Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Peer reviewe

Vacuum Rabi splitting and strong coupling dynamics for surface plasmon polaritons and Rhodamine 6G molecules

We report on strong coupling between surface plasmon polaritons (SPP) and Rhodamine 6G (R6G) molecules, with double vacuum Rabi splitting energies up to 230 and 110 meV. In addition, we demonstrate the emission of all three energy branches of the strongly coupled SPP-exciton hybrid system, revealing features of system dynamics that are not visible in conventional reflectometry. Finally, in analogy to tunable-Q microcavities, we show that the Rabi splitting can be controlled by adjusting the interaction time between waveguided SPPs and R6G deposited on top of the waveguide. The interaction time can be controlled with sub-fs precision by adjusting the length of the R6G area with standard lithography methods.Comment: 4 pages, 4 figure

Altered expiratory flow dynamics at peak exercise in adult men with well-controlled type 1 diabetes.

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Airway obstruction in competetive swimmers.

Background: Swimming has been shown to cause beneficial effects on lung function. However, increased adverse effects have been hypothesized due to the air quality of indoor swimming pools. Objectives: To compare competitive swimmers present lung function to swimmers twenty to thirty years ago and examine the associations between lung function and medical history and reported respiratory symptoms in present swimmers. Methods: One hundred swimmers, 47 females and 53 males were studied with flow-volume spirometry. These findings were compared with ones obtained 20 - 30 years ago among 98 swimmers, 40 females and 58 males. Forced expiratory volume in one second (FEV1), forced expiratory volume (FVC) and their ratio (FEV%) were analysed for airways obstruction. Associations between lung function and asthma, allergy, and respiratory symptoms were examined using questionnaire. In addition airways inflammation was measured with exhaled nitric oxide measurement (FENO) in present swimmers. Airborne trichloramine was measured in air of indoor swimming pools. Results: Airway obstruction was found in 15%, 15 out of 100 studied swimmers, which all reported physician diagnosed asthma and/or family history of asthma. Most, 12 out of 15 of swimmers with obstruction finding, were males. Twenty to thirty years ago obstruction was found in 17 of the 98 swimmers. Airborne concentrations of trichloramine in the present swimming pools, were low, less than 0.1 mg/m3. Conclusion: Airway obstruction was associated with asthma and family history of asthma. There was no increase in obstruction findings among competitive swimmers within 2 - 3 decades. Measured concentrations of trichloramine raised no concern on swimmers health.</p

Calculated beam quality correction factors for ionization chambers in MV photon beams

The beam quality correction factor, , which corrects for the difference in the ionization chamber response between the reference and clinical beam quality, is an integral part of radiation therapy dosimetry. The uncertainty of is one of the most significant sources of uncertainty in the dose determination. To improve the accuracy of available data, four partners calculated factors for 10 ionization chamber models in linear accelerator beams with accelerator voltages ranging from 6 MV to 25 MV, including flattening-filter-free (FFF) beams. The software used in the calculations were EGSnrc and PENELOPE, and the ICRU report 90 cross section data for water and graphite were included in the simulations. Volume averaging correction factors were calculated to correct for the dose averaging in the chamber cavities. A comparison calculation between partners showed a good agreement, as did comparison with literature. The values from TRS-398 were higher than our values for each chamber where data was available. The values for the FFF beams did not follow the same , relation as beams with flattening filter (values for 10 MV FFF beams were below fits made to other data on average by 0.3%), although our FFF sources were only for Varian linacs.Peer reviewe

First-principles simulation of intrinsic collision cascades in KCl and NaCl to test interatomic potentials at energies between 5 and 350 eV

Theoretical interatomic potentials for KCl and NaCl are tested at energies 5–350 eV against experimental data from intrinsic collision cascades. The collisional scattering of Cl with Cl, K, and Na atoms was observed from Doppler-shifted γ rays depopulating an excited state in recoiling Cl36 produced through the thermal neutron capture Cl35(n,γ)36Cl. The collisional scattering was simulated with molecular dynamics. Interatomic potentials from the present Iab initioP atomic cluster calculations are proposed for the Cl-Cl, Cl-K, and Cl-Na interactions in KCl and NaCl.Peer reviewe

The Association between Cardiorespiratory Fitness and Gut Microbiota Composition in Premenopausal Women

The aim of this study was to investigate the association between cardiorespiratory fitness and gut microbiota composition in premenopausal women. The participants consisted of 71 premenopausal Finnish women ( aged 19-49 years). Gut microbiota were analyzed using flow cytometry, 16S rRNA gene hybridization and DNA-staining. Maximum oxygen uptake (VO2max) was assessed by respiratory gas analyzer and body composition by Bioimpdance. We found that participants with low VO2max had lower Bacteroides, but higher Eubacterium rectale-Clostridium coccoides than the high VO2max group (p < 0.05 for all). VO2max was inversely associated with EreC (r = 0.309, p = 0.01) but not with other bacteria. VO2max also negatively correlated with fat% (r = 0.755, p < 0.001), triglycerides (r = -0.274, p = 0.021) and leptin (r = -0.574, p < 0.001). By contrast, EreC was positively associated with fat% (r = 0.382, p = 0.002), dietary fat intake (r = 0.258, p = 0.034), triglycerides (r = 0.390, p = 0.002) and leptin (r = 0.424, p = 0.001), but negatively with carbohydrate intake (r = -0.252, p = 0.034) and HDL (r = -0.26, p = 0.028). After adjusting for age and dietary intake, all the significant associations remained. However, after adjusting for fat%, the associations between VO2max and EreC disappeared. Our results suggest that cardiorespiratory fitness is associated with gut microbiota composition, independent of age and carbohydrate or fat intake. The association between VO2max and EreC, however, appears to be mediated by body fatness