Pathologic assessment of tumor-associated macrophages and their histologic localization in invasive breast carcinoma.

BACKGROUND: Tumor-associated macrophages (TAMs) are important in regulating cross-talk between tumor cells and tumor microenvironment. TAMs are involved in multiple steps of tumor progression and invasion. This study aimed to compare CD163 expression with the widely used CD68 pan-macrophage marker in invasive breast carcinoma. Furthermore, it focused on assessing the significance of TAMs localization in relation to clinicopathological parameters. RESULTS: CD68 and CD163 immunohistochemical expressions within TAMs infiltrating both tumor nest (TN) and tumor stroma (TS) were evaluated in 60 specimens with invasive breast carcinoma. High CD68-positive stromal TAMs was significantly related to larger tumor, nodal metastasis and vascular invasion (p = 0.003, 0.037, 0.032, respectively), whereas high CD163-positive stromal TAMs was significantly related to larger tumors, nodal metastasis, stage III tumors, vascular invasion, estrogen receptor (ER) negativity, and triple-negative subtype (p = 0.023, < 0.001, 0.001, 0.022, 0.002, 0.017, respectively). On multivariate analysis, high CD68-positive TAMs infiltrating TS was significantly associated with larger tumor and positive nodal metastasis (p = 0.006 and 0.016, respectively), whereas high CD163 TAMs density within TS was significantly associated with positive vascular invasion, nodal metastasis, and molecular subtypes (p = 0.003, 0.001, and 0.009, respectively). CONCLUSION: TAMs within tumor stroma and tumor nest have different levels of association with poor prognostic parameters. So, it is of great importance to consider the histologic localization of TAMs in addition to the degree of TAMs infiltration.

Mechanistic insights into the effects of quercetin and/or GLP-1 analogue liraglutide on high-fat diet/streptozotocin-induced type 2 diabetes in rats.

BACKGROUND: The development of complementary treatment strategies that focuses on achieving a balance between adaptive and apoptotic unfolded protein response (UPR), enhancing endoplasmic reticulum (ER) homeostasis, and thus preserving ß cell mass and function is particularly warranted. AIM: This study was designed to investigate the effectiveness of the combined treatment by Quercetin (QUE) and Liraglutide (LIRA) in modulating hyperglycemia, insulin-insensitivity, UPR/ER stress markers, apoptosis, oxidative stress and inflammation using a high-fat diet/streptozotocin -induced type 2 diabetic rat model. METHODS: Sixty male albino rats were allocated into five equal groups: normal control, diabetic control, LIRA treated diabetic; QUE treated diabetic and combined treatment diabetic groups. Fasting glucose, insulin, CHOP, macrophage inflammatory protein -1 α (MIP-1α) and Bax, Bcl2 levels were estimated by ELISA; mRNA expression levels of the spliced X-box binding protein 1 (XBP1) were estimated using quantitative real-time RT-PCR, while MDA, advanced oxidation protein products, reduced glutathione levels and protein disulfide isomerase (PDI) activity were evaluated spectrophotometrically. Pancreatic tissues were also subjected to histopathological examination. RESULTS: The combined treatment with both LIRA and QUE causes significant improvements in all the studied parameters; including XBP1 splicing, CHOP, MIP-1α, Bax/Bcl2 ratio, PDI activity, as well as oxidative stress markers as compared to either treatment alone. It also attenuated pancreatic histopathological damage. IN CONCLUSION: Our study nominates this combination to be used in T2DM to achieve adequate glycaemic control and to preserve optimal ß cell function.