CXCL12 impact on glioblastoma cells behaviors under dynamic culture conditions: Insights for developing new therapeutic approaches.

Glioblastoma multiforme (GBM) is the most prevalent malignant brain tumor, with an average survival time of 14 to 20 months. Its capacity to invade brain parenchyma leads to the failure of conventional treatments and subsequent tumor recurrence. Recent studies have explored new therapeutic strategies using a chemoattracting gradient to attract GBM cells into a soft hydrogel trap where they can be exposed to higher doses of radiation or chemotherapy.

Macroporous chitosan/alginate hydrogels crosslinked with genipin accumulate and retain glioblastoma cancer cells.

Grade IV multiforme glioblastoma (GBM) is an aggressive cancer that remains incurable due to the GBM cells invading and proliferating in the surrounding healthy tissues, even after tumor resection. A new therapeutic paradigm to treat GBM is to attract and accumulate GBM cells in a macroporous hydrogel inserted in the surgical cavity after tumor resection, followed by a targeted high dose of radiotherapy. This work presents a molding-based method to prepare macroporous hydrogels composed of sodium alginate and chitosan, homogeneously mixed in solution using sodium bicarbonate, and subsequently crosslinked with genipin and calcium chloride.

Combination of radiotherapy and immunotherapy in duality with the protumoral action of radiation.

Radiotherapy is widely used to treat various cancers. Its combination with immune checkpoint inhibitors is intensively studied preclinically and clinically. Although the first results were very encouraging, the number of patients who respond positively remains low, and the therapeutic benefit is often temporary.

The role of pore size and mechanical properties on the accumulation, retention and distribution of F98 glioblastoma cells in macroporous hydrogels.

Glioblastoma (GBM) accounts for half of all central nervous system tumors. Once the tumor is removed, many GBM cells remain present near the surgical cavity and infiltrate the brain up to a distance of 20-30 mm, resulting in recurrence a few months later. GBM remains incurable due to the limited efficiency of current treatments, a result of the blood-brain barrier and sensitivity of healthy brain tissues to chemotherapy and radiation.

Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy.

Background:  Radioresistance of HNSCCs remains a major challenge for effective tumor control. Combined radiotherapy (RT) and immunotherapy (IT) treatment improved survival for a subset of patients with inflamed tumors or tumors susceptible to RT-induced inflammation. To overcome radioresistance and improve treatment outcomes, an understanding of factors that suppress anti-tumor immunity is necessary.

behavior of [Cu]NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer.

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope Cu. stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [Cu]NOTA-C3-TP were determined. The current experimental studies show that [Cu]NOTA-C3-TP is stable , rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.

Effect of Chitosan on Alginate-Based Macroporous Hydrogels for the Capture of Glioblastoma Cancer Cells.

Glioblastoma multiforme is a type of brain cancer associated with a very low survival rate since a large number of cancer cells remain infiltrated in the brain despite the treatments currently available. This work presents a macroporous hydrogel trap, destined to be implanted in the surgical cavity following tumor resection and designed to attract and retain cancer cells, in order to eliminate them afterward with a lethal dose of stereotactic radiotherapy. The biocompatible hydrogel formulation comprises sodium alginate (SA) and chitosan (CHI) bearing complementary electrostatic charges and stabilizing the gels in saline and cell culture media, as compared to pristine SA gels.

Drug Delivery Systems in the Development of Novel Strategies for Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is a grade IV glioma considered the most fatal cancer of the central nervous system (CNS), with less than a 5% survival rate after five years. The tumor heterogeneity, the high infiltrative behavior of its cells, and the blood-brain barrier (BBB) that limits the access of therapeutic drugs to the brain are the main reasons hampering the current standard treatment efficiency. Following the tumor resection, the infiltrative remaining GBM cells, which are resistant to chemotherapy and radiotherapy, can further invade the surrounding brain parenchyma.

Downregulation of KRAB zinc finger proteins in 5-fluorouracil resistant colorectal cancer cells.

Radio-chemotherapy with 5-flu orouracil (5-FU) is the standard of care treatment for patients with colorectal cancer, but it is only effective for a third of them. Despite our understanding of the mechanism of action of 5-FU, drug resistance remains a significant limitation to the clinical use of 5-FU, as both intrinsic and acquired chemoresistance represents the major obstacles for the success of 5-FU-based chemotherapy. In order to identify the mechanism of acquired resistance, 5-FU chemoresistance was induced in CRC cell lines by passaging cells with increasing concentrations of 5-FU.

Estimation of the Internal Dose Imparted by F-Fluorodeoxyglucose to Tissues by Using Fricke Dosimetry in a Phantom and Positron Emission Tomography.

Purpose: Assessment of the radiation dose delivered to a tumor and different organs is a major issue when using radiolabelled compounds for diagnostic imaging or endoradiotherapy. The present article reports on a study to correlate the mean F-fluorodeoxyglucose (F-FDG) activity in different tissues measured in a mouse model by positron emission tomography (PET) imaging, with the dose assessed by Fricke dosimetry.

Methods: The dose-response relationship of the Fricke dosimeter and PET data was determined at different times after adding F-FDG (0-80 MBq) to a Fricke solution (1 mM ferrous ammonium sulfate in 0.

Design, Synthesis, and Cytotoxicity Assessment of [Cu]Cu-NOTA-Terpyridine Platinum Conjugate: A Novel Chemoradiotherapeutic Agent with Flexible Linker.

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (Cu). The decay of Cu produces numerous low-energy electrons, enabling the Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA.

Reconciling two opposing effects of radiation therapy: stimulation of cancer cell invasion and activation of anti-cancer immunity.

Purpose: The damage caused by radiation therapy to cancerous and normal cells inevitably leads to changes in the secretome profile of pro and anti-inflammatory mediators. The inflammatory response depends on the dose of radiation and its fractionation, while the inherent radiosensitivity of each patient dictates the intensity and types of adverse reactions. This review will present an overview of two apparently opposite reactions that may occur after radiation treatment: induction of an antitumor immune response and a protumoral response.

An alginate-based macroporous hydrogel matrix to trap cancer cells.

To overcome the radioresistance of glioblastoma (GBM) cells infiltrated in the brain, we propose to attract these cancer cells into a trap to which a lethal radiation dose can be delivered safely. Herein, we have prepared and characterized a sodium alginate-based macroporous hydrogel as a potential cancer cell trap. Microcomputed X-ray tomography shows that the hydrogel matrices comprise interconnected pores with an average diameter of 300 μm.

High Cytotoxic Effect by Combining Copper-64 with a NOTA-Terpyridine Platinum Conjugate.

Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (Cu), the decay characteristics of which include emission of β and Auger electrons for radiotherapy and β particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells.

Erratum: Gascon S.; et al. Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells. 2020, , 356.

The authors wish to make the following correction to this paper [...

Brain irradiation leads to persistent neuroinflammation and long-term neurocognitive dysfunction in a region-specific manner.

Long-term cognitive deficits are observed after treatment of brain tumors or metastases by radiotherapy. Treatment optimization thus requires a better understanding of the effects of radiotherapy on specific brain regions, according to their sensitivity and interconnectivity. In the present study, behavioral tests supported by immunohistology and magnetic resonance imaging provided a consistent picture of the persistent neurocognitive decline and neuroinflammation after the onset of irradiation-induced necrosis in the right primary somatosensory cortex of Fischer rats.

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells.

Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them.

Cerebrovascular inflammation promotes the formation of brain metastases.

Brain metastases are the most prevalent intracranial malignancy. Patient outcome is poor and treatment options are limited. Hence, new avenues must be explored to identify potential therapeutic targets.

Intratumoral F-FLT infusion in metabolic targeted radiotherapy.

Background: The goal of targeted radiotherapy (TRT) is to administer radionuclides to tumor cells, while limiting radiation exposure to normal tissues. 3'-Deoxy-3'-[F]-fluorothymidine (F-FLT) is able to target tumor cells and emits a positron with energy appropriate for local (~ 1 mm range) radiotherapy. In the present work, we investigated the potential of TRT with a local administration of F-FLT alone or in combination with 5-fluorouracil (5FU), which acts as a chemotherapeutic agent and radiosensitizer.

Liposomal formulations of carboplatin injected by convection-enhanced delivery increases the median survival time of F98 glioma bearing rats.

Background: Effectiveness of chemotherapy for treating glioblastoma (GBM) brain tumors is hampered by the blood-brain barrier which limits the entry into the brain of most drugs from the blood. To bypass this barrier, convection-enhanced delivery (CED) was proposed to directly inject drugs in tumor. However, the benefit of CED may be hampered when drugs diffuse outside the tumor to then induce neurotoxicity.

Diffusion MRI monitoring of specific structures in the irradiated rat brain.

Purpose: The analysis of biological and mesoscopic structures properties by diffusion MRI (dMRI) in brain after radiation therapy remains challenging. In our study, we described the consequences associated with an unwanted dose to healthy tissue, assessing radiation-induced brain alterations of living rats with dMRI compared to histopathology and behavioral assays.

Methods: The right primary motor cortex M of the rat brain was targeted by stereotactic radiosurgery with a mean radiation dose of 41 Gy.

Tumor Cell Invasion Induced by Radiation in Balb/C Mouse is Prevented by the Cox-2 Inhibitor NS-398.

Radiation stimulates the expression of inflammatory mediators known to increase cancer cell invasion. Therefore, it is important to determine whether anti-inflammatory drugs can prevent this adverse effect of radiation. Since cyclooxygenase-2 (COX-2) is a central player in the inflammatory response, we performed studies to determine whether the COX-2 inhibitor NS-398 can reduce the radiation enhancement of cancer cell invasion.

Radiation-induced lung metastasis development is MT1-MMP-dependent in a triple-negative breast cancer mouse model.

Background: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases.

Induction of interleukin-1β by mouse mammary tumor irradiation promotes triple negative breast cancer cells invasion and metastasis development.

Purpose: Radiotherapy increases the level of inflammatory cytokines, some of which are known to promote metastasis. In a mouse model of triple negative breast cancer (TNBC), we determined whether irradiation of the mammary tumor increases the level of key cytokines and favors the development of lung metastases.

Materials And Methods: D2A1 TNBC cells were implanted in the mammary glands of a Balb/c mouse and then 7 days old tumors were irradiated (4 × 6 Gy).

Understanding the continuum of radionecrosis and vascular disorders in the brain following gamma knife irradiation: An MRI study.

Purpose: The radiation dose delivered to brain tumors is limited by the possibility to induce vascular damage and necrosis in surrounding healthy tissue. In the present study, we assessed the ability of MRI to monitor the cascade of events occurring in the healthy rat brain after stereotactic radiosurgery, which could be used to optimize the radiation treatment planning.

Methods: The primary somatosensory forelimb area (S1FL) and the primary motor cortex in the right hemisphere of Fischer rats (n = 6) were irradiated with a single dose of Gamma Knife radiation (Leksell Perfexion, Elekta AG, Stockholm, Sweden).