RESUMO
Comprehensive molecular characterization of and novel therapeutic approaches to glioblastoma have been explored as a result of advancements in biotechnologies. In this study, we aimed to bring basic research discoveries closer to clinical practice and ultimately incorporate molecular classification into the routine histopathological evaluation of grade IV gliomas. Integrated results of genome-wide sequencing, transcriptomic and epigenomic analyses by The Cancer Genome Atlas Network defined the classic, proneural, neural and mesenchymal subtypes of this tumor. In a retrospective cohort, we analyzed selected subgroup-defining molecular markers in formalin-fixed paraffin-embedded surgical specimens by immunohistochemistry. Quantitative and qualitative scores of marker expression were tested in hierarchical cluster analyses to evaluate segregations of the molecular subgroups, which then were correlated with clinical parameters including patients' age, gender and overall survival. Our study has confirmed the separation of molecular glioblastoma subgroups with clear trends regarding clinical correlations. Future analyses in a larger, prospective cohort using similar methods are expected to facilitate the development of a molecular diagnostic panel that may complement routine histological work up and support prognostication as well as treatment decisions in glioblastoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/classificação , Glioblastoma/patologia , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are critically involved in the central regulation of fertility; these cells regulate pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid feedback signals to GnRH neurons. Fine structural analysis of the human KP system is complicated by the use of post mortem tissues. To gain better insight into the neuroanatomy of the somato-dendritic cellular compartment, we introduced the diolistic labeling of immunohistochemically identified KP neurons using a gene gun loaded with the lipophilic dye, DiI. Confocal microscopic studies of primary dendrites in 100-µm-thick tissue sections established that 79.3% of KP cells were bipolar, 14.1% were tripolar, and 6.6% were unipolar. Primary dendrites branched sparsely, contained numerous appendages (9.1 ± 1.1 spines/100 µm dendrite), and received rich innervation from GABAergic, glutamatergic, and KP-containing terminals. KP neuron synaptology was analyzed with immunoelectron microscopy on perfusion-fixed specimens. KP axons established frequent contacts and classical synapses on unlabeled, and on KP-immunoreactive somata, dendrites, and spines. Synapses were asymmetric and the presynaptic structures contained round and regular synaptic vesicles, in addition to dense-core granules. Although immunofluorescent studies failed to detect vesicular glutamate transporter isoforms in KP axons, ultrastructural characteristics of synaptic terminals suggested use of glutamatergic, in addition to peptidergic, neurotransmission. In summary, immunofluorescent and DiI labeling of KP neurons in thick hypothalamic sections and immunoelectron microscopic studies of KP-immunoreactive neurons in brains perfusion-fixed shortly post mortem allowed us to identify previously unexplored fine structural features of KP neurons in the mediobasal hypothalamus of humans.
Assuntos
Hipotálamo/citologia , Kisspeptinas/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Idoso , Idoso de 80 Anos ou mais , Autopsia , Axônios/metabolismo , Axônios/ultraestrutura , Carbocianinas/metabolismo , Corpo Celular/ultraestrutura , Dendritos/metabolismo , Dendritos/ultraestrutura , Ácido Glutâmico/metabolismo , Humanos , Imageamento Tridimensional , Kisspeptinas/ultraestrutura , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Microscopia Confocal , Microscopia Imunoeletrônica , Pessoa de Meia-Idade , Rede Nervosa/metabolismo , Rede Nervosa/ultraestrutura , Sinapses/metabolismo , Sinapses/ultraestrutura , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/ultraestrutura , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/ultraestrutura , Ácido gama-Aminobutírico/metabolismoRESUMO
Retroperitoneal liposarcomas are the most frequent soft tissue sarcomas and the second most frequent retroperitoneal tumours. They represent less then 0.1% of all human malignancies. Hereby we describe the treatment of our patient where of a 15-kg giant retroperitoneal liposarcoma was successfully removed and a local recurrence two years later was operated on as well. This was the 3rd largest retroperitoneal malignant tumor that was successfully removed according to the available literature of the last five decades. These typically symptom-free tumors usually grow extreme size before diagnosed. The "gold-standard" of treatment remains surgical total excision, but the high local recurrence rate (50-60%) hopefully can be reduced by adjuvant radio- and chemotherapy. Multidisciplinary treatment and long-time follow-up can provide as high as 40% 5-year survival rate. We summarize the recent clinical, diagnostic and therapeutic methods of this rare condition.