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Frontiers in Immunology 2024To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis... (Review)
Review
OBJECTIVE
To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).
METHODS
A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.
RESULTS
A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.
CONCLUSION
The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.
Topics: Humans; Female; Child; Churg-Strauss Syndrome; Treatment Outcome; Granulomatosis with Polyangiitis; Cyclophosphamide; Antibodies, Antineutrophil Cytoplasmic
PubMed: 38812515
DOI: 10.3389/fimmu.2024.1406424 -
Scientific Reports May 2024Radiotherapy is the standard treatment for glioblastoma (GBM), but the overall survival rate for radiotherapy treated GBM patients is poor. The use of adjuvant and...
Radiotherapy is the standard treatment for glioblastoma (GBM), but the overall survival rate for radiotherapy treated GBM patients is poor. The use of adjuvant and concomitant temozolomide (TMZ) improves the outcome; however, the effectiveness of this treatment varies according to MGMT levels. Herein, we evaluated whether MGMT expression affected the radioresponse of human GBM, GBM stem-like cells (GSCs), and melanoma. Our results indicated a correlation between MGMT promoter methylation status and MGMT expression. MGMT-producing cell lines ACPK1, GBMJ1, A375, and MM415 displayed enhanced radiosensitivity when MGMT was silenced using siRNA or when inhibited by lomeguatrib, whereas the OSU61, NSC11, WM852, and WM266-4 cell lines, which do not normally produce MGMT, displayed reduced radiosensitivity when MGMT was overexpressed. Mechanistically lomeguatrib prolonged radiation-induced γH2AX retention in MGMT-producing cells without specific cell cycle changes, suggesting that lomeguatrib-induced radiosensitization in these cells is due to radiation-induced DNA double-stranded break (DSB) repair inhibition. The DNA-DSB repair inhibition resulted in cell death via mitotic catastrophe in MGMT-producing cells. Overall, our results demonstrate that MGMT expression regulates radioresponse in GBM, GSC, and melanoma, implying a role for MGMT as a target for radiosensitization.
Topics: Humans; Glioblastoma; Tumor Suppressor Proteins; DNA Repair Enzymes; Melanoma; DNA Modification Methylases; Cell Line, Tumor; Radiation Tolerance; Neoplastic Stem Cells; Promoter Regions, Genetic; DNA Methylation; DNA Repair; DNA Breaks, Double-Stranded; Gene Expression Regulation, Neoplastic; Temozolomide; Brain Neoplasms; Purines
PubMed: 38811596
DOI: 10.1038/s41598-024-61240-x -
Acta Cirurgica Brasileira 2024To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
PURPOSE
To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma.
METHODS
In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue.
RESULTS
IC50 value of temozolomide in MCF7 cell has been obtained as 103 μM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events.
CONCLUSIONS
The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.
Topics: Temozolomide; Animals; Apoptosis; Female; ErbB Receptors; Rats, Wistar; Antineoplastic Agents, Alkylating; Matrix Metalloproteinase 1; Cell Proliferation; Dacarbazine; Breast Neoplasms; Humans; MCF-7 Cells; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Reproducibility of Results; Rats; Mammary Neoplasms, Experimental
PubMed: 38808816
DOI: 10.1590/acb391624 -
Targeting ARNT attenuates chemoresistance through destabilizing p38α-MAPK signaling in glioblastoma.Cell Death & Disease May 2024Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. This study aimed to investigate the functional significance of aryl hydrocarbon receptor...
Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. This study aimed to investigate the functional significance of aryl hydrocarbon receptor nuclear translocator (ARNT) in the pathogenesis of GBM. Analysis of public datasets revealed ARNT is upregulated in GBM tissues compared to lower grade gliomas or normal brain tissues. Higher ARNT expression correlated with the mesenchymal subtype and poorer survival in GBM patients. Silencing ARNT using lentiviral shRNAs attenuated the proliferative, invasive, and stem-like capabilities of GBM cell lines, while ARNT overexpression enhanced these malignant phenotypes. Single-cell RNA sequencing uncovered that ARNT is highly expressed in a stem-like subpopulation and is involved in regulating glycolysis, hypoxia response, and stress pathways. Mechanistic studies found ARNT activates p38 mitogen-activated protein kinase (MAPK) signaling to promote chemoresistance in GBM cells. Disrupting the ARNT/p38α protein interaction via the ARNT PAS-A domain restored temozolomide sensitivity. Overall, this study demonstrates ARNT functions as an oncogenic driver in GBM pathogenesis and represents a promising therapeutic target.
Topics: Humans; Glioblastoma; Aryl Hydrocarbon Receptor Nuclear Translocator; Drug Resistance, Neoplasm; Cell Line, Tumor; Brain Neoplasms; MAP Kinase Signaling System; Animals; Cell Proliferation; Mitogen-Activated Protein Kinase 14; Mice; Gene Expression Regulation, Neoplastic; Temozolomide; Mice, Nude; Signal Transduction
PubMed: 38806469
DOI: 10.1038/s41419-024-06735-1 -
Cell Death Discovery May 2024Inducing necroptosis in cancer cells has emerged as an effective strategy to overcome drug resistance. However, while organic small molecules have been extensively...
Inducing necroptosis in cancer cells has emerged as an effective strategy to overcome drug resistance. However, while organic small molecules have been extensively studied for this purpose, metal-based compounds have received relatively little attention as triggers of necroptosis. The development of ruthenium (II) hybrid compounds, particularly those containing triazene (Ru-TRZ), highlights a novel avenue for modulating necroptotic cell death. Here we show that incorporating a methyltriazene moiety, a known alkylating warhead, confers superior mitochondrial-targeting properties and enhances cell death compared to amide-containing counterparts. Ru-hybrid TRZ2 exhibits also antitumor efficacy against in vivo drug-resistant cancer cells. Mechanistically, we demonstrate that Ru-TRZ hybrids induce apoptosis. In addition, by activating downstream RIPK3-driven cell death, TRZ2 proficiently restrains normal mitochondrial function and activity, leading to cancer cell necroptosis. Finally, TRZ2 synergizes anti-proliferative activity and cell death effects induced by conventional drugs. In conclusion, Ru-TRZ2 stands as a promising ruthenium-based chemotherapeutic agent inducing necroptosis in drug resistant cancer cells.
PubMed: 38806468
DOI: 10.1038/s41420-024-02033-z -
Frontiers in Neuroscience 2024Glioblastoma multiforme (GBM) is one of the most common and lethal forms of brain cancer, carrying a very poor prognosis (median survival of ~15 months...
Glioblastoma multiforme (GBM) is one of the most common and lethal forms of brain cancer, carrying a very poor prognosis (median survival of ~15 months post-diagnosis). Treatment typically involves invasive surgical resection of the tumour mass, followed by radiotherapy and adjuvant chemotherapy using the alkylating agent temozolomide, but over half of patients do not respond to this drug and considerable resistance is observed. Tumour heterogeneity is the main cause of therapeutic failure, where diverse progenitor glioblastoma stem cell (GSC) lineages in the microenvironment drive tumour recurrence and therapeutic resistance. The apelin receptor is a class A GPCR that binds two endogenous peptide ligands, apelin and ELA, and plays a role in the proliferation and survival of cancer cells. Here, we used quantitative whole slide immunofluorescent imaging of human GBM samples to characterise expression of the apelin receptor and both its ligands in the distinct GSC lineages, namely neural-progenitor-like cells (NPCs), oligodendrocyte-progenitor-like cells (OPCs), and mesenchymal-like cells (MES), as well as reactive astrocytic cells. The data confirm the presence of the apelin receptor as a tractable drug target that is common across the key cell populations driving tumour growth and maintenance, offering a potential novel therapeutic approach for patients with GBM.
PubMed: 38803685
DOI: 10.3389/fnins.2024.1379658 -
Cancers May 2024Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and... (Review)
Review
Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and pharmacologists for decades, focusing either on the isolation of compounds with cytotoxic properties from plants or on screening thousands of synthetic molecules. Compounds that could potentially become candidates for new anticancer drugs must have the ability to inhibit proliferation and/or induce apoptosis in cancer cells without causing too much damage to normal cells. Some anticancer compounds were discovered by accident, others as a result of long-term research. In this review, we have presented a brief history of the development of the most important groups of anticancer drugs, pointing to the fact that they all have many side effects.
PubMed: 38791957
DOI: 10.3390/cancers16101878 -
Photodiagnosis and Photodynamic Therapy Feb 2024For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is...
BACKGROUND
For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma.
METHODS
Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery.
RESULTS
In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months.
CONCLUSIONS
PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions.
Topics: Humans; Photochemotherapy; Male; Female; Photosensitizing Agents; Porphyrins; Middle Aged; Glioma; Aged; Adult; Brain Neoplasms; Neoplasm Recurrence, Local; Temozolomide
PubMed: 38787766
DOI: 10.1016/j.pdpdt.2023.103869 -
Marine Drugs May 2024Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this...
Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this study, we utilized the monosodium iodoacetate (MIA)-induced OA model to investigate the efficacy of oligo-fucoidan-based formula (FF) intervention in mitigating OA progression. Through its capacity to alleviate joint bearing function and inflammation, improvements in cartilage integrity following oligo-fucoidan-based formula intervention were observed, highlighting its protective effects against cartilage degeneration and structural damage. Furthermore, the oligo-fucoidan-based formula modulated the p38 signaling pathway, along with downregulating cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, contributing to its beneficial effects. Our study provides valuable insights into targeted interventions for OA management and calls for further clinical investigations to validate these preclinical findings and to explore the translational potential of an oligo-fucoidan-based formula in human OA patients.
Topics: Nitric Oxide Synthase Type II; Osteoarthritis; Animals; Cyclooxygenase 2; Polysaccharides; Male; Mice; Disease Models, Animal; Iodoacetic Acid; Oxidative Stress; Humans; Cartilage, Articular; Iodoacetates
PubMed: 38786602
DOI: 10.3390/md22050211 -
Biomolecules May 2024berries contain many compounds with potential benefits for human health. The food flavonoids quercetin and rutin, found in significant amounts in the fruits of , are...
berries contain many compounds with potential benefits for human health. The food flavonoids quercetin and rutin, found in significant amounts in the fruits of , are known to have favourable effects on animal and human organisms. However, data on the effect of flavonols isolated from black chokeberry on immune functions during immunosuppression are not available in the literature. Thus, the aim of this study was to evaluate the effect of flavonol fraction isolated from fruits, in comparison with pure quercetin and rutin substances, on the dysfunctional state of rat thymus and spleen in immunodeficiency. The study was performed on Wistar rats. The animals were orally administered solutions of the investigated substances for 7 days: water, a mixture of quercetin and rutin and flavonol fraction of . For induction of immunosuppression, the animals were injected once intraperitoneally with cyclophosphamide. Substance administration was then continued for another 7 days. The results showed that under the influence of flavonols, there was a decrease in cyclophosphamide-mediated reaction of lipid peroxidation enhancement and stimulation of proliferation of lymphocytes of thymus and spleen in rats. At that, the effect of the flavonol fraction of aronia was more pronounced.
Topics: Animals; Photinia; Cyclophosphamide; Rats; Rats, Wistar; Fruit; Thymus Gland; Flavonols; Spleen; Male; Plant Extracts; Immunosuppression Therapy; Quercetin; Lipid Peroxidation; Immunosuppressive Agents; Cell Proliferation; Rutin
PubMed: 38785985
DOI: 10.3390/biom14050578