Publications by authors named "Blacher S"

In Brief: The impact of adenomyosis on reproductive health needs to be fully understood. By using a murine model, this study provides novel insights into the nuanced mechanisms associated with fertility challenges and offers a foundation for targeted interventions.

Abstract: This study investigates the intricate relationship between adenomyosis and reproductive health using a murine model, offering novel insights into this prevalent gynecological disorder.

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Several types of cancer spread through the lymphatic system via the sentinel lymph nodes (LNs). Such LN-draining primary tumors, modified by tumor factors, lead to the formation of a metastatic niche associated with an increased number of Foxp3+ regulatory T cells (Tregs). These cells are expected to contribute to the elaboration of an immune-suppressive environment.

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Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3' untranslated region of the gene, thus leading to the expression of transcripts containing expanded CUG repeats (). The pathophysiology is explained by a toxic RNA gain of function where RNAs form nuclear aggregates that sequester and alter the function of MBNL splicing factors, triggering splicing misregulation linked to the DM1 symptoms. There is currently no cure for DM1, and most therapeutic strategies aim at eliminating transcripts.

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Introduction: Solid tumors consist of tumor cells associated with stromal and immune cells, secreted factors and extracellular matrix (ECM), which together constitute the tumor microenvironment. Among stromal cells, activated fibroblasts, known as cancer-associated fibroblasts (CAFs) are of particular interest. CAFs secrete a plethora of ECM components including collagen and modulate the architecture of the ECM, thereby influencing cancer cell migration.

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The effects of the COVID-19 pandemic have exponentially increased stress, anxiety and burnout levels for all healthcare professionals and students. The psychological effects of working with COVID-19 patients and the physical stress of working under distressing conditions exacerbate an already stressed workforce. Working long hours, shift work, short staffing, demanding workloads, dealing with death and dying and conflicts with management, other staff and disciplines and poor communication between disciplines are among the issues that can lead to burnout, anxiety and depression.

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Lymphedema (LD) refers to a condition of lymphatic dysfunction associated with excessive fluid accumulation, fibroadipose tissue deposition and swelling. In industrialized countries, LD development mainly results from a local disruption of the lymphatic network by an infection or cancer-related surgery (secondary LD). In the absence of efficient therapy, animal models are needed to decipher the cellular and molecular mechanisms underlying LD and test putative drugs.

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BCL6 (B-cell lymphoma 6) is a proto-oncogene and transcriptional repressor initially described as being involved in B-cell lymphoma. Recently, this factor has been identified as a promising tissue biomarker which could be used to diagnose women affected by endometriosis. Previous studies used HSCORE for BCL6 staining quantification in the endometrium.

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Article Synopsis
  • Autophagy helps keep lymphatic endothelial cells (LECs) healthy, but scientists didn't know how it worked for them until now.! -
  • When LECs don't have autophagy, they struggle to respond to signals that help new lymphatic vessels grow and can't do their job properly.! -
  • Improving the way LECs use fats can help them work better, suggesting that fatty acids are important for keeping LECs healthy and ready to grow new vessels.!
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Although lymph node (LN) metastasis is an important prognostic parameter in cervical cancer, the tissue remodeling at a pre-metastatic state is poorly documented in LNs. We here identified periostin (POSTN) as a component of non-metastatic LNs by applying proteomic analyses and computerized image quantifications on LNs of patients with cervical cancer. We provide evidence for remarkable modifications of POSTN and lymphatic vessel distributions and densities in non-metastatic sentinel and metastatic human LNs, when compared to distant non-metastatic LNs.

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The capacity of ADAMTS3 to cleave pro-VEGFC into active VEGFC able to bind its receptors and to stimulate lymphangiogenesis has been clearly established during embryonic life. However, this function of ADAMTS3 is unlikely to persist in adulthood because of its restricted expression pattern after birth. Because ADAMTS2 and ADAMTS14 are closely related to ADAMTS3 and are mainly expressed in connective tissues where the lymphatic network extends, we hypothesized that they could substitute for ADAMTS3 during adulthood in mammals allowing proteolytic activation of pro-VEGFC.

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Purpose: Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. Some clinical studies demonstrated that both timing of surgery and RT schedule influence tumor dissemination, and subsequently patient overall survival. Previously, we developed a pre-clinical model demonstrating the impact of NeoRT schedule and timing of surgery on metastatic spreading.

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Article Synopsis
  • Delocalization of ZO-1 from tight junctions is crucial for the plasticity of epithelial cells during tumor progression.
  • Increased levels of ZO-1 in the cytoplasm and nucleus influence the secretion of pro-inflammatory chemokines and aid in the recruitment of immune cells.
  • A correlation exists between higher densities of specific immune cells in lung tumors and cyto-nuclear expression of ZO-1, suggesting that this expression may facilitate tumor progression by altering immune cell dynamics.
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Background: The effects of endocrine-disrupting chemicals (EDCs) on fertility and reproductive development represent a rising concern in modern societies. Although the neuroendocrine control of sexual maturation is a major target of EDCs, little is known about the potential role of the hypothalamus in puberty and ovulation disruption transmitted across generations.

Objectives: We hypothesized that developmental exposure to an environmentally relevant dose of EDC mixture could induce multi- and/or transgenerational alterations of sexual maturation and maternal care in female rats through epigenetic reprograming of the hypothalamus.

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Article Synopsis
  • There is a clinical demand for new hormone therapies that reduce breast cancer risk, leading researchers to explore estetrol (E4) as a viable natural estrogen alternative for menopause hormone therapies (MHT) and combined oral contraceptives (COC).
  • Though E4 does not promote breast cancer growth, it can still be active in the endometrium, necessitating the addition of a progestogen to prevent potential complications like hyperplasia and cancer in women without a hysterectomy.
  • Research suggests that combining E4 with progesterone or drospirenone is promising and could improve the safety profile for women compared to existing hormonal treatments, but significant long-term studies are still needed to accurately assess breast cancer risks associated with new therapies
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Problem: Tumor recurrence is a major clinical issue that represents the principal cause of cancer-related deaths, with few targetable common pathways. Mechanisms by which residual tumors persist and progress under a continuous shift between hypoxia-reoxygenation after neoadjuvent-therapy are unknown. In this study, we investigated the role of lipid metabolism and tumor redox balance in tumor recurrence.

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Objective: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically.

Methods: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals.

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Article Synopsis
  • Solid tumors have cancer cells and special cells called lymphatic endothelial cells (LEC) that help with the movement of other cells.
  • New research shows that when LEC are around tumors, they can actually help cancer cells grow and invade more.
  • A specific molecule called interleukin-6 (IL6) plays a big role in this process, and stopping IL6 can reduce the effects that LEC have on tumor cells.
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Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in aging populations. Here, we applied metabolomics to human sera of patients with nAMD during an active (exudative) phase of the pathology and found higher lactate levels and a shift in the lipoprotein profile (increased VLDL-LDL/HDL ratio). Similar metabolomics changes were detected in the sera of mice subjected to laser-induced choroidal neovascularization (CNV).

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The encapsulation into liposomes of several types of molecules presents the advantages to protect the activity of these molecules and to target specific tissues. Nevertheless, a major obstacle remains the incomplete understanding of nano-bio interactions. Specifically, the impact that inclusion of drug into liposomes or of drug-in-cyclodextrin-in liposomes (DCL) could have on the molecular and cellular mechanism of drug action is largely unknown.

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In non-metastatic non-small-cell lung cancer (NSCLC), outcomes remain poor. Adjuvant chemotherapies provide a limited improvement in disease-free survival. Recent exploratory studies on early-stage NSCLC show that immunotherapy given according to Programmed Death-Ligand 1 expression generates variable results, emphasizing a need to improve tumor characterization.

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Exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to differences in dose and period of exposure. Little is known about the effects of adult exposure to environmentally relevant doses of this EDC and the differences in effect after neonatal exposure.

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Objectives: The current opioid addiction crisis highlights two chronic health conditions which have traditionally received relatively little emphasis in nursing curricula: addiction and chronic pain. In an effort to provide direction to nursing programs in the US on the curriculum needed to prepare students to care for patients and meaningfully intervene in the opioid crisis, this paper presents an overview of the curricular elements which require integration.

Design And Data Sources: Specifically, the state of current nursing education in pain and addiction are reviewed, followed by foundational knowledge for nursing practice to address the opioid crisis.

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Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors such as breast cancer (BC). Herein, we identify an integrin α11/PDGFRβ+ CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin α11-deficiency led to a drastic reduction of tumor progression and metastasis.

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Background: Air pollution, including particulates and gazes such as ozone (O), is detrimental for patient's health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O exposure and metastatic dissemination to lungs.

Objectives: To outline the mechanisms through which pulmonary O exposure modulates metastasis kinetics in an experimental mouse model of O exposure.

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