scholarly journals Global Assessment of IRF8 as a Novel Cancer Biomarker

2021 ◽  
Author(s):  
Daniel C. McQuaid ◽  
Gauri Panse ◽  
Wei-Lien Wang ◽  
Samuel G. Katz ◽  
Mina L. Xu
Keyword(s):  
Triple Negative ◽  
Plasmacytoid Dendritic Cell ◽  
Differential Diagnoses ◽  
Expression Data ◽  
Breast Cancers ◽  
Regulatory Factor ◽  
Mrna Expression Data ◽  
Weak Staining ◽  
Synovial Sarcomas ◽  
Round Cell Tumors

AbstractInterferon regulatory factor 8 (IRF8) is a member of the IRF family that is specific to the hematopoietic cell and is involved in regulating the development of human monocytic and dendritic-lineage cells, as well as B cells. Since its utility as a sensitive and specific monoblast marker in the context of acute monocytic leukemias has been recently demonstrated, we hypothesized that it may also be useful as a novel immunohistochemical marker in myeloid sarcomas and blastic plasmacytoid dendritic cell neoplasms (BPDCN) with respect to their differential diagnoses. In this retrospective study, we analyzed the IHC expression pattern of IRF8 in 385 patient samples across 30 types of cancers, referenced to their mRNA expression data available through TCGA. In addition, we assessed IRF8 in 35 myeloid sarcomas, and 13 BPDCNs. Twenty-four of 35 cases of myeloid sarcomas (68.5%) showed positivity for IRF8, with six cases (17.1%) demonstrating IRF8 expression in the absence of CD34 and MPO. All 13 of 13 BPDCNs (100%) showed strong uniform expression of IRF8 and was occasionally more definitive than CD123. IRF8 was negative in all desmoplastic small round cell tumors, Ewing sarcomas, synovial sarcomas, and undifferentiated pleomorphic sarcomas, as well as all epithelial malignancies tested except for 2 triple negative breast cancers that showed subset weak staining. In conclusion, IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers.

scholarly journals mRNA expression data in breast cancers before and after consumption of walnut by women

Data in Brief ◽  
2019 ◽  
Vol 25 ◽  
pp. 104050 ◽  
Author(s):  
W. Elaine Hardman ◽  
Donald A. Primerano ◽  
Mary T. Legenza ◽  
James Morgan ◽  
Jun Fan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Data ◽  
Breast Cancers ◽  
Mrna Expression Data ◽  
Before And After

scholarly journals Triple-negative breast cancers are increased in black women regardless of age or body mass index

2009 ◽  
Vol 11 (2) ◽  
Author(s):  
Lesley A Stead ◽  
Timothy L Lash ◽  
Jerome E Sobieraj ◽  
Dorcas D Chi ◽  
Jennifer L Westrup ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Black Women ◽  
Body Mass ◽  
Triple Negative ◽  
Breast Cancers

scholarly journals Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hormone Replacement ◽  
Breast Cancers ◽  
Younger Women ◽  
Alternative Pathways ◽  
Increased Risk ◽  
History Of ◽  
Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

scholarly journals INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Samuel J. Rodgers ◽  
Lisa M. Ooms ◽  
Viola M. J. Oorschot ◽  
Ralf B. Schittenhelm ◽  
Elizabeth V. Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Akt Signaling ◽  
Late Endosome ◽  
Breast Cancers ◽  
Lysosomal Degradation ◽  
Late Endosomes ◽  
Mrna And Protein Expression

AbstractINPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P2 to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER+ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER+ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P2 to PI(3)P conversion, late endosome/lysosome number and cargo trafficking, resulting in enhanced GSK3β lysosomal degradation and activation of Wnt/β-catenin signaling. Mechanistically, Wnt inhibition or depletion of the PI(3)P-effector, Hrs, reduced INPP4B-mediated cell proliferation and tumor growth. Therefore, INPP4B facilitates PI3Kα crosstalk with Wnt signaling in ER+ breast cancer via PI(3,4)P2 to PI(3)P conversion on late endosomes, suggesting these tumors may be targeted with combined PI3K and Wnt/β-catenin therapies.

scholarly journals The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stijn Moens ◽  
Peihua Zhao ◽  
Maria Francesca Baietti ◽  
Oliviero Marinelli ◽  
Delphi Van Haver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Mitotic Checkpoint ◽  
Breast Cancers ◽  
Checkpoint Kinases ◽  
Xenograft Models ◽  
Potential Strategy ◽  
Shrna Screen ◽  
Resistant Cells

AbstractTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking effective therapy. Many TNBCs show remarkable response to carboplatin-based chemotherapy, but often develop resistance over time. With increasing use of carboplatin in the clinic, there is a pressing need to identify vulnerabilities of carboplatin-resistant tumors. In this study, we generated carboplatin-resistant TNBC MDA-MB-468 cell line and patient derived TNBC xenograft models. Mass spectrometry-based proteome profiling demonstrated that carboplatin resistance in TNBC is linked to drastic metabolism rewiring and upregulation of anti-oxidative response that supports cell replication by maintaining low levels of DNA damage in the presence of carboplatin. Carboplatin-resistant cells also exhibited dysregulation of the mitotic checkpoint. A kinome shRNA screen revealed that carboplatin-resistant cells are vulnerable to the depletion of the mitotic checkpoint regulators, whereas the checkpoint kinases CHEK1 and WEE1 are indispensable for the survival of carboplatin-resistant cells in the presence of carboplatin. We confirmed that pharmacological inhibition of CHEK1 by prexasertib in the presence of carboplatin is well tolerated by mice and suppresses the growth of carboplatin-resistant TNBC xenografts. Thus, abrogation of the mitotic checkpoint by CHEK1 inhibition re-sensitizes carboplatin-resistant TNBCs to carboplatin and represents a potential strategy for the treatment of carboplatin-resistant TNBCs.

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