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1.
Zootaxa ; 4691(4): zootaxa.4691.4.1, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31719385

RESUMO

Crangonyx ephemerus n. sp. and Crangonyx pseudoephemerus n. sp. are described from the headwaters of the St. Marks River in Leon County, Florida, based on detailed morphological and molecular comparisons with the closely related species Crangonyx floridanus Bousfield, 1963. The morphological and molecular data, including three species delimitation models, lend support to the hypothesis that the taxon C. floridanus sensu lato represents a species complex. Diagnostic morphological characteristics are highlighted and discussed within this group to assist in future morphological analyses.


Assuntos
Anfípodes , Animais , Filogenia , Rios
2.
Cancer Immunol Res ; 5(12): 1074-1085, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29051161

RESUMO

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR.


Assuntos
Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Receptores Androgênicos/genética , Especificidade do Receptor de Antígeno de Linfócitos T , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunização , Imuno-Histoquímica , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Receptores Androgênicos/imunologia , Receptores Androgênicos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Prostate ; 77(7): 812-821, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28181678

RESUMO

BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. METHODS: Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. RESULTS: No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. CONCLUSIONS: These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Neoplasias da Próstata , Receptores Androgênicos/imunologia , Vacinas de DNA , Adjuvantes Imunológicos/administração & dosagem , Animais , Masculino , Camundongos , Monitorização Imunológica/métodos , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Vacinas de DNA/imunologia
4.
Zootaxa ; 4067(1): 88-94, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-27395865

RESUMO

A relatively large, distinct new species of the subterranean amphipod crustacean genus Stygobromus (Amphipoda: Crangonyctidae) measuring 13 mm in length is described from Skipper Spring, a cave spring in the northwestern "panhandle" of Florida, USA. This is the first species of the genus described from the state of Florida where it is described from only 3 females. A fourth much smaller specimen of this species was collected from nearby Miller's Crossing Spring on Holmes Creek. All other stygomorphic amphipod species recorded from the state of Florida have been in the genus Crangonyx.


Assuntos
Anfípodes/classificação , Anfípodes/anatomia & histologia , Anfípodes/crescimento & desenvolvimento , Distribuição Animal , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Tamanho Corporal , Cavernas , Ecossistema , Feminino , Florida , Tamanho do Órgão
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