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2.
World J Gastroenterol ; 25(36): 5569-5577, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576101

RESUMO

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a type of tumor that presents in the intra- or extrahepatic bile ducts. Cystic-type intrahepatic IPNB often mimics simple liver cysts, making the diagnosis difficult. Because the growth of IPNB is slow, careful follow-up and timely therapeutic intervention is recommended. There are few reports with a follow-up period longer than a decade; thus, we report the case of a patient with an IPNB that grew for over 13 years. CASE SUMMARY: A 65-year-old man was diagnosed, 13 years prior with a cystic hepatic tumor with abnormal imaging findings. The targeted tumor biopsy results showed no malignancy. Biannual follow-up examinations were performed because of the potential for malignancy. The cystic lesions showed gradual enlargement over 11 years and a 4 mm papillary proliferation appeared on the cyst wall, which is compatible with IPNB. The tumor was observed for another 2 years because of the patient's wishes. The imaging findings showed enlargement to 8 mm and a new 9 mm papillary proliferation of the cystic tumor. Contrast-enhanced ultrasonography showed hyperenhancement during the arterial phase in both cyst walls, indicating intraductal tumor progression in both tumors. Thus, liver segment 8 subsegmentectomy was performed. The pathological findings indicated that the tumors contained mucin, and high-grade atypia was observed in the papillary lesions, showing IPNB. CONCLUSION: The development of IPNB should be monitored in patients with cystic lesions and ultrasonography are useful tool for the evaluation.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Papilar/diagnóstico , Cistos/patologia , Idoso , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Biópsia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Colangiografia , Cistos/cirurgia , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
3.
Immunol Med ; 42(2): 94-98, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31469613

RESUMO

Giant cell arteritis (GCA) is a type of large vessel vasculitis, and it involves the aorta, large vessels and terminal branches of the external carotid artery, especially the temporal artery. Temporal artery biopsy is a simple tool for the diagnosis of vasculitis, however, the histopathological findings do not always differentiate between the small-vessel vasculitis and GCA. We report the case of 72-year-old male who initially had a clinical diagnosis of GCA, then in the course of treatment, diagnostic histopathological approach revealed the necrotizing vasculitis with bronchocentric granulomatosis in the inflammatory nodule of the lung. The manifestations of patients with systemic vasculitis represent the disorders of multiple organ systems thus are diverse and may vary through the course of the disease. Presentation of unexpected features such as insufficient response to antibiotics, sinusitis, runny nose, discomfort of frontal region or pachymeningitis which anticipates re-evaluation of systemic vasculitis that may lead us to an appropriate diagnosis and the treatment.


Assuntos
Arterite de Células Gigantes/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/patologia , Arterite de Células Gigantes/terapia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Radiografia Torácica , Rinite/etiologia , Sinusite/etiologia , Artérias Temporais/patologia , Tomografia Computadorizada por Raios X
4.
Neuroradiology ; 60(5): 479-486, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29546484

RESUMO

PURPOSE: To explore the utility of the apparent diffusion coefficient (ADC) and tumor volume to predict histological grade and prognosis in patients with choroid plexus tumors. METHODS: ADC and tumor volumes were retrospectively evaluated in 25 patients with choroid plexus papilloma (CPP; WHO grade 1 [n = 13]), atypical CPP (aCPP; grade 2 [n = 8]), or choroid plexus carcinoma (grade 3 [n = 4]) The prognostic roles of ADC and tumor volume were assessed. RESULTS: There were significant differences in mean and minimum ADC values, and tumor volume among the WHO grades (p = 0.033, p = 0.044, and p = 0.014, respectively). Receiver-operating characteristic analysis revealed a mean cutoff ADC value ≤ 1.397 × 10-3 mm2/s for aCPP (sensitivity = 0.667, specificity = 0.923). Multiple linear regression analysis demonstrated that both mean ADC (ß = - 0.455, p = 0.005) and tumor volume (ß = 0.513, p = 0.002) were correlated with WHO grade (adjusted R2 = 0.520, p = 0.005). Kaplan-Meier curve analysis identified poorer survival in patients with WHO grade 2 and 3 tumors than in those with WHO grade 1 disease (p = 0.049 and p = 0.012, respectively). A mean ADC ≤ 1.397 × 10-3 mm2/s (p = 0.001) and tumor volume 21.05 ml (p = 0.031) predicted significantly poorer survival. CONCLUSION: Mean ADC and tumor volume were correlated with WHO grade of choroid plexus tumors. A lower ADC value and a larger tumor volume predicted a poorer prognosis.


Assuntos
Neoplasias do Plexo Corióideo/patologia , Imagem de Difusão por Ressonância Magnética , Adolescente , Adulto , Feminino , Humanos , Masculino , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga Tumoral
5.
Transpl Infect Dis ; 19(4)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28474756

RESUMO

We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post-mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide/cirurgia , Transtornos Parkinsonianos/diagnóstico por imagem , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Encéfalo/patologia , Evolução Fatal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/etiologia , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Cerebral/patologia
6.
Pathol Int ; 66(12): 701-705, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27714938

RESUMO

We present a rare case of giant cell-rich solitary fibrous tumor (SFT) arising at the left external auditory canal in a 31-year-old woman. The tumor was well-circumscribed and composed of spindle-shaped cells with abundant collagenous bands. Scattered multinucleate giant cells were observed, some of which lined pseudovascular spaces. Although a focal mild-hypercellular area was observed, mitoses were rare and necrosis was absent. Interstitial mast cells were scattered, especially in the hypercellular area. Immunohistochemically, CD34, vimentin, and Bcl-2 presented diffuse positivity. Moreover, both mononuclear spindle cells and multinucleate cells showed nuclear STAT6 positivity, while NAB2-STAT6 fusion gene could not be detected by reverse transcription polymerase chain reaction using formalin-fixed specimen. These findings suggest the pathological diagnosis of giant cell-rich SFT, previously known as giant cell angiofibroma, which is a rare variant of SFT with multinucleate giant cells and occurs predominantly in orbital region. Although giant cell-rich SFTs of extra-orbital sites have been reported, to our knowledge, this is the first case arising in the external auditory canal. Giant cell-rich SFT should be considered as a differential diagnosis of spindle cell lesion with multinucleate giant cells, and STAT6 immunohistochemistry should be performed to distinguish this rare tumor from other mesenchymal neoplasms.


Assuntos
Angiofibroma/diagnóstico , Meato Acústico Externo/patologia , Tumores Fibrosos Solitários/patologia , Adulto , Angiofibroma/patologia , Biomarcadores Tumorais , Feminino , Células Gigantes , Humanos , Imuno-Histoquímica , Fator de Transcrição STAT6/metabolismo , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/fisiopatologia
7.
Brain Tumor Pathol ; 33(4): 237-247, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27624470

RESUMO

Meningioma is the most common intracranial tumor, arising from arachnoid cells of the meninges. Monosomy 22 and inactivating mutations of NF2 are well-known genetic alterations of meningiomas. More recently, mutations in TRAF7, AKT1, KLF4, SMO, and PIK3CA were identified by next-generation sequencing. We here reviewed 553 meningiomas for the mutational patterns of the six genes. NF2 aberration was observed in 55 % of meningiomas. Mutations of TRAF7, AKT1, KLF4, PIK3CA, and SMO were identified in 20, 9, 9, 4.5, and 3 % of cases, respectively. Altogether, 80 % of cases harbored at least one of the genetic alterations in these genes. NF2 alterations and mutations of the other genes were mutually exclusive with a few exceptions. Clinicopathologically, tumors with mutations in TRAF7/AKT1 and SMO shared specific features: they were located in the anterior fossa, median middle fossa, or anterior calvarium, and most of them were meningothelial or transitional meningiomas. TRAF7/KLF4 type meningiomas showed different characteristics in that they occurred in the lateral middle fossa and median posterior fossa as well as anterior fossa and median middle fossa, and contained a secretory meningioma component. We also discuss the mutational hotspots of these genes and other genetic/cytogenetic alterations contributing to tumorigenesis or progression of meningiomas.


Assuntos
Estudos de Associação Genética , Neoplasias Meníngeas/genética , Meningioma/genética , Transtornos Cromossômicos , Cromossomos Humanos Par 22 , Classe I de Fosfatidilinositol 3-Quinases , Progressão da Doença , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/metabolismo , Meningioma/patologia , Mosaicismo , Mutação , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Base do Crânio/metabolismo , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo
8.
Mod Pathol ; 29(7): 708-16, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27102344

RESUMO

Recent genetic analyses using next-generation sequencers have revealed numerous genetic alterations in various tumors including meningioma, which is the most common primary brain tumor. However, their use as routine laboratory examinations in clinical applications for tumor genotyping is not cost effective. To establish a clinical sequencing system for meningioma and investigate the clinical significance of genotype, we retrospectively performed targeted amplicon sequencing on 103 meningiomas and evaluated the association with clinicopathological features. We designed amplicon-sequencing panels targeting eight genes including NF2 (neurofibromin 2), TRAF7, KLF4, AKT1, and SMO. Libraries prepared with genomic DNA extracted from PAXgene-fixed paraffin-embedded tissues of 103 meningioma specimens were sequenced using the Illumina MiSeq. NF2 loss in some cases was also confirmed by interphase-fluorescent in situ hybridization. We identified NF2 loss and/or at least one mutation in NF2, TRAF7, KLF4, AKT1, and SMO in 81 out of 103 cases (79%) by targeted amplicon sequencing. On the basis of genetic status, we categorized meningiomas into three genotype groups: NF2 type, TRAKLS type harboring mutation in TRAF7, AKT1, KLF4, and/or SMO, and 'not otherwise classified' type. Genotype significantly correlated with tumor volume, tumor location, and magnetic resonance imaging findings such as adjacent bone change and heterogeneous gadolinium enhancement, as well as histopathological subtypes. In addition, multivariate analysis revealed that genotype was independently associated with risk of recurrence. In conclusion, we established a rapid clinical sequencing system that enables final confirmation of meningioma genotype within 7 days turnaround time. Our method will bring multiple benefits to neuropathologists and neurosurgeons for accurate diagnosis and appropriate postoperative management.


Assuntos
Genômica , Genótipo , Neoplasias Meníngeas/genética , Meningioma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Mutação , Neurofibromina 2/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor Smoothened/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Adulto Jovem
9.
Am J Surg Pathol ; 40(8): 1031-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26927892

RESUMO

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor that can affect virtually any region of the body. SFT/HPC of the thoracic cavity and soft tissue has been histologically considered a single biological entity termed SFT; in fact, NAB2-STAT6 gene fusion was recently identified in both diseases. In contrast, meningeal SFT and HPC still need to be investigated in detail with regard to gene fusion variants. The aim of this study was to verify the frequency of NAB2-STAT6 fusion and the relationship between fusion variants and clinicopathologic findings of SFT/HPC, especially meningeal SFT/HPC. We examined the NAB2-STAT6 fusion by reverse transcription polymerase chain reaction with 4 cases of meningeal SFT and 13 cases of meningeal HPC. NAB2-STAT6 fusion transcripts were identified in 12 of 17 cases, including NAB2ex6-STAT6ex17 (4/17, 24%), NAB2ex6-STAT6ex16 and NAB2ex4-STAT6ex2 (3/17, 18%, respectively), and NAB2ex5-STAT6ex16 (2/17, 12%). Three cases showed a pseudopapillary pattern, and 2 of them carried NAB2ex6-STAT6ex17. In addition, our meta-analysis revealed that the major fusion variant in meningeal SFT/HPC was NAB2ex6-STAT6ex16/17 (29/54, 54%), which was also common in soft tissue and intraperitoneum/retroperitoneum but rare in thoracic SFT. Fusion variant significantly correlated with age and histologic diagnosis in meningeal SFT/HPC but not with prognosis. Our results represented that meningeal SFT and HPC were in a single biological spectrum with NAB2-STAT6 gene fusion as was nonmeningeal SFT and further confirmed the organ-specific tumorigenic process and morphologic differences on the basis of fusion variants in meningeal SFT/HPC.


Assuntos
Neoplasias Meníngeas/genética , Meningioma/genética , Proteínas Repressoras/genética , Fator de Transcrição STAT6/genética , Humanos , Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Eur J Nucl Med Mol Imaging ; 43(8): 1469-76, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26841941

RESUMO

PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose
11.
Brain Tumor Pathol ; 33(1): 63-70, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26614252

RESUMO

Astroblastoma is a rare neuroepithelial neoplasm of unknown origin, usually occurring in children and young adults. Here we report a case of astroblastoma with uncommon features in an 18-year-old female. The tumor was a well-circumscribed cystic and solid mass with marked gadolinium enhancement in the right frontal lobe. Cytological examination showed polarized monopolar cells with diminished cohesiveness. Tumor cells possessed eccentric round to oval nuclei with abundant eosinophilic cytoplasm, sometimes having cytoplasmic processes. Histopathologically, the tumor showed perivascular pseudorosettes with prominent vascular sclerosis. Foam cells were frequently infiltrated around blood vessels and among tumor cells. In some areas, a solid growth pattern of plump tumor cells with abundant inclusion-like eosinophilic cytoplasm showing rhabdoid appearance was observed. The immunohistochemical study revealed strong and diffuse positivity for vimentin and epithelial membrane antigen. Tumor cells were focally positive for glial fibrillary acidic protein and cytokeratin AE1/AE3. Nuclear immunoreactivity for INI1 protein was evident. The Ki-67 labeling index was 10.8%. This tumor was finally diagnosed as low-grade astroblastoma and the patient had no evidence of recurrence without postoperative radiotherapy or chemotherapy during the last 6 months of follow-up. This report describes novel cytological, histopathological, and immunohistochemical features of the rare tumor.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/ultraestrutura , Feminino , Seguimentos , Proteína Glial Fibrilar Ácida/análise , Humanos , Queratinas/análise , Antígeno Ki-67/análise , Mucina-1/análise , Gradação de Tumores , Neoplasias Neuroepiteliomatosas/cirurgia , Neoplasias Neuroepiteliomatosas/ultraestrutura , Tumor Rabdoide , Resultado do Tratamento , Vimentina/análise
12.
Intern Med ; 52(18): 2051-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24042511

RESUMO

Solid-pseudopapillary neoplasms (SPN) are rare pancreatic tumors. The etiology of SPN involves mutations in the gene that encodes ß-catenin (CTNNB1). We herein report the case of a 23-year-old woman with a large SPN with proliferating tumor cells that displayed both solid and pseudo-papillary patterns. The simultaneous nuclear accumulation and loss of membrane localization of ß-catenin and E-cadherin was specifically observed in the tumor cells. Further, the tumor cells were shown to harbor a missense mutation in exon 3 of CTNNB1. We also present a review of the literature describing the clustering of CTNNB1 mutations in patients with SPN.


Assuntos
Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Caderinas/metabolismo , Carcinoma Papilar/diagnóstico , Núcleo Celular/metabolismo , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Neoplasias Pancreáticas/diagnóstico , Adulto Jovem
13.
Neuro Oncol ; 15(7): 853-64, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23539121

RESUMO

BACKGROUND: CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. METHODS: First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. RESULTS: Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. CONCLUSIONS: To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose , Proliferação de Células , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neoplasias Meníngeas/prevenção & controle , Meningioma/patologia , Receptores de Superfície Celular/metabolismo , Adulto , Idoso , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Adulto Jovem
14.
Brain Tumor Pathol ; 30(3): 167-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23180004

RESUMO

Recent progress in molecule-targeting therapy may yield personalized therapeutic strategies for patients with metastatic brain tumors (MBT), the most frequently encountered intracranial tumors. For this purpose, we investigated the molecular expression profile of MBT to establish the pathological basis for personalized diagnosis. We studied 166 MBT specimens including 70 cases of lung cancer and 34 cases of breast cancer, and performed immunostaining for EGFR, COX-2, and O-6-methylguanine-DNA methyltransferase (MGMT), among others, which could be target molecules for therapeutic agents or enable prediction of drug efficacy. Loss of MGMT expression was observed in approximately 20-40% of MBT derived from lung, breast, and gastrointestinal cancers, indicating the possibility of treatment of MBT patients with temozolomide. In addition, MBT expressed a variety of receptor tyrosine kinases, for example EGFR and HER2, and signal transduction molecules, for example phospho-mTOR and COX-2, irrespective of tumor origin, enabling individualized medication with molecule-targeting drugs. We also identified alteration of molecular expression profile in 4 MBT cases during recurrence. Our results not only reveal the molecular characteristics of MBT but also suggest the possibility of potent personalized medicine for MBT patients.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Metilases de Modificação do DNA/análise , Enzimas Reparadoras do DNA/análise , Regulação Neoplásica da Expressão Gênica , Terapia de Alvo Molecular , Medicina de Precisão , Proteínas Supressoras de Tumor/análise , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Receptores ErbB/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Temozolomida
15.
Med Oncol ; 29(4): 2824-30, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22403002

RESUMO

Pancreatic adenocarcinoma is a lethal disease that often develops a desmoplastic reaction in tumor stroma. In general, desmoplasia is thought to promote tumor growth. However, its molecular pathology and prognostic potential have not been fully investigated. Here, we investigate 26 cases of pancreatic ductal adenocarcinoma and examine the clinicopathological association between survival and expression levels of several molecular markers for stromal cells. These include alpha-smooth muscle actin (SMA) and platelet-derived growth factor (PDGF) receptor ß (PDGFRß). Both are markers of activated fibroblasts or pancreatic stellate cells (PSCs) that play an important role in desmoplasia. The staining patterns of both molecular markers were not uniform, so we categorized them into 3 grades (high, middle, and low) according to intensity. Interestingly, Kaplan-Meier analysis revealed that higher expression of PDGFRß matched shorter prognosis (p=0.0287, log-rank test) as well as lymphatic invasion and lymph node metastasis, whereas SMA did not (p=0.6122). Our results suggest the prognostic potential of cancer stroma via PDGF-B signaling. Regulation of PDGF-B-associated signaling crosstalk between cancer cells and stroma cells, therefore, may indicate a possible therapeutic target for desmoplastic malignant tumors such as pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/mortalidade , Neoplasias Pancreáticas/mortalidade , Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise , Actinas/análise , Adenocarcinoma/química , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologia , Prognóstico , Taxa de Sobrevida
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