Search results for "Triple-negative"

The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT

2021

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients’ outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative…

Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells

2021

Triple-negative breast cancer (TNBC) is a highly aggressive disease with invasive and metastasizing properties associated with a poor prognosis. The STAT3 signaling pathway has shown a pivotal role in cancer cell migration, invasion, metastasis and drug resistance of TNBC cells. IL-6 is a main upstream activator of the JAK2/STAT3 pathway. In the present study we examined the impact of the NO-donor glyceryl trinitrate (GTN) on the activation of the JAK2/STAT3 signaling pathway and subsequent migration, invasion and metastasis ability of TNBC cells through in vitro and in vivo experiments. We used a subtoxic dose of carboplatin and/or recombinant IL-6 to activate the JAK2/STAT3 signaling path…

Abstract A18: miR-9 and miR-200 regulate PDGFRβ-mediated endothelial differentiation of neoplastic cells in triple-negative breast cancer

2016

Abstract Tumor vascularization is a fundamental step in solid tumor progression and is orchestrated by different pathways of vasculogenesis. In malignant tumors, neoplastic cells can differentiate into endothelial-like cells acquiring the expression of endothelial markers (i.e. CD31 and CD34) and participating in the formation of vascular-like structures that functionally deliver oxygen and nutrients to the tumor site. We recently identified PDGFRβ as an important player of this process in triple negative breast cancer (TNBC). Interestingly, increasing evidence supported a connection between PDGFRβ and epithelial to mesenchymal transition (EMT), important step for the endothelial trans-diff…

Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects

2022

Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging out-comes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen depo-sition. Furthermore, FMD reduces the occurrence of immune-related adve…

Synthesis of curcumin derivatives and analysis of their antitumor effects in triple negative breast cancer (TNBC) cell lines

2019

We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC50 in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least eq…

The C-X-C Motif Chemokine Ligand 1 Sustains Breast Cancer Stem Cell Self-Renewal and Promotes Tumor Progression and Immune Escape Programs

2021

Breast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, includingSPP1/OPN,ACKR3/CXCR7,TLR4,TNFSF10/TRAILandCCL18and, to a lesser exte…

Identification and analysis of tumor-associated antigens in triple-negative breast cancer (TNBC)

2020

Triple-Negativity Identifies a Subgroup of Patients with Better Overall Survival in Essential Thrombocythemia

2022

Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed…

Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer

2019

There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on health…

(+)-Dehydroabietylamine derivatives target triple-negative breast cancer.

2015

Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)…