Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Docetaxel is a semisynthetic taxane that acts by binding to the beta-tubulin subunit of the microtubules, resulting in cell-cycle arrest and apoptosis. It is approved for the management of early and advanced breast cancer, locally advanced and metastatic lung cancer and hormone refractory prostate cancer. Docetaxel has also shown significant antitumor activity in ovarian and gastric tumors and has very recently been approved for the treatment of advanced gastric cancer. Severe neutropenia is the major dose-limiting toxicity with the approved three-weekly regimens, although alternate weekly schedules with less myelotoxicity have been developed for patients with poor bone marrow reserve. This article will review the pharmacology and trials leading to the clinical approval of this agent.
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PMID:Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. 1670 23

Phaeoacremonium parasiticum is an agent of opportunistic phaeohyphomycosis belonging to a genus encompassing numerous recently described and soon-to-be-described, difficult-to-identify human pathogens. It appears in the literature to be an uncommon etiologic agent, yet we encountered several cases in a single year. Each presented problems in laboratory identification and case management. We present two cases of invasive disease with definite identification and susceptibility results. These cases are analyzed in relation to a brief review of previous cases known to have been caused by this species. Our first case involved a 40-year-old male cardiac transplant recipient with multiple localized skin lesions. The second featured a 31-year-old female with aplastic anemia and prolonged neutropenia who developed disseminated disease, with multiple positive blood cultures and skin lesions. Both patients died despite aggressive surgical and antifungal therapy. Fungal susceptibility testing showed that our isolates appeared to be susceptible to amphotericin B, itraconazole, voriconazole, ravuconazole, and posaconazole. Because phenotypic identification of Phaeoacremonium is notably problematic, sequence-based confirmation was performed using a recently proposed standard based on use of a segment of the 5' end of the beta-tubulin gene. Sequences from both isolates involved in the cases were over 99% similar to the corresponding sequence of the ex-type isolate of P. parasiticum. The close DNA similarity, corroborated by relevant morphological similarities (e.g., long, thin phialides and tuberculate hyphae bearing warts up to 3 mum high), confirms these two isolates as P. parasiticum.
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PMID:Phaeoacremonium parasiticum infections confirmed by beta-tubulin sequence analysis of case isolates. 1675 22

Patients with advanced or metastatic breast cancer commonly develop disease resistant to chemotherapy (typically anthracyclines and taxanes), which presents a major obstacle to therapy and leaves few effective treatment options. Drug resistance can occur due to various mechanisms including modification of drug efflux membrane transporters such as P-glycoprotein, as well as alterations in beta-tubulin. The novel epothilone B analog, ixabepilone, which has low susceptibility to various drug-resistance mechanisms, has demonstrated preclinical activity in drug-resistant breast cancer. The clinical activity of ixabepilone was evaluated in metastatic breast cancer patients with highly pretreated and/or resistant/refractory disease. Results were reviewed from three phase II trials in which ixabepilone was administered as monotherapy and one phase III trial that evaluated ixabepilone in combination with capecitabine. As a single agent, ixabepilone demonstrated activity in women who were heavily pretreated and resistant to an anthracycline, a taxane, and/or capecitabine. The combination of ixabepilone and capecitabine was significantly more active than capecitabine alone in patients with prior treatment or resistance to anthracyclines and taxanes. Treatment-related adverse events were generally low grade except for grade 3/4 toxicities, including neutropenia (53-54%) and reversible peripheral sensory neuropathy (14-16%). Ixabepilone has significant activity in patients with heavily pretreated metastatic breast cancer who are disease resistant or refractory to anthracyclines and taxanes. Further clinical evaluation of this agent in patients with drug-resistant breast cancer and in specific patient subsets is warranted.
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PMID:Implications of anthracycline-resistant and taxane-resistant metastatic breast cancer and new therapeutic options. 2040 28