Publications by authors named "Ladjohounlou R"

Article Synopsis
  • The immune response to radiation therapy (RT) is becoming better understood, but the specific role of Natural Killer (NK) cells in this process is still unclear.
  • Characterizing NK cells in irradiated tumors is crucial for understanding how RT works and improving its effectiveness, possibly in combination with other treatments.
  • The authors introduce a flow cytometry method to analyze NK cell characteristics in colorectal tumors in mice treated with RT, which can also apply to various solid tumors.
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Preclinical development of cancer treatments including radiotherapy (RT) is now crucial to optimize all the treatment aspects for a better efficacy and to help clinicians to build new clinical trials based on robust results. More and more teams use preclinical irradiators to deliver radiotherapy in a comparable way to clinical treatments (image-based RT, arc therapy, stereotactic body RT…). In daily conditions, users usually need to develop easy to use techniques (for applicator technicians for example), allowing to treat many mice per day with a high level of reproducibility.

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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.

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Natural killer (NK) cells are innate lymphoid cells that play an essential role in the anti-tumor response through immunosurveillance, multiple mechanisms of cytotoxicity and the synthesis of cytokines modulating the immune tumor microenvironment (TME). After the dramatic advances in immunotherapy targeting T cells including the success of checkpoint inhibitors or autologous chimeric antigen receptor (CAR) expressing T cells in clinical practice, NK cells have gained growing interest for the development of new therapies. Although NK cells have shown promising responses in leukemia patients, the effects of NK-targeted therapies are currently limited in the treatment of solid tumors.

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Article Synopsis
  • Targeted radionuclide therapy (TRT) is an alternative approach for treating metastatic tumors, offering lower side effects compared to conventional external beam radiotherapy (EBRT) by delivering continuous low doses of radiation.
  • The effectiveness of TRT and EBRT differs, with TRT needing adjustments to traditional models like the sigmoid curve to account for tissue repair times and additional biological factors such as bystander effects and immune response.
  • Researchers suggest that the dose rate in TRT significantly influences the balance between direct DNA damage and broader biological responses involving cellular communication and the immune system.
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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.

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Some patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (Lu)-lilotomab (Betalutin) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts, Lu-lilotomab significantly delayed tumor growth, even at low activity (100 MBq/kg).

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Article Synopsis
  • The study aims to understand the impact of targeted and nontargeted effects of new cancer therapies using radioimmunotherapy (RIT) that utilizes alpha particle emitters and Auger emitters, highlighting their potential influence on treatment outcomes and side effects.
  • Researchers found that a significant portion of cancer cell death was due to directed radiation effects, but a notable percentage was also attributed to nontargeted effects in surrounding cells, driven in part by biochemical processes involving lipid rafts and reactive oxygen species.
  • The findings suggest that altering the cellular environment with specific drugs like statins could enhance survival rates and decrease damage during RIT, indicating that nontargeted effects are crucial considerations for improving cancer treatment efficacy.
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Article Synopsis
  • Researchers created a mouse monoclonal antibody, 16F12, that targets a receptor in ovarian tumors and tested its potential for both therapeutic and diagnostic applications in treating small-volume ovarian peritoneal carcinomatosis.
  • They radiolabeled the antibody with different particles for therapy and imaging and applied two methods of administration: conventional intraperitoneal radioimmunotherapy (IP-RIT) and a brief intraperitoneal method (BIP-RIT).
  • The study found that Bi-16F12 was more effective in BIP-RIT for tumor targeting, while Lu-16F12 performed better in delaying tumor growth in IP-RIT, indicating potential for 16F12 as a new treatment tool for ovarian
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Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose.

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Aims: We investigated whether radiation-induced nontargeted effects are involved in the cytotoxic effects of anticell surface monoclonal antibodies labeled with Auger electron emitters, such as iodine 125 (monoclonal antibodies labeled with (125)I [(125)I-mAbs]).

Results: We showed that the cytotoxicity of (125)I-mAbs targeting the cell membrane of p53(+/+) HCT116 colon cancer cells is mainly due to nontargeted effects. Targeted and nontargeted cytotoxicities were inhibited in vitro following lipid raft disruption with Methyl-β-cyclodextrin (MBCD) or filipin or use of radical oxygen species scavengers.

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