A method for assessing an effect of hypoxia on a tissue includes providing a sample of the tissue in a hermetically sealed container, determining a first amount of a reaction substrate(e.g., protocatechuic acid) to be introduced into the sealed container and determining a second amount of a reaction enzyme (e.g., protocatechuate dioxygenase) to be introduced into the sealed container. The method further includes introducing the reaction substrate and the reaction enzyme into the sealed container. At least one of the first amount of the reaction substrate and the second amount of the reaction enzyme is selected to induce at least one of a predetermined amount of hypoxia less than anoxia and a predetermined rate of hypoxia in the tissue during a reaction between the reaction substrate and the reaction enzyme. Values of properties of the tissue can be measured before and after the reaction to assess effects of hypoxia.

The present invention relates to a composition for detecting hydrogen sulfide or measuring a concentration of hydrogen sulfide, and a composition comprising same as an effective ingredient for diagnosing or imaging in vivo inflammation, tissues having hypoxic damage, or cancer. The composition for detecting hydrogen sulfide or measuring a concentration of hydrogen sulfide according to the present invention, which comprises the compound represented by formula 1 (.sup.99mTc-alpha-hydroxy acid) having alpha-hydroxy acid labeled with .sup.99mTc, enables the detection or concentration measurement of hydrogen sulfide in in-vitro and in-vivo levels and, as such, can be advantageously used for detecting hydrogen sulfide and measuring a concentration of hydrogen sulfide and furthermore for discovering biological roles of hydrogen sulfide in vivo, especially, for detecting, imaging, and quantitatively measuring hydrogen sulfide in a disease selected from the group consisting of angiogenesis, inflammation, cancer, Alzheimer's disease, cardiovascular ischemia, and cerebrovascular ischemia, or in hypoxic tissues.

Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

A method for measuring levels of specific biomarkers in exhaled breath. Specific compounds such as nitric oxide and isoprene can be monitored from a subject's breath. The resultant measurements can provide indications of the subject's medical condition, or response to an applied stress.

Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

Enolase levels are predictive of the probability that a cancer patient will respond favorably to cancer therapy involving administration of hypoxia-activated achiral phosphoramide mustards.

Compositions, methods and apparatus for diagnosing and/or monitoring a hypoxic condition by measurement of a hypoxia-associated gene signature can be used for diagnosis including early diagnosis, monitoring, making treatment decisions, or management of subjects suspected of having a disease or condition that is associated with a hypoxic condition (e.g., a hypoxic condition). Nucleic acid and protein biomarkers can be used for specifically determining the likelihood of the presence or absence of a hypoxic condition in a subject.

A compound and method for detecting hypoxic cells and tissue are provided. The compound includes a probe selected from the group consisting of a hypoxia sensitive 2-nitroimidazole containing fluorescence imaging probe, a hypoxia sensitive reversible ON-OFF fluorescence imaging probe, a hypoxia sensitive azo-based fluorescence imaging probe, and combinations thereof. The method includes contacting the cells or tissue with the probe of any one of claims 1-13 and detecting fluorescent intensity of the cell or tissue, wherein increased fluorescent intensity indicates that the cells or tissue is hypoxic. Also provided are a method of synthesizing the compound and a method for synthesizing a therapeutic agent including the compound.

Detection of under-expression of selected genes in NK cells is used to confirm a hypoxic tumor microenvironment that is ordinarily suppressive with respect to ADCC and cytotoxic cell killing of NK cells. Most notably, while hypoxia is known to upregulate HIF-1 and genes under the control of HIF-1, hypoxia in a tumor microenvironment led to under-expression of selected genes, including HIF-1. Thus, gene expression analysis of certain genes on NK cells can be used to detect conditions in a tumor that would indicate use of haNK cells.

The present disclosure provides, among other things, methods and compositions for diagnosing and treating stress-induced injuries, hypoxia in particular. The present invention is based, in part, on the novel discovery that a metabolite, L-2-hydroxyglutarate, and certain enzymes and substrates regulating its metabolism, mediate stress-induced cellular mechanisms. In some embodiments, provided methods and compositions are used to diagnose and treat diseases with hypoxia-induced injuries. In some embodiments, provided methods and compositions are used to modulate cell pluripotency or differentiation in vivo or in vitro.