Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case-control study.

PURPOSE: Triple negative breast cancer (TNBC) is more common in African American (AA) than Non-AA (NAA) population. We hypothesize that tumor microenvironment (TME) contributes to this disparity. Here, we use multiplex quantitative immunofluorescence to characterize the expression of immunologic biomarkers in the TME in both populations. PATIENTS AND METHODS: TNBC tumor resection specimen tissues from a 100-patient case: control cohort including 49 AA and 51 NAA were collected. TME markers including CD45, CD14, CD68, CD206, CD4, CD8, CD20, CD3, Ki67, GzB, Thy1, FAP, aSMA, CD34, Col4, VWF and PD-L1 we quantitatively assessed in every field of view. Mean expression levels were compared between cases and controls. RESULTS: Although no significant differences were detected in individual lymphoid and myeloid markers, we found that infiltration with CD45+ immune cells (p = 0.0102) was higher in TNBC in AA population. AA TNBC tumors also had significantly higher level of lymphocytic infiltration defined as CD45+ CD14- cells (p = 0.0081). CD3+ T-cells in AA tumors expressed significantly higher levels of Ki67 (0.0066) compared to NAAs, indicating that a higher percentage of AA tumors contained activated T-cells. All other biomarkers showed no significant differences between the AA and NAA group. CONCLUSIONS: While the TME in TNBC is rich in immune cells in both racial groups, there is a numerical increase in lymphoid infiltration in AA compared to NAA TNBC. Significantly, higher activated T cells seen in AA patients raises the possibility that there may be a subset of AA patients with improved response to immunotherapy.

Comparison of Vestibular Depth Relapse and Wound Healing After Reconstructive Preprosthetic Surgery Using Cryopreserved Amniotic Membrane and Acellular Dermal Matrix - A Comparative Study.

INTRODUCTION: The significance of membranes as wound dressing in oral surgeries has been reported by previous studies. The aim of the present split-mouth randomized clinical study was to assess and compare the wound dressing properties of acellular dermal matrix (ADM) and cryopreserved human amniotic membrane (AM) after reconstructive preprosthetic oral surgery. MATERIALS AND METHODS: Twenty-eight patients with complete mandibular edentulism and resorbed alveolar bone were included. After taking mandibular impression, a clear acrylic splint with increased labial flange height was created. In each participant, labial vestibular depth was elevated using the Clark's technique. Subsequently, half of the exposed periosteum was covered with ADM while the other half was covered with cryopreserved human AM. Vestibule depth and relapse in the two sides were measured immediately after vestibuloplasty and at the end of the 1st week, 2nd week, 1st month, and 3rd months with graduations of 0.1 mm. Furthermore, after 3 and 7 days, samples were collected from graft material, and the macrophage population was analyzed by flow cytometry. RESULTS: There was no significant difference in the relapse of vestibule depth between the two grafts at different time intervals. However, the frequency of wound-infiltrating macrophages (CD68+ cells) was significantly higher in areas covered by ADM after 3 and 7 days. DISCUSSION: ADM is as effective as cryopreserved AM in terms of maintaining the postoperative vestibular depth. On the other hand, our results suggested that the onset of healing phase in ADM-covered areas occurs faster compared to the periosteum covered with cryopreserved human AM. This clinical trial showed significantly faster postoperative healing onset when ADM was used than when cryopreserved human AM was applied on the periosteum.

The effects of mineral trioxide aggregate on osteo/odontogenic potential of mesenchymal stem cells: a comprehensive and systematic literature review.

The significance of dental materials in dentin-pulp complex tissue engineering is undeniable. The mechanical properties and bioactivity of mineral trioxide aggregate (MTA) make it a promising biomaterial for future stem cell-based endodontic therapies. There are numerous in vitro studies suggesting the low cytotoxicity of MTA towards various types of cells. Moreover, it has been shown that MTA can enhance mesenchymal stem cells' (MSCs) osteo/odontogenic ability. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), a literature review was conducted in the Medline, PubMed, and Scopus databases. Among the identified records, the cytotoxicity and osteo/odontoblastic potential of MTA or its extract on stem cells were investigated. Previous studies have discovered the differentiation-inducing potential of MTA on MSCs, providing a background for dentin-pulp complex cell therapies using the MTA, however, animal trials are needed before moving into clinical trials. In conclusion, MTA can be a promising candidate dental biomaterial for futuristic stem cell-based endodontic therapies.

MTA Enhances the Potential of Adipose-Derived Mesenchymal Stem Cells for Dentin-Pulp Complex Regeneration.

The aim of the current study was to investigate the effects of mineral trioxide aggregate (MTA) on the proliferation and differentiation of human adipose-derived mesenchymal stem cells (Ad-MSCs) as a surrogate cell source in futuristic stem-cell-based endodontic therapies. Human Ad-MSCs and mesenchymal stem cells derived from bone marrow (BM-MSCs) were isolated from liposuction waste adipose tissue and femur, respectively, and the effects of MTA-conditioned media on their viability, mineralization potential, and osteo/odontogenic differentiation capacity were subsequently evaluated. Alkaline phosphatase (ALP) activity, quantitative alizarin red S staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and compare the osteo/odontogenic induction potential of MTA on the Ad/BM-MSCs. The results of cytotoxicity assay revealed that at different concentrations, MTA-conditioned medium was not only biocompatible toward both cell types, but also capable of promoting cell proliferation. ALP activity assay showed that 0.2 mg/mL was the optimal concentration of MTA-conditioned medium for osteo/odontogenic induction in Ad/BM-MSCs. The expression of osteo/odontogenic gene markers was increased in Ad/BM-MSCs treated with 0.2 mg/mL MTA-conditioned media. Our results indicated that MTA can efficiently enhance the osteo/odontogenic potential of Ad-MSCs, and thus they can be considered as a better cell source for dentin-pulp complex regeneration. However, further investigations are required to test these potentials in animal models.