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Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Proteína 1 Homóloga a MutL , Neoplasias Primárias Múltiplas , Adulto , Feminino , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Genômica , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/genética , Neoplasias Primárias Múltiplas/genéticaRESUMO
BACKGROUND: Large non-apoptotic vesicles released from the plasma membrane protrusions are classified as large-EVs (LEVs). However, the triggers of LEV secretion and their functions in tumors remain unknown. METHODS: Coculture system of cancer cells, peritoneal mesothelial cells (PMCs), and macrophages (MΦs) was conducted to observe cell-cell contact-mediated LEV secretion. Lineage tracing of PMCs was performed using Wt1CreERT2-tdTnu mice to explore the effects of LEVs on PMCs in vivo, and lymphangiogenesis was assessed by qRT-PCR and flow-cytometry. RESULTS: In peritoneal dissemination, cancer cells expressing Ephrin-B (EFNB) secreted LEVs upon the contact with PMCs expressing ephrin type-B (EphB) receptors, which degraded mesothelial barrier by augmenting mesothelial-mesenchymal transition. LEVs were incorporated in subpleural MΦs, and these MΦs transdifferentiated into lymphatic endothelial cells (LEC) and integrated into the lymphatic vessels. LEC differentiation was also induced in PMCs by interacting with LEV-treated MΦs, which promoted lymphangiogenesis. Mechanistically, activation of RhoA-ROCK pathway through EFNB reverse signaling induced LEV secretion. EFNBs on LEVs activated EphB forward signaling in PMC and MΦs, activating Akt, ERK and TGF-ß1 pathway, which were indispensable for causing MMT and LEC differentiation. LEVs accelerated peritoneal dissemination and lymphatic invasions by cancer cells. Blocking of EFNBs on LEVs using EphB-Fc-fusion protein attenuated these events. CONCLUSIONS: EFNBhigh cancer cells scattered LEVs when they attached to PMCs, which augmented the local reactions of PMC and MΦ (MMT and lymphangiogenesis) and exaggerated peritoneal dissemination.
RESUMO
PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.
Assuntos
Neoplasias Encefálicas , Glândula Pineal , Pinealoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Pinealoma/genética , Pinealoma/terapia , Pinealoma/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Estudos de Coortes , Intervalo Livre de Progressão , Glândula Pineal/patologia , Estudos RetrospectivosRESUMO
Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-ß-cyclodextrin and increased using the methyl-ß-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Colesterol , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Aluminum potassium sulfate and tannic acid sclerotherapy for hemorrhoids produced almost the same effects as excisional hemorrhoidectomy. However, its long-term effectiveness remains unknown. OBJECTIVE: The purpose of this study was to investigate the long-term results of sclerotherapy using aluminum potassium sulfate and tannic acid for treating prolapsed hemorrhoids. DESIGN: This was a retrospective review of a single-institution experience. SETTINGS: This study was conducted within a coloproctology unit at a community-based hospital. PATIENTS: In total, 1180 patients with grade II to IV hemorrhoids treated with injection sclerotherapy were enrolled. MAIN OUTCOME MEASURES: Efficacy measures included cumulative recurrence rates and postoperative complications. RESULTS: Recurrence rates at 3, 6, and 9 years were 7.4%, 27.2%, and 47.5%. Postoperative complications included fever ≥38°C in 16 (1.4%) patients, rectal ulcer in 10 (0.9%) patients, rectal stricture in 5 (0.4%) patients, and perianal abscess in 4 (0.3%) patients. LIMITATIONS: This was a retrospective, nonrandomized, single-center study. In addition, office visits after 3 years were optional and the number of follow-ups steadily decreased. CONCLUSIONS: Sclerotherapy using aluminum potassium sulfate and tannic acid offers reasonable long-term results and is associated with low complication rates. Therefore, it seems to be an attractive alternative for patients with prolapsed hemorrhoids. See Video Abstract at http://links.lww.com/DCR/B733.RESULTADOS A LARGO PLAZO DE LA ESCLEROTERAPIA CON SULFATO DE ALUMINIO Y POTASIO, Y ÁCIDO TÁNICO PARA LAS HEMORROIDES PROLAPSADAS: ESTUDIO OBSERVACIONAL DE UN SOLO CENTRO. ANTECEDENTES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico para las hemorroides produjo casi los mismos efectos que la hemorroidectomía por escisión. Sin embargo, se desconoce su eficacia a largo plazo. OBJETIVO: El propósito de este estudio fue investigar los resultados a largo plazo de la escleroterapia con sulfato de aluminio y potasio, y ácido tánico para tratar las hemorroides prolapsadas. DISEO: Revisión retrospectiva de la experiencia de una sola institución. ENTORNO CLINICO: Este estudio se realizó dentro de una unidad de coloproctología en un hospital comunitario. PACIENTES: En total, 1.180 pacientes fueron inscritos con hemorroides grado II a IV tratados con inyecciones esclerosantes. PRINCIPALES MEDIDAS DE VALORACION: Las medidas de eficacia incluyeron tasas acumulativas de recurrencia y complicaciones posoperatorias. RESULTADOS: La tasa de recurrencia a los 3, 6 y 9 años fue del 7,4%, 27,2% y 47,5%, respectivamente. Las complicaciones posoperatorias incluyeron fiebre ≥ 38 grados Celsius en 16 pacientes (1,4%), úlcera rectal en 10 (0,9%), estenosis rectal en 5 (0,4%) y absceso perianal en 4 (0,3%) pacientes. LIMITACIONES: Este fue un estudio retrospectivo, no aleatorio, de un solo centro. Adicionalmente, las visitas al consultorio después de 3 años eran opcionales y el número de seguimientos disminuyó constantemente. CONCLUSIONES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico ofrece resultados razonables a largo plazo y está asociada con bajas tasas de complicaciones. Por tanto, parece ser una alternativa atractiva para pacientes con hemorroides prolapsadas. Consulte Video Resumen en http://links.lww.com/DCR/B733. (Traducción- Dr. Francisco M. Abarca-Rendon).
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Compostos de Alúmen/uso terapêutico , Hemorroidas/terapia , Escleroterapia , Taninos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Ultrasonography (US) is a noninvasive and patient-friendly tool for the evaluation of peripheral nerves. In motor neuron diseases, amyotrophic lateral sclerosis (ALS) has been reported to show the atrophy of peripheral nerves on US. However, the US findings are still unclear in spinal and bulbar muscular atrophy (SBMA), an adult-onset lower motor neuron disease caused by an abnormal CAG repeat expansion in the androgen receptor gene. METHODS: We prospectively recruited and evaluated 11 patients with genetically confirmed SBMA and 9 patients with ALS diagnosed according to the revised El Escorial ALS criteria or the Awaji electrodiagnostic criteria. The C5-C7 cervical nerve roots and the median and ulnar nerves were evaluated ultrasonographically. RESULTS: The cross-sectional areas (CSAs) of the C6 and C7 nerve roots, the median nerve in the upper arm and forearm, and the ulnar nerve in the upper arm were smaller in patients with SBMA than those in patients with ALS (p < 0.05), whereas the CSAs of the C5 nerve root and the ulnar nerve in the forearm were not smaller. CONCLUSIONS: US showed that the peripheral nerves in patients with SBMA were thinner than those in patients with ALS despite similar degrees of weakness and motor neuron loss. Possible causes include additional sensory nerve involvement and longer disease duration in patients with SBMA than those in patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica , Atrofia Bulboespinal Ligada ao X , Doença dos Neurônios Motores , Atrofia Muscular Espinal , Adulto , Esclerose Lateral Amiotrófica/diagnóstico , Atrofia Bulboespinal Ligada ao X/diagnóstico por imagem , Humanos , Atrofia Muscular Espinal/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Raízes Nervosas Espinhais/diagnóstico por imagemRESUMO
Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.
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Apoptose/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Fagocitose/genética , Proteínas rac1 de Ligação ao GTP/fisiologia , Aminoquinolinas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Células Cultivadas , Progressão da Doença , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Neoplasias Bucais/genética , Fagócitos/efeitos dos fármacos , Fagócitos/fisiologia , Fagocitose/efeitos dos fármacos , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Fagossomos/patologia , Pirimidinas/farmacologia , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidoresRESUMO
Ficus carica produces, in addition to the cysteine protease ficin, a serine protease. Earlier study on a serine protease from F. carica cultivar Brown Turkey showed that it specifically degraded collagen. In this study, we characterized the collagenolytic activity of a serine protease in the latex of F. carica cultivar Masui Dauphine. The serine protease degraded denatured, but not undenatured, acid-solubilized type I collagen. It also degraded bovine serum albumin, while the collagenase from Clostridium histolyticum did not. These results indicated that the serine protease in Masui Dauphine is not collagen-specific. The protease was purified to homogeneity by two-dimensional gel electrophoresis, and its partial amino acid sequence was determined by liquid chromatography-tandem mass spectrometry. BLAST searches against the Viridiplantae (green plants) genome database revealed that the serine protease was a subtilisin-like protease. Our results contrast with the results of the earlier study stating that the serine protease from F. carica is collagen-specific.
Assuntos
Colágeno/química , Ficus/química , Látex/química , Proteínas de Plantas/metabolismo , Serina Proteases/metabolismo , Subtilisinas/metabolismo , Sequência de Aminoácidos , Animais , Bovinos , Eletroforese em Gel Bidimensional , Ficus/enzimologia , Expressão Gênica , Temperatura Alta , Látex/metabolismo , Extratos Vegetais/química , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Desnaturação Proteica , Proteólise , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Serina Proteases/química , Serina Proteases/genética , Serina Proteases/isolamento & purificação , Especificidade por Substrato , Subtilisinas/química , Subtilisinas/genética , Subtilisinas/isolamento & purificaçãoRESUMO
Reports on patients with moyamoya disease presenting cerebral ischemic complications after the onset of intraventricular hemorrhage (IVH) and/or intracerebral hemorrhage (ICH) are limited. Herein, we report a case of a 7-year-old girl with moyamoya disease with severe cerebral vasospasm and delayed cerebral infarction following an IVH. Although the case is rare, the potential for vasospasm-induced cerebral infarction should be carefully considered and thus, intensive treatment should be immediately initiated.
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Doença de Moyamoya , Vasoespasmo Intracraniano , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Criança , Feminino , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/diagnóstico por imagemRESUMO
OBJECTIVE: Symptomatic Tarlov cysts in children are not sufficiently reported and treatment methods for Tarlov cysts are still controversial. The goal of this manuscript is to introduce a new variation of the surgical technique. METHODS: We performed surgery to eliminate the one-way check valve mechanism of the Tarlov cyst in a 7-year-old female who presented with urinary and fecal incontinence. A relatively large S3 nerve root cyst showed a one-way check valve on computed tomography myelography. The inlet of the check valve was enlarged with rotation flap reconstruction. RESULTS: Two months after surgery, the patient had established normal sphincter control. MRI performed two years later showed that the treated cyst was collapsing, and no recurrence occurred. CONCLUSIONS: Rotation flap enlargement of the check valve inlet is a safe and efficacious option for the treatment of pediatric patients with sacral Tarlov cysts.
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Cistos de Tarlov , Criança , Feminino , Humanos , Mielografia , Recidiva Local de Neoplasia , Sacro/diagnóstico por imagem , Sacro/cirurgia , Retalhos Cirúrgicos , Cistos de Tarlov/diagnóstico por imagem , Cistos de Tarlov/cirurgiaRESUMO
A 72-year-old man had a chief complaint of anal pain and difficulty in defecation. He was diagnosed with adenocarcinoma by biopsy from a tumor of the anal canal. A computed tomography scan revealed neither regional lymph node metastasis nor distant metastasis. Hence, he was diagnosed with cT3N0M0, cStage â ¡a anal canal cancer. Preoperative capecitabine- based chemoradiotherapy(CRT)(50.4 Gy in 28 fractions of 1.8 Gy each)was implemented. Digital rectal examination and imaging evaluation 8 weeks after preoperative CRT revealed that the tumor had shrunk. Fifteen weeks after preoperative CRT, laparoscopic abdominoperineal resection was performed. The pathological findings showed mucinous adenocarcinoma associated with anal fistula. At present, 12 months after the operation, no local recurrence and distant metastasis has been detected under follow-up evaluations.
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Adenocarcinoma , Laparoscopia , Protectomia , Fístula Retal , Neoplasias Retais , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia , Humanos , Masculino , Fístula Retal/cirurgia , Fístula Retal/terapia , Neoplasias Retais/cirurgia , Neoplasias Retais/terapiaRESUMO
Permethylation is useful for glycosidic linkage analysis, but is often accompanied by a large proportion of by-products, especially for glycans containing sialic acids (Sia). Unlike hydroxyl groups of glycans, which are converted to stable methyl ethers by permethylation, the carboxylic acids on Sia are converted to methyl esters, which are easily reversible to carboxylate under alkaline conditions. To overcome this problem, we used linkage-specific alkylamidation to protect Sia prior to the permethylation. This method not only decreased the levels of by-products, but also enabled us to distinguish isomers of α2,3- and α2,6-Sia while simultaneously determining other glycosidic linkages.
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Polissacarídeos/química , Ácidos Siálicos/química , Cromatografia Líquida , Glicosídeos/química , Humanos , Metilação , Orosomucoide/química , Espectrometria de Massas por Ionização por Electrospray , gama-Globulinas/químicaRESUMO
PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Interferon beta/uso terapêutico , Temozolomida/uso terapêutico , Adulto , Idoso , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Telomerase/genética , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
In this study, I investigated the allergy suppressive effect of tea made from fig (Ficus carica L.) leaves. In the rat basophil cell line RBL-2H3, degranulation was significantly suppressed by treatment with fig tea at the same time as addition of IgE antibodies (sensitization). IgE bound to the cell surface was liberated in the medium depending on the treatment time with fig tea. Therefore, it was suggested that the mechanism of action of fig tea is promotion of dissociation of IgE from FcεRI receptors. Such a mechanism is novel in food materials. On oral administration to mice, fig tea showed an inhibitory effect on allergic dermatitis. Furthermore, in tests using an atopic dermatitis model in NC/Nga mice, continued administration of fig tea suppressed symptom exacerbation after antigen administration.Abbreviations: AD: atopic dermatitis; ß-Hex: ß-hexosaminidase; FCM: flow cytometory; OA: oral administration; TA: transdermal administration.
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Antialérgicos/uso terapêutico , Complexo Antígeno-Anticorpo/efeitos dos fármacos , Dermatite Atópica/tratamento farmacológico , Ficus/química , Imunoglobulina E/imunologia , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Receptores de IgE/imunologia , Chás de Ervas , Animais , Antialérgicos/farmacologia , Basófilos/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Feminino , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia , Ratos , Receptores de IgE/metabolismo , Resultado do TratamentoRESUMO
Wounding is a serious environmental stress in plants. Oxylipins such as jasmonic acid play an important role in defense against wounding. Mechanisms to adapt to wounding have been investigated in vascular plants; however, those mechanisms in nonvascular plants remain elusive. To examine the response to wounding in Physcomitrella patens, a model moss, a proteomic analysis of wounded P. patens was conducted. Proteomic analysis showed that wounding increased the abundance of proteins related to protein synthesis, amino acid metabolism, protein folding, photosystem, glycolysis, and energy synthesis. 12-Oxo-phytodienoic acid (OPDA) was induced by wounding and inhibited growth. Therefore, OPDA is considered a signaling molecule in this plant. Proteomic analysis of a P. patens mutant in which the PpAOS1 and PpAOS2 genes, which are involved in OPDA biosynthesis, are disrupted showed accumulation of proteins involved in protein synthesis in response to wounding in a similar way to the wild-type plant. In contrast, the fold-changes of the proteins in the wild-type plant were significantly different from those in the aos mutant. This study suggests that PpAOS gene expression enhances photosynthesis and effective energy utilization in response to wounding in P. patens.
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Bryopsida/metabolismo , Ácidos Graxos Insaturados/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Oxirredutases Intramoleculares/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Aminoácidos/genética , Aminoácidos/metabolismo , Bryopsida/genética , Cromatografia Líquida , Ciclo do Ácido Cítrico/genética , Ciclopentanos/metabolismo , Metabolismo Energético/genética , Ácidos Graxos Insaturados/deficiência , Ácidos Graxos Insaturados/genética , Glicólise/genética , Oxirredutases Intramoleculares/genética , Oxilipinas/metabolismo , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Biossíntese de Proteínas/genética , Dobramento de Proteína , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética , Espectrometria de Massas em TandemRESUMO
Hemorrhagic stroke associated with essential thrombocythemia (ET) is very infrequent. Herein, we report a case of a 33-year-old woman with a 2-year history of ET who developed intracerebral and subarachnoid hemorrhage. Angiography demonstrated severe vessel irregularity in the bilateral cerebral arteries. Molecular genetic testing revealed a calreticulin mutation. To our knowledge, hemorrhagic stroke has been reported in only six other patients with ET, and this is the first report of hemorrhagic stroke in an ET patient with a calreticulin mutation. We review the current literature and discuss the possible underlying mechanisms.
Assuntos
Hemorragia Cerebral/etiologia , Acidente Vascular Cerebral/etiologia , Hemorragia Subaracnóidea/etiologia , Trombocitemia Essencial/complicações , Adulto , Calreticulina/genética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Craniotomia , Feminino , Predisposição Genética para Doença , Humanos , Mutação , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Resultado do TratamentoRESUMO
(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.
Assuntos
Estenose das Carótidas/cirurgia , Angiografia por Ressonância Magnética/métodos , Neovascularização Patológica/diagnóstico por imagem , Pericitos/metabolismo , Placa Aterosclerótica/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos/metabolismo , Antígeno CD146/metabolismo , Angiografia Coronária/métodos , Endarterectomia das Carótidas/efeitos adversos , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/patologia , Feminino , Glicoforinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/etiologia , Pericitos/patologia , Placa Aterosclerótica/patologia , Proteoglicanas/metabolismoRESUMO
We reported 10 cases of lumbo-peritoneal(L-P)shunt placement using the lateral approach without repositioning. Each patient was placed in a left lateral position under general anesthesia and fixed so that the spine did not rotate. The skin incision on the flank was made at the height of the L4 vertebral body, 4 cm in the left-right direction and 3cm in front of the vertebral body. The external oblique, internal oblique, and transverse abdominal muscles were dissected to reach the peritoneum and confirm that the intestinal tract was peristaltic below the peritoneum. The peritoneum was lifted with hooked tweezers in order to separate them from the intestinal tract, and the peritoneum was incised with a scalpel to reach the peritoneal cavity. Using a finger and a shunt passer, the ventral catheter was guided between the muscle layers. Preoperative abdominal CT showed that all 10 kidneys in this case series were cephalic from the predicted approach route. The ascending colons of three patients were partially in contact with the predicted approach route. During surgery, a ventral catheter could be inserted in all 10 cases. Postoperative abdominal CT showed no intraperitoneal hemorrhage or invasion into the retroperitoneal cavity of the ventral catheter. During the follow-up period, no invasion into the abdominal wall or infection was observed. The average operation time was 52.2 minutes. In order to avoid invasion into the retroperitoneal cavity, a surgical incision was performed without complications by incising the outer side of the lower abdomen and approaching via the external oblique aponeurosis.
Assuntos
Cateteres de Demora , Cavidade Peritoneal , Abdome , Humanos , Instrumentos Cirúrgicos , Derivação VentriculoperitonealRESUMO
A 48-year-old female discovered a mass in her left axilla. A thorough examination resulted in a diagnosis of left invasive lobular carcinoma(ILC)of the accessory mammary gland with wide ductal spread. Considering the wide ductal spread, massive resection of the left axilla mass, left lymph node dissection, and a latissimus dorsi musculocutaneous flap procedure were performed. However, histological analysis revealed ILC measuring 80×50 mm with lymph node metastases(5/23)and extensive cancer spread, resulting in a positive surgical margin. It is important to recognize the characteristics of ILC, axillary accessory breast cancer, and the axilla in a treatment strategy.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Glândulas Mamárias Humanas , Axila , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Pessoa de Meia-IdadeRESUMO
Sialic acids (Sia) are involved in various biological and pathological processes, and are often found attached to non-reducing ends of glycans through either α2,3- or α2,6-linkages. To quantitatively analyze glycan structures with these linkage isoforms by liquid chromatography-mass spectrometry (LC-MS), we established a linkage-specific two-step alkylamidation method for N-glycans. Using this method, carboxyl groups of α2,3- and α2,6-linked Sia are derivatized with two kinds of alkylamines with different mass values in a linkage-specific manner, allowing products to be easily distinguished. The reaction efficiencies for di-, tri-, and tetra-sialyl PA-N-glycans were >94%, with few by-products. Mixtures of 2-aminopyridine (PA)-tagged N-glycans from human α1-acid glycoprotein were subjected to the method, and products were analyzed by LC-MS and MS/MS, and simultaneously monitored with a fluorescence detector. The relative content of Siaα2-3Gal and Siaα2-6Gal was estimated from the integrated fluorescence intensity of each peak. Moreover, MS/MS data clearly indicated characteristic B-ion fragments of N-glycan branches, such as the sialyl Lex sequence, with Sia linkage-specific alkylamidation, suggesting that this method also provides useful information of branch sequences. We optimized the method with the aim of (1) enabling high-throughput analysis and (2) maximizing the analysis of glycans from various types of samples, including highly heterogeneous glycans.