WNT1 (wingless-type MMTV integration site family, member 1)

Review on WNT1, with data on DNA/RNA, on the protein encoded and where the gene is implicated

The evolving role of oestrogen receptor beta in clinical breast cancer

Controversy surrounds the potential clinical importance of oestrogen receptor (ER)β in breast cancer, and three recent papers have sought to resolve this. In the present issue of Breast Cancer Research Novelli and colleagues explored the significance of ERβ1 expression in 936 breast cancer patients, and they showed diverse relationships according to lymph node status. A second paper examined 442 breast cancers in which ERβ1 was an independent predictor of recurrence, disease-free survival and overall survival. Finally a third paper showed that ERβ2 was a powerful prognostic indicator in 757 breast cancers but this was dependent on cellular location, with nuclear ERβ2 expression predicting good survival whilst cytoplasmic expression predicted worse outcome. These papers point to a clinical role for ERβ in breast cancer and shall be discussed

The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis

To study the influence of microwave induced thermo-chemotherapy on high-grade urothelial cell carcinomas. Five groups of each three patients were formed of whom initial biopsies and cystectomy samples were collected. Patients were treated 2 days prior to cystectomy with mitomycin-C (group 1), hyperthermia (group 2) or thermo-chemotherapy (group 3). Group 4 patients had been treated with a cycle of six thermo-chemotherapy treatments prior to cystectomy and group 5 patients served as control (no treatment). Tumour samples were stained with Haematoxylin and Eosin, monoclonal antibody Ki-67 and the monoclonal antibody p53. In six out of the nine patients treated with hyperthermia a decrease in proliferation activity in the tumour was found. Seven out of nine patients treated with hyperthermia showed a decrease in p53 activity. A decrease in proliferation activity and p53 activity illustrate the potential role of thermo-chemotherapy as a promising intravesical treatment

The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis

To study the influence of microwave induced thermo-chemotherapy on high-grade urothelial cell carcinomas. Five groups of each three patients were formed of whom initial biopsies and cystectomy samples were collected. Patients were treated 2 days prior to cystectomy with mitomycin-C (group 1), hyperthermia (group 2) or thermo-chemotherapy (group 3). Group 4 patients had been treated with a cycle of six thermo-chemotherapy treatments prior to cystectomy and group 5 patients served as control (no treatment). Tumour samples were stained with Haematoxylin and Eosin, monoclonal antibody Ki-67 and the monoclonal antibody p53. In six out of the nine patients treated with hyperthermia a decrease in proliferation activity in the tumour was found. Seven out of nine patients treated with hyperthermia showed a decrease in p53 activity. A decrease in proliferation activity and p53 activity illustrate the potential role of thermo-chemotherapy as a promising intravesical treatment

A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR)2. A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m−2. A further dose level of 190 mg m−2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m−2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m−2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m−2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m−2 without unacceptable toxicity. The 145 mg m−2 dose level is thus the recommended dose for future study

Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα) expression level in postoperative NSCLC patients who received adjuvant chemotherapy.</p> <p>Methods</p> <p>Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed.</p> <p>Results</p> <p>TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopIIα (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopIIα expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopIIα expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopIIα to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy.</p> <p>Conclusions</p> <p>High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.</p