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Modulation of angiogenesis with siRNA inhibitors for novel therapeutics.

Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are cur

Cannabis Biomolecule Effects on Cancer Cells and Cancer Stem Cells: Cytotoxic, Anti-Proliferative, and Anti-Migratory Activities.

Cancer is a complex family of diseases affecting millions of people worldwide. Gliomas are primary brain tumors that account for ~80% of all malignant brain tumors. Glioblastoma multiforme (GBM) is the most common, invasive, and lethal subtype of glioma. Therapy resistance and intra-GBM tumoral heterogeneity are promoted by subpopulations of glioma stem cells (GSCs). Cannabis sativa produces hundreds of secondary metabolites, such as flavonoids, terpenes, and phytocannabinoids. Around 160 phytocannabinoids have been identified in C. sativa. Cannabis is commonly used to treat various medical co

Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway.

Osteolytic lesions and pathological fractures are hallmark manifestations of multiple myeloma (MM), profoundly influencing the quality of life and self-care ability of MM patients. By analyzing transcriptome data and single-cell RNA-seq data from our center and the GEO database, a subset of MM cells with high expression levels of chemokine CXCL7 was identified. This subset of MM cells possesses a high capacity for proliferation and activation of osteoclast signaling pathway. CXCL7 might be a crucial regulator of osteolytic damage in MM. Subsequently, the association between the expression leve

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

Effect of pilose antler polypeptide on the mechanism of bone homeostasis in osteoporosis.

Osteoporosis stands out as a prevalent metabolic disorder, bearing significant repercussions on human well-being and overall quality of life. It remains an urgent concern within the global public health framework due to its widespread occurrence. Osteoporosis arises from an abnormal metabolism in osteoblasts and osteoclasts, resulting in a disruption of the delicate equilibrium between bone formation and bone resorption. Within this context, deer antler peptides emerge as natural active compounds, wielding a pivotal role in governing the differentiation, proliferation, and mineralization of os

Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186.

BackgroundDespite clinical success with T cell engagers (TCEs) targeting hematological malignancies, achieving a safe and efficacious dose in patients with solid tumors remains challenging. Due to potency, low levels of target antigen expression on normal tissues may not be tolerated. To overcome this, we engineered a novel conditionally active TCE design called COBRA (Conditional Bispecific Redirected Activation). Administered as prodrugs, COBRAs bind to cell surface antigens on both normal and tumor tissues but are preferentially activated within the tumor microenvironment.MethodsA COBRA was

Molecular Pathogenesis and Diagnostic Imaging of Metastatic Jaw Tumors.

Metastasis is the spread of malignant cells from a primary tumor to distant sites through lymphatics or blood vessels. Malignant lesions metastasizing to the oral and perioral region are a rarity indeed. Malignant lesions could metastasize to both soft tissue of oral cavity and the hard tissues of the jaws and recent meta-analysis showed that metastasis is more common in the jaws than oral soft tissues because of rich vascular supply. The incidence is very low when compared to the incidence of primary oral cancers; nevertheless, one has to include in the diagnostic workup, metastatic malignant

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increa

More Than an Adipokine: The Complex Roles of Chemerin Signaling in Cancer.

Chemerin is widely recognized as an adipokine, with diverse biological roles in cellular differentiation and metabolism, as well as a leukocyte chemoattractant. Research investigating the role of chemerin in the obesity-cancer relationship has provided evidence both for pro- and anti-cancer effects. The tumor-promoting effects of chemerin primarily involve direct effects on migration, invasion, and metastasis as well as growth and proliferation of cancer cells. Chemerin can also promote tumor growth via the recruitment of tumor-supporting mesenchymal stromal cells and stimulation of angiogenes

Фармакологическое ингибирование микроглиального распространения поддерживает целостность барьера крови и мозга в экспериментальном аутоиммунном энцефаломелите.

Дефункция мозга в крови (ББД) является основной характеристикой экспериментального аутоиммунного энцефаломиелита (EAE) — экспериментальной модели множественного склероза (MS). Ранее мы показали, что блокирование микроглиального распространения с использованием GW2580, селективного ингибитора CSF1R (колонический стимулирующий фактор 1 рецептор), снижает прогрессию и остроту заболеваний и предотвращает фазу рецидива. Однако вопрос о том, вызвано ли это воздействием GW2580 на функциональную целостность ББД, не был определен. Таким образом, здесь мы изучаем свойства ББД у крыс во время лечения EAE

Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial.

BackgroundAlthough, doxycycline use is associated with improved outcomes in amyloidosis in retrospective studies, evidence from clinical trials is limited.MethodsThis phase 2 trial of doxycycline (clinicaltrials.gov: NCT02207556) in newly diagnosed light chain (AL) amyloidosis enrolled 25 patients with systemic AL amyloidosis on treatment with doxycycline for 1 year along with chemotherapy. Outcomes of interest included mortality, organ response, and hematologic response rates at 1 year.FindingsThe median age was 62 years, 64% were male, and 68% had the AL lambda subtype. Patients had Mayo 201

Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

Ferret coronavirus-associated diseases.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

Increased risk of bisphosphonate-related osteonecrosis of the jaw in patients with Sjögren's syndrome: nationwide population-based cohort study.

OBJECTIVE: The aim of this study was to explore whether patients with Sjögren's syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan. DESIGN: A nationwide population-based retrospective cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database (NHIRD). METHODOLOGY: Medical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and o

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.

Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… The proteolytic cleavage process is mediated by various intra- and extracellular serine (Ser) and threonine (Thr) proteinases, including matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 12 (MMP-12), matrix metalloproteinase 14 (MMP-14), a disintegrin and metalloproteinase with thrombospondin …

Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain se

Медицинский каннабис и признаки рака: критический обзор.

Онкология остаётся сложным и гетерогенным заболеванием, вызывающим значительную morbidity и mortality по всему миру, несмотря на продвижение в диагностике и лечении. Характерные черты онкологии раскрывают биологические механизмы, поддерживающие развитие опухолей и злокачественное эволюцию, а также помогают выявить потенциальные мишени для терапии. Медикаментозный кресс-масло в основном используется в онкологии для поддерживающей терапии, но растущее предклиническое доказательство указывает на взаимодействие с сигнальными путями, связанными с онкологией. Этот обзорный материал обобщает текущие