scholarly journals “γδT Cell-IL17A-Neutrophil” Axis Drives Immunosuppression and Confers Breast Cancer Resistance to High-Dose Anti-VEGFR2 Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhigang Zhang ◽  
Chenghui Yang ◽  
Lili Li ◽  
Ying Zhu ◽  
Ke Su ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Low Dose ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Γδ T Cells ◽  
High Dose ◽  
Therapeutic Effects ◽  
Cancer Resistance ◽  
Breast Cancer Patients

Angiogenesis is an essential physiological process and hallmark of cancer. Currently, antiangiogenic therapy, mostly targeting the vascular endothelial growth factor (VEGF)/VEGFR2 signaling axis, is commonly used in the clinic for solid tumors. However, antiangiogenic therapies for breast cancer patients have produced limited survival benefits since cancer cells rapidly resistant to anti-VEGFR2 therapy. We applied the low-dose and high-dose VEGFR2 mAb or VEGFR2-tyrosine kinase inhibitor (TKI) agents in multiple breast cancer mouse models and found that low-dose VEGFR2 mAb or VEGFR2-TKI achieved good effects in controlling cancer progression, while high-dose treatment was not effective. To further investigate the mechanism involved in regulating the drug resistance, we found that high-dose anti-VEGFR2 treatment elicited IL17A expression in γδ T cells via VEGFR1-PI3K-AKT pathway activation and then promoted N2-like neutrophil polarization, thus inducing CD8+ T cell exhaustion to shape an immunosuppressive microenvironment. Combining anti-VEGFR2 therapy with immunotherapy such as IL17A, PD-1 or Ly-6G mAb therapy, which targeting the immunomodulatory axis of “γδT17 cells-N2 neutrophils” in vivo, showed promising therapeutic effects in breast cancer treatment. This study illustrates the potential mechanism of antiangiogenic therapy resistance in breast cancer and provides synergy treatment for cancer.

scholarly journals Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients

Breast Care ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. 272-276 ◽  
Author(s):  
Slavomir Krajnak ◽  
Marco Battista ◽  
Walburgis Brenner ◽  
Katrin Almstedt ◽  
Tania Elger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Side Effects ◽  
Low Dose ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Therapeutic Effects ◽  
Breast Cancer Patients ◽  
Phase Ii Studies

Background: Low-dose metronomic chemotherapy (LDMC) is increasingly used in metastatic breast cancer (MBC). In this retrospective analysis, we examined the therapeutic effects and side effects of LDMC in a cohort of MBC patients. Methods: Patients with MBC were included when LDMC with oral cyclophosphamide (CTX) and methotrexate (MTX) was administered between 2009 and 2015. The primary endpoint was disease control rate (DCR) ≥ 24 weeks after the start of LDMC. Secondary endpoints were duration of progression-free survival (PFS), rates of discontinuation due to side effects, and DCR with regard to subgroups. Results: Retrospective data of 35 patients were available for this analysis. 31% patients achieved DCR. The median PFS was 12 weeks. 9% of patients discontinued LDMC due to adverse events. DCR was 37% in the first 2 lines and 25% in further lines of therapy. 22% of patients with multiple metastases and 35% with ≤2 different metastatic sites achieved DCR. DCR was achieved in 33% of hormone receptor(HR)-positive patients and 27% of HR-negative patients. Conclusion: The DCR of 31% is in line with the results of previous phase II studies. LDMC was well tolerated. Subgroup analysis was not able to identify a group in which LDMC was more efficient.

Estimation of maximum tolerated dose and minimum efficient dose of BP-C1 in the treatment of stage IV breast cancer patients: A phase I response surface pathway designed study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11022-e11022
Author(s):  
Stig Einride Larsen ◽  
Sagita Dewi ◽  
Vichien Srimuninnimit ◽  
Yen-Shen Lu ◽  
Tjakra Manuaba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Dose ◽  
Dose Group ◽  
Low Dose ◽  
Stage Iv ◽  
Maximum Tolerated Dose ◽  
High Dose Group ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Stage Iv Breast Cancer

e11022 Background: The aims were to establish a treatment routine and to estimate the Maximum Tolerated Dose (MTD) and the Minimum Efficient Dose (MED) of a novel anti-cancer agent named BP-C1. Methods: The material consists of 15 Stage IV breast cancer patients with a mean age of 51 years. The study was performed as a non-randomized multi-centre trial with between patient 3-level Response Surface Pathway design. BP-C1 was given intramuscularly once daily during 32 days. The given cumulative dose window was 0.16 to 1.12 mg/kg bw, resulting in a starting dose of 0.64 mg/kg bw. The main variable was the National Cancer Institute common toxicity criteria (NCI-CTC) Bethesda. If the increase in toxicity was classified as moderate or less, the next patient in the sequence was allocated to an increased dose. In case of severe toxicity increase, the dose was reduced. Patients receiving cumulative dose of 0.96 mg/kg bw or higher was defines as the high-dose group. Results: Three of the five patients on the first design level recorded unchanged toxicity, one mild and one moderate increased Max NCI-CTC. Of the four patients receiving 0.96 mg/kg bw, three obtained no change and one a mild toxicity increase. The four patients on the third design level received the maximal dose of 1.12 mg/kg bw without any change in Max NCI-CTC. The Sum NCI-CTC increased (p= 0.07) in the low-dose group, but reduced (p=0.09) in the high-dose group. The cumulative dose of BP-C1 was found significantly (p=0.048) and negatively correlated (r = - 0.52) to the increase in toxicity. Only mild to moderate Adverse Events were reported and the prevalence was found largest in the high dose group (p=0.06). In the high-dose group 62.5% of the patients were classified as responders compared to 28.6% in the low-dose group. One of the patients in the high-dose group was classified as complete responder. The development in both Karnofsky Scale of Performance Status and patient wellbeing was found obviously better in the high-dose group. Conclusions: BP-C1 can safely be administrated continuously during a period of 32 days. The MTD seem to be at least 1.12 mg/kg bw and the MED to be 0.96 mg/kg bw.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1918
Author(s):  
Mio Yamaguchi ◽  
Kiyoshi Takagi ◽  
Koki Narita ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Human Breast Carcinoma ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

scholarly journals Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsunori Tozuka ◽  
Pattama Wongsirisin ◽  
Shigenori E. Nagai ◽  
Yasuhito Kobayashi ◽  
Miki Kanno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Recurrent Breast Cancer ◽  
Stage I ◽  
Breast Cancer Patients ◽  
Potential Biomarker ◽  
Phosphatase 2A ◽  
Mcf 7

AbstractTo understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60–70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I–III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I–III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.

265 Endocrine effects of low dose aminoglutethimide without hydrocortisone in breast cancer patients

1983 ◽  
Vol 19 ◽  
pp. 88
Author(s):  
R. Stuart-Harris ◽  
M. Dowsett ◽  
A. D'Souza ◽  
S.L. Jeffcoate ◽  
I.E. Smith
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Low Dose ◽  
Breast Cancer Patients ◽  
Endocrine Effects
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