Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the study was to evaluate the safety, pharmacokinetics, and antitumor activity of ispinesib, a kinesin spindle protein inhibitor. Patients with locally advanced or metastatic breast cancer who had received only prior neoadjuvant or adjuvant chemotherapy were treated with escalating doses of ispinesib administered as a 1-h infusion on days 1 and 15 every 28 days until toxicity or progression of disease. Doses were escalated until dose-limiting toxicity was observed in two out of six patients during cycle 1. A total of 16 patients were treated at three dose levels: 10 mg/m (n=3), 12 mg/m (n=6), and 14 mg/m (n=7). Forty-four percent of the patients had locally advanced disease and 56% had metastatic disease; 50% were estrogen receptor positive, 44% were progesterone receptor positive, 25% human epidermal growth factor 2 were positive, and 31% triple (estrogen receptor, progesterone receptor, human epidermal growth factor 2) negative. Sixty-nine percent of patients were chemo-naive. The maximum tolerated dose was 12 mg/m and dose-limiting toxicity was grade 3 increased aspartate aminotransferase and alanine aminotransferase. The most common toxicities included neutropenia (88%; 38% grade 3 and 44% grade 4), increased alanine aminotransferase (56%), anemia (38%), increased aspartate aminotransferase (31%), and diarrhea (31%). No neuropathy, mucositis, or alopecia was reported. Among the 15 patients evaluable for antitumor activity, there were three partial responses, one confirmed by the response evaluation criteria in solid tumors (7% response rate). Nine patients (60%) had stable disease lasting at least 42 days, with four (27%) lasting for at least 90 days. Disease stabilization (partial responses+stable disease) was observed in 11 (73.3%) patients. In conclusion, ispinesib was well tolerated when administered on days 1 and 15 every 28 days. Limited activity was observed with this schedule in patients with previously untreated advanced breast cancer.
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PMID:Phase I dose-escalation and pharmacokinetic study of ispinesib, a kinesin spindle protein inhibitor, administered on days 1 and 15 of a 28-day schedule in patients with no prior treatment for advanced breast cancer. 2212 35

We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein. No remarkable irritation was observed at the site of injection. NOMAC-MS treatment significantly reduced the volume of the endometrial autografts, decreased serum levels of estradiol, progesterone, triiodothyronine, and alanine aminotransferase, and decreased levels of estrogen receptor alpha protein. Furthermore, NOMAC-MS at the highest dose significantly reduced serum aspartate aminotransferase and endometrial antibody, reduced the Bcl-2/Bax protein ratio, and increased caspase-3 and caspase-9 proteins. There was no pronounced difference observed in alkaline phosphatase, carbohydrate antigen 125, progesterone receptor, or vascular endometrial growth factor receptor 2 (VEGFR2) in any of the tested groups relative to the control. NOMAC-MS significantly changed the expression of apoptotic protein only at the highest dose. Our findings warrant the further investigation of sustained application of steroid hormone via microspheres for the treatment of endometriosis.
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PMID:Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis. 2520 Nov 68

We describe a 39-year-old woman with metastatic breast cancer who had grade 4 epistaxis induced by bevacizumab. The patient visited our outpatient clinic with complaints of a lump in her right breast, fatigue, dyspnea, abdominal distention, appetite loss, and weight loss of 10 kg over 1 year. Liver dysfunction was detected, with elevated levels of aspartate aminotransferase (271 IU/L), alanine aminotransferase (100 IU/L), alkaline phosphatase (4,205 IU/L), total bilirubin (2.7 mg/dL), and direct bilirubin (2.1 mg/dL). A secondary liver tumor that occupied most of the liver volume was found, and bone metastasis, ascites, and pleural effusion were also discovered. The Eastern Cooperative Oncology Group performance status was 2. A core needle biopsy of the right breast tumor revealed invasive ductal carcinoma of the breast (nuclear grade 1) that was positive for estrogen receptor and progesterone receptor and negative for human epidermal growth factor receptor 2 overexpression and had a high Ki-67 score. We chose combination chemotherapy with paclitaxel (80 mg/m(2) on days 1, 8, and 15) and bevacizumab (10 mg/kg on days 1 and 15) for 28 days (1 cycle). After completion of the first cycle of chemotherapy, the ascites and pleural effusion decreased, and the metastatic liver tumor shrank. The performance status improved from 2 to 1. On day 3 of the third cycle of chemotherapy, however, she began having persistent epistaxis. On day 6, she lost consciousness and was transported to the emergency room of our hospital. The hemoglobin level was 5.6 g/dL. Blood transfusion and endoscopic hemostasis were immediately started. Bevacizumab was discontinued, and paclitaxel alone was continued; after this change, epistaxis did not recur.
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PMID:Grade 4 epistaxis in a woman with metastatic breast cancer treated with bevacizumab: a case report. 2539 3