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Gaucher disease, state of the art and perspectives.

Knowledge about Gaucher disease (GD), considered a model for rare diseases, has considerably increased since its discovery. The pathophysiology of this lysosomal disorder is better known, and specific therapies that can control many aspects of the disease have been developed, particularly for the most common form, Type 1 GD. Yet, in part because of the rarity of GD, but also because of a lack of awareness by physicians, diagnostic delay too often leads to a belated management of patients having accumulated comorbidities. Gaucher cells, the most visible consequence of glucocerebrosidase deficie

Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.

New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

Beta-blockers disrupt mitochondrial bioenergetics and increase radiotherapy efficacy independently of beta-adrenergic receptors in medulloblastoma.

BackgroundMedulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with low toxicity. Here, we showed the ability of β-blockers to potentiate radiotherapy in medulloblastoma with bad prognosis.MethodsMedulloblastoma cell lines, patient-derived xenograft cells, 3D spheroids and an innovative cerebellar organotypic model were used to identify synergistic interactions between β-blockers and ionising radiations. Gene expre

Development and validation of a novel modified cancer cachexia index in patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy: a multicenter cohort study.

BACKGROUND: Although the cachexia index (CXI) is a well-established prognostic predictor in gastric cancer (GC) patients, its effectiveness in patients with locally advanced gastric cancer (LAGC) who have undergone neoadjuvant chemotherapy (NACT) remains unclear. METHODS: This multicenter study included 600 LAGC patients treated with NACT from January 2010 to June 2022. A modified CXI was constructed based on Random Forest model, calculated as (post-NACT subcutaneous adipose tissue area at L3) × (post-NACT serum albumin)/(post-NACT platelet count) . Patients were categorized into mCXI-low and

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer.

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-canc

Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.

Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC50 values ranging

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

Cancer-Induced Cardiac Dysfunction: Mechanisms, Diagnostics, and Emerging Therapeutics in the Era of Onco-Cardiology.

Cancer-induced cardiac dysfunction has become a major clinical challenge as advances in cancer therapies continue to extend patient survival. Once regarded as a secondary concern, cardiotoxicity is now recognized as a leading contributor to morbidity and mortality among cancer patients and survivors. Its pathophysiology is multifactorial, involving systemic inflammation (e.g., TNF-α, IL-6), oxidative stress driven by reactive oxygen species (ROS), neurohormonal imbalances (e.g., angiotensin II, endothelin-1), and metabolic disturbances. These mechanisms collectively promote cardiomyocyte apopt

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… Peak oxygen consumption (VO 2 peak) and metabolic equivalents (METs) are key indicators. CRF derived from CPET is a strong, independent predictor of cardiovascular health, overall mortality, and risk classification. …

Patterns and Outcomes of Permanent Vascular Access in End-Stage Kidney Disease: A Multicenter Experience.

Background End-stage kidney disease (ESKD) is a growing health problem worldwide, with hemodialysis serving as the main treatment when transplantation is not feasible. Permanent vascular access is essential for effective dialysis, yet its patterns and outcomes remain variable across patient populations. Aim This multicenter study aimed to describe the patterns of vascular access use and evaluate the outcomes of permanent vascular access in patients with ESKD undergoing hemodialysis. Methods A retrospective multicenter cross-sectional study (January-June 2024) was conducted at two tertiary hosp

Effects of a Cognitive Behavioral Digital Therapeutic on Anxiety and Depression Symptoms in Patients With Cancer: A Randomized Controlled Trial.

PURPOSE: Patients with cancer often experience elevated levels of distress. This double-blind, randomized controlled trial compared the impact of an app-based version of cognitive behavioral stress management (CBSM) versus a health education sham app on anxiety and depression symptoms. METHODS: Patients with nonmetastatic (stage I-III) cancer who were receiving or recently completed (≤6 months) systemic treatment were recruited nationwide. The primary outcome of change in anxiety symptoms (PROMIS-Anxiety) over 12 weeks and the top secondary outcome of change in depression symptoms (PROMIS-Dep

Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection.

Multiple myeloma (MM) is one the most common hematological malignancies, and despite the survival prolongation offered by proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and anti-CD38 monoclonal antibodies, the need for novel agents is prominent. Selinexor is a first-in-class, oral, selective inhibitor of exportin-1 (XPO1), a vital protein for the exportation of more than 200 tumor suppressor proteins from the nucleus. Both in solid tumors and hematologic malignancies, selinexor-mediated inhibition of nucleus export seems to effectively lead to cancer cell death. Selinexor in combi

From the nephrologist's point of view: diversity of causes and clinical features of acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with multiple entities. Although AKI implies renal damage, functional impairment or both, diagnosis is solely based on the functional parameters of serum creatinine and urine output. The latest definition was provided by the Kidney Disease Improving Global Outcomes (KDIGO) working group in 2012. Independent of the underlying disease, and even in the case of full recovery, AKI is associated with an increased morbidity and mortality. Awareness of the patient's individual risk profile and the diversity of causes and clinical features of AKI is pivo

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

Herpes Simplex Virus and Varicella Zoster Virus Infections in Cancer Patients.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunit

Pectin: A Bioactive Food Polysaccharide with Cancer Preventive Potential.

Pectin is an acidic heteropolysaccharide found in the cell walls and the primary and middle lamella of land plants. To be authorized as a food additive, industrial pectins must meet strict guidelines set forth by the Food and Agricultural Organization and must contain at least 65% polygalacturonic acid to achieve the E440 level. Fruit pectin derived from oranges or apples is commonly used in the food industry to gel or thicken foods and to stabilize acid-based milk beverages. It is a naturally occurring component and can be ingested by dietary consumption of fruit and vegetables. Preventing lo

Critically ill cancer patient's resuscitation: a Belgian/French societies' consensus conference.

To respond to the legitimate questions raised by the application of invasive methods of monitoring and life-support techniques in cancer patients admitted in the ICU, the European Lung Cancer Working Party and the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, set up a consensus conference. The methodology involved a systematic literature review, experts' opinion and a final consensus conference about nine predefined questions1. Which triage criteria, in terms of complications and considering the underlying neoplastic disease and possible therapeutic limitations, should be

Dasatinib as a bone-modifying agent: anabolic and anti-resorptive effects.

BACKGROUND: Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function. METHODS: For studies on osteoblasts, primary human bone marrow mensenchymal stem cells (hMSCs) together with the hMSC-TERT

Pre-Engraftment Syndrome After Autologous Stem Cell Transplantation in Relapsed or Refractory Hodgkin Lymphoma: An Association with Prior PD-1 Inhibitor Exposure.

Background and Objectives: Autologous stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory Hodgkin lymphoma (R/R HL), and an increasing proportion of patients receive programmed cell death protein 1 (PD-1) inhibitors prior to transplantation. Engraftment syndrome (ES) is a noninfectious inflammatory complication classically associated with neutrophil recovery; however, early peri-transplant inflammatory manifestations remain poorly characterized and may mimic infectious complications. We aimed to evaluate peri-transplant inflammatory events after ASCT, with