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1.
Drug Test Anal ; 13(10): 1791-1796, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34342157

RESUMO

Erythropoietin receptor agonists (ERAs) are drugs acting on the early erythropoietic stages developed to treat anemia and other erythropoiesis disease and are prohibited by the World Anti-Doping Agency (WADA). As an alternative to ERAs, a new drug, belonging to the transforming growth factor-b inhibitors family, was recently developed to treat diseases linked to ineffective erythropoiesis. This drug, named as Luspatercept (Reblozyl®), is acting on the later stages of erythropoiesis to promote erythrocytes. This drug might be used by cheating athletes either independently or in combination with ERAs. Indeed, it was shown that Luspatercept and recombinant erythropoietin (rEPO) can act synergistically to increase red blood cells production, potentially allowing the use of lower doses for an efficient effect. Our aim was to find a way to combine the detection of ERAs and Luspatercept without impacting the sensitivity and specificity of ERAs detection from the current techniques implemented in antidoping laboratories and to reduce the time of analysis and total sample volume needed. Magnetic beads coated with antibodies were preferred for IP of samples for its potential multiplexing. Then, the following steps of the method were selected considering that SAR/SDS-PAGE are the electrophoretic methods authorized for initial testing procedure by WADA and that biotinylated primary antibodies used for the immunodetection results in the best sensitivity and specificity and is time saving. The method developed in this work for the combined detection of agents affecting erythropoiesis (AAEs) showed specificity, sensitivity, and robustness and is easily and quickly implementable to all antidoping laboratories.


Assuntos
Receptores de Activinas Tipo II/análise , Dopagem Esportivo/prevenção & controle , Hematínicos/análise , Fragmentos Fc das Imunoglobulinas/análise , Proteínas Recombinantes de Fusão/análise , Detecção do Abuso de Substâncias/métodos , Eletroforese em Gel de Poliacrilamida , Eritropoese/efeitos dos fármacos , Humanos , Sensibilidade e Especificidade
2.
Turk Patoloji Derg ; 37(2): 172-177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973641

RESUMO

ALK positive histiocytosis is a relatively new histiocytic proliferation disease with a characteristic gene translocation involving fusion of the ALK gene with different partners, mostly KIF5B. We report a case of ALK-positive histiocytosis with literature review. A 27-year-old male patient presented mainly with progressive lower limb weakness. Imaging studies showed an intradural extramedullary enhancing lesion at the L3 level. A 1.5 cm mass was excised from the sensory nerve root in the filum terminale at the level of L3. Histologic examination showed infiltration of the nerve by numerous histiocytes with moderate to abundant eosinophilic to clear-foamy and variably-vacuolated cytoplasm with irregular-to-smooth contoured nuclei. The histiocytes were positive for CD68 and ALK1 and negative for S100 and CD1a. KIF5B-ALK fusion was detected by real time-polymerase chain reaction. The patient is asymptomatic nine months after surgical excision. This is the first reported localized case occurring in the nerve root of an adult patient, thus expanding the clinical manifestations of this disease. An integrated histological, immunohistochemical and molecular approach is recommended for diagnosis. We recommend performing ALK1 immunohistochemical stain on all histiocytosis cases to increase awareness and detection of this newly described entity.


Assuntos
Receptores de Activinas Tipo II/análise , Histiocitose/metabolismo , Adulto , Fusão Gênica , Histiocitose/genética , Histiocitose/patologia , Histiocitose/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento
3.
Int J Obes (Lond) ; 45(2): 316-325, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873911

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is a therapeutic intervention for morbid obesity and type 2 diabetes (T2D) that improves metabolic regulation. Follistatin (Fst) could be implicated in improved glycemia as it is highly regulated by RYGB. However, it is unknown if metabolic status, such as T2D, alters the Fst response to RYGB. In addition, the effect of RYGB on the Fst target, activin A, is unknown in individuals with obesity and T2D, but is needed to interpret the functional effects of altering Fst. Finally, whether Fst-regulated intracellular signaling contributes to beneficial effects of RYGB is undetermined. METHODS: Circulating Fst and activin A were measured before, 1 week, and 1 year after RYGB surgery in a total of 20 individuals with obesity, 10 with normoglycemia (NGT) and 10 with preoperative T2D. Intracellular signaling downstream of the Activin receptor type IIB (ActRIIB) signaling pathway was analyzed in skeletal muscle and adipose tissue. RESULTS: The doubling in circulating Fst observed in subjects with NGT 1-week and 1-year post surgery was absent in T2D. After 1 week, RYGB reduced activin A by 27% (p < 0.001) and 20% (p < 0.01) in subjects with NGT and T2D, respectively; a reduction that tended to be maintained in the subjects with T2D at 1-year post-RYGB (-15%; p = 0.0592). RYGB had no effects on skeletal muscle ActRIIB signaling. In contrast, adipose tissue phosphorylation of SMAD2Ser465/467, p70S6KThr389, S6RPSer235/236, and 4E-BP1Thr37/49 was highly regulated, particularly 1-year post-RYGB (p < 0.05). CONCLUSIONS: In subjects with preoperative T2D, RYGB did not increase circulating Fst contrasting subjects with NGT, while the reduction in activin A was maintained. ActRIIB signaling was upregulated in adipose tissue, but not skeletal muscle, following RYGB in both individuals with NGT and T2D. Our results suggest a role of adipose tissue ActRIIB signaling for the beneficial effects of RYGB surgery.


Assuntos
Receptores de Activinas Tipo II/análise , Ativinas/sangue , Ativinas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Folistatina/sangue , Folistatina/metabolismo , Obesidade Mórbida , Tecido Adiposo/metabolismo , Adulto , Biópsia , Glicemia , Feminino , Seguimentos , Derivação Gástrica , Glucose/metabolismo , Controle Glicêmico , Humanos , Subunidades beta de Inibinas/metabolismo , Masculino , Pessoa de Meia-Idade , Músculos/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Transdução de Sinais , Fatores de Tempo
4.
Cell Mol Gastroenterol Hepatol ; 10(4): 779-796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32561494

RESUMO

BACKGROUND & AIMS: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn's disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. METHODS: microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. RESULTS: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3'-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. CONCLUSIONS: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients.


Assuntos
Receptores de Activinas Tipo II/análise , Colo/patologia , Doença de Crohn/patologia , Mucosa Intestinal/patologia , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Adulto , Colo/metabolismo , Doença de Crohn/genética , Doença de Crohn/metabolismo , Regulação para Baixo , Ativação Enzimática , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade
5.
Balkan Med J ; 37(1): 43-46, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31594285

RESUMO

Aims: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4, and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families. Methods: Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files. Results: We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM_000118.3 (ENG): c.416delC (p.P139fs*24) and NM_000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM_000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM_000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab. Conclusion: In HHT certain type of mutations correlates with disease phenotypes and with next generation sequencing method, new pathogenic variations can be revealed which might help managing HHT patients.


Assuntos
Telangiectasia Hemorrágica Hereditária/sangue , Fatores de Virulência , Receptores de Activinas Tipo II/análise , Receptores de Activinas Tipo II/sangue , Adulto , Idoso , Endoglina/análise , Endoglina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Smad4/análise , Proteína Smad4/sangue , Telangiectasia Hemorrágica Hereditária/fisiopatologia , Turquia
6.
Drug Test Anal ; 11(1): 168-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30091846

RESUMO

Iso-electric focusing (IEF) was the first method established to discriminate endogenous and recombinant erythropoietins (rEPOs). It is still approved by the World Anti-Doping Agency (WADA) as an initial testing procedure to detect erythropoiesis stimulating agents (ESAs) in doping control samples. However EPO-Fc, one of the prohibited rEPOs designated by WADA, is not detectable with the actual IEF conditions. Other newly developed ESAs - luspatercept and sotatercept, both activin receptor type II-Fc fusion proteins (ActRII-Fc) - are also now prohibited and could be used in combination with rEPOs. Methods of identification of ActRII-Fc in blood by SAR/SDS-PAGE have been described, but not by IEF. Here we detail improvements in blood sample preparation and IEF analysis: A combined immuno-purification of EPOs and ActRII-Fc proteins in a single procedure, an appropriate isoforms separation for all proteins using new pre-loading and gel conditions, and a single detection of all rEPOs and ActRII-Fc proteins after successive incubation with anti-EPO and anti-ActRII antibodies. With these changes, distinctive profiles for all the ESAs were obtained by IEF. Therefore, IEF could be used as a screening method to detect a wide spectrum of prohibited ESAs in blood samples prior to specific confirmation for the identified rEPO or ActRII-Fc.


Assuntos
Receptores de Activinas Tipo II/análise , Dopagem Esportivo/prevenção & controle , Eritropoetina/análise , Proteínas Recombinantes/análise , Detecção do Abuso de Substâncias/métodos , Receptores de Activinas Tipo II/imunologia , Eritropoetina/imunologia , Humanos , Focalização Isoelétrica/métodos , Focalização Isoelétrica/normas , Proteínas Recombinantes/imunologia , Detecção do Abuso de Substâncias/normas
7.
Ann Pathol ; 38(2): 143-146, 2018 Apr.
Artigo em Francês | MEDLINE | ID: mdl-29397221
8.
Indian J Pathol Microbiol ; 60(2): 275-278, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28631654

RESUMO

Composite lymphoma is a rare tumor composed of two or more distinct lymphomas in the same topographic site or tissue. Several combinations of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, and Hodgkin lymphoma can occur with different prognoses and treatments. The coexistence of a B-cell NHL and a T-cell NHL is unusual. The exact etiology of composite lymphoma is unknown; however, few mechanisms have been proposed to explain its pathogenesis. The chemotherapeutic protocols are heterogeneous but are essentially targeted against the high-grade component. Most of the cases show worse outcome with a median survival of 12 months. In this article, we report a case of composite lymphoma which was initially diagnosed as diffuse large B-cell lymphoma, and the presence of CD3-positive atypical cells in the bone marrow urged us to re-evaluate the lymph node biopsy following which a focus of Alk-1-positive anaplastic large cell lymphoma was identified.


Assuntos
Linfoma Composto/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Anaplásico de Células Grandes/diagnóstico , Receptores de Activinas Tipo II/análise , Medula Óssea/patologia , Complexo CD3/análise , Linfoma Composto/patologia , Técnicas Citológicas , Humanos , Imuno-Histoquímica , Linfoma de Células B/complicações , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Linfoma Anaplásico de Células Grandes/complicações , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Microscopia , Pessoa de Meia-Idade
9.
J Hypertens ; 34(7): 1371-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27176145

RESUMO

OBJECTIVE: Preeclampsia is a pregnancy-related syndrome. Shallow invasion of uterine wall by trophoblast cells has been generally accepted as the major pathological change of this disorder. We previously found downregulation of miR-195 in preeclamptic placentas. Bioinformatic analysis predicted a type II activin receptor, activin receptor type-2B (ActRIIB), as one of the potential targets of miR-195. Considering the key function of activin A on trophoblast cell behaviors and placenta development, we proposed miR-195 may affect trophoblast cell invasion by repressing the expression of ActRIIB. METHODS: The colocalization of ActRIIB and miR-195 in human placenta was measured by in-situ hybridization and immunohistochemistry. Western blotting, real-time PCR and dual luciferase assay were performed in human trophoblast cell line, HTR8/SVneo cells, to validate the targeting of ActRIIB by miR-195. Cell invasiveness was analyzed using transwell insert invasion assay in HTR8/SVneo cells. RESULTS: In human placenta, ActRIIB and miR-195 exhibited similar localization in various subtypes of trophoblast cells, including villous and extravillous trophoblasts. The protein expressions of ActRIIB in preeclamptic placenta were significantly higher as compared with the normal controls, which was opposite to the changing pattern of miR-195. In HTR8/SVneo cells, miR-195 could directly target and suppress the expression of ActRIIB. Meanwhile, the invasion-promoting effect of miR-195 on trophoblast cells could be largely impeded by ActRIIB overexpression. CONCLUSION: In human trophoblast cells, miR-195 could promote cell invasion via directly targeting ActRIIB. The impaired miR-195 expression may contribute to the occurrence or development of preeclampsia through interfering with activin/nodal signaling in the placenta.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Movimento Celular , MicroRNAs/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Trofoblastos/fisiologia , Receptores de Activinas Tipo II/análise , Receptores de Activinas Tipo II/genética , Adulto , Estudos de Casos e Controles , Linhagem Celular , Feminino , Humanos , Hibridização In Situ , MicroRNAs/análise , MicroRNAs/genética , Placenta/química , Pré-Eclâmpsia/genética , Gravidez
10.
Int J Gynecol Pathol ; 34(5): 419-23, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26262452

RESUMO

Inflammatory myofibroblastic tumor has been described in a wide variety of anatomic sites, although in the gynecologic tract, it has mostly been documented in the uterus, and has never been described in the placenta. Two patients presented with well-circumscribed placental masses that showed classic histologic features of inflammatory myofibroblastic tumor including a proliferation of myofibroblastic cells, a mixed inflammatory infiltrate, and a myxoid background. One case was positive by immunohistochemistry for anaplastic lymphoma kinase (ALK-1), whereas the other was negative by immunohistochemistry and fluorescent in situ hybridization. Inflammatory myofibroblastic tumors should be differentiated from other more aggressive uterine tumors that may involve the placenta by direct extension/metastasis because they can be managed conservatively, and in these 2 cases, did not seem to affect the course of the patient's pregnancies.


Assuntos
Inflamação/patologia , Neoplasias de Tecido Muscular/patologia , Placenta/patologia , Complicações Neoplásicas na Gravidez/patologia , Actinas/análise , Receptores de Activinas Tipo II/análise , Adulto , Apresentação Pélvica , Cesárea , Decídua/patologia , Feminino , Morte Fetal , Idade Gestacional , Humanos , Imuno-Histoquímica , Miofibroblastos/patologia , Neprilisina/análise , Gravidez , Resultado da Gravidez , Receptores de Progesterona/análise
11.
Fertil Steril ; 104(3): 744-52.e1, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26086422

RESUMO

OBJECTIVE: To evaluate the expression pattern of activins and related growth factor messenger RNA (mRNA) levels in adenomyotic nodules and in their endometrium. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Symptomatic premenopausal women scheduled to undergo hysterectomy for adenomyosis. INTERVENTION(S): Samples from adenomyotic nodules and homologous endometria were collected. Endometrial tissue was also obtained from a control group. MAIN OUTCOME MEASURE(S): Quantitative real-time polymerase chain reaction (PCR) analysis and immunohistochemical localization of activin-related growth factors (activin A, activin B, and myostatin), binding protein (follistatin), antagonists (inhibin-α, cripto), and receptors (ActRIIa, ActRIIb) were performed. RESULT(S): Myostatin mRNA levels in adenomyotic nodule were higher than in eutopic endometrium and myostatin, activin A, and follistatin concentrations were higher than in control endometrium. No difference was observed for inhibin-α, activin B, and cripto mRNA levels. Increased mRNA levels of ActRIIa and ActRIIb were observed in adenomyotic nodules compared with eutopic endometrium and control endometrium. Immunofluorescent staining for myostatin and follistatin confirmed higher protein expression in both glands and stroma of patients with adenomyosis than in controls. CONCLUSION(S): The present study showed for the first time that adenomyotic tissues express high levels of myostatin, follistatin, and activin A (growth factors involved in proliferation, apoptosis, and angiogenesis). Increased expression of their receptors supports the hypothesis of a possible local effect of these growth factors in adenomyosis. The augmented expression of ActRIIa, ActRIIb, and follistatin in the endometrium of these patients may play a role in adenomyosis-related infertility.


Assuntos
Receptores de Activinas Tipo II/análise , Adenomiose/metabolismo , Endométrio/química , Folistatina/análise , Miostatina/análise , Receptores de Activinas Tipo II/genética , Ativinas/análise , Adenomiose/genética , Adenomiose/cirurgia , Adulto , Estudos de Casos e Controles , Endométrio/cirurgia , Feminino , Folistatina/genética , Humanos , Imuno-Histoquímica , Miostatina/genética , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Brain Tumor Pathol ; 32(1): 66-71, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24807104

RESUMO

Histiocytic sarcoma is a rare malignant neoplasm of hematopoietic origin composed of cells showing morphologic and immunophenotypic evidence of histiocytic differentiation. We describe the 2nd case of primary histiocytic sarcoma of the cavernous sinus/Meckel's cave, and the 8th case involving the CNS. A 61-year-old Caucasian man presented with numbness on the entire left side of his face, shooting pain in the left frontal region, and headaches. Imaging revealed an enhancing extra axial soft tissue mass located in the left cavernous sinus and left Meckel's cave. Diagnosis was established through open biopsy, after failed attempts via CT-guided trans-foramen ovale fine-needle aspiration biopsy and keyhole biopsy. The tumor was composed of large non-cohesive epithelioid cells invading nerves and ganglion cells. Tumor cells were immunopositive for CD68, CD163, and immunonegative for the anaplastic large cell lymphoma marker ALK-1 as well as other lymphoid, myeloid, and dendritic cell markers. Histiocytic sarcoma has strong potential for systemic spread; early diagnosis and treatment are important. Our patient was initially treated with radiation therapy but subsequently developed metastases.


Assuntos
Seio Cavernoso , Sarcoma Histiocítico/diagnóstico , Neoplasias Vasculares/diagnóstico , Receptores de Activinas Tipo II/análise , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Proteínas da Matriz Extracelular/análise , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/radioterapia , Humanos , Receptores de Hialuronatos/análise , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Vasculares/patologia , Neoplasias Vasculares/radioterapia
13.
J Exp Biol ; 216(Pt 19): 3742-50, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23788712

RESUMO

The activin type IIB receptor (Acvr2b) is the cell surface receptor for multiple transforming growth factor ß (TGF-ß) superfamily ligands, several of which regulate muscle growth in mammals. To investigate the role of the Acvr2b signaling pathway in the growth and development of skeletal muscle in teleost fish, transgenic rainbow trout (RBT; Oncorhynchus mykiss) expressing a truncated form of the acvr2b-2a (acvr2b(▵)) in muscle tissue were produced. High levels of acvr2b(▵) expression were detected in the majority of P1 transgenic fish. Transgenic P1 trout developed enhanced, localized musculature in both the epaxial and hypaxial regions (dubbed 'six pack'). The F1 transgenic offspring did not exhibit localized muscle growth, but rather developed a uniform body morphology with greater girth, condition factor and increased muscle fiber hypertrophy. There was a high degree of variation in the mass of both P1 and F1 transgenic fish, with several fish of each generation exhibiting enhanced growth compared with other transgenic and control siblings. The 'six pack' phenotype observed in P1 transgenic RBT overexpressing acvr2b(▵) and the presence of F1 individuals with altered muscle morphology provides compelling evidence for the importance of TGF-ß signaling molecules in regulating muscle growth in teleost fish.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Proteínas de Peixes/metabolismo , Desenvolvimento Muscular , Truta/crescimento & desenvolvimento , Receptores de Activinas Tipo II/análise , Receptores de Activinas Tipo II/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Feminino , Proteínas de Peixes/análise , Proteínas de Peixes/genética , Masculino , Dados de Sequência Molecular , Fator de Crescimento Transformador beta/metabolismo , Truta/genética , Truta/metabolismo
14.
Am J Dermatopathol ; 35(4): 403-8; quiz 409-11, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23689691

RESUMO

The use of anaplastic lymphoma kinase antibodies (ALK1) as a diagnostic aid has expanded since becoming a routinely available immunohistochemical stain. Because the skin may be the site of a wide variety of hematolymphoid and fibroblastic proliferations, dermatopathologists commonly use ALK1 as part of a broader staining panel in diagnosing soft tissue and cutaneous hematolymphoid neoplasms. Furthermore, new entities and differential diagnostic contexts are emerging, which broaden the utility of ALK1 immunohistochemistry. We review the expanding role of ALK1 immunohistochemistry in contemporary dermatopathology.


Assuntos
Receptores de Activinas Tipo II/análise , Biomarcadores Tumorais/análise , Dermatologia/métodos , Imuno-Histoquímica , Patologia/métodos , Neoplasias Cutâneas/enzimologia , Pele/enzimologia , Receptores de Activinas Tipo II/genética , Biomarcadores Tumorais/genética , Biópsia , Humanos , Valor Preditivo dos Testes , Prognóstico , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
15.
Dis Esophagus ; 26(3): 323-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23072221

RESUMO

Inflammatory myofibroblastic tumors are rare lesions that have been described in virtually every organ including the gastrointestinal tract. The esophagus is an extremely unusual site for these tumors, with only a few cases described in the literature. Surgery has been the most common therapeutic approach used for the resection of these lesions. In the present case, a patient diagnosed with an inflammatory myofibroblastic tumor of the upper esophagus was reported, and it was successfully removed by endoscopy with no complications.


Assuntos
Doenças do Esôfago/cirurgia , Esofagoscopia/métodos , Granuloma de Células Plasmáticas/cirurgia , Actinas/análise , Receptores de Activinas Tipo II/análise , Eletrocirurgia/instrumentação , Eletrocirurgia/métodos , Esofagoscópios , Feminino , Humanos , Linfócitos/patologia , Pessoa de Meia-Idade , Plasmócitos/patologia , Pólipos/cirurgia
16.
Pathol Res Pract ; 209(1): 14-8, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23177617

RESUMO

Bone formation is a rarely encountered finding during histological examination of papillary thyroid carcinoma (PTC). This study aimed to analyze clinicopathological parameters in patients with PTC showing bone formation, to document histological features of bone formation in PTC, and to investigate osteogenic proteins. Bone morphogenic protein (BMP)-9 is known as the most potent osteoinductive protein of the BMP subtypes. Recent research suggests that the activin receptor-like kinase (ALK) 1 is an essential cellular receptor that mediates BMP-9-induced osteogenic signaling. A retrospective review of tumor sections from 567 patients with a diagnosis of PTC was performed. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of ALK1 and BMP-9 in normal thyroid tissue and PTC samples with and without bone formation. Bone formation was found in 13% of patients with PTC. A significant association was seen between bone formation and old age. BMP-9 expression in tumors was increased compared to that in normal thyroid tissues. BMP-9 expression in tumors with bone formation was not significantly different from that in tumors without bone formation. ALK1 expression in tumors with bone formation was increased compared to that in normal thyroid tissue and tumors without bone formation. Our study suggests that upregulation of ALK1 might be an underlying molecular mechanism that explains osteogenesis in PTC.


Assuntos
Carcinoma/patologia , Ossificação Heterotópica/patologia , Neoplasias da Glândula Tireoide/patologia , Receptores de Activinas Tipo II/análise , Receptores de Activinas Tipo II/biossíntese , Adulto , Fatores Etários , Carcinoma/metabolismo , Carcinoma Papilar , Feminino , Fator 2 de Diferenciação de Crescimento/análise , Fator 2 de Diferenciação de Crescimento/biossíntese , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismo
17.
Am J Surg Pathol ; 36(7): 1000-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22613996

RESUMO

We report 13 cases of anaplastic large cell lymphoma (ALCL) associated with breast implants. Patient age ranged from 39 to 68 years, and the interval from implant to ALCL was 4 to 29 years. All tumors were composed of large, pleomorphic cells that were CD30 and ALK1, and all 7 cases assessed had monoclonal T-cell receptor γ-chain rearrangements. Two patient subgroups were identified. Ten patients presented with effusion surrounded by fibrous capsule without a grossly identifiable tumor mass. Nine patients had stage I and 1 had stage II disease. Eight patients underwent implant removal and capsulectomy. Four patients received chemotherapy and 4 radiation therapy. All patients were alive without disease at last follow-up. A second subgroup of 3 patients had effusion and a distinct mass adjacent to the implant. One patient had stage I and 2 stage II disease. One patient had a 3-year history of lymphomatoid papulosis, and 1 patient had a 1-year history of CD30 T-cell lymphoma adjacent to the breast before the diagnosis of ALCL associated with breast implant. Two patients received chemotherapy and 1 radiation therapy. Two patients died 2 and 12 years after diagnosis, respectively. We conclude that the clinical behavior of ALCL associated with breast implants is heterogeneous. Patients who present with effusion without a distinct mass have an indolent disease course, similar to CD30 lymphoproliferative disorder of skin. In contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis.


Assuntos
Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Linfoma Anaplásico de Células Grandes/etiologia , Receptores de Activinas Tipo II/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Implante Mamário/mortalidade , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Remoção de Dispositivo , Feminino , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Genes Codificadores da Cadeia delta de Receptores de Linfócitos T , Humanos , Antígeno Ki-1/análise , Linfoma Anaplásico de Células Grandes/química , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/mortalidade , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Texas , Fatores de Tempo , Resultado do Tratamento
18.
Fertil Steril ; 97(5): 1115-23, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22425195

RESUMO

OBJECTIVE: To investigate the role of activin-ßA subunit, activin type II receptors, inducible nitric oxide synthase (iNOS), and MUC1 in the pathogenesis of ectopic pregnancy (EP) and their involvement in the determination of the implantation site. DESIGN: Observational study. SETTING: Academic unit of reproductive and developmental medicine. PATIENT(S): Four women at the luteal phase, three pseudopregnant women at the time of hysterectomy for benign disease, and 10 archived cases of EP. We collected 14 Fallopian tubes were collected from four women at the luteal phase and three pseudopregnant women at the time of hysterectomy for benign disease; specimens from implantation site, trophoblast and remote sites from the implantation site were collected from 10 archived cases of EP. INTERVENTION(S): Immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression of candidate molecules between the different groups. RESULT(S): The expression of activin-ßA subunit, activin type II receptors, and iNOS was statistically significantly increased and expression of MUC1 statistically significantly decreased in tubes bearing an EP. There was no statistically significant difference in the expression of the candidate molecules between the implantation and remote sites. Candidate molecules were also expressed in the trophoblast. CONCLUSION(S): The pathological expression of candidate molecules by tubes bearing an EP is not involved in the determination of implantation site. Additionally, candidate molecules may play a role in the regulation of trophoblast cells in vivo during early pregnancy.


Assuntos
Implantação do Embrião , Tubas Uterinas/enzimologia , Tubas Uterinas/imunologia , Subunidades beta de Inibinas/análise , Mucina-1/análise , Óxido Nítrico Sintase Tipo II/análise , Gravidez Ectópica/etiologia , Receptores de Activinas Tipo II/análise , Adulto , Inglaterra , Tubas Uterinas/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Subunidades beta de Inibinas/genética , Mucina-1/genética , Óxido Nítrico Sintase Tipo II/genética , Gravidez , Gravidez Ectópica/enzimologia , Gravidez Ectópica/genética , Gravidez Ectópica/imunologia , Gravidez Ectópica/fisiopatologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Trofoblastos/enzimologia , Trofoblastos/imunologia , Adulto Jovem
19.
FASEB J ; 26(6): 2509-21, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22403007

RESUMO

Human aging is accompanied by a progressive loss of muscle mass (sarcopenia). We tested the hypothesis that older males (OMs, 70±4 yr, n=9) would have a blunted myogenic response to a physiological stimulus compared to younger controls (21±3 yr, n=9). Subjects completed an acute bout of intense unilateral muscle loading. Young healthy males matched for body mass and activity level served as the control group. Muscle biopsies and blood were obtained before and at 3, 24, and 48 h after muscle loading. The muscle stem cell response was analyzed using flow cytometry, immunofluorescent microscopy, and standard protein and mRNA analysis. OMs had 35% fewer basal stem cells and a type II fiber-specific impairment in stem cell content and proliferation. Myogenic determination factor staining and cell cycle analysis illustrated a severely blunted progression through the myogenic program. Myostatin protein and mRNA were 2-fold higher in OMs. Stem cell-specific myostatin levels were not different at baseline; however, there were 67% more myostatin-positive type II-associated stem cells in OMs at 24 h. These data illustrate an age-related impairment of stem cell function in a fiber type-specific manner. The greater colocalization of myostatin with stem cells provides a mechanism for the impaired myogenic capacity of aged muscle.


Assuntos
Miostatina/fisiologia , Sarcopenia/fisiopatologia , Células-Tronco/fisiologia , Receptores de Activinas Tipo II/análise , Idoso , Envelhecimento/fisiologia , Ciclo Celular/fisiologia , Exercício Físico/fisiologia , Humanos , Masculino , Músculo Esquelético/patologia , Proteína MyoD/análise , Fator de Transcrição PAX7 , RNA Mensageiro/metabolismo , Células Satélites de Músculo Esquelético/fisiologia , Adulto Jovem
20.
Actas Urol Esp ; 36(4): 259-64, 2012 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-22030117

RESUMO

OBJECTIVE: The inflammatory pseudotumor is a rare lesion, having benign behavior and some histological heterogeneity that appears in the genitourinary tract. A series of urogenital inflammatory pseudotumors are reviewed with emphasis on their clinicopathological and immunohistochemical characteristics. MATERIAL AND METHODS: A retrospective study the causistics treated between January 1981 in December 2010 was performed. It identified the cases of inflammatory pseudotumor with urogenital localization. The variables age, gender, symptoms, topography, treatment and anatomopathological and immunohistochemical characteristics of each case were analyzed. RESULTS: A total of 8 cases of the urogenital-located inflammatory pseudotumor are described. Of these, 6 were located in the bladder, one in the kidney and one in the epididymis. Mean age of the patients was 46.75 (± 19.84) years. Tumor presentation symptoms were macroscopic hematuria, single symptom or accompanied by symptoms of the lower urinary tract and inguinoscrotal mass. In regards to treatment in the cases of bladder localization, transuretheral ± cystectomy were performed. In the case of kidney localization, treatment was made by means of pyelotomy and exeresis, and in the case of epididymis localization, simple exeresis was performed. The anatomopathological study showed inflammatory pseudotumor in every cases, having a mesenchymal and myxoid appearance, with fusiform cells of eosinophil cytoplasm, with presence of frequent inflammatory cells. The most common immunohistochemical pattern shows positivity for the muscle-specific actin (HHF-35), vimentin and negativity for protein S-100. ALK-1 was positive and 87.5% of the cases. CONCLUSION: The inflammatory pseudotumor is a condition having good prognosis which, when there is a good histopathological and immunohistochemical diagnosis, every urologist should recognize and distinguish in order to carry out as conservative a surgical treatment as possible.


Assuntos
Granuloma de Células Plasmáticas/epidemiologia , Doenças da Bexiga Urinária/epidemiologia , Actinas/análise , Receptores de Activinas Tipo II/análise , Adolescente , Adulto , Idoso , Biomarcadores , Cistectomia , Diagnóstico Diferencial , Diagnóstico por Imagem , Epididimo/patologia , Epididimo/cirurgia , Feminino , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/epidemiologia , Doenças dos Genitais Masculinos/metabolismo , Doenças dos Genitais Masculinos/patologia , Doenças dos Genitais Masculinos/cirurgia , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/metabolismo , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Queratinas/análise , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/diagnóstico , Espanha/epidemiologia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/cirurgia , Vimentina/análise
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