Inducible 70kDa Heat Shock Protein and Autophagy-related Protein P62 Levels in Women With Breast Cancer: an Exploratory Investigation

Abstract Background: Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. The inducible 70kDa heat shock protein (HSPA1A) protects proteins from degradation. Autophagy is an intracellular process that removes damaged proteins and recycles their components to the cytoplasm. Sequestosome-1 (p62) is a protein consumed during autophagy. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSPA1A and a decrease in intracellular p62.Methods: In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSPA1A and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. Results: A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSPA1A levels were 79.3 ng/ml in PBMCs from women with a malignant lesion and 44.2 ng/ml in controls (p=0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p<0.001). Mean p62 levels were also lower in women with invasive carcinoma and a positive lymph node biopsy when compared to those with in-situ carcinoma or absence of lymphadenopathy, respectively. Conclusion: Intracellular HSPA1A and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.

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Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer

Scientific Reports ◽

10.1038/s41598-021-01683-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Theofano Orfanelli ◽

Spyridon Giannopoulos ◽

Eleni Zografos ◽

Aikaterini Athanasiou ◽

Ann Marie Bongiovanni ◽

...

Keyword(s):

Breast Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Breast Lesion ◽

Breast Mass ◽

Benign Breast Lesion ◽

Sequestosome 1 ◽

Malignant Breast ◽

Heat Shock Protein Hsp70 ◽

Intracellular Hsp70

AbstractPeripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy. P62 is also a regulator of intracellular kinase activity and cell differentiation. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSP70 and a decrease in intracellular p62. In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSP70 and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSP70 levels were 79.3 ng/ml in PBMCs from women with a malignant lesion as opposed to 44.2 ng/ml in controls (p = 0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p < 0.001). Mean p62 levels were lowest in women with invasive carcinoma and a positive lymph node biopsy when compared to those with in-situ carcinoma or absence of lymphadenopathy, respectively. Intracellular HSP70 and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.

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Elevated 70kDa heat shock protein (hsp70) and autophagy levels in peripheral blood mononuclear cells (PBMCs) in women with a malignant breast mass

Annals of Oncology ◽

10.1093/annonc/mdy269.146 ◽

2018 ◽

Vol 29 ◽

pp. viii47

Author(s):

A.I. Athanasiou ◽

T. Orfanelli ◽

D. Lapolla ◽

E. Andreopoulou ◽

T.A. Moo ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Breast Mass ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Malignant Breast ◽

Heat Shock Protein Hsp70

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Correlation Between Ultrasound BI-RADS 4 Breast Lesions and Fine Needle Cytology Categories in a Sample of Iraqi Female Patients

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2021-0048 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Hiba Mohammed Abdulwahid ◽

Zahraa Yahya Mohammed ◽

Furat Nidhal ◽

Farah A.J. AL Zahwi ◽

Muna Jumaa Ali

Keyword(s):

Breast Cancer ◽

Fine Needle Aspiration ◽

Breast Lesion ◽

Malignant Lesion ◽

Needle Aspiration ◽

Accurate Estimation ◽

Breast Lesions ◽

Fine Needle ◽

Case Series Study ◽

Malignant Breast

Abstract Background: Breast cancer is the most common malignancy in female and the most registered cause of women’s mortality worldwide. BI-RADS 4 breast lesions are associated with an exceptionally high rate of benign breast pathology and breast cancer, so BI-RADS 4 is subdivided into 4A, 4B and 4C to standardize the risk estimation of breast lesions. The aim of the study: to evaluate the correlation between BI-RADS 4 subdivisions 4A, 4B & 4C and the categories of reporting FNA cytology results. Patients and Methods: A case series study was conducted in the Oncology Teaching Hospital in Baghdad from September 2018 to September 2019. Included patients had suspicious breast findings and given BI-RADS 4 (4A, 4B, or 4C) in the radiological report accordingly. Fine needle aspiration was performed under the ultrasound guide and the results were classified into five categories. The biopsy was performed for suspicious, malignant or equivocal FNA findings. Results: This study included 158 women with BIRADS 4 breast lesions with the mean age of (44.6 years); There was a highly significant association between BI-RADS 4 breast lesion and FNA results (p<0.001); 51.9% of BI-RADS IV-C had C5 FNA results. There was a highly significant association between BI-RADS 4 lesion and the final diagnosis (p<0.001); 41.2% of BI-RADS 4 B had a malignant breast lesion, while 37.3% of BIRADS 4 C had a malignant lesion. Conclusion: A clear relationship was observed between BI-RADS 4 subcategories and the fine needle aspiration cytology subgroups. BI-RADS 4-B is helpful in the discrimination between benign and malignant breast lesions; furthermore BI-RADS 4C has more acceptable validity in the diagnosis of breast malignancy. Therefore, BI-RADS subcategories are encouraged to be included and mentioned in the ultrasound report for more accurate estimation of the lesion nature.

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Design, Synthesis, and Evaluation of Heat Shock Protein 90 Inhibitors in Human Breast Cancer and Its Metastasis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201017666161031105815 ◽

2016 ◽

Vol 17 (14) ◽

pp. 1231-1245 ◽

Cited By ~ 9

Author(s):

Mehmet Gümus ◽

Aykut Ozgur ◽

Lutfi Tutar ◽

Ali Disli ◽

Irfan Koca ◽

...

Keyword(s):

Breast Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Human Breast Cancer ◽

Heat Shock Protein 90 ◽

Human Breast ◽

Design Synthesis

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The Expression of Heat Shock Protein 60 kDa in Tissues and Cell Lines of Breast Cancer

Journal of Breast Cancer ◽

10.4048/jbc.2008.11.4.161 ◽

2008 ◽

Vol 11 (4) ◽

pp. 161

Author(s):

Byung Chul You ◽

Seung Yeon Park ◽

Young Don Lee ◽

Jung Nam Lee ◽

Yu Jin Hwang ◽

...

Keyword(s):

Breast Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Cell Lines ◽

Heat Shock Protein 60

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Proliferating cell nuclear antigen and heat shock protein 70 immuno-localization in invasive ductal breast cancer not otherwise specified

Breast Cancer Research and Treatment ◽

10.1023/a:1005706110275 ◽

1997 ◽

Vol 43 (1) ◽

pp. 43-51 ◽

Cited By ~ 63

Author(s):

Andreas Ch. Lazaris ◽

Emmy B. Chatzigianni ◽

Dimitris Panoussopoulos ◽

George N. Tzimas ◽

Panayotis S. Davaris ◽

...

Keyword(s):

Breast Cancer ◽

Heat Shock ◽

Heat Shock Protein ◽

Proliferating Cell Nuclear Antigen ◽

Heat Shock Protein 70 ◽

Nuclear Antigen ◽

Invasive Ductal Breast Cancer ◽

Not Otherwise Specified ◽

Ductal Breast Cancer ◽

Proliferating Cell

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A 70-Kilodalton Recombinant Heat Shock Protein ofCandida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis

Infection and Immunity ◽

10.1128/iai.66.5.2154-2162.1998 ◽

1998 ◽

Vol 66 (5) ◽

pp. 2154-2162 ◽

Cited By ~ 52

Author(s):

Carla Bromuro ◽

Roberto La Valle ◽

Silvia Sandini ◽

Francesca Urbani ◽

Clara M. Ausiello ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Mononuclear Cells ◽

Cell Mediated Immunity ◽

Healthy Human ◽

Peripheral Blood Mononuclear ◽

Necrosis Factor Alpha ◽

Ifn Γ

ABSTRACT The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-γ), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-γ was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-γ upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

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