European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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Many different schedules are used world wide for radiotherapy (RT) of metastatic spinal cord compression (MSCC). Non-small cell lung cancer (NSCLC) patients have an extraordinarily poor survival prognosis and would benefit from a short overall treatment time. This retrospective study compares short-course RT (1 x 8 Gy/1 day, 5 x 4 Gy/1 week) and long-course RT (10 x 3 Gy/2 weeks, 15 x 2.5 Gy/3 weeks, 20 x 2 Gy/4 weeks) for functional outcome in 252 NSCLC patients developing MSCC. ⋯ In the short-course RT group, functional outcome was similar for 1 x 8 Gy and 5 x 4 Gy (P=0.94). Short-course and long-course RT appear similarly effective for MSCC in NSCLC patients. As 1 x 8 Gy and 5 x 4 Gy showed comparable results, 1 x 8 Gy can be considered appropriate.
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In vitro and in vivo studies have demonstrated inhibition of glioblastoma growth by imatinib mesylate (Gleevec). Imatinib is an inhibitor of the tyrosine kinase activities of platelet-derived growth factor receptor (PDGF-r), which is involved in glioblastoma aggressiveness. ⋯ Furthermore, strong correlations between cellular 99mTc-(V)-DMSA uptake and the effect of imatinib therapy on U87-MG proliferation (r=0.896), invasion (r=0.621) and migration (r=0.822) were obtained, likewise for 99mTc-(V)-DMSA uptake and PDGF-r expression (r=0.958). Our results show that the biological effects of imatinib therapy on tumour cells properties are linked to PDGF-r phosphorylation and could be traced with 99mTc-(V)-DMSA, which also seems to be a potential tracer to evaluate the response to imatinib therapy in glioblastoma.
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Pathological mutations in BRCA1, BRCA2 and TP53 are associated with an increased risk of breast cancer. This study evaluated mutation frequency of these genes in early-onset breast cancer patients, and correlated this with family history and determined relative risks to family members. Patients with breast adenocarcinoma diagnosed 30 years were ascertained between 1980 and 1997. ⋯ Relative risks associated with mutations were consistent with previous studies. BRCA1 and BRCA2 mutations in patients with breast cancer 30 years are predicted strongly by family history. The majority of families with ovarian cancer were due to mutations in BRCA1/2 whereas these mutations only accounted for 30-50% of the excess breast cancers.
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Multicenter Study
The association between Akt activation and resistance to hormone therapy in metastatic breast cancer.
In this retrospective study, the relationship between Akt activation and the efficacy of endocrine therapy for metastatic breast cancer was investigated. Thirty-six metastatic breast cancer patients, treated with endocrine therapy, were evaluated for the activation of Akt by an immunohistochemical assessment of the expression of phosphorylated Akt at Ser 473 (pAkt). The relationship between the efficacy of endocrine therapy and Akt activation, HER2 status and hormone receptor expression was also investigated. ⋯ These findings, therefore, suggest that Akt activation induces endocrine resistance in metastatic breast cancer, irrespective of the kind of endocrine agents that were administered. Our findings suggest that the activation of Akt in the downstream pathway of HER2 plays an important role in the resistance to endocrine therapy for breast cancer. Although our study was small in scope and retrospective in design, our findings suggest that pAkt may be a useful predictor of resistance to endocrine therapy for breast cancer, while also suggesting that the inhibition of Akt may increase the efficacy of endocrine therapy.
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In the European Union (EU) 20 anticancer agents have been successfully authorised via the Centralised Procedure since its implementation in 1995. Public information on these 20 agents has been reviewed in order to evaluate the effectiveness of the available regulatory mechanisms to facilitate the marketing authorisation of such drugs in the EU. These mechanisms include orphan drug legislation, exceptional circumstances provision and the accelerated evaluation procedure. ⋯ However, this mechanism does not influence the administrative time at the authorities, which accounted for almost one-third of the overall duration of the EU marketing authorisation procedures for oncology drugs. Revision of the EU drug legislation brings about some changes to the above-described provisions, with the potential for an improvement in the current situation. Thus, its implementation offers the chance to reduce the time that innovative oncology agents take to reach the market, although -- based on experience with the current procedures -- more effort is likely to be required to achieve this goal.