Vitamin D and prostate cancer prognosis: a Mendelian randomization study

Purpose

Decreased vitamin D levels have been associated with prostate cancer, but it is unclear whether this association is causal. A functional single-nucleotide polymorphism (SNP) in the group-specific component (GC) gene (T > G, rs2282679) has been associated with 25-hydroxy (25-OH) vitamin D and 1.25 dihydroxy (1.25-OH2) vitamin D levels.

Methods

To examine the hypothesized inverse relationship between vitamin D status and prostate cancer, we studied the association between this SNP and prostate cancer outcome in the prospective PROCAGENE study comprising 702 prostate cancer patients with a median follow-up of 82 months.

Results

GC rs2282679 genotypes were not associated with biochemical recurrence [hazard ratios (HR) 0.91, 95 % confidence interval (CI) 0.73–1.12; p = 0.36], development of metastases (HR 1.20, 95 % CI 0.88–1.63; p = 0.25) or overall survival (HR 1.10; 95 % CI 0.84–1.43; p = 0.50).

Conclusions

A causal role of vitamin D status, as reflected by GC rs2282679 genotype, in disease progression and mortality in prostate cancer patients is unlikely.

     

Gene expression in bipolar disorder and schizophrenia: new approaches to old problems

Bahn S. Gene expression in bipolar disorder and schizophrenia: new approaches to old problems. Bipolar Disord 2002: 4(Suppl. 1): 70–72. © Blackwell Munksgaard, 2002     

Randomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer - EORTC 08062

Purpose

The EORTC 08062 phase II randomised trial investigated the activity and safety of single agent amrubicin, cisplatin combined with amrubicin, and cisplatin combined with etoposide as first line treatment in extensive disease (ED) small cell lung cancer (SCLC).

Patients and methods

Eligible patients with previously untreated ED-SCLC, WHO performance status (PS) 0–2 and measurable disease were randomised to 3 weekly cycles of either amrubicin alone 45 mg/m² i.v. day(d) 1–3 (A), cisplatin 60 mg/m² i.v. d1 and amrubicin 40 mg/m² i.v. d1–3 (PA), or cisplatin 75 mg/m² i.v. d1 and etoposide 100 mg/m² d1, d2–3 i.v./po (PE). The primary end-point was overall response rate (ORR) as assessed by local investigators (RECIST1.0 criteria). Secondary end-points were treatment toxicity, progression-free survival and overall survival.

Results

The number of randomised/eligible patients who started treatment was 33/28 in A, 33/30 in PA and 33/30 in PE, respectively. Grade (G) ?3 haematological toxicity in A, PA and PE was neutropenia (73%, 73%, 69%); thrombocytopenia (17%, 15%, 9.4%), anaemia (10%, 15%, 3.1%) and febrile neutropenia (13%, 18%, 6%). Early deaths, including treatment related, occurred in 1, 3 and 3 patients in A, PA and PE arms, respectively. Cardiac toxicity did not differ among the 3 arms. Out of 88 eligible patients who started treatment, ORR was 61%, (90% 1-sided confidence intervals [CI] 47–100%), 77% (CI 64–100%) and 63%, (CI 50–100%) for A, PA and PE respectively.

Conclusion

All regimens were active and PA met the criteria for further investigation, despite slightly higher haematological toxicity.     

Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates

Purpose  

To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates.     

Dose-intensified epirubicin versus standard-dose epirubicin/cyclophosphamide followed by CMF in breast cancer patients with 10 or more positive lymph nodes: Results of a randomised trial (GABG-IV E-93) – The German Adjuvant Breast Cancer Group

To compare dose-intensified epirubicin monotherapy with a standard sequential regimen, patients with primary breast cancer and ?10 involved axillary nodes were randomised to either four 21-day cycles of epirubicin 120 mg/m² (E120; n = 202) or four 21-day cycles of epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² (EC) followed by three 28-day cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF; n = 209). Simultaneous hormonal treatment was applied in both arms. At 5 years’ median follow-up, the 5-year event-free survival (EFS) rates were 47.7% (95% confidence interval [CI], 40.2–55.2%) for E120 and 45.9% (38.5–53.3%) for EC-CMF. E120 was as effective as EC-CMF with regard to EFS (hazard ratio [HR] for E120 versus EC-CMF 1.04; 95% CI, 0.79–1.36; p = 0.79) and overall survival (HR 1.06; 95% CI 0.77–1.46; p = 0.72). The data demonstrate that 4 cycles of dose-intensified epirubicin monotherapy can be as effective as 7 cycles of standard sequential polychemotherapy in high-risk breast cancer patients with ?10 positive lymph nodes, despite treatment with a single agent and a shorter treatment duration.     

EpCAM-autoantibody levels in the course of disease of ovarian cancer patients

EpCAM is a tumor-associated antigen, which is frequently expressed in ovarian cancer. Recently, autoantibodies against EpCAM have been identified in patients with ovarian cancer. It is not clear whether these autoantibodies are of prognostic importance. We evaluated whether EpCAM-autoantibodies have an impact on the clinical course of patients with ovarian cancer. EpCAM-autoantibodies were determined in sera of 28 healthy voluntary age-matched women and 84 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-protein for antibody detection by ELISA technique. The median follow-up time was 18 months. Samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. The antibody titer of healthy controls was 0.061 ± 0.015. Using a cut-off value of 0.091, we found 3/84 (4%) patients before and 12/61 (20%) patients with ovarian cancer to be positive for EpCAM-autoantibodies after first-line treatment. Using the paired T-Test, we noted a significant post-therapeutic increase of AABs (P < 0.0001). Notably, AAB-levels after first-line therapy were found to be correlated with the tumor resection status in primary surgery. Analysis of progression-free survival, FIGO stage, grading, age and sensitivity to platinum-based chemotherapy did not reveal significant associations with EpCAM-AAB titers. We observed an increase in AAB-levels during the first-line treatment of patients with ovarian cancer. EpCAM-AAB-levels after first-line treatment appear to correlate with macroscopic tumor residuals after initial surgery.     

Oxytocin attenuates amygdala responses to emotional faces regardless of valence.

BACKGROUND: Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS: In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS: Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS: Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.