British journal of cancer
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British journal of cancer · Oct 2005
Biography Historical ArticleSir Richard Doll, epidemiologist - a personal reminiscence with a selected bibliography.
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British journal of cancer · Oct 2005
Under utilisation of the 2-week wait initiative for lung cancer by primary care and its effect on the urgent referral pathway.
The '2-week wait' scheme for referral of patients with cancer to secondary care coincided with the introduction of Department of Health (DoH) Guidelines on referral of patients with suspected lung cancer. The aim of this study was to examine the impact of this process on the urgent referral pathway for lung cancer. Medical records of all patients referred with suspected lung cancer were reviewed for the year prior to introduction of the 2-week wait and DoH guidelines and for the subsequent 24 months. ⋯ The findings of this study suggest that this is partly due to continued usage of urgent referral routes outside the 2-week wait scheme and secondly due to a large increase in referrals, probably generated by the introduction of the DoH guidelines. Some adjustment to the guidelines may be appropriate to reflect more emphasis on the early performance of a chest X-ray and the use of direct access to other imaging modalities such as CT. Patients referred outside the 2-week wait are disadvantaged and thus practitioners would be wise to refer all their patients through the 2-week wait system.
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British journal of cancer · Sep 2005
Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.
Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. ⋯ Anticipating an earlier than ideal point along the drug approval path and the use of not fully validated surrogate end points in nonrandomised trials looks like a dangerous shortcut that might jeopardise consumers' health, leading to unsafe and ineffective drugs being marketed and prescribed. The present Note for Guidance for new anticancer agents needs revising. Drugs must be rapidly released for patients who need them but not be at the expense of adequate knowledge about the real benefit of the drugs.
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British journal of cancer · Aug 2005
Angiotensin II directly induces muscle protein catabolism through the ubiquitin-proteasome proteolytic pathway and may play a role in cancer cachexia.
The ability of angiotensin I (Ang I) and II (Ang II) to induce directly protein degradation in skeletal muscle has been studied in murine myotubes. Angiotensin I stimulated protein degradation with a parabolic dose-response curve and with a maximal effect between 0.05 and 0.1 microM. The effect was attenuated by coincubation with the angiotensin-converting enzyme (ACE) inhibitor imidaprilat, suggesting that angiotensin I stimulated protein degradation through conversion to Ang II. ⋯ Protein degradation induced by Ang II was inhibited by insulin-like growth factor and by the polyunsaturated fatty acid, eicosapentaenoic acid. These results suggest that Ang II has the potential to cause muscle atrophy through an increase in protein degradation. The highly lipophilic ACE inhibitor imidapril (Vitortrade mark) (30 mg kg(-1)) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model.
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British journal of cancer · Aug 2005
The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers.
There is increased incidence of microsatellite instability (MSI) in patients who develop multiple primary colorectal cancers (CRC), although the association with hereditary nonpolyposis colon cancer (HNPCC) is unclear. This study aims to evaluate the underlying genetic cause of MSI in these patients. Microsatellite instability was investigated in 111 paraffin-embedded CRCs obtained from 78 patients with metachronous and synchronous cancers, and a control group consisting of 74 cancers from patients with a single CRC. ⋯ Methylation was identified in 11 out of 17 (65%) multiple and three out of six (50%) single MSI-H cancers that failed to express MLH1. Mutational analysis of 10 MSI-H multiple cancers that expressed MLH1, MSH2 and MSH6 failed to demonstrate mutations in the MLH1 or MSH2 genes. We suggest that, although MSI-H is more commonly identified in those with multiple colorectal cancers, this does not commonly arise from a classical HNPCC pathway.