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A preoperative diagnosis of the peripheral small lung nodule is often difficult, and an intraoperative frozen section diagnosis (FSD) is performed to guide treatment strategy. However, invasive mucinous adenocarcinoma (IMA) is prone to be overlooked because of the low sample quality and weak atypia. We herein report a case of IMA, in which touch imprint cytology (TIC) revealed diagnostic efficacy. A 74-year-old male with a small, subsolid nodule in the right upper lobe underwent a thoracoscopic wedge resection. A grayish brown, 10 × 7 mm-sized nodule was observed on the cut surface. Intraoperative FSD revealed lung tissue with mild alveolar septal thickening and stromal fibrosis but without overt atypia. Meanwhile, TIC revealed mucus and a few epithelial cells with intranuclear inclusions, which pathologists evaluated as reactive. Finally, focal organizing pneumonia was tentatively diagnosed, and surgery was finished without any additional resection. However, permanent section diagnosis revealed a microinvasive mucinous adenocarcinoma. Nuclear inclusions were confirmed in tumor cells. In the intraoperative setting, TIC may be more advantageous than FSD in observing nuclear inclusions and mucus. Mucinous background and nuclear inclusion on TIC may suggest IMA even if FSD does not suggest malignancy in an intraoperative diagnosis of the peripheral small lung nodule.
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Homopurine strands are known to form antiparallel triplexes stabilized by G*G and A*A Hoogsteen pairs, which have two hydrogen bonds. But there has been no report on the parallel triplex formation of homopurine involving both adenosine and guanosine to the duplex. In this paper, we first report parallel triplex formation between a homopurine serinol nucleic acid (SNA) strand and an RNA/SNA duplex. Melting profiles revealed that the parallel SNA:RNA*SNA triplex was remarkably stable, even though the A*A pair has a single hydrogen bond. An L-acyclic threoninol nucleic acid (L-aTNA) homopurine strand also formed a stable parallel triplex with an L-aTNA/RNA duplex.
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Butileno Glicoles , Ácidos Nucleicos , Propanolaminas , Glicoles de Propileno , Ácidos Nucleicos/química , ARN/química , Amino Alcoholes/química , Conformación de Ácido NucleicoRESUMEN
Endoscopic ultrasound-guided fine-needle aspiration has become the common procedure for the diagnosis of pancreatic mass, and cytological examination is usually the first approach. Solid pseudopapillary neoplasm (SPN) cytologically represents papillary structures of branching capillaries surrounded by discohesive neoplastic cells. However, it may present various degrees of tissue degeneration, causing diagnostic challenges. Here, we report a 21-year-old female who had a 2-cm-sized mass in the pancreas head. Cytological examination revealed clumps of small round/oval cells that represented microcystic configurations with mucus, mimicking adenoid cystic carcinoma or mucinous adenocarcinoma. Cercariform cells, nuclear grooves/folding, and cytoplasmic vacuoles were not observed. Histopathological examination revealed confluent small glandular structures containing acidic mucus. The tumor cells were positively stained for ß-catenin, CD10, and CD56, and negative for chromogranin A and E-cadherin, suggesting SPN, micropseudocystic variant. This variant has been scarcely described, but we should recognize it for accurate cytological triage of pancreatic tumors.
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We previously synthesized phosphoramidite monomers bearing Boc-protected 2,6-diaminopurine (D) and 2-methyl-4-methoxybenzyl-protected 2-thiouracil (sU) as building blocks for the preparation of pseudo-complementary serinol nucleic acids (SNAs). Since SNA is stable under acidic conditions, an acid-deprotection step could be inserted into the work-up. However, as the 4,4'-dimethoxytrityl group was concurrently removed at this step, purification of SNA by reversed-phase HPLC was difficult. Here, we report the syntheses of SNA and acyclic l-threoninol nucleic acid (l-aTNA) phosphoramidite monomers with bis(phenoxyacetyl)-protected D and 4-acetoxybenzyl-protected sU, both of which can be deprotected under mild basic conditions. Using these monomers, we prepared pseudo-complementary SNA and l-aTNA in high yield using conventional oligonucleotide synthesis protocols. These monomers can be used for large-scale syntheses of SNAs and l-aTNAs.
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A 61-year-old man with a history of total gastrectomy for cancer with Roux-en-Y reconstruction showed severe postprandial hypoglycemia accompanied by endogenous hyperinsulinemia. Abdominal ultrasonography and contrast-enhanced computed tomography showed no abnormal findings in the pancreas. A selective arterial secretagogue injection test showed the marked induction of serum immunoreactive insulin when calcium was injected into the splenic artery. A pathological analysis following distal pancreatectomy with splenectomy revealed a pancreatic neuroendocrine microadenoma containing insulin-producing cells in the resected pancreas. This case highlights the importance of carefully evaluating refractory and severe hypoglycemia in patients with a history of gastric surgery to exclude insulinoma.
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Derivación Gástrica , Hipoglucemia , Insulinoma , Neoplasias Pancreáticas , Derivación Gástrica/efectos adversos , Humanos , Hipoglucemia/etiología , Insulina , Insulinoma/complicaciones , Insulinoma/diagnóstico , Insulinoma/cirugía , Masculino , Persona de Mediana Edad , Pancreatectomía/métodos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugíaRESUMEN
The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly.
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Osteoblasts arise from bone-surrounding connective tissue containing tenocytes and fibroblasts. Lineages of these cell populations and mechanisms of their differentiation are not well understood. Screening enhancer-trap lines of zebrafish allowed us to identify Ebf3 as a transcription factor marking tenocytes and connective tissue cells in skeletal muscle of embryos. Knockout of Ebf3 in mice had no effect on chondrogenesis but led to sternum ossification defects as a result of defective generation of Runx2+ pre-osteoblasts. Conditional and temporal Ebf3 knockout mice revealed requirements of Ebf3 in the lateral plate mesenchyme cells (LPMs), especially in tendon/muscle connective tissue cells, and a stage-specific Ebf3 requirement at embryonic day 9.5-10.5. Upregulated expression of connective tissue markers, such as Egr1/2 and Osr1, increased number of Islet1+ mesenchyme cells, and downregulation of gene expression of the Runx2 regulator Shox2 in Ebf3-deleted thoracic LPMs suggest crucial roles of Ebf3 in the onset of lateral plate mesoderm differentiation towards osteoblasts forming sternum tissues.
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Factores de Transcripción/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Embrión no Mamífero/metabolismo , Femenino , Fibroblastos/metabolismo , Hibridación in Situ , Proteínas con Homeodominio LIM/metabolismo , Ratones , Ratones Noqueados , Osteoblastos/metabolismo , Embarazo , RNA-Seq , Esternón/metabolismo , Factores de Transcripción/genética , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Serinol nucleic acid (SNA) is a promising candidate for nucleic acid-based molecular probes and drugs due to its high affinity for RNA. Our previous work revealed that incorporation of 2,6-diaminpurine (D), which can form three hydrogen bonds with uracil, into SNA increases the melting temperature of SNA-RNA duplexes. However, D incorporation into short self-complementary regions of SNA promoted self-dimerization and hindered hybridization with RNA. Here we synthesized a SNA monomer of 2-thiouracil (sU), which was expected to inhibit base pairing with D by steric hindrance between sulfur and the amino group. To prepare the SNA containing D and sU in high yield, we customized the protecting groups on D and sU monomers that can be readily deprotected under acidic conditions. Incorporation of D and sU into SNA facilitated stable duplex formation with target RNA by suppressing the self-hybridization of SNA and increasing the stability of the heteroduplex of SNA and its complementary RNA. Our results have important implications for the development of SNA-based probes and nucleic acid drugs.
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2-Aminopurina/análogos & derivados , Oligonucleótidos/química , Propanolaminas/química , Glicoles de Propileno/química , ARN/química , Tiouracilo/química , 2-Aminopurina/química , Emparejamiento Base , Enlace de Hidrógeno , Hibridación de Ácido Nucleico , Oligonucleótidos/síntesis química , Oligonucleótidos/genética , Transición de Fase , ARN/genética , Temperatura de TransiciónRESUMEN
Mid-regional pro-adrenomedullin (MR-proADM) is suggested to be a prognostic indicator for various diseases. Plasma MR-proADM concentration is commonly measured using immunoassays based on its immunochemical characteristics. However, some immunological interactions affect the measured concentration. We developed and validated a sensitive and selective method for measuring plasma MR-proADM concentration using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and evaluated its clinical applicability. Plasma samples were prepared by protein precipitation and solid-phase extraction. Samples obtained from healthy volunteers (nâ¯=â¯38), patients with chronic kidney disease (CKD) stages 3 and 4-5 (non-dialysis; nâ¯=â¯20 and 17, respectively), and CKD stage 5D (dialysis; nâ¯=â¯34) were analyzed. Within-batch and batch-to-batch accuracy of the UPLC-MS/MS assay for quality control samples ranged from -0.69 % to 8.05 % and from 1.72 % to 5.76 %, respectively. The lower limit of quantification was 0.4â¯ng mL-1. The MR-proADM concentration determined using the UPLC-MS/MS assay correlated strongly with that determined using the immunoassay (Pearson's product-moment correlation coefficient [r]â¯=â¯0.7875, pâ¯<â¯0.001). Median (range) plasma MR-proADM concentrations of healthy volunteers, patients with CKD stages 3 and 4-5, and patients with CKD stage 5D were 0.67 (0.43-1.27), 1.89 (0.65-6.68), 3.86 (1.60-8.75) and 3.97 (0.66-9.20) ng mL-1, respectively, and a significant difference among four groups was confirmed. We established a sensitive and selective method for determining plasma MR-proADM concentration using UPLC-MS/MS. Our novel UPLC-MS/MS assay for determining plasma MR-proADM concentration can be used in the clinical setting and may have better selectivity than the immunoassay method.
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Adrenomedulina/sangre , Plasma/química , Precursores de Proteínas/sangre , Anciano , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Inmunoensayo/métodos , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Insuficiencia Renal Crónica/sangre , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.
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Endoscopía/métodos , Laparoscopía/métodos , Nefrectomía/métodos , Recolección de Tejidos y Órganos/métodos , Anciano , Analgésicos/uso terapéutico , Pérdida de Sangre Quirúrgica , Creatinina/sangre , Endoscopía/efectos adversos , Femenino , Supervivencia de Injerto , Humanos , Japón , Trasplante de Riñón/métodos , Laparoscopía/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Tempo Operativo , Complicaciones Posoperatorias , Espacio Retroperitoneal , Estudios Retrospectivos , Cirujanos , Recolección de Tejidos y Órganos/efectos adversos , Resultado del Tratamiento , Isquemia TibiaRESUMEN
In higher vertebrates, cephalic neural crest cells (NCCs) form craniofacial skeleton by differentiating into chondrocytes and osteoblasts. A subpopulation of cephalic NCCs, cardiac NCCs (CNCCs), migrates to the heart. However, CNCCs mostly do not yield skeletogenic derivatives, and the molecular mechanisms of this fate restriction remain elusive. We identify a disintegrin and metalloprotease 19 (Adam19) as a position-specific fate regulator of NCCs. Adam19-depleted mice abnormally form NCC-derived cartilage in their hearts through the upregulation of Sox9 levels in CNCCs. Moreover, NCC-lineage-specific Sox9-overexpressing mice recapitulate CNCC chondrogenesis. In vitro experiments show that Adam19 mediates the cleavage of bone morphogenic protein (BMP) type I receptor Alk2 (Acvr1), whereas pharmacogenetic approaches reveal that Adam19 inhibits CNCC chondrogenesis by suppressing the BMP-Sox9 cascade, presumably through processing Alk2. These findings suggest a metalloprotease-dependent mechanism attenuating cellular responsiveness to BMP ligands, which is essential for both the positional restriction of NCC skeletogenesis and normal heart development.
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Proteínas ADAM/metabolismo , Cresta Neural/metabolismo , Transducción de Señal , Proteínas ADAM/deficiencia , Proteínas ADAM/genética , Receptores de Activinas Tipo I/genética , Receptores de Activinas Tipo I/metabolismo , Animales , Proteína Morfogenética Ósea 6/metabolismo , Cartílago/crecimiento & desarrollo , Cartílago/metabolismo , Cartílago/patología , Diferenciación Celular , Condrogénesis , Embrión de Mamíferos/metabolismo , Células HEK293 , Humanos , Ratones , Ratones Noqueados , Miocardio/citología , Miocardio/metabolismo , Cresta Neural/citología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Regulación hacia ArribaRESUMEN
Blood concentrations of tacrolimus show large variability among patients and the narrow therapeutic range is related to adverse effects. Therefore, therapeutic drug monitoring is needed for strict management. 13-O-Demethyl tacrolimus (13-O-DMT) was reported as the major metabolite formed by cytochrome P450 (CYP)3A such as CYP3A5. In previous studies, the best lower limit of quantification (LLOQ) was 0.1 ng/mL for both substances. However, this LLOQ may not be low enough now because the dosage of tacrolimus has decreased in recent years. The purpose of this study was to develop and validate a high-sensitivity and high-throughput assay for simultaneous quantification of tacrolimus and 13-O-DMT in human whole blood using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). Thirty-five stable kidney transplant recipients receiving tacrolimus were recruited in this study. The calibration curve range was 0.04-40 ng/mL. All calibration samples and quality control samples fulfilled the requirements of the US Food and Drug Administration and the European Medicines Agency guidelines for assay validation. Trough concentrations of tacrolimus and 13-O-DMT in 35 stable kidney transplant recipients receiving tacrolimus were within the range of the respective calibration curve. Our novel UPLC-MS/MS method is more sensitive than previous methods for quantification of tacrolimus and 13-O-DMT.
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Cromatografía Líquida de Alta Presión/métodos , Tacrolimus/análogos & derivados , Tacrolimus/sangre , Espectrometría de Masas en Tándem/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Límite de Detección , Modelos Lineales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tacrolimus/química , Adulto JovenRESUMEN
Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self-renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate the proliferation and differentiation of SMSCs and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes the effects of hypoxia on preferential self-renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to the tricarboxylic acid (TCA) cycle by producing acetyl coenzyme A from pyruvate. PDH kinase 1, highly expressed under hypoxia, is down-regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin-deficient mouse model of Duchenne muscular dystrophy. Thus, the flow from glycolysis to the TCA cycle mediated by PDH plays a pivotal role in the differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.-Hori, S., Hiramuki, Y., Nishimura, D., Sato, F., Sehara-Fujisawa, A. PDH-mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice.
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Diferenciación Celular , Cetona Oxidorreductasas/metabolismo , Fibras Musculares Esqueléticas/fisiología , Regeneración , Células Satélite del Músculo Esquelético/enzimología , Animales , Línea Celular , Ciclo del Ácido Cítrico , Eliminación de Gen , Glucólisis , Cetona Oxidorreductasas/genética , Ratones , Ratones Noqueados , Fibras Musculares Esqueléticas/citología , Células Satélite del Músculo Esquelético/citologíaRESUMEN
BACKGROUND: Phenoconversion is a phenomenon whereby some genotypic extensive metabolizers transiently exhibit drug metabolizing enzyme activity at similar level as that of poor metabolizers. Renal failure is known to decrease CYP3A activity in humans. Indoxyl sulfate, parathyroid hormone (PTH), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) have been reported to cause CYP3A downregulation in renal failure. We measured plasma concentrations of the above compounds in stable kidney transplant recipients, and evaluated their relations with phenoconversion of CYP3A evaluated by plasma concentration of 4ß-hydroxycholesterol, a biomarker of CYP3A activity. Phenoconversion was defined as a genotypic extensive/intermediate metabolizer exhibiting CYP3A activity below the cutoff value that discriminates extensive/intermediate from poor metabolizers. METHODS: Sixty-three Japanese kidney transplant recipients who underwent transplantation more than 180 days prior to the study were included. Morning blood samples were collected, and CYP3A5 polymorphism as well as plasma concentrations of 4ß-hydroxycholesterol, indoxyl sulfate, intact-PTH, IL-6 and TNF-α were determined. RESULTS: Significantly higher plasma 4ß-hydroxycholesterol concentration was observed in recipients with CYP3A5*1 allele (n = 23) compared to those without the allele (n = 40), and the cut-off value was 40.0 ng/mL. Ten recipients with CYP3A5*1 allele exhibited CYP3A activity below 40.0 ng/mL (phenoconversion). Only plasma indoxyl sulfate concentration was significantly higher in recipients with CYP3A phenoconversion compared to those without phenoconversion. CONCLUSIONS: These findings suggest that higher plasma indoxyl sulfate concentration may be involved in CYP3A phenoconversion. Dose adjustment of drugs metabolized by CYP3A may be needed in patients with CYP3A5*1 allele and high blood indoxyl sulfate.
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Citocromo P-450 CYP3A/genética , Hidroxicolesteroles/metabolismo , Indicán/sangre , Trasplante de Riñón , Adulto , Anciano , Alelos , Citocromo P-450 CYP3A/metabolismo , Femenino , Genotipo , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenAsunto(s)
Laparoscopía , Neoplasias de la Vejiga Urinaria/cirugía , Cistectomía , Humanos , Japón , ReoperaciónRESUMEN
PURPOSE: Recently, several studies have shown that renal failure decreases the metabolic clearance of drugs and the transportation capability of some drug transporters. However, whether organic anion transporting polypeptide (OATP)1B activities decrease in renal failure remains unknown. In this study, we measured plasma concentrations of coproporphyrin-I (CP-I), a specific endogenous OATP1B probe, in patients with end stage renal disease before and after living kidney transplantation and evaluated the effect of renal function on OATP1B activity. METHODS: This prospective study recruited 13 patients with end-stage renal disease. Plasma CP-I concentrations were measured before and 7, 14, 30 and 90 days after living kidney transplantation. RESULTS: Plasma CP-I concentrations decreased over time after living kidney transplantation and showed significant difference on day 90 compared with before living kidney transplantation [1.12 ± 0.59 vs 0.65 ± 0.27 ng/mL, p < 0.05 (95% CI of difference - 0.927, -0.013)]. A significant negative correlation was observed between estimated glomerular filtration rate and plasma CP-I concentration (r = -0.30, p < 0.05), suggesting recovery of OATP1B activity with improvement in renal function. CONCLUSIONS: OATP1B activity may decrease in renal failure and dose adjustment of OATP1B substrates may be needed in patients with renal failure.
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Coproporfirinas/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Transportadores de Anión Orgánico/metabolismo , Adulto , Anciano , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
INTRODUCTION: Concurrence of clear cell renal cell carcinoma and angiomyolipoma is quite rare. We report a case of large localized clear cell renal cell carcinoma with concurrent multiple angiomyolipomas mimicking lymph node metastases. CASE PRESENTATION: A 60-year-old woman presented with general malaise, weight loss, and intermittent fever. Computed tomography scan demonstrated an 8-cm mass in the left kidney, enlarged para-aortic lymph nodes, and small renal nodules adjacent to the main tumor. She was diagnosed preoperatively as having clear cell renal cell carcinoma (cT3a) with multiple para-aortic lymph node metastases, and underwent laparoscopic radical nephrectomy and dissection of the para-aortic lymph nodes. Pathologically, the main tumor was diagnosed as clear cell renal cell carcinoma. By contrast, both the para-aortic lymph nodes and nodules were diagnosed as lipid-poor angiomyolipomas. CONCLUSION: With the expanding first-line use of molecular targeted therapy for metastatic renal cell carcinoma, nephrectomy may be avoided by overdiagnosis. Upfront nephrectomy can avoid overdiagnosis and undertreatment of nonmetastatic renal cell carcinoma.
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BACKGROUND: Echinoderms and hemichordates are sister taxa that both have larvae with tripartite coeloms. Hemichordates inherit the coelom plan and ectoderm from larvae, whereas echinoderms form the adult rudiment comprising rearranged coeloms and a vestibule that then develops into adult oral ectoderm. Molecular networks that control patterns of the ectoderm and the central nervous system along the anteroposterior (AP) axis are highly conserved between hemichordates and chordates, respectively. In echinoderms, however, little is known about the AP registry in the ectoderm. RESULTS: We isolated ectodermal AP map genes from the sand dollar Peronella japonica and examined their expression. Comparative expression analyses showed that (1) P. japonica orthologs of hemichordate anterior markers are expressed in the larval apical plate, which degenerates during metamorphosis; (2) P. japonica orthologs of the medial markers are expressed in the ambulacral ectoderm of the rudiment; and (3) few P. japonica orthologs of the posterior markers are expressed in ectoderm. CONCLUSIONS: We suggest that echinoids only inherit the ambulacral ectoderm from a common ambulacrarian ancestor, which largely corresponds to the collar ectoderm in hemichordates. The ectodermal AP registry provides insights into the AP axis and evolutionary processes of echinoderms from a common ambulacrarian ancestor. Developmental Dynamics 247:1297-1307, 2018. © 2018 Wiley Periodicals, Inc.
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Evolución Biológica , Tipificación del Cuerpo , Cordados/embriología , Ectodermo/embriología , Desarrollo Embrionario , Larva/citología , Animales , Embrión no Mamífero , Metamorfosis Biológica , Erizos de MarRESUMEN
PURPOSE: A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups. RESULTS: A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019). CONCLUSIONS: Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.
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Vacuna BCG/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Proteínas Activadoras de GTPasa/inmunología , Inmunoterapia Activa/métodos , Cinesinas/inmunología , Proteínas de Neoplasias/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Vacunas de Subunidad/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Vacunas contra el Cáncer/inmunología , Supervivencia sin Enfermedad , Femenino , Antígeno HLA-A24/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/uso terapéutico , Linfocitos T Citotóxicos/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Vacunas de Subunidad/inmunologíaRESUMEN
We performed Pfannenstiel laparoendoscopic reduced-port bilateral radical nephrectomy on a patient with renal cell carcinoma undergoing hemodialysis. A 4-cm Pfannenstiel incision was made, and a GelPOINT access was inserted. Three trocars were placed through the access platform, and additional 5- and 3-mm trocars were inserted in the umbilicus and paraumbilical area, respectively. After left nephrectomy, right nephrectomy was successfully completed in 401 min, with an estimated blood loss of 70 mL. There were no intraoperative or postoperative complications, and the patient was discharged 10 days postoperatively. The umbilical scar was concealed within the umbilical fold, and the scar from the 3-mm trocar was almost invisible. The Pfannenstiel scar was minimal and concealed by the patient's underwear. Pfannenstiel laparoendoscopic reduced-port simultaneous bilateral radical nephrectomy is a safe and technically feasible procedure that offers great cosmesis for patients with bilateral renal tumors and end-stage renal disease.