Search

Introduction: The basaloid triple-negative breast cancer (B-TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Current models do not recapitulate the basaloid phenotype of TNBC, thus limiting the understanding of its biology and designing new treatments. We identified HCC1806 as a line expressing typical B-TNBC markers, engineered a subline with traceable reporters, and determined growth, drug sensitivity, recurrence, and vascular and metastatic patterns of orthotopic xenografts in immunodeficient mice. Methods: mRNA and protein analyses showed that HCC1806 expresses basal but not luminal or mesenchymal markers. HCC1806-RR subline stably expressing red fluorescent protein and Renilla luciferase was generated and characterized for sensitivity to chemodrugs, orthotopic growth, vascular properties, recurrence, metastasis, and responsiveness in vivo . Results: The HCC1806 cells were highly sensitive to paclitaxel, but cytotoxicity was accompanied by pro-survival vascular endothelial growth factor-A loop. In vivo , HCC1806-RR tumors display linear growth, induce peritumoral lymphatics, and spontaneously metastasize to lymph nodes (LNs) and lungs. Similarly to human B-TNBC, HCC1806-RR tumors were initially sensitive to taxane therapy but subsequently recur. Bevacizumab significantly suppressed recurrence by 50% and reduced the incidence of LN and pulmonary metastases by, respectively, 50% and 87%. Conclusions The HCC1806-RR is a new model that expresses bona fide markers of B-TNBC and traceable markers for quantifying metastases. Combination of bevacizumab with nab-paclitaxel significantly improved the outcome, suggesting that this approach can apply to human patients with B-TNBC. This model can be used for defining the metastatic mechanisms of B-TNBC and testing new therapies.

In this study, the rostro-caudal localization of the perikaryons of the intermedio-lateral nucleus (ILN), examination of the cytoarchitectonics and measurement of the short diameters of the cells are measured. For this purpose, serial transverse sections 6 cats and serial sagittal sections 2 cats of the spinal cord were stained with Kluver-Barrera; the Golgi-Cox method was also used (2 cats). Results were as follows : 1) The ILN neurons were found to extend from C_8 to L_4. 2) The cells in the ILN were grouped rostro-caudally (i.e. longitudinally) especially those in the T_2,T_3 and T_5-T_10 segments. 3) The cells in the ILN could be classified into three types : A) multipolar large cells : about 30μ. B) small round cells : about lOμ. C) spindle form cells : 10-30μ. 4) No difference in cell number between each half of the neurons could be observed. 5) The total neuron number ranged from 10,000 to 17,000 in each half. 6) The average number of neurons in one segment was about 700.