photobiomodulation (PBM) regarding OM prevention and treatment, and more precisely to focus on the effect of PBM on tumor and healthy cells.

Combining radiation to EGFR and Bcl-2 blockade: a new approach to target cancer stem cells in head and neck squamous cell carcinoma.

Purpose: The clinical outcome of head and neck squamous cell carcinoma (HNSCC) remains poor, partly due to the presence of resistant cancer stem cells (CSCs) which are responsible of recurrences. CSCs have low EGFR expression and, conversely, overexpress the anti-apoptotic Bcl-2 protein, which is involved in resistance to apoptosis and the invasion/migration capacities of tumour cells.

Methods: The combination therapy of ABT-199, a Bcl-2 inhibitor, cetuximab an EGFR inhibitor, and radiation using an HNSCC model (SQ20B cell line) and its corresponding CSC subpopulation were evaluated in vitro (2D/3D cell proliferation; invasion/migration and apoptosis using videomicroscopy) and in vivo.

Routine Molecular Screening of Patients with Advanced Non-SmallCell Lung Cancer in Circulating Cell-Free DNA at Diagnosis and During Progression Using OncoBEAM EGFR V2 and NGS Technologies.

Background And Objectives: The use of ultra-sensitive diagnostic tests to detect clinically actionable somatic alterations within the gene encoding the epidermal growth factor receptor (EGFR) within circulating cell-free DNA is an important first step in determining the eligibility of patients with non-small cell lung cancer to receive tyrosine kinase inhibitors.

Methods: We present the clinical validation (accuracy, sensitivity, and specificity) of a highly sensitive OncoBEAM EGFR V2 test, which we compare to a custom next-generation sequencing assay, for the treatment of patients with non-small cell lung cancer with EGFR tyrosine kinase inhibitor therapies. The OncoBEAM digital-polymerase chain reaction method detects 36 different EGFR alterations in circulating cell-free DNA, whereas the next-generation sequencing assay covers major solid tumor oncodrivers.

Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells.

DNA double-strand breaks (DSBs) induced by photon irradiation are the most deleterious damage for cancer cells and their efficient repair may contribute to radioresistance, particularly in hypoxic conditions. Carbon ions (C-ions) act independently of the oxygen concentration and trigger complex- and clustered-DSBs difficult to repair. Understanding the interrelation between hypoxia, radiation-type, and DNA-repair is therefore essential for overcoming radioresistance.

Photobiomodulation by a new optical fiber device: analysis of the in vitro impact on proliferation/migration of keratinocytes and squamous cell carcinomas cells stressed by X-rays.

Photobiomodulation-based (PBM-based) therapies show promising results in mucositis and dermatitis treatment by stimulating wound healing mechanisms such as cell proliferation and migration. The aim of the present study is to investigate the in vitro effects of CareMin650 on the proliferation and migration of two different types of cells, namely cancer and non-cancer cells, with or without X-ray radiation. Study design used PBM through a combination of 0-3-6 J/cm doses-with or without X-ray radiation-on the proliferation and migration capabilities of a keratinocyte cell line (HaCaT) and a squamous cell carcinoma line (SCC61).

Ceramide-Enriched Membrane Domains Contribute to Targeted and Nontargeted Effects of Radiation through Modulation of PI3K/AKT Signaling in HNSCC Cells.

We investigated the potential involvement of ceramide-enriched membrane domains in radiation-induced targeted and nontargeted effects using head and neck squamous cell carcinoma with opposite radiosensitivities. In radiosensitive SCC61 cells, the proportion of targeted effects was 34% and nontargeted effects killed 32% of cells. In contrast, only targeted effects (30%) are involved in the overall death of radioresistant SQ20B cells.

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.

Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression.

Comparison of biophysical models with experimental data for three cell lines in response to irradiation with monoenergetic ions.

The relative biological effectiveness (RBE) in particle therapy is currently estimated using biophysical models. We compared experimental measurements to the α curves as function of linear energy transfer computed by the Local Effect Model (LEM I-IV), the Microdosimetric Kinetic Model (MKM) and the NanOx model for HSG, V79 and CHO-K1 cells in response to monoenergetic irradiations. Although the LEM IV and the MKM predictions accurately reproduced the trend observed in the data, NanOx yielded a better agreement than the other models for more irradiation configurations.

Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence.

Circulating tumor cells (CTCs) derived from the primary tumor are shed into the bloodstream or lymphatic system. These rare cells (1-10 cells per mL of blood) warrant a poor prognosis and are correlated with shorter overall survival in several cancers (e.g.