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Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-β/ALK5 inhibitor.

Radio-resistance resulting from radiotherapy-induced fibrosis is a major clinical obstacle in breast cancer treatment because it typically leads to cancer recurrence, treatment failure, and patient death. Transforming growth factor-β (TGF-β) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-β/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation

Analysis of differential gene immune infiltration and clinical characteristics of skin cutaneous melanoma based on systems biology and drug repositioning methods to identify drug candidates for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 da

Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy.

In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct

Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies.

The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from Cannabis sativa, it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD's biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate

IL-6 and NFE2L2: A putative role for the hepatoprotective effect of N. Sativa, P. Ginseng and C. Sempervirens in AFB-1 induced hepatocellular carcinoma in rats.

In this study, we investigated possible hepato-protective effects of N. Sativa, P. Ginseng, and C. Sempervirens in Aflatoxin B1 (AFB-1) induced hepatocellular carcinoma rat model. Fifty-four male albino rats were randomly assigned to experimental groups. Alcoholic extracts of aforementioned herbs were administered orally for 28 days at different doses. IL-6, hs-CRP, MDA, SOD and NFE2L2 were determined using ELISA. Histopathological changes in treated groups were examined. Herbal treatment significantly reduced IL-6, hs-CRP, and MDA (P C. Sempervirens 600 and N. Sativa 1000 increased NFE2L2 lev

Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.

BackgroundMultiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance.MethodsThis study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO.Resu

UEG Week 2015 Poster Presentations

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Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions.

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the appro

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Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.

Reactive oxygen species (ROS) encompass a diverse group of chemically reactive molecules or ions distinguished by their substantial oxidative potential. Empirical studies have shown that the targeted administration of high toxic concentrations of ROS can effectively induce tumor cell death in various types. Numerous bioactive ingredients derived from traditional Chinese medicine (TCM), recognized for their ROS-inducing properties, have demonstrated significant anti-tumor activity. Nonetheless, their clinical application has been hindered by challenges such as low solubility, limited bioavailab

Non-Curcuminoids from Turmeric and Their Potential in Cancer Therapy and Anticancer Drug Delivery Formulations.

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, wh

Chimeric antigen receptor modified T-cells for cancer treatment.

T cells engineered with the chimeric antigen receptor (CAR) are rapidly emerging as an important immunotherapy for hematologic malignancies. The anti-cluster of differentiation (CD)19 CAR-T cell therapy has been remarkably successful against refractory/relapsed acute lymphoblastic leukemia (ALL), and a complete remission rate as high as 90% was observed, in both children and adults. Although the achievement of clinical efficacy using CAR-T cell therapy for solid tumors has encountered several obstacles that were associated with the multiple mechanisms contributing to an immunosuppressive micro

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

Algae-Derived Bioactive Compounds as Platforms for Translational Biotechnology and Health Applications.

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although e

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… Additionally, laminarin-based creams are linked to accelerated collagen deposition and re-epithelialization in rats and protected skin cells from oxidative stress [ 162 ]. 4.2.5. …

33rd Европейский конгресс патологии - резюме.

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YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet

Progress of immune senescence in multiple myeloma treatment resistance.

Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.

Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies. NRF2 is the master regulator for oxidative stress management. However, the overall oxidative stress varies with PCa clinical stage, metabolic state and therapy used for the cancer.

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enha

Parasites' immunomodulators: a breakthrough in immunotherapeutics displaying antineoplastic activity against human colorectal and hepatocellular carcinoma cells.

The complex interplay between parasites and cancer is yielding promising advances in the field of cancer therapeutics. This study explored the in vitro anti-cancer potential of parasite immunomodulators (antigens and antibodies) of Schistosoma mansoni, Trichinella spiralis, and Toxoplasma gondii on human HT-29 colorectal and HepG2 hepatocellular carcinoma cells using the MTT assay. Results revealed that those parasites' immunomodulators exhibited antineoplastic activity and demonstrated a statistically significant inhibition of both cancer cell lines' proliferation (P ˂0.05). Notably, Trichine