British journal of cancer
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British journal of cancer · Sep 2001
CDKN2A and CDK4 mutation analysis in Italian melanoma-prone families: functional characterization of a novel CDKN2A germ line mutation.
Physical interaction between CDKN2A/p16 and CDK4 proteins regulates the cell cycle progression through the G1 phase and dysfunction of these proteins by gene mutation is implicated in genetic predisposition to melanoma. We analysed 15 Italian melanoma families for germ line mutations in the coding region of the CDKN2A gene and exon 2 of the CDK4 gene. One novel disease-associated mutation (P48T), 3 known pathological mutations (R24P, G101W and N71S) and 2 common polymorphisms (A148T and Nt500 G>C) were identified in the CDKN2A gene. ⋯ No variant in the p16-binding region of CDK4 was identified in our families. Our results, obtained in a heterogeneous group of families, support the view that inactivating mutations of CDKN2A contribute to melanoma susceptibility more than activating mutations of CDK4 and that other genetic factors must be responsible for melanoma clustering in a high proportion of families. In addition, they indicate the need for a combination of functional assays to determine the pathogenetic nature of new CDKN2A mutations.
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British journal of cancer · Aug 2001
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialPharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.
The ATAC trial evaluates in a randomized, double-blind design, Arimidextrade mark (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for > or =3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. ⋯ Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1)prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1)after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together.
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British journal of cancer · Jul 2001
Body surface area estimation in children using weight alone: application in paediatric oncology.
The majority of chemotherapy regimens and trials specify doses of cytotoxic drugs normalized to body surface area. Estimation of BSA in paediatric patients is particularly problematic, as conventional nomograms require accurate determination of both height and weight. The chemotherapy standards group of the UKCCSG (United Kingdom Children's Cancer Study Group) has evaluated a method for calculation of body surface area (BSA) estimation, based solely on patient weight. ⋯ Until better correlates of drug clearance, such as GFR for carboplatin, are identified BSA is used to standardize doses for most chemotherapeutic agents. The formula presented here provides a more robust and reliable method of calculation of BSA from weight alone. Although this approach has been shown to be equivalent to other currently used methods, care should be taken extending this calculation of BSA to children less than 10 kg, to obese patients and to those with cachexia.
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British journal of cancer · Jun 2001
Pathological serosa and node-based classification accurately predicts gastric cancer recurrence risk and outcome, and determines potential and limitation of a Japanese-style extensive surgery for Western patients: a prospective with quality control 10-year follow-up study.
UICC classification accurately predicts overall survival but not recurrence-risk. We report here data of overall and first site-specific recurrence following curative surgery useful for the development of recurrence-oriented preventive target therapies. Patients who underwent resection for gastric cancer were stratified according to curability of surgery [curative (R0) vs non-curative resection], extent of surgery [limited (D1) vs extended (D2) node dissection] and pathological nodal/serosal status. ⋯ First site-specific recurrence analysis revealed: low rate of loco-regional recurrence alone (12%), serosa state determinant factor of the site-recurrence (peritoneal for serosa-positive and haematogenous for serosa-negative cancers) and dramatic increase of all types of recurrence by the presence of nodal metastases. Our findings demonstrate that a pathological serosa- and node-based classification is very simple and predicts accurately site-specific recurrence-risks. Furthermore they reveal that risk of recurrence following curative D2 surgery alone is low for serosa- and node-negative cancers, but very high in serosa- and node-positive cancers suggesting the need for new therapeutic strategies in this subgroup of patients.