Ratio of CD68/CD163 in Breast Carcinoma with and without Axillary Lymph Node Metastatic

Tumor and its microenvironment can interact each other. Macrophage is part of tumor microenvironment. New drugs targeting specific superficial receptor of macrophage or cytokine of macrophage polarization have been found. Therefore, macrophage phenotype and its ratio of M1/M2 macrophage need to be identified. This identification could lead us to prognose breast cancer and monitor its therapy. Analytical observational study with cross sectional approach, conducted on paraffin block sample of breast carcinoma from Anatomical Pathology Laboratory of Dr. Soetomo General Hospital. The samples divided into four groups based on nodal metastasis staging (N0, N1, N2, and N3) and stained with antibody against CD68 and CD163. The ratio of CD68 and CD163 were analyzed with Anova test. There were difference expression of CD68 as M1 macrophage marker in various axillary node metastasis groups (p=0.015). There were difference ratio of CD68 as M1 macrophage marker and CD163 as M2 macrophage marker in various axillary node metastasis groups (p=0.005). There were difference ratio of macrophage M1 and macrophage M2 between N0 and N3 group, N2 and N3 group also.

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GRP94 regulates M1 macrophage polarization and insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00542.2019 ◽

2020 ◽

Vol 318 (6) ◽

pp. E1004-E1013 ◽

Cited By ~ 2

Author(s):

Lili Song ◽

Do-sung Kim ◽

Wenyu Gou ◽

Jingjing Wang ◽

Ping Wang ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Macrophage Polarization ◽

Conditional Knockout ◽

Marker Genes ◽

M2 Macrophage ◽

Macrophage Marker ◽

M1 Macrophage ◽

Lower Expression

Macrophage polarization contributes to obesity-induced insulin resistance. Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER) chaperone specialized for folding and quality control of secreted and membrane proteins. To determine the role of GRP94 in macrophage polarization and insulin resistance, macrophage-specific GRP94 conditional knockout (KO) mice were challenged with a high-fat diet (HFD). Glucose tolerance, insulin sensitivity, and macrophage composition were compared with control mice. KO mice showed better glucose tolerance and increased insulin sensitivity. Adipose tissues from HFD-KO mice contained lower numbers of M1 macrophages, with lower expression of M1 macrophage markers, than wild-type (WT) mice. In vitro, WT adipocytes cocultured with KO macrophages retained insulin sensitivity, whereas those cultured with WT macrophages did not. In addition, compared with WT bone marrow-derived macrophages (BMDMs), BMDMs from GRP94 KO mice exhibited lower expression of M1 macrophage marker genes following stimulation with LPS or IFN-γ, and exhibited partially increased expression of M2 macrophage marker genes following stimulation with interleukin-4. These findings identify GRP94 as a novel regulator of M1 macrophage polarization and insulin resistance and inflammation.

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Anti-Inflammatory Effect of Curcumin on the Mouse Model of Myocardial Infarction through Regulating Macrophage Polarization

Mediators of Inflammation ◽

10.1155/2021/9976912 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Shaoxi Yan ◽

Mo Zhou ◽

Xiaoyun Zheng ◽

Yuanyuan Xing ◽

Juan Dong ◽

...

Keyword(s):

Myocardial Infarction ◽

Ventricular Remodeling ◽

Macrophage Polarization ◽

M2 Macrophage ◽

M1 Macrophages ◽

Macrophage Marker ◽

M1 Macrophage ◽

Anti Inflammatory

Inflammation causes tissue damage and promotes ventricular remodeling after myocardial infarction (MI), and the infiltration and polarization of macrophages play an important role in regulating inflammation post-MI. Here, we investigated the anti-inflammatory function of curcumin after MI and studied its relationship with macrophage polarization. In vivo, curcumin not only attenuated ventricular remodeling 3 months after MI but also suppressed inflammation during the first 7 days post-MI. Importantly, the results of qPCR and immunochemistry showed that curcumin decreased M1 (iNOS, CCL2, and CD86) but increased M2 macrophage (Arg1, CD163, and CD206) marker expression in the myocardium of MI mice during the first 7 days post-MI. And flow cytometry analysis indicated that curcumin suppressed M1 (CD45+Gr-1-CD11b+iNOS+ cells) but enhanced M2 macrophage (CD45+Gr-1-CD11b+Arg+ cells) expansion in the myocardium of MI mice during the first 7 days post-MI. In vitro, curcumin decreased LPS/IFNγ-elevated M1 macrophage marker (iNOS and CD86) expression and the proportion of M1 macrophages (iNOS+F4/80+ cells) but increased LPS/IFNγ-suppressed M2 macrophage marker (Arg1 and CD206) expression and the proportion of M2 macrophages (Arg1+F4/80+ cells). In addition, curcumin modulates M1/M2 macrophage polarization partly via AMPK. In conclusion, curcumin suppressed the MI-induced inflammation by modulating macrophage polarization partly via the AMPK pathway.

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Pathologic complete remission of cytologically proven axillary node metastases may be a strong prognostic factor in HER2-positive breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21149 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21149-21149

Author(s):

M. Sakakibara ◽

T. Nagashima ◽

R. Nakamura ◽

H. Fujimoto ◽

M. Arai ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Preoperative Chemotherapy ◽

Axillary Node ◽

Axillary Lymph ◽

Her2 Positive ◽

Node Metastasis ◽

Pathologic Complete Remission ◽

Axillary Node Metastasis ◽

Positive Breast Cancer

21149 Background: Preoperative chemotherapy has become one of the standard modes of treatment in patients with breast cancer, and pathologic complete remission (pCR) thus obtained has become an important prognostic factor. However, the number of cells in the main lesion is enormous and changes over time in a heterogeneous manner. Thus, time and individual differences in sensitivity influence the acquisition of pCR, and questions about the coincidence with the effects of metastatic lesions also remain. On the other hand, although pCR of axillary lymph node metastasis lesions with relatively lower numbers of the cells is considered one of the best surrogate prognostic markers, evaluation criteria have not yet been established because definitive preoperative diagnosis is difficult. In our department, preoperative axillary cytodiagnosis has been conducted in all surgical breast cancer cases. In this study, we investigated pCR of the axillary lymph nodes (ALN- pCR) in cytologically proven axillary node metastasis cases. Subjects and Methods: ALN-pCR, DFS, and OS were investigated in 52 surgical breast cancer cases (observation period: 15–52 months; medial level: 28 months) positive for cytological axillary metastasis and received preoperative chemotherapy (AC-Paclitaxel) during the period from 2002 to 2005. Results: ALN-pCR was found in 21 of 52 cases (40.4%). Rates of disease-free survival (DFS) at 36 months in ALN-pCR and non-ALN-pCR cases were 85.0% and 42.3% (P=0.031) and those of overall survival (OS; 48 months) were 100% and 87.9% (P=0.353), respectively. DFS (36 months) was very favorable 100% in ALN-pCR cases that obtained the effect of 1b or higher on evaluation of the main lesion effect and ALN-pCR cases with Her2-positive results on sub-type analysis. Conclusions: ALN-pCR of cytologically proven axillary node metastasis was indicated to be a prognostic factor in cases of breast cancer. Especially, its importance was demonstrated in HER2-positive breast cancer. From these findings, HER2-positive and cytologically axillary lymph node-positive cases were considered the best indications for preoperative chemotherapy. No significant financial relationships to disclose.

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Is there a safe tumor size for identification of breast carcinoma without axillary node metastasis?

Mastology ◽

10.29289/2594539420190000433 ◽

2019 ◽

Vol 29 (1) ◽

pp. 25-31

Author(s):

René Aloisio da Costa Vieira ◽

◽

Idam de Oliveira- Junior ◽

Thaissa Daud de Faria Cavalin ◽

Rhaissa Iara Magano Tabuti ◽

...

Keyword(s):

Breast Carcinoma ◽

Tumor Size ◽

Axillary Node ◽

Node Metastasis ◽

Axillary Node Metastasis

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Image analysis of imprint cytology from invasive breast carcinoma and its relation to axillary node metastasis

European Journal of Cancer ◽

10.1016/s0959-8049(98)80478-4 ◽

1998 ◽

Vol 34 ◽

pp. S114

Author(s):

I. Idvall ◽

L. Ingvaldsson ◽

Y. Knutsson ◽

T. Lindén ◽

M. Fernö

Keyword(s):

Image Analysis ◽

Breast Carcinoma ◽

Axillary Node ◽

Invasive Breast Carcinoma ◽

Imprint Cytology ◽

Node Metastasis ◽

Axillary Node Metastasis

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Effect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization

International Journal of Molecular Sciences ◽

10.3390/ijms22052336 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2336

Author(s):

Ryoka Uchiyama ◽

Eriko Toyoda ◽

Miki Maehara ◽

Shiho Wasai ◽

Haruka Omura ◽

...

Keyword(s):

Culture Media ◽

Platelet Rich Plasma ◽

Point Of Care ◽

Macrophage Polarization ◽

Osteoarthritis Of The Knee ◽

M2 Macrophage ◽

Related Factors ◽

Humoral Factors ◽

M1 Macrophage ◽

M2 Macrophage Polarization

Osteoarthritis of the knee (OAK) is a chronic degenerative disease and progresses with an imbalance of cytokines and macrophages in the joint. Studies regarding the use of platelet-rich plasma (PRP) as a point-of-care treatment for OAK have reported on its effect on tissue repair and suppression of inflammation but few have reported on its effect on macrophages and macrophage polarization. Based on our clinical experience with two types of PRP kits Cellaid Serum Collection Set P type kit (leukocyte-poor-PRP) and an Autologous Protein Solution kit (APS leukocyte-rich-PRP), we investigated the concentrations of humoral factors in PRPs prepared from the two kits and the effect of humoral factors on macrophage phenotypes. We found that the concentrations of cell components and humoral factors differed between PRPs purified using the two kits; APS had a higher concentration of M1 and M2 macrophage related factors. The addition of PRP supernatants to the culture media of monocyte-derived macrophages and M1 polarized macrophages revealed that PRPs suppressed M1 macrophage polarization and promoted M2 macrophage polarization. This research is the first to report the effect of PRPs purified using commercial kits on macrophage polarization.

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847 Inflammasome activation in M2 macrophage restrain the immune suppressive function

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0847 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A900-A900

Author(s):

Ronghua Zhang ◽

Tienan Wang ◽

Qing Lin

Keyword(s):

T Cell ◽

T Cell Activation ◽

Culture System ◽

Cell Activation ◽

Macrophage Polarization ◽

Inflammasome Activation ◽

M2 Macrophage ◽

M1 Macrophage ◽

Suppressive Phenotype

BackgroundMacrophage is an important component in tumor microenvironment (TME) and plays multiple roles in tumor initiation, progression and metastases. In response to various stimuli within TME, macrophage exhibits high level of functional heterogeneity. There are two distinct groups of macrophages: M1 macrophage exhibits pro-inflammatory phenotype with high levels of TNF-a, IL-6, and IL-1ß, while M2 macrophage displays immune suppressive phenotype with high levels of anti-inflammatory cytokines such as IL-10 and TGF-ß. In response to the M2 cytokines, myeloid cells within the TME further acquire higher expression of PD-L1 and thus inactivate T cells. M2 cytokines can also directly inhibit T cell activation. As a result, re-polarizing M2 macrophages becomes a key concept for cancer immunotherapy. The NLRP3 inflammasome is acquired by macrophages to fight against endogenous danger signals. Macrophage NLRP3 activation has been observed in several tumor models, but the function of NLRP3 on macrophage polarity remains controversial. Inflammasome activation with IL-1ß/IL-18 secretion was reported to promote M1 polarization. However, NLRP3 activation was also reported to promote M2 polarity through up-regulation of IL4 in asthma modelMethodsHere, we have established an in vitro human macrophage NLRP3 activation system (figure 1), coupled with M2 macrophage polarization assay, to dissect the role of NLRP3 in macrophage phenotype.ResultsOur results indicate that NLRP3 activation restrained M2 phenotype and further enhanced T cell activation in an M2/T cell co-culture system (figure 2).Abstract 847 Figure 1Inflammasome activation polarize M2 macrophage intUse LPS/ATP to stimulate NLRP3 in M2 macrophage and demonstrate NLRP3 activation could reduce CD163 and increase CD86Abstract 847 Figure 2Inflammasome in M2 rescue T cell activationestablish M2/T co-culture system in vitro to demonstrate M2 could suppress T activation while Inflammatory M2 could partial rescue the suppressive phenotypeConclusionsInflammasome could be the potential target for cancer by modulating T cell activation through macrophage polarization regulation

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Grading, staging and Nottingham prognostic index scoring of breast carcinoma

Journal of Pathology of Nepal ◽

10.3126/jpn.v7i1.16951 ◽

2017 ◽

Vol 7 (1) ◽

pp. 1078-1083

Author(s):

A Pradhan ◽

P Paudyal ◽

AK Sinha ◽

CS Agrawal

Keyword(s):

Lymph Node ◽

Breast Carcinoma ◽

Lymph Node Metastasis ◽

Prognostic Index ◽

Nottingham Prognostic Index ◽

Eastern Region ◽

Axillary Lymph ◽

Cross Sectional ◽

Tnm System ◽

Node Metastasis

Background: Breast carcinoma is the most frequent malignant tumor in women accounting for approximately 15% of female cancer deaths. It is the second most common malignancy among women in Nepal. Our objectives were to study the extent and spread of different histological types breast carcinoma in the eastern region of Nepal, to grade and stage the tumors, score the prognosis.Materials and Methods: A cross-sectional descriptive study of mastectomy specimens with axillary lymph node sampling was done for a period of two years. Diagnosis was done using WHO classification. Modified Bloom Richardson score and TNM system was used to grade and stage the tumors. Nottingham Prognostic index was applied to score the prognosis.Results: Out of 31 total cases, the most common histologic type was Invasive Carcinoma of No Special Type (67.74%). The largest tumor size was of 12cm which had poor NPI score. Most tumors were of grade II and T2. Out of 30 cases with lymph nodes, 13 were negative for metastasis pN0, 10 were pN1 and 7 were pN2. Extranodal spread was observed in 6 out of 17 cases with lymph node metastasis and was associated with higher grades and poor prognosis.Conclusion: Higher grade tumors, lymph node metastasis and extranodal extension are associated with higher Nottingham Prognostic Index score.

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