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Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma.

Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1-4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related

CAR T-cells in hematologic malignancies: Advances, challenges, and future directions.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of hematologic malignancies, achieving high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma. By redirecting autologous or allogeneic T lymphocytes against tumor-associated antigens such as CD19 and TNFRSF17, CAR T-cells overcome resistance to conventional therapies. Progressive optimization of CAR design-from early constructs to armored and logic-gated platforms-has enhanced persistence, specificity, and safety. Pivotal trials and real-world e

Piper nigrum Extract: Dietary Supplement for Reducing Mammary Tumor Incidence and Chemotherapy-Induced Toxicity.

A low piperine fractional Piper nigrum extract (PFPE) was prepared by mixing cold-pressed coconut oil and honey in distilled water, namely, PFPE-CH. In this study, PFPE-CH was orally administered as a dietary supplement to decrease the risk of tumor formation and reduce the side effects of chemotherapeutic drugs during breast cancer treatment. The toxicity study demonstrated no mortality or adverse effects after administrating PFPE-CH at 5000 mg/kg during a 14-day observation period. Additionally, PFPE-CH at 86 mg/kg BW/day did not cause any harm to the kidney or liver function of the rats for

Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. Th

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

Linking Air Pollution and Hematologic Malignancies: From Epidemiology to Molecular Mechanisms.

PURPOSE OF REVIEW: Outdoor air pollution (OAP) is a major global environmental health threat associated with respiratory disease and solid tumors, with growing evidence linking it to hematologic malignancies. This review summarizes the molecular mechanisms and epidemiologic evidence connecting OAP exposure to acute and chronic leukemias, lymphomas, myelodysplastic syndromes (MDS), clonal hematopoiesis of indeterminate potential (CHIP), and multiple myeloma (MM). RECENT FINDINGS: Pollutants implicated in hematologic carcinogenesis include particulate matter (PM), benzene, nitrogen dioxide (NO₂

Monoclonal Antibodies Against Myeloid Leukemia Cells: Current Knowledge and Future Directions.

Monoclonal antibodies targeting specific cell surface antigens have emerged as a promising therapeutic approach for acute myeloid leukemia (AML), thus widening the treatment landscape of this heinous disease. These antibodies have been designed to selectively target and eliminate leukemic cells while limiting damage to the normal hematopoietic counterpart. Among the potential targets on AML cells, CD33, CD123, and CD47 have shown the major potential in preclinical and clinical trials. Additionally, conjugation of monoclonal antibodies with cytotoxic agents has further enhanced their therapeuti

Ganglioside therapy in cancer molecular insights and therapeutic opportunities.

Gangliosides, a class of glycosphingolipids located on the plasma membrane of nearly all cells, play a crucial role in cell signaling and lipid raft dynamics. Their expression is notably high during embryonic development, markedly reduced in most adult tissues, but significantly elevated in various tumor tissues. This distinct expression pattern highlights gangliosides as promising therapeutic targets due to their roles in tumor progression, metastasis, and therapeutic resistance. Targeted ganglioside therapies, particularly monoclonal antibodies against GD2, have already demonstrated clinical

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising appr

Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.

Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradatio

The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.

In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an emergent property resulting from spatial and temporal in

Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.

Advances in immunotherapy, particularly with immune checkpoint inhibitors, have improved clinical outcomes in various cancer subtypes; however, resistance often occurs because these treatments rely on single agents and show limited translational success when combined. Therefore, it is necessary to develop immune checkpoint inhibitor-based combination strategies by integrating next-generation immunotherapies and innovative biomarkers. This review highlights the emerging combinatorial approaches that can be tailored to the distinct tumor microenvironment types to overcome resistance to immune ch

CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.

Several landmark studies over the past decade have uncovered a critical role of the CRL3KBTBD4 ubiquitin ligase complex in regulating stability of corepressor of repressor element 1 silencing transcription factor (CoREST) complex proteins and normal hematopoietic stem cell self-renewal. There is now mounting evidence that the CoREST complex plays oncogenic roles, although the contributions of its catalytic versus noncatalytic functions remain unclear. Here, we summarize and discuss mechanisms whereby the CoREST complex coopts tissue-specific transcription factors to elicit pathogenic activity

A Literature Review on the Impact of the Gut Microbiome on Cancer Treatment Efficacy, Disease Evolution and Toxicity: The Implications for Hematological Malignancies.

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by

The Precision Revolution in Hematologic Malignancies: A Decade of Transformative Immunotherapies and Targeted Agents.

This review describes the dramatic transformation that has occurred in the last ten years in the therapeutic landscape for hematologic malignancies, such as leukemias, lymphomas, myelomas, and myelodysplastic syndromes. Treatment paradigms have quickly changed from depending solely on cytotoxic chemotherapy to embracing precision medicine, driven by a previously unprecedented understanding of disease biology and precise molecular changes. The development of powerful immunotherapies (such as CAR T-cell therapy and bispecific antibodies) and innovative targeted agents (like BTK inhibitors, BCL-2

Osteoclast Activation and Inflammatory Bone Diseases: Focusing on Receptors in Osteoclasts.

Bone homeostasis depends on the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. An increasing number of studies have revealed that under inflammatory conditions, osteoclast overactivation is responsible for bone loss in relevant bone diseases. Multiple signaling pathways such as receptor activator of nuclear factor-kappa B ligand (RANKL) signaling are involved in osteoclast activation. These signaling pathways rely on various receptors expressed on the surface of osteoclast progenitor cells (OPCs) or osteoclasts, which are activated by their correspo

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats.

Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA),

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… Reduced spermatozoa functionality during stress is the consequence of adrenergic-mediated disturbance of mitochondrial dynamics markers Sci. Rep. 2020 10 16813 10.1038/s41598-020-73630-y 33033347 PMC7544694 92. Abdullah D.M. Alsemeh A.E. Khamis T. …

Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.

The transforming properties of oncogenes are derived from gain-of-function mutations, shifting cell signaling from highly regulated homeostatic to an uncontrolled oncogenic state, with the contribution of the inactivating mutations in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional and target-directed therapy. On the other hand, this scenario fulfills two requirements for oncolytic virus infection in tumor cells: inactivation of tumor suppressors and presence of oncoproteins, also the requirements to engage malignancy. Several of these oncogenes have a negative i

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая