Targeting the Oxytocin Receptor for Breast Cancer Management: A Niche for Peptide Tracers.

Breast cancer is a leading cause of death in women, and its management highly depends on early disease diagnosis and monitoring. This remains challenging due to breast cancer's heterogeneity and a scarcity of specific biomarkers that could predict responses to therapy and enable personalized treatment. This Perspective describes the diagnostic landscape for breast cancer management, molecular strategies targeting receptors overexpressed in tumors, the theranostic potential of the oxytocin receptor (OTR) as an emerging breast cancer target, and the development of OTR-specific optical and nuclear tracers to study, visualize, and treat tumors. A special focus is on the chemistry and pharmacology underpinning OTR tracer development, preclinical in vitro and in vivo studies, challenges, and future directions. The use of peptide-based tracers targeting upregulated receptors in cancer is a highly promising strategy complementing current diagnostics and therapies and providing new opportunities to improve cancer management and patient survival.

Oral Supplementation with L-Carnosine Attenuates Social Recognition Deficits in CD157KO Mice via Oxytocin Release.

The outcomes of supplementation with L-carnosine have been investigated in clinical trials in children with autism spectrum disorder (ASD). However, reports on the effects of L-carnosine in humans have been inconsistent, and the efficacy of L-carnosine supplementation for improving ASD symptoms has yet to be investigated in animal studies. Here, we examined the effects of oral supplementation with L-carnosine on social deficits in CD157KO mice, a murine model of ASD. Social deficits in CD157KO mice were assessed using a three-chamber social approach test. Oral supplementation with L-carnosine attenuated social behavioral deficits. The number of c-Fos-positive oxytocin neurons in the supraoptic nucleus and paraventricular nucleus was increased with L-carnosine supplementation in CD157KO mice after the three-chamber social approach test. We observed an increase in the number of c-Fos-positive neurons in the basolateral amygdala, a brain region involved in social behavior. Although the expression of oxytocin and oxytocin receptors in the hypothalamus was not altered by L-carnosine supplementation, the concentration of oxytocin in cerebrospinal fluid was increased in CD157KO mice by L-carnosine supplementation. These results suggest that L-carnosine supplementation restores social recognition impairments by augmenting the level of released oxytocin. Thus, we could imply the possibility of a safe nutritional intervention for at least some types of ASD in the human population.

[Oxytocin and its receptor: molecular and therapeutic approaches]. / Approches moléculaires et thérapeutiques des interactions entre l'ocytocine et son récepteur.

It is known since the fifties that oxytocin is a neurohormone synthesized in the brain and released in blood circulation to trigger uterus contraction during delivery. It is also involved in milk ejection during breast-feeding. Over the past 25 years, many other central and peripheral functions have been discovered, in particular for attachment between child and parents as well as between individuals and interaction between a human being and its social group. Over this period, we have studied the functional supramolecular architecture of the hormone bound to its receptor. This information was used to design pharmacological probes and drug candidates. This led to the discovery of the first non-peptide oxytocin receptor full agonist. This molecule, LIT-001, restores social interaction in an animal model of autism and paves the way for a treatment of this neurodevelopmental disorder.

Title: Approches moléculaires et thérapeutiques des interactions entre l'ocytocine et son récepteur. Abstract: L'ocytocine est une neurohormone connue à l'origine pour son rôle dans les contractions de l'utérus au moment de l'accouchement et les contractions des glandes mammaires pour permettre l'éjection du lait lors de la tétée. Depuis les 25 dernières années, de multiples autres effets centraux et périphériques ont été identifiés, notamment dans les processus d'attachement entre parents et enfant, entre adultes et entre un individu et son groupe social. Nous avons abordé au cours de cette période la question fondamentale de l'architecture structurale et fonctionnelle du complexe formé par l'ocytocine et son récepteur et l'application de ce savoir à la conception de candidats médicaments. Ceci a conduit à la découverte du premier agoniste non peptidique de l'ocytocine, le LIT-001, restaurant l'interaction sociale dans un modèle animal d'autisme.

LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.

Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.

Correlatos neurobiológicos de la intervención psicoterapéutica / Neurobiological Correlates of Psychotherapeutic Intervention

Los avances en neurociencia permiten profundizar la comprensión de los correlatos neurobiológicos de las diferentes intervenciones psicoterapéuticas. Con el objetivo de presentar un panorama abarcativo de esta temática, se presentan estudios que dan cuenta de los efectos neurales de las psicoterapias, y que se enfocan en las diferentes áreas cerebrales involucradas y los posibles mecanismos subyacentes en los diferentes niveles, incluyendo tanto los moleculares como los que están relacionados con modificaciones en los circuitos. El artículo contiene también, una referencia a los procesos de memoria que podrían estar vinculados con los efectos de las psicoterapias. Se realiza una breve referencia a la comunicación empática, y a la neurobiología del apego, procesos posiblemente involucrados también en el trabajo psicoterapéutico, incluyendo una mención al rol de la oxitocina. Dada la importancia que en los últimos años ha adquirido el concepto de epigénesis y la posibilidad de que la eficacia de las psicoterapias pueda ser incrementada a través de la aplicación de fármacos moduladores de eventos epigenéticos, se incluye también una referencia a estos hallazgos

Advances in neuroscience allow to deepen the understanding of the different psychotherapeutic interventions and its neurobiological correlations. With the aim of presenting a comprehensive overview of this topic, studies that focus on the neural effects of psychotherapies, the different brain areas involved on it and the possible underlying mechanisms at different levels, including both the molecular as those that are linked to changes in the cicuits, are presented. The article also includes a reference to the processes of memory that could be linked with the effects of psychotherapies. it's also made a brief reference to empathic communication and the neurobiology of attachment, processes possibly also involved in psychoterpaeutic work, including a mention of the role of oxytocin. Given the importance that has acquired the concept of epigenesis and the possibility that the effectiveness of pscychotherapies could be increased through the application of modulating drugs of epigenetic events in recent years, a reference to these findings was also included

[Tocolytic therapy in threatened preterm labor]. / Leczenie tokolityczne w zagrazajacym porodzie przedwczesnym.

The most important benefit of tocolysis is a 48-hour prolongation of gestational age in order to administer corticosteroids to reduce perinatal mortality and morbidity as well as, if necessary to gain time for "in utero" transfer to a tertiary centre with neonatal facilities. The tocolytic agents used in clinical practice can be grouped into six classes, namely: calcium channel blockers, betamimetics, magnesium sulfate, cyclooxygenase inhibitors, oxytocin receptor antagonists and nitric oxide donors. The use of them should be individualized and based on tocolytic effectiveness, safety gestational age as well as maternal, fetal and neonatal outcomes. Data from clinical trials suggests that nifedipine appears to be the drug of first choice in the management of preterm labor.