scholarly journals Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 127 ◽  
Author(s):  
Yueh-Chun Lee ◽  
Wen-Ling Wang ◽  
Wei-Chao Chang ◽  
Yu-Hao Huang ◽  
Guan-Ci Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Triple Negative ◽  
Mass Spectrometry Analysis ◽  
Radiation Response ◽  
Stem Cell Population ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Poor Prognostic Factor

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

scholarly journals Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Lama Abujamous ◽  
Mahmoud Abunasser ◽  
Sara Edaily ◽  
Rayan Bater
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Young Patients ◽  
Personal History ◽  
Mutation Rates ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Variant Of Uncertain Significance

AbstractBRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88–10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52–7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62–7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.

Comparison of serum levels of CEA and CA 15–3 in triple-negative breast cancer at the time of metastases and serum levels at the time of first diagnosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12017-e12017
Author(s):  
D. Sener Dede ◽  
S. Aksoy ◽  
N. Bulut ◽  
O. Dizdar ◽  
Z. Arik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Serum Levels ◽  
Breast Cancers ◽  
Negative Group ◽  
Breast Cancer Patients ◽  
Serum Cea

e12017 Background: Cancer antigen 15–3 (CA 15–3) and carcinoembryonic antigen (CEA), are often used in follow up care of breast cancer and provide important clues to the clinicians for disease progression in metastatic and recurrent breast cancer. Triple-negative breast cancers are frequently defined as a single group identifiable using routine clinical tests. They are negative for estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), the so-called triple-negative breast cancers. In this study we compared the tumor markers of triple negative breast cancer and non-triple negative patients. Methods: We retrospectively analyzed serum CEA and CA 15–3 levels of both triple negative and non-triple negative breast cancer patients at the time of first diagnosis and when they developed metastatic disease. Results: 544 consecutive nonmetastatic breast cancer patients presenting at Hacettepe University Institute of Oncology, Ankara, Turkey, with a median age of 49 were evaluated. 15.1% of the patients were triple negative breast cancer. At the time of diagnosis triple negative group had lower serum CEA (2.5 ± 5.9 vs 4.0 ±16.4 p = 0.35) and CA 15–3 (23.7 ± 14.6 vs 37.1 ± 117; p = 0.021) levels compared to non-triple negative group. In patients who developed metastasis during follow up; the CEA (3.2 ± 3.8 vs 29.6 ± 106.4 p = 0.022) and CA15–3 (46.9 ± 46.3 vs 203.2 ± 534 p = 0.008) levels were also significantly lower in triple negative breast cancer group compared to non-triple negative group.In non-triple negative breast cancer patients who developed metastasis, mean serum levels of CEA and CA15–3 significantly increased compared to baseline, whereas in triple negative group who developed metastasis CEA and CA 15–3 levels did not differ significantly. Conclusions: While being a good laboratory parameter in the follow-up of patients with breast cancer metastases, tumor markers may not show the increased tumor burden in the triple-negative breast cancer patients. No significant financial relationships to disclose.

Triple-negative breast cancer in Hong Kong Chinese patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22127-e22127
Author(s):  
J. Tsang ◽  
T. L. Lai ◽  
D. H. Lau ◽  
G. K. Au ◽  
D. T. Chua
Keyword(s):  
Breast Cancer ◽  
Hong Kong ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Hong Kong Chinese ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her 2

e22127 Background: There is increasing data showing that breast cancer is a heterogeneous disease which should be assessed separately in different populations, as it differs substantially between Chinese and Caucasian women. Triple-negative breast tumours which are negative for ER, PR and HER-2 neu receptors are associated with younger age at presentation, tumour of higher grade with larger size and a poorer prognosis. There is recent suggestion that the prognostic outlook of Chinese triple-negative breast cancers might be somewhat different from those in the Western population, but few studies have attempted to understand the role of ethnic factor in the triple-negative entity. Methods: We conducted a preliminary retrospective comparison of 170 Hong Kong Chinese primary breast cancer patients seen as new cases during January 2004 and December 2004 in a teaching hospital. Clinico-pathological features of triple-negative tumours were compared to their non-triple-negative counterpart. Results: Triple negative breast cancer accounted for 12.4% of all breast cancer patients seen in the year of 2004 (n = 21). It is associated with more cancers with grade 3 tumour (68.4% vs 36.8%; p = 0.02) but there was no statistically difference between the age of presentation, tumour size, extensive intraductal component, lymph node status and rate of local relapse or metastasis after adjuvant therapy. Subset analysis further revealed that when triple negative breast cancer patients (n = 21) were compared to the HER-2 positive patients (n = 40) in the studied population, HER-2 positive patients were still associated with higher proportion of node positive disease (57.5% vs 30.0%; p = 0.04). Disease free survival and overall survival were not studied due to limited follow-up time. Conclusions: Our preliminary findings suggested that Hong Kong Chinese triple-negative breast cancers are associated with a more favourable outlook and might behave differently when compared to their Western counterpart. Further large-scale study of the ethnic factor with long-term follow-up is warranted. No significant financial relationships to disclose.

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