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Effects of re-challenge with temozolomide in grade 2/3 IDH mutant gliomas at first progression

Background Patients with WHO grade 2 and 3 isocitrate dehydrogenase mutation (IDHmt) gliomas commonly receive temozolomide (TMZ), with or without radiation therapy, as initial therapy. At progression, TMZ is sometimes reinstated despite a paucity of data on effectiveness. Methods We reviewed imaging outcomes of patients with WHO 2016 grade II/III IDHmt gliomas re-treated with TMZ at first progression between 2007 and 2019. Tumor growth rates were calculated over the year preceding re-treatment and throughout the re-treatment period, ranging from 3 to 41 months. RANO criteria were utilized to assess TMZ response rate. Results 15 subjects included six grade II, five grade III oligodendrogliomas, one grade II and three grade III astrocytomas. Median time between completion of the first TMZ course and initiation of re-treatment was 47 months. Median progression-free survival with TMZ re-treatment was 27.4 months and median overall survival was 47.8 months. Mean rate of tumor growth by bidimensional product increased from 0.29 cm2 /month, in the year prior to first tumor progression, to 0.47 cm2/month during re-treatment, ranging from 3 to 41 months, with monotherapy TMZ. Volumetric mean rate of tumor growth was 1.12 cc/month in the year prior to first tumor progression versus 1.29 cc/month during TMZ re-treatment. Five patients experienced tumor growth rate reduction, of whom 3 patients experienced tumor shrinkage as measured by 2D; 2 of these 3 patients also experienced tumor shrinkage as measured by 3D. There was no radiographic response by RANO criteria. Conclusion These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to TMZ, underscoring the need for alternative approaches.

Piperlongumine induces meningioma cell death via the ROS-mediated endoplasmic reticulum stress and the alteration of the ubiquitin-proteasome system

Meningiomas, the most common primary tumors of the central nervous system, are curable by surgical resection and radiotherapy. However, systemic therapeutic chemotherapy for meningiomas has not existed. Piperlongumine (PL), a natural alkaloid extracted from the long pepper (Piper longum), has emerged as a promising candidate for cancer treatment due to its multimodal anti-cancer effects. However, the effects of PL in meningiomas are limited.

We examined the anti-cancer effect of PL in vitro using primary benign meningioma cells and malignant meningioma cells. The underlying mechanism of PL in meningiomas was investigated through gene expression experiments at both mRNA and protein levels.

PL inhibited meningioma cell growth, evidenced by inducing G2/M phase arrest via the up-regulation of cell cycle regulators including TP53 and CDKN1A/p21 and enhancing cell apoptosis via the up-regulation of cleaved caspase 3 and cleaved PARP1. PL-induced meningioma cell death was triggered via the activation of intracellular reactive oxygen species production leading to endoplasmic reticulum stress and the alteration of ubiquitin-proteasome system resulting in the accumulation of poly-ubiquitinated proteins.

New research on liver cell diversity could help scientists understand tumor complexity

Hepatocytes, the main cell type in the liver, differ in function according to their location in the liver. A new study shows that mitochondrial responses to nutrients drive this diversity — a finding that could help researchers better understand tumor cell heterogeneity.

From trips to treatments: how psychedelics could revolutionise anti-inflammatory medicine

Once synonymous with hippies and hallucinatory experiences, psychedelic drugs are now being explored for their medical potential. The stigma of that era resulted in research being suppressed by drug laws, yet with mental health treatments hitting limits, scientists have returned to this controversial corner of medicine.

Substances like psilocybin (found in magic mushrooms) and ayahuasca are now being taken seriously by scientists and doctors, not for the visions they induce, but for the healing potential they possess.

Initially, this focused on treating mental health conditions like depression, where currently prescribed drugs only help a minority of patients. But these investigations have now expanded to include diseases driven by inflammation, which psychedelic drugs may help reduce by calming down the immune system.


Magic mushrooms and LSD may do more than bend minds: they could fight inflammation linked to depression, arthritis and heart disease.

Breakthrough mirror-image nanopores open door to new biomedical applications

For the first time, researchers have successfully fabricated and characterized a fully functional mirror-image nanopore—a molecular gateway built entirely from D-amino acids, the mirror-image forms of the natural building blocks of proteins. The work, led by Prof. Dr. Kozhinjampara R. Mahendran at the Rajiv Gandhi Center for Biotechnology (India) in collaboration with Constructor University and other partners, demonstrates not only a major milestone in nanoscience but also opens promising biomedical applications, including potential cancer therapies.

Proteins in nature are almost exclusively built from L-amino acids, while their D-amino acid counterparts usually play only minor roles. Constructing entire proteins from D-amino acids is extremely challenging, yet offers striking advantages: Such mirror-image structures are often more resistant to degradation and may interact differently with biological systems.

In this study, the team designed a synthetic stable and well-defined D-peptide called DpPorA. Remarkably, by modifying the charge distribution, they were able to create superior versions of these pores with enhanced conductance and selectivity under different salt conditions.

Safer Knee Osteoarthritis Treatment Provides Relief Without Surgery

Placebo-controlled clinical trial shows that non-invasive radiation therapy provides a conservative option compared to medications and joint surgery. A new randomized, placebo-controlled clinical trial suggests that a single round of low-dose radiation therapy could serve as a safe and effective

For the first time, scientists pinpoint brain cells linked to depression

Scientists identified two types of brain cells, neurons and microglia, that are altered in people with depression. Through genomic mapping of post-mortem brain tissue, they found major differences in gene activity affecting mood and inflammation. The findings reinforce that depression has a clear biological foundation and open new doors for treatment development.

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