Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case review describes a case of a patient, hospitalized with T3N0M1 carcinoma of the splenic flexure, with multiple metastases in the both liver lobes. The patient underwent left-sided hemicolectomy with cholecystectomy. Having considered the inoperable liver findings, a chemoport was implanted. The patient underwent 10 chemotherapy cycles with no major complications recorded. The chemotherapy cycle included Campto, Leucovorin, 5FU and, concomittantly, 5FU as a continual 22-hour infusion into the port. After completion of the Cycle 10, the ultrasound and CT findings showed marked regression of the metastases, by half to two thirds. Following consultation at the onco-surgical seminar, extended left-sided hemihepatectomy was performed. The procedure lasted 6 hours, the blood loss was 3.500 ml, the period of warm ischemia was 8 minutes. Based on the oncologists' recommendation, the chemoport was preserved. The latest abdominal ultrasound detected no focal liver changes, a hypechogenic to unechogenic septed formation, v.s. a postoperative hematoma, was detected near the medial liver margin. Based on the conclusion of the oncological assessment, the patient was indicated for adjuvant chemotherapy, containing the same agents, for a period of 2-3 months. The aim of this report is to present a case of downstaging of the originally inoperable finding of the liver metastases.
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PMID:[An example of the liver metastases downstaging following chemoport implantation]. 1845 43

A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of vorinostat with bevacizumab and CPT-11 in recurrent glioblastoma. Vorinostat was combined with bevacizumab and CPT-11 and was escalated using a standard 3 + 3 design. Vorinostat was escalated up to 2 actively investigated doses of this compound or until the MTD was identified on the basis of DLTs. Correlative science involving proteomic profiling of serial patient plasma samples was performed. Nineteen patients were treated. The MTD of vorinostat was established at 400 mg on days 1-7 and 15-21 every 28 days when combined with bevacizumab and CPT-11. Common toxicities were fatigue and diarrhea. DLTs included fatigue, hypertension/hypotension, and central nervous system ischemia. Although the MTD was established, CPT-11 dose reductions were common early in therapy. High-dose vorinostat had an improved progression-free survival and overall survival when compared with low-dose vorinostat. Serum proteomic profiling identified IGFBP-5 and PDGF-AA as markers for improved PFS and recurrence, respectively. A MTD for the combination of vorinostat with bevacizumab and CPT-11 has been established, although it has poor long-term tolerability. With the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial.
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PMID:Phase I trial of vorinostat combined with bevacizumab and CPT-11 in recurrent glioblastoma. 2202 88

Chemotherapeutic enteritis is a major dose-limiting adverse reaction to chemotherapy, with few effective drugs in clinic. Intestinal ischemic injury plays prominent role in chemotherapeutic enteritis clinically. However, mechanism is not clear. In this article, irinotecan (CPT-11) was used to establish chemotherapeutic enteritis mice model. Western blotting, gelatin zymography, immunohistochemistry (IHC), Laser Doppler flowmetry (LDF) were used to detect the pathogenesis of ischemia-hypoxia injury. CPT-11 increased levels of tissue factor (TF) both in the blood and in intestines, and decreased the intestinal blood flow in mice. Interestingly, the elevation of TF in the blood displayed "double-peak," which was consistent with the intestinal mucosal "double-strike" injury trend. Intestinal microthrombus and mixed thrombus formation were detectable in chemotherapeutic enteritis. Furthermore, ozone therapy relieved chemotherapeutic enteritis in mice. Ozone inhibited TF expression induced by CPT-11 via activating AMPK/SOCS3, and effectively ameliorated the intestinal mucosal injury in mice. Moreover, ozone autotransfusion therapy effectively attenuated chemotherapeutic enteritis and the blood hypercoagulability in patients. For the first time, we proposed that TF-induced thrombotic intestinal ischemic injury is a core trigger pathological mechanism of chemotherapeutic enteritis, and provided a new treatment strategy, ozone therapy, to suppress TF expression and treat chemotherapeutic enteritis.
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PMID:AMPK activation by ozone therapy inhibits tissue factor-triggered intestinal ischemia and ameliorates chemotherapeutic enteritis. 3277 74