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The Role of IL-33/ST2 Pathway in Tumorigenesis.

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane o

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… Using reciprocal bone marrow chimeras, simultaneous loss of IL-33 signaling in both radioresistant non-hematopoietic and radiosensitive hematopoietic compartments resulted in increased tumor burden. …

Генетическая основа болезни.

Генетика в той или иной степени играет определенную роль во всех заболеваниях. Изменения в нашей ДНК и различия в том, как эта ДНК функционирует (одиночка или комбинация), наряду с окружающей средой (которая включает образ жизни), способствуют болезнетворным процессам. В рамках этого обзора изучается генетическая основа человеческих заболеваний, включая однородные генетические расстройства, хромосомные диспропорции, эпигенетические, раковые и сложные расстройства, и рассматривается вопрос о том, каким образом наше понимание и технологические достижения могут быть использованы для обеспечения н

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… Very rarely fusion of two embryos will generate a chimera: an individual that has two genetically distinct cell lines present. …

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

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… error-prone PCR followed by a staggered extension process to generate a library of Cap mutants of VP1 – 3 to identify variants with altered affinities for heparin for immune escaping. 82 In addition, a DNA shuffling-based approach has been utilized to generate diverse and extensive libraries of random chimeras …

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

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… Monoclonal antibodies and proteolysis‐targeting chimeras (PROTACs) are two therapeutic agents under development that selectively target EMT proteins [ 114 ]. Metabolic resetting, which includes changes in glycolysis, lipid metabolism, and amino acid synthesis, occurs simultaneously with EMT. …

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

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… Interspecies aminopeptidase-N chimeras reveal species-specific receptor recognition by canine coronavirus, feline infectious peritonitis virus, and transmissible gastroenteritis virus J Virol 71 1997 734 737 8985407 10.1128/jvi.71.1.734-737.1997 PMC191108 62 Hegyi A. Kolb A.F. …

Abstracts from the ISSAID 2021 Periodic Congress : Virtual. May - Dec 2021

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… IL-1RA and GFP chimeras were injected intraperitoneally with MSU crystals to induce IL-1 mediated inflammation. After 6 hours, peritoneal cells were collected, and the percentage of neutrophils (CD11b+Ly6G+ cells) was determined by flow cytometry. … In IL-1RA chimeras, HSPC transduction with IL-1RA-LV led to robust and sustained IL-1RA levels in plasma. Supraphysiological expression of IL-1RA did not impact the engraftment and the clonogenic potential of HSPCs in vivo . …

Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomod

Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.

The need for new, more effective drugs to treat cancer, infectious diseases, various parasitic infestations, and metabolic disorders requires innovative approaches to the design of promising molecules. One of these areas is the creation of hybrid structures. Lupane triterpenoids are of significant interest for such research due to their high abundance in natural sources and their renewable nature, their molecular architecture, presence of several easily modifiable functional groups, enantiomeric purity, broad spectrum of biological activity, and low toxicity. Active research into the biologica

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… Introduction Triterpenoids of the lupane series, such as betulin (BE) 1 , lupeol 2 and betulinic acid (BA) 3 ( Figure 1 ), have been attractive molecular platforms for the synthesis of biologically active hybrid compounds, conjugates or so-called chimeras in the last two decades, in the structure of …

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc

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… In addition to direct or allosteric modulation of cellular targets, strategies for indirect manipulation of cellular targets [e.g., posttranslational modification 179 or targeted protein degradation using proteolysis-targeting chimera (PROTAC) 180 ] based on biological and functional studies for cancer-specific …

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reacti

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… New ways to interfere with MDM2 function are currently being developed, including proteolysis targeting chimera (PROTAC) degraders. However, it remains unclear whether these will improve efficacy without substantially increasing toxicity in human cancer patients ( 31 , 39 ). …

Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia.

Secondary immunodeficiency is reported in most patients with hematological malignancies such as chronic lymphocytic leukemia and multiple myeloma. The aim of our review was to evaluate the existing literature data on patients with hematological malignancies, with regard to the effect of immunodeficiency on the outcome, the clinical and therapeutic approach, and on the onset of noninfectious complications, including thrombosis, pleural effusion, and orofacial complications. Immunodeficiency in these patients has an intense impact on their risk of infection, in turn increasing morbidity and mort

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… A Model for Human B-Chronic Lymphocytic Leukemia in Human/Mouse Radiation Chimera: Evidence for Tumor-Mediated Suppression of Antibody Production in Low-Stage Disease . Blood ( 1997 ) 89 ( 6 ): 2210–8 . doi: 10.1182/blood.V89.6.2210 9058746 95 Forconi F Moss P . …

Emerging roles for the IL-6 family of cytokines in pancreatic cancer.

Pancreatic cancer has one of the poorest prognoses of all malignancies, with little improvement in clinical outcome over the past 40 years. Pancreatic ductal adenocarcinoma is responsible for the vast majority of pancreatic cancer cases, and is characterised by the presence of a dense stroma that impacts therapeutic efficacy and drives pro-tumorigenic programs. More specifically, the inflammatory nature of the tumour microenvironment is thought to underlie the loss of anti-tumour immunity and development of resistance to current treatments. Inflammatory pathways are largely mediated by the exp

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… Production of IL-6 by TAMs was shown to influence tumour development via bone-marrow chimeras, as mice reconstituted with IL-6 knockout (KO) ( Il6 -/- ) myeloid cells developed low-grade PanINs, whilst those reconstituted with IL-6 WT cells developed PanIN-3 lesions [ 172 ]. …

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, inc

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… Proteolysis‐targeting chimeras (PROTACs) represent a novel approach for the degradation of target proteins via the Ubiquitin‐Proteasome System (UPS), which has garnered significant attention in recent years. …

RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

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… . · Adenovirus chimeras · Ad5-D24: serogroup 5, E1A-/Rb-binding site negative; selectively kills cells with an abnormal p16/Rb pathway [ 195 ] · CRAd: Ad5-D24 plus serogroup 3 knob [ 196 ] · DNX-2401: Ad5-D24 plus RDG (integrin receptor) [ 197 ] · Ad5/3-D24-GMCSF and CGTG-102: CRAd and DNX-2401 plus …

In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

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… Using transfer of naive CFSE-labeled TCR transgenic T cells and mixed bone marrow chimeras, we show that activation of naive PLP139-151-specific T cells in SJL mice undergoing PLP178-191-induced R-EAE occurs directly in the CNS and not in the cervical lymph nodes, spleen or other peripheral lymphoid …

Recent advances in the bench-to-bedside translation of cancer nanomedicines.

Cancer remains a complex and challenging medical problem, driving extensive research efforts. Despite significant progress in understanding its genetic and molecular aspects, the quest for effective treatments continues. Nanomedicines have shown great potential for revolutionizing cancer treatment by offering targeted and controlled drug delivery, reducing side effects, and improving patient outcomes. Accordingly, nanomedicines have been the focus of extensive research and development for clinical translation. As of September 2024, a search on the ClinicalTrials.gov website using the term "nan

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… Xu et al. 189 showed that X-ray–responsive, proteolysis-targeting chimera (PROTAC) NPs degraded bromodomain-containing protein 4 (BRD4), enhancing tumor radiosensitivity and achieving a 92.61% tumor volume reduction compared to controls. …

Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy-A Narrative Review.

Modern oncology increasingly relies on the role of proteins as key components in cancer diagnosis, prognosis, and targeted therapy. This review examines advancements in protein biomarkers across several cancer types, including breast cancer, lung cancer, ovarian cancer, and hepatocellular carcinoma. These biomarkers have proven critical for early detection, treatment response monitoring, and tailoring personalized therapeutic strategies. The article highlights the utility of targeted therapies, such as tyrosine kinase inhibitors and monoclonal antibodies, in improving treatment efficacy while

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… An example of this technology is PROTACs (Proteolysis Targeting Chimeras), which consist of two ligands linked by a linker: one ligand binds the kinase, while the other recruits the E3 ligase. …

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune

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… As has been previously mentioned, CAR-T cells produced by transducing a chimera of an antibody subdomain (single-chain variable fragment) and TCR activation (and costimulatory) motifs have shown substantial clinical success in hematological cancers, such as multiple myeloma and B-cell malignancies. …