Adjuvant treatment of high-risk stage II breast cancer with doxorubicin followed by high-dose chemotherapy and autologous stem-cell transplantation: a single-institution experience with 132 consecutive patients

Several studies have shown conflicting results with the use of intensive consolidation chemotherapy for breast cancer. The aim of the present study was to investigate the efficacy, feasibility and toxicity of high-dose chemotherapy with stem cell support in patients with high-risk stage II breast cancer. From February 1994 to November 1998, 132 consecutive patients with multinode positive breast cancer were entered to the study. In total, 86 patients had >or=10 positive axillary lymph nodes, and 46 had 4-9 positive axillary lymph nodes with at least two additional predetermined risk factors at diagnosis. All patients were offered adjuvant chemotherapy (doxorubicin, 75 mg/m(2) x 4) followed by high-dose chemotherapy (cyclophosphamide 6000 mg/m(2), carboplatin 800 mg/m(2) and thio-tepa 500 mg/m(2)) and autologous stem cell support with growth factor. In all, 131 patients also received local radiation therapy and tamoxifen based on receptor status. After a median follow-up of 51 months (range 27-87), the disease-free and overall survival rates were 72 and 81%, respectively. There was no difference in the outcome for high-risk patients with > or < than 10 positive axillary lymph nodes. On Cox regression analysis only progesterone receptor status was predictive of disease-free, but not overall survival. There were no treatment-related deaths; grades III-IV toxicity was relatively low. This combined approach of doxorubicin followed by high-dose chemotherapy and stem-cell support, followed by locoregional radiotherapy, was safe and seems to be effective in patients with multinode positive stage II breast cancer. In previous trials of adjuvant high-dose therapy in this patient population, treatment-related morbidity and mortality markedly influenced the outcome. For this high-risk patient population, further testing of intensive chemotherapy regimens with a lower toxicity profile is warranted.     

Diffused coronary involvement in Takayasu arteritis with concomitant malignancy

Clinical Rheumatology - Large vessel vasculitis (LVV) is composed of conditions in which inflammation of blood vessel walls affects mainly large arteries, such as the aorta and its main branches,...     

Next-generation sequencing in thyroid cancers: do targetable alterations lead to a therapeutic advantage?: A multicenter experience

Radioiodine-refractory thyroid cancers (IRTCs) are uncommon and have a poor prognosis. Treatment options for radioiodine-refractory and anaplastic tumors (ATCs) are limited. Although the genomic landscape of thyroid cancer has been studied, there is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control.We analyzed all patients with IRTC and ATC who underwent commercially available NGS in 3 cancer centers.Twenty-two patients were identified, 16 patients with IRTCs and 6 patients with ATCs. Eighteen (82%) had targetable findings in NGS, nine patients were treated accordingly. Median progression-free survival for targeted treatment was 50 months [95% confidence interval (CI95%) 9.8–66.6] and2 months (CI95% 0.2–16.5) for IRTC and ATC, respectively. Of 4 patients who achieved durable responses of 7 to 50 months, 2 are ongoing. The estimated median OS of IRTC receiving targeted treatment was not reached (CI95% 89.7–111.4 months) and was 77.8 months (CI95% 52.5–114.6) for patients treated conventionally (P = .3).NGS may detect clinically significant genetic alterations and benefit patients with advanced thyroid cancers.     

Increase of Cholesterol Level in the Surface Membrane of Lymphoma Cells and Its Inhibitory Effect on Ascites Tumor Development

An ascites form of malignant transformed lymphoma cells were treated in vitro with liposomes of 1:1 lecithin-cholesterol in order to increase the cholesterol level of the cell-surface membranes and thereby to increase the rigidity of the lipid layer. This treatment was found to inhibit the rate of killing by ascites tumor after intraperitoneal inoculation into adult mice of 10(4) and 10(5) treated cells per animal. With 10(3) treated cells per animal, full survival was observed up to 90 days after inoculation, whereas with the same number of untreated cells all infected mice died within 30 days after inoculation. An analogous treatment of the malignant lymphoma cells with liposomes of pure lecithin did not result in any appreciable inhibitory effect on the ascites tumor development in vivo, as initiated by inoculation of 10(5), 10(4), or 10(3) cells per animal.     

The influence of the sequential delivery of angiogenic factors from affinity-binding alginate scaffolds on vascularization

This study describes the features of tissue-engineering scaffold capable of sequentially delivering three angiogenic factors. The scaffold consists of alginate-sulfate/alginate, wherein vascular endothelial growth factor (VEGF) platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) are bound to alginate-sulfate with an affinity similar to that realized upon their binding to heparin. Factor release rate from the scaffold was correlated with the equilibrium binding constants of the factors to the matrix, thus enabling the sequential delivery of VEGF, PDGF-BB and TGF-β1. In alginate scaffolds lacking alginate-sulfate, release of the adsorbed proteins was instantaneous. After subcutaneous implantation for 1 and 3 months in rats, the blood vessel density and percentage of mature vessels were 3-fold greater in the triple factor-bound scaffolds than in the factor-adsorbed or untreated scaffolds. Moreover, vascularization within the triple factor-bound scaffolds was superior to that found in scaffolds delivering only basic fibroblast growth factor. Application of this novel scaffold may be extended to the combined delivery of additional heparin-binding angiogenic factors or combinations of growth factors active in different tissue regeneration processes.     

Does power indicate capacity? 30-s Wingate anaerobic test vs. maximal accumulated O2 deficit

The purpose of this study was to evaluate the relationship between anaerobic power and capacity. Seven men and seven women performed a 30-s Wingate Anaerobic Test on a cycle ergometer to determine peak power, mean power, and the fatigue index. Subjects also cycled at a work rate predicted to elicit 120 % of peak oxygen uptake to exhaustion to determine the maximal accumulated O (2) deficit. Peak power and the maximal accumulated O (2) deficit were significantly correlated (r = 0.782, p = 0.001). However, when the absolute difference in exercise values between groups (men and women) was held constant using a partial correlation, the relationship diminished (r = 0.531, p = 0.062). In contrast, we observed a significant correlation between fatigue index and the maximal accumulated O (2) deficit when controlling for gender (r = - 0.597, p = 0.024) and the relationship remained significant when values were expressed relative to active muscle mass. A higher anaerobic power does not indicate a greater anaerobic capacity. Furthermore, we suggest that the ability to maintain power output during a 30-s cycle sprint is related to anaerobic capacity.