Результаты поиска

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

Совпадение в полном тексте источника
… RT can also promote tumor cell secretion of M-CSF via the NF-κB-p65 pathway, inducing TAM polarization toward an M2 phenotype and increasing secretion of IL-10 and Arginase 1 ( 54 ). …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

Совпадение в полном тексте источника
… Additional immunosuppressive activities of MDSCs are regulated by CCAAT/enhancer binding protein β (C/EBPβ) which controls the expression of arginase (ARG1) and inducible nitric oxide synthase (iNOS). …

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

Совпадение в полном тексте источника
… . | [ 179 , 180 ] R162 | GLUD1 inhibitor | Lung carcinoma xenografts | 20 μM and 20 mg/kg/day | Both in vivo and in vitro | Limits tumor progression, metastasis, and reverses drug resistance | [ 181 , 182 ] ADI‐PEG 20 | Arginase | Metastatic melanoma | 36 mg/m 2 | Clinical trials | Prevent metastasis …

Medicinal chemistry perspectives on anticancer drug design based on clinical applications (2015-2025).

Cancer therapy has undergone a remarkable evolution over the past few decades, driven largely by innovations in medicinal chemistry. This review explores the pivotal role of medicinal chemistry in designing, optimizing, and classifying anticancer agents, from traditional cytotoxics to modern targeted therapies, immunotherapies, and radiotheranostics. The article categorizes FDA-approved anticancer drugs (2015-2025), evaluates their mechanisms of action, structural features, and structure-activity relationships (SAR), and highlights both success stories and challenges in clinical translation. A

Совпадение в полном тексте источника
… Similarly, pegylated arginases such as BCT-100 achieve far greater stability and exposure than the unmodified enzyme 187–189 ( Fig. 3C ). …

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Совпадение в полном тексте источника
… These members are able to amplify each other's suppressive functions and promote the differentiation of additional immunosuppressive cells. 86 , 87 Immunosuppressive cells release immunosuppressive factors such as ROS, IL‐10, transforming growth factor beta (TGF‐β), indoleamine 2,3‐dioxygenase, and arginase …

Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery.

Surgical resection is the foundation for the curative treatment of solid tumors. However, metastatic recurrence due to the difficulty in eradicating micrometastases remain a feared outcome. Paradoxically, despite the beneficial effects of surgical removal of the primary tumor, the physiological stress resulting from surgical trauma serves to promote cancer recurrence and metastasis. The postoperative environment suppresses critical anti-tumor immune effector cells, including Natural Killer (NK) cells. The literature suggests that NK cells are critical mediators in the formation of metastases i

Совпадение в полном тексте источника
… IL-6 also serves as the switch between pro- and anti-inflammatory phases by inducing anti-inflammatory factors including glucocorticoids, soluble TNFα receptors, PGE2-dependent IL-10, arginase-1 (ARG1) expression in MDSCs, and TGFβ1 [ 172 , 182 ]. …

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Совпадение в полном тексте источника
… TET2 was associated with a normal karyotype, high WBC count, low PLT count and high age. 238 , 255 , 267 Arginase 1 overexpression was related to DNMT3A and TET2 mutations in lower-grade MDS and CMML. 268 Besides the genetic alteration of TET2 , the expression of TET2 protein was also different between …

Резюме ЭСП 2013.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy.

Engineering cells to express chimeric antigen receptors (CARs) represents a novel approach in cancer immunotherapy, demonstrating remarkable efficacy in the treatment of hematologic malignancies while also encountering numerous challenges. Against the backdrop of the widespread application of COVID-19 mRNA vaccines, the integration of mRNA technology to produce CAR cells and enhance CAR therapies marks the cutting edge of cancer treatment innovation, offering potential solutions to the challenges faced by traditional CAR therapies. This convergence offers distinct advantages. It enables the ge

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein

Совпадение в полном тексте источника
… MDSCs affect TIME via several mechanisms, such as depletion of tryptophan by indoleamine 2,3‐dioxygenase (IDO), cytokine secretion (e.g., TGF‐β, IL‐10), activation of arginase‐1 (ARG1) and inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) [ 165 ]. …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

Совпадение в полном тексте источника
… MDSCs and TAM are known to be heterogeneous and plastic cell populations capable of hindering anti-tumor immunity by blocking effector T cell functioning through iNOS and arginase production, which would respectively lead to increased ROS production and arginine depletion ( 12 ). …

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream p

Совпадение в полном тексте источника
… This treatment affected the accumulation and tolerogenic activity of MDSCs in tumors and inhibited the expression of immunosuppressive factors arginase I and inducible nitric oxide synthase ( 137 ). …

ISEV2018 абстрактная книга

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

Совпадение в полном тексте источника
… Arg1: arginase 1; iNOS: inducible nitric oxide synthase; IL-10: interleukin 10; PGE2: prostaglandin E2; CCL17/22: C motif chemokine Ligand 17/22; PD-L1/2: programmed death ligand ½; Tex: exhausted T cell; Treg: regulatory T-cell [ 129 , 130 ] Signalling pathways, niche factors, and therapeutic implications …

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes sha

Совпадение в полном тексте источника
… Furthermore, cAMP has been shown in other tissues to induce monocyte recruitment in a manner dependent on PKA and MCP1/CCR2 signaling and to promote reprogramming of bone-marrow-derived macrophages to a M2 phenotype as seen by increased Arginase-1/CD206/Ym-1 expression and IL-10 levels (M2 markers ( …

"Complimenting the Complement": Mechanistic Insights and Opportunities for Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of death in the US and worldwide. HCC remains a global health problem and is highly aggressive with unfavorable prognosis. Even with surgical interventions and newer medical treatment regimens, patients with HCC have poor survival rates. These limited therapeutic strategies and mechanistic understandings of HCC immunopathogenesis urgently warrant non-palliative treatment measures. Irrespective of the multitude etiologies, the liver microenvironment in HCC is intricately associated with chronic

Совпадение в полном тексте источника
… The immunosuppressive TME is further elevated by MDSCs, a heterogeneous inhibitory cell population with increased arginase-1, nitric oxide, ROS, and TGF-β activities that promote induction of Tregs ( 46 ). …

62nd Annual Conference of the Indian Society of Gastroenterology, February 10th - 13th, 2022, Pune.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.