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A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity

Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell qual

Замена иммуноглобулина: Понятия управления несколькими миеломами.

Immunoglobulin (Ig) - заместительная терапия (IGRT) - состоит из применения низкодозированных поликлонных иг человека для лечения первичной и вторичной гипогаммаглобулинемии, которая связана с периодическими инфекциями и иммунной дисфункцией. ИГРТ восстанавливает физиологические уровни антител и вызывает иммуномумудуляторный эффект путем укрепления клеток иммунного эффекта, тем самым уменьшая инфекцию. Здесь мы описываем фармакологию различных составов иг с уделением особого внимания их механизму действий как низкодозированный ИГРТ, включая прямой антимикробный эффект и иммунодуляторную функци

Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines.

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a coope

SOX10 - Mediadated Regulation of Entertic Glial Fenotyp in vitro и его значение для нейроинфламационных расстройств.

Коэффициент транскрипции SOX10 является одним из ключевых регуляторов фенотипа и функции mielinated glial celleris (MS). SOX10 также выражается в энтогенных глиальных клетках (ЭГК) внутри кишечника, однако его регулятивные функции в ЭСУ по-прежнему плохо понимаются. Это исследование было направлено на выявление целевых генов SOX10, которые влияют на фенотип ЭСУ и могут иметь последствия для MS. Была установлена клеточная линия EGC для перевыражения доксициклина SOX10. Воздействие перевыражения SOX10 на фенотип ЭСУ оценивалось с помощью анализа всего генома, а результаты проверялись с помощью R

RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANK

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to tradition

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

An Italian cartography of VEXAS-related thrombosis.

Thrombotic events (TEs) occur in up to 40% of patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome, but data on its clinical-genomics features and anticoagulation strategies are limited. To gain more insight into this, we conducted a two-step study evaluating the prevalence and outcome of TE in VEXAS. First, among 1086 patients followed for TEs, 198 were men aged >40 years with unprovoked thrombosis and no known thrombophilia; 21 also had at least one VEXAS-compatible feature and underwent UBA1 exon 3 testing. No UBA1 mutation was detected in these 21 pat

Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research.

T lymphocytes (T cells) are essential components of the adaptive immune system that play a vital role in identifying and eliminating infected and tumor cells. In tumor immunotherapy, T cells have emerged as a promising therapeutic strategy due to their high specificity, potent cytotoxic capability, long-lasting immune memory, and adaptability within immunotherapeutic approaches. However, tumors can evade the immune system by depleting T cells through various mechanisms, such as inhibitory receptor signaling, metabolic exhaustion, and physical barriers within the tumor microenvironment. This re

Treatment of Established Chemotherapy-Induced Neuropathy with N-Palmitoylethanolamide: A Randomized, Double-Blind Phase II Pilot Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) from oxaliplatin and taxane drugs is a bothersome toxicity. Palmitoylethanolamide (PEA) has been reported to improve myelinated nerve fiber function in patients experiencing painful CIPN. We conducted a double-blind, placebo-controlled, randomized trial of PEA in patients with established CIPN. Methods: Eligible patients were adults who had pain, numbness, tingling, or other symptoms of CIPN for at least three months following completion of paclitaxel, oxaliplatin, or cisplatin-based chemotherapy. Study patients were randomized to o

Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?

Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable va

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

Oxidized Lipids in Persistent Pain States.

Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; f

The neurotoxic legacy of CAR-T cells: where do we stand?

Chimeric antigen receptor T (CAR-T) cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies and is increasingly reshaping the therapeutic landscape of autoimmune disorders and solid tumors, offering curative potential where options were previously limited. Its broader deployment is, however, constrained by immune-mediated toxicities, chiefly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS spans a heterogeneous spectrum from mild aphasia and tremor to seizures, cerebral edema, coma, and death, and remains diffic

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

Каннабиноиды в раке: Молекулярные механизмы смерти клеток и возможности перевода.

Каннабиноиды представляют собой терпенофенолические соединения, полученные из Cannabis sativa L., которые осуществляют широкий спектр биологической и фармакологической деятельности. Растущие данные свидетельствуют об их потенциале как модуляторов развития рака, особенно посредством подавления роста клеток опухоли, ангиогенеза и метастаза в различных моделях опухоли. В настоящем обзоре содержится всеобъемлющий обзор молекулярных механизмов, с помощью которых природные и синтетические каннабиноиды вызывают регулируемую смерть раковых клеток. Текущие данные свидетельствуют о том, что каннабиноиды

Artificial Intelligence for Risk Stratification in Diffuse Large B-Cell Lymphoma: A Systematic Review of Classification Models and Predictive Performances.

Background: Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous malignancy, with various outcomes despite significant advances in therapeutic options. Current conventional prognostic tools, e.g., the International Prognostic Index (IPI), lack sufficient precision at an individual patient level. However, artificial intelligence (AI), including machine learning (ML) and deep learning (DL), can enable specialists to navigate complex datasets, with the final aim of improving prognostic models for DLBCL. Objectives: This scoping review aims to systematically map the current litera

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… .) | Multi-view learning: SVM with kernel canonical correlation analysis (SVM-2 KCCA) | Prognosis/survival classification | AUC = 0.921; Accuracy = 96.9%; F1 = 92.8%; Sensitivity = 90.9% | Train/test split with comparison to 3 other MVL models; metrics: AUC, accuracy, F1, G-mean Pinochet (2021) [ 41 …

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,