Characterization of a B16-F10 melanoma model locally implanted into the ear pinnae of C57BL/6 mice

<div><p>The common experimental use of B16-F10 melanoma cells focuses on exploring their metastatic potential following intravenous injection into mice. In this study, B16-F10 cells are used to develop a primary tumor model by implanting them directly into the ears of C57BL/6J mice. The model represents a reproducible and easily traceable tool for local tumor growth and for making additional <i>in vivo</i> observations, due to the localization of the tumors. This model is relatively simple and involves (i) surgical opening of the ear skin, (ii) removal of a square-piece of cartilage followed by (iii) the implantation of tumor cells with fibrin gel. The remodeling of the fibrin gel within the cartilage chamber, accompanying tumor proliferation, results in the formation of blood vessels, lymphatics and tissue matrix that can be readily distinguished from the pre-existing skin structures. Moreover, this method avoids the injection-enforced artificial spread of cells into the pre-existing lymphatic vessels. The tumors have a highly reproducible exponential growth pattern with a tumor doubling time of around 1.8 days, reaching an average volume of 85mm³ 16 days after implantation. The melanomas are densely cellular with proliferative indices of between 60 and 80%. The induced angiogenesis and lymphangiogenesis resulted in the development of well-vascularized tumors. Different populations of immunologically active cells were also present in the tumor; the population of macrophages decreases with time while the population of T cells remained quasi constant. The B16-F10 tumors in the ear frequently metastasized to the cervical lymph nodes, reaching an incidence of 75% by day 16. This newly introduced B16-F10 melanoma model in the ear is a powerful tool that provides a new opportunity to study the local tumor growth and metastasis, the associated angiogenesis, lymphangiogenesis and tumor immune responses. It could potentially be used to test different treatment strategies.</p></div

Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner

Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses

Microbeam Radiation Therapy controls local growth of radioresistant melanoma and treats out-of-field locoregional metastasis.

PURPOSE Synchrotron-generated microbeam radiotherapy (MRT) represents an innovative preclinical type of cancer radiotherapy with an excellent therapeutic ratio. Beyond local control, metastatic spread is another important endpoint to assess the effectiveness of radiotherapy treatment. Currently, no data exists on an association between MRT and metastasis. Here, we evaluated the ability of MRT to delay B16F10 murine melanoma progression and locoregional metastatic spread. METHODS AND MATERIALS We assessed the primary tumor response and the extent of metastasis in sentinel lymph nodes in two cohorts of C57BL/6J mice, one receiving a single MRT and another receiving two MRT delivered with a 10-day interval. We compared these two cohorts with synchrotron broad beam-irradiated and non-irradiated mice. In addition, using multi-plex quantitative platforms, we measured plasma concentrations of 34 pro- and anti-inflammatory cytokines and frequencies of immune cell subsets infiltrating primary tumors that received either one or two MRT treatments. RESULTS Two MRT treatments were significantly more effective for local control than single MRT. Remarkably, the second MRT also triggered a pronounced regression of out-of-radiation field locoregional metastasis. Augmentation of CXCL5, CXCL12 and CCL22 levels after the second MRT indicated that inhibition of melanoma progression could be associated with increased activity of anti-tumor neutrophils and T-cells. Indeed, we demonstrated elevated infiltration of neutrophils and activated T-cells in the tumors following the second MRT. CONCLUSIONS Our study highlights the importance of monitoring metastasis following MRT and provides the first MRT fractionation schedule that promotes local and locoregional control with the potential to manage distant metastasis

Regulation of mitochondrial morphogenesis by annexin a6.

Mitochondrial homeostasis is critical in meeting cellular energy demands, shaping calcium signals and determining susceptibility to apoptosis. Here we report a role for anxA6 in the regulation of mitochondrial morphogenesis, and show that in cells lacking anxA6 mitochondria are fragmented, respiration is impaired and mitochondrial membrane potential is reduced. In fibroblasts from AnxA6(-/-) mice, mitochondrial Ca(2+) uptake is reduced and cytosolic Ca(2+) transients are elevated. These observations led us to investigate possible interactions between anxA6 and proteins with roles in mitochondrial fusion and fission. We found that anxA6 associates with Drp1 and that mitochondrial fragmentation in AnxA6(-/-) fibroblasts was prevented by the Drp1 inhibitor mdivi-1. In normal cells elevation of intracellular Ca(2+) disrupted the interaction between anxA6 and Drp1, displacing anxA6 to the plasma membrane and promoting mitochondrial fission. Our results suggest that anxA6 inhibits Drp1 activity, and that Ca(2+)-binding to anxA6 relieves this inhibition to permit Drp1-mediated mitochondrial fission

Apical Function in Neocortical Pyramidal Cells: A Common Pathway by Which General Anesthetics Can Affect Mental State

It has been argued that general anesthetics suppress the level of consciousness, or the contents of consciousness, or both. The distinction between level and content is important because, in addition to clarifying the mechanisms of anesthesia, it may help clarify the neural bases of consciousness. We assess these arguments in the light of evidence that both the level and the content of consciousness depend upon the contribution of apical input to the information processing capabilities of neocortical pyramidal cells which selectively amplify relevant signals. We summarize research suggesting that what neocortical pyramidal cells transmit information about can be distinguished from levels of arousal controlled by sub-cortical nuclei and from levels of prioritization specified by interactions within the thalamocortical system. Put simply, on the basis of the observations reviewed, we hypothesize that when conscious we have particular, directly experienced, percepts, thoughts, feelings and intentions, and that general anesthetics affect consciousness by interfering with the subcellular processes by which particular activities are selectively amplified when relevant to the current context

Malo (Henri) — Villes de Picardie (Collection des Villes meurtries de France), 1920

Potez Henri. Malo (Henri) — Villes de Picardie (Collection des Villes meurtries de France), 1920. In: Revue du Nord, tome 7, n°26, mai 1921. pp. 147-148

Malo (Henri) — Villes de Picardie (Collection des Villes meurtries de France), 1920

Potez Henri. Malo (Henri) — Villes de Picardie (Collection des Villes meurtries de France), 1920. In: Revue du Nord, tome 7, n°26, mai 1921. pp. 147-148

The evolution of psychological factors during the adult HIV screening process : DEPSYV study

S’engager dans une démarche de dépistage du VIH, c’est accepter le risque d’apprendre être atteint d’une maladie chronique sexuellement transmissible. Communément perçue comme anxiogène, cette démarche est largement préconisée dans le cadre de la lutte contre le VIH, mais à ce jour peu d’études ont porté sur l’ajustement psychologique à cette situation. Notre étude a pour objectif d’étudier l’implication des facteurs psychologiques tout au long de la période de dépistage du VIH. 266 personnes (hommes et femmes majeurs) venues réaliser un test de dépistage du VIH (TDVIH) dans un CeGIDD ont été inclus dans notre étude. D’après les résultats de notre modélisation appliquée en situation pré-test, l’optimisme et les croyances reliées à la santé ont un effet direct sur l’anxiété envers la santé, contrairement au contrôle interne de la santé et aux stratégies de coping centrées sur le problème et sur les émotions positives. De plus, nos analyses longitudinales ont montré qu’après l’annonce d’un résultat négatif les connaissances relatives au VIH s’améliorent et le niveau de croyances reliées à la santé augmente, tandis que le niveau d’anxiété envers la santé diminue très significativement. Nous espérons que notre étude et les propositions qui en découlent pourront être utiles aux professionnels impliqués dans la prévention et le dépistage du VIH. Puissent-elles également encourager les recherches longitudinales pendant la période de réalisation du TDVIH, en prenant en compte l’état d’avancement des travaux sur les traitements disponibles pour lutter contre cette maladie sexuellement transmissible.Being engaged in an HIV screening test process consists in accepting a risk of an HIV positive outcome, and thus of being infected with a sexually transmitted disease. Generally perceived as an anxiety-inducing process, this is largely recommended to tackle the issue of HIV. However few researches have dealt with the psychological adjustment to this process yet. The objective of our DEPSYV research is to study the consequences of psychological factors throughout the HIV testing period. Our study included 266 outpatients (men and women of legal age) coming for an HIV screening in a CeGIDD (Free Information, Screening and Diagnostic Center). Our model’s results, in a pre-screening situation, have suggested that optimism and health-related beliefs have a direct impact on health anxiety, whereas internal control of health, problem-focused and positive-emotions focused coping strategies do not have such an impact on health anxiety. Moreover our longitudinal follow-up studies put the stress on the fact that, after announcing an HIV negative result, knowledge about HIV and level of health-related beliefs have increased, while level of health anxiety have decreased very significantly. In hope that our study and the practical perspectives thus arising shall be useful to any professionals in the fields of preventing and screening the HIV disease. May our studies encourage more the longitudinal researches upon the whole HIV screening procedure, taking in consideration the newest studies on treatments for this sexual transmitted disease

Lucien de Chilly, lieutenant au 135e régiment d'infanterie. — Le premier ministre constitutionnel de la guerre : La Tour du Pin. Les origines de l 'armée nouvelle sous la Constituante, 1909

Potez Henri. Lucien de Chilly, lieutenant au 135e régiment d'infanterie. — Le premier ministre constitutionnel de la guerre : La Tour du Pin. Les origines de l 'armée nouvelle sous la Constituante, 1909. In: Revue du Nord, 1ᵉ année, n°2, mai 1910. pp. 172-173