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Background: PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previously generated a conditionally activatable Pik3caH1047R;MMTV-Cre mouse model and found a few malignant sarcomatoid (spindle cell) carcinomas that had acquired spontaneous dominant-negative Trp53 mutations.
Methods: A Pik3caH1047R;Trp53R270H;MMTV-Cre double mutant mouse breast cancer model was generated. Tumors were characterized by histology, marker analysis, transcriptional profiling, single-cell RNA-seq, and bioinformatics. Cell lines were developed from mutant tumors and used to identify and confirm genes involved in metastasis.
Results: We found Pik3caH1047R and Trp53R270H cooperate in driving oncogenesis in mammary glands leading to a shorter latency than either alone. Double mutant mice develop multiple histologically distinct mammary tumors, including adenocarcinoma and sarcomatoid (spindle cell) carcinoma. We found some tumors to be invasive and a few metastasized to the lung and/or the lymph node. Single-cell RNA-seq analysis of the tumors identified epithelial, stromal, myeloid, and T cell groups. Expression analysis of the metastatic tumors identified S100a4 as a top candidate gene associated with metastasis. Metastatic tumors contained a much higher percentage of epithelial-mesenchymal transition (EMT)-signature positive and S100a4-expressing cells. CRISPR/CAS9-mediated knockout of S100a4 in a metastatic tumor-derived cell line disrupted its metastatic potential indicating a role for S100a4 in metastasis.
Conclusions: Pik3caH1047R;Trp53R270H;MMTV-Cre mouse provides a preclinical model to mimic a subtype of human breast cancers that carry both PIK3CA and TP53 mutations. It also allows for understanding the cooperation between the two mutant genes in tumorigenesis. Our model also provides a system to study metastasis and develop therapeutic strategies for PIK3CA/TP53 double-positive cancers. S100a4 found involved in metastasis in this model can be a potential diagnostic and therapeutic target.
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http://dx.doi.org/10.1186/s13058-019-1238-5 | DOI Listing |
Clin Transl Oncol
December 2024
Centro Oncológico Integral Canario, Hospital Universitario San Roque, Las Palmas, Spain.
Aim: To assess for the first time the safety and feasibility of combining photon-IntraOperative RadioTherapy (ph-IORT) with hypofractionated whole-breast irradiation (hWBI) in patients referred to adjuvant radiotherapy after Breast-Conserving Surgery (BCS).
Methods: From February 2019 to August 2020, patients referred for breast-conserving surgery (BCS) in our institution were prospectively included in the present trial. BCS was discussed in the multidisciplinary tumor board (MTB).
Aesthetic Plast Surg
December 2024
Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun City, 130033, Jilin Province, China.
Background: Oncoplastic surgery for breast cancer patients poses the challenge of achieving optimal aesthetic outcomes without increasing the risk of complications. Omental flap has emerged as n reconstructive option in breast surgery, yet the efficacy and safety of large omental flaps remain uncertain. This study aims to conduct a systematic review and single-arm meta-analysis to comprehensively evaluate the effectiveness, safety, and cosmetic outcomes of large omental flap breast reconstruction, providing updated evidence for clinical practice.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Institute of Sports Medicine & Prevention, University Leipzig, Leipzig, Germany.
Purpose: The reduced cardiorespiratory fitness (CRF) and functional capacity following surgical procedures and during cancer treatments is a major risk factor for morbidity and mortality among patients with cancer. We aimed to assess the impact of endurance and combined resistance exercise interventions during the postoperative rehabilitation period for patients with colorectal, breast, and prostate cancer.
Methods: A systematic search was conducted in MEDLINE Pubmed, Web of Science, and Cochrane Library until October 2023 for randomized controlled trials that assessed exercise interventions (aerobic/endurance; resistance or combined training) on postoperative patients with cancer.
Mamm Genome
December 2024
Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No. 61# Jiefang West Road, Changsha, 410005, Hunan, China.
Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease, which have function on maintaining genomic stability. Elevated expression of EXO1 has been reported in certain cancers. However, a comprehensive pan-cancer analysis of EXO1 is still lacking and its role in human cancer development remains poorly understood.
View Article and Find Full Text PDFArh Hig Rada Toksikol
December 2024
1University of Belgrade Faculty of Pharmacy, Department of Pathobiology, Belgrade, Serbia.
Medicinal mushroom extracts, i.e. their dried biomass, have long been known as sources of bioactive compounds with positive effects on the human health.
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