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4.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815687

RESUMO

To date, only twenty cases of cutaneous legionellosis have been reported. Cutaneous legionellosis has heterogeneous manifestations including abscesses, nodules, and cellulitis. The detection of most cutaneous Legionella species requires specific diagnostic cultures and assays. Herein, we report a case of cutaneous legionella in a hematopoietic cell transplantation recipient with culture-negative nodules unresponsive to empiric antibiotics. We also discuss the varied morphology of cutaneous legionellosis and important diagnostic considerations.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Legionella , Legionelose/patologia , Dermatopatias Bacterianas/patologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Humanos , Legionella/isolamento & purificação , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico
5.
J Am Acad Dermatol ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389716

RESUMO

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consults. Inpatient access to dermatologists is limited, illustrating an opportunity to utilize teledermatology. Little is known about the ability of dermatologists to accurately diagnose and manage inpatients using teledermatology, particularly utilizing non-dermatologist generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose and manage 41 dermatology consults from a large urban tertiary care center utilizing internal medicine referral documentation and photos. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the kappa statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median kappa = 0.83), substantial agreement in laboratory work-up decisions (median kappa = 0.67), almost perfect agreement in imaging decisions (median kappa = 1.0), and moderate agreement in biopsy decisions (median kappa = 0.43). There was almost perfect agreement in treatment (median kappa = 1.0), but no agreement in follow-up planning (median kappa = 0.0). There was no association between raw photo quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

6.
J Am Acad Dermatol ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32171811

RESUMO

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are associated with high morbidity and mortality in patients with cancer. Early identification and treatment of SCARs may improve outcomes. OBJECTIVE: To identify biomarkers to predict outcomes in hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 144 hospitalized patients with cancer with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor [TNF]-α) or elafin, and a dermatology consultation. Rashes were categorized as simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifty-four of 144 (37.5%) patients died during follow-up. Elevated levels of IL-6, IL-10, and TNF-α were associated with decreased survival. Overall survivals in patients with elevated levels of IL-6, IL-10, and TNF-α were 53.7%, 56.6%, 53.6%, respectively, compared with 85.7%, 82.5% and 83.6%, respectively, in those with lower levels. Patients with increased levels of both IL-6 and TNF-α had a nearly 6-fold increase in mortality (hazard ratio, 5.82) compared with patients with lower levels. LIMITATIONS: Retrospective design, limited sample size, and high-risk population. CONCLUSIONS: Hospitalized patients with cancer with rash and elevated IL-6 and TNF-α were nearly 6 times more likely to die over the course of follow-up. These biomarkers may serve as prognostic biomarkers and therapeutic targets for this high-risk population.

7.
J Am Acad Dermatol ; 82(6): 1553-1567, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32151629

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

8.
JAMA Dermatol ; 156(5): 587-588, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32211818
9.
Photochem Photobiol Sci ; 18(10): 2461-2468, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31410432

RESUMO

Complexes of photosensitizers with blood proteins play an essential role in their delivery to the cell, as well as in the efficacy of photodynamic therapy. Biscarbocyanine dye non-covalently binds human serum albumin (HSA), the dissociation constant of the dye with albumin being Kd = (1.7 ± 0.1) × 10-5 M. According to time correlated single photon counting (TCSPC) fluorescence lifetime spectroscopy data, two types of complexes with lifetimes of 1.0 ns and 2.5 ns are formed between the dye and HSA. Confocal fluorescence microscopy has unambiguously shown the penetration of biscarbocyanine into endoplasmic reticulum, lysosomes, mitochondria and nuclei of the cells. The dye demonstrates photocytotoxicity towards the colon carcinoma HCT116 cells with IC50 = 0.3 µM. Hydrophobicity of the polymethine chain and the presence of two positive charges on the dye molecule contribute to the effective binding of the dye with HSA and the penetration into cells. These facts allow considering the biscarbocyanine dye as a promising agent for the photodynamic therapy of cancer.


Assuntos
Carbocianinas/química , Corantes Fluorescentes/química , Albumina Sérica/química , Carbocianinas/metabolismo , Carbocianinas/farmacologia , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/metabolismo , Células HCT116 , Humanos , Lisossomos/metabolismo , Ligação Proteica , Albumina Sérica/metabolismo
10.
Biol Blood Marrow Transplant ; 25(11): 2172-2180, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31306779

RESUMO

Although histopathological differences have been reported between acute graft-versus-host disease (aGVHD) rash and non-aGVHD rash in CD34+-selected peripheral blood stem cell transplantation (PBSCT) recipients, skin biopsy alone is usually insufficient to determine rash etiology. As such, distinguishing inflammatory non-aGVHD rashes, such as drug eruptions, from cutaneous aGVHD after CD34+-selected PBSCT remains challenging and relies on clinical presentation. This study aimed to identify etiologies of skin rash in the first year after CD34+-selected PBSCT and to assess whether laboratory serologic markers, transplant characteristics, and rash morphology and symptomatology aid in differentiation of cutaneous aGVHD rash versus non-aGVHD rash. We conducted a retrospective study of 243 adult patients who underwent CD34+-selected PBSCT at Memorial Sloan Kettering Cancer Center between 2008 and 2011. Among this cohort of transplant recipients, only 43 patients (17.7%) developed cutaneous aGVHD. A total of 152 patients (63%) were identified with rash within 1 year after PBSCT. The proportion of patients who experienced peripheral eosinophilia was not different between those with an aGVHD versus non-aGVHD rash (P ≥ .90), nor when stratified by CD34+ selection method (Isolex, P = .70; CliniMACS, P≥ .90). The proportion of patients with pruritus was also not different between those with an aGVHD rash versus non-aGVHD rash (P= .20), or when stratified by CD34+ selection modality (Isolex, P = .20; CliniMACS, P = .50). The most common cause of non-aGVHD rash among those with a clear etiology was drug (39% of Isolex; 26% of CliniMACS). Single drug culprits were identified in 51% of drug rashes. The most commonly reported offending agents included antibiotics, keratinocyte growth factor, chemotherapy, and recombinant glycosylated human IL-7.


Assuntos
Exantema , Transplante de Células-Tronco de Sangue Periférico , Prurido , Doença Aguda , Aloenxertos , Antígenos CD34 , Exantema/induzido quimicamente , Exantema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Prurido/epidemiologia , Prurido/patologia , Estudos Retrospectivos
11.
J Clin Oncol ; 37(30): 2746-2758, 2019 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-31216228

RESUMO

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Fatores Imunológicos/efeitos adversos , Dermatopatias/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
J Am Acad Dermatol ; 81(3): 740-748, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102603

RESUMO

BACKGROUND: Readmissions for skin disease, particularly for the same diagnosis and over time, have not been well studied. OBJECTIVE: To characterize hospital readmissions for skin disease. METHODS: A cross-sectional observational study examined the Nationwide Readmissions Database from 2010 to 2014, a national sample of hospital discharges in the United States. RESULTS: Of the patients in 3,602,599 dermatologic hospitalizations from 2010 to 2014, 9.8% were readmitted for any cause, 3.3% were admitted for the same diagnosis within 30 days, and 7.8% were readmitted for the same diagnosis within the calendar year (CY). The cost of all CY same-cause readmissions was $508 million per year. Mycosis fungoides had the highest 30-day all-cause readmission rate (32%), vascular hamartomas and dermatomyositis had the highest 30-day same-cause readmission rates (21% and 18%, respectively), and dermatomyositis and systemic lupus erythematosus had the highest CY same-cause readmission rates (31% and 24%, respectively). Readmission rates stayed stable from 2010 to 2014. Readmission for the same diagnosis was strongly associated with Medicaid and morbid obesity. LIMITATIONS: This study is a broad description of hospitalizations for skin disease. Conclusions for individual diseases are not intended. CONCLUSION: The rates and costs of readmissions for skin diseases remained high from 2010 to 2014. This study identifies diseases associated with high risk of hospital readmission, but disease-specific studies are needed. The diseases and risk factors presented should guide additional studies focused on strategies to reduce readmissions in specific skin diseases.


Assuntos
Custos Hospitalares/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Dermatopatias/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Custos Hospitalares/tendências , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/economia , Readmissão do Paciente/tendências , Fatores de Risco , Dermatopatias/economia , Estados Unidos , Adulto Jovem
14.
J Am Acad Dermatol ; 80(3): 608-616, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30612984

RESUMO

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are frequent in inpatient oncology. Early intervention might reduce morbidity, mortality, and hospitalization costs; however, current clinical and histologic features are unreliable SCAR predictors. There is a need to identify rational markers of SCARs that could lead to effective therapeutic interventions. OBJECTIVE: To characterize the clinical and serologic features of hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 49 hospitalized cancer patients with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL] 6, IL-10, and tumor necrosis factor [TNF] α) or elafin, and a prior dermatology consultation. Patients were categorized as having a simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifteen out of 49 patients (30.6%) were deceased at 6 months from time of dermatologic consultation. Elafin, IL-6, and TNF-α were significantly higher in patients who died compared with patients who were still alive at 6 months. IL-6 and IL-10 were significantly higher in patients with a drug-related complex rash. LIMITATIONS: Retrospective design, limited sample size, and high-risk patient population. CONCLUSION: In cancer patients with SCARs, elafin, IL-6, and TNF-α levels might predict a poor outcome. Agents directed against these targets might represent rational treatments for the prevention of fatal SCARs.


Assuntos
Citocinas/sangue , Síndrome de Hipersensibilidade a Medicamentos/sangue , Elafina/sangue , Mortalidade Hospitalar , Neoplasias/tratamento farmacológico , Síndrome de Stevens-Johnson/sangue , Adulto , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Superfície Corporal , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Edema/etiologia , Eosinofilia/etiologia , Face , Feminino , Febre/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Hospitalização , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Linfócitos/patologia , Masculino , Púrpura/etiologia , Estudos Retrospectivos , Síndrome de Stevens-Johnson/etiologia , Fator de Necrose Tumoral alfa/sangue
15.
J Mater Chem B ; 6(16): 2450-2459, 2018 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32254462

RESUMO

We describe the synthesis and properties of a new composite material based on heparin and MIL-101(Fe) metal-organic framework. The intrinsic instability of MIL-101(Fe) towards hydrolysis enables binding of heparin molecules to the framework structure as is evidenced by DFT calculations and adsorption experiments. The de novo formed heparin-MOF composites showed good biocompatibility in in vitro and demonstrated pronounced anticoagulant activity. The specific interaction between the bioactive molecule and the carrier is critical for the selective degradation of the complex in the body fluids and for the enhanced activity. Hep_MIL-101(Fe) composite could serve as a drug-releasing depot for nanofabrication and to introduce anticoagulant activity to medical devices and biocoatings. Addition of Hep_MIL-101(Fe) to a sol-gel derived thrombolytic matrix allowed the combination of anticoagulant and thrombolytic activities in a single hybrid nanomaterial that could be applied as a bioactive nanocoating for PTFE vein implants.

16.
Anticancer Agents Med Chem ; 18(4): 617-627, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28730961

RESUMO

BACKGROUND: Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium. OBJECTIVE: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors. METHOD: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were conjugated to the porphyrin ring in meso-positions. Two derivatives were tested as the solutions prepared either from a dimethylformamide stock ('free' formulation) or from a perfluorocarbon emulsion in which the photosensitizer is entrapped in the oxygenated medium. RESULTS: In the emulsion the hydrophobic photosensitizer and the gas transporting liquid represented a biocompatible composition. Free formulations or perfluorocarbon emulsions of fluorinated porphyrins evoked little-to-null dark cytotoxicity. In contrast, each formulation triggered cell death upon light activation. Photodamage in the presence of fluorinated porphyrins was achievable not only at normoxic (20.9% O2 v/v) conditions but also in hypoxia (0.5% O2). With new compounds dissolved in the medium the cell photodamage in hypoxia was negligible whereas a significant photodamage was achieved with the emulsions of fluorinated porphyrins. The derivative with the fluoroalkyl substituent was more potent than its structurally close analog carrying the fluoroaryl moiety. CONCLUSION: Our new fluorinated porphyrin derivatives, especially their emulsions in which the photosensitizer and the oxygenated medium are coupled into one phase, can be perspective for photoelimination of hypoxic tumor cells.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Hidrocarbonetos Fluorados/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/química , Hipóxia/metabolismo , Estrutura Molecular , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
17.
J Am Acad Dermatol ; 78(6): 1102-1109, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29273489

RESUMO

BACKGROUND: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. OBJECTIVE: To characterize inpatient dermatology consultations at a large comprehensive cancer center. METHODS: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January-December 2015. RESULTS: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35-8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. LIMITATIONS: The study's retrospective nature and single-institution setting are potential limitations. CONCLUSION: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.


Assuntos
Dermatite/epidemiologia , Dermatite/etiologia , Erupção por Droga/epidemiologia , Hospitalização/estatística & dados numéricos , Neoplasias/complicações , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Institutos de Câncer , Estudos de Coortes , Bases de Dados Factuais , Dermatite/patologia , Erupção por Droga/etiologia , Feminino , Humanos , Incidência , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Cidade de Nova Iorque , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/etiologia
18.
J Cutan Pathol ; 44(11): 969-973, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28796338

RESUMO

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by overgrowth of flat warts, pityriasis versicolor-like lesions and an increased propensity for developing cutaneous squamous cell carcinomas due to abnormal susceptibility to infection with beta-human papilloma viruses. Adnexal tumors are not typically associated with EV. Here we report a spectrum of hybrid adnexal tumors with divergent eccrine and folliculosebaceous differentiation, and cytologic features ranging from benign to frankly atypical, in a patient with inherited EV.


Assuntos
Epidermodisplasia Verruciforme/complicações , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/virologia , Carcinoma de Células Escamosas/virologia , Humanos , Masculino , Neoplasias Primárias Múltiplas/virologia , Neoplasias Cutâneas/virologia , Adulto Jovem
19.
J Cutan Pathol ; 44(10): 878-881, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28675468

RESUMO

Acral angiokeratoma-like pseudolymphoma is a rare type of pseudolymphoma presenting as dark-red papules on the hand or foot. We describe a 59-year-old woman who presented with an unusual unilateral, clustered aggregate of scaly violaceous papules on the toe with an indolent course. Skin biopsy showed a prominent vascular proliferation associated with a dermal infiltrate of monoclonally rearranged T-follicular helper phenotype T-cells, in keeping with CD4+ small/medium T-cell lymphoproliferative disorder (SMPTC-LPD). Based on the unique clinical morphology, distribution of the lesions and dermoscopic appearance, a clinicopathologic diagnosis of acral angiokeratoma-like pseudolymphoma was favored. This case demonstrates the importance of clinicopathological correlation in such diagnostically challenging patients who present with overlapping features on the spectrum of pseudolymphoma and cutaneous T-cell lymphoma.


Assuntos
Angioceratoma , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Linfócitos T Auxiliares-Indutores , Angioceratoma/diagnóstico , Angioceratoma/metabolismo , Angioceratoma/patologia , Feminino , Humanos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/metabolismo , Linfoma Cutâneo de Células T/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/patologia , Dedos do Pé/patologia
20.
Anticancer Agents Med Chem ; 17(13): 1814-1823, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28356005

RESUMO

OBJECTIVE: To synthesize a novel chemotype based on the naphthoquinone scaffold with retained cytotoxicity and provisionally low intracellular oxidation potential. BACKGROUND: Derivatives of naphthoquinone, although potent anticancer agents, can exert heart toxicity due to generation of free oxygen species. METHODS: In this study, we modified the scaffold by replacing one carbonyl group with the oxime moiety. Interestingly, only one carbonyl group in 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 2-oxides reacted with hydroxylamine. The spatial structure was determined by X-ray analysis. New compounds were tested for the ability to form stable complexes with double stranded DNA by spectroscopy and molecular docking and to induce death of tumor cell lines and non-malignant counterparts. RESULTS: The resulting 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 4-oxime 2-oxides were further acylated to produce a series of 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 4-(O-acyloxime) 2-oxides. Newly synthesized compounds demonstrated a higher (in submicromolar or low micromolar range) cytotoxic potency against human colon and breast adenocarcinoma cell lines than to non-malignant skin fibroblasts. Spectroscopic measurements revealed that, unlike other classes of quinone derivatives, new naphthotriazoledione oxides did not form stable complexes with double stranded DNA regardless of their fitting to the DNA minor groove (as determined by molecular modeling). CONCLUSION: Thus, our chemical modifications yielded a new chemotype with good cytotoxic properties and yet-to-be-identified intracellular target(s).


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Oximas/química , Triazóis/química , Triazóis/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Análise Espectral/métodos , Relação Estrutura-Atividade , Triazóis/síntese química
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