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1.
Nat Commun ; 12(1): 1308, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637728

RESUMO

The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.


Assuntos
Moléculas de Adesão Celular/metabolismo , Divisão Celular/fisiologia , Células Epidérmicas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Células-Tronco/metabolismo , Animais , Carcinoma Basocelular/patologia , Proteínas de Transporte/metabolismo , Adesão Celular , Proliferação de Células , Desenvolvimento Embrionário/fisiologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Feminino , Junções Intercelulares , Queratinócitos , Camundongos , Mitose , Morfogênese , Organogênese
2.
Nat Commun ; 12(1): 160, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420020

RESUMO

We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a cross-sectional and longitudinal dataset of 210,000 consented research participants who responded to an online survey covering personal and family history of skin cancer, skin susceptibility, and UV exposure. We developed a primary disease risk score (DRS) that combined all 32 identified genetic and non-genetic risk factors. Top percentile DRS was associated with an up to 13-fold increase (odds ratio per standard deviation increase >2.5) in the risk of developing skin cancer relative to the middle DRS percentile. To derive lifetime risk trajectories for the three skin cancers, we developed a second and age independent disease score, called DRSA. Using incident cases, we demonstrated that DRSA could be used in early detection programs for identifying high risk asymptotic individuals, and predicting when they are likely to develop skin cancer. High DRSA scores were not only associated with earlier disease diagnosis (by up to 14 years), but also with more severe and recurrent forms of skin cancer.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Modelos Estatísticos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/etiologia , Estudos Transversais , Conjuntos de Dados como Assunto , Triagem e Testes Direto ao Consumidor/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Incidência , Estudos Longitudinais , Masculino , Anamnese , Melanoma/etiologia , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Razão de Chances , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Inquéritos e Questionários/estatística & dados numéricos , Raios Ultravioleta/efeitos adversos
3.
Adv Exp Med Biol ; 1287: 123-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034030

RESUMO

Since many decades, nonmelanoma skin cancer (NMSCs) is the most common malignancy worldwide. Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the major types of NMSCs, representing approximately 70% and 25% of these neoplasias, respectively. Because of their continuously rising incidence rates, NMSCs represent a constantly increasing global challenge for healthcare, although they are in most cases nonlethal and curable (e.g., by surgery). While at present, carcinogenesis of NMSC is still not fully understood, the relevance of genetic and molecular alterations in several pathways, including evolutionary highly conserved Notch signaling, has now been shown convincingly. The Notch pathway, which was first developed during evolution in metazoans and that was first discovered in fruit flies (Drosophila melanogaster), governs cell fate decisions and many other fundamental processes that are of high relevance not only for embryonic development, but also for initiation, promotion, and progression of cancer. Choosing NMSC as a model, we give in this review a brief overview on the interaction of Notch signaling with important oncogenic and tumor suppressor pathways and on its role for several hallmarks of carcinogenesis and cancer progression, including the regulation of cancer stem cells, tumor angiogenesis, and senescence.


Assuntos
Carcinogênese , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica , Receptores Notch/metabolismo , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Animais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Cutâneas/irrigação sanguínea
4.
JAMA Netw Open ; 3(12): e2030107, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33326027

RESUMO

Importance: The incidence of skin cancer is increasing and evaluation of the utility of total body skin examination (TBSE) in detecting incidental skin cancers is warranted. Objectives: To evaluate the proportion and rate of incidental skin cancer detection in urgent skin cancer clinics and investigate the rate of incidental skin cancer detection in 2 groups based on the degree of clinical suspicion of the index lesion for malignancy. Design, Setting, and Participants: A multicenter retrospective cohort study with a case note review of consecutive secondary care consultations was conducted using data from 2 urgent suspected skin cancer screening clinics in UK National Health Service trusts. The study was performed from January 1, 2015, to March 31, 2016, and data analysis was performed from October 14, 2018, to February 1, 2019. Patients included those presenting with a skin lesion suspicious of malignancy who were referred to the urgent suspected skin cancer clinic (N = 5944) over 15 months. Patients who accepted and received a TBSE were subsequently included in the analysis. Main Outcomes and Measures: The proportion and rate of incidental skin cancer detection through TBSE and whether a clinically suspicious (malignant) index lesion was associated with a higher chance of having a malignant incidental lesion. Results: Of the 5944 patients referred to the clinic, 4726 individuals (79.5%) were evaluated. In the cohort included in the analyses, the median age was 57 years (interquartile range, 39-73 years); 2567 patients (54.3%) were women. A total of 1117 skin cancers were identified; of these, 242 lesions (21.7%) were detected incidentally through TBSE, including 197 of 570 (34.6%) basal cell carcinomas, 16 of 250 (6.4%) squamous cell carcinomas, and 25 of 215 (11.6%) melanomas. The detection rate of incidental malignant lesions was 5.1 lesions per 100 patients examined (5.1%; 95% CI, 4.5%-5.8%). There was a higher detection rate of histologically confirmed incidental malignant lesions in individuals with clinically suspicious index lesions requiring biopsy (10.9%; 95% CI, 9.5%-12.5%) compared with those presenting with clinically benign index lesions (2.0%; 95% CI, 1.6%-2.5%) (P < .001). Conclusions and Relevance: The findings of this study support the use of TBSE for urgent skin cancer referrals, highlighting the potential harms of solitary lesion assessment in a subgroup. Individuals presenting with a clinically suspicious index lesion requiring biopsy are most likely to benefit from TBSE and should be counseled regarding the benefit.


Assuntos
Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Melanoma/patologia , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias Cutâneas , Biópsia/métodos , Biópsia/estatística & dados numéricos , Dermatologia/métodos , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico/métodos , Exame Físico/estatística & dados numéricos , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Reino Unido
5.
Medicine (Baltimore) ; 99(44): e22913, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126349

RESUMO

INTRODUCTION: Malignant cutaneous epithelial tumors comprise various skin malignancies originating from the cutaneous epithelium, including cutaneous squamous cell carcinoma, basal cell carcinoma, and malignant cutaneous adnexal tumors. Treatment options are limited, as the rarity of these tumors, especially among Asians, renders well-controlled clinical trials extremely challenging to conduct. Thus, we designed a clinical trial to evaluate the efficacy and safety of the anti-programmed cell death-1 (PD-1) monoclonal antibody nivolumab in patients with metastatic cutaneous squamous cell carcinomas and other rare metastatic cutaneous epithelial tumors. METHODS AND ANALYSIS: This is an open-label, single-arm, multicenter, phase 2 clinical trial involving patients with metastatic malignant cutaneous epithelial tumors. Nivolumab (480 mg) will be administered intravenously every 4 weeks for a maximum of 26 doses. The primary outcome of the study will be the response rate based on response evaluation criteria in solid tumors, version 1.1. Assuming a null hypothesis of a response rate ≤5% and an alternative hypothesis of a 25% response rate, a minimum of 26 patients are required to achieve a 5% two-sided type I error and 80% power based on the exact binomial distribution. Finally, a target cohort size of 30 patients was determined as some patient dropout will be expected. DISCUSSION: This is the first phase 2 clinical trial evaluating the efficacy and safety of the PD-1 inhibitor nivolumab in Asian patients with metastatic malignant cutaneous epithelial tumors. The findings of the study will contribute to the development of novel treatment approaches for patients with rare cutaneous malignancies, which remains an unmet clinical need. TRIAL REGISTRATION: Registry number: jRCT 2031190048.


Assuntos
Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Anexos e de Apêndices Cutâneos/tratamento farmacológico , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Japão , Masculino , Estadiamento de Neoplasias , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Cutâneas/patologia
7.
Anticancer Res ; 40(7): 4017-4022, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620646

RESUMO

BACKGROUND/AIM: Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. PATIENTS AND METHODS: We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. RESULTS: KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. CONCLUSION: KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.


Assuntos
Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Transplante de Rim , Neoplasias Cutâneas/patologia , Pele/patologia , Idoso , Humanos , Pessoa de Meia-Idade
8.
Niger J Clin Pract ; 23(7): 1022-1025, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620735

RESUMO

Maxillofacial prosthetics is the branch of prosthodontics which involves rehabilitation of the defects in the maxillofacial region involving the hard and soft tissue with the prosthesis. Facial defects that occur in the midfacial regions are commonly due to trauma and neoplasms like basal cell carcinoma which involves the nose. Reconstruction of the nose is an important esthetic challenge due to its esthetic and retention problems. This article emphasis rehabilitation of the nasal defect of a patient with nasal prosthesis using donor method.


Assuntos
Carcinoma Basocelular/cirurgia , Neoplasias Nasais/reabilitação , Nariz/cirurgia , Desenho de Prótese , Procedimentos Cirúrgicos Reconstrutivos/métodos , Carcinoma Basocelular/patologia , Carcinoma Basocelular/reabilitação , Humanos , Masculino , Prótese Maxilofacial , Implante de Prótese Maxilofacial , Pessoa de Meia-Idade , Neoplasias Nasais/patologia , Neoplasias Nasais/cirurgia , Implantação de Prótese , Doadores de Tecidos , Resultado do Tratamento
9.
Dermatol Online J ; 26(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621693

RESUMO

Erythema ab igne is a skin condition mainly caused by heat exposure. Erythema ab igne usually follows a favorable prognosis. However, it may increase the risk of developing cutaneous malignancy in the involved skin. Being familiar with the type of cutaneous malignancies that may arise in the site of erythema ab igne is considerably important. To our knowledge, this letter presents the first case that shows the association between erythema ab igne and basal cell carcinoma.


Assuntos
Carcinoma Basocelular/etiologia , Eritema/complicações , Neoplasias Cutâneas/etiologia , Pele/patologia , Biópsia , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Temperatura Alta/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia
10.
Breast Cancer Res ; 22(1): 59, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493400

RESUMO

BACKGROUND: Breast cancer is a heterogeneous disease. Hence, stratification of patients based on the subtype of breast cancer is key to its successful treatment. Among all the breast cancer subtypes, basal-like breast cancer is the most aggressive subtype with limited treatment options. Interestingly, we found focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, is highly overexpressed and activated in basal-like breast cancer. METHODS: To understand the role of FAK in this subtype, we generated mice with conditional deletion of FAK and a knock-in mutation in its kinase domain in MMTV-Wnt1-driven basal-like mammary tumors. Tumor initiation, growth, and metastasis were characterized for these mice cohorts. Immunohistochemical and transcriptomic analysis of Wnt1-driven tumors were also performed to elucidate the mechanisms underlying FAK-dependent phenotypes. Pharmacological inhibition of FAK and mTOR in human basal-like breast cancer cell lines was also tested. RESULTS: We found that in the absence of FAK or its kinase function, growth and metastasis of the tumors were significantly suppressed. Furthermore, immunohistochemical analyses of cleaved caspase 3 revealed that loss of FAK results in increased tumor cell apoptosis. To further investigate the mechanism by which FAK regulates survival of the Wnt1-driven tumor cells, we prepared an isogenic pair of mammary tumor cells with and without FAK and found that FAK ablation increased their sensitivity to ER stress-induced cell death, as well as reduced tumor cell migration and tumor sphere formation. Comparative transcriptomic profiling of the pair of tumor cells and gene set enrichment analysis suggested mTOR pathway to be downregulated upon loss of FAK. Immunoblot analyses further confirmed that absence of FAK results in reduction of AKT and downstream mTOR pathways. We also found that inhibition of FAK and mTOR pathways both induces apoptosis, indicating the importance of these pathways in regulating cell survival. CONCLUSIONS: In summary, our studies show that in a basal-like tumor model, FAK is required for survival of the tumor cells and can serve as a potential therapeutic target.


Assuntos
Carcinoma Basocelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Wnt1/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transformação Celular Neoplásica , Modelos Animais de Doenças , Progressão da Doença , Feminino , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Proteína-Tirosina Quinases de Adesão Focal/genética , Humanos , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Vírus do Tumor Mamário do Camundongo/genética , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Células Tumorais Cultivadas , Proteína Wnt1/genética
11.
Breast Cancer Res ; 22(1): 63, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527287

RESUMO

BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/metabolismo , Animais , Apoptose/fisiologia , Neoplasias da Mama/patologia , Carcinoma Basocelular/patologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Cromatina/genética , Cromatina/metabolismo , Dano ao DNA , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Prognóstico , Proteogenômica , Células Tumorais Cultivadas
12.
Hautarzt ; 71(8): 580-587, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32533202

RESUMO

Basal cell carcinoma is the most common type of cancer in Central Europe and has a high medical relevance. Due to its high tendency of recurrence, an important parameter in the planning of therapy is the risk of recurrence. After clinical and histological diagnosis, the majority of tumors are treated surgically, although radiation and topical procedures are also possible therapeutic alternatives in certain constellations. Hedgehog inhibitors, a completely new class of substances, have recently been approved for rare metastatic and locally advanced diseases, thus significantly expanding the range of treatments. This article provides an overview of the current guideline-based diagnosis and therapy of basal cell carcinomas in Germany.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/terapia , Procedimentos Cirúrgicos Dermatológicos/métodos , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Carcinoma Basocelular/patologia , Europa (Continente) , Alemanha , Proteínas Hedgehog , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Cutâneas/patologia
13.
Sci Rep ; 10(1): 7387, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355183

RESUMO

Asian population is a low-risk group for basal cell carcinoma (BCC) and there is little data available in this setting. Sun-exposed BCC (SEBCC) may possess a different pathogenic mechanism from non-sun-exposed BCC (NSEBCC). To compare the histopathological profiles and outcomes between SEBCC and NSEBCC, and to assess the risk factors for tumor recurrences. Retrospective cohort study on 372 patients with pathologically diagnosed BCC from January 1, 1990 to August 31, 2017. Data were derived from a single medical center in Taiwan. SEBCC presented with higher Clark level and more high-risk factors for recurrence than NSEBCC. Nodular, micronodular, infiltrating/mixed infiltrating, basosquamous, and adenoid types were predominant in SEBCC, as superficial type in NSEBCC. Risk factors for recurrence included infiltrating/mixed-infiltrating subtypes and synchronous basosquamous cell carcinoma. No recurrence events were observed in NSEBCC. Our study showed an acceptable recurrence rate (4.2%) of the whole population after excision even under a smaller surgical margin width than suggested by current guidelines. SEBCC had a higher recurrence rate with a significantly different tumor characteristic from NSEBCC and a greater tumor depth than NSEBCC. A wider surgical margin in SEBCC than NSEBCC is suggested.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Luz Solar/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
14.
Ann Vasc Surg ; 68: 185-191, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32422291

RESUMO

BACKGROUND: The main risk factor associated with basal cell carcinomas (BCCs) is believed to be exposure to ultraviolet radiation (UVR). In the case of lower limb BCC, the frequency is higher in women, possibly because of greater exposure of the leg to UVR. Chronic venous insufficiency (CVI), also more common in women, may have some association with leg BCCs. METHODS: We retrospectively evaluated the histopathological features of leg BCCs removed between 1993 and 2017 in a tertiary referral center. The patients' clinical data were obtained from medical records, considering, in particular, CVI. RESULTS: We selected 149 patients with leg BCCs, predominately occurring in elderly Caucasian women. Of those, 71 had a clinical diagnosis of CVI in whom the clinical tumor size and frequency of recurrences were significantly higher than patients without CVI. There was an association between clinical diagnosis of CVI and histological findings of (1) follicular induction in epidermis and (2) distal sweat duct hyperplasia. CONCLUSIONS: CVI, besides the already known UVR exposure, is probably associated with leg BCCs and may determine a worse BCC course.


Assuntos
Carcinoma Basocelular/etiologia , Perna (Membro)/irrigação sanguínea , Neoplasias Cutâneas/etiologia , Insuficiência Venosa/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Doença Crônica , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Insuficiência Venosa/diagnóstico
15.
Surg Clin North Am ; 100(3): 629-634, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402305

RESUMO

Anal cancer is a rare cancer, comprising less than 5% of gastrointestinal tract malignancies. Diagnosis of anal canal cancer can be difficult given that presenting symptoms are similar to those of benign anorectal diseases. General surgeons who encounter suspected anal canal cancer need to have a good understanding of the anatomy of the anal canal, high index of suspicion for malignancy, and low threshold to biopsy lesions when indicated. This article discusses the most commonly encountered anal canal tumors, the evaluation of these tumors, and their management. The foundation for successful therapy includes timely diagnosis, accurate staging, and routine surveillance.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias do Ânus/cirurgia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Melanoma/cirurgia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Canal Anal/patologia , Canal Anal/cirurgia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/patologia , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Diagnóstico Diferencial , Seguimentos , Metástase Linfática/patologia , Metástase Linfática/terapia , Melanoma/diagnóstico , Melanoma/patologia , Estadiamento de Neoplasias , Proctoscopia , Prognóstico
16.
Int J Comput Assist Radiol Surg ; 15(5): 887-896, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323209

RESUMO

PURPOSE: Basal cell carcinoma (BCC) is the most commonly diagnosed cancer and the number of diagnosis is growing worldwide due to increased exposure to solar radiation and the aging population. Reduction of positive margin rates when removing BCC leads to fewer revision surgeries and consequently lower health care costs, improved cosmetic outcomes and better patient care. In this study, we propose the first use of a perioperative mass spectrometry technology (iKnife) along with a deep learning framework for detection of BCC signatures from tissue burns. METHODS: Resected surgical specimen were collected and inspected by a pathologist. With their guidance, data were collected by burning regions of the specimen labeled as BCC or normal, with the iKnife. Data included 190 scans of which 127 were normal and 63 were BCC. A data augmentation approach was proposed by modifying the location and intensity of the peaks of the original spectra, through noise addition in the time and frequency domains. A symmetric autoencoder was built by simultaneously optimizing the spectral reconstruction error and the classification accuracy. Using t-SNE, the latent space was visualized. RESULTS: The autoencoder achieved an accuracy (standard deviation) of 96.62 (1.35%) when classifying BCC and normal scans, a statistically significant improvement over the baseline state-of-the-art approach used in the literature. The t-SNE plot of the latent space distinctly showed the separability between BCC and normal data, not visible with the original data. Augmented data resulted in significant improvements to the classification accuracy of the baseline model. CONCLUSION: We demonstrate the utility of a deep learning framework applied to mass spectrometry data for surgical margin detection. We apply the proposed framework to an application with light surgical overhead and high incidence, the removal of BCC. The learnt models can accurately separate BCC from normal tissue.


Assuntos
Carcinoma Basocelular/cirurgia , Aprendizado Profundo , Margens de Excisão , Neoplasias Cutâneas/cirurgia , Carcinoma Basocelular/patologia , Estudos de Viabilidade , Humanos , Procedimentos Cirúrgicos Reconstrutivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia
17.
An Bras Dermatol ; 95(3): 379-382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32276794

RESUMO

In situations in when a dermoscopic record of a large lesion is desirable, the resulting images are usually restricted to a small field of view due to the limited diameter of dermatoscope lenses. This limitation often produces several photographs separately, thus losing the possibility of a single-image global evaluation. In these case reports, we show examples of a recently published image montage technique called Wide Area Digital Dermoscopy, in this case, applied to basal cell carcinomas.


Assuntos
Carcinoma Basocelular/diagnóstico por imagem , Dermoscopia/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Carcinoma Basocelular/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Neoplasias Cutâneas/patologia , Software
18.
Arq. bras. oftalmol ; 83(2): 153-156, Mar.-Apr. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1088973

RESUMO

ABSTRACT A 45-year-old man presented with a 3-month history of a mass located in the caruncle of his right eye. An incisional biopsy had been performed one month prior by another specialist, and the histopathology report showed basal cell carcinoma. The mass was completely excised with a 2 mm safety margin, and the large conjunctival defect was reconstructed with one sheet of amniotic membrane allograft. A histological diagnosis of pilomatrix carcinoma was established. To prevent recurrence after surgery, we added bevacizumab (25 mg/mL, 1.25 mg/mL per drop) eye drops four times per day for three months. At the one-year follow-up, the patient showed no evidence of local recurrence or distant metastasis after initial excision and remains under close follow-up. Pilomatrix carcinoma should be considered in the differential diagnosis of a caruncular mass.


RESUMO Um homem de 45 anos apresentou história de massa na carúncula no olho direito durante 3 meses. Uma biópsia incisional foi realizada 1 mês antes por outro especialista e o laudo histopatológico mostrava carcinoma basocelular. A massa foi completamente excisada, com uma margem de segurança de 2 mm, e a grande lesão conjuntival foi reconstruída com uma folha de aloenxerto de membrana amniótica. Foi estabelecido um diagnóstico histológico de carcinoma pilomatricial. Para evitar a recorrência após a cirurgia, adicionamos colírio de bevacizumabe (25 mg/mL, 1,25 mg/mL por gota) quatro vezes ao dia durante três meses. No seguimento de 1 ano, o paciente não apresentou evidência de recidiva local ou metástase distante após a excisão inicial e continua sob acompanhamento próximo. O carcinoma pilomatricial deve ser considerado no diagnóstico diferencial de uma massa caruncular.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Basocelular/patologia , Pilomatrixoma/patologia , Neoplasias da Túnica Conjuntiva/patologia , Doenças do Aparelho Lacrimal/patologia , Biópsia , Carcinoma Basocelular/cirurgia , Pilomatrixoma/cirurgia , Neoplasias da Túnica Conjuntiva/cirurgia , Folículo Piloso/patologia , Doenças do Cabelo/patologia , Doenças do Aparelho Lacrimal/cirurgia
19.
Prostate ; 80(6): 508-517, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32119131

RESUMO

BACKGROUND: As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. METHODS: Here, we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34ßE12+ /P63+ /PAP- /PSA- ). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained. RESULTS: The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells. CONCLUSIONS: This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.


Assuntos
Carcinoma Basocelular/genética , Neoplasias da Próstata/genética , Biópsia por Agulha , Carcinoma Basocelular/patologia , Amplificação de Genes , Perfilação da Expressão Gênica/métodos , Frequência do Gene , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias da Próstata/patologia , Análise de Célula Única/métodos , Células Estromais/patologia , Transcriptoma , Sequenciamento Completo do Exoma
20.
Arq Bras Oftalmol ; 83(2): 153-156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159597

RESUMO

A 45-year-old man presented with a 3-month history of a mass located in the caruncle of his right eye. An incisional biopsy had been performed one month prior by another specialist, and the histopathology report showed basal cell carcinoma. The mass was completely excised with a 2 mm safety margin, and the large conjunctival defect was reconstructed with one sheet of amniotic membrane allograft. A histological diagnosis of pilomatrix carcinoma was established. To prevent recurrence after surgery, we added bevacizumab (25 mg/mL, 1.25 mg/mL per drop) eye drops four times per day for three months. At the one-year follow-up, the patient showed no evidence of local recurrence or distant metastasis after initial excision and remains under close follow-up. Pilomatrix carcinoma should be considered in the differential diagnosis of a caruncular mass.


Assuntos
Carcinoma Basocelular/patologia , Neoplasias da Túnica Conjuntiva/patologia , Doenças do Aparelho Lacrimal/patologia , Pilomatrixoma/patologia , Biópsia , Carcinoma Basocelular/cirurgia , Neoplasias da Túnica Conjuntiva/cirurgia , Doenças do Cabelo/patologia , Folículo Piloso/patologia , Humanos , Doenças do Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Pilomatrixoma/cirurgia
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