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1.
Aging Cell ; : e14186, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38761001

RESUMO

Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue. Mitochondria play an important role for the development of cellular senescence, in particular stress-induced senescence of human cells. However, many aspects of mitochondrial physiology relevant to cellular senescence and extrinsic skin aging remain to be unraveled. Here, we demonstrate that mitochondria damaged by UVB irradiation of human dermal fibroblasts (HDF) are eliminated by NIX-dependent mitophagy and that this process is important for cell survival under these conditions. Additionally, UVB-irradiation of human dermal fibroblasts (HDF) induces the shedding of extracellular vesicles (EVs), and this process is significantly enhanced in UVB-irradiated NIX-depleted cells. Our findings establish NIX as the main mitophagy receptor in the process of UVB-induced senescence and suggest the release of EVs as an alternative mechanism of mitochondrial quality control in HDF.

2.
Cancers (Basel) ; 15(10)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37345114

RESUMO

A single immediate reconstruction with free tissue transfer is the method of choice after major head and neck cancer (HNC) resection, but this is frequently associated with long operating hours. Considering regulatory working hour constraints, we investigated whether a two-staged reconstructive approach with temporary defect coverage by an artificial tissue substitute would be feasible. HNC patients underwent either immediate or delayed reconstruction after tumor resection. Patients with delayed reconstruction received preliminary reconstruction with an artificial tissue substitute followed by definitive microvascular reconstruction in a separate, second procedure. Of the 33 HNC patients, 13 received delayed reconstruction and 20 received immediate reconstruction. Total anesthesia time (714 vs. 1011 min; p < 0.002) and the total duration of hospital stay (34 ± 13 vs. 25 ± 6 days; p = 0.03) were longer in the delayed reconstruction group. Perioperative morbidity (p = 0.58), functional outcome (p > 0.1) and 5-year postoperative survival rank (p = 0.28) were comparable in both groups. Delayed reconstruction after HNC resection was feasible. Perioperative morbidity, functional outcome and overall survival were comparable to immediate reconstruction.

3.
Cancers (Basel) ; 15(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37173928

RESUMO

The globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient's neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n = 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.

5.
J Plast Reconstr Aesthet Surg ; 81: 76-82, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37121045

RESUMO

In head and neck oncology, surgical treatment frequently results in microvascular reconstruction. Oncologic resection followed by immediate reconstruction is often associated with prolonged working and surgical duration, challenging a surgeon's concentration level and potentially worsening patient outcome. To improve the surgeon's performance and to reduce risk of potential complications, we implemented a two-stage procedure in patients with head and neck cancer. This study critically analyzed the surgical outcomes, organizational benefits, and investigated job satisfaction among affected health care professionals. A retrospective data analysis of patients who had undergone microvascular reconstruction after oncologic head and neck surgery between 2010 and 2021 included 33 patients (n = 33). Twenty patients underwent single-stage reconstruction (group 1, n = 20) and 13 patients underwent two-stage reconstruction (group 2, n = 13) with 12.2 (± 7.4) days between surgeries. The mean surgical duration, and mean start and end time of the reconstructive surgery component differed significantly (p = 0.002). The mean total complication rate (p = 0.58) did not differ significantly, although a trend toward higher demands for blood products was observed in group 1. There was no significant difference in five-year survival (p = 0.28). A questionnaire on subjective work performance was answered by the affected health care professionals (n = 34) and it revealed that 88% preferred long surgeries to be scheduled first and that 97% work most efficiently in the morning. In conclusion, two-stage reconstruction is a suitable option in selected head and neck cancer patients offering the possibility of optimizing preoperative planning and organization. This may result in regular working hours, reduced surgeon fatigue, and improved job satisfaction without compromising patient outcomes or survival.


Assuntos
Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/cirurgia , Pescoço/cirurgia , Cabeça/cirurgia
6.
Cell Death Discov ; 8(1): 443, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329012

RESUMO

Misalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery. We show that circadian synchronization by serum-shock or stimulation with adipogenic stimuli leads to a different expression pattern of ARNTL2 relative to its well-studied paralogue ARNTL1. We demonstrate that ARNTL2 mRNA is downregulated in ASCs upon weight-loss (WL) whereas ARNTL2 protein is rapidly induced in the course of adipogenic differentiation and highly abundant in adipocytes. ARNTL2 protein is maintained in ASCs cooperatively by mechanistic Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPK) signalling pathways while ARNTL2 functions as an inhibitor on both circuits, leading to a feedback mechanism. Consistently, ectopic overexpression of ARNTL2 repressed adipogenesis by facilitating the degradation of ARNTL1, inhibition of Kruppel-Like Factor 15 (KLF15) gene expression and down-regulation of the MAPK-CCAAT/enhancer-binding protein ß (C/EBPß) axis. Western blot analysis of sWAT samples from normal-weight, obese and WL donors revealed that ARNTL2 protein was solely elevated by WL compared to ARNTL1 which underscores unique functions of both transcription factors. In conclusion, our study reveals ARNTL2 to be a WL-regulated inhibitor of adipogenesis which might provide opportunities to develop strategies to ameliorate obesity.

7.
Adipocyte ; 11(1): 601-615, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36168895

RESUMO

The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1-/CD34+/CD45-/CD31- ASC pool of human white adipose tissues (WATs) into two large populations. Ex vivo, DPP4+ ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4- ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34+ ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.


Assuntos
Adipócitos , Dipeptidil Peptidase 4 , Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Antígenos CD34/metabolismo , Diferenciação Celular , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Humanos , Células-Tronco/metabolismo
8.
JPRAS Open ; 33: 131-138, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35935516

RESUMO

Introduction: This study aims to analyze whether autologous breast reconstruction as compared to expander/implant reconstruction has a higher risk of postoperative wound healing problems (WHPs) and thus potentially delays chemotherapy start. Methods: Between January 2012 and December 2019, a total of 64 women with NSME/SSME and autologous (Group1, n = 33) or expander/implant reconstruction (Group2, n = 31) and adjuvant chemotherapy were enrolled in this study conducted at Innsbruck Medical University Hospital. Immediate postoperative WHPs in each group were compared, and the time from operation to initiation of chemotherapy was analyzed. If the start of chemotherapy was postponed for more than six weeks postoperatively due to WHP, it was defined as delayed. Statistical analysis was performed with SPSS and Fisher's exact test. Results: More postoperative WHP occurred in Group 1 than in Group 2 (51.6% vs. 9.7%, p < 0.001). Due to WHP, chemotherapy start was delayed for more than six weeks postoperatively in 30.3% of Group 1 patients and 3.2% of Group 2 patients. Only small differences in age (Group 1: 47±1 vs. Group 2: 46±2 years) and BMI (Group 1: 24.3 ± 0.6 vs. Group 2: 23.3 ± 0.7 kg/m2) were found. Conclusion: Our study shows a far smaller risk for postoperative WHP and delay of chemotherapy start in the expander/implant group in comparison with the autologous group. In some selected patients with high urgency for adjuvant chemotherapy, a bridging operation by means of expander reconstruction prior to chemotherapy could be an oncologically safe pathway.

9.
Plast Reconstr Surg Glob Open ; 10(3): e4216, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35356041

RESUMO

The impact of previous radiotherapy on free flap outcome is still a subject of debate. Clinical investigations have come to divergent conclusions and the true effect of radiotherapy (XRT) on flap survival is not definitely known. Most studies investigating the factor often have their methodological limitations such as lack of statistical power as a consequence of the overall low failure rates together with few irradiated cases. This study will attempt to address the question whether previous radiotherapy is associated with a significantly higher incidence of flap failure or not. Methods: A systematic review and meta-analysis were conducted in concordance with the PRISMA protocol using the PubMed database. Fixed-effect and random-effect models were applied to obtain the odds ratio of total flap failure and partial flap failure between radiation and nonradiation groups. Statistical heterogeneity and publication bias were assessed and forest plots and funnel plots were constructed for graphic illustration. Results: A total of 43 studies were included for qualitative and quantitative analysis involving 18,776 flaps in 17,532 patients. Patients with preoperative XRT were significantly associated with an increased risk for total (odds ratio fixed = 1.675, 95% confidence interval [CI] = 1.405-1.996, P < 0.001) and partial free flap failure (odds ratio fixed = 2.161, 95% CI = 1.472-2.172, P < 0.001). Conclusion: The study suggests that preoperative radiotherapy is associated with an increased risk for total and partial free flap failure. Further studies are needed to investigate the effect of total XRT dose and time after radiation on free flap outcome.

10.
Plast Reconstr Surg Glob Open ; 10(1): e4074, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35186629

RESUMO

The reconstruction of medial canthal defects is often challenging in achieving continuity of color and texture, obtaining adequate tissue for large defects, and the reproduction of natural external appearance with inconspicuous scars. We describe a technique for reconstruction of the medial canthal area, using a modified rhomboid flap. METHODS: The technique is based on the use of a modified rhomboid flap for medial canthal defects-superiorly based on the root of the nose for defects mostly above the medial canthal tendon, inferiorly based on the cheek for defects mostly below the medial canthal tendon, and in cases of large defects, using a combination of the two flaps. We present a case series of five patients successfully reconstructed with the mentioned technique after resection of medial canthal basal cell carcinoma. RESULTS: Of the five patients with a mean age of 76.2 years (range 62-84 years), reconstruction was performed in three patients with a superiorly based rhomboid flap, in one patient with an inferiorly based rhomboid flap, and in another patient with a large defect using a combination of the two flaps. Mean follow-up was 374.4 days (range 30-1247 days). All patients achieved a complete primary closure with no further surgery and satisfactory cosmetic and functional results. CONCLUSION: The modified rhomboid flap is a simple and reliable technique for all defects of the medial canthal area.

11.
J Dtsch Dermatol Ges ; 19(11): 1571-1580, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34811913

RESUMO

Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun-exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology. Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/diagnóstico , Face , Humanos , Invasividade Neoplásica , Neoplasias Cutâneas/diagnóstico
12.
Healthcare (Basel) ; 9(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34574932

RESUMO

BACKGROUND: The pedicled pectoralis major muscle flap (PMMF) is a well established flap for fistula prophylaxis after salvage laryngectomy. To reduce donor site morbidity, we established a modified muscle-sparing harvesting technique. We herein investigate postoperative shoulder function and health-related quality of life (HRQOL). METHODS: A chart review of patients receiving the modified muscle-sparing pectoralis major muscle flap between 2013-2020 was performed. Nineteen patients (male = 18, female = 1) were potentially eligible and six male patients were ultimately enrolled. Postoperative shoulder function was assessed on both sides (flap side versus non-flap side) using the Constant Murley Score and the Bak criteria. Health-related quality of life was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire in cancer patients (EORTC QLQ-C30) and head and neck cancer patients (EORTC H&N35). RESULTS: No Constant Murley Score subscale was statistically significant (p ≥ 0.180). Bak criteria was overall rated "Good". Solely upper extremity adduction force was significantly altered on the flap side (p = 0.039). Median EORTC QLQ-C30 score was 82.2 (IQR 11.1) on the functional scale and 10.3 (IQR 2.6) on the symptomatic scale. Median quality of life score was 75.0 (IQR 33.3) and median EORTC QLQ-H&N35 was 20.6 (IQR 9.8). CONCLUSIONS: Postoperative shoulder function after modified muscle-sparing pectoralis major muscle flap surgery is comparable to function of the healthy side with a significant deficiency in adduction force not compromising daily life in this small study cohort.

13.
Head Neck ; 43(10): 3238-3244, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34268827

RESUMO

Orbital exenteration is a disfiguring procedure that often results in free tissue transfer for reconstructive purposes. The reconstructive focus is the obliteration of dead space while sparing the nasal airway, particularly if the medial orbital wall was resected. Prolapse of transferred tissue into the nasal airway may cause breathing difficulties drastically compromising quality of life. The objective of this study was to demonstrate the effectiveness and feasibility of temporary nasal septum splints as mechanical support for transferred tissue, to prevent airway obstruction. This novel application technique was employed in three patients between 2017 and 2018. No flap loss or sino-orbital fistulas were observed. On postoperative MRI and endoscopy, a patent nasal airway was observed at all times. Temporary nasal splinting in combination with free tissue transfer proved to be a simple, but effective reconstructive option for securing the nasal airway following orbital exenteration with resection of the medial orbital wall.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Órbita/cirurgia , Exenteração Orbitária , Qualidade de Vida
14.
Cells ; 10(2)2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33498986

RESUMO

We explore the status of quiescence, stemness and adipogenic differentiation capacity in adipose stem/progenitor cells (ASCs) ex vivo, immediately after isolation from human subcutaneous white adipose tissue, by sorting the stromal vascular fraction into cell-surface DLK1+/CD34-, DLK1+/CD34dim and DLK1-/CD34+ cells. We demonstrate that DLK1-/CD34+ cells, the only population exhibiting proliferative and adipogenic capacity, express ex vivo the bonafide quiescence markers p21Cip1, p27Kip1 and p57Kip2 but neither proliferation markers nor the senescence marker p16Ink4a. The pluripotency markers NANOG, SOX2 and OCT4 are barely detectable in ex vivo ASCs while the somatic stemness factors, c-MYC and KLF4 and the early adipogenic factor C/EBPß are highly expressed. Further sorting of ASCs into DLK1-/CD34+/CD24- and DLK1-/CD34+/CD24+ fractions shows that KLF4 and c-MYC are higher expressed in DLK1-/CD34+/CD24+ cells correlating with higher colony formation capacity and considerably lower adipogenic activity. Proliferation capacity is similar in both populations. Next, we show that ASCs routinely isolated by plastic-adherence are DLK1-/CD34+/CD24+. Intriguingly, CD24 knock-down in these cells reduces proliferation and adipogenesis. In conclusion, DLK1-/CD34+ ASCs in human sWAT exist in a quiescent state, express high levels of somatic stemness factors and the early adipogenic transcription factor C/EBPß but senescence and pluripotency markers are barely detectable. Moreover, our data indicate that CD24 is necessary for adequate ASC proliferation and adipogenesis and that stemness is higher and adipogenic capacity lower in DLK1-/CD34+/CD24+ relative to DLK1-/CD34+/CD24- subpopulations.


Assuntos
Adipogenia , Tecido Adiposo Branco/citologia , Antígenos CD34/metabolismo , Antígeno CD24/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Ciclo Celular , Proteínas de Membrana/metabolismo , Células-Tronco/citologia , Adipogenia/genética , Biomarcadores/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Ciclo Celular/genética , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Interferente Pequeno/metabolismo , Células-Tronco/metabolismo , Células Estromais/metabolismo , Gordura Subcutânea/citologia
15.
Transpl Int ; 33(12): 1762-1778, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32970891

RESUMO

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.


Assuntos
Rejeição de Enxerto , Transplante de Mão , Antebraço , Humanos , Qualidade de Vida , Estudos Retrospectivos
16.
Breast Care (Basel) ; 15(3): 265-271, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32774221

RESUMO

BACKGROUND: The aim of this study was to determine whether there is a difference in results between the radial and the inframammary approach in nipple-/skin-sparing mastectomy and immediate reconstruction. METHODS: The patients were divided into two groups (group 1: radial incision; group 2: inframammary fold incision [IMF]), each consisting of two subgroups for direct-to-implant reconstruction (1a, 2a) and expander reconstruction (1b, 2b). The patients were operated on between March 2012 and May 2017. Preoperative tumor parameters, reconstruction parameters, postoperative tumor parameters, and immediate and late complications were assessed. Postoperative photographs were evaluated by the patients and 8 plastic surgeons by means of grading (1-5) and the visual analog scale (VAS; 1-10). RESULTS: Enrolled in this study were 28 patients, namely, 7 patients in each subgroup. The median age was 46 years, and the median follow-up period was 40 months. No immediate complications occurred. Three patients had late complications, but there was no case of evident capsular fibrosis. Twenty-seven patients (96.42%) evaluated the postoperative result as excellent/good. The postoperative evaluation by the plastic surgeons was excellent/good for a median of 18 patients (64.28%). Group 1 showed a median VAS score of 7.63 (expander group: 7.50; direct-to-implant group: 7.75); the median VAS score for group 2 was 8.25 (expander group: 8.75; direct-to-implant group: 7.50). CONCLUSIONS: Our study shows good results for implant breast reconstruction in both groups, with minimally better results for the IMF group. In the direct-to-implant subgroups, the radial group showed slightly better results.

17.
Mech Ageing Dev ; 190: 111318, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32710895

RESUMO

Accumulation of senescent cells promotes the development of age-related pathologies and deterioration. In human skin, senescent cells potentially impair structure and function by secreting a mixture of signaling molecules and proteases that influence neighboring cells and degrade extracellular matrix components, such as elastin and collagen. One of the key underlying mechanisms of senescence and extrinsic skin aging is the increase of intracellular reactive oxygen species and resulting oxidative stress. Tert-butyl hydroperoxide (tBHP) is a known inducer of oxidative stress and cellular damage, acting at least in part by depleting the antioxidant glutathione. Here, we provide a detailed characterization of tBHP-induced senescence in human dermal fibroblasts in monolayer culture. In addition, results obtained with more physiological experimental models revealed that tBHP treated 3D reconstructed skin and ex vivo skin developed signs of chronic tissue damage, displaying reduced epidermal thickness and collagen fiber thinning. We, therefore, propose that tBHP treatment can be used as a model to study the effects of extrinsic skin aging, focusing mainly on the influence of environmental pollution.


Assuntos
Poluição Ambiental , Fibroblastos , Glutationa/metabolismo , Envelhecimento da Pele , Pele , terc-Butil Hidroperóxido/metabolismo , Antioxidantes/metabolismo , Células Cultivadas , Senescência Celular , Poluição Ambiental/efeitos adversos , Poluição Ambiental/análise , Epiderme/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/fisiologia , Humanos , Modelos Teóricos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Pele/patologia , Envelhecimento da Pele/patologia , Envelhecimento da Pele/fisiologia
18.
J Gerontol A Biol Sci Med Sci ; 75(12): 2308-2319, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32304210

RESUMO

The role of Ras-Mitogen-activated protein kinase (MAPK) signaling in cellular aging is not precisely understood. Recently, we identified Sprouty1 (SPRY1) as a weight-loss target gene in human adipose stem/progenitor cells (ASCs) and showed that Sprouty1 is important for proper regulation of adipogenesis. In the present study, we show that loss-of-function of Sprouty1 by CRISPR/Cas9-mediated genome editing in human ASCs leads to hyper-activation of MAPK signaling and a senescence phenotype. Sprouty1 knockout ASCs undergo an irreversible cell cycle arrest, become enlarged and stain positive for senescence-associated ß-galactosidase. Sprouty1 down-regulation leads to DNA double strand breaks, a considerably increased number of senescence-associated heterochromatin foci and induction of p53 and p21Cip1. In addition, we detect an increase of hypo-phosphorylated Retinoblastoma (Rb) protein in SPRY1 knockout ASCs. p16Ink4A is not induced. Moreover, we show that Sprouty1 knockout leads to induction of a senescence-associated secretory phenotype as indicated by the activation of the transcription factors NFκB and C/EBPß and a significant increase in mRNA expression and secretion of interleukin-8 (IL-8) and CXCL1/GROα. Finally, we demonstrate that adipogenesis is abrogated in senescent SPRY1 knockout ASCs. In conclusion, this study reveals a novel mechanism showing the importance of Sprouty1 for the prevention of senescence and the maintenance of the proliferation and differentiation capacity of human ASCs.


Assuntos
Tecido Adiposo/citologia , Senescência Celular/genética , Proteínas de Membrana/genética , Fosfoproteínas/genética , Células-Tronco/citologia , Adipogenia/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Mutação com Perda de Função , Fenótipo , Transdução de Sinais , beta-Galactosidase/metabolismo
19.
Laryngorhinootologie ; 99(4): 229-236, 2020 04.
Artigo em Alemão | MEDLINE | ID: mdl-32079025

RESUMO

BACKGROUND: In recurrent hypopharyngeal/laryngeal squamous cell carcinoma after radiation salvage-laryngectomy (salvage-LE) represents the best curative treatment option. Pre-irradiation promotes development of pharyngocutaneous fistulas (pc-fistula). Transfer of unirradiated tissue to the surgical site reduces fistula rate. Frequently, a myocutaneous Pectoralis-major-flap (PMF) is applied. We describe a muscle sparing, myofascial PMF (ms-PMF) and its functional & aesthetic results. METHODS: For the ms-PMF, the pectoralis major is exposed via two 8 cm long subclavicular & submammary horizontal incisions. The pectoral branch of the thoracoacromial artery, which represents the blood supply for the ms-PMF, is identified between the clavicular and sternocostal aspect of the muscle. A craniocaudal stripe of the pectoralis major is recovered and supraclaviculary transposed towards the pharynx. The clavicular and sternocostal part of the muscle remain untouched.The clear-margin resection rate (CMRR), mean overall survival (OS), complications, median length of hospital stay, & functional & aesthetic outcome were assessed. RESULTS: In 25 patients, salvage-LE with ms-PMF was performed. The CMRR was 100 %, median OS 1.3 (follow-up 2.8) years, complications rate 16 % (4 complete lobe necroses, 3 pc-fistulas) and median inpatient stay 20 (11-78) days. Good functional outcome were observed: limitations of oral food intake occurred in 2-, limitations in voice rehabilitation in 3 patients. Wound healing disorders without lobe necrosis were not observed. The aesthetic results were appealing. CONCLUSION: The ms-PMF is a less invasive & safe procedure for fistula prophylaxis in salvage-LE with favorable functional & aesthetic results.


Assuntos
Fístula Cutânea/cirurgia , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas/cirurgia , Doenças Faríngeas/cirurgia , Humanos , Laringectomia , Músculos Peitorais/cirurgia , Estudos Retrospectivos , Terapia de Salvação
20.
ORL J Otorhinolaryngol Relat Spec ; 81(5-6): 327-337, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31698360

RESUMO

BACKGROUND: Pectoralis major flap reconstruction is often associated with large unappealing scars in head-neck surgery. We recently established an alternative harvesting technique that improves aesthetic outcome. OBJECTIVES: The objective of this study was to demonstrate a modified surgical technique that harvests the pectoralis major muscle as an island flap and focuses on minimizing incision lines and applying a muscle-sparing approach. METHODS: A retrospective analysis covering the period 2008-2018 was conducted. Patients who underwent pectoralis major island flap reconstruction for fistula prophylaxis after salvage laryngectomy at the Medical University of Innsbruck were included. Flap harvesting was performed subcutaneously using two small incision lines, thereby sparing the clavicular and upper sternocostal aspects of the pectoralis muscle. RESULTS: Twenty-three patients with squamous cell carcinoma of the larynx (n = 19) or pharynx (n = 4) underwent salvage laryngectomy and consecutive reconstruction using a pectoralis major island flap and our muscle-sparing technique. Mean overall operation time was 147 ± 48.6 min. The majority (70%) of patients had an uneventful course of recovery and showed satisfying aesthetic results and low donor site morbidity as compared to traditional harvesting techniques. Six (26%) patients had major complications that required surgical revision. Three (13%) cases were complicated with fistulas. CONCLUSION: The pectoralis major island flap is shown to be reliable in otolaryngeal surgery. This surgical technique minimizes scarring and preserves thoracic wall architecture by taking a less invasive approach, thereby improving aesthetic outcome and reducing overall patient morbidity.


Assuntos
Cicatriz/prevenção & controle , Estética , Neoplasias Laríngeas/cirurgia , Laringectomia , Músculos Peitorais/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Coleta de Tecidos e Órgãos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Terapia de Salvação
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