There’s a long-held belief in diabetes prevention that weight loss is the main way to lower disease risk. Our new study challenges this.

For decades, people diagnosed with prediabetes—a condition affecting up to one in three adults depending on age—have been told the same thing by their doctors: eat healthily and lose weight to avoid developing diabetes.

This approach hasn’t been working for all. Despite unchanged medical recommendations for more than 20 years, diabetes prevalence continues rising globally. Most people with prediabetes find weight-loss goals hard to reach, leaving them discouraged and still at high risk of diabetes.

In a new study, Yale researchers tracked the initial metabolic response to a pair of cancer mutations that are typically tolerated in skin.

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.

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.

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.