Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients

AbstractCurrently, there are no markers to identify patients with liver-only or liver-dominant metastases that would benefit from hepatic surgery. Here we characterized histopathological growth patterns (HGPs) of liver metastases in a consecutive series of 36 breast cancer patients who underwent hepatic surgery. Survival analyses showed that the presence of a desmoplastic HGP in the liver metastases (a rim of fibrous tissue separating cancer cells from the liver parenchyma, present in 20 (56%) patients) is independently associated with favorable progression-free and overall survival when compared with the replacement HGP (cancer cells growing into the liver parenchyma, present in 16 (44%) patients).

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Abstract P3-01-13: Association between the histopathological growth patterns (HGP) of liver metastases (LM) and survival after hepatic surgery in patients with oligometastatic breast cancer (BC)

10.1158/1538-7445.sabcs19-p3-01-13 ◽

2020 ◽

Author(s):

Peter B Vermeulen ◽

Ali Bohlok ◽

Sophia Leduc ◽

François Richard ◽

Lara Botzenhart ◽

...

Keyword(s):

Breast Cancer ◽

Liver Metastases ◽

Growth Patterns ◽

Hepatic Surgery ◽

Histopathological Growth Patterns

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Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

Cancer Biomarkers ◽

10.3233/cbm-210111 ◽

2021 ◽

pp. 1-10

Author(s):

Yu Wang ◽

Han Zhao ◽

Ping Zhao ◽

Xingang Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Cancers ◽

10.3390/cancers13051119 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1119

Author(s):

Ivonne Nel ◽

Erik W. Morawetz ◽

Dimitrij Tschodu ◽

Josef A. Käs ◽

Bahriye Aktas

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Hematopoietic Cells ◽

Surrogate Marker ◽

Clinical Samples ◽

Breast Cancer Patients ◽

Shape Restoration

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.

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Major Histocompatibility Complex Class II+ Invariant Chain Negative Breast Cancer Cells Present Unique Peptides that Activate Tumor-specific T Cells from Breast Cancer Patients

Molecular & Cellular Proteomics ◽

10.1074/mcp.m112.019232 ◽

2012 ◽

Vol 11 (11) ◽

pp. 1457-1467 ◽

Cited By ~ 12

Author(s):

Olesya Chornoguz ◽

Alexei Gapeev ◽

Michael C. O'Neill ◽

Suzanne Ostrand-Rosenberg

Keyword(s):

Breast Cancer ◽

T Cells ◽

Cancer Cells ◽

Cancer Patients ◽

Mhc Class Ii ◽

Breast Cancer Cells ◽

Class Ii ◽

Breast Cancer Patients ◽

Mhc Ii ◽

Peptide Loading

The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes. Because Ii prevents peptide loading in neutral subcellular compartments, we reasoned that Ii− cells may present peptides not presented by Ii+ cells. Based on the hypothesis that patients are tolerant to MHC II-restricted tumor peptides presented by Ii+ cells, but will not be tolerant to novel peptides presented by Ii− cells, we generated MHC II vaccines to activate cancer patients' T cells. The vaccines are Ii− tumor cells expressing syngeneic HLA-DR and the costimulatory molecule CD80. We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii− MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii− cells present novel peptides. Ii expression was induced in the HLA-DR7 transfectants by transfection of Ii, and inhibited in the CIITA transfectants by RNA interference. Peptides were analyzed and binding affinity predicted by artificial neural net analysis. HLA-DR7-restricted peptides from Ii− and Ii+ cells do not differ in size or in subcellular location of their source proteins; however, a subset of HLA-DR7-restricted peptides of Ii− cells are not presented by Ii+ cells, and are derived from source proteins not used by Ii+ cells. Peptides from Ii− cells with the highest predicted HLA-DR7 binding affinity were synthesized, and activated tumor-specific HLA-DR7+ human T cells from healthy donors and breast cancer patients, demonstrating that the MS-identified peptides are bonafide tumor antigens. These results demonstrate that Ii regulates the repertoire of tumor peptides presented by MHC class II+ breast cancer cells and identify novel immunogenic MHC II-restricted peptides that are potential therapeutic reagents for cancer patients.

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Mitochondrial Malic Enzyme 2 Promotes Breast Cancer Metastasis via Stabilizing HIF-1α Under Hypoxia

10.21203/rs.3.rs-138425/v1 ◽

2021 ◽

Author(s):

Duo You ◽

Danfeng Du ◽

Xueke Zhao ◽

Xinmin Li ◽

Minfeng Ying ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

High Expression ◽

Breast Cancer Patients ◽

Cancer Model ◽

Breast Cancer Model

Abstract Background: α-ketoglutarate (α-KG) is the substrate to hydoxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies showed that upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes HIF-1α via depleting α-KG in breast cancer cells. We propose that mitochondrial malate enzyme 2 (ME2) may also affect HIF-1α via modulating α-KG level in breast cancer cells. Methods: ME2 protein expression was evaluated by immunohistochemistry on 100 breast cancer patients and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated by an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α protein in breast cancer cell lines (4T1 and MDA-MB-231) was determined in vitro and in vivo.Results: The high expression of ME2 was observed in the human breast cancerous tissues compared to the matched precancerous tissues (P=0.000). The breast cancer patients with a high expression of ME2 had an inferior survival than the patients with low expression of ME2 (P=0.019). ME2 high expression in breast cancer tissues was also related with lymph node metastasis (P=0.016), pathological staging (P=0.033) and vascular cancer embolus (P=0.014). In a 4T1 orthotopic breast cancer model, ME2 knockout significantly inhibited lung metastasis. In the tumors formed by ME2 knockout 4T1 cells, α-KG level significantly increased, collagen hydroxylation level did not change significantly, but HIF-1α protein level significantly decreased, in comparison to control. In cell culture, ME2 knockout or knockdown cells demonstrated a significantly higher α-KG level but significantly lower HIF-1α protein level than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Treatment with malate significantly decreased 4T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α level in human breast cancer samples (P=0.027).Conclusion: We provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.

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