Anti-obesity drug orlistat inhibits Her-2/neu
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Orlistat has recently been demonstrated to exhibit antitumor properties towards prostate cancer cells by virtue of its ability to block the lipogenic activity of fatty acid synthase (FAS). FAS is up-regulated in about 50% of breast cancers, is an indicator of poor prognosis, and it has been functionally associated with the Her-2/neu (erbB-2) oncogene.

In this issue, Menendez et al. report on an in vitro study that aimed to assess the antitumor effects of orlistat against the human breast cancer cell line SK-Br3. These authors report that orlistat induces potent anti-proliferative and apoptotic effects in these breast cancer cells through its ability to block the lipogenic activity of FAS. They further demonstrate a close involvement of the Her-2/neu (erbB-2) oncogene. They suggest that more potent and/or bioavailable variants of orlistat targeting the lipogenic activity of FAS may provide a novel therapeutic approach to treating Her-2/neu-overexpressing breast carcinomas.


    Mucinous histology predicts reduced 5-FU responsiveness in advanced CRC
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Mucinous adenocarcinoma is one of the histological subtypes of colorectal cancer (CRC) and accounts for some 5–15% of all primary CRC. While it has been suggested that mucinous adenocarcinoma behaves differently to more common histological subtypes of CRC its clinical implications remain unclear. A poor prognosis has been reported by most studies, but some have failed to show a correlation with prognosis or found a prognostic significance only for certain subgroups. In this issue, Negri et al. report a case-control study that aimed to compare the responsiveness of the mucinous and non-mucinous subtypes of CRC to 5-fluorouracil (5-FU). These authors report that patients with advanced mucinous CRC have a poorer response to 5-FU-based first line chemotherapy and reduced survival compared with patients with non-mucinous CRC.


    Prognosis and treatment in elderly AML
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Epidemiologic studies show that more than half of the patients with acute myeloid leukemia (AML) are older than 60 years. However, due to the selected nature of patients who enter trials, old age patients constitute only about one-third of the total study population in large clinical trials with AML. Accumulating evidence indicates that AML in older patients is biologically different from that in younger patients, and it may be that treatment guidelines and predictive prognostic models for AML patients developed from large randomized trials are inappropriate to the elderly. In this issue, Chen et al. report a study of 205 AML patients aged 65 or above that aimed to analyze the prognostic factors and treatment outcomes for these patients. These authors report finding five poor prognostic factors for overall survival: poor performance status, presence of comorbidities, elevated serum LDH level, extreme leukocytosis, and thrombocytopenia.

Age was not an independent contributing factor either in terms of attaining complete response or duration of overall survival.


    Antimicrobial prophylaxis in allogeneic bone marrow transplantation
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Patients undergoing allogeneic stem cell transplantation are highly susceptible to acquisition and reactivation of infectious diseases. In this issue, Krüger et al., on behalf of the Infectious Diseases Working Party of the German Society of Haematology and Oncology, present their recommendations for the prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. These authors report that the recommendations were prepared according to the principles of evidence-based medicine and they discuss a number of problems arising in the literature that hampered this approach; these include recent changes in the practice of allogeneic stem cell transplantation, the rarity of placebo-controlled trials in this field, and that during the 1990s many clinical trials were not restricted to patients receiving an allograft.


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"These revolting doctors! Businesslike, determined and so ignorant of healing that, if this businesslike determination were to leave them, they would stand at sickbeds like schoolboys."

Franz Kafka records in his diary for 5 March 1912 his thoughts on the medical profession.





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