Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ran is a 25-kDa Ras-related nuclear GTP-binding protein which is very highly conserved in humans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. Ran has been found to form a stable, noncovalent complex with the chromatin-associated protein RCC1, a negative regulator of mitosis. In Sch. pombe, a temperature-sensitive mutation in the RCC1 homolog encoded by the pim1 gene causes premature induction of mitosis, and this mutation can be suppressed by overexpression of the Ran homolog encoded by spi1. We report here the cloning of three Ran cDNAs from tomato. The Ran protein is very highly conserved among plants, animals, and fungi. In tomato, Ran mRNA is expressed in all tissues examined, even those with little or no cell division, indicating that Ran in plants may have functions other than just control of mitosis. We have found that the tomato Ran protein can direct a beta-glucuronidase reporter protein to the plant cell nucleus, confirming that Ran is a nuclear protein in plants. We show that the tomato Ran protein can suppress the Sch. pombe pim1 mutation, indicating that the tomato Ran protein and the Sch. pombe spi1 protein are functionally homologous.
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PMID:A small nuclear GTP-binding protein from tomato suppresses a Schizosaccharomyces pombe cell-cycle mutant. 801 79

The aim of the paper was to study the urinary beta-glucuronidase activity in 30 patients with renal cell carcinoma (RCC), histopathologically proven after surgery, and 32 healthy subjects taken as controls. Classification of patients was done using the TNM system. A statistically significant increase (p < 0.01) in this enzyme was found in RCC patients, without relation to the changes in the urinary sediment (hematuria, pyuria, bacteriuria) or tumor dissemination. Urinary beta-glucuronidase is a useful marker in the diagnosis of malignant renal tumors.
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PMID:Urinary beta-glucuronidase in renal cell carcinoma. 1080 17

A beta-glucuronide-based linker for attaching cytotoxic agents to monoclonal antibodies (mAbs) was designed and evaluated. We employed the cytotoxic auristatin derivatives MMAE (1a) and MMAF (1b) and doxorubicin propyloxazoline (DPO, 2) to give the beta-glucuronide drug-linkers 9a, 9b, and 17, respectively. Cysteine-quenched derivatives of 9b and 17 were determined to be substrates for E. coli beta-glucuronidase, resulting in facile drug release. The beta-glucuronide MMAF drug-linker 9b was highly stable in rat plasma with an extrapolated half-life of 81 days. Each drug-linker when conjugated to mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) gave monomeric antibody-drug conjugates (ADCs) with as many as eight drugs per mAb and had high levels of immunologically specific cytotoxic activity on cancer cell lines. cAC10-9a displayed pronounced antitumor activity in a subcutaneous Karpas 299 lymphoma tumor model. A single dose treatment led to cures in all animals at the 0.5 mg/kg dose level and above, and the conjugate was well tolerated at 100 mg/kg. In mice with subcutaneous renal cell carcinoma xenografts, the MMAF conjugate c1F6-9b was tolerated at 25 mg/kg and efficacious at 0.75 mg/kg. These results demonstrate that the beta-glucuronide linker system is an effective strategy for targeting cytotoxic agents providing ADCs with high degrees of efficacy at well-tolerated doses.
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PMID:Development and properties of beta-glucuronide linkers for monoclonal antibody-drug conjugates. 1670 24