Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

The RECIST criteria compared to conventional response evaluation after peptide receptor radionuclide therapy in patients with neuroendocrine neoplasms

Annals of Nuclear Medicine - The Response Evaluation Criteria In Solid Tumors (RECIST) is the most used radiological method for evaluating response after peptide receptor radionuclide therapy...     

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography

Transforaminal injections are sometimes used for the diagnosis and treatment of painful conditions in the lumbar and to a lesser degree in the cervical spine. The technique is most often used when investigating/treating radiculopathy caused by degenerative disease. But how selective are the nerve root blocks? What possible structures other than the intended nerve root are affected from such injections? This study was undertaken in order to try to answer these questions, as no study focusing on the possible spread from the transforaminal selective nerve root blocks in the cervical spine has been performed earlier. In three groups of patients, each group including three patients, we injected three different volumes (0.6, 1.1 and 1.7 ml) with a transforaminal technique in the cervical spine. In all the injections, a small amount of contrast media was added. The spread of the injections were then investigated using multi-slice computed tomography with reconstructions. The imaging revealed a possible effect on other nerve roots than the intended ones when a larger volume was used for the root blocks. The spread was related to the injected volume as well as to local anatomy (size of foraminal area). In this study, only 0.6-ml injections could be accepted for being selective enough for diagnostic investigations.     

Renal growth after neonatal urinary tract infection

This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.     

5-HT-receptor-induced changes of the intracellular cAMP level monitored by a hyperpolarization-activated cation channel

The HvCNG channel from the moth Heliothis virescens is highly sensitive to cAMP concentrations ranging between 0.1 microM and 5 microM. This HvCNG channel was over-expressed in Spodoptera frugiperda (Sf.9) cells to measure endogenous cAMP levels. Hyperpolarization-activated inward currents were measured in the whole-cell patch-clamp configuration with pipettes filled with different cAMP concentrations to calibrate the system. Varying the cAMP concentration between 0 microM and 100 microM in the pipette, the half-maximal activation voltage ( V1/2) was shifted by +28.5+/-1.7 mV. The activation time constant (tau(a)) was used as a parameter for cAMP quantification because it was independent of the expression level of HvCNG channels. tau(a) changed from 1106+/-60 ms at 0 microM cAMP to 265+/-7 ms at a saturating concentration of 1 mM cAMP. A dose-response relationship yielded values of 0.6 microM for the half-maximal cAMP concentration and 1.5 for the Hill coefficient. Activation of endogenous adenylyl cyclases by 50 microM forskolin induced an elevation of the cAMP level by about 1.6+/-0.2 microM. Co-expressions of HvCNG channels in combination with the mouse 5-HT4a- or 5-HT1A- receptors and the corresponding Gs- or Gi-proteins were successful and allowed us to also verify receptor-induced changes of the cAMP level. Stimulation of m5-HT4a-receptors by 0.1 microM 5-HT induced an increase of cAMP of about 4.6+/-1.5 microM, whereas cAMP levels decreased from a control value of 1+/-0.2 microM to 0.41+/-0.1 microM after stimulation of the m5-HT1A-receptors.