Long‐Term Survival After Choriocarcinoma Transmitted by Liver Graft: A Successful Report in Pediatric Transplantation

Background: LT is the standard of care for many pediatric liver disorders. Although long-term outcomes have improved, some rare complications such as transmission of occult donor tumors have been reported. Case report: An adolescent diagnosed with tyrosinemia was submitted to LT from a previous healthy donor due to HCC. Almost 8 months after LT, the patient presented a nodular hepatic lesion. Clinically, he had mild weight loss, lower limb edema, and gynecomastia. Thorax CT found lesions in the left lung parenchyma, which showed no increased uptake in PET SCAN. Liver biopsy revealed a carcinoma with desmoplastic stroma. ISS was withdrawn, and palliative chemotherapy was started for presumptive HCC relapse. AFP remained normal, but HCG had reached unexpected values of 1984 IU/L. As we requested detailed information about the other organ recipients from the same donor, we found that one of them passed away due to disseminated tumor. Five months after the beginning of chemotherapy, the patient underwent resection of liver segments V and VI. Histological examination confirmed liver metastatic choriocarcinoma. At the time of writing, with 11 years of follow-up, the patient had sustained remission with no signs of relapse. Discussion: This case reports a diagnostic challenge in an adolescent with a particular unique background and a very rare pattern of tumor transmission. The authors aim to highlight the risk of cancer-bearing organs reveled post-LT and to testimony the experience of the successful outcome after a choriocarcinoma transmitted by liver graft.info:eu-repo/semantics/publishedVersio

MELHORAMENTO DAS CARACTERISTICAS FÍSICAS E SENSORIAIS DO LEITE DE CABRA FERMENTADO

Introdução e objetivos: O leite caprino possui elevada digestibilidade e baixo potencial alergênico 1 em relação ao leite bovino, entretanto apresenta dificuldades tecnológicas associadas à formação de um coágulo firme e a aceitação sensorial devido ao sabor e ao odor peculiares 2. O objetivo deste estudo foi desenvolver leites fermentados a partir de leite de cabra com características físicas e atributos sensoriais atrativos ao consumidor. Metodologia: O estudo foi desenvolvido no Laboratório de Análises de Alimentos e Águas da Faculdade de Farmácia/UFJF, onde foram preparadas 3 formulações de leite fermentado a partir da matriz láctea , realizando 5 repetições de cada uma. A matriz láctea foi submetida a tratamento térmico a 90ºC com homogeneização constante por 30 minutos para concentração dos sólidos. Na formulação LF 1 (controle) utilizou-se somente Fermento Bio Rich®; LF2 além do fermento foi adicionado inulina 3% (p/v) e sacarose 6% (p/v) durante o tratamento térmico; e LF3 difere do LF2 pelo acréscimo de polpa de morango 7% (p/v). Os atributos sensoriais dos leites fermentados foram avaliados pela escala hedônica e os dados obtidos foram submetidos à Análise de Componentes Principais. Resultados e discussões: A concentração dos sólidos por evaporação foi realizada em todos os tratamentos. As formulações LF2 e LF3 elaboradas com sólidos solúveis apresentaram viscosidade superior à formulação LF1. Na Análise dos Componentes Principais, a formulação LF3 foi correlacionada aos atributos sabor e acidez, enquanto que as amostras LF1 e LF2 apresentaram correlação com a viscosidade e aroma. Conclusão: A adição de inulina, sacarose e polpa de fruta associada à concentração por evaporação melhorou a viscosidade do produto. Além disso, a adição de polpa de fruta contribuiu para aceitabilidade do leite fermentado de leite de cabra. Agradecimentos: Agradecemos o apoio da Fundação de Amparo a Pesquisa do Estado de Minas Gerais – FAPEMIG, a Christian-Hansen, a Embrapa Gado de Leite – Juiz de Fora - MG, ao Laboratório de Análises de Alimentos e Águas – LAAA da Faculdade de Farmácia - Universidade Federal de Juiz de Fora - UFJF- MG

Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice

Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as “erva-cidreira” or “melissa”, it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance

Polycomb-mediated silencing in neuroendocrine prostate cancer

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PCa) for which the median survival remains less than a year. Current treatments are only palliative in nature, and the lack of suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established the first in vivo model of complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa and relapsed NEPC, suggesting that NEPC likely results from alterations that are epigenetic in nature. Thus, we sought to identify targetable epigenetic regulators whose expression was elevated in NEPC using genome-wide profiling of patient-derived xenografts and clinical samples. RESULTS: Our data indicate that multiple members of the polycomb group (PcG) family of transcriptional repressors were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently the most highly overexpressed epigenetic regulators across multiple datasets from clinical and xenograft tumor tissues. Given the striking upregulation of PcG genes and other transcriptional repressors, we derived a 185-gene list termed 'neuroendocrine-associated repression signature' (NEARS) by overlapping transcripts downregulated across multiple in vivo NEPC models. In line with the striking upregulation of PcG family members, NEARS was preferentially enriched with PcG target genes, suggesting a driving role for PcG silencing in NEPC. Importantly, NEARS was significantly associated with high-grade tumors, metastatic progression, and poor outcome in multiple clinical datasets, consistent with extensive literature linking PcG genes and aggressive disease progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and provided evidence of increased PcG-mediated silencing associated with aberrant transcriptional regulation of key differentiation genes. Our results position CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities to explore novel strategies aimed at reversing epigenetic alterations driving this lethal disease

Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+T cells in aged rats

Background: Aging influences immune response and susceptibility to EAE in a strain specific manner. The study was designed to examine influence of aging on EAE induction in Albino Oxford (AO) rats. Results: Differently from 3-month-old (young) rats, which were resistant to EAE induction, the majority of aged (24-26-month-old) rats developed mild chronic form of EAE. On 16th day post-immunization, when in aged rats the neurological deficit reached plateau, more mononuclear cells, including CD4+ T lymphocytes was retrieved from spinal cord of aged than young rats. The frequencies of IL-17+ and GM-CSF+ cells within spinal cord infiltrating CD4+ lymphocytes were greater in aged rats. To their increased frequency contributed the expansion of GM-CSF + IL-17 + IFN-gamma+ cells, which are highly pathogenic in mice. The expression of the cytokines (IL-1 beta and IL-23/p19) driving GM-CSF + IL-17 + IFN-gamma + cell differentiation in mice was also augmented in aged rat spinal cord mononuclear cells. Additionally, in aged rat spinal cord the expansion of GM-CSF + IL-17-IFN-gamma- CD4+ T lymphocytes was found. Consistently, the expression of mRNAs for IL-3, the cytokine exhibiting the same expression pattern as GM-CSF, and IL-7, the cytokine driving differentiation of GM-CSF + IL-17-IFN-gamma- CD4 + lymphocytes in mice, was upregulated in aged rat spinal cord mononuclear cells, and the tissue, respectively. This was in accordance with the enhanced generation of the brain antigen-specific GM-CSF+ CD4+ lymphocytes in aged rat draining lymph nodes, as suggested by (i) the higher frequency of GM-CSF+ cells (reflecting the expansion of IL-17-IFN-gamma- cells) within their CD4+ lymphocytes and (ii) the upregulated GM-CSF and IL-3 mRNA expression in fresh CD4+ lymphocytes and MBP-stimulated draining lymph node cells and IL-7 mRNA in lymph node tissue from aged rats. In agreement with the upregulated GM-CSF expression in aged rats, strikingly more CD11b + CD45(int) (activated microglia) and CD45(hi) (mainly proinflammatory dendritic cells and macrophages) cells was retrieved from aged than young rat spinal cord. Besides, expression of mRNA for SOCS1, a negative regulator of proinflammatory cytokine expression in innate immunity cells, was downregulated in aged rat spinal cord mononuclear cells. Conclusions: The study revealed that aging may overcome genetic resistance to EAE, and indicated the cellular and molecular mechanisms contributing to this phenomenon in AO rats