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Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells., Competing Interests: Competing interests: All authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Melanomas have a high potential to metastasize to the brain. Recent advances in targeted therapies and immunotherapies have changed the therapeutical landscape of extracranial melanomas. However, few patients with melanoma brain metastasis (MBM) respond effectively to these treatments and new therapeutic strategies are needed. Cabozantinib is a receptor tyrosine kinase (RTK) inhibitor, already approved for the treatment of non-skin-related cancers. The drug targets several of the proteins that are known to be dysregulated in melanomas. The anti-tumor activity of cabozantinib was investigated using three human MBM cell lines. Cabozantinib treatment decreased the viability of all cell lines both when grown in monolayer cultures and as tumor spheroids. The in vitro cell migration was also inhibited and apoptosis was induced by cabozantinib. The phosphorylated RTKs p-PDGF-Rα, p-IGF-1R, p-MERTK and p-DDR1 were found to be downregulated in the p-RTK array of the MBM cells after cabozantinib treatment. Western blot validated these results and showed that cabozantinib treatment inhibited p-Akt and p-MEK 1/2. Further investigations are warranted to elucidate the therapeutic potential of cabozantinib for patients with MBM.

The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further support of less carbohydrate oxidation, plasma concentrations of glucose and those of the glucose metabolite lactate were lower in fed mice that consumed the hydrolyzed compared with the intact casein diet. Concomitantly, the plasma insulin concentration was strongly reduced in fed mice given hydrolyzed casein relative to those given intact casein. The mice fed hydrolyzed casein had greater ex vivo inguinal white adipose tissue non-CO2 β-oxidation capacity along with induced expression of genes involved in mitochondrial fatty acid oxidation and mitochondrial uncoupling. The physiological changes induced by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses. We conclude that chronic consumption of extensively hydrolyzed casein reduces body mass gain and diet-induced obesity in male C57BL/6J mice.

Fifteen patients were treated in the Gamma Knife Unit and followed for 18 months or longer. Four patients had Cushing's disease, 4 had acromegaly, 3 had Nelson's syndrome and 3 had prolactinomas. One patient had no endocrinopathy. One of the patients with acromegaly and 2 of those with prolactinomas had been operated prior to Gamma Knife treatment. Radiological tumor localization was not an insuperable problem in this series. The effect of Gamma Knife treatment on the anterior pituitary neoplasia, as such, was consistently successful. All the tumors which received 10 Gy or more to the edge showed either a reduction in volume or at least cessation of growth. On the other hand, the effect of the treatment was less consistent in respect to the endocrinopathies. These results are discussed in respect of dose and tumor size. It is suggested that the role of the Gamma Knife in the treatment of pituitary adenomas requires further clarification, based on prospective studies.

A study was made of the interaction between Gamma Knife shots of different diameters, located at the same target coordinates. The effect of the doses was calculated by the Kula program and confirmed by film dosimetry. It could be shown that intermediate collimator sizes can be simulated in this way, so that, for example, a 4- and 8-mm shot with the same target coordinates simulates a 6-mm collimator. A coaxial 8- and 14-mm shot simulates an 11-mm collimator and a coaxial 14- and 18-mm shot simulates a 16-mm collimator. Additional intermediate collimator sizes can be simulated by changing the weighting of the two coaxial shots. The sharpness of the dose fall of the simulated coaxial shots is of the same order as that of single shots, indicating that the technique does not depart from ordinary Gamma Knife technique in any significant way.

In Bergen, 20 patients with meningiomas have been treated with a follow-up period in excess of 1 year. While this is too short a period to allow more than tentative conclusions to be drawn, some trends can be determined nonetheless. There has been some variation in the reporting of the results of treatment of meningiomas, with one group producing a reduction in size in 7% of patients and another in 34%. In the current material, 10 patients received 10 Gy or less to the edge of the tumor. In 4 of these 12 patients there was increase in the volume of the tumor within 1 year of treatment. Ten of the patients received 12 Gy or more to the edge of the tumor. Of these 10 patients, 4 had tumors which showed a reduction in volume. It is suggested that the difference in the reported rate of tumor volume reduction is related to differences in dose, which is discussed in relation to other treatment parameters.