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Prostate cancer (PCa) is the most common malignancy in men and represents the second leading cause of cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived endogenous metabolite kynurenic acid (KYNA) and of the lactam form of 3-2′-pyrrilonidinyl-kynurenic acid (3-PKA-L), alkaloids usually present in combination in chestnut honey. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell colony formation assay, and Western blot analysis of the major mediator proteins involved in apoptotic processes. In all experiments, KYNA was scarcely or not active while 3-PKA-L showed anticancer activity in the high concentration range (0.01 mM – 1 mM) from 24 to 72 h. The results obtained showed that cell death was induced by extrinsic apoptotic pathway, by cell morphological changes and reduction of cell colonies number. find more These novel results represent the first promising step to the accurate description of 3-PKA-L cytotoxic effect, not observed with KYNA, paving the way to the search of new anticancer agents, as well as to the better understanding of the physiopathological role of this interesting natural product.The nervous system disorders caused by doxorubicin (DOX) are among the severe adverse effects that dramatically reduce the quality of life of cancer survivors. Astragali Radix (AR), a popular herbal drug and dietary supplement, is believed to help treat brain diseases by reducing oxidative stress and maintaining metabolic homeostasis. Here we show the protective effects of AR against DOX-induced oxidative damage in rat brain via regulating amino acid homeostasis. By constructing a clinically relevant low-dose DOX-induced toxicity rat model, we first performed an untargeted metabolomics analysis to discover specific metabolic features in the brain after DOX treatment and AR co-treatment. It was found that the amino acid (AA) metabolism pathways altered most significantly. To accurately characterize the brain AA profile, we established a sensitive, fast, and reproducible hydrophilic interaction chromatography-tandem mass spectrometry method for the simultaneous quantification of 22 AAs. The targeted analysis further confirmed the changes of AAs between different groups of rat brain. Specifically, the levels of six AAs, including glutamate, glycine, serine, alanine, citrulline, and ornithine, correlated (Pearson |r| >  0.47, p  less then  0.05) with the brain oxidative damage that was caused by DOX and rescued by AR. These findings present that AAs are among the regulatory targets of DOX-induced brain toxicity, and AR is a promising therapeutic agent for it.

Primary brain malignancies (PBMs) pose significant morbidity and poor prognosis. Despite NCCN recommendations that palliative care should be integrated into general oncologic care plans, it has been historically underused in patients with PBM. We sought to examine trends and factors associated with inpatient palliative care use in patients with PBM.

Data from the 2007-2016 National (Nationwide) Inpatient Sample was analyzed for descriptive statistics and trends. Multivariable logistic regression was used to identify factors associated with inpatient palliative care in patients with PBMs.

Of the 510,238 observed hospitalizations of adults with PBM in a 10-year period, 37,365 (7.3%) had an associated inpatient palliative care consult. Rates of inpatient palliative care have increased significantly over the 10-year period, from 2.3 in 2007 to 11.9% in 2011. Patients receiving inpatient palliative care were less likely to receive inpatient oncologic treatment such as brain surgery, chemotherapy, or radiatio 2007 and 2016, though the service is still underutilized in the context of the severe symptoms and poor prognosis associated with PBM.

To identify predictors of financial hardship, operationalized as foregoing health care, making financial sacrifices, and being concerned about having inadequate financial and insurance information.

Cancer survivors (n = 346) identified through the New Jersey State Cancer Registry were surveyed from August 2018 to September 2019. Multivariable logistic regression analyses were performed.

Cancer survivors with household incomes less than $50,000 annually were more likely than those earning $50,0000-$90,000 to report foregoing health care (15.8 percentage points, p < 0.05). Compared to retirees, survivors who were currently unemployed, disabled, or were homemakers were more likely to forego doctor’s visits (11.4 percentage points, p < 0.05), more likely to report borrowing money (16.1 percentage points, p < 0.01), and more likely to report wanting health insurance information (25.7 percentage points, p < 0.01). Employed survivors were more likely than retirees to forego health care (16.8 percendesirable.Most spiders use major ampullate silk (MAS) to perform many functions across their lifetimes, including prey capture, vibratory signal detection, and safety/dragline. To accommodate their various needs, adult spiders can use inducible variability to tailor MAS with specific mechanical properties. However, it is currently unknown whether this inducible mechanical variability develops gradually or remains consistent across spider size. Supercontraction -a process by which “native-state” silk fibers axially shrink when exposed to water or high humidity-can be used to reveal the extent of inducible variability in MAS. Supercontraction removes some processing effects that occur during the spinning of the solid fiber from its liquid precursor by allowing a native-state MAS fiber to return to a low energy “ground-state”. Here, we examined the relative extent of inducible variability of MAS across spider size by assessing supercontraction properties and the difference between ground- and native-state MAS tensile properties using silk from the huntsman spider Heteropoda venatoria (Sparassidae).