Impact of diffuse large B-cell lymphoma on visits to different provider specialties among elderly Medicare beneficiaries: challenges for care coordination

Newly diagnosed diffuse large B-cell lymphoma (DLBCL) can pose significant challenges to care coordination. We utilized a social-ecological model to understand the impact of DLBCL diagnosis on visits to primary care providers (PCPs) and specialists, a key component of care coordination, over a 3-year period of cancer diagnosis and treatment. We used hurdle models and multivariable logistic regression with the Surveillance Epidemiology and End Result-Medicare linked dataset to analyze visits to PCPs and specialists by DLBCL patients (n = 5,455) compared with noncancer patients (n = 14,770). DLBCL patients were more likely to visit PCPs (adjusted odds ratio, AOR [95% confidence interval, CI]: 1.25 [1.18, 1.31]) and had greater number of visits to PCPs (β, SE: 0.384, −0.014) than noncancer patients. Further, DLBCL patients were more likely to have any visit to cardiologists (AOR [95% CI]: 1.40 [1.32, 1.47]), endocrinologists (1.43, [1.21, 1.70]), and pulmonologists (1.51 [1.36, 1.67]) than noncancer patients. Among DLBCL patients, the number of PCP visits markedly increased during the treatment period compared with the baseline period (β, SE: 0.491, −0.028) and then decreased to baseline levels (−0.464, −0.022). Visits to PCPs and specialists were much more frequent for DLBCL patients than noncancer patients, which drastically increased during the DLBCL treatment period for chronic care. More chronic conditions, treatment side effects, and frequent testing may have increased visits to PCPs and specialists. Interventions to improve care coordination may need to target the DLBCL treatment period, when patients are most vulnerable to poor care coordination

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling.

Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade. Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling

Breaking and entering into the CNS: clues from solid tumor and nonmalignant models with relevance to hematopoietic malignancies

Various malignancies invade the CNS sanctuary site, accounting for the vast majority of CNS neoplastic foci and contributing to significant morbidity as well as mortality. The blood–brain barrier (BBB) exhibits considerable impermeability to chemotherapeutic agents, severely limiting therapeutic options available for patients developing metastatic CNS involvement, accounting for poor outcomes. The mechanisms by which malignant cells breach the highly exclusive BBB and subsequently survive in this unique anatomical site remain poorly understood, with most of the current knowledge stemming from non-malignant and solid malignancy models. While solid and hematologic malignancies may face different challenges once within the CNS (e.g., solid tumor parenchymal metastasis compared to masses/nodules/leptomeningeal disease in hematologic malignancies), commonality exists in the process of migrating across the BBB from the circulation. Specifically considering this last point, this review aims to survey the current mechanistic knowledge regarding malignant migration across the BBB, necessarily emphasizing the better studied solid tumor and nonmalignant models with the intention of highlighting both the current knowledge gap and additional work required to effectively consider how hematopoietic malignancies breach the CNS