Annals of Oncology 2005 16(8):1215; doi:10.1093/annonc/mdi297
© 2005 European Society for Medical Oncology
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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.
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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.
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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.
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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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Quote
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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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Anti-obesity drug orlistat...
Mucinous histology predicts...