Self-report Versus Measured Physical Activity Levels During Outpatient Cardiac Rehabilitation

Purpose: Many patients with coronary artery disease (CAD) do not achieve the recommended physical activity (PA) levels during and after cardiac rehabilitation (CR). The aim of this study was to analyze moderate to vigorous physical activity (MVPA) levels and the differences between perceived (self-reported) and measured (activity monitor) MVPA in CAD patients during CR. The second aim was to analyze which patient characteristics were associated with this difference. Methods: A two-center observational-sectional study was conducted within the Department of Rehabilitation Medicine of the University Medical Center Groningen between January and April 2018. Adults with CAD, following an outpatient CR program, were included. Perceived MVPA was assessed with the Short Questionnaire to Assess Health-enhancing Physical Activity and compared with ActivPAL3 activity monitor outcomes over a period of 7 d. Results: Fifty-one patients with CAD (age 59.4 ± 7.1 yr, eight females) were recruited. Four patients (8%) did not achieve the recommended guideline level of ≥150 min/wk of MVPA. Patients spent ≥80% of the week in sedentary activities. Patients overestimated MVPA with a median of 805 (218, 1363) min/wk (P < .001). The selected patient characteristics (age, body mass index, type of CAD, type of CR, social support, and self-efficacy) were not associated with this overestimation. Conclusions: Most patients with CAD, participating in an outpatient CR program, do achieve MVPA exercise recommendations but spend simultaneously too much time in sedentary activities

Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the ApcMin/+ mouse, a model for spontaneous intestinal polyposis. PRKO-ApcMin/+mice exhibited no change in polyp number, size or localization compared to ApcMin/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis

Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring

Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors

Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the Apc(Min/+) mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+) mice exhibited no change in polyp number, size or localization compared to Apc(Min/+). To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis

Antibodies used for immunohistochemical detection of PR.

<p>Antibodies used for immunohistochemical detection of PR.</p

The Progesterone receptor has no influence on intestinal polyposis.

<p>A–C) Development of spontaneous polyposis in the <i>Apc^Min/+</i> mouse is not altered by <i>PRKO</i> (10 female animals per genotype).</p

Lack of off-target effects from progestins on intestinal proliferation or development of acfs.

<p>A) Treatment of a panel of colon cancer cell lines with MPA or progesterone (P4) has no effect on viability at relevant concentrations. B) BrdU incorporation in small intestine or colon after challenging female animals with MPA or progesterone (P4) for four consecutive days. C–E) Acf count in the Azoxymethane treated rat shows acf number (C), localization of acfs throughout the colon (D) and multiplicity (E) (number of crypts per acf).</p

Progesterone Receptor expression in mesenchymal cells in the intestine, not in the epithelium.

<p>A–E) PR immunohistochemistry on the mouse colon (A) and small intestine (B,C) where rare cells express PR (arrowhead). And in an adenoma of an <i>Apc^Min/+</i> mouse (D). PR is widely expressed in the mouse uterus (E). F,G) <i>In situ</i> hybridization in mouse uterus (F) and small intestine (G). All murine tissue shown was taken from A female animal in diestrous stage, when progesterone is high <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022620#pone.0022620-Wood1" target="_blank">[39]</a>. H–J) PR Expression in the human colon is located in mesenchymal cells (I) and the smooth muscle layer (J), similar to the mouse intestine. For <i>in situ</i> hybridization, thick (10 µm) sections were used, which makes identification of mesenchymal cells difficult. K) PR immunoblot on the mouse colon and small intestine. L) PR immunoblot on a panel of colon cancer cell lines shows no expression of either PR-A or PR-B isoform. The breast cancer cell line T47D is used as a positive control.</p

Table_1_Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring.docx

Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors.</p