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Glioblastoma spheroid growth and chemotherapeutic responses in single and dual-stiffness hydrogels.

Glioblastoma (GBM) is the deadliest brain tumor for which there is no cure. Bioengineered GBM models, such as hydrogel-encapsulated spheroid … y, size, invasion, laminin expression, hypoxia, proliferation, and response to the chemotherapeutic temozolomide (TMZ). We noted excellent cell viability in all hydrogels, and higher infiltration in soft compared to stiff hydrogels for U87 spheroids. In dual gels spheroids mostly infiltrated away from the stiffness interface with minimal crossing over it and s …

Comparison of Elemental Anomalies Following Implantation of Different Cell Lines of Glioblastoma Multiforme in the Rat Brain: A Total Reflection X-ray Fluorescence Spectroscopy Study.

Glioblastoma multiforme (GBM) is a primary brain tumor with a very high degree of malignancy and is classified by WHO as a glioma IV. At present, the treatment of patients suffering from GBM is based on surgical resection of the tumor with maximal protection of surrounding tissues followed by radio- and pharmacological therapy using temozolomide as the most frequently recommended drug. This strategy, however, does not guarantee success and has devastating consequences. Testing of new substances or therapies having potential in the treatment of GBM as well as detection of their side effects can…

Efficacy and safety of targeted therapies for glioblastoma: a systematic review and network meta-analysis.

PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor with a poor prognosis. The current standard regimen of surgery combined with concurrent temozolomide chemoradiotherapy has limited efficacy. Multiple targeted therapies have been evaluated in randomized controlled trials (RCTs), but results are inconsistent and lack systematic comparisons. This review used network meta-analysis (NMA) to assess the relative efficacy and safety of different targeted drugs vs. standard treatment. METHODS: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Scienc…

Химиотерапия вызывает множество склерозовых нейропатологий, которые могут быть спасены клобетозом.

Химиотерапия имеет важное значение для лечения рака, но часто сопровождается неблагоприятными последствиями, особенно для темозоломида (TMZ) - переднего химиотерапии для глиомы. Несмотря на наблюдавшиеся клинические неврологические аномалии, связанные с ТМЗ, механизмы, лежащие в основе нарушений нервной системы ТМЗ, по-прежнему плохо понимаются, а эффективные меры вмешательства отсутствуют. Здесь мы продемонстрировали, что химиотерапия TMZ вызвала нейродегенерацию, которая воспроизвела патологические особенности множественного склероза, включая демиелинацию, нейрофламмацию и аксонное дегенерац

Совпадение в аннотации оригинала
Chemotherapy is essential for cancer management yet frequently accompanied with adverse effects, particularly for temozolomide (TMZ), a frontline chemotherapeutic agent for glioma. Although clinical neurological abnormalities linked to TMZ have been observed, mechanisms underlying TMZ-induced neural impairments remain poorly understood, and effective interve…

Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial.

BACKGROUND: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs. METHODS: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/plac…

Fluorescent Polymer Nanocomposites as Novel Drug-Loading and Targeted Delivery Nanocarriers for Glioma Therapy by Modulating ERBB4.

Gliomas are the most common type of tumor in the human central nervous system, characterized by high aggressiveness, elevated mortality, and poor prognosis. Therefore, developing new therapeutic strategies is crucial for improving glioma treatment. Temozolomide (TMZ) is widely used in glioma therapy due to its excellent ability to penetrate the blood-brain barrier. In this study, we synthesized HA-PEG@ICG using hyaluronic acid (HA) and polyethylene glycol (PEG), modified with the fluorescent compound indocyanine green (ICG), and thoroughly characterized the product's structure. Subsequently, c…

CDK2/9 blockade remodels chromatin and drives phenotypic plasticity in glioblastoma organoids.

BACKGROUND: Glioblastoma (GBM) remains a highly lethal brain tumor with limited therapeutic options and pervasive resistance to standard treatments. Cyclin-dependent kinases (CDKs), key regulators of cell cycle progression and transcription, are frequently dysregulated in GBM and contribute to tumor pathogenesis. METHODS: We employed a range of preclinical GBM models-including 2D cultures, 3D spheroids, patient-derived organoids (PDOs), and multicellular 3D bioprints-to evaluate the effects of the CDK2/9 inhibitor fadraciclib in comparison to the standard-of-care temozolomide. Endpoints inclu…

A Transcriptome-Wide Analysis Nominates DIO3OS and C9orf139 as Survival-Associated Long Non-Coding RNAs in Glioblastoma.

Background: Long non-coding RNAs (lncRNAs) are widely proposed as determinants of temozolomide response in glioblastoma (GBM), but many nominations rest on analyst-derived survival endpoints, screens unadjusted for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and models evaluated with the same data used to select them. We asked which lncRNA-outcome associations remain when endpoint definition, confounder adjustment, and external validation are addressed explicitly. Methods: We analyzed 94 IDH-wildtype, temozolomide-treated primary GBM patients from The Cancer Genome Atla…

Primary glioblastoma with spontaneous transdural invasion and contiguous calvarial/mastoid osteolysis: a case report and literature review.

BACKGROUND: Glioblastoma (GBM) is the most common and most aggressive primary malignant tumor of the central nervous system in adults. Altho … tumor bed (60 Gy/30 fractions) and surrounding low-risk field (54 Gy/30 fractions) with concurrent temozolomide, followed by adjuvant temozolomide. Early postoperative MRI indicated gross total resection. At 3-month follow-up, the patient remained alive without radiographic progression, with relief of headache and no new neurological deficits. CONCLUSION: Th …

Taxifolin promotes glioma stem cell differentiation via CYP1B1-mediated EMT suppression.

BACKGROUND: Glioblastoma (GBM) progresses aggressively and resists therapy largely due to glioma stem cells (GSCs), which drive recurrence a … were evaluated using bioluminescence imaging, histopathology and immunohistochemistry in vivo, with temozolomide as a positive control. RESULTS: Purified TAX (92.47%) from Larix olgensis roots inhibited the proliferation, self-renewal of GSCs and induced apoptosis. TAX promoted GSCs differentiation toward neuronal lineages, supporting its potential as a diffe …

Perioperative leukocyte-plateletcrit shift as a prognostic signature in glioblastoma.

PURPOSE: Circulating inflammatory indices derived from routine blood counts may offer pragmatic prognostic information in glioblastoma (GB), … maries; a multivariable model adjusted for age, sex, extent of resection, radiotherapy, concomitant temozolomide (TMZ), and number of adjuvant TMZ cycles was calculated. RESULTS: Median overall survival (OS) was 406 days, with 80 deaths. In univariate models, dynamic indices predominated: the post-operative rise in leukocytes relative to plateletcrit (Δ post- …

[Choice of fractionation regimen for Grade IV gliomas depending on rapid early progression].

OBJECTIVE: To investigate the effect of two fractionation regimens on survival in patients with Grade IV gliomas depending on rapid early pr … cance of isoeffective doses <59.5Gy≥ is slightly lower (p=0.020). Radiotherapy on the background of temozolomide is equally important (p=0.007). UNLABELLED: In patients with grade 4 gliomas and REP, 3 Gy (n=30) fractionation regimen was followed by median overall survival 17.18 (95% CI 14.2-20.2) months, 2 Gy (n=30) - 12.88 (95% CI 5.4-20.3) months (p=0.849). …

DNA Repair Enzyme Regulation Strategy for Enhanced Pancreatic Neuroendocrine Tumor Therapy via Targeting siRNA-Lipid Nanoparticles.

Pancreatic neuroendocrine tumors (panNETs) originate from neuroendocrine cells with high rates of metastasis, rendering many patients ineligible for surgical resection. The first-line chemotherapeutic agent Temozolomide (TMZ) for metastatic panNETs faces challenges related to resistance, primarily mediated by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). This resistance limits the long-term efficacy of TMZ in many patients. To overcome these challenges, we developed the lipid nanoparticles (LNPs) modified with somatostatin receptors (SSTRs) targeting peptide of Octreotid…

[Drug Therapy for Glioblastoma:Standard and Novel Treatments].

Glioblastoma (GBM) is the most aggressive primary brain tumor, with a poor prognosis despite advances in multimodal treatment. Current standard of care includes maximal safe resection and radiotherapy with concomitant and adjuvant temozolomide, which is called the Stupp regimen. Tumor-treating fields are incorporated into standard therapies and have demonstrated survival benefits in newly diagnosed GBM. Bevacizumab improves progression-free survival; however, its effect on overall survival remains limited. Recent advances in comprehensive molecular analyses have accelerated the development of …

Lung Carcinoids: A Comprehensive Review for Clinicians.

Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most … tients with distant metastases may be treated with somatostatin analogues, chemotherapy, preferably temozolomide-based, mTOR inhibitors, or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Most patients have an excellent prognosis. Poor prognostic factors include atypical histology and lymph node metastases at diagnosis. Long-term follow-up is …

Multicentric Exophytic Primary Spinal Cord Glioblastoma Mimicking Teratoma.

Primary spinal cord glioblastoma is an extremely rare disease that shows dismal prognosis. Here we report the first case, to our knowledge, … stoma. After surgery, the patient underwent further adjuvant therapy consisting of radiotherapy and temozolomide. However, 8 months after surgery, the follow-up magnetic resonance imaging scan revealed tumor recurrence with intracranial dissemination. The patient is still alive at the current stage (9 months after surgery).

Estimating Permeabilities from Biased Molecular Dynamics with a Green-Kubo Formalism for Transport across the Blood-Brain Barrier.

In this work, we explore the uses of biased sampling simulations including constant-velocity SMD (cv-SMD) and umbrella sampling to study molecular permeation of three highly distinct solutes spanning over 3 orders of magnitude in the permeability space, across a model of the blood-brain barrier (BBB). These molecules range from among the slowest permeants known (temozolomide; Papp ∼ 10-6 cm s-1) to among the fastest compound known (ethanol; Papp ∼ 10-3 cm s-1). We arrive at the transmembrane solute permeability, Psim, by the Inhomogeneous Solubility-Diffusion equation combined with an unbiasin…

Case Report: Clinicopathological and Genetic Features of IDH-Mutant Brainstem Glioma in Adults: Report of Five Cases.

Adult brainstem gliomas are rare central nervous system tumors that represent a heterogeneous group of tumors. Somatic IDH mutations are uncommon in adult brainstem gliomas and there are few relevant clinical studies. Here, we reported five patients with IDH1 mutations associated with brainstem gliomas, including four cases of IDH1 R132H mutations and one case of R132G mutation. All patients were treated with focal intensity-modulated radiation therapy (IMRT) with concurrent temozolomide (TMZ). One patient died, one relapsed, and three survived to date. All these cases carried a pathogenic var…

Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes.

Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 20…