scholarly journals Second-generation optoacoustic imaging of breast cancer patients

2021 ◽  
Author(s):  
Jan Kukacka ◽  
Stephan Metz ◽  
Christoph Dehner ◽  
Korbinian Paul-Yuan ◽  
Alexander Muckenhuber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Second Generation ◽  
Cancer Imaging ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Breast Cancer Imaging ◽  
Optoacoustic Imaging ◽  
Experimental Systems ◽  
Partial View

Since the initial breast transillumination almost a century ago, breast cancer imaging using light has been considered in different implementations aiming to improve diagnostics, minimize the number of available biopsies, or monitor treatment. However, due to strong photon scattering, conventional optical imaging yields low resolution images, challenging quantification and interpretation. Optoacoustic imaging addresses the scattering limitation and yields high-resolution visualization of optical contrast, offering great potential value for breast cancer imaging. Nevertheless, the image quality of experimental systems remains limited due to a number of factors, including signal attenuation with depth and partial view angle and motion effects, particularly in multi-wavelength measurements. We developed data analytics methods to improve the accuracy of handheld optoacoustic breast cancer imaging, yielding second-generation optoacoustic imaging performance operating in tandem with ultrasonography. We produced the best images yet with handheld optoacoustic examinations of the human breast and breast cancer, in terms of resolution and contrast. Using these advances, we examined optoacoustic markers of malignancy, including vasculature abnormalities, hypoxia, and inflammation, on images obtained from breast cancer patients. We achieved the best optoacoustic images of the human breast ever obtained using handheld examination, advancing the diagnostic and theranostic potential of the hybrid optoacoustic-ultrasound (OPUS) examination over routine ultrasonography.

scholarly journals Sex steroid-producing enzymes in human breast cancer

2005 ◽  
Vol 12 (4) ◽  
pp. 701-720 ◽  
Author(s):  
Takashi Suzuki ◽  
Yasuhiro Miki ◽  
Yasuhiro Nakamura ◽  
Takuya Moriya ◽  
Kiyoshi Ito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Patients ◽  
Stromal Cells ◽  
Cellular Localization ◽  
Sex Steroid ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Estrogen Production ◽  
Aromatase Mrna

It is well known that sex steroids are involved in the growth of breast cancers, and the great majority of breast carcinomas express estrogen (ER), progesterone (PR), and androgen (AR) receptors. In particular, recent studies have demonstrated that estrogens and androgens are locally produced in breast carcinoma tissues, and total blockade of in situ estrogen production potentially leads to an improvement in prognosis of breast cancer patients. Therefore, it is important to obtain a better understanding of sex steroid-producing enzymes in breast carcinoma tissues. In this review, we summarize recent studies on the expression and regulation of enzymes related to intratumoral production of estrogens (aromatase, 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1), and steroid sulfatase (STS) etc) and androgens (17βHSD5 and 5α-reductase) in human breast carcinoma tissues, and discuss the biological and/or clinical significance of these enzymes. The cellular localization of aromatase in breast carcinoma tissues still remains controversial. Therefore, we examined localization of aromatase mRNA in breast carcinoma tissues by laser capture microdissection/real time-polymerase chain reaction. Aromatase mRNA expression was detected in both carcinoma and intratumoral stromal cells, and the expression level of aromatase mRNA was higher in intratumoral stromal cells than in carcinoma cells in the cases examined. We also examined an association among the immunoreactivity of enzymes related to intratumoral estrogen production and ERs in breast carcinoma tissues, but no significant association was detected. Therefore, the enzymes responsible for the intratumoral production of estrogen may not always be the same among breast cancer patients, and not only aromatase but also other enzymes such as STS and 17βHSD1 may have important therapeutic potential as targets for endocrine therapy in breast cancer patients.

scholarly journals Antiestrogen-resistant human breast cancer cells require activated Protein Kinase B/Akt for growth

2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.

scholarly journals Potential Involvement of Jagged1 in Metastatic Progression of Human Breast Carcinomas

2016 ◽  
Vol 62 (2) ◽  
pp. 378-386 ◽  
Author(s):  
Natalia Bednarz-Knoll ◽  
Antonia Efstathiou ◽  
Frauke Gotzhein ◽  
Harriet Wikman ◽  
Volkmar Mueller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Progressive Disease ◽  
Metastatic Progression ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Free Survival ◽  
Human Breast Carcinomas

Abstract BACKGROUND Jagged1, the ligand of Notch, has been shown to be involved in formation of bone metastases in an experimental study. Here, clinical relevance of Jagged1 expression in tumor progression was assessed in human breast carcinomas. METHODS Jagged1 expression was evaluated by immunohistochemistry in 228 tumor tissue samples and compared to clinicopathologic parameters and patients' outcomes. Furthermore, circulating tumor cells (CTCs) from peripheral blood of 100 unmatched metastatic cancer patients with progressive disease were enriched using Ficoll density gradient centrifugation and detected by pan-keratin/Jagged1/CD45 immunofluorescent staining. RESULTS Jagged1 expression was detected in 50% of 228 tumors. Jagged1 expression was correlated with higher tumor grade (P = 0.047), vascular invasion (P = 0.026), luminal B subtype (P = 0.016), overexpression of Her-2 (P = 0.001), high Ki-67 expression (P = 0.035), and aldehyde dehydrogenase 1 (ALDH1) positivity (P = 0.013). Jagged 1 expression indicated shorter disease-free survival (DFS) (P = 0.040) and metastasis-free survival (P = 0.048) in lymph node–negative breast cancer for which it was the only independent predictor of DFS (multivariate analysis, P = 0.046). Tumors characterized by the strongest Jagged1 staining intensity (7.5% of cases) correlated with lymph node positivity (P = 0.037), metastatic relapse (P = 0.049), and higher number of disseminated tumor cells in bone marrow aspirates (P = 0.041). Twenty-one unmatched metastatic breast cancer patients with progressive disease were positive for CTCs, and 85.7% of the CTCs also expressed Jagged1. The presence of Jagged1(+) CTCs was significantly associated with shorter progression-free survival in patients treated with bisphosphonates (P = 0.013). CONCLUSIONS Jagged1 expression characterizes more aggressive breast carcinoma and might be involved in tumor cell dissemination, metastatic progression, and resistance to bone-targeting therapy in breast cancer patients.

The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients

2015 ◽  
Vol 129 (9) ◽  
pp. 809-822 ◽  
Author(s):  
Miao He ◽  
Yingzi Fu ◽  
Yuanyuan Yan ◽  
Qinghuan Xiao ◽  
Huizhe Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Human Breast Cancer ◽  
Drug Response ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Hedgehog Signalling ◽  
Hedgehog Signalling Pathway ◽  
Xenograft Mice ◽  
Mcf 7

Our study showed that Hh signalling activation contributed to BCSC-mediated chemoresistance in cultured breast cancer MCF-7 MS cells, in xenograft mice and in human breast cancer patients.

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