Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.National Institutes of Health (U.S.) (grant 5-UO1-CA84306)National Cancer Institute (U.S.) (CA034992

Toleration, Reasonableness, and Power

This chapter explores Rainer Forst’s justification-centric view of nondomination toleration. This view places an idea of equal respect and a corresponding requirement of reciprocal and general justification at the core of non-domination toleration. After reconstructing this view, this chapter addresses two issues. First, even if this idea of equal respect requires the limits of non-domination toleration to be drawn in a manner that is equally justifiable to all affected people, equal justifiability should not be understood in terms of Forst’s requirement of reciprocal and general acceptability. Second, for the equal justifiability of relevant constraints to ensure non-domination outcomes, discursive equality must be understood in substantive, purchase-sensitive terms. This means that a justification-centric view of non-domination toleration stands or falls with the participation value of what it regards as the standards of justification. This places reasonably contested matters of value at the heart of such views

ПОВЫШЕНИЕ ЭКОЛОГИЧЕСКОЙ БЕЗОПАСНОСТИ РИСОВЫХ СИСТЕМ

W artykule opisano sposoby zwiększenia bezpieczeństwa ekologicznego systemów nawadniających uprawy ryżu oparte na ponownym wykorzystaniu oczyszczonej wody ściekowej.Ways to increase the environmental safety of rice irrigation systems based on reuse of drainage water were considered.Рассмотрены способы повышения экологической безопасности рисовых оросительных систем за счет повторного использования дренажно-сбросных вод

ЗАХОДИ З ПІДВИЩЕННЯ ЕФЕКТИВНОСТІ РОБОТИ ДРЕНАЖУ РИСОВИХ СИСТЕМ

Обґрунтована необхідність та доцільність застосування глибокого розпушення для підвищення загальної ефективності роботи дренажу рисових зрошувальних систем України

ДО РОЗРАХУНКУ ПРИКАНАЛЬНОГО ДРЕНАЖУ НА ПРИДУНАЙСЬКИХ РИСОВИХ ЗРОШУВАЛЬНИХ СИСТЕМАХ

Обґрунтовано необхідність влаштування і параметри приканального дренажу на рисових системах дельти Дунаю

ПРИЧИНИ ЗНИЖЕННЯ ПРОДУКТИВНОСТІ ЗРОШУВАНИХ ЗЕМЕЛЬ РИСОВИХ СИСТЕМ УКРАЇНИ

Проаналізовані причини зниження продуктивності зрошуваних земель рисових систем і наведені рекомендації з її збільшення

Out of the doll's house Reflections on feminism and autonomy

SIGLEAvailable from British Library Document Supply Centre-DSC:9350.3175(17) / BLDSC - British Library Document Supply CentreGBUnited Kingdo