Connecting people with cancer to physical activity and exercise programs: a pathway to create accessibility and engagement.

Recent guidelines concerning exercise for people with cancer provide evidence-based direction for exercise assessment and prescription for clinicians and their patients. Although the guidelines promote exercise integration into clinical care for people with cancer, they do not support strategies for bridging the guidelines with related resources or programs. Exercise program accessibility remains a challenge in implementing the guidelines, but that challenge might be mitigated with conceptual frameworks ("pathways") that connect patients with exercise-related resources. In the present paper, we describe a pathway model and related resources that were developed by an expert panel of practitioners and researchers in the field of exercise and rehabilitation in oncology and that support the transition from health care practitioner to exercise programs or services for people with cancer. The model acknowledges the nuanced distinctions between research and exercise programming, as well as physical activity promotion, that, depending on the available programming in the local community or region, might influence practitioner use. Furthermore, the pathway identifies and provides examples of processes for referral, screening, medical clearance, and programming for people after a cancer diagnosis. The pathway supports the implementation of exercise guidelines and should serve as a model of enhanced care delivery to increase the health and well-being of people with cancer.

A quantitative analysis of the reduction in oxygen levels required to induce up-regulation of vascular endothelial growth factor (VEGF) mRNA in cervical cancer cell lines.

The presence of hypoxia (low oxygen concentrations) in solid tumours correlates with poor prognosis, increased metastasis, and resistance to radiotherapy and some forms of chemotherapy. Malignant cells produce an angiogenesis factor, vascular endothelial growth factor (VEGF), which may increase metastatic ability and is up-regulated in the presence of hypoxia. Clinical data for cancers of the cervix and head and neck relate oxygen levels in the tumour to treatment outcome. This suggests the possibility that the presence of VEGF mRNA might be used as a marker for relevant levels of hypoxia. Suspension cultures of three human cervical cancer cell lines, SiHa, ME-180 and HeLa, were used to investigate up-regulation of VEGF mRNA levels following exposure to precisely defined oxygen concentrations for 2 or 4 h. An oxygen sensor was used to confirm the actual levels of dissolved oxygen present. The oxygen concentrations which caused half-maximal upregulation (the Km value) of VEGF mRNA level in the three cell lines were similar except for one instance (Km at 4 h: SiHa 27.0 +/- 5.7 microM, ME-180 16.8 +/- 3.3 microM, HeLa 13.0 +/- 1.8 microM, SiHa and HeLa P = 0.01). The Km values for the HeLa cell line as measured at 2 h (24.9 +/- 0.8 microM) and 4 h (13.0 +/- 1.8 microM) were significantly different (P < 0.0001). VEGF mRNA half-lives measured in air were consistent with values in the literature (SiHa 59.8 +/- 5.8 min, ME-180 44.4 +/- 7.2 min, HeLa 44.5 +/- 6.3 min). Differences in oxygen consumption at low oxygen concentrations were noted between the different cell lines. Stirring in suspension culture was found to induce VEGF mRNA in SiHa cells. The presence of VEGF mRNA may be a marker for radiobiologic hypoxia.

Determination of metyrapone and the enantiomers of its chiral metabolite metyrapol in human plasma and urine using coupled achiral-chiral liquid chromatography.

A coupled achiral-chiral liquid chromatographic assay has been developed to determine the concentrations of metyrapone and the enantiomers of its chiral metabolite metyrapol in plasma and urine. The chromatographic system consisted of a silica precolumn (75 x 4.6 mm I.D.) coupled in-line to a 250 x 4.6 mm I.D. column containing cellulose tris(4-methylbenzoate) coated on silica gel (Chiralcel OJ-CSP). When plasma samples were analyzed, the mobile phase was hexane-ethanol (92:8, v/v) modified with 0.1% diethylamine and when urine samples were analyzed the mobile phase was hexane-ethanol (94:6, v/v) modified with 0.2% diethylamine. Under these chromatographic conditions the chromatographic retentions [expressed as capacity factors (k')] for metyrapone were k' = 2.35 (plasma) and 2.52 (urine); for (-)-metyrapol k' = 4.22 (plasma) and 4.62 (urine); for (+)-metyrapone k' = 5.16 (plasma) and 5.86 (urine); enantioselectivities (alpha) were 1.09 (plasma) and 1.13 (urine). The assay has been validated for use in metabolic studies. The analyses of plasma and urine samples from one subject following oral administration of 750 mg of metyrapone indicated that the enzymatic reduction of myterapone by aldo-keto reductase was enantiospecific.