Our novel findings indicate that CD44(+)ALDH1(+)Ki-67(-) tumor cells may favor distant metastasis and can predict overall survival in patients with ductal carcinomas of the breast. More importantly, quiescence may have a crucial role for tumor progression, treatment resistance and metastatic ability of BCSCs.
Breast cancer epithelial cells with the CD44/CD24 phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44/CD24/cytokeratin(Ck)/CD45 cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44/CD24/Ck/CD45 cells. E-Cadherin and vimentin immunohistochemistry was performed on sections from the corresponding formalin-fixed, paraffin-embedded (FFPE) blocks. The percentage of CD44/CD24/Ck/CD45 cells increased significantly from non-malignant to malignant lesions and in association with a significant increase in the expression of vimentin. Non-malignant lesions harbored only a single-nucleotide polymorphism (SNP). Mutations in the tumor suppressor p53 (TP53), NOTCH homolog 1 (NOTCH1), phosphatase and tensin homolog (PTEN), and v-akt murine thymoma viral oncogene homolog 1 (AKT1) genes were found in isolated CD44/CD24/Ck/CD45 cells from ductal carcinomas in situ (DCIS). Additional mutations in the colony-stimulating factor 1 receptor (CSF1R), ret proto-oncogene (RET), and TP53 genes were also identified in invasive ductal carcinomas (IDCs). The use of massive parallel sequencing technology for this type of application revealed to be extremely effective even when using small amounts of DNA extracted from a low number of cells. Additional studies are now required using larger cohorts to design an appropriate mutational profile for this phenotype.
The American Association of Oral and Maxillofacial Surgeons (AAOMS) reported in 2004 a new pathology that causes osteonecrosis in the Maxillomandibular complex. The condition was named Bisphosphonate-related osteonecrosis of the jaw (BRONJ), and later renamed by medication related to jaw osteonecrosis due to the appearance of severe alveolar bone loss in the Maxillomandibular complex resulting from the use of different drugs other than Bisphosphonates. Odontology, especially oral surgery, a field concerned with new biotechnologies, has been introducing innovations in tissue engineering. Oro-maxillofacial reconstruction is of great interest to current oral and maxillofacial surgeons, as part of the search for strategies in bioengineering and biomaterials, a major promoter of bio-dental research in our times. In order to verify the scientific evidences to analyse the effectiveness of leukocyte and platelet rich fibrin (L-PRF) on bone neoformation in Maxillomandibular complex's surgical procedures, a search for qualified articles was conducted in the Medline (PubMed), Embase and Cochrane Central Register of Controlled Trials databases. The works analysed were published from 2013 to 2018. This review concludes that the use of platelet rich fibrin (L-PRF) is significant in the complete healing of the lesion in short postoperative periods and in the resolution of the treatments, reducing the need for postoperative re-interventions, resulting in lower morbidity for the patients.
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