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Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS.

BACKGROUND: Low-doses of bone modifying agents (LD-BMAs) compared to those used to treat bone metastases are used in breast or prostate cancer patients on adjuvant endocrine therapy to prevent Cancer Treatment Induced Bone Loss (CTIBL). Their use is associated with an increased risk of developing Medication-Related Osteonecrosis of the Jaw (MRONJ). However, there is not clarity about strategies aimed to minimize the MRONJ risk in cancer patients at different conditions as low- vs high-doses of BMA. This joint report from the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Itali

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. The advent of approved treatments for this devastating condition has significantly changed SMA patients' life expectancy and quality of life. Nevertheless, these are not without limitations, and research efforts are underway to develop new approaches for improved and long-lasting benefits for patients. Protein arginine methyltransferases (PRMTs) are emerging as druggable epigenetic targets, with several small-molecule PRMT inhibitors already in clinical trials. From a screen of epigenetic molecules, we have identifie

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… Dev Neurobiol 74: 319–332 Fallini C, Donlin‐Asp PG, Rouanet JP, Bassell GJ, Rossoll W (2016) Deficiency of the survival of motor neuron protein impairs mRNA localization and local translation in the growth cone of motor neurons. … Hum Mol Genet 24: 4094–4102 Rossoll W, Jablonka S, Andreassi C, Kröning AK, Karle K, Monani UR, Sendtner M (2003) Smn, the spinal muscular atrophy‐determining gene product, modulates axon growth and localization of β‐Actin mRNA in growth cones of motoneurons. …

Revolutionary drug repositioning: the preventive and therapeutic potential of metformin and other antidiabetic drugs in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections remain the first-line therapy for AMD. However, their high cost and the need for frequent administration pose challenges to long-term adherence, highlighting the need for accessible and cost-effective preventive strategies. Emerging evidence suggests that traditional antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones, may offer neuroprotective benefits, opening new avenues for AMD prevention. Among these, me

Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.

The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS. Yet, romidepsin has noted toxicities in humans and so here we aimed to define the primary mechanisms through which HDAC1/2 mediate O

Сфингосин-1-Фосфатная модуляция в неврологических расстройствах: Отчёты от MS и Stroke.

Множественный склероз — это хроническое аутоиммунное заболевание, при котором иммунная система атакует защитную оболочку или миелин, покрывающую нервные волокна, что влияет на способность мозга общаться с другими частями тела. Эта аномальная иммунная реакция привлекает подстрекательские вещества, которые выглядят как повреждения мозга и спинного мозга. Инсульт характеризуется внезапным ухудшением неврологической функции в результате потери или ограничения кровотока в результате острого повреждения локального участка центральной нервной системы, включая мозг, сетчатку или спинной мозг. В то вре

Selegiline induces neuroprotection via PGC-1α/Nrf2 gene upregulation in H2O2 -treated hippocampal-derived neural stem/progenitor cells.

Oxidative stress mediated by reactive oxygen species (ROS) is a major contributor to the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis, and amyotrophic lateral sclerosis. Selegiline, a monoamine oxidase B inhibitor, has been reported to exert neuroprotective effects, although its precise cytoprotective mechanisms remain unclear. In this study, we investigated the effects of selegiline on apoptosis, necrosis, and cell survival in hydrogen peroxide (H₂O₂)-treated hippocampal-derived neural stem/progenitor cells (HD-NSPCs) in vitr

Antiphospholipid Antibodies and Lipids in Hematological Malignancies.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL.

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy,

Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches.

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has be

The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.

Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awaren

Hormone replacement therapy and cancer survival: a longitudinal cohort study: protocol paper.

IntroductionHormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined due to uncertainty around risks of cancer and some cardiovascular diseases (CVD). Moreover, improved cancer survival rates mean that more women who survive cancer go on to experience menopausal symptoms. Understanding these relationships is important so that women and their clinicians can make informed decisions around the risks and benefits of HRT. This study's primary aim is to determine the association between HRT use after cancer diagnosis and the risk of cancer-specific mo

Multi-omics Analysis Reveals the Correlation of Gut Microbiota and Metabolites With Thalidomide Treatment for Chemotherapy-Induced Nausea and Vomiting in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a highly aggressive malignancy, and chemotherapy frequently causes nausea and vomiting, which can impair treatment tolerance. Because thalidomide (THD) has shown potential clinical benefit in alleviating nausea and anorexia, we investigated whether its effects might be associated with changes in gut microbial composition and metabolite profiles. Fecal samples were collected from patients with SCLC and categorized into THD-treated and control groups. Metagenomic sequencing and nontargeted metabolomic profiling were performed to characterize microbial composition

Положительная аллостерическая модуляция рецепторов АМПА с помощью PF4778574 приводит к снижению степени демиэлизации и клинической инвалидности в экспериментальных моделях множественного склероза.

ВВЕДЕНИЕ: Множественный склероз (МС) — расстройство центральной нервной системы (КНС), характеризующееся воспалением, обезвоживанием и нейронным дегенерацией. Несмотря на достижения в области иммуномодуляционного лечения, нейрозащитные или восстановительные стратегии по-прежнему являются неадекватными. Наши исследования сосредоточены на потенциале позитивного аллостерического модулятора рецепторов AMPA (AMPA-PAM), PF4778574, в борьбе с симптомами MS. Мы использовали MOG35-55 Продуктированная экспериментальная аутоиммунная энцефаломиелитная модель (EAE) в мышах C57BL6J для изучения терапевтичес

Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypo

Overview of Ankle Arthropathy in Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) is an autosomal recessive bleeding disorder characterized by tissue overload of iron. Clinical systemic manifestations in HH include liver disease, cardiomyopathy, skin pigmentation, diabetes mellitus, erectile dysfunction, hypothyroidism, and arthropathy. Arthropathy with joint pain is frequently reported at diagnosis and mainly involves the metacarpophalangeal and ankle joints, and more rarely, the hip and knee. Symptoms in ankle joints are in most cases non-specific, and they can range from pain and swelling of the ankle to deformities and joint destruction.

Treatment of Stage 2 Medication-Induced Osteonecrosis of the Jaw: A Case Series.

Medication-induced jaw osteonecrosis (MRONJ) is a rare and serious disease with a negative impact on patients' quality of life, whose exact cause remains unclear and which may have a multifactorial origin. Although there are different therapeutic protocols, there is still no consensus. This case series evaluated three patients diagnosed with staged 2 MRONJ treated at the University of Murcia dental clinic according to the protocols described by the Spanish Society of Oral and Maxillofacial Surgery and the American Association of Oral and Maxillofacial Surgeons. Within 12 months of the applicat

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as bein

The Potential Role of Sildenafil in Cancer Management through EPR Augmentation.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ul