Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

Towards optimization of machining performance and sustainability aspects when turning AISI 1045 steel under different cooling and lubrication strategies

In this work, an extensive analysis has been presented and discussed to study the effectiveness of using different cooling and lubrication techniques when turning AISI 1045 steel. Three different approaches have been employed, namely dry, flood, and minimum quantity lubrication based nanofluid (MQL-nanofluid). In addition, three multi-objective optimization models have been employed to select the optimal cutting conditions. These cases include machining performance, sustainability effectiveness, and an integrated model which covers both machining outputs (i.e., surface roughness and power consumption) and sustainability aspects (carbon dioxide emissions and total machining cost). The results provided in this work offer a clear guideline to select the optimal cutting conditions based on different scenarios. It should be stated that MQL-nanofluid offered promising results through the three studied cases compared to dry and flood approaches. When considering both sustainability aspects and machining outputs, it is found that the optimal cutting conditions are cutting speed of 147 m/min, depth of cut of 0.28 mm and feed rate of 0.06 mm/rev using MQL-nanofluid. The three studied multi-objective optimization models obtained in this work provide flexibility to the decision maker(s) to select the appropriate cooling/lubrication strategy based on the desired objectives and targets, whether these targets are focused on machining performance, sustainability effectiveness, or both. Thus, this work offers a promising attempt in the open literature to optimize the machining process from the performance–sustainability point of view

Broad targeting of angiogenesis for cancer prevention and therapy

tTargeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms.Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship.Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships.These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered