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1.
Nat Commun ; 8(1): 2177, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29238042

RESUMO

The original version of this article contained an error in Fig. 3. The calculated patterns of quasiparticle interference in the figure were incorrect due to the wrong Wannier transformation in the calculation. This correction does not affect the discussion or the conclusion of the article.

2.
Nat Commun ; 8(1): 976, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29042547

RESUMO

A bulk superconductor possessing a topological surface state at the Fermi level is a promising system to realise long-sought topological superconductivity. Although several candidate materials have been proposed, experimental demonstrations concurrently exploring spin textures and superconductivity at the surface have remained elusive. Here we perform spectroscopic-imaging scanning tunnelling microscopy on the centrosymmetric superconductor ß-PdBi2 that hosts a topological surface state. By combining first-principles electronic-structure calculations and quasiparticle interference experiments, we determine the spin textures at the surface, and show not only the topological surface state but also all other surface bands exhibit spin polarisations parallel to the surface. We find that the superconducting gap fully opens in all the spin-polarised surface states. This behaviour is consistent with a possible spin-triplet order parameter expected for such in-plane spin textures, but the observed superconducting gap amplitude is comparable to that of the bulk, suggesting that the spin-singlet component is predominant in ß-PdBi2.Although several materials have been proposed as topological superconductors, spin textures and superconductivity at the surface remain elusive. Here, Iwaya et al. determine the spin textures at the surface of a superconductor ß-PdBi2 and find the superconducting gap opening in all spin-polarised surface states.

4.
Nat Commun ; 7: 11747, 2016 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-27230420

RESUMO

The central issue in the physics of cuprate superconductivity is the mutual relationship among superconductivity, pseudogap and broken-spatial-symmetry states. A magnetic field B suppresses superconductivity, providing an opportunity to investigate the competition among these states. Although various B-induced electronic superstructures have been reported, their energy, spatial and momentum-space structures are unclear. Here, we show using spectroscopic-imaging scanning tunnelling microscopy on Bi2Sr2CaCu2O8+δ that there are two distinct B-induced electronic superstructures, both being localized in the vortex core but appearing at different energies. In the low-energy range where the nodal Bogoliubov quasiparticles are well-defined, we observe the so-called vortex checkerboard that we identify as the B-enhanced quasiparticle interference pattern. By contrast, in the high-energy region where the pseudogap develops, the broken-spatial-symmetry patterns that pre-exist at B=0 T is locally enhanced in the vortex core. This evidences the competition between superconductivity and the broken-spatial-symmetry state that is associated with the pseudogap.

5.
Br J Cancer ; 112(4): 739-44, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25628093

RESUMO

BACKGROUND: High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers. METHODS: Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters. RESULTS: Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P<0.01). In addition, negative HtrA2 expression was identified as an independent worse prognostic factor for progression-free survival and overall survival by multivariate analyses. Furthermore, HtrA2 downregulation modulated sensitivity to platinum in serous ovarian cancer cells in vitro. CONCLUSIONS: HtrA2 expression was a predictor for sensitivity to chemotherapy, and could be a candidate of molecular target in the treatment of high-grade serous ovarian cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/tratamento farmacológico , Proteínas Mitocondriais/fisiologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Serina Endopeptidases/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Feminino , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Resultado do Tratamento
6.
Br J Cancer ; 110(12): 2881-6, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24853184

RESUMO

BACKGROUND: X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti-apoptotic proteins leading to chemoresistance in several cancers. The aim of this study is to evaluate the impact of XIAP expression upon ovarian clear cell carcinoma (CCC) that has a platinum-resistant phenotype. METHODS: Tissue microarrays made from 90 CCC patients were analysed for immunohistochemical expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines were evaluated whether XIAP silencing could modulate sensitivity to platinum agent in vitro. RESULTS: High XIAP expression was observed in 30 (33%) of 90 CCC cases, and was associated with c-Met (<0.01) and Bcl-XL (<0.01) expression. Cases with high XIAP expression had lower response rate to primary platinum-based chemotherapy (10% vs 65%, P=0.02). In stages II-IV tumours, high XIAP expression was related with worse progression-free survival (PFS, P=0.02). Furthermore, high XIAP expression was identified as an independent worse prognostic factor for PFS and overall survival. Finally, downregulation of XIAP using XIAP-specific small interfering RNA increased sensitivity to cisplatin in human cancer cells derived from CCC. CONCLUSIONS: X-chromosome-linked inhibitor of apoptosis expression was correlated with chemoresistance of primary chemotherapy, and identified as a prognostic marker for CCC. X-chromosome-linked inhibitor of apoptosis could be a candidate for new therapeutic target in CCC.


Assuntos
Adenocarcinoma de Células Claras/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Proteínas Proto-Oncogênicas c-met/biossíntese , Interferência de RNA , RNA Interferente Pequeno , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/biossíntese , Proteína bcl-X/biossíntese
7.
Phys Rev Lett ; 111(12): 126104, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-24093280

RESUMO

Li(x)CoO(2) exhibits intriguing electronic properties due to a strong electron correlation and complex interplay between Co and Li ions. However, fundamental understanding of the nanoscale distribution of Li ions and its effect on the electronic properties remains unclear. We use scanning tunneling microscopy and density functional theory to elucidate the degree of Li(x)CoO(2) surface electronic state modification that can be achieved by Li ordering. The surface Li ions are highly mobile and preferentially form a (1 × 1) hexagonal lattice, whereas the surface CoO(2) layer shows metallic and insulating phases, indicating the coexistence of ordered and disordered Li ions in the subsurface layer. These results provide evidence of novel electronic properties produced by spatially inhomogeneous Li-ordering patterns.

8.
J Thromb Haemost ; 10(10): 2137-48, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22905905

RESUMO

BACKGROUND: We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV [H12])-coated, ADP-encapsulated liposome (H12-[ADP]-liposome) that accumulates at bleeding sites via interaction with activated platelets via glycoprotein IIb-IIIa and augments platelet aggregation by releasing ADP. OBJECTIVE: To evaluate the efficacy of H12-(ADP)-liposomes for treating liver hemorrhage in rabbits with acute thrombocytopenia. METHODS: Thrombocytopenia (platelets < 50 000 µL(-1)) was induced in rabbits by repeated blood withdrawal (100 mL kg(-1) in total) and isovolemic transfusion of autologous washed red blood cells. H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP, ADP liposomes with PPP or H12-(PBS)-liposomes/PPP, were administered to the thrombocytopenic rabbits, and liver hemorrhage was induced by penetrating liver injury. RESULTS: Administration of H12-(ADP)-liposomes and of PRP rescued all thrombocytopenic rabbits from liver hemorrhage as a result of potent hemostasis at the liver bleeding site, although rabbits receiving PPP or ADP liposomes showed 20% survival in the first 24 h. Administration of H12-(ADP)-liposomes and of PRP suppressed both bleeding volume and time from the site of liver injury. H12-(phosphate-buffered saline)-liposomes lacking ADP also improved rabbit survival after liver hemorrhage, although their hemostatic effect was weaker. In rabbits with severe thrombocytopenia (25 000 platelets µL(-1)), the hemostatic effects of H12-(ADP)-liposomes tended to be attenuated as compared with those of PRP treatment. Histologic examination revealed that H12-(ADP)-liposomes accumulated at the bleeding site in the liver. Notably, neither macrothombi nor microthrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. CONCLUSIONS: H12-(ADP)-liposomes appear to be a safe and effective therapeutic tool for acute thrombocytopenic trauma patients with massive bleeding.


Assuntos
Difosfato de Adenosina/administração & dosagem , Fibrinogênio/administração & dosagem , Hemorragia/tratamento farmacológico , Hemostáticos/administração & dosagem , Hepatopatias/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Trombocitopenia/tratamento farmacológico , Ferimentos Penetrantes/tratamento farmacológico , Doença Aguda , Animais , Testes de Coagulação Sanguínea , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Modelos Animais de Doenças , Estudos de Viabilidade , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/patologia , Hemostasia/efeitos dos fármacos , Lipossomos , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Microscopia Imunoeletrônica , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Coelhos , Trombocitopenia/sangue , Trombocitopenia/complicações , Trombocitopenia/patologia , Fatores de Tempo , Ferimentos Penetrantes/sangue , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/patologia
9.
Nat Commun ; 2: 558, 2011 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-22127054

RESUMO

Graphitic systems have an electronic structure that can be readily manipulated through electrostatic or chemical doping, resulting in a rich variety of electronic ground states. Here we report the first observation and characterization of electronic stripes in the highly electron-doped graphitic superconductor, CaC(6), by scanning tunnelling microscopy and spectroscopy. The stripes correspond to a charge density wave with a period three times that of the Ca superlattice. Although the positions of the Ca intercalants are modulated, no displacements of the carbon lattice are detected, indicating that the graphene sheets host the ideal charge density wave. This provides an exceptionally simple material-graphene-as a starting point for understanding the relation between stripes and superconductivity. Furthermore, our experiments suggest a strategy to search for superconductivity in graphene, namely in the vicinity of striped 'Wigner crystal' phases, where some of the electrons crystallize to form a superlattice.


Assuntos
Carbono/química , Grafite/química , Condutividade Elétrica , Microscopia de Tunelamento , Nanoestruturas/química , Nanotecnologia
10.
Phys Rev Lett ; 99(5): 057208, 2007 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-17930789

RESUMO

The local spectroscopic signatures of metamagnetic criticality in Sr(3)Ru(2)O(7) were explored using scanning tunneling microscopy (STM). Singular features in the tunneling spectrum were found close to the Fermi level, as would be expected in a Stoner picture of itinerant electron metamagnetism. These features showed a pronounced magnetic field dependence across the metamagnetic critical point, which cannot be understood in terms of a naive Stoner theory. In addition, a pseudogap structure was observed over several tens of meV, accompanied by a c(2 x 2) superstructure in STM images. This result represents a new electronic ordering at the surface in the absence of any measurable surface reconstruction.

11.
Phys Rev Lett ; 93(9): 097004, 2004 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-15447131

RESUMO

The spatial variation of electronic states was imaged in the lightly doped Mott insulator Ca(2-x)NaxCuO2Cl2 using scanning tunneling microscopy or spectroscopy. We observed nanoscale domains with a high local density of states within an insulating background. The observed domains have a characteristic length scale of 2 nm (approximately 4-5a, a: lattice constant) with preferred orientations along the tetragonal [100] direction. We argue that such spatially inhomogeneous electronic states are inherent to slightly doped Mott insulators and play an important role for the insulator to metal transition.

13.
Cancer Res ; 61(15): 5707-9, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11479202

RESUMO

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown recently to be carcinogenic, but little is currently known about the molecular mechanism of TCDD affecting cell proliferation and carcinogenesis. In this report, we demonstrate that TCDD suppresses the expression of the checkpoint protein, Mad2. Suppression of Mad2 was also observed in aryl hydrocarbon receptor-deficient mouse embryonic fibroblasts, suggesting that TCDD suppresses Mad2 by a novel TCDD receptor signaling mechanism. In addition, HeLa cells treated with TCDD failed to arrest in mitosis after nocodazole treatment. The Mad2 protein plays a significant role in accurate chromosome segregation in mitotic cells. Our data suggest that TCDD may increase chromosomal instability through the suppression of Mad2 expression.


Assuntos
Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Carcinógenos Ambientais/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/fisiologia , Animais , Proteínas de Ligação ao Cálcio/biossíntese , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular , Cruzamentos Genéticos , Poluentes Ambientais/toxicidade , Feminino , Células HeLa , Humanos , Proteínas Mad2 , Camundongos , Camundongos Endogâmicos C57BL , Mitose/efeitos dos fármacos , Mitose/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas Repressoras
14.
Enantiomer ; 5(3-4): 369-75, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11126877

RESUMO

Enantiomeric ratio of hyoscyamine from Scopolia extract was determined by chiral HPLC-CD analysis. It was found that circular dichroism (CD) detection allowed the analysis of the sample without any special pretreatment whereas UV detection required an ammonia-ether extraction. To obtain a shorter analysis time for the determination, reversed-phase HPLC-CD analysis was applied by using a g-factor calibration curve (EE% vs. CD/UV). The analysis time was shortened from 35 to 18 min. EE% values obtained were consistent with those by chiral HPLC analysis.


Assuntos
Atropina/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Plantas Medicinais/química , Atropina/química , Calibragem , Dicroísmo Circular , Espectrofotometria Ultravioleta , Estereoisomerismo
15.
Pathol Int ; 50(10): 858-62, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11107060

RESUMO

An 18-year-old man who suffered from panniculitis involving the entire left lower limb after exertional rhabdomyolysis is reported. A high fever (>39 degrees C) and leukocytosis (>20,000/microL) persisted for 1 week, and his general status deteriorated rapidly into pre-disseminated intravascular coagulation, complicated by pleural effusion and prolonged clotting time. His condition was dramatically improved by steroid pulse therapy and he has remained in good health for the 20 months since discharge. Histologic examination of subcutaneous tissue from the swollen left lower limb revealed pleomorphic small, medium or large lymphocytes, macrophages and neutrophils infiltrating the edematous subcutaneous adipose tissue in a lobular panniculitis-like pattern. The majority of inflammatory cells were T lymphocytes, with equal proportions of CD4+ and CD8+ cells. As polymerase chain reaction did not show bands suggesting T cell receptor gamma gene rearrangement, the proliferation of T lymphocytes was considered to be polyclonal. The T lymphocytes also expressed Fas ligand, suggesting the involvement of Fas-mediated cytotoxicity. This case may represent a new category of cytophagic histiocytic panniculitis induced by exertional rhabdomyolysis.


Assuntos
Paniculite Nodular não Supurativa/patologia , Esforço Físico , Rabdomiólise/patologia , Adolescente , Antibacterianos/uso terapêutico , Relação CD4-CD8 , Proteína Ligante Fas , Histiócitos/patologia , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Metilprednisolona/administração & dosagem , Paniculite Nodular não Supurativa/tratamento farmacológico , Paniculite Nodular não Supurativa/etiologia , Pulsoterapia , Rabdomiólise/complicações , Pele/metabolismo , Pele/patologia , Linfócitos T/metabolismo , Linfócitos T/patologia
16.
Phys Rev Lett ; 85(17): 3716-9, 2000 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-11030989

RESUMO

We studied the conduction noise spectrum in the vortex state of a high-temperature superconductor, Bi(2)Sr(2)CaCu(2)O(y), subject to a uniform driving force. Two characteristic features, a broad-band noise (BBN) and a narrow-band noise (NBN), were observed in the vortex-solid phase. The origin of the large BBN was determined to be plastic motion of the vortices, whereas the NBN was found to originate from the washboard modulation of the translational velocity of the driven vortices. We believe this to be the first observation of washboard noise of dc driven vortices in any superconductor.

17.
Virchows Arch ; 437(5): 508-13, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11147171

RESUMO

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.


Assuntos
Adenocarcinoma/metabolismo , Núcleo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias Gástricas/metabolismo , Transativadores , Adenocarcinoma/patologia , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias Gástricas/patologia , Fatores de Tempo , beta Catenina
18.
Neurosurgery ; 44(3): 589-95; discussion 595-6, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10069596

RESUMO

OBJECTIVE: The aim of the present study was to determine whether neurotrophic factors (NTFs) exogenously administered in fibrin glue assisted cut dorsal root axons of adult rats to regenerate into the spinal cord. METHODS: Rats received intraspinal implants of fibrin glue containing neurotrophin-3, brain-derived NTF, ciliary NTF, or Dulbecco's modified Eagle's medium (control) into left dorsal quadrant cavities aspirated in the lumbar enlargement. The transected L5 dorsal root stump was placed at the bottom of the lesion cavity and was secured between the fibrin glue and the spinal cord. Regenerated dorsal root axons were subsequently labeled with immunohistochemical methods to demonstrate those that contained calcitonin gene-related peptide. RESULTS: Calcitonin gene-related peptide-immunoreactive dorsal root axons regenerated across the dorsal root-spinal cord interface of rats with fibrin glue containing neurotrophin-3, brain-derived NTF, or ciliary NTF, entered the spinal cord, and frequently arborized within clusters of motoneuronal cell bodies. Only a few axons regenerated into the spinal cord of animals with fibrin glue implants that lacked NTF, and their growth within the spinal cord was extremely limited. The results of quantitative studies confirmed these observations. CONCLUSION: Our results indicate that neurotrophin-3, brain-derived NTF, and ciliary NTF enhance dorsal root regeneration into spinal cord and that fibrin glue is an effective medium for intraspinal delivery of NTF. This method of delivering NTF may therefore provide a strategy for restoring injured spinal reflex arcs.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Adesivo Tecidual de Fibrina/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa/fisiologia , Medula Espinal/metabolismo , Raízes Nervosas Espinhais/metabolismo , Animais , Feminino , Neurônios Motores/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Biosci Biotechnol Biochem ; 62(6): 1216-24, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-27388647

RESUMO

An intramolecular hydrogen bond between NH•••O2N in insecticide, imidacloprid (1), and its nitromethylene analog 15 was proved by NMR and IR spectra. That electron delocalization over their planar moieties was disrupted by alkylation at the imidazolidine nitrogen atom is demonstrated by the hypsochromic shifts in UV and deshielding effect in NMR spectra. Interestingly, the N-alkyl derivatives (C1-5) had greater water solubility than 1, although increasing alkyl chain length decreased the solubility. The hydrophilicity of the alkyl derivatives would result from remote charge heads being formed as a result of the conjugation disruption by alkylation, while the hydrophobicity of 1 could be ascribed to the charge distribution over the conjugated system coupled with the intramolecular H-bonding. The greater water solubility of 15 than 1 and contrastively small solubility of the cyanoimine analogue are discussed based on the difference in their steric crowding.

20.
J Hepatol ; 26(6): 1266-73, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9210613

RESUMO

BACKGROUND/AIMS: Ubiquitin covalently attaches to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tumors. To clarify the change in protein metabolism during hepatocarcinogenesis, we studied ubiquitin immunoreactivity in hepatocellular carcinomas (HCCs) and precancerous lesions using immunohistochemistry and immunoblot analysis. METHODS: A total of 72 HCCs (37 advanced, 19 early, 16 early-advanced (advanced HCC component in early HCC nodule) type HCCs) and 18 precancerous lesions (8 atypical adenomatous hyperplasias (AAHs), 10 adenomatous hyperplasias (AHs)) were studied immunohistochemically. Immunoblot analysis was also performed in advanced HCC and early HCC cases. RESULTS: Non-tumorous hepatocytes were either immunonegative or weakly stained in their nuclei. Advanced HCCs showed strong immunoreactivity in most cases, while early HCCs showed relatively weaker immunoreactivity. In 14 of 16 early-advanced type tumors, the inner portion of the nodules, which corresponds to advanced HCC, showed stronger immunoreactivity than the outer low-grade portion. In 8 of 8 AAHs and 7 of 10 AHs, positive but weak staining was found. Immunoblot analysis showed an increase in 42 kDa ubiquitinated protein(s) in 8 of 16 advanced HCC cases (50%) and in 1 of 6 early HCC cases (16.7%), as well as an increase in several other bands in tumor tissues. CONCLUSIONS: The intensity of ubiquitin staining appeared to increase in a stepwise manner from AH to advanced HCC, and the results suggest a possible correlation between changes in the ubiquitinated proteins and multistep hepatocarcinogenesis.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Lesões Pré-Cancerosas/patologia , Ubiquitinas/análise , Adenoma/patologia , Proteínas de Choque Térmico HSP72 , Proteínas de Choque Térmico/análise , Humanos , Hiperplasia , Immunoblotting , Imuno-Histoquímica , Fígado/citologia , Cirrose Hepática/patologia , Estadiamento de Neoplasias , Valores de Referência
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