A gap between the philosophy and the practice of palliative healthcare: sociological perspectives on the practice of nurses in specialised palliative homecare

Medicine, Health Care and Philosophy - Palliative care philosophy is based on a holistic approach to patients, but research shows that possibilities for living up to this philosophy seem limited by...     

Detection of tumors with fluoromarker-releasing bacteria

Combining the specificity of tumor-targeting bacteria with the sensitivity of biomarker detection would create a screening method able to detect small tumors and metastases. To create this system, we genetically modified an attenuated strain of Salmonella enterica to release a recombinant fluorescent biomarker (or fluoromarker). Salmonella expressing ZsGreen were intravenously administered to tumor-bearing mice and fluoromarker production was induced after 48 hr. The quantities and locations of bacteria and ZsGreen were measured in tumors, livers and spleens by immunofluorescence, and the plasma concentration of ZsGreen was measured using single-layer ELISA. In the plasma, the ZsGreen concentration was in the range of 0.5–1.5 ng/ml and was dependent on tumor mass (with a proportion of 0.81 ± 0.32 ng·ml⁻¹·g⁻¹). No adverse reaction to ZsGreen or bacteria was observed in any mice. ZsGreen was released at an average rate of 4.3 fg·CFU⁻¹·hr⁻¹ and cleared from the plasma with a rate constant of 0.259 hr⁻¹. ZsGreen production was highest in viable tissue (7.6 fg·CFU⁻¹·hr⁻¹) and lowest in necrotic tissue (0.47 fg·CFU⁻¹·hr⁻¹). The mass transfer rate constant from tumor to blood was 0.0125 hr⁻¹. Based on these measurements, this system has the capability to detect tumors as small as 0.12 g. These results demonstrate four essential mechanisms of this method: (i) preferential tumor colonization by bacteria, (ii) fluoromarker release in vivo, (iii) fluoromarker transport through tumor tissue and (iv) slow enough systemic clearance to enable measurement. This bacteria-based blood test would be minimally invasive and has the potential to identify previously undetectable microscopic tumors.     

IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.     

Fruit and Vegetable Intake and Stomach Cancer among Male Adults: A Case-Control Study in Northern Viet Nam

Objective: This study investigated the association between fruit and vegetable intake and stomach cancer, with considering the impacts of Helicobacter pylori (H. pylori) infection and tobacco smoking. Methods: A case-control study featuring 80 male incident stomach-cancer cases and 126 male controls was conducted in a general hospital in Viet Nam. A semi-quantitative food frequency and demographic lifestyle questionnaire were used; and venous blood samples were collected to determine H. pylori status by IgG ELISA. The respective associations between fruit and vegetable intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Results: Fruit intake and stomach cancer showed a weak inverse association when this became non-significant after adjusting for H. pylori infection (OR = 0.50, 95%CI: 0.22–1.12, p trend = 0.094). Stratifying by H. pylori status returned a negative trend for fruit intake and stomach cancer among H. pylori-negative participants (OR = 0.21, 95%CI: 0.06–0.69, p trend = 0.010), but no significant interaction for H. pylori-positive participants (OR = 0.76, 95%CI: 0.21–2.68, p trend = 0.670). Vegetable intake and stomach cancer showed no association, regardless of H. pylori status. Compared to ever-smokers with low intake, never-smokers with high vegetable (OR = 0.25, 95% CI: 0.06–0.95) and fruit intake (OR = 0.20, 95%CI: 0.06–0.65) showed the lowest odds of stomach cancer. Conclusions: Fruit, but not vegetable, intake showed a weak inverse association with stomach cancer. H. pylori infection and tobacco-smoking status may influence the protective effects of fruit and vegetable intake on stomach cancer.     

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

Familial Cancer - In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our...