Inhibition of cancer cell invasion and metastasis by genistein

Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein’s antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-β signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis

FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis

Background 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. Methods We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. Findings We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10.0 months (95% CI 4.0-16.0) to 32.7 months (23.1-42.3) across studies with a pooled patient-level median overall survival of 24.2 months (95% CI 21.7-26.8). Median progression-free survival ranged from 3.0 months (95% CI not calculable) to 20.4 months (6.5-34.3) across studies with a patient-level median progression-free survival of 15.0 months (95% 13.8-16.2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60.4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63.5% (95% CI 43.3-81.6, I-2 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25.9% (95% CI 20.2-31.9, I-2 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78.4% (95% CI 60.2-92.2, I-2 64%). Interpretation Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24.2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX

Characteristics of innovation policy mixes in multi-level government system: the case of the Baltic Sea Region countries

Elektroniskā versija nesatur pielikumusPromocijas darbā pētīts, kā notiek inovācijas rīcībpolitikas paralēla plānošana un ieviešana dažādos pārvaldes līmeņos – vietējā, nacionālā un pārnacionālā. Analizētas divas gadījumu grupas – Baltijas valstis un Somija, Zviedrija un Dānija – kas atšķiras pēc inovācijas rīcībpolitikas īstenošanā aktīvi iesaistīto pārvaldes līmeņu skaita. Darba teorētiskais ietvars ir daudzlīmeņu pārvaldības un rīcībpolitiku kombināciju koncepti, kas izmantoti kvalitatīvo datu analīzes kategoriju izstrādei. Gadījumi analizēti un salīdzināti, izmantojot politikas plānošanas dokumentus un veicot padziļinātās intervijas ar rīcībpolitikas veidotājiem katrā pārvaldes līmenī. Hipotēze, kurā tika pieņemts, ka daudzlīmeņu inovācijas rīcībpolitikas kombinācijas raksturo nesaskaņotība, netika pierādīta, taču starp pārvaldes līmeņiem nevar novērot arī pozitīvu sinerģiju.Dissertation explores how innovation policy is planned and implemented at different levels of government - local, national and transnational. Two groups of cases are analysed - the Baltic States and Denmark, Sweden and Finland. The groups of cases differ according to the number of government levels involved in the innovation policy making. The theoretical frameworks of the thesis are the concepts of policy mix and multi-level governance. Both are used to develop the categories for qualitative data analysis. The cases are analysed and compared using the policy planning documents and conducting in-depth interviews with policy makers at each level of government. The hypothesis, which assumed that multi-level innovation policy mixes are incoherent, was not proved, however, interaction between government levels was not identified either