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 ◽  
...  

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.

2021 ◽  
Vol 22 (4) ◽  
pp. 1918
Author(s):  
Mio Yamaguchi ◽  
Kiyoshi Takagi ◽  
Koki Narita ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
...  

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.


2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  

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.


2018 ◽  
Vol 4 (2) ◽  
pp. 96-98
Author(s):  
Soumi Pathak ◽  
Ajay Kumar Bhargava

Breast cancer is the commonest cancer in women worldwide. In the developing countries of Asia, the health care burden on account of breast cancer has been steadily mounting. Over 100,000 new breast cancer patients are estimated to be diagnosed annually in India.1 As per the ICMR-PBCR data, breast cancer is the commonest cancer among women in urban registries of Delhi, Mumbai, Ahmedabad, Calcutta, and Trivandrum where it constitutes > 30% of all cancers in females. Previous literature on mastectomy indicates that the operation may be perceived by the patient as a threat to her feminity. Breast cancer survivors have dissatisfaction with appearance, perceived loss of femininity and body integrity, self-consciousness about appearance, and dissatisfaction with surgical scars… Journal of Society of Anesthesiologists of NepalVol. 4, No. 2, 2017, Page: 96-98 


Author(s):  
Anjan Adhikari ◽  
Dipesh Chakraborty ◽  
Rania Indu ◽  
Sangita Bhattacharya ◽  
Moumita Ray ◽  
...  

 Objective: Cancer is a disease of uncontrolled division of cells in any part of the body. Breast cancer most common in women accounts for 13% of the death worldwide. The objective of the present study was to evaluate the drug prescription pattern of breast carcinoma patients in a tertiary care hospital of West Bengal.Methods: This was a cross-sectional observational questionnaire-based study done for a period of 6 months at the Department of Pharmacology in Collaboration with the Department of Surgery and Department of Radiotherapy of a Tertiary Care Hospital at Kolkata, West Bengal, India. Female patients with breast cancer (originated from epithelial tissues) of different types and grade attending surgery outdoor patient department were taken as subjects for the study, after signing informed consent.Results: The present study evaluated 28 patients (n=28) diagnosed as breast cancer by the physicians of the department of surgery and radiotherapy. It was observed that breast cancer was mostly found in the middle age group. Breast carcinoma in postmenopausal women accounted to 75%. The most prevalent breast cancer was invasive ductal carcinoma, accounting to 75% of the study population. 5-Fluorouracil, epirubicin, doxorubicin, cyclophosphamide, docetaxel/paclitaxel, and carboplatin were mostly used as chemotherapeutic agent.Conclusion: Breast carcinoma being a prevalent type of cancer in females, the present study tried to evaluate the pattern of prescribing chemotherapeutic agents for breast cancer patients in a tertiary care hospital. Such study is essential to evaluate and refine the therapeutic regimen of the cancer patients to reduce their sufferings.


2016 ◽  
Vol 62 (2) ◽  
pp. 378-386 ◽  
Author(s):  
Natalia Bednarz-Knoll ◽  
Antonia Efstathiou ◽  
Frauke Gotzhein ◽  
Harriet Wikman ◽  
Volkmar Mueller ◽  
...  

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.


2015 ◽  
Vol 129 (9) ◽  
pp. 809-822 ◽  
Author(s):  
Miao He ◽  
Yingzi Fu ◽  
Yuanyuan Yan ◽  
Qinghuan Xiao ◽  
Huizhe Wu ◽  
...  

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.


2021 ◽  
Author(s):  
Jan Kukacka ◽  
Stephan Metz ◽  
Christoph Dehner ◽  
Korbinian Paul-Yuan ◽  
Alexander Muckenhuber ◽  
...  

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.


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