The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.

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Purpose Breast cancer subtypes (BCS) determined from IHC staining have been correlated with molecular subtypes and associated with prognosis/outcomes, but there are limited data correlating these BCS and axillary node involvement. This study was conducted to assess whether BCS predicted for nodal metastasis or was associated with other clinical-pathologic features at presentation. Methods Stage I/II patients who underwent breast-conserving surgery and axillary surgical assessment with available tissue blocks underwent a institutional pathological review and construction of a tissue microarray(TMA). The slides were stained for ER/PR/HER2-neu for classification into BCS. Nodal involvement and other clinical-pathologic features were analyzed to assess associations between BCS and patient/tumor characteristics. Outcomes were calculated a function of BCS. Results The study cohort consisted of 453 patients(LA 48.6%, LB 16.1%, HER2 11.0%, TN 24.2%), of which 22%(n=113) were node+. There were no significant associations with BCS and pN stage, node positivity, or absolute number of nodes involved (all p>0.05). However, there were significant associations with subtype and age at presentation (< 0.001), method of detection (p=0.049), tumor histology (p<0.001), race (p=0.041), and tumor size (pT stage, p<0.001) by univariate and multivariate analysis. As expected, 10-year outcomes differed by BCS, with TN & HER2/neu subtypes having the worse overall(p=0.03), disease-free(p=0.03) and distant metastasis-free survival(p< 0.01). Conclusions Our findings suggest that there is a significant association between BCS and age, T stage, histology, method of detection and race, but no associations to predict nodal involvement. If additionally validated, these findings suggest that BCS should not strongly influence regional management considerations.

Breast-conserving surgery followed by radiation therapy has become the standard of care for early stage breast cancer. However, there are some patients that develop a local failure. We have previously shown that Bcl-2 overexpression was associated with an increased risk of local recurrence in patients with early stage breast cancer. The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. siRNAs were employed to silence myeloid cell leukemia 1 (Mcl-1). A small molecule inhibitor of Bcl-2, ABT-737, was used to target anti-apoptotic Bcl-2 family proteins. Apoptosis was identified by FITC Annexin V, PI staining and Western blot analysis. The sensitivity to ionizing radiation and ABT-737 were measured by clonogenic assays. The effect of radiation and ABT-737 was also tested in a MCF-7 xenograft mouse model. Our data demonstrate that the combination of ABT-737 and radiation-induced apoptosis had an inhibitory effect on breast cancer cell proliferation. However, treatment with ABT-737 resulted in elevated Mcl-1 in breast cancer cell lines. Targeting Mcl-1 by siRNA sensitized MCF-7 cells to ABT-737. We revealed that radiation blunted Mcl-1 elevation induced by ABT-737, and that radiation downregulated Mcl-1 by promoting its degradation. Our results indicate that radiation and ABT-737 exert a synergistic effect on breast cancer cell lines through downregulating Mcl-1 and activating the bak-apoptotic pathway. These results support the combination of radiation and pro-survival Bcl-2 family inhibitor as a potential novel therapeutic strategy in the local-regional management of breast cancer.

Racial/ethnic disparities persist in the pediatric HL population despite modern treatment; underlying causes of these disparities are complex and need further examination.

Background/Aims: Leukocyte adhesion to the endothelium is abnormal in hypertension. We have recently shown that spontaneously hypertensive rats (SHRs) have circulating leukocytes with enhanced CD18 receptor cleavage. In the current study, we investigate expression levels of its counter receptor, intercellular adhesion molecule (ICAM-1), and its possible proteolytic cleavage in the SHR and control Wistar rat. Methods: ICAM-1 was labeled on tissue sections with two antibodies targeting its extracellular and intracellular domains and evaluated by light absorption measurements. The in situ cleavage of ICAM-1 was assessed by treating vessel sections with matrix metalloproteinase (MMP)-7, MMP-9 and elastase. Results: SHRs showed a significant increase in ICAM-1 expression in liver and kidney compared with Wistar rats. The liver and kidney glomeruli exhibit a discrepancy in label density between intra- and extracellular antibodies, which suggests that enzymatic cleavage may be a factor determining ICAM-1 distribution. MMP-7 and MMP-9, which are elevated in SHR plasma, and elastase, which has elevated activity in SHR neutrophils, cleave the extracellular domain of ICAM-1 when applied to the tissue. Conclusion: ICAM-1 expression in SHRs is upregulated in a tissue-specific manner. Proteolytic cleavage of the extracellular domain of ICAM-1 and accumulation in kidney glomeruli may play a role in the renal involvement of inflammation.

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