Abstract 1311: PET-MRI microdosing can determine the delivery of the experimental cancer therapeutic, MN-anti-miR10b, to metastatic lesions in a murine model of breast cancer

Abstract Background In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases. Results In this study, we devised a method to efficiently radiolabel MN-anti-miR10b with Cu-64 (64Cu) and evaluated the pharmacokinetics and biodistribution of the radiolabeled product at two different doses: a therapeutic dose, referred to as macrodose, corresponding to 64Cu-MN-anti-miR10b co-injected with non-labeled MN-anti-miR10b, and a tracer-level dose of 64Cu-MN-anti-miR10b, referred to as microdose. In addition, we evaluated the uptake of 64Cu-MN-anti-miR10b by metastatic lesions using both in vivo and ex vivo positron emission tomography–magnetic resonance imaging (PET–MRI). A comparable distribution of the therapeutic was observed after administration of a microdose or macrodose. Uptake of the therapeutic by metastatic lymph nodes, lungs, and bone was also demonstrated by PET–MRI with a significantly higher PET signal than in the same organs devoid of metastatic lesions. Conclusion Our results demonstrate that PET–MRI following a microdose injection of the agent will accurately reflect the innate biodistribution of the therapeutic. The tools developed in the present study lay the groundwork for the clinical testing of MN-anti-miR10b and other similar therapeutics in patients with cancer.

Download Full-text

Clinical relevance of a degree of extracapsular extension in a sentinel lymph node in breast cancer patients: a single-centre study

Scientific Reports ◽

10.1038/s41598-021-88351-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tomasz Nowikiewicz ◽

Andrzej Kurylcio ◽

Iwona Głowacka-Mrotek ◽

Maria Szymankiewicz ◽

Magdalena Nowikiewicz ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Term Treatment ◽

Extracapsular Extension ◽

Group Iii ◽

Metastatic Lesions ◽

Cancer Metastases ◽

Group I ◽

Long Term Treatment

AbstractIn some breast cancer (BC) patients, an examination of lymph nodes dissected during sentinel lymph node biopsy (SLNB) demonstrates a presence of metastatic lesions and extracapsular extension (ECE) in a SLN. This study aimed to evaluate clinical relevance of ECE in BC patients. This is a retrospective analysis of 891 patients with cancer metastases to SLN, referred to supplementary axillary lymph node dissection (ALND), hospitalized between Jan 2007 and Dec 2017. Clinical and epidemiological data was evaluated. Long-term treatment outcomes were analysed. In 433 (48.6%) patients, cancer metastases were limited to the SLN (group I), in 61 (6.8%) patients the SLN capsule was exceeded focally (≤ 1 mm—group II). In 397 (44.6%) patients, a more extensive ECE was found (> 1 mm—group III). Metastases to non-sentinel lymph nodes (nSLNs) were diagnosed in 27.0% patients from group I, 44.3% patients from group II and in 49.6% patients from group III. No statistically significant differences were observed in long-term treatment outcomes for compared groups. The presence of ECE is accompanied by a higher stage of metastatic lesions in the lymphatic system. The differences in this respect were statistically significant, when compared to the group of ECE(−) patients. ECE, regardless of its extent, did not impact the long-term treatment results. ECE remains an indication for supplementary ALND and for other equivalent cancer treatment procedures, regardless of ECE size.

Download Full-text

Opposite effects of protein kinase C beta1 (PKCβ1) and PKCε in the metastatic potential of a breast cancer murine model

Breast Cancer Research and Treatment ◽

10.1007/s10549-008-0299-4 ◽

2009 ◽

Vol 118 (3) ◽

pp. 469-480 ◽

Cited By ~ 19

Author(s):

Valeria C. Grossoni ◽

Laura B. Todaro ◽

Marcelo G. Kazanietz ◽

Elisa D. Bal de Kier Joffé ◽

Alejandro J. Urtreger

Keyword(s):

Breast Cancer ◽

Protein Kinase C ◽

Protein Kinase ◽

Murine Model ◽

Metastatic Potential ◽

Kinase C

Download Full-text

Lipofilling Reduces Dormant Breast Cancer Outgrowth as Opposed to Adipocutaneous Flap Controls in a New Murine Model of Postlumpectomy Breast Reconstruction

Plastic & Reconstructive Surgery Global Open ◽

10.1097/01.gox.0000721052.71225.8b ◽

2020 ◽

Vol 8 (9S) ◽

pp. 140-141

Author(s):

Benjamin Thomas ◽

Jan Warzsawski ◽

Florian Falkner ◽

Amir K. Bigdeli ◽

Boyan K. Garvalov ◽

...

Keyword(s):

Breast Cancer ◽

Breast Reconstruction ◽

Murine Model

Download Full-text

Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v3 ◽

2020 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

Download Full-text

BRAF V600E Mutation in Triple-Negative Breast Cancer: A Case Report and Literature Review

Oncology Research and Treatment ◽

10.1159/000520453 ◽

2021 ◽

pp. 1-7

Author(s):

Liye Wang ◽

Qianyi Lu ◽

Kuikui Jiang ◽

Ruoxi Hong ◽

Shusen Wang ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Progression Free Survival ◽

Multiple Organ ◽

Braf V600e ◽

Case Presentation ◽

Free Survival ◽

Metastatic Lesions ◽

Potential Prognostic Factor ◽

New Mutations

Background: The B-Raf proto-oncogene (BRAFV600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAFV600E mutant breast cancer (BC) has been reported. Case Presentation: We reported a 60-year-old woman with confirmed triple-negative BC with BRAFV600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAFV600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. Conclusions: The BRAFV600E mutation may be a potential prognostic factor and therapeutic target for BC.

Download Full-text

Clinical, morphological, and molecular genetic predictors of metastatic lesions in the regional lymph nodes in breast cancer

Advances in molecular oncology ◽

10.17650/2313-805x-2018-5-3-8-16 ◽

2018 ◽

Vol 5 (3) ◽

pp. 8-16

Author(s):

Yu. A. Dergunova ◽

V. V. Podionov ◽

V. K. Bozhenko ◽

V. V. Kometova ◽

M. V. Dardyk

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Molecular Genetic ◽

Regional Lymph Nodes ◽

Genetic Characteristics ◽

Metastatic Lesions ◽

Genetic Predictors ◽

Node Metastases ◽

High Degree

Despite the sufficient amount of data accumulated in the literature, there are still no factors, on the basis of which it would be possible to estimate the regional lymph nodes status in breast cancer with a high degree of accuracy. The review presents literature data relating to the influence of clinicopathological, molecular-biological and genetic characteristics of primary tumor on lymph node metastases. Data of 66 foreign and Russian articles are included.

Download Full-text

Immunotherapeutic efficacy of a Lactobacillus casei lysate as an adjuvant combined with a heated-4T1 mammary carcinoma cell lysate in a murine model of breast cancer

Asian Biomedicine ◽

10.5372/1905-7415.1004.494 ◽

2017 ◽

Vol 10 (4) ◽

pp. 327-334 ◽

Cited By ~ 1

Author(s):

Ruhollah Dorostkar ◽

Mohammad Sadegh Hashemzadeh ◽

Sajjad Jafari ◽

Mahdi Tat ◽

Majdedin Ghalavand ◽

...

Keyword(s):

Breast Cancer ◽

Murine Model ◽

Mammary Carcinoma ◽

Tumor Size ◽

Lactobacillus Casei ◽

Tumor Antigens ◽

Carcinoma Cell ◽

Mammary Carcinoma Cell ◽

Cell Lysate ◽

4T1 Cells

Abstract Background Immunotherapy, during which the immune system of the patient is manipulated to act against tumors has been among the most successful methods in the treatment of breast cancer, a leading cause of mortality among women worldwide. Objectives To investigate the immunotherapeutic efficacy of Lactobacillus casei lysate as an adjuvant in combination with a heated-4T1 mammary carcinoma cell lysate in a model of breast cancer. Methods After ethics committee approval of all animal procedures, a murine model of breast cancer was induced in BALB/c mice using 4T1 cells. These mice were immunized with a combination of lysates of heated 4T1 cells and L. casei. Subsequent changes in tumor size and weight, and the production of TNF-α, IL-2, IL-12, IL-17, and IL13 were measured. Lung weights were measured as an indicator of metastasis to other organs. Results The tumor size and weight in mice immunized with the combined vaccine were significantly reduced compared with controls. The combined immunotherapy altered the pattern of cytokine production to the advantage of antitumor immunity, and was significantly more potent than immunization with heated-4T1-cell lysate or L. casei lysate alone. Conclusions Coadministration of L. casei lysate enhanced the immunotherapeutic efficacy of the heated-4T1-cell lysate as a source of tumor-associated antigens. L. casei can potentially be used as an adjuvant combined with sources of tumor antigens in the treatment of cancers, and as a safe alternative to the current adjuvants that cause greater irritation to hosts. Further studies are required to clarify the mechanisms underlying these effects.

Download Full-text