Geographic Distribution of Clinical Trials for Advanced-Stage Cancer.

This quality improvement study evaluates the geographic distribution of clinical trials and assesses the distances patients with cancer must travel to access a clinical trial site.

Thank You for Being Here: Insights From Rural Oncology Practice.

Rural oncologist reflects on 20 years of providing vital cancer care in underserved areas.

Tobacco carcinogen mediated up-regulation of AP-1 dependent pro-angiogenic cytokines in head and neck carcinogenesis.

Tobacco is notably genotoxic and associated with head and neck carcinogenesis. Cigarette carcinogens have the capacity to alter early response gene expression in tobacco-related malignancies via genes such as nuclear factor kappa B (NFκB). A number of early response gene activation events are also facilitated by fos/jun activator protein 1 (AP-1) associated pathways. In the present study, we hypothesize that tobacco products may induce microenvironment alterations, promoting angiogenesis and providing a permissive environment for head and neck cancer progression. In an in vitro analysis, we employed immortalized oral keratinocyte (HOK-16B) and laryngeal squamous carcinoma (UM-SCC-11A) cells to investigate interleukin (IL)-8 and vascular endothelial growth factor (VEGF) induction by cigarette smoke condensate (CSC). IL-8 and VEGF expression is based on interactions between NFκB, AP-1, and NF-IL6. We identified at least 1.5-fold dose-dependent induction of AP-1, VEGF, and IL-8 promoter/reporter gene activity after 24 h exposure to CSC. Next, we stably transfected UM-SCC-11A cells with A-Fos, a dominant negative AP-1 protein. Treatment with CSC of the A-Fos cell lines compared to empty vector controls significantly down-regulated AP-1, VEGF, and IL-8 promoter/reporter gene expression. We also performed ELISAs and discovered significant up-regulation of IL-8 and VEGF secretion by UMSCC 11A after treatment with phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, and CSC, which was down-regulated by the A-Fos dominant negative protein. We conclude tobacco carcinogens up-regulate AP-1 activity and AP-1 dependent IL-8 and VEGF gene expression in head and neck cancer. This up-regulation may promote an angiogenic phenotype favoring invasion in both premalignant and squamous cancer cells of the head and neck.

Monomeric IgG is neuroprotective via enhancing microglial recycling endocytosis and TNF-alpha.

In brain, monomeric immunoglobin G (IgG) is regarded as quiescent and only poised to initiate potentially injurious inflammatory reactions via immune complex formation associated with phagocytosis and tumor necrosis factor alpha (TNF-alpha) production in response to disease. Using rat hippocampal slice and microglial cultures, here we show instead that physiological levels (i.e., 0.2-20 microg/ml) of monomeric IgG unassociated with disease triggered benign low-level proinflammatory signaling that was neuroprotective against CA1 area excitotoxicity and followed a U-shaped or hormetic dose-response. The data indicate that physiological IgG levels activated microglia by enhancing recycling endocytosis plus TNF-alpha release from these cells to produce the neuroprotection. Minocycline, known for its anti-inflammatory and neuroprotective effects when given after disease onset, abrogated IgG-mediated neuroprotection and related microglial effects when given before injury. In contrast, E-prostanoid receptor subtype 2 (EP2) activation, which served as an exemplary paracrine stimulus like the one expected from neuronal activity, amplified IgG-mediated increased microglial recycling endocytosis and TNF-alpha production. Furthermore, like monomeric IgG these EP2 related effects took days to be effective, suggesting both were adaptive anabolic effects consistent with those seen from other long-term preconditioning stimuli requiring de novo protein synthesis. The data provide the first evidence that brain monomeric IgG at physiological levels can have signaling function via enhanced recycling endocytosis/TNF-alpha production from microglia unassociated with disease and that these IgG-mediated changes may be a means by which paracrine signaling from neuronal activity influences microglia to evoke neuroprotection. The data provide further support that low-level proinflammatory neural immune signaling unassociated with disease enhances brain function.

Improved survival of follicular lymphoma patients in the United States.

PURPOSE: Despite several new treatment options, single- and multi-institution analyses have not clarified whether survival patterns in follicular lymphoma (FL) patients have changed in recent decades. We undertook a study using a large population-based registry to analyze survival patterns among patients with FL. PATIENTS AND METHODS: Surveillance, Epidemiology, and End Results morphology codes were used to identify 14,564 patients diagnosed with FL between 1978 and 1999. Observed median survival times, Kaplan-Meier survival curves, proportional death hazard ratios, and relative survival rates were calculated. Joinpoint regression analysis was used to identify trends in annual adjusted death hazard ratios. RESULTS: An improvement in survival of all patients with FL was observed between each of three diagnosis eras (1978 to 1985, 1986 to 1992, and 1993 to 1999) by log-rank tests. Among patients with stage-specific data, the median survival time improved from 84 months (95% CI, 81 to 88 months) in the 1983 to 1989 era to 93 months (95% CI, 89 to 97 months) in the 1993 to 1999 era. Similar findings were identified across sex and age groups and for subsets including advanced-stage, large-cell FL and the combined subset of small cleaved- and mixed-cell FL. The inter-era survival advantage observed in white patients was not observed for black patients. The relative risk of death decreased by 1.8% per year over the 1983 to 1999 observation period. CONCLUSION: The survival of patients with FL in the United States has improved over the last 25 years. The survival improvement may be a result of the sequential application of effective therapies and improved supportive care.