Reciprocal links between methionine metabolism, DNA repair and therapy resistance in glioblastoma.

Glioblastoma (GBM) is uniformly lethal due to profound treatment resistance. Altered cellular metabolism is a key mediator of GBM treatment resistance. Uptake of the essential sulfur-containing amino acid methionine is drastically elevated in GBMs compared to normal cells, however, it is not known how this methionine is utilized or whether it relates to GBM treatment resistance.

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

Background: Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk.

Methods: A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink.

Benign and Malignant Outcomes in the Offspring of Females Exposed In Utero to Diethylstilbestrol (DES): An Update from the NCI Third Generation Study.

Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring.

Social determinants of health and depressive symptoms before and after cancer diagnosis.

Despite frequent reports of mental health needs among older women with cancer, depressive symptoms often go unrecognized and untreated, particularly in socially vulnerable survivors. Here, we examined associations of sociodemographic factors and social limitations with depressive symptoms from pre-diagnosis to post-diagnosis in older women diagnosed with breast or gynecological cancer. Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked dataset, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between sociodemographic factors (race, ethnicity, marital status, rurality) and social limitations (i.

PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer.

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition.