Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article describes the current approach to the systematic management of both small cell and non-small cell lung cancer (NSCLC). The treatment of stages I, II, and IIIa NSCLC is surgical resection. Although adjuvant chemotherapy in stage I disease offers no survival benefit, the role of adjuvant chemotherapy in stage II and IIIa NSCLC remains controversial. Results of pilot studies using neoadjuvant chemotherapy in stage IIIa NSCLC are encouraging and data from ongoing randomized trials are awaited with interest. For locally advanced NSCLC, chest irradiation remains the standard of care. However, the addition of systemic chemotherapy holds promise. The impact of cisplatin-based regimens on overall survival in stage IV NSCLC remains disappointing. The introduction of newer agents, such as 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), a topoisomerase-I inhibitor, has shown early favorable results. Chemotherapy is the most important therapeutic modality in the management of small cell lung cancer because of this cancer's propensity for early dissemination. In limited stage small cell lung cancer, chest radiotherapy, particularly if used early and concurrently with chemotherapy, may improve survival, but at the expense of increased toxicity. The role of prophylactic brain irradiation remains controversial in limited-stage disease. Chemotherapy is also the most important treatment modality in extensive-stage disease, but its role is only palliative. Radiotherapy is reserved primarily for disease-related complications in patients in whom chemotherapy has failed.
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PMID:Lung cancer: a review of current therapeutic modalities. 132 79

Gemifloxacin is a novel antibiotic and the first fluoroquinolone with a pyrrolidine derivative at the C-7 position. Because of the added pyrrolidine substitute, gemifloxacin has an enhanced spectrum of activity against Gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus, in addition to its activity against Gram-negative bacteria. Like other fluoroquinolones, gemifloxacin's mechanism of action focuses on inhibiting DNA gyrase and topoisomerase, thus preventing cellular replication. In addition, in vitro and in vivo data have shown that the compound exhibits excellent activity against Enterobacteriaceae and other respiratory pathogens. Furthermore, it has been demonstrated that gemifloxacin has potential activity in vitro against anaerobic bacteria. With a broad spectrum of activity, convenient once-daily administration, good bio-availability and tolerability, gemifloxacin will be an important addition to our armamentarium against a wide range of infections, from urinary tract infections to community-acquired pneumonia. (c) 2001 Prous Science. All rights reserved.
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PMID:Gemifloxacin. 1276 26

Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4, 5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to topo II inhibitors (adriamycin and etoposide), antimicrotubule agents (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and antifolate (methotrexate). Interestingly, the resistant subline reserved the sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased topo I and II activity compared to the parent cells. The SN-38-resistant cell line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the topo I inhibitors.
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PMID:Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line. 1573 31

Cerebral metastases remain a common complication among patients with cancer. Historically, whole-brain radiotherapy has remained the standard of care, with surgery being reserved for selected cases. Recent advances have changed our practice, however. In particular, stereotactic radiosurgery has emerged as a vital treatment modality for this disease. In addition, chemotherapy, including temozolomide, topoisomerase inhibitors and antimetabolites, and treatment sensitizers, such as efaproxiral and motexafin gadolinium, are actively being assessed in clinical trials, and are likely to play an increasing role in the management of cerebral metastases in the future. Nonetheless, many uncertainties remain, such as the optimal combination and timing of therapeutics. As the arsenal of therapeutics expands, it will be increasingly important to select appropriate patients for a particular treatment paradigm. Understanding the efficacy and toxicity of treatment is essential to this task.
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PMID:Cerebral metastases--a therapeutic update. 1693 1

Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. It is a rare condition that affects mostly young and middle-aged women, resulting in disproportionate morbidity and mortality. Currently, interstitial lung disease is the most common cause of death among patients with systemic sclerosis, with a prevalence of up to 30% and a 10-year mortality of up to 40%. Interstitial lung disease is more common among African Americans and in people with the diffuse cutaneous form of systemic sclerosis or anti-topoisomerase 1 antibodies. Systemic sclerosis-associated interstitial lung disease most commonly presents with dyspnoea, cough, and a non-specific interstitial pneumonia pattern on CT scan, with a minority of cases fulfilling the criteria for usual interstitial pneumonia. The standard therapy has traditionally been combinations of immunosuppressants, particularly mycophenolate mofetil or cyclophosphamide. These immunosuppressants can be supplemented by targeted biological and antifibrotic therapies, whereas autologous haematopoietic stem-cell transplantation and lung transplantation are reserved for refractory cases.
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PMID:Systemic sclerosis-associated interstitial lung disease. 3211 72