RESUMO
A 53-year-old female patient was diagnosed with a left renal mass incidentally detected on an abdominal computed tomography (CT) scan. Further examination revealed a slightly contrast-enhancing mass 2.0 cm in diameter, in the left kidney on a contrast-enhanced CT scan. A diagnosis of left renal cell carcinoma (cT1aN0M0) was made and a robotic-assisted laparoscopic partial nephrectomy was performed. The excised tissue specimen exhibited a clearly circumscribed tumor. On hematoxylin eosin staining, the small uniform tumor cells appeared organized in glandular luminal arrangements, with lacking nuclear atypia and any malignant features. Immunostaining confirmed the diagnosis as metanephric adenoma, as indicated by positive results for WT1 and negative results for alpha-methylacyl-CoA race mase. Metanephric adenoma is an uncommon benign epithelial tumor of the kidney, which frequently poses a challenge in differential diagnosis with renal carcinoma on preoperative imaging. Pathologically, it can be challenging to differentiate from papillary renal cell carcinoma, and immunostaining can be used to effectively differentiate between the two entities.
Assuntos
Adenoma , Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/cirurgiaRESUMO
Introduction: Neurofibromatosis type 1 is a hereditary condition often associated with pheochromocytomas but rarely with malignant pheochromocytomas. Neurofibromatosis type 1 is often associated with bone lesions, which complicates the distinction between malignant and benign tumors. Case presentation: A 46-year-old man with a medical history of neurofibromatosis type 1 presented with right abdominal pain. Computed tomography revealed a right adrenal tumor, and metaiodobenzylguanidine scintigraphy showed accumulation in the right adrenal gland and thoracic vertebrae. He was diagnosed with pheochromocytoma, and a right adrenalectomy was performed. After surgery, a bone biopsy was conducted on the spinal lesion, confirming metastasis of pheochromocytoma, prompting irradiation. After that, lung and liver metastases emerged, and chemotherapy with cyclophosphamide, vincristine, and dacarbazine was initiated; however, the disease progressed, and he died 11 months after surgery. Conclusion: We report a case of malignant pheochromocytoma associated with neurofibromatosis type 1 in which bone metastasis was difficult to diagnose.
RESUMO
The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.
RESUMO
TRIOBP remodels the cytoskeleton by forming unusually dense F-actin bundles and is implicated in human cancer, schizophrenia, and deafness. Mutations ablating human and mouse TRIOBP-4 and TRIOBP-5 isoforms are associated with profound deafness, as inner ear mechanosensory hair cells degenerate after stereocilia rootlets fail to develop. However, the mechanisms regulating formation of stereocilia rootlets by each TRIOBP isoform remain unknown. Using 3 new Triobp mouse models, we report that TRIOBP-5 is essential for thickening bundles of F-actin in rootlets, establishing their mature dimensions and for stiffening supporting cells of the auditory sensory epithelium. The coiled-coil domains of this isoform are required for reinforcement and maintenance of stereocilia rootlets. A loss of TRIOBP-5 in mouse results in dysmorphic rootlets that are abnormally thin in the cuticular plate but have increased widths and lengths within stereocilia cores, and causes progressive deafness recapitulating the human phenotype. Our study extends the current understanding of TRIOBP isoform-specific functions necessary for life-long hearing, with implications for insight into other TRIOBPopathies.
Assuntos
Audição/fisiologia , Proteínas dos Microfilamentos/fisiologia , Estereocílios/fisiologia , Actinas/fisiologia , Animais , Surdez/etiologia , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/deficiência , Isoformas de Proteínas/fisiologia , Estereocílios/ultraestruturaRESUMO
Diaphanous-related formin, mDia, is an actin nucleation/polymerization factor functioning downstream of the small GTPase Rho. Although Rho is critically involved in cytokinesis, it remains elusive how Rho effectors and other regulators of cytoskeletons work together to accomplish this process. Here we focused on mDia2, an mDia isoform involved in cytokinesis of NIH 3T3 cells, and analyzed mechanisms of its localization in cytokinesis. We found that targeting of mDia2 to the cleavage furrow requires not only its binding to RhoA but also its diaphanous-inhibitory domain (DID). We then performed pulldown assays using a fragment containing the latter domain as a bait and identified anillin as a novel mDia2 interaction partner. The anillin-binding is competitive with the diaphanous autoregulatory domain (DAD) of mDia2 in its autoinhibitory interaction. A series of RNA interference and functional rescue experiments has revealed that, in addition to the Rho GTPase-mediated activation, the interaction between mDia2 and anillin is required for the localization and function of mDia2 in cytokinesis.