The role of angiogenesis, inflammation and estrogen receptors in breast implant capsules development and remodeling

Segreto, Francesco; Carotti, Simone; Marangi, Giovanni Francesco; Tosi, Daniele; Zingariello, Maria; Pendolino, Alfonso Luca; Sancillo, Laura; Morini, Sergio; Persichetti, Paolo

doi:10.1016/j.bjps.2017.12.003

Cited by 13 publications

(23 citation statements)

References 29 publications

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“…38,39 Additionally, tamoxifen has a potent antiangiogenic effect, which was also validated by our current 40,41 These findings are relevant because higher Baker grades of capsular contracture are associated with greater levels of angiogenesis. 3 Although the total numbers of CD68+ cells were decreased in tamoxifen-treated mice, total amounts of both pro-inflammatory iNOS+ and anti-inflammatory CD163+ macrophages were not affected. This difference may be explained by the promiscuity of the CD68 cellular marker, which stains not only macrophages but also fibroblasts.…”

Section: Discussionmentioning

confidence: 90%

“…18 In addition, estrogen signaling has been noted to play a role in capsule formation, particularly with higher amounts of estrogen increasing the presence of myofibroblasts and collagen surrounding implants. 3 Correspondingly, capsular contracture is less common in patients on antiestrogen therapy. 17 Tamoxifen, a selective estrogen receptor modulator, is clinically indicated in estrogen receptor-positive breast cancer treatment for which it has a potent antitumor effect.…”

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confidence: 99%

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Tamoxifen reduces silicone implant capsule formation in a mouse model

et al. 2022

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Capsular contracture as a result of the foreign body response (FBR) is a common issue after implant‐based breast reconstruction, affecting up to 20% of patients. New evidence suggests that tamoxifen may mitigate the FBR. C57BL/6 female mice were treated with daily tamoxifen or control injections and implanted with bilateral silicone implants in the submammary glandular plane. Implants were removed en bloc after 2 weeks and the implant capsules were evaluated histologically. Tamoxifen treatment decreased capsule thickness, decreased the number of αSMA+ cells (477 ± 156 cells/mm control vs 295 ± 121 cells/mm tamoxifen, p = 0.005 unpaired t test), and decreased CD31+ cells (173.9 ± 96.1 cells/mm2 control vs 106.3 ± 51.8 cells/mm2 tamoxifen, p = 0.043 unpaired t test). There were similar amounts of pro‐ and anti‐inflammatory macrophages (iNOS 336.1 ± 226.3 cells/mm control vs 290.6 ± 104.2 cells/mm tamoxifen, p > 0.999 Mann–Whitney test and CD163 136.6 ± 76.4 cells/mm control vs 94.1 ± 45.9 cells/mm tamoxifen, p = 0.108 unpaired t test). Tamoxifen treatment in the mouse silicone breast implant model decreased capsule formation through modulation of myofibroblasts, neovascularization, and collagen deposition. Tamoxifen may be useful for reducing or preventing capsule formation in clinical breast implantations.

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Section: Discussionmentioning

confidence: 90%

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confidence: 99%

Tamoxifen reduces silicone implant capsule formation in a mouse model

et al. 2022

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“…They were subsequently stained by haematoxylin/eosin and immunohistochemistry antibodies for alpha smooth muscle actin (α‐SMA, as a marker of myofibroblasts, Clone 1A4 Dako), CD34 (as a marker of neo‐angiogenesis, Clone QBEnd/10 Biocare Medical), Ki67 (in keratinocytes and dermal fibroblasts, as a marker of cell proliferation, Clone MIB‐1 Dako), collagen type 1 (COL I Polyclonal IgG, AbD Serotec) and collagen type 3 (COL III, Polyclonal IgG, AbD Serotec). Secondary antibodies and processing were performed as previously described 8 . The positivity for α‐SMA was evaluated at a 400x magnification in three randomly chosen fields, then averaged and expressed a percentage of positive cells.…”

Section: Methodsmentioning

confidence: 99%

“…Neo‐angiogenesis was evaluated by CD34 positivity, with the Weidner method 9 . Collagen positivity was assessed as previously described, 8 Ki67 positivity of keratinocytes and dermal cells was evaluated as the average percentage of positive cells in three randomly chosen 400 x fields. Light microscopy images were captured by a videocam (SPOT Insight; Diagnostic Instrument, Inc., Sterling Heights, Michigan) connected to an Olympus BX‐51 light microscope (Olympus, Tokyo, Japan) and processed with an image analysis system (Delta Sistemi, Rome, Italy).…”

Section: Methodsmentioning

confidence: 99%

The use of acellular porcine dermis, hyaluronic acid and polynucleotides in the treatment of cutaneous ulcers: Single blind randomised clinical trial

Segreto

Carotti

Marangi

et al. 2020

International Wound Journal

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Reconstruction of chronic ulcers is often hampered by lack of local tissues and poor general conditions. Conservative approaches with debridement and advanced medications, such as polyurethane foam, stand as mainstays. However, the healing process is often slow, thus increasing the risk for infection or other complications. In such cases, porcine dermis (PD) and polynucleotides‐added hyaluronic acid (PAHA) were previously reported to accelerate healing. The aim of the study was to compare the efficacy of PD, PAHA and polyurethane foam in chronic ulcers. Thirty patients were randomly divided into 3 groups: group 1 was treated with advanced medications, group 2 with PD, group 3 with PAHA. Standardised photographs and biopsies were taken before treatment and at 30‐day follow‐up. Photographs were processed to calculate the wound area. Specimens were stained with Haematoxylin/Eosin, Masson trichrome, and immunohistochemically for CD34, alpha‐Smooth Muscle Actin (α‐SMA), Collagen types I and III, Ki67. The re‐epithelialized area was larger in patients treated with PD and PAHA compared with those treated with polyurethane foam (P < .05 and P < .01, respectively). Specimens from patients treated with PD and PAHA showed a higher number of myofibroblasts (α‐SMA+, P < .01), neo‐angiogenesis (CD34+, P < .01), proliferating dermal cells (Ki67+, P < .01), proliferating keratinocytes (Ki67+, P < .01) and collagen type 1 deposition (P < .05). No difference was found between PD and PAHA. PD and PAHA proved to be more effective than polyurethane foam in the treatment of chronic ulcers. These approaches are a versatile and reliable option to address such cases.

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“…Within normal breast tissue, fibroblasts and myofibroblasts promote inflammation and angiogenesis. Following breast implant surgery, fibroblasts in patient samples of breast capsular tissue were found to secrete pro-inflammatory and pro-fibrotic signals stimulating differentiation among other fibroblasts and increasing collagen deposition (Segreto et al, 2017 ). Importantly, CAFs drive angiogenesis of tumors by secreting VEGFA and initiating pro-angiogenic paracrine loops with themselves by secreting PDGFC.…”

Section: Introductionmentioning

confidence: 99%

Engineering Breast Cancer Microenvironments and 3D Bioprinting

Belgodere

King

Bursavich

et al. 2018

Front. Bioeng. Biotechnol.

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The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments.

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The role of angiogenesis, inflammation and estrogen receptors in breast implant capsules development and remodeling

Cited by 13 publications

References 29 publications

Tamoxifen reduces silicone implant capsule formation in a mouse model

Tamoxifen reduces silicone implant capsule formation in a mouse model

The use of acellular porcine dermis, hyaluronic acid and polynucleotides in the treatment of cutaneous ulcers: Single blind randomised clinical trial

Engineering Breast Cancer Microenvironments and 3D Bioprinting

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