Institut Gustave Roussy

Other

Université Paris-saclay

Centralesupelec

Clevexel Pharma

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Assistance Publique-hopitaux De Paris

Institut Curie

Université Paris Sud Xi

Université René Descartes (paris V)

Eric Deutsch

Guido Kroemer

Jean-Christophe Cintrat

Eric Tartour

Jean-Luc Perfettini

Frederic Taran

Catherine Brenner

Jean Bourhis

Frédéric Taran

Jean Luc Perfettini

Awatef Allouch

Perrine Pivette

Charles Ferte

Xiuping Wang-Zhang

Karine Gonzalez

Marvin Lerousseau

Céline Clemenson

Bassam Abdulkarim

Elaine Johanna Limkin

Roger Sun

Johannes Ludger

Mevyn Nizard

Thi Tran

Marie Catherine Vozenin

Michèle Mondini

A method implemented by computer means for training a decision system for segmenting medical images from a training set of annotated medical images, the segments belonging to at least one class, each annotation of the medical images including quantitative information about a number of pixels of the image that belongs to each of the classes, the method using weakly-supervised algorithm based on a percentage of the pixels of the image belonging to a concerned class.

Method for training a decision system for segmenting medical images

Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here the present inventors show that ionizing radiation induces the expression of interferon-regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. They reveal that the activation of the Ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with &#x3b3;-interferon, lipopolysaccharide or chemotherapeutic agent (such as cis-platin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a proinflammatory phenotype. They further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process. They also report that hypoxic conditions and the inhibition of any component of this signaling pathway (NOX2, ROS and ATM) impairs pro-inflammatory activation of macrophages and predicts a poor tumor response to preoperative radiotherapy in locally advanced rectal cancer. Altogether, these results identify a novel signaling pathway involved in macrophage activation that may enhance effectiveness of radiotherapy through the re-programming of tumor infiltrating macrophages.

NOX2 as a biomarker of radiotherapy efficiency in cancer patients

The present invention is drawn to the use of Minaprine dihydrochloride and analogs thereof, for reducing tumor growth when administered to a patient suffering from cancer.

Use of minaprine to reduce tumor growth

The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called 'enhancers of IR-mediated cellular cannibalism'. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.

Enhancers of cellular cannibalism for use to sensitize tumors to radiation therapy

A process for the preparation of freeze-dried 2-[(3-aminopropyl)amino]ethanethiol including the following steps: a) the reaction of a solution of amifostine with a strong acid, to obtain a solution of 2-[(3-aminopropyl)amino]ethanethiol, and b) the freeze-drying of the solution of 2-[(3-aminopropyl)amino]ethanethiol, with or without addition of excipients.

Process for the preparation of freeze-dried 2-[(3-aminopropyl)amino] ethanethiol formulation

The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as &#x394;133TP53, TP53&#x3b2;, TP53&#x3b3; or &#x394;40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Simultaneous detection of cannibalism and senescence as prognostic marker for cancer

The invention relates to an antiviral agent for use in combination with an anticancer agent, for the treatment of cancer. Especially, the invention provides means for the treatment of non-virus-associated cancer.

Antiviral agent for use in treatment of cancer

Growing community of inventors

Paris, France

Eric Deutsch