Substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones with antitumor activity. In depth study of the effect on growth of breast cancer cells.
(33/69)
Xenohormetic, hormetic and cytostatic selective forces driving longevity at the ecosystemic level.
(34/69)
We recently found that lithocholic acid (LCA), a bile acid, extends yeast longevity. Unlike mammals, yeast do not synthesize bile acids. We therefore propose that bile acids released into the environment by mammals may act as interspecies chemical signals providing longevity benefits to yeast and, perhaps, other species within an ecosystem. (+info)
Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model.
(35/69)
Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery: drug discovery for targeting the tumor microenvironment.
(39/69)
The tumor microenvironment, characterized by regions of hypoxia, low nutrition, and acidosis due to incomplete blood vessel networks, has been recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also malignant progression and metastasis. However, exploiting such a cumbersome tumor microenvironment for cancer treatment could provide tumor-specific therapeutic approaches. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment in which hypoxia inducible factor (HIF)-1-mediated gene regulation is considered essential for angiogenesis and tumor development. Additional oxygen sensitive signaling pathways including mammalian target of rapamycin (mTOR) signaling and signaling through activation of the unfolded protein response (UPR) also contribute to the adaptation in the tumor microenvironment. This in turn has led to the current extensive interest in the signal molecules related to adaptive responses in the tumor microenvironment as potential molecular targets for cancer therapy against refractory cancer and recurrence in preparation for the aging society. Therefore, we should focus on the drug discovery for targeting the tumor microenvironment to develop tumor-specific cytostatic agents including angiogenesis inhibitors. In this paper, the development of hypoxia-selective prodrugs, HIF-1 inhibitors, and modulators of the tumor microenvironment will be discussed. (+info)
Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery:hypoxia-inducible factor-1 (HIF-1)-active cells as a target for cancer therapy.
(40/69)
The microenvironment of solid tumors is characterized by low pO(2) that is well below physiological levels. Intratumoral hypoxia is a major factor contributing to cancer progression and is exacerbated as a result of oxygen consumption by rapidly proliferating tumor cells near blood vessels, poor lymphatic drainage resulting in high interstitial pressure, and irregular blood supply through immature tumor vasculature. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor that regulates cellular responses to hypoxia. Cellular changes induced by HIF-1 are extremely important targets for cancer therapy. Therefore, targeting strategies to counteract HIF-1-active cells are essential for cancer therapy. In this study, we introduce a novel strategy for targeting HIF-1-active cells. (+info)