Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer

Authors: Carolina Panis, Luciana Pizzatti, Aedra Carla Bufalo, Ana Cristina Herrera, Vanessa Jacob Victorino, Rubens Cecchini, Eliana Abdelhay

Published in: Tumor Biology | Issue 3/2016

Login to get access

Abstract

Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic–proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m2) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.
Appendix
Available only for authorised users
Literature
1.
Cecilio AP, Takakura ET, Jumes JJ, Dos Santos JW, Herrera AC, Victorino VJ, et al. Breast cancer in Brazil: epidemiology and treatment challenges. Breast Cancer. 2015;7:43–9.PubMedPubMedCentral
2.
3.
Prietsman TJ. Results of a prospective clinical trial comparing two cytotoxic regimes containing adriamycin in women with advanced breast cancer. Clin Oncol. 1975;1(3):207–11.
4.
Sparano JA, Makhson AN, Semiglazov VF, Tjulandin SA, Balashova OI, Bondarenko IN, et al. Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel Monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol. 2009;20(27):4522–9.CrossRef
5.
Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229.CrossRefPubMed
6.
Kim ES, Cha Y, Ham M, Jung J, Kim SG, Hwang S, et al. Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression. Oncogene. 2014;33(27):3583–93.CrossRefPubMed
7.
Ham M, Moon A. Inflammatory and microenvironmental factors involved in breast cancer progression. Arch Pharm Res. 2013;36(12):1419–31.CrossRefPubMed
8.
Lakota K, Zigon P, Mrak-Poljsak K, Rozman B, Shoenfeld Y, Sodin-Semrl S. Antibodies against acute phase proteins and their functions in the pathogenesis of disease: a collective profile of 25 different antibodies. Autoimmun Rev. 2011;10(12):779–89.CrossRefPubMed
9.
Pensa S, Watson CJ, Poli V. Stat3 and the inflammation/acute phase response in involution and breast cancer. J Mammary Gland Biol Neoplasia. 2009;14(2):121–9.CrossRefPubMed
10.
Tisdale MJ. Pathogenesis of cancer cachexia. J Support Oncol. 2003;1(3):159–68.PubMed
11.
Coventry BJ, Ashdown ML, Quinn MA, Markovic SN, Yatomi-Clarke SL, Robinson AP. CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool? J Transl Med. 2009;7:102.CrossRefPubMedPubMedCentral
12.
13.
Noguchi Y, Yoshikawa T, Matsumoto A, Svaninger G, Gelin J. Are cytokines possible mediators of cancer cachexia? Surg Today. 1996;26(7):467–75.CrossRefPubMed
14.
Stephens NA, Skipworth RJ, Fearon KC. Cachexia, survival and the acute phase response. Curr Opin Support Palliat Care. 2008;2(4):267–74.CrossRefPubMed
15.
Michlmayr A, Bachleitner-Hofmann T, Baumann S, Marchetti-Deschmann M, Rech-Weichselbraun I, Burghuber C, et al. Modulation of plasma complement by the initial dose of epirubicin/docetaxel therapy in breast cancer and its predictive value. Br J Cancer. 2010;103(8):1201–8.CrossRefPubMedPubMedCentral
16.
Panis C, Pizzatti L, Herrera AC, Cecchini R, Abdelhay E. Putative circulating markers of the early and advanced stages of breast cancer identified by high-resolution label-free proteomics. Cancer Lett. 2013;330(1):57–66.CrossRefPubMed
17.
Panis C, Pizzatti L, Herrera AC, Corrêa S, Binato R, Abdelhay E. Label-free proteomic analysis of breast cancer molecular subtypes. J Proteome Res. 2014;13(11):4752–72.CrossRefPubMed
18.
Panis C, Pizzatti L, Corrêa S, Binato R, Lemos GF, Herrera AC, et al. The positive is inside the negative: HER2-negative tumors can express the HER2 intracellular domain and present a HER2-positive phenotype. Cancer Lett. 2015;357(1):186–95.CrossRefPubMed
19.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Clin Pract Urol. 2005;2(8):416–22.CrossRefPubMed
20.
Panis C, Pizzatti L, Abdelhay E. How can proteomics reach cancer biomarkers? Curr Proteomics. 2013;10(2):136–49.CrossRef
21.
Pizzatti L, Panis C, Lemos G, Rocha M, Cecchini R, Souza GH, et al. Label-free MSE proteomic analysis of chronic myeloid leukemia bone marrow plasma: disclosing new insights from therapy resistance. Proteomics. 2012;12(17):2618–31.CrossRefPubMed
22.
Chen ST, Pan TL, Tsai YC, Huang CM. Proteomics reveals protein profile changes in doxorubicin--treated MCF-7 human breast cancer cells. Cancer Lett. 2002;181(1):95–107.CrossRefPubMed
23.
Kumar SN, Konorev EA, Aggarwal D, Kalyanaraman B. Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte. J Proteomics. 2011;74(5):683–97.CrossRefPubMedPubMedCentral
24.
Lee SH, Kim SY, Kim JH, Jung HY, Moon JH, Bae KH, et al. Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model. Mol Med Rep. 2012;6(1):157–62.PubMed
25.
Panis C. Unraveling oxidation-induced modifications in proteins by proteomics. Adv Protein Chem Struct Biol. 2014;94:19–38.CrossRefPubMed
26.
Kono H, Onda A, Yanagida T. Molecular determinants of sterile inflammation. Curr Opin Immunol. 2014;26:147–56.CrossRefPubMed
27.
Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122(4):143–59.CrossRef
28.
29.
Panis C, Victorino VJ, Herrera AC, Freitas LF, De Rossi T, Campos FC, et al. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer. Breast Cancer Res Treat. 2012;133(3):881–8.CrossRefPubMed
30.
Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.CrossRefPubMed
31.
Hamaguchi T, Wakabayashi H, Matsumine A, Sudo A, Uchida A. TNF inhibitor suppresses bone metastasis in a breast cancer cell line. Biochem Biophys Res Commun. 2011;407(3):525–30.CrossRefPubMed
32.
Yu M, Zhou X, Niu L, Lin G, Huang J, Zhou W, et al. Targeting transmembrane TNF-α suppresses breast cancer growth. Cancer Res. 2013;73(13):4061–74.CrossRefPubMed
33.
Fruehauf JP, Sinha BK. Selective formation of tumor necrosis factor-alpha (TNF) degradation products contributes to TNF mediated cytotoxicity. Oncol Res. 1992;4(3):91–101.PubMed
34.
Suswam EA, Nabors LB, Huang Y, Yang X, King PH. IL-1beta induces stabilization of IL-8 mRNA in malignant breast cancer cells via the 3′ untranslated region: involvement of divergent RNA-binding factors HuR, KSRP and TIAR. Int J Cancer. 2005;113(6):911–9.CrossRefPubMed
35.
Schwartz Y, Avraham R, Benish M, Rosenne E, Ben-Eliyahu S. Prophylactic IL-12 treatment reduces postoperative metastasis: mediation by increased numbers but not cytotoxicity of NK cells. Breast Cancer Res Treat. 2008;107(2):211–23.CrossRefPubMed
36.
Derynck R, Muthusamy BP, Saeteurn KY. Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition. Curr Opin Cell Biol. 2014;31:56–66.CrossRefPubMedPubMedCentral
37.
Zarzynska JM. Two faces of TGF-beta1 in breast cancer. Mediat Inflamm. 2014;2014:141747.CrossRef
38.
Falgarone G, Chiocchia G. Chapter 8: clusterin: a multifacet protein at the crossroad of inflammation and autoimmunity. Adv Cancer Res. 2009;104:139–70.CrossRefPubMed
39.
40.
Niu ZH, Wang Y, Chun B, Li CX, Wu L. Secretory clusterin (sCLU) overexpression is associated with resistance to preoperative neoadjuvant chemotherapy in primary breast cancer. Eur Rev Med Pharmacol Sci. 2013;17(10):1337–44.PubMed
41.
Li GH, Arora PD, Chen Y, McCulloch CA, Liu P. Multifunctional roles of gelsolin in health and diseases. Med Res Rev. 2012;32(5):999–1025.CrossRefPubMed
42.
Van den Abbeele A, De Corte V, Van Impe K, Bruyneel E, Boucherie C, Bracke M, et al. Downregulation of gelsolin family proteins counteracts cancer cell invasion in vitro. Cancer Lett. 2007;255(1):57–70.CrossRefPubMed
43.
Metadata
Title
Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer
Authors
Carolina Panis
Luciana Pizzatti
Aedra Carla Bufalo
Ana Cristina Herrera
Vanessa Jacob Victorino
Rubens Cecchini
Eliana Abdelhay
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4203-7

Other articles of this Issue 3/2016

Tumor Biology 3/2016 Go to the issue

Original Article

Role of Helicobacter pylori on cancer of human adipose-derived mesenchymal stem cells and metastasis of tumor cells—an in vitro study

Original Article

Effects of silibinin on growth and invasive properties of human ovarian carcinoma cells through suppression of heregulin/HER3 pathway

Original Article

Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients

Original Article

Diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo cells and carcinoembryonic antigen in differentiating malignant from benign pleural effusion

Original Article

The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas

Original Article

The SDF-1/CXCR4 chemokine axis in uveal melanoma cell proliferation and migration
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits