Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU-rich elements has long been known, the expected connection between GAPDH and control of mRNA stability has never been made. Recently, we described GAPDH binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3' untranslated region (UTR), which we showed to be an mRNA decay element in ovarian cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients with ovarian cancer. We investigated the functional significance of GAPDH's association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half-lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates with a large AU-rich-containing region. The effects of binding of GAPDH protein or ovarian extracts to mutations of the AU-rich regions within the footprint were consistent with this finding. In a tissue array containing 256 ovarian and fallopian tube cancer specimens, we found that GAPDH was regulated in these cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008). In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. We are the first to evaluate the clinical role of GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is regulated, and we now recognize that one of the many functions of GAPDH is to promote mRNA stability of CSF-1, an important cytokine in tumor progression.
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PMID:The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both regulated and controls colony-stimulating factor-1 messenger RNA stability in ovarian cancer. 1870 68

We retrospectively evaluated the efficacy and toxicity of docetaxel and carboplatin in patients with platinum and paclitaxel-pretreated recurrent ovarian, fallopian tube, and peritoneal cancer. Forty-two women (38 with ovarian cancer, 1 with fallopian tube cancer, 3 with peritoneal cancer) whose cancer had progressed within 12 months of their last treatment with both a platinum agent and paclitaxel were treated with docetaxel (70 mg/m(2), day 1) and carboplatin (area under the curve of 4-6, day 1). Thirty-four patients had measurable disease. The objective response rate was 23% within 0-6 months of the progression-free interval, 50% within 6-12 months, and 32% (11 of 34 patients) for both groups. The median time to tumor progression was 28, 49, 34 weeks, and the median overall survival time was 94, 224, 111 weeks, respectively. The most common toxicity was grade 3/4 neutropenia (98% of patients), with 15 episodes (8.4% of courses) of neutropenic fever. The main nonhematologic toxicity was hypersensitivity; 7 patients (17%) required discontinuation of the therapy. The results of our study indicate that the combination of docetaxel and carboplatin is effective against recurrent ovarian, fallopian tube, and peritoneal cancer with progression-free interval of 6-12 months from previous treatment by paclitaxel and platinum. On the other hand, single-agent chemotherapy would be better than this regimen considering its low response rate and severe hematological toxicity for patients with progression-free interval less than 6 months.
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PMID:Second-line chemotherapy with docetaxel and carboplatin in paclitaxel and platinum-pretreated ovarian, fallopian tube, and peritoneal cancer. 2138 Jul 84