RESUMO
BACKGROUND: Collagenomas are rare connective tissue hamartomas composed of dermal collagen. Patients infected with human immunodeficiency virus (HIV) can present with HIV-related lipodystrophy or lipomas. There are no known associations between HIV and collagenomas. CASE PRESENTATION: Here we describe a case of an isolated collagenoma in an HIV patient on ART. The lesion was a seven by four-centimeter subcutaneous nodule with no epidermal changes located on the occipital scalp. This lesion was excised, and histopathology showed thick and randomly arranged collagen bundles, consistent with a collagenoma. CONCLUSION: This case represents an isolated collagenoma presenting in a patient with HIV. It is unclear whether HIV or ART contributed to the development of this collagenoma. Treatment of collagenomas include surgical excision and intralesional corticosteroids. In addition to lipoma or lipodystrophy, it is important to keep collagenoma in the differential diagnosis in a patient presenting with an isolated large indurated subcutaneous nodule.
Assuntos
Infecções por HIV , Soropositividade para HIV , Hamartoma , Lipodistrofia , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológicoRESUMO
INTRODUCTION: Gene fusion variants in ALK-rearranged NSCLC may predict patient outcomes, but previous results have been inconclusive. Fusion isoforms coexisting in the same tumor may affect the efficacy of targeted therapy, but they have not been investigated. METHODS: Patients with ALK-rearranged NSCLC who received crizotinib treatments were recruited. Precrizotinib tumor tissues were analyzed by the anchored multiplex polymerase chain reaction for targeted RNA sequencing. Kaplan-Meier and Cox regression were used to compare overall and progression-free survivals. RESULTS: Of the 51 studied subjects, EML4-ALK variant types v1, v2, v3, and others were detected in 23 (45.1%), five (9.8%), 19 (37.3%), and four patients (7.8%), respectively. Multiple EML4-ALK RNA isoforms were detected in 24 tumors (47.1%), and single isoform in 27 (52.9%). Most of the v3 tumors (16 of 19) harbored both v3a and v3b RNA isoforms. Multiple isoforms were also detected in eight non-v3 tumors (33.3% of all 24 multiple isoforms; five v1, two v5', and one v2). Compared with patients with single isoform, those with multiple isoforms had worse progression-free (hazard ratio and 95% confidence interval: 2.45 [1.06-5.69]) and overall (hazard ratio [95% confidence interval]: 3.74 [1.26-11.13]) survivals after adjusting for potential confounders including variant type. Using the patient-derived H2228 cells known to express v3a and v3b, our single-cell polymerase chain reaction detected either v3a or v3b in most single cells. Treatment of H2228 cells by three ALK inhibitors revealed increased ratios of v3a-to-v3b expression over time. CONCLUSIONS: Intratumoral EML4-ALK isoforms may predict the efficacy of targeted therapy in ALK-rearranged NSCLC. Temporal changes of intratumoral fusion isoforms may result from differential selection pressures that a drug might have on one isoform over another. Larger studies on fusion heterogeneity using RNA sequencing are warranted.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Crizotinibe/uso terapêutico , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Fusão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , RNA , Receptores Proteína Tirosina Quinases/genética , Análise de Sequência de RNA , Resultado do TratamentoAssuntos
Dermatofibrossarcoma/patologia , Neoplasias Cutâneas/patologia , Antígenos CD34/metabolismo , Atrofia/patologia , Dermatofibrossarcoma/congênito , Dermatofibrossarcoma/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/diagnóstico , Adulto JovemAssuntos
Anestesia Local/efeitos adversos , Anestésicos Locais/efeitos adversos , Paralisia de Bell/induzido quimicamente , Paralisia de Bell/diagnóstico por imagem , Lidocaína/efeitos adversos , Idoso , Diagnóstico Diferencial , Nervo Facial , Feminino , Humanos , Cirurgia de Mohs/efeitos adversos , Acidente Vascular Cerebral/diagnósticoAssuntos
Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Infecções por HIV/imunologia , Margens de Excisão , Neoplasias Cutâneas/cirurgia , Contagem de Linfócito CD4 , Carcinoma Basocelular/complicações , Carcinoma de Células Escamosas/complicações , Estudos de Casos e Controles , Infecções por HIV/complicações , Humanos , Cirurgia de Mohs , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/complicaçõesRESUMO
BACKGROUND: Surgical and nonsurgical methods are used for treating basal cell carcinoma (BCC). Few randomized controlled trials exist on the effectiveness of the pulsed dye laser (PDL) on BCC treatment. OBJECTIVE: We investigated the effectiveness of PDL treatment in a single session for the management of nodular and superficial BCCs on the trunk and extremities of adults using a randomized, double-blind, controlled technique. METHODS: We used settings of fluence 7.5 J/cm2, 3-ms pulse duration, no dynamic cooling, 10-mm spot size, 10% overlap between pulses, and 2 stacked pulses on a 595-nm wavelength laser. Histopathologic clearance on excision of tumor with 4-mm margins was the primary outcome measure. RESULTS: Twenty-four patients were included in the study, with 14 in the laser treatment group and 10 patients in the sham/control group. In total, 10/14 (71.4%) of the tumors in the treatment group were successfully treated with no residual tumor on excisional specimen histology, compared with 3/10 (30.0%) of the control group (p = .045). CONCLUSION: Our study shows that PDL may be an effective treatment for low-risk BCCs of the trunk and extremities, but the cure rate is lower than those of other treatments for BCC. Thus, PDL under the current settings cannot be recommended.
Assuntos
Carcinoma Basocelular/cirurgia , Lasers de Corante/uso terapêutico , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Relação CD4-CD8 , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Infecções por HIV/complicações , Neoplasias Cutâneas/imunologia , Carcinoma Basocelular/sangue , Carcinoma Basocelular/imunologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Cirurgia de Mohs/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral/imunologiaAssuntos
Poluentes Ocupacionais do Ar/normas , Infecções por Coronavirus/prevenção & controle , Procedimentos Cirúrgicos Dermatológicos/normas , Máscaras/normas , Exposição Ocupacional/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Humanos , Saúde Ocupacional/normas , Salas Cirúrgicas/organização & administração , Padrões de Prática Médica , SARS-CoV-2 , Dermatopatias/cirurgiaRESUMO
We present a CRISPR-based multi-gene knockout screening system and toolkits for extensible assembly of barcoded high-order combinatorial guide RNA libraries en masse. We apply this system for systematically identifying not only pairwise but also three-way synergistic therapeutic target combinations and successfully validate double- and triple-combination regimens for suppression of cancer cell growth and protection against Parkinson's disease-associated toxicity. This system overcomes the practical challenges of experimenting on a large number of high-order genetic and drug combinations and can be applied to uncover the rare synergistic interactions between druggable targets.
Assuntos
Sistemas CRISPR-Cas , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Ensaios de Triagem em Larga Escala/métodos , Animais , Antineoplásicos/farmacologia , Drosophila melanogaster , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , RNA Guia de CinetoplastídeosAssuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Gerenciamento Clínico , Oncologia/métodos , Pneumonia Viral/complicações , Neoplasias Cutâneas/complicações , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Neoplasias Cutâneas/terapiaAssuntos
Proteínas de Ligação a DNA/genética , DNA/genética , Histonas/genética , Neoplasias/genética , Proliferação de Células/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , DNA/ultraestrutura , Proteínas de Ligação a DNA/ultraestrutura , Histonas/ultraestrutura , Humanos , Mutação/genética , Neoplasias/patologia , Conformação de Ácido Nucleico , Nucleossomos/genética , Oncogenes/genética , FenótipoRESUMO
Although biomimetic stimuli, such as microgroove-induced alignment (µ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined µ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-ß signaling was downregulated; the TGF-ß receptor agonist and antagonist TGF-ß1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.