Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Breast preservation versus mastectomy--recurrence and survival rates of primary breast cancer patients treated at the UFK Bonn.

The aim of this retrospective long-term analysis was to evaluate the approach of breast conservation in the light of the results obtained, on the basis of mastectomy, in patients with early breast carcinoma. Additionally, the effect of internal mammary and supraclavicular radiotherapy was analyzed. Therefore, local-regional recurrence (LRR) and survival rates were examined in 411 patients with T1 and T2 stages who had undergone either breast-preserving surgery with radiation or mastectomy. Individual risk factors such as nodal status, lymphangiosis carcinomatosa and age of the patients were evaluated, too. The rate of local-regional recurrence in patients who were treated by mastectomy and conservative surgery was 9.2% and 11.0%, respectively, with relapse happening earlier in the latter group (median of 16 vs. 24 months). Survival rates, however, were not different in the two groups. Tumour stage and nodal status had no influence on the local-regional recurrence rate in either group. In connection with lymphangiosis carcinomatosa, however, the rate increased to 14.5% (mastectomy) and 19.0% (breast-preserving surgery), respectively. Patients < or = 40 years had an even higher risk of LRR, with 20.6% when they underwent mastectomy and 30.8% following breast conservation. Internal mammary and supraclavicular radiotherapy had no positive effect on the survival rates, neither in the mastectomy nor in the breast conservation group. As a conclusion, in more than 60% of all T1 stages. and more than 50% of all T2 stages, the therapeutic concept of breast preservation seems to be justified.

[Potassium citrate versus potassium chloride in essential hypertension. Effects on hemodynamic, hormonal and metabolic parameters]. / Kaliumcitrat versus Kaliumchlorid bei essentieller Hypertonie. Wirkung auf hämodynamische, hormonelle und metabolische Parameter.

A study was conducted on 25 patients (18 men, seven women; mean age 48 [24-70] years) with essential hypertension (EH) to see whether an increase in potassium supply influences blood pressure as well as metabolic and hormonal parameters, and whether the anion administered together with potassium affects the results. In a randomized, cross-over trial sequence the patients daily received 120 mmol potassium chloride, 120 mmol potassium citrate or a placebo, each for 8 weeks. Between each of the three periods there was a "wash-out" phase of 4 weeks each. After 8 weeks of potassium citrate intake the systolic and diastolic pressures were reduced significantly, by a mean of 6.2/3.8 mm Hg (P < 0.05). But after potassium chloride there was only a small, not significant, reduction. Metabolic and hormonal parameters (fasting glucose concentration, glucose tolerance test, lipid electrophoresis; plasma renin activity, plasma concentration of aldosterone, noradrenaline and insulin) were not significantly changed.--These findings suggest that an increased supply of potassium has a favourable haemodynamic effect, but this varies markedly between different potassium salts. An increase in potassium supply should thus be considered as an additional measure in the treatment of EH. As long as renal function is normal no unfavourable metabolic effect need be feared.