Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer NBTXR3.

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR).

Radiotherapy-activated NBTXR3 nanoparticles promote ferroptosis through induction of lysosomal membrane permeabilization.

Purpose: Radiotherapy-activated NBTXR3 (NBTXR3 + RT) has demonstrated superior efficacy in cancer cell destruction and tumor growth control, compared to radiotherapy (RT), in preclinical and clinical settings. Previous studies highlighted the immunomodulatory properties of NBTXR3 + RT, such as modification of tumor cell immunogenicity/adjuvanticity, producing an effective local tumor control and abscopal effect, related to an enhanced antitumor immune response. Furthermore, NBTXR3 + RT has shown potential in restoring anti-PD1 efficacy in a refractory tumor model.

Deep audio embeddings for vocalisation clustering.

The study of non-human animals' communication systems generally relies on the transcription of vocal sequences using a finite set of discrete units. This set is referred to as a vocal repertoire, which is specific to a species or a sub-group of a species. When conducted by human experts, the formal description of vocal repertoires can be laborious and/or biased.

Nanoparticle-enhanced proton beam immunoradiotherapy drives immune activation and durable tumor rejection.

The combination of radiation therapy (RT) and immunotherapy has emerged as a promising treatment option in oncology. Historically, x-ray radiation (XRT) has been the most commonly used form of RT. However, proton beam therapy (PBT) is gaining recognition as a viable alternative, as it has been shown to produce similar outcomes to XRT while minimizing off-target effects.

NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model.

The efficacy of immunoradiotherapy consisting of radiation therapy and immune checkpoint blockade relies on effectively promoting the systemic antitumor immune response's activation while simultaneously reducing local factors favoring immune suppression. We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung cancer model. We hypothesize that radioactivated-NBTXR3 addition to anti-PD1 and a second-generation anti-CTLA4 could improve treatment effectiveness.

Combining a nanoparticle-mediated immunoradiotherapy with dual blockade of LAG3 and TIGIT improves the treatment efficacy in anti-PD1 resistant lung cancer.

Background: While improvements in immunoradiotherapy have significantly improved outcomes for cancer patients, this treatment approach has nevertheless proven ineffective at controlling the majority of malignancies. One of the mechanisms of resistance to immunoradiotherapy is that immune cells may be suppressed via the myriad of different immune checkpoint receptors. Therefore, simultaneous blockade of multiple immune checkpoint receptors may enhance the treatment efficacy of immunoradiotherapy.

Temporal evolution of the Mediterranean fin whale song.

We present an analysis of fin whale (Balaenoptera physalus) songs on passive acoustic recordings from the Pelagos Sanctuary (Western Mediterranean Basin). The recordings were gathered between 2008 and 2018 using 2 different hydrophone stations. We show how 20 Hz fin whale pulses can be automatically detected using a low complexity convolutional neural network (CNN) despite data variability (different recording devices exposed to diverse noises).

Radiotherapy-activated NBTXR3 nanoparticles modulate cancer cell immunogenicity and TCR repertoire.

Background: Radiotherapy is a powerful and widely used technique for the treatment of solid tumors. Beyond its ability to destroy tumor cells, it has been demonstrated that radiotherapy can stimulate the anti-tumor immune response. Unfortunately, this effect is mainly restricted to the irradiated lesion, as tumor control outside the treated field (called the 'abscopal effect') is rarely obtained.

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model.

Background: Combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer.

Methods: Mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor).

Radiation Therapy Enhanced by NBTXR3 Nanoparticles Overcomes Anti-PD1 Resistance and Evokes Abscopal Effects.

Purpose: Radiation combined with PD1 blockade offers significant treatment benefits in several tumor types; however, anti-PD1 resistance precludes such benefits in many cases. Here we attempted to overcome anti-PD1 resistance by combining localized radiation with a radioenhancing nanoparticle (NBTXR3) and systemic anti-PD1 treatment to achieve abscopal effects in an anti-PD1-resistant mouse model of lung cancer.

Methods And Materials: Female 129Sv/Ev mice were inoculated with 344SQ anti-PD1-resistant (344SQR) or anti-PD1-sensitive (344SQP) metastatic lung cancer cells in the right leg on day 0 ("primary" tumor) and the left leg on day 4 ("secondary" tumor).

NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models.

Purpose: The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy.

Patients And Methods: Thanks to its physical mode of action, NBTXR3 has the potential to be used to treat any type of solid tumor.

Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model.

Purpose: Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect).

DNA damage enhancement by radiotherapy-activated hafnium oxide nanoparticles improves cGAS-STING pathway activation in human colorectal cancer cells.

The cGAS-STING pathway can be activated by radiation induced DNA damage and because of its important role in anti-cancer immunity activation, methods to increase its activation in cancer cells could provide significant therapeutic benefits for patients. We explored the impact of hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy on cell death, DNA damage, and activation of the cGAS-STING pathway. We demonstrate that NBTXR3 activated by radiotherapy enhances cell destruction, DNA double strand breaks, micronuclei formation and cGAS-STING pathway activation in a human colorectal cancer model, compared to radiotherapy alone.

Combining radiation plus immunotherapy to improve systemic immune response.

Over the past decade, the fields of oncology have made great strides in therapies. The development of new therapeutics and increased understanding of the role of the immune system in the development and treatment of cancer has led to increased collaboration between oncologic fields. Recent technologic advancements in radiation therapy (RT), including stereotactic beam radiation therapy (SBRT), have improved local control and offer an alternative to surgery for the control of oligometastatic disease.

Efficient strategies for TALEN-mediated genome editing in mammalian cell lines.

TALEN is one of the most widely used tools in the field of genome editing. It enables gene integration and gene inactivation in a highly efficient and specific fashion. Although very attractive, the apparent simplicity and high success rate of TALEN could be misleading for novices in the field of gene editing.

Classification of mysticete sounds using machine learning techniques.

Automatic classification of mysticete sounds has long been a challenging task in the bioacoustics field. The unknown statistical properties of the signals as well as the use of different recording apparatus and low signal-to-noise ratio conditions often lead to non-optimal systems. The goal of this paper is to design methods for the automatic classification of mysticete sounds using a restricted Boltzmann machine and a sparse auto-encoder that are widely used in the field of artificial intelligence.

A compact tunable diode laser absorption spectrometer to monitor CO2 at 2.7 μm wavelength in hypersonic flows.

Since the beginning of the Mars planet exploration, the characterization of carbon dioxide hypersonic flows to simulate a spaceship's Mars atmosphere entry conditions has been an important issue. We have developed a Tunable Diode Laser Absorption Spectrometer with a new room-temperature operating antimony-based distributed feedback laser (DFB) diode laser to characterize the velocity, the temperature and the density of such flows. This instrument has been tested during two measurement campaigns in a free piston tunnel cold hypersonic facility and in a high enthalpy arc jet wind tunnel.

Activity-driven populace: a cognitive approach to crowd simulation.

Simulating a natural-looking virtual populace requires modeling different behavioral levels to mimic how people choose and organize their activities. A multilayer behavior model for crowd simulation can help developers endow each entity with high-level objectives built on top of a reactive and cognitive decision system.

Opposing roles of syndecan-1 and syndecan-2 in polyethyleneimine-mediated gene delivery.

Polyethyleneimines (PEIs) are efficient non-viral vectors for gene transfer. Heparan sulfate proteoglycans have been proposed to be the cell-surface receptors for PEI.DNA complexes (polyplexes).

[The fluorescence: a "bright" concept for the study of the metastatic process].

The forming of secondary tumors, called metastases, constitutes the first cause of death of the patients reached by a cancer and represents one of the major obstacles in the fight against this disease. The characterization of mechanisms governing the passage of the cancerous phenotype into metastasis thus turns out to be a crucial stage for the discovery of new treatments. The understanding, and finally the inhibition of a so complex and multifactorial process, require the implementation of various strategies of study (e.

Limiting factors governing protein expression following polyethylenimine-mediated gene transfer in HEK293-EBNA1 cells.

Transient gene expression in mammalian cells is intensively used for the rapid generation of recombinant proteins for biochemical, biophysical and pre-clinical studies. Still, the principles behind DNA transfer to the cells and the cellular cascade of events that ultimately dictate protein expression levels are not fully understood. Using polyethylenimine (PEI) mediated transfection of HEK293-EBNA1 cells, we sought to determine the most critical parameters that drive and limit recombinant protein production.

Hyaluronectin modulation of lung metastasis in nude mice.

Hyaluronectin (HN) is a glycoprotein with a high affinity to hyaluronic acid (HA) and known to be a component of the extracellular matrix of tumours. Clinical studies have shown that a low level of HN correlates to tumours with poor prognosis, whereas a high level of HN correlates to tumours with good prognosis. We previously demonstrated in vitro that hyaluronidase activity, which promotes tumour progression and metastatic spread by degradation of HA into angiogenic oligosaccharides, was inhibited or promoted by HN, according to the level of HN-expression.

Casein kinase 2 inhibition decreases hypoxia-inducible factor-1 activity under hypoxia through elevated p53 protein level.

HIF-1 (hypoxia-inducible factor-1) is the main transcription factor involved in the adaptation of cells to hypoxia. In addition to regulation of HIF-1alpha protein level, HIF-1 activity is also enhanced by several pathways involving asparagine hydroxylation and phosphorylation. Here, we investigated the relationship between casein kinase 2 (CK2), p53 and HIF-1.

Up-regulation of 94-kDa glucose-regulated protein by hypoxia-inducible factor-1 in human endothelial cells in response to hypoxia.

Hypoxic environment in solid tumor is known to favor cell survival and to initiate the formation of new capillaries. In this work, we identified by 2D gel analysis 94-kDa glucose-regulated protein (GRP94) as being upregulated in human endothelial cells in response to hypoxia. Three putative hypoxia responsive elements (HRE) were found in the GRP94 promoter.