Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Using advanced wound care and hyperbaric oxygen to manage wound complications following treatment of vulvovaginal carcinoma

Postoperative management of patients with vulvar cancer is associated with a high incidence of poor wound healing and radiation -induced late tissue necrosis. This case series demonstrates the impact on wound healing with the use of hyperbaric oxygen therapy and advanced wound care following radical vulvectomy and/or radiation therapy.A retrospective case series was performed of all patients from 2016 to 2017 with lower genital cancer who underwent radical surgery with or without chemoradiation treatment, experienced wound dehiscence or late tissue radionecrosis, and were treated with advanced wound care, including hyperbaric oxygen therapy (HBO).Five patients were included with a mean age of 63; four had squamous cell carcinoma and one patient had vaginal adenocarcinoma secondary to prior diethylstilbestrol exposure. Three patients underwent radical vulvectomy. All received pelvic radiation therapy, subsequently experienced wound complications, and were managed with advanced wound care and HBO. The mean reduction in wound area at the final wound follow up visit after completion of HBO therapy was found to be 76%, ranging 42–95%, with an average follow up of five months. The mean number of HBO sessions per patient was 58. Complete tissue granulation or significant improvement in tissue radionecrosis was present in all patients.Advanced wound care and hyperbaric oxygen therapy are beneficial in the management of postoperative wound complications. Prospective studies are needed to identify the optimal use of perioperative hyperbaric oxygen and appropriate wound care for patients with gynecologic malignancies. Keywords: Hyperbaric oxygen therapy, Radiation tissue necrosis, Vulvar carcinom

The effect of herbal materials on the p-glycoprotein activity and function

P-glycoprotein (P-gp) encoded by the MDR1 (multidrug resistance 1) gene is ATP-dependent transporting protein which is localizated in the cell membrane. P-gp is expressed Review Article 130 A. Bogacz, D. Deka-Pawlik, J. Bartkowiak-Wieczorek, M. Karasiewicz, R. Kujawski, A. Kowalska, A. Chałas, B. Czerny, E. Grześkowiak, P. M. Mrozikiewicz mainly in organs with the secretory functions and its physiological role concerns tissue protection against xenobiotics. P-glycoprotein is involved in the permeability barriers of the blood-brain, blood-placenta directly protecting these organs. It participates in the transport of many drugs and other xenobiotics affecting their absorption, distribution, metabolism and excretion. The high P-gp activity in the cell membranes of cancer tissue is a major cause of lack of effectiveness of chemotherapy. Hence, the methods which could increase the sensibility of these pathological cells to cytostatics are still being searched. In the experimental studies it was shown that natural plant substances may have an effect on the expression level and activity of P-glycoprotein. Hypericum perforatum, Ginkgo biloba and Camellia sinensis increase P-gp activity while curcumin from Curcuma longa, piperine and silymarin inhibit this protein. Taking into account a wide substrate spectrum of P-gp, application of our knowledge on interactions of herbals and synthetic drugs should be considered in order to improve drug impact on different tissues.Glikoproteina P (P-gp) kodowana przez gen oporności wielolekowej MDR1 to ATP-zależne białko transportowe zlokalizowane w błonach komórkowych. P-gp ulega ekspresji głównie w obrębie narządów pełniących funkcje wydzielnicze, a jej fizjologiczna rola polega na ochronie tkanek przed ksenobiotykami. Glikoproteina P bierze udział w barierach przepuszczalności krew-mózg, krew-łożysko, chroniąc bezpośrednio te organy. Uczestniczy w transporcie leków i innych ksenobiotyków, wpływając na ich absorpcję, dystrybucję, metabolizm i wydalanie. Wysoka aktywność P-gp w błonach komórek nowotworowych jest główną przyczyną braku skuteczności chemioterapii. Poszukiwane są więc sposoby zwiększenia wrażliwości tych patologicznych komórek na cytostatyki. Badane są w tym kierunku naturalne substancje roślinne, ponieważ zaobserwowano ich wpływ na stopień ekspresji oraz aktywność glikoproteiny P. Hypericum perforatum, Ginkgo biloba i Camellia sinensis to surowce zwiększające aktywność P-gp, natomiast kurkumina z korzenia ostryża długiego, piperyna oraz sylimaryna hamują działanie tego białka. Ze względu na tak wielokierunkowe oddziaływanie fitoterapii oraz szerokie spektrum substratowe P-gp, stosując wiedzę na temat interakcji surowców roślinnych z lekami syntetycznymi należy zawsze mieć na uwadze zwiększenie biodostępności stosowanych leków

Wpływ surowców roślinnych an aktywność i funkcje glikoproteiny P

P-glycoprotein (P-gp) encoded by the MDR1 (multidrug resistance 1) gene is ATP-dependent transporting protein which is localizated in the cell membrane. P-gp is expressed Review Article 130 A. Bogacz, D. Deka-Pawlik, J. Bartkowiak-Wieczorek, M. Karasiewicz, R. Kujawski, A. Kowalska, A. Chałas, B. Czerny, E. Grześkowiak, P. M. Mrozikiewicz mainly in organs with the secretory functions and its physiological role concerns tissue protection against xenobiotics. P-glycoprotein is involved in the permeability barriers of the blood-brain, blood-placenta directly protecting these organs. It participates in the transport of many drugs and other xenobiotics affecting their absorption, distribution, metabolism and excretion. The high P-gp activity in the cell membranes of cancer tissue is a major cause of lack of effectiveness of chemotherapy. Hence, the methods which could increase the sensibility of these pathological cells to cytostatics are still being searched. In the experimental studies it was shown that natural plant substances may have an effect on the expression level and activity of P-glycoprotein. Hypericum perforatum, Ginkgo biloba and Camellia sinensis increase P-gp activity while curcumin from Curcuma longa, piperine and silymarin inhibit this protein. Taking into account a wide substrate spectrum of P-gp, application of our knowledge on interactions of herbals and synthetic drugs should be considered in order to improve drug impact on different tissues.Glikoproteina P (P-gp) kodowana przez gen oporności wielolekowej MDR1 to ATP-zależne białko transportowe zlokalizowane w błonach komórkowych. P-gp ulega ekspresji głównie w obrębie narządów pełniących funkcje wydzielnicze, a jej fizjologiczna rola polega na ochronie tkanek przed ksenobiotykami. Glikoproteina P bierze udział w barierach przepuszczalności krew-mózg, krew-łożysko, chroniąc bezpośrednio te organy. Uczestniczy w transporcie leków i innych ksenobiotyków, wpływając na ich absorpcję, dystrybucję, metabolizm i wydalanie. Wysoka aktywność P-gp w błonach komórek nowotworowych jest główną przyczyną braku skuteczności chemioterapii. Poszukiwane są więc sposoby zwiększenia wrażliwości tych patologicznych komórek na cytostatyki. Badane są w tym kierunku naturalne substancje roślinne, ponieważ zaobserwowano ich wpływ na stopień ekspresji oraz aktywność glikoproteiny P. Hypericum perforatum, Ginkgo biloba i Camellia sinensis to surowce zwiększające aktywność P-gp, natomiast kurkumina z korzenia ostryża długiego, piperyna oraz sylimaryna hamują działanie tego białka. Ze względu na tak wielokierunkowe oddziaływanie fitoterapii oraz szerokie spektrum substratowe P-gp, stosując wiedzę na temat interakcji surowców roślinnych z lekami syntetycznymi należy zawsze mieć na uwadze zwiększenie biodostępności stosowanych leków

Auditory Categorization of Man-Made Sounds Versus Natural Sounds by Means of MEG Functional Brain Connectivity

Previous neuroimaging studies have shown that sounds can be discriminated due to living-related or man-made-related characteristics and involve different brain regions. However, these studies have mainly provided source space analyses, which offer simple maps of activated brain regions but do not explain how regions of a distributed system are functionally organized under a specific task. In the present study, we aimed to further examine the functional connectivity of the auditory processing pathway across different categories of non-speech sounds in healthy adults, by means of MEG. Our analyses demonstrated significant activation and interconnection differences between living and man-made object sounds, in the prefrontal areas, anterior-superior temporal gyrus (aSTG), posterior cingulate cortex (PCC), and supramarginal gyrus (SMG), occurring within 80–120 ms post-stimulus interval. Current findings replicated previous ones, in that other regions beyond the auditory cortex are involved during auditory processing. According to the functional connectivity analysis, differential brain networks across the categories exist, which proposes that sound category discrimination processing relies on distinct cortical networks, a notion that has been strongly argued in the literature also in relation to the visual system