Disease relevance of NSC318502

• Hypoxic regions of human carcinomas were chemically marked with pimonidazole [1].
• We assessed cellular hypoxia by pimonidazole staining and blotting of the O2-labile HIF-1 alpha-subunit in human osteosarcoma cell cultures (U2OS and 143B) [2].
• Pimonidazole, a "hypoxia marker" normally delivered i.v. or i.p., was instead administered in the drinking water of tumor-bearing mice [3].
• Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker [4].
• Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer [5].

High impact information on NSC318502

• Consistent with the ability of Ho perfusion to simulate the level of oxygenation, bone marrow fractions separately enriched for HSCs were found to be the most positive for the binding of the hypoxic marker pimonidazole [6].
• At an intermediate oxygen concentration (3% O2) pimonidazole staining and HIF-alpha expression were detectable but strongly reduced after ETC inhibition in conventional cell cultures [2].
• This effect was also associated with improved tumor oxygenation as assessed by pimonidazole staining, decreased HIF-1alpha protein levels, and microtubule destabilization as assessed by deacetylation [7].
• We compared the degree of colocalization of two endogenous markers for hypoxia, HIF-1alpha and carbonic anhydrase IX (CAIX), with a chemical marker for hypoxia, pimonidazole [8].
• The accuracy of GFP fluorescence in reporting hypoxia was confirmed by flow cytometry analysis and by immunohistochemical comparison with pimonidazole, a well-established hypoxia marker drug [9].

Chemical compound and disease context of NSC318502

• This study correlated the exogenous 2-nitroimidazole hypoxia marker 1-[(2-hydroxy-3-piperidinyl)propyl]-2-nitroimidazole hydrochloride (pimonidazole) with the endogenous hypoxia-related marker carbonic anhydrase 9 (CA9) and with vascular parameters using immunohistochemical techniques and a computerized image analysis system [5].
• In addition to showing tumor growth inhibition, we identified three potential surrogate biomarkers to determine the efficacy of 2-methoxyestradiol therapy: decreased HIF-1alpha levels, alpha-tubulin acetylation, and degree of hypoxia as determined by pimonidazole staining [7].
• Tissue hypoxia was confirmed by an exogenous marker, pimonidazole, and by an elevated concentration of lactate, an endogenous marker [10].
• PURPOSE: Pimonidazole binding (hypoxia) and involucrin expression (differentiation) overlap extensively in squamous cell carcinomas [11].
• EXPERIMENTAL DESIGN: HIF-1alpha expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9 [12].

Biological context of NSC318502

• These cells stained positively for pimonidazole and therefore generated hypoxic stress within the target tissue, a prerequisite for the differentiation of stem cells to chondrocytes and subsequent heterotopic bone formation [13].
• METHODS: Using punch biopsy wounds in rats as a wound healing model, the distributions of vascular endothelial growth factor, transforming growth factor-beta, tumor necrosis factor-alpha, and pimonidazole adducts (as a hypoxia marker) were followed immunohistochemically during the healing process [14].
• Recent studies show that carbonic anhydrase 9 (CA9) is up-regulated by hypoxia and that its immunohistochemical tissue distribution follows the distribution of the radiosensitizer pimonidazole (C. C. Wykoff et al., Cancer Res. 60: 7075-7083, 2001) [15].
• CONCLUSIONS: Colocalization of immunostaining for involucrin and pimonidazole binding is consistent with oxygen regulation, but the lack of involucrin expression in hypoxic regions of poorly differentiated tumors indicates that its transcriptional status with respect to hypoxia induction is altered by cell differentiation [11].
• Accelerated elimination of pimonidazole following microsomal enzyme induction in mice: a possible approach to reduced neurotoxicity of the pimonidazole-etanidazole combination [16].

Anatomical context of NSC318502

• The distribution patterns of pimonidazole and CA9 were similar, although the CA9 signal was generally observed already at shorter distances from blood vessels [5].
• One week after bile duct ligation, hypoxia was demonstrated by the immunodetection of pimonidazole adducts unevenly distributed throughout the lobule [17].
• Hypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix [12].
• Hypoxia and vascular hot spots were detected by immunohistochemistry using pimonidazole as a hypoxia marker and anti-CD31 antibody to visualize endothelial cells [18].
• Catechin (30 mg/kg i.v. upon reperfusion), a free radical scavenger, and Carolina Rinse solution, which contains several agents that inhibit free radical formation, minimized disturbances in microcirculation and prevented pimonidazole adduct formation significantly [19].

Associations of NSC318502 with other chemical compounds

• Protein-bound pimonidazole adducts were identified on formalin-fixed, paraffin-embedded tissue with immunohistochemistry [20].
• Qualitative and quantitative analyses for involucrin expression, pimonidazole binding, and human MT-IIa mRNA expression were performed [11].
• Abnormal clinical pharmacokinetics of the developmental radiosensitizers pimonidazole (Ro 03-8799) and etanidazole (SR 2508) [21].
• The hypoxic cytotoxicities of misonidazole and pimonidazole (Ro 03-8799) towards the human tumor cell lines HT-1080 and LoVo have been compared with those seen with Chinese hamster V79-379A cells [22].
• METHODS AND MATERIALS: RIF-1 tumors implanted intradermally in C3H mice were treated with either 50J photodynamic therapy or with 120 min clamping in combination with either misonidazole, pimonidazole, metronidazole, nimorazole, RB6145, RSU1069, SR4233, mitomycin-C, or RB90740 [23].

Gene context of NSC318502

• In comparison with vascular endothelial growth factor mRNA, expression of CA IX demonstrated a similar, although more tightly circumscribed, pattern of expression around regions of necrosis and showed substantial although incomplete overlap with activation of the hypoxia marker pimonidazole [24].
• Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding [25].
• Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding [25].
• Percentage of expression was scored as well as colocalization of pimonidazole with CA IX [26].
• In general, cells immunostaining for MIB-1 and PCNA did not immunostain for pimonidazole binding [27].

Analytical, diagnostic and therapeutic context of NSC318502

• Using a monoclonal antibody and cell sorting, CA9-positive cells in SiHa cervical carcinoma xenografts growing in immunodeficient mice were found to be clonogenic, resistant to killing by ionizing radiation, and preferentially able to bind the hypoxia marker pimonidazole [28].
• Thus, in addition to its convenience and versatility when compared with hypoxia marker injection, oral administration of pimonidazole appears to permit identification of all of the physiologically and therapeutically relevant hypoxic tumor cells [3].
• Immunofluorescence analysis of the hypoxia marker, pimonidazole, showed that collecting ducts and many developing tubules undergo severe hypoxia in developing kidney [29].
• Using the hypoxia marker pimonidazole, we now provide immunohistochemical evidence that in the most frequently used animal model system of inbred mice Mtb-induced granulomas, even after more than one year of aerogenic infection, are not severely hypoxic [30].
• Comparison between the comet assay and pimonidazole binding for measuring tumour hypoxia [31].

References