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1.
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
2.
Medicine (Baltimore) ; 99(40): e22550, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019466

RESUMO

This study aimed to investigate the associations between the sonographic findings and duration of symptoms in children with pilomatricoma.This study included 86 children with 95 lesions confirmed to be pilomatricoma after pathological examination. The associations between symptom duration and sonographic observations, including the presence or absence of peritumoral hyperechogenicity, calcification, and vascularity were investigated. The internal echogenicity of each pilomatricoma was scored using a 5-point scale based on echogenic spots and calcification with posterior acoustic shadowing. The Mann-Whitney U and Kruskal-Wallis tests were used for statistical analysis.We found that the absence of peritumoral hyperechogenicity and severity of calcification were associated with increased symptom duration. Calcification, (present, 19.19 ±â€Š18.99 months vs absent, 4.31 ±â€Š3.24 months; P < .01) and peritumoral hyperechogenicity (present, 5.02 ±â€Š5.80 months vs absent, 16.17 ±â€Š18.24 months; P < .01), and grade of internal echogenicity (grade 0/1/2/3/4 = 3 months [1 patient]/4.33 ±â€Š3.26 months [range, 1-12]/4.57 ±â€Š3.46 months [range, 2-12]/10.89 ±â€Š9.17 months [range, 3-28]/35.27 ±â€Š19.16 months [range, 9-60], respectively; P = .01 and <.01) were associated with significant differences in symptom duration. There were no significant between-group differences in vascularity (6.01 ±â€Š7.24 months; range, 1-48 vs 15.50 ±â€Š19.12 months; range, 1-60; P = .08).Pilomatricomas with a relatively short symptom duration were more likely to exhibit peritumoral hyperechogenicity and calcification with less severe posterior acoustic shadowing compared to lesions with a longer symptom duration. These sonographic findings provided useful information that facilitated the correct and rapid diagnosis of pilomatricoma.


Assuntos
Pilomatrixoma/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Avaliação de Sintomas/estatística & dados numéricos , Ultrassonografia/métodos , Calcificação Fisiológica , Calcinose/diagnóstico por imagem , Calcinose/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Avaliação de Sintomas/tendências
3.
Adv Exp Med Biol ; 1268: 257-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918223

RESUMO

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.


Assuntos
Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Vitamina D/química , Animais , Progressão da Doença , Humanos , Receptores de Calcitriol/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo , Vitamina D/farmacologia , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
4.
BMJ ; 370: m2942, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878860

RESUMO

OBJECTIVE: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years. EXPOSURE: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes. MAIN OUTCOME MEASURES: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models. RESULTS: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair. CONCLUSION: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Tinturas para Cabelo/efeitos adversos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto , Neoplasias Encefálicas/induzido quimicamente , Neoplasias da Mama/induzido quimicamente , Carcinoma Basocelular/induzido quimicamente , Estudos de Casos e Controles , Neoplasias Colorretais/induzido quimicamente , Feminino , Humanos , Neoplasias Renais/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/induzido quimicamente
5.
Chirurgia (Bucur) ; 115(4): 476-485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32876021

RESUMO

Background: The accuracy of the staging, along with the reproductibility of intraoperative lymph car-tography, and lymph node biopsy in patients with malignant melanoma was unanimously validated in the last decade. This technique allows the discovery of lymph node micrometastses with the help of immunohistochemical methods. The goal of the present study is to present the experience of our clinic in identification and biopsy protocol of the lymph node. Methods: A year-long retrospective analysis was running between March 2019 - December 2019 con-cerning 57 patients with cutaneous melanoma on which detection and excisional biopsy of the lymph node was performed. The procedure was performed by the double method using vital dye and a ra-dio-active tracer. Demographic information was filed, as well as data on location of primary tumors, tumor histology, and radioactivity level. Results: The mean Breslow thickness of primary skin melanomas was 2.7 mm. At least one lymph node was identified in 56 of the 57 patients included in the study. Among those, 15 (26%) had at least one metastatic node. The mean number of excised lymph nodes per patient was 1.6. Conclusions: The cartography and biopsy of lymph nodes need the involvement of a complex multi disciplinary team made of nuclear medicine, surgery, and anatomopathology specialists. This way one provides both a correct staging of the patient with melanoma and access to adjuvant innovative therapies, thus considerably improving the prognosis.


Assuntos
Melanoma/patologia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Resultado do Tratamento
6.
Immunotherapy ; 12(15): 1133-1138, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32900245

RESUMO

Background: Little is known about the 2019 novel coronavirus disease (COVID-19) course and outcomes in patients receiving immunotherapy. Here we describe a metastatic Merkel cell carcinoma patient with a severe acute respiratory syndrome coronavirus 2 infection while receiving pembrolizumab. Case presentation: A 66-year-old man, with a metastatic Merkel cell carcinoma receiving pembrolizumab, presented with fever. Chest computed tomography (CT) showed pulmonary ground-glass opacities, suggesting viral or immuno-related etiology. On day 7, the patient was hospitalized due to dyspnea and worsening of the radiological findings. Real time polymerase chain reaction (RT-PCR) testing confirmed COVID-19. The patient developed acute respiratory distress syndrome and acute kidney injury. Hydroxychloroquine was administered for 5 days, but discontinued after supraventricular extrasystoles. Clinical improvement allowed the patient's discharge after 81 days of hospitalization. Conclusion: A careful evaluation of oncologic patients receiving immunotherapy during the COVID-19 pandemic is of utmost importance.


Assuntos
Carcinoma de Célula de Merkel/terapia , Infecções por Coronavirus/diagnóstico , Imunoterapia , Pneumonia Viral/diagnóstico , Neoplasias Cutâneas/terapia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Betacoronavirus , Carcinoma de Célula de Merkel/complicações , Carcinoma de Célula de Merkel/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Humanos , Imunoterapia/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(39): e22252, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991421

RESUMO

A 31-year-old male patient with psoriasis received administration of traditional Chinese medicine (TCM) during a disease course of 14 years. He showed multiple keratoma together with squamous cell carcinoma (SCC) in left lower limbs. After admission, the conditions were stable after treatment, and received surgery for treating SCC. The skin defect was treated using full-thickness skin graft. The postoperative survival of the flap was satisfactory, and the conditions of psoriasis were well controlled. In this case, we presented the feasibility of graft in the donor site from a psoriatic lesion. Besides, we analyzed the possibility of SCC and keratinizing lesions.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Cutâneas/cirurgia , Transplante de Pele/métodos , Retalhos Cirúrgicos/transplante , Adulto , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Medicina Tradicional Chinesa , Psoríase/complicações , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia
8.
N Z Med J ; 133(1520): 50-60, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994593

RESUMO

AIM: Therapeutic lymphadenectomy remains the gold standard for surgical management of clinically evident regional cervical disease for cutaneous malignancy. However, international consensus on adequate lymphadenectomy is lacking. Attempts have been made to establish quality measures; suggested benchmarks for minimum and average nodal yield, as well as recurrence and complication rates have been quoted. We aim to compare our key performance indicators to those benchmarks published in the literature. METHODS: This is a retrospective observational study conducted with prospectively maintained data, over an 11-year period (2007-2018). RESULTS: Of 91 cervical lymphadenectomies included, mean nodal yield for ≤3 and ≥4 dissection levels were 19.7 and 38.7 respectively. We observed a combined locoregional recurrence rate of 25%. Subgroup analysis for melanoma (60) and cSCC (28) revealing regional nodal recurrence of 15% and 11%, respectively. We observed a 38.5% complication rate; however, less than 5.5% was considered grade IIIb/IIIb(d) [Clavein-Dindo]. Median follow-up of 19.3 months, five-year survivial rate of 38% and 32% for melanoma and cSCC, respectively. CONCLUSION: Our data indicates that we are meeting quality measures, set by higher volume centres. We believe that any surgeon with subspecialty training in head and neck surgery can meet quality measures with regards to cervical lymphadenopathy for cutaneous malignancy.


Assuntos
Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Pescoço/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Metástase Linfática/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Nova Zelândia/epidemiologia , Guias de Prática Clínica como Assunto , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Neoplasias Cutâneas/secundário , Cirurgiões/educação , Taxa de Sobrevida
10.
PLoS Pathog ; 16(8): e1008792, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813746

RESUMO

Tumor suppressors can exert pro-proliferation functions in specific contexts. In the beta human papillomavirus type 38 (HPV38) experimental model, the viral proteins E6 and E7 promote accumulation of a wild-type (WT) p53 form in human keratinocytes (HKs), promoting cellular proliferation. Inactivation of p53 by different means strongly decreases the proliferation of HPV38 E6/E7 HKs. This p53 form is phosphorylated at S392 by the double-stranded RNA-dependent protein kinase PKR, which is highly activated by HPV38. PKR-mediated S392 p53 phosphorylation promotes the formation of a p53/DNMT1 complex, which inhibits expression of integrin alpha 1 (ITGA1), a repressor of epidermal growth factor receptor (EGFR) signaling. Ectopic expression of ITGA1 in HPV38 E6/E7 HKs promotes EGFR degradation, inhibition of cellular proliferation, and cellular death. Itga1 expression was also inhibited in the skin of HPV38 transgenic mice that have an elevated susceptibility to UV-induced skin carcinogenesis. In summary, these findings reveal the existence of a specific WT p53 form that displays pro-proliferation properties.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Proliferação de Células , Queratinócitos/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/etiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Humanos , Queratinócitos/imunologia , Queratinócitos/virologia , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/isolamento & purificação , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genética
11.
Nat Commun ; 11(1): 3946, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770055

RESUMO

Melanomas can switch to a dedifferentiated cell state upon exposure to cytotoxic T cells. However, it is unclear whether such tumor cells pre-exist in patients and whether they can be resensitized to immunotherapy. Here, we chronically expose (patient-derived) melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observe strong enrichment of a pre-existing NGFRhi population. These fractions are refractory also to T cells recognizing non-differentiation antigens, as well as to BRAF + MEK inhibitors. NGFRhi cells induce the neurotrophic factor BDNF, which contributes to T cell resistance, as does NGFR. In melanoma patients, a tumor-intrinsic NGFR signature predicts anti-PD-1 therapy resistance, and NGFRhi tumor fractions are associated with immune exclusion. Lastly, pharmacologic NGFR inhibition restores tumor sensitivity to T cell attack in vitro and in melanoma xenografts. These findings demonstrate the existence of a stable and pre-existing NGFRhi multitherapy-refractory melanoma subpopulation, which ought to be eliminated to revert intrinsic resistance to immunotherapeutic intervention.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Melanoma/tratamento farmacológico , Proteínas do Tecido Nervoso/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fator de Crescimento Neural/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Linfócitos T Citotóxicos/imunologia , Animais , Antineoplásicos Imunológicos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Masculino , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , RNA-Seq , Receptores de Fator de Crescimento Neural/antagonistas & inibidores , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/metabolismo , Evasão Tumoral/genética , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Nat Commun ; 11(1): 4306, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855398

RESUMO

Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.


Assuntos
Evolução Clonal , Heterogeneidade Genética , Melanoma/genética , Neoplasias Cutâneas/genética , Idoso , Biópsia , Análise Mutacional de DNA , Humanos , Masculino , Melanoma/secundário , Estudos Prospectivos , Pele/patologia , Neoplasias Cutâneas/patologia , Sequenciamento Completo do Genoma
13.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815685

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignancy of the upper limb, and can pose a significant therapeutic challenge. Early treatment needs to be radical whilst maintaining function. METHODS: We describe two cases of upper limb squamous cell carcinoma treated with radiotherapy, review the literature on radiotherapy as a primary treatment modality, and discuss the specific difficulties treating SCC in the hand. RESULTS: Radiation therapy was inadequate in tumor clearance in both cases, with recurrence both extensive and distal to the initial focus. Moreover, both patients developed progressive functional loss related to pain, swelling, and stiffness. CONCLUSION: The evidence basis for radiation therapy as a primary modality is limited, although clearance rates are comparable to surgery. Both radiotherapy and surgery can be utilized to treat SCC. However, we make the case for the hand being especially susceptible to the unwanted side effects of radiotherapy.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Carcinoma de Células Escamosas/patologia , Feminino , Mãos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Lesões por Radiação/patologia , Radioterapia/efeitos adversos , Neoplasias Cutâneas/patologia
14.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815690

RESUMO

Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between the long arms of chromosomes 9 and 22 leading to the formation of a constitutively active tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the treatment of choice for patients diagnosed with CML and have many associated side effects including the rarely-reported eruption of squamous cell carcinomas (SCCs). Herein, we report a patient with CML who presented with sudden onset of multiple scaly lesions on his legs and trunk after beginning treatment with nilotinib, a novel TKI. Six biopsies were performed at his initial presentation and four of these lesions were confirmed to be keratoacanthoma-type SCCs. One month later, the patient reported the development of multiple new similar lesions on his legs, arms, and face. Four more biopsies were performed revealing keratoacanthoma-type and well-differentiated SCCs. Certain tyrosine kinase inhibitors such as sorafenib and quizartinib have been reported to cause eruptive keratoacanthoma (KA)-type SCCs as seen in our patient. However, there is only one other report in the literature of nilotinib promoting the development of SCCs or KAs. Physicians should be aware of this potential adverse effect and patients taking nilotinib should be closely monitored by a dermatologist.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Idoso , Carcinoma de Células Escamosas/patologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pirimidinas/uso terapêutico , Neoplasias Cutâneas/patologia
15.
PLoS Pathog ; 16(8): e1008562, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32833988

RESUMO

Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR. Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses.


Assuntos
Carcinoma de Célula de Merkel/patologia , Reparo do DNA por Junção de Extremidades , Poliomavírus das Células de Merkel/genética , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Integração Viral , Replicação Viral , Antígenos Virais de Tumores , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias Ósseas/virologia , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/virologia , Humanos , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/virologia , Recombinação Genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia , Proteínas Virais/genética
16.
Anticancer Res ; 40(7): 3723-3732, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620611

RESUMO

BACKGROUND/AIM: Skin melanoma belongs to the most invasive malignancies with no cure for a progressing disease. Personalized therapy would allow for the selection of patients that will benefit from treatment. For this purpose, proper predictive biomarkers must be defined. MATERIALS AND METHODS: Allogeneic whole-cell gene-modified therapeutic melanoma vaccine (AGI-101H) was applied in advanced melanoma patients. Humoral responses were analyzed using SEREX, and in silico gene expression analysis in TCGA melanoma patients was performed. RESULTS: A specific antibody response was raised against an antigen identified as BNIP3L, which correlated with a good prognosis. Moreover, AGI-101H directs an immune response against autophagy, as BNIP3L is a marker of this process. Medium and high expression of BNIP3L was also linked with longer overall survival. CONCLUSION: BNIP3L is a candidate prognostic marker of clinical outcome of melanoma patients treated with AGI-101H, and may be considered as a prediction marker for patient survival.


Assuntos
Autofagia/fisiologia , Biomarcadores Tumorais/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Vacinas Anticâncer/imunologia , Feminino , Humanos , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia
17.
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
18.
Cancer Treat Rev ; 88: 102060, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32619863

RESUMO

Phenotypic plasticity of malignant melanoma is a well-known phenomenon. Several translational studies and small case series have reported this clinical and biological entity, particularly in metastatic melanoma, showing frequent aberrant expression of non-melanocytic differentiation markers of different lineages, posing remarkable challenges due to several alternative differential diagnoses including undifferentiated carcinoma and sarcomas. When melanoma loses its typical morpho-phenotype by routinely used diagnostic immunohistochemical markers, it is defined as "dedifferentiated melanoma". Historically, this process was closely related to diagnostic interpretative difficulties. In recent years, however, dedifferentiation has been increasingly recognized as an important biological phenomenon that demonstrates the phenotypic and genetic plasticity of melanoma, and specifically the non-irreversibility of the multistep cancerogenesis. Furthermore, dedifferentiation emerged as a general hallmark of cancer evolution and a common denominator of cross-resistance to both targeted and immunotherapy. In this review, we summarize the histopathological features, the genetic and epigenetic bases underlying the dedifferentiated phenotype in melanomas and provide additional support that dedifferentiation is a mechanism of resistance to immunotherapy and targeted therapy.


Assuntos
Melanoma/genética , Melanoma/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Animais , Desdiferenciação Celular/fisiologia , Reprogramação Celular/fisiologia , Epigênese Genética , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia
20.
Cancer Invest ; 38(7): 415-423, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643437

RESUMO

The aim of the study was to investigate if there was an association between intraoperative NSAID use and recurrence or survival. A cohort of patients who underwent sentinel lymph node biopsy for the treatment of cutaneous melanoma was retrospectively recruited. After applying inclusion and exclusion criteria, 516 were included (NSAIDs = 307). The 10-year melanoma-specific survival was 63.2%. Log-rank test showed no statistically significant differences in time to treatment failure, melanoma-specific survival, disease-free survival, and overall survival between the study groups. The current study did not support the use of intraoperative NSAIDs in preventing death or recurrence in patients with melanoma.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Idoso , Estudos de Coortes , Feminino , Humanos , Isoxazóis/uso terapêutico , Estimativa de Kaplan-Meier , Cetorolaco/uso terapêutico , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Perioperatório , Piroxicam/análogos & derivados , Piroxicam/uso terapêutico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento
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