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1.
Cancers (Basel) ; 13(21)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34771721

RESUMO

Background-Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods-Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results-A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions-Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.

2.
Front Genet ; 12: 705019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539738

RESUMO

Epidermolysis bullosa (EB) is a group of devastating genetic diseases characterized by skin and mucosal fragility and formation of blisters, which develop either spontaneously or in response to minor mechanical trauma. There is no definitive therapy for any form of EB. Intermediate junctional EB (JEB) caused by mutations in the gene LAMB3 has been the first genetic skin disease successfully tackled by ex vivo gene therapy. Here, we present a multicenter, open-label, uncontrolled phase II/III study that aims at confirming the efficacy of Hologene 5, a graft consisting of cultured transgenic keratinocytes and epidermal stem cells and meant to combine cell and gene therapy for the treatment of LAMB3-related JEB. Autologous clonogenic keratinocytes will be isolated from patients' skin biopsies, genetically corrected with a gamma-retroviral vector (γRV) carrying the full-length human LAMB3 cDNA and plated onto a fibrin support (144cm2). The transgenic epidermis will be transplanted onto surgically prepared selected skin areas of at least six JEB patients (four pediatric and two adults). Evaluation of clinical efficacy will include, as primary endpoint, a combination of clinical parameters, such as percentage of re-epithelialization, cellular, molecular, and functional parameters, mechanical stress tests, and patient-reported outcome (PRO), up to 12months after transplantation. Safety and further efficacy endpoints will also be assessed during the clinical trial and for additional 15years in an interventional non-pharmacological follow-up study. If successful, this clinical trial would provide a therapeutic option for skin lesions of JEB patients with LAMB3 mutations and pave the way to a combined cell and gene therapy platform tackling other forms of EB and different genodermatoses. Clinical Trial Registration: EudraCT Number: 2018-000261-36.

3.
Skin Res Technol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34555218

RESUMO

BACKGROUND: Both mesenchymal stromal cells (MSCs) and acellular dermal matrices (ADMs) represent fascinating therapeutic tools in the wound healing scenario. Strategies aimed at combining these two treatment modalities are currently under investigation. Moreover, scarcity of quantitative, nondestructive techniques for quality assessment of engineered tissues poses great limitations in regenerative medicine and collagen autofluorescence-based imaging techniques are acquiring great importance in this setting. OBJECTIVE: Our goals were to assess the in vitro interactions between ADSCs and ADMs and to analyze extracellular-matrix production. METHODS: Adipose-derived MSCs (ADSC) were plated on 8-mm punch biopsies of a commercially available ADM (Integra®). Conventional histology with hematoxylin-eosin staining, environmental scanning electron microscopy, and confocal-laser scanning microscopy were used to obtain imaging of ADSC-seeded ADMs. Collagen production by ADSCs was quantified by mean fluorescence intensity (MFI), expressed in terms of positive pixels/field, obtained through ImageJ software processing of three-dimensional projections from confocal scanning images. Control conditions included: fibroblast-seeded ADM, ADSC- and fibroblast-induced scaffolds, and Integra® alone. RESULTS: ADSCs were efficiently seeded on Integra® and were perfectly incorporated in the pores of the scaffold. Collagen production was revealed to be significantly higher when ADSCs were seeded on ADM rather than in all other control conditions. Collagen autofluorescence was efficiently used as a surrogate marker of ECM production. CONCLUSIONS: Combined therapies based on MSCs and collagenic ADMs are promising therapeutic options for chronic wounds. Not only ADSCs can be efficiently seeded on ADMs, but ADMs also seem to potentiate their regenerative properties, as highlightable from fluorescence confocal imaging.

4.
Cancers (Basel) ; 13(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34439130

RESUMO

Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions ("cases"; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400-430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

5.
Sci Rep ; 11(1): 10472, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006909

RESUMO

The association between the metabolic profile and inflammatory cytokines in psoriasis is poorly understood. We analyzed the metabolic and cytokine/chemokine profiles in serum and skin from patients with new-onset psoriasis and healthy subjects (n = 7/group) by HR-MAS NMR and Bio-Plex immunoassay. Immuno-metabolic correlation matrix was analyzed in skin and serum to identify a potential immune-metabolic signature. Metabolomics analysis showed a significant increase in ascorbate and a decrease in scyllo-inositol, and a trend towards an increase in eight other metabolites in psoriatic skin. In serum, there was a significant increase of dimethylglycine and isoleucine. In parallel, psoriatic skin exhibited an increase of early inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1ß) and correlation analysis highlighted some major clusters of immune-metabolic correlations. A cluster comprising scyllo-inositol and lysine showed correlations with T-cell cytokines; a cluster comprising serine and taurine showed a negative correlation with early inflammatory cytokines (IL-6, G-CSF, CCL3). A strong positive correlation was enlightened between glutathione and inflammatory cytokines/angiogenesis promoters of psoriasis. The integration of metabolic and immune data indicated a molecular signature constituted by IL-6, IL1-ra, DMG, CCL4, Ile, Gly and IL-8, which could discriminate patients and healthy subjects and could represent a candidate tool in the diagnosis of new-onset psoriasis.


Assuntos
Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Metabolômica , Estudos de Casos e Controles , Citocinas/sangue , Humanos , Mediadores da Inflamação/sangue , Isoleucina/sangue , Espectroscopia de Ressonância Magnética/métodos , Sarcosina/análogos & derivados , Sarcosina/sangue , Pele/metabolismo
6.
Ital J Dermatol Venerol ; 156(2): 244-247, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33960754

RESUMO

Reconstruction of large defects of the upper cheek defects still remains a challenge for the surgeon, who can apply different techniques. We present a new method involving the use of a dermal regeneration template to achieve an improved, faster healing of pedicled buccal fat flap in a 75-year-old woman affected by melanoma of the upper-middle cheek. The tumor involved soft tissue, zygomatic arch and periocular fact. The choice of the surgical technique consisted first in the creation of a buccal fat pad to restore the important lack of tissue over the underlying bones, and then in the position of a dermal acellular matrix (Integra® Dermal Regeneration Template; Integra LifeSciences Holdings Corporation, Plainsboro, NJ, USA). Three weeks later, once the neodermal formation was finished, a split thickness graft was placed. This is a not yet described association that represents a good surgical option for the restoration of large cheek defects that allows good functional and cosmetic result in older patient when minimal surgical invasion and operative duration are necessary because of a patient's general condition. The postoperative course with this surgical technique was regular and a good functional result was achieved. This technique provides an adequate functional coverage, a restoration of soft tissue lacking and an acceptable cosmetic result without ectropion.


Assuntos
Procedimentos Cirúrgicos Reconstrutivos , Tecido Adiposo/transplante , Idoso , Bochecha/cirurgia , Feminino , Humanos , Retalhos Cirúrgicos , Cicatrização
7.
Photobiomodul Photomed Laser Surg ; 39(1): 53-61, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33332238

RESUMO

Background: Several noninvasive diagnostic tools have been developed to aid the early detection of oral cancer and for evaluation before definitive biopsy. Among these, devices evaluating a tissues autofluorescence (AF) are emerging. In particular, the most well known of these is the VELscope® system (LED Medical Diagnostics, Inc., Barnaby, Canada), which emits a light of 400-460 nm. This study has been developed to describe the most relevant clinicopathological features associated with AF alterations in a set of patients with oral squamous cell carcinoma and potentially malignant disorders (PMDs). Materials and methods: Overall, 108 lesions from 60 patients with clinical diagnoses of potentially malignant oral disorders and carcinomas were included in the study. For each case, the following variables were recorded and compared with the AF pattern: (1) clinical appearance (white, red, and white/red); (2) histological diagnosis (no dysplasia, mild/moderate dysplasia, severe dysplasia/in situ carcinoma, invasive carcinoma, and verrucous carcinoma); and (3) clinicopathological diagnosis. Binomial logistic regression was performed to investigate whether clinical appearance and/or histological diagnosis were significant in determining the degree of AF. Results: Among the white lesions, 66% resulted in hyper-fluorescence, whereas the red lesions appeared hypo-fluorescent in 95.2% of cases. The AF was altered (both hypo-fluorescent and hyper-fluorescent) in 36% of lesions without dysplasia; in 75.9% of lesions with mild or moderate dysplasia and in the totality of the in situ, invasive, and verrucous carcinomas (p < 0.0001). With regard to the binomial logistic regression, variables were separately considered and both were extremely significant in determining the degree of AF. Conclusions: Promising evidence for the use of AF as an adjunctive tool to conventional oral examinations (COEs) has been demonstrated. However, although the sensitivity of AF examination associated with COE is very high, both the literature and this study agree to indicate a low specificity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/diagnóstico , Detecção Precoce de Câncer , Fluorescência , Humanos , Neoplasias Bucais/diagnóstico , Lesões Pré-Cancerosas/diagnóstico
8.
Skin Appendage Disord ; 6(4): 195-201, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32903939

RESUMO

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degrees of efficacy, have been developed. However, in most cases of advanced HS, the definitive treatment option is often represented by surgical excisions. Objective: Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this review we analyze the possible surgical treatments and local wound care. Methods: A MEDLINE search was performed on the various surgical treatments, reconstructive techniques, and local wound care. Results: Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and post-surgical wound care approaches are described for the management of HS patients. Conclusions: There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies, making comparisons between them difficult. Nonetheless, research on different surgical approaches and wound care management has increased substantially in the past decade and it has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care, and medical therapies will be a matter of future research for the definition of the optimal management of the HS patient.

10.
Adv Skin Wound Care ; 33(7): 367-374, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32544116

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of a biologically engineered dermal matrix used in reconstructive surgery after skin tumor resection, focusing on the frequency of successful grafting and identifying potential factors influencing treatment outcomes. DESIGN AND PARTICIPANTS: This retrospective analysis involved consecutive patients diagnosed with skin cancer in any area of the body and for which treatment with a dermal skin template was recommended as alternative to traditional surgery. MAIN OUTCOME MEASURES: Percentage of successful grafting and the patient and tumor characteristics influencing treatment outcome via univariate analysis. MAIN RESULTS: A total of 302 patients were included. Surgical reconstruction with the matrix was effective in 88.9% of the patients within 21 days of surgery. Notably, the matrix was successful regardless of tumor location, type, or size. Infection was the only variable significantly associated with graft failure (P < .001). CONCLUSIONS: The studied dermal matrix provides an efficient alternative to traditional reconstructive surgery in patients who present specific comorbidities or risk factors. The only variable significantly associated with graft failure was infection, which should be properly controlled through appropriate treatment.


Assuntos
Derme Acelular , Neoplasias Cutâneas/terapia , Retalhos Cirúrgicos/transplante , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante de Pele , Resultado do Tratamento , Cicatrização/fisiologia
11.
Int Wound J ; 17(4): 937-943, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32232964

RESUMO

Perioperative antibiotic treatment duration in skin reconstruction with dermal substitutes is not well established. This study compares the incidence of infective complications after two different durations of perioperative antibiotic treatment in patients undergoing surgical reconstruction with skin dermal substitutes (SDS) after excision of skin cancer. Infective complications at the site of SDS were compared in subjects undergoing surgical reconstruction who received either a > 24-hour (extended protocol) or a ≤ 24-hour (short protocol) perioperative antibiotic treatment. Of 116 patients undergoing SDS surgical reconstruction, 62 (53.4%) received an extended schedule, and 54 (46.6%) received a short schedule. The two groups were similar for gender, age, comorbidities, American Society of Anesthesiologists score, and type of skin cancer. Overall incidence rate of infection was 20.7% (24/116). No differences in terms of risk of infection were observed between the two groups (OR: 1.04, 95% CI: 0.42-2.55; P = .937). Patients undergoing SDS reconstruction in the limb/foot had a higher risk of infection in comparison with those undergoing SDS reconstruction in the chest/head (OR: 2.69, 95% CI: 1.06-6.86; P = .038). The short protocol was demonstrated to be beneficial to patients undergoing surgical reconstruction with SDS. A ≤ 24-hour perioperative antibiotic schedule did not increase the infection rate, potentially allowing a reduction of antibiotic exposure.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias Cutâneas/cirurgia , Transplante de Pele/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Derme Acelular/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/estatística & dados numéricos , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/estatística & dados numéricos , Procedimentos Cirúrgicos Reconstrutivos/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Transplante de Pele/estatística & dados numéricos
12.
Oral Dis ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045089

RESUMO

Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as "autofluorescence" (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.

13.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019170

RESUMO

: Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: "Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?" METHODS: The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health "Study Quality Assessment Tool" and the classification of the Oxford Center for Evidence-Based Medicine. RESULTS: Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having "good" quality, the rest being scored as "intermediate" (8; 73%) and "poor" (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer. CONCLUSIONS: Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers.


Assuntos
Doenças Autoimunes/diagnóstico , Biomarcadores/análise , Inflamação/diagnóstico , MicroRNAs/genética , Neoplasias/diagnóstico , Saliva/metabolismo , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
14.
Dermatol Ther ; 33(3): e13282, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32083788

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degree of efficacy, have been developed. However, in most cases of advanced (HS), the definitive treatment option is often represented by surgical excisions. Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this letter, we analyzed the possible surgical treatments and local wound care. A literature review was performed on the various surgical treatments, reconstructive techniques, and local wound care. Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and postsurgical wound care approaches are described for the management of HS patients. There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies making comparison between them difficult. Nonetheless, research into different surgical approaches and wound care management has increased substantially in the past decade and has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care and medical therapies, will be a matter of future research for the definition of the optimal management of HS patient.


Assuntos
Hidradenite Supurativa , Procedimentos Cirúrgicos Reconstrutivos , Doença Crônica , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/cirurgia , Humanos
17.
Arch Dermatol Res ; 312(4): 295-299, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31616972

RESUMO

Cell-based strategies are today widely studied as possible therapies for wound healing. In this setting, fibroblasts play a key role since they are the main dermal cellular component and are responsible for extracellular matrix secretion. Several works report on the possibility of using fibroblast-derived extracellular matrix scaffolds for wound healing in skin injuries. While fibroblast-based substitutes have already been intensively studied by other groups, we focused our attention on the possibility of creating an adipose-derived stem cell (ADSC)-induced dermal scaffold for wound healing. ADSCs are a particular subset of mesenchymal stem cells present in the stromal vascular fraction of the adipose tissue. The aim of our work was to compare the ability of ADSCs and fibroblast to produce in vitro a scaffolding material, both in terms of collagen and fibronectin production. ADSCs turned out to be capable of efficiently producing a collagen and fibronectin-containing dermal matrix upon stimulation with ascorbic acid. We observed fibronectin and collagen production by ADSCs to be even more abundant when compared to fibroblasts'. Our results support the use of ADSC-induced sheets instead of fibroblast-based dermal substitutes as wound-healing strategies in full-thickness skin injuries.


Assuntos
Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Pele/lesões , Células-Tronco/metabolismo , Tecidos Suporte , Tecido Adiposo/citologia , Células Cultivadas , Colágeno/metabolismo , Fibronectinas/metabolismo , Humanos , Cultura Primária de Células , Cicatrização
18.
Sci Rep ; 9(1): 11515, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395965

RESUMO

Actinic keratosis (AK) is a skin premalignant lesion, which progresses into squamous cell carcinoma (SCC) if left untreated. Ingenol mebutate gel is approved for local treatment of non-hyperkeratotic, non-hypertrophic AK; it also has the potential to act as a field cancerization therapy to prevent the progression of AK to SCC. To gain better insights into the mechanisms of ingenol mebutate beyond the mere clinical assessment, we investigated, for the first time, the metabolome of skin tissues from patients with AK, before and after ingenol mebutate treatment, with high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. The metabolomic profiles were compared with those of tissues from healthy volunteers. Overall, we identified a number of metabolites, the homeostasis of which became altered during the process of tumorigenesis from healthy skin to AK, and was restored, at least partially, by ingenol mebutate therapy. These metabolites may help to attain a better understanding of keratinocyte metabolism and to unmask the metabolic pathways related to cell proliferation. These results provide helpful information to identify biomarkers with prognostic and therapeutic significance in AK, and suggest that field cancerization therapy with ingenol mebutate may contribute to restore skin metabolism to a normal state in patients with AK.


Assuntos
Biomarcadores Tumorais/metabolismo , Diterpenos/farmacologia , Ceratose Actínica/tratamento farmacológico , Metabolômica , Pele/metabolismo , Estudos de Casos e Controles , Humanos , Ceratose Actínica/metabolismo , Espectroscopia de Prótons por Ressonância Magnética
19.
BMC Oral Health ; 19(1): 186, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416455

RESUMO

BACKGROUND: The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. CASE PRESENTATION: Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. DISCUSSION AND CONCLUSION: In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.


Assuntos
Proliferação de Células , Antígeno Ki-1 , Úlceras Orais , Linfócitos T , Língua , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
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