Physical measures and biomarker collection in health surveys: Propensity to participate

Population-based surveys have long been a key tool for health researchers, policy makers and program managers. The addition of bio-measures, including physical measures and specimen collection, to self-reported health and health behaviors can increase the value of the research for health sciences. At the same time, these bio-measures are likely to increase the perceived burden and intrusiveness to the respondent. Relatively little research has been reported on respondent willingness to participate in surveys that involve physical measures and specimen collection and whether there is any associated non-response bias.This paper explores the willingness of respondents to participate in surveys that involve physical measures and biomarkers. A Census-balanced sample of nearly 2000 adults from a national mobile panel of persons residing in the U.S. were interviewed. Willingness to participate in six specific bio-measures was assessed. The survey finds a high correlation in the willingness of respondents to participate among these specific bio-measures. This suggests there is a general propensity towards (and against) bio-measures among potential respondents, despite some differences in willingness to participate in the more sensitive, intrusive or burdensome biomarkers. This study finds the general propensity to participate in bio-measures is correlated with a number of key measures of health and illness. This suggests that the inclusion of biomarkers in health surveys may introduce some bias in key measures that need to be balanced against the value of the additional information.     

Revisiting colorectal cancer animal model – An improved metastatic model for distal rectosigmoid colon carcinoma

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model.We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1?×?10⁷ cells/animal) in RNU rats (n?=?55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, β-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (^99mTc-MIBI).Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake.With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.     

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8⁺ T‐cell response, but also to induce long‐term specific T‐cell tumor memory. Accordingly, we have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/kg) or TMZ (range 140–240 mg/kg) metronomic administration (every 6 days) were performed in tumor‐bearing mice. Tumor evolution was monitored at 7 T with MRI (T₂‐weighted, diffusion‐weighted imaging) and MRSI‐based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6 ± 21.0 days, n = 30) compared with control (19.4 ± 2.4 days, n = 18). Best results were obtained with 140 mg/kg TMZ (treated, 44.9 ± 29.0 days, n = 12, versus control, 19.3 ± 2.3 days, n = 12), achieving a longer survival rate than previous group work using three cycles of TMZ therapy at 60 mg/kg (33.9 ± 11.7 days, n = 38). Additional interesting findings were, first, clear edema appearance during chemotherapeutic treatment, second, the ability to apply the semi‐supervised source analysis previously developed in our group for non‐invasive TMZ therapy response monitoring to detect CPA‐induced response, and third, the necropsy findings in mice cured from GBM after high TMZ cumulative dosage (980–1400 mg/kg), which demonstrated lymphoma incidence. In summary, every 6 day administration schedule of TMZ or CPA improves survival in orthotopic GL261 GBM with respect to controls or non‐metronomic therapy, in partial agreement with previous work on subcutaneous GL261.     

A rare cause of severe mitral stenosis and reversible pulmonary hypertension

Myxoma is a rare cause of severe mitral stenosis. We describe a challenging case of severe mitral stenosis and reversible pulmonary hypertension produced by a giant left atrial myxoma. The greatest risk is a diagnostic delay due to focus on discarding a pulmonary etiology of dyspnea. Physical examination and early echocardiographic assessment are the keys to avoid overlooking this uncommon pathology.