Evaluation of the Antiproliferative Effects of Essiac™ on In Vitro and In Vivo Models of Prostate Cancer Compared to Paclitaxel

Essiac?, a widely consumed, sparsely tested herbal tea, was evaluated for preparation consistency and antiproliferative effects on prostate cancer cells and xenografts. High performance liquid chromatography (HPLC) was used to compare different lots of Essiac and evaluate extraction consistency by comparing peak areas in concentrated preparations. Repeated analysis of one lot showed < 2% RSD between corresponding peaks. Absolute peak areas varied widely between lots, but similarity in relative size of corresponding peaks was observed. Cytotoxic effects of Essiac were tested in vitro by crystal violet assay and analysis of cell cycle distribution by flow cytometry, but no differences between control and treatment groups was observed. Paclitaxel was used as a positive control in cell cycle analysis and was the only treatment which showed significant effects on cell cycle distribution. Toxicity in nude mice was tested, and efficacy in inhibiting PC-3 xenograft growth. No toxicity or tumour size difference was observed dosing up to 240 mg/kg QD, over 28 days, excepting the positive control group treated with paclitaxel. Ki-67 and PCNA expression was analyzed in treated tumors, but no difference in expression of either marker was observed. These evaluations suggest Essiac has no marked antiproliferative effect on the models tested.     

A Study of the Frequency and Social Determinants of Exposure to Cancer-Related Direct-to-Consumer Advertising Among Breast,Prostate, and Colorectal Cancer Patients

Cancer-related direct-to-consumer advertising (DTCA) is controversial because cancer treatment is complex and entails more risks and costs than typical treatments that are advertised for other conditions. Drawing from the Structural Influence Model of Communication, this study explores communication inequalities in DTCA exposure across social determinants among a population-based sample of 2013 patients diagnosed with breast, prostate, or colorectal cancers. Three survey items assessed patients’ frequency of encountering ads concerning treatment alternatives for cancer, dealing with side effects of treatment, and doctors or hospitals offering services for cancer following their diagnosis. The analysis showed that overall exposure to DTCA in this study population was modest (median was once per week). Breast cancer patients reported significantly higher exposure to all three ad categories and overall DTCA exposure than prostate and colorectal cancer patients. Older patients consistently reported lower overall exposure to DTCA across the three cancer types. Other significant correlates included ethnicity (higher exposures among African American prostate cancer patients vs. White; lower exposures in Hispanic colorectal cancer patients vs. White) and cancer stage (higher exposures in Stage IV prostate cancer patients vs. Stages 0–II). Education level did not predict patients’ DTCA exposure. The implications of these observed inequalities in DTCA exposure on cancer outcomes are discussed.     

Navigating the Cancer Information Environment: The Reciprocal Relationship Between Patient–Clinician Information Engagement and Information Seeking from Nonmedical Sources

Prior theory has argued and empirical studies have shown that cancer patients rely on information from their health care providers as well as lay sources to understand and make decisions about their disease. However, research on the dynamic and interdependent nature of cancer patients’ engagement with different information sources is lacking. This study tested the hypotheses that patient–clinician information engagement and information seeking from nonmedical sources influence one another longitudinally among a representative cohort of 1,293 cancer survivors in Pennsylvania. The study hypotheses were supported in a series of lagged multiple regression analyses. Baseline seeking information from nonmedical sources positively predicted subsequent patient–clinician information engagement at 1-year follow-up. The reverse relationship was also statistically significant; baseline patient–clinician information engagement positively predicted information seeking from nonmedical sources at follow-up. These findings suggest that cancer survivors move between nonmedical and clinician sources in a dynamic way to learn about their disease.     

Who’s Responsible? Media Framing of Pediatric Environmental Health and Mothers’ Perceptions of Accountability

How the media frames issues of environmental health may affect mothers’ views of who is responsible for addressing environmental risks to pediatric health and, ultimately, their protective behaviors. This article describes how information-oriented media sources attribute responsibility for such risks and examines associations between mothers’ routine media exposure, or scanning, and perceptions of responsibility. First, a content analysis was conducted on a sample of 474 media stories (i.e., Associated Press, parenting magazines, and websites) about childhood exposure to environmental chemicals over a 6-month period (September 2012–February 2013). We found that media stories attributed responsibility most frequently to parents, though significant differences were observed across media sources, such that websites focused more on parents and general news more on government agencies and manufacturers. Next, we conducted an online survey of mothers (N = 819) and revealed that website scanning during the prior 6 months was significantly associated with perceived personal responsibility, even after we adjusted for potential confounders. Scanning general news was also significantly associated with perceived government and manufacturer responsibility. Understanding media framing of these issues highlights opportunities for health communicators to offset pressure placed on mothers by encouraging greater social and policy support in and exposure to certain media.     

Millennium development health metrics: where do Africa’s children and women of childbearing age live?

The Millennium Development Goals (MDGs) have prompted an expansion in approaches to deriving health metrics to measure progress toward their achievement. Accurate measurements should take into account the high degrees of spatial heterogeneity in health risks across countries, and this has prompted the development of sophisticated cartographic techniques for mapping and modeling risks. Conversion of these risks to relevant population-based metrics requires equally detailed information on the spatial distribution and attributes of the denominator populations. However, spatial information on age and sex composition over large areas is lacking, prompting many influential studies that have rigorously accounted for health risk heterogeneities to overlook the substantial demographic variations that exist subnationally and merely apply national-level adjustments.Here we outline the development of high resolution age- and sex-structured spatial population datasets for Africa in 2000-2015 built from over a million measurements from more than 20,000 subnational units, increasing input data detail from previous studies by over 400-fold. We analyze the large spatial variations seen within countries and across the continent for key MDG indicator groups, focusing on children under 5 and women of childbearing age, and find that substantial differences in health and development indicators can result through using only national level statistics, compared to accounting for subnational variation.Progress toward meeting the MDGs will be measured through national-level indicators that mask substantial inequalities and heterogeneities across nations. Cartographic approaches are providing opportunities for quantitative assessments of these inequalities and the targeting of interventions, but demographic spatial datasets to support such efforts remain reliant on coarse and outdated input data for accurately locating risk groups. We have shown here that sufficient data exist to map the distribution of key vulnerable groups, and that doing so has substantial impacts on derived metrics through accounting for spatial demographic heterogeneities that exist within nations across Africa.     

PI3K/mTOR inhibition can impair tumor invasion and metastasis in vivo despite a lack of antiproliferative action in vitro: implications for targeted therapy

Oncogenic PI3K/mTOR activation is frequently observed in human cancers and activates cell motility via p27 phosphorylations at T157 and T198. Here we explored the potential for a novel PI3K/mTOR inhibitor to inhibit tumor invasion and metastasis. An MDA-MB-231 breast cancer line variant, MDA-MB-231-1833, with high metastatic bone tropism, was treated with a novel catalytic PI3K/mTOR inhibitor, PF-04691502, at nM doses that did not impair proliferation. Effects on tumor cell motility, invasion, p27 phosphorylation, localization, and bone metastatic outgrowth were assayed. MDA-MB-231-1833 showed increased PI3K/mTOR activation, high levels of cytoplasmic p27pT157pT198 and increased cell motility and invasion in vitro versus parental. PF-04691502 treatment, at a dose that did not affect proliferation, reduced total and cytoplasmic p27, decreased p27pT157pT198 and restored cell motility and invasion to levels seen in MDA-MB-231. p27 knockdown in MDA-MB-231-1833 phenocopied PI3K/mTOR inhibition, whilst overexpression of the phosphomimetic mutant p27T157DT198D caused resistance to the anti-invasive effects of PF-04691502. Pre-treatment of MDA-MB-231-1833 with PF-04691502 significantly impaired metastatic tumor formation in vivo, despite lack of antiproliferative effects in culture and little effect on primary orthotopic tumor growth. A further link between cytoplasmic p27 and metastasis was provided by a study of primary human breast cancers which showed cytoplasmic p27 is associated with increased lymph nodal metastasis and reduced survival. Novel PI3K/mTOR inhibitors may oppose tumor metastasis independent of their growth inhibitory effects, providing a rationale for clinical investigation of PI3K/mTOR inhibitors in settings to prevent micrometastasis. In primary human breast cancers, cytoplasmic p27 is associated with worse outcomes and increased nodal metastasis, and may prove useful as a marker of both PI3K/mTOR activation and PI3K/mTOR inhibitor efficacy.     

Effect of prophylactic fluconazole on oral mucositis and candidiasis during radiation therapy for head-and-neck cancer

PurposeRadiation therapy (RT) or chemoradiation therapy (CRT) for carcinoma of the head and neck can result in high rates of candidiasis and mucositis. Prophylactic fluconazole (FCZ) has been shown to reduce the incidence of candidiasis. We report our outcomes of patients with head-and-neck cancer undergoing CRT treated prophylactically with FCZ.Methods and MaterialsAn institutional review board-approved database of head-and-neck cancer patients treated with RT or CRT was reviewed to identify patients treated between 2004 and 2009 who received at least 50 Gy to approximately two-thirds of the oral cavity or oropharynx mucosa. Eligible patients were divided into 2 groups: the usual care group and the prophylaxis group. The primary endpoints were the incidence of mucositis and candidiasis.ResultsA total of 181 patients were eligible for analysis: 72 patients in the prophylactic group and 109 patients in the usual care group. Patient characteristics and radiation dose were comparable between groups. RT alone was given in 28 patients (16%). Mucositis data were available in 161 (89%) patients. Grade 2 or higher mucositis was seen in 131 (81%) patients. Prophylactic FCZ had significantly decreased grade 2 or higher mucositis. In the usual care group and prophylaxis group patients, 83 of 93 patients (89.3%) and 48 of 68 patients (70.6%), respectively, developed grade 2 or higher mucositis (P = .003).ConclusionsProphylactic administration of FCZ twice weekly during CRT for head-and-neck cancer reduces incidence of mucositis and thrush.