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2.
Sci Rep ; 13(1): 22883, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38129553

RESUMO

Boron neutron capture therapy (BNCT) is a high-dose-intensive radiation therapy that has gained popularity due to advancements in accelerator neutron sources. To determine the dose for BNCT, it is necessary to know the difficult-to-determine boron concentration and neutron fluence. To estimate this dose, we propose a method of measuring the prompt γ-rays (PGs) from the boron neutron capture reaction (BNCR) using a Compton camera. We performed a fundamental experiment to verify basic imaging performance and the ability to discern the PGs from 511 keV annihilation γ-rays. A Si/CdTe Compton camera was used to image the BNCR and showed an energy peak of 478 keV PGs, separate from the annihilation γ-ray peak. The Compton camera could visualize the boron target with low neutron intensity and high boron concentration. This study experimentally confirms the ability of Si/CdTe Compton cameras to image BNCRs.


Assuntos
Terapia por Captura de Nêutron de Boro , Compostos de Cádmio , Pontos Quânticos , Terapia por Captura de Nêutron de Boro/métodos , Boro/uso terapêutico , Telúrio , Nêutrons
3.
Br J Surg ; 107(9): 1192-1198, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32335898

RESUMO

BACKGROUND: The right hepatic venous system consists of the right hepatic vein (RHV) and inferior RHVs (IRHVs). When the right posterior section is used as a graft for liver transplantation, understanding variations and relationships between the RHV and IRHVs is critical for graft venous return and hepatic vein reconstruction. This study aimed to evaluate variations in the hepatic veins and the relationships between them. METHODS: The medical records and CT images of patients who underwent hepatectomy as liver donors were assessed retrospectively. The relationship between the veins was evaluated by three-dimensional CT. RESULTS: The configuration of the posterior section was classified into one of eight types based on the RHV and IRHVs in 307 patients. Type 1a (103 of 307), type 1b (139 of 307) and type 2a (40 of 307) accounted for 91·9 per cent of the total. The diameter of the RHV extending towards the inferior vena cava had a significant inverse correlation with that of the IRHV (r2  = -0·615, P < 0·001). Type 1a, which had no IRHVs, had the RHV with the largest diameter; conversely, type 2a, which had a large IRHV, had the RHV with the smallest diameter. CONCLUSION: The hepatic venous system of the right posterior section was classified into eight types, with an inverse relationship between RHV and IRHV sizes. This information is useful for segment VII resection or when the right liver is used as a transplant graft.


ANTECEDENTES: El sistema venoso hepático derecho consiste en la vena hepática derecha (right hepatic vein, RHV) y las RHVs inferiores (IRHVs). Cuando se utiliza la sección posterior derecha hepática como injerto para el trasplante hepático, es fundamental conocer las variaciones e interrelaciones entre la RHV y las IRHVs para el retorno venoso del injerto y la reconstrucción de la vena hepática. El objetivo de este estudio fue determinar las variaciones en las venas hepáticas y sus interrelaciones. MÉTODOS: Se evaluaron retrospectivamente las historias clínicas y las imágenes de la tomografía computarizada de los pacientes que se sometieron a una hepatectomía como donantes vivos para trasplante hepático. La interrelación entre las venas se evaluó mediante imágenes de CT tridimensional. RESULTADOS: La configuración de la sección posterior clasificó a 307 pacientes en base a la RHV y a las IRHVs. Se clasificaron en 8 tipos, de los cuales el Tipo 1a (103/307), el Tipo 1b (139/307) y el Tipo 2a (40/307) representaron el 92% del total. El diámetro de la RHV que se extiende hacia la vena cava inferior presentó una correlación inversa significativa con la de las IRHV (r2: −0,632, P < 0,0001). El diámetro mayor de la RHV se observó en el Tipo 1a, que no presentaba IRHVs; por el contrario, el diámetro más pequeño se observó en el Tipo 2a que presentaba una IRHV grande. CONCLUSIÓN: El sistema venoso hepático de la sección posterior derecha se clasificó en 8 subtipos con una relación inversa entre los tamaños de la RHV y las IRHV. Esta información es útil cuando se practica una resección del segmento 7 o cuando se utiliza el hígado derecho como injerto para el trasplante.


Assuntos
Veias Hepáticas/diagnóstico por imagem , Doadores de Tecidos , Veias Hepáticas/anatomia & histologia , Veias Hepáticas/cirurgia , Humanos , Imageamento Tridimensional , Fígado/irrigação sanguínea , Transplante de Fígado/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
4.
Br J Cancer ; 113(3): 443-52, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26125445

RESUMO

BACKGROUND: The aim of this study was to clarify the role of bone marrow-derived stromal cells (BM-SCs) expressing CD271 in the development of gastric cancer. METHODS: The effect of human BM-SCs on the proliferation and motility of six gastric cancer cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, NUGC-3, and MKN-74, was examined. CD271 expression levels in BM-SCs were analysed by flow cytometry. We also generated a gastric tumour model by orthotopic inoculation of OCUM-2MLN cells in mice that had received transplantation of bone marrow from the CAG-EGFP mice. The correlation between the clinicopathological features of 279 primary gastric carcinomas and CD271 expression in tumour stroma was examined by immunohistochemistry. RESULTS: Numerous BM-SCs infiltrated the gastric tumour microenvironment; CD271 expression was found in ∼25% of BM-SCs. Conditioned medium from BM-SCs significantly increased the proliferation of gastric cancer cell lines. Furthermore, conditioned medium from gastric cancer cells significantly increased the number of BM-SCs, whereas migration of OCUM-12 and NUGC-3 cells was significantly increased by conditioned medium from BM-SCs. CD271 expression in stromal cells was significantly associated with macroscopic type-4 cancers, diffuse-type tumours, and tumour invasion depth. The overall survival of patients (n=279) with CD271-positive stromal cells was significantly worse compared with that of patients with CD271-negative stromal cells. This is the first report of the significance of BM-SCs in gastric cancer progression. CONCLUSIONS: Bone marrow-derived stromal cells might have an important role in gastric cancer progression, and CD271-positive BM-SCs might be a useful prognostic factor for gastric cancer patients.


Assuntos
Medula Óssea/patologia , Carcinoma/patologia , Células-Tronco Mesenquimais/patologia , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos Transgênicos , Microambiente Tumoral
5.
Oncogene ; 34(15): 1949-60, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-24882578

RESUMO

Although CD133 has been considered to be a molecular marker for cancer stem cells, its functional roles in tumorigenesis remain unclear. We here examined the molecular basis behind CD133-mediated signaling. Knockdown of CD133 resulted in the retardation of xenograft tumor growth of colon cancer-derived HT-29 and LoVo cells accompanied by hypophosphorylation of AKT, which diminished ß-catenin/T-cell factor-mediated CD44 expression. As tyrosine residues of CD133 at positions 828 and 852 were phosphorylated in HT-29 and SW480 cells, we further addressed the significance of this phosphorylation in the tumorigenesis of SW480 cells expressing mutant CD133, with substitution of these tyrosine residues by glutamate (CD133-EE) or phenylalanine (CD133-FF). Forced expression of CD133-EE promoted much more aggressive xenograft tumor growth relative to wild-type CD133-expressing cells accompanied by hyperphosphorylation of AKT; however, CD133-FF expression had negligible effects on AKT phosphorylation and xenograft tumor formation. Intriguingly, the tyrosine phosphorylation status of CD133 was closely linked to the growth of SW480-derived spheroids. Using yeast two-hybrid screening, we finally identified receptor-type protein tyrosine phosphatase κ (PTPRK) as a binding partner of CD133. In vitro studies demonstrated that PTPRK associates with the carboxyl-terminal region of CD133 through its intracellular phosphatase domains and also catalyzes dephosphorylation of CD133 at tyrosine-828/tyrosine-852. Silencing of PTPRK elevated the tyrosine phosphorylation of CD133, whereas forced expression of PTPRK reduced its phosphorylation level markedly and abrogated CD133-mediated AKT phosphorylation. Endogenous CD133 expression was also closely associated with higher AKT phosphorylation in primary colon cancer cells, and ectopic expression of CD133 enhanced AKT phosphorylation. Furthermore, lower PTPRK expression significantly correlated with the poor prognosis of colon cancer patients with high expression of CD133. Thus, our present findings strongly indicate that the tyrosine phosphorylation of CD133, which is dephosphorylated by PTPRK, regulates AKT signaling and has a critical role in colon cancer progression.


Assuntos
Antígenos CD/metabolismo , Neoplasias do Colo/metabolismo , Glicoproteínas/metabolismo , Peptídeos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Antígeno AC133 , Animais , Células CACO-2 , Proliferação de Células/fisiologia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Células HT29 , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fosforilação , Transdução de Sinais , beta Catenina/metabolismo
6.
Dis Esophagus ; 27(1): 63-71, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23480452

RESUMO

Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N-status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total number of MLNs including occult MLNs could contribute to evaluating the precise stage of patients with esophageal cancer.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Excisão de Linfonodo , Linfonodos/patologia , Recidiva Local de Neoplasia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
7.
Dis Esophagus ; 27(3): 285-93, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23902537

RESUMO

Both internal and external oxidative stresses act on DNA and can induce carcinogenesis. 8-hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and it leads to transversion mutations and carcinogenesis. 8-OHdG is excision-repaired by 8-OHdG DNA glycosylase (OGG1). The purpose of this study is to clarify the effect of oxidative DNA damage and repair enzymes on esophageal carcinogenesis. The levels of 8-OHdG and OGG1 were immunohistochemically evaluated in resected specimens, including squamous cell carcinoma (SCC) in 97 patients with esophageal cancer. Higher levels of 8-OHdG in normal esophageal epithelium were associated with a higher smoking index (P = 0.0464). The 8-OHdG level was higher in cancerous areas than in normal epithelia (P = 0.0061), whereas OGG1 expression was weaker in cancerous areas than in normal epithelia (P < 0.0001). An increase of OGG1 expression in normal epithelium was observed as 8-OHdG levels increased (P = 0.0011). However, this correlation was not observed in cancerous areas. High OGG1 expression in the cytoplasm was related to deeper tumors (P = 0.0023), node metastasis (P = 0.0065) and stage (P = 0.0019). Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis and its progression.


Assuntos
Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Dano ao DNA , DNA Glicosilases/análise , Desoxiguanosina/análogos & derivados , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Enzimas Reparadoras do DNA/análise , Desoxiguanosina/análise , Epitélio/enzimologia , Neoplasias Esofágicas/genética , Esôfago/enzimologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estresse Oxidativo , Fumar
8.
Transplant Proc ; 45(9): 3432-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24182831

RESUMO

Adult-onset type II citrullinemia (CTLN2), an autosomal recessive disorder caused by a mutation in the SLC25A13 gene, is characterized by increased serum citrulline and ammonia levels. Patients with CTLN2 also display various neuropsychiatric symptoms. Many individuals with CTLN2 are fond of protein-rich and/or lipid-rich foods with an aversion to carbohydrate-rich foods. We herein report two cases of CTLN2 treated with living donor liver transplantation (LDLT) and provide a review of the pertinent literature. Case 1 was a 43-year-old man admitted to our hospital for repetitive episodes of consciousness disturbance. Case 2 was a 37-year-old man admitted to our hospital because of abnormal behavior associated with hyperammonemia. A definitive diagnosis of CTLN2 was accomplished by DNA analysis in both patients, who successfully underwent LDLT using liver segments from donor siblings with confirmed heterozygous gene expression. Case 2 also underwent conservative therapy with arginine and a high-fat, carbohydrate-restricted diet prior to LDLT. Postoperative recovery was uneventful and food was unrestricted in both patients. We also identified 77 cases of CTLN2 in the literature and reviewed them in terms of outcome of both liver transplantation and conservative therapy. The survival rate in patients treated by liver transplantation was 100%, whereas that in patients treated by conservative treatment showed improvement from 39.5% to 76.5% over the years. Liver transplantation is a practical treatment that fundamentally improves patient quality of life after transplantation. However, recent studies have suggested that arginine and sodium pyruvate administration combined with intensive nutritional support is also an effective therapy for CTLN2. Further development of conservative therapy may provide a safer, more affordable alternative to liver transplantation in the near future.


Assuntos
Citrulinemia/terapia , Transplante de Fígado , Adulto , Citrulinemia/cirurgia , Humanos
9.
Br J Cancer ; 106(10): 1668-74, 2012 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-22569001

RESUMO

BACKGROUND: It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma. METHODS: We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines. RESULTS: Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-ß augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown. CONCLUSION: Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma.


Assuntos
Carcinoma de Células em Anel de Sinete/imunologia , Fatores de Transcrição Forkhead/fisiologia , Neoplasias Gástricas/imunologia , Carcinoma de Células em Anel de Sinete/química , Carcinoma de Células em Anel de Sinete/patologia , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/análise , Fatores de Transcrição Forkhead/genética , Humanos , Tolerância Imunológica , Imuno-Histoquímica , RNA Mensageiro/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Linfócitos T Reguladores/imunologia , Evasão Tumoral
10.
Br J Cancer ; 105(12): 1885-93, 2011 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-22068819

RESUMO

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a fundamental process governing not only morphogenesis in multicellular organisms, but also cancer progression. During EMT, epithelial cadherin (E-cadherin) is downregulated while neural cadherin (N-cadherin) is upregulated, referred to as 'cadherin switch'. This study aimed to investigate whether cadherin switch promotes cancer progression in cholangiocarcinoma (CC). METHODS: CC cell lines were examined for migration, invasion, and morphological changes with typical EMT-induced model using recombinant TGF-ß1. The changes in E-cadherin and N-cadherin expression were investigated during EMT. We also examined E-cadherin and N-cadherin expression in resected specimens from extrahepatic CC patients (n=38), and the associations with clinicopathological factors and survival rates. RESULTS: TGF-ß1 treatment activated cell migration, invasion, and fibroblastic morphological changes, especially in extrahepatic CC HuCCT-1 cells. These changes occurred with E-cadherin downregulation and N-cadherin upregulation, that is, cadherin switch. Patients with low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression (P=0.0059). Patients with decreasing E-cadherin and increasing N-cadherin expression had a significantly lower survival rate than patients with increasing E-cadherin and decreasing N-cadherin expression (P=0.017). CONCLUSION: Cadherin switch promotes cancer progression via TGF-ß-induced EMT in extrahepatic CC, suggesting a target for elucidating the mechanisms of invasion and metastasis in extrahepatic CC.


Assuntos
Caderinas/metabolismo , Colangiocarcinoma/patologia , Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta/fisiologia , Idoso , Western Blotting , Proliferação de Células , Colangiocarcinoma/metabolismo , Progressão da Doença , Eletroforese em Gel de Poliacrilamida , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Transdução de Sinais
11.
Allergy ; 64(3): 387-97, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19175598

RESUMO

BACKGROUND: Gene silencing using small interfering RNA (siRNA) is a potent method of specifically knocking down molecular targets. Small interfering RNA is therapeutically promising, however, treatment of allergic diseases with siRNA has not been explored in vivo. The aim of this study was to evaluate therapeutic effects of CD40 siRNA on inhibition of allergic responses. METHODS: Mice sensitized with ovalbumin (OVA) and alum were treated with CD40 siRNA, scrambled siRNA, or phosphate buffer saline (PBS) alone, and then challenged intranasally with OVA. RESULTS: A significant reduction in nasal allergic symptoms was observed in the CD40 siRNA treated OVA-allergic mice compared to the controls of scrambled siRNA and PBS alone, which is correlated with the decrease of local eosinophil accumulation. CD40 siRNA treatment knocked down CD40 expression on dendritic cells (DCs) in vivo and impaired their antigen presenting function. Treatment with CD40 siRNA resulted in inhibition of OVA-specific T cell response and decrease of interleukin-4 (IL-4), IL-5, and interferon-gamma production from T cells stimulated with OVA. Administration of CD40 siRNA also suppressed CD40 expression on B cells, resulting in down-regulation of OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a levels. Additionally, increased regulatory T cells were observed in the CD40 siRNA treated mice. CONCLUSIONS: The present study demonstrates a novel therapeutic use for siRNA in allergy. CD40 siRNA attenuated allergy through inhibition of DC and B cell functions and generation of regulatory T (Treg) cells.


Assuntos
Antígenos CD40/genética , Antígenos CD40/imunologia , Inativação Gênica , Hipersensibilidade/genética , Alérgenos/imunologia , Animais , Linfócitos B/imunologia , Células Dendríticas/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Ativação Linfocitária/imunologia , Teste de Cultura Mista de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Reguladores/imunologia
12.
Oncol Rep ; 17(4): 887-93, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17342332

RESUMO

The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptors. EGFR and other members of the EGFR family have been shown to play significant roles in human cancer cell proliferation and therefore present important molecular targets for the treatment of cancer. The purpose of this study was to examine the effect of the pan-erbB tyrosine kinase inhibitor CI-1033 against esophageal squamous cell carcinoma in vitro and in vivo. We selected 4 human esophageal squamous cell carcinoma cell lines (TT, TE2, TE6, and TE10), and determined their expression of EGFR and HER2. We examined the ability of CI-1033 to inhibit cell growth in vitro and in vivo. EGFR and HER2 were overexpressed in all 4 esophageal cancer cells. We found that CI-1033 could inhibit the growth of esophageal cancer cell lines in a dose-dependent manner with the inhibition of phosphorylation of both MAPK and AKT. The oral administration of CI-1033 exerted a significant antitumor effect on esophageal cancer tumors in athymic nude mice. Our results suggest that CI-1033 effectively inhibits the growth of esophageal squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of both MAPK and AKT. Furthermore, in vivo animal studies of CI-1033 suggest that CI-1033 holds significant clinical potential in esophageal cancer.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Esofágicas/tratamento farmacológico , Morfolinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Animais , Carcinoma de Células Escamosas/enzimologia , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias Esofágicas/enzimologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Morfolinas/administração & dosagem , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Theor Appl Genet ; 114(1): 81-91, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17039346

RESUMO

A linkage map of Chinese cabbage (Brassica rapa) was constructed to localize the clubroot resistance (CR) gene, Crr3. Quantitative trait loci analysis using an F(3) population revealed a sharp peak in the logarithm of odds score around the sequence-tagged site (STS) marker, OPC11-2S. Therefore, this region contained Crr3. Nucleotide sequences of OPC11-2S and its proximal markers showed homology to sequences in the top arm of Arabidopsis chromosome 3, suggesting a synteny between the two species. For fine mapping of Crr3, a number of STS markers were developed based on genomic information from Arabidopsis. We obtained polymorphisms in 23 Arabidopsis-derived STS markers, 11 of which were closely linked to Crr3. The precise position of Crr3 was determined using a population of 888 F(2) plants. Eighty plants showing recombination around Crr3 locus were selected and used for the mapping. A fine map of 4.74 cM was obtained, in which two markers (BrSTS-41 and BrSTS-44) and three markers (OPC11-2S, BrSTS-54 and BrSTS-61) were cosegregated. Marker genotypes of the 21 selected F(2) families and CR tests of their progenies strongly suggested that the Crr3 gene is located in a 0.35 cM segment between the two markers, BrSTS-33 and BrSTS-78.


Assuntos
Brassica rapa/genética , Mapeamento Cromossômico , Genes de Plantas , Doenças das Plantas/genética , Arabidopsis/genética , Marcadores Genéticos , Genoma de Planta , Locos de Características Quantitativas
14.
Eur J Surg Oncol ; 32(10): 1191-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16797159

RESUMO

AIM: Following distal gastrectomy, carcinogenesis has been suggested to result from gastroduodenal reflux. In this study, surgical cases of gastric cancer arising after distal gastrectomy were analyzed clinico-pathologically and the possible link to reflux examined. PATIENTS: Thirty-two patients (24 males, 8 females; mean age, 68.7 years; age range, 33-84 years) with gastric cancer arising in the remnant stomach after gastrectomy (also known as gastric stump cancer) were included in this study. Patients were divided into two groups on the basis of the initial diagnosis (benign or malignant) prompting surgery, and distal gastrectomy reconstruction method (Billroth I or II). RESULTS: The interval between distal gastrectomy and detection of cancer in the remnant stomach of patients treated initially for a benign gastric condition vs. malignancy was 360+/-33.04 and 63+/-19.16 months (median+/-SE), respectively (p<0.0001). However, the benign and malignant groups did not differ significantly in the clinicopathological analysis of their stump cancers. All 10 patients in whom gastric cancer was diagnosed within five years of initial surgery had initially been surgically treated for malignancy. The interval between surgery and detection of gastric cancer in the Billroth I and Billroth II groups was 84+/-26.67 and 276+/-44.26 months (median+/-SE), respectively (p<0.01). In the remnant stomach, cancer tended to occur near the site of gastrojejunostomy in the Billroth II group (p=0.05). Helicobacter pylori infection was only detected histologically in four patients who had undergone Billroth I reconstructions after distal gastrectomy for malignancy. CONCLUSION: After distal gastrectomy, careful periodic endoscopic examination for microcarcinoma is required in patients, particularly in those who undergo surgery for malignancy, to maximize detection of gastric cancer.


Assuntos
Coto Gástrico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Refluxo Duodenogástrico/complicações , Feminino , Gastrectomia/efeitos adversos , Derivação Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
15.
Theor Appl Genet ; 112(2): 243-50, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16240105

RESUMO

A population of F7 recombinant inbred lines (RILs) was made from a cross between susceptible ('Santou') and resistant (PI197088-1) lines of cucumber in order to study powdery mildew resistance loci. Susceptibility to powdery mildew in the F7 RIL individuals showed a continuous distribution from susceptible to resistant, suggesting that powdery mildew resistance is controlled by quantitative trait loci (QTLs). A QTL analysis identified two and three loci for powdery mildew resistance under 26 and 20 degrees C conditions, respectively. One QTL was found in the same position under both temperature conditions. Therefore, it is more likely that one major QTL acts under both temperature conditions and that other QTLs are specific to the two temperature conditions. The above results suggest that the four QTLs are controlled in a different temperature manner, and that their combination played an important role in expressing a high level of resistance to powdery mildew in this cucumber population. Sequence-tagged site (STS) markers associated with each QTL were developed and would be useful for breeding a cucumber line with a high level of powdery mildew resistance.


Assuntos
Cucumis sativus/genética , Cucumis sativus/microbiologia , Imunidade Inata/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Locos de Características Quantitativas/genética , Segregação de Cromossomos , Polimorfismo Genético/genética , Sitios de Sequências Rotuladas
16.
Theor Appl Genet ; 110(6): 995-1002, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15754209

RESUMO

The mitochondrial rps2 gene from barley, like that of rice, wheat, and maize, has an extended open reading frame (ORF) at the 3'-region when compared to that from lower plants. However, the extended portions are variable among these cereals. Since barley and wheat belong to the same tribe (Triticeae), it would be interesting to know when and where the two types of rps2 were generated during evolution. To determine this, we utilized the mitochondrial (mt) DNA sequence to examine variations of the rps2 genes in the tribe Triticeae. By means of the variable 3'-region, the distribution of barley (B)-type and wheat (W)-type rps2 sequences was studied in 19 genera of the tribe. The B-type sequence was identified in 10 of the 19 genera, whereas the W-type sequence was present in all 19 genera. Thus, ten of the examined genera have both types of rps2 sequences due to the presence of two copies of the gene. The W-type sequence was also present in the tribe Bromeae and the B-type sequence was also found in Aveneae and Poeae. Phylogenetic trees based on the B-type and W-type sequences were different from those based on other molecular data. This suggests that the mitochondrial genome in Triticeae has a unique evolutionary history.


Assuntos
DNA Mitocondrial/genética , Evolução Molecular , Genes de Plantas/genética , Variação Genética , Filogenia , Poaceae/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Primers do DNA , Biblioteca Gênica , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie
17.
Heart ; 90(2): 181-5, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14729792

RESUMO

OBJECTIVE: To compare the effects of nicorandil (a hybrid ATP sensitive potassium channel (K+(ATP) channel) opener/nitric oxide donor) with those of isosorbide dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients with acute myocardial infarction (AMI) who had undergone reperfusion treatment by direct balloon angioplasty. DESIGN: Double blind randomised study. PATIENTS: 60 patients with AMI in Killip class I. INTERVENTIONS: Patients were assigned into two treatment groups: a nicorandil group (n = 30) and an ISDN group (n = 30). Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty. RESULTS: Compared with ISDN, nicorandil more frequently caused recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the nicorandil group v 5 of 26 (19.2%) in the ISDN group, p = 0.006). The nicorandil group had higher values of averaged peak velocity 40 minutes after reperfusion (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p = 0.045) and higher values of regional wall motion of the infarcted area three weeks after onset of AMI (-1.78 (1.11) v -2.50 (1.04) SD/chord, p = 0.046). CONCLUSIONS: A combination of nicorandil drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area. The nicorandil regimen resulted in better left ventricular regional wall motion.


Assuntos
Angioplastia com Balão/métodos , Dinitrato de Isossorbida/uso terapêutico , Infarto do Miocárdio/terapia , Nicorandil/uso terapêutico , Vasodilatadores/uso terapêutico , Quimioterapia Adjuvante , Circulação Coronária/efeitos dos fármacos , Método Duplo-Cego , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica/métodos , Estudos Prospectivos , Resultado do Tratamento
18.
Theor Appl Genet ; 108(4): 639-43, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14551685

RESUMO

An inbred turnip ( Brassica rapa syn. campestris) line, N-WMR-3, which carries the trait of clubroot resistance (CR) from a European turnip, Milan White, was crossed with a clubroot-susceptible doubled haploid line, A9709. A segregating F(3) population was obtained by single-seed descent of F(2) plants and used for a genetic analysis. Segregation of CR in the F(3) population suggested that CR is controlled by a major gene. Two RAPD markers, OPC11-1 and OPC11-2, were obtained as candidates of linkage markers by bulked segregant analysis. These were converted to sequence-tagged site markers, by cloning and sequencing of the polymorphic bands, and named OPC11-1S and OPC11-2S, respectively. The specific primer pairs for OPC11-1S amplified a clear dominant band, while the primer pairs for OPC11-2S resulted in co-dominant bands. Frequency distributions and statistical analyses indicate the presence of a major dominant CR gene linked to these two markers. The present marker for CR was independent of the previously found CR loci, Crr1 and Crr2. Genotypic distribution and statistical analyses did not show any evidence of CR alleles on Crr1 and Crr2 loci in N-WMR-3. The present study clearly demonstrates that B. rapa has at least three CR loci. Therefore, the new CR locus was named Crr3. The present locus may be useful in breeding CR Chinese cabbage cultivars to overcome the decay of present CR cultivars.


Assuntos
Brassica rapa/genética , Mapeamento Cromossômico , Imunidade Inata/genética , Doenças das Plantas/microbiologia , Cruzamentos Genéticos , Fungos , Polimorfismo Genético/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Sitios de Sequências Rotuladas
19.
Nucl Med Commun ; 24(6): 625-31, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12766597

RESUMO

Previous studies have demonstrated that myocardial perfusion imaging using 99mTc-tetrofosmin at rest allows viability assessment similar to that obtained with 201Tl imaging and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). The simultaneous assessment of perfusion and regional function is now available by quantitative gated myocardial perfusion single-photon emission computed tomography (SPECT). This study was designed to evaluate the utility of quantitative values of wall motion and wall thickening, calculated by quantitative gated myocardial perfusion SPECT, for the prediction of functional recovery after coronary bypass grafting (CABG). Fifty-six patients with coronary artery disease scheduled for CABG were included prospectively. All patients underwent 99mTc-tetrofosmin gated SPECT imaging at rest preoperatively and 3 months after CABG. The myocardium was divided into nine segments and the average quantitative values of regional perfusion (percentage uptake) (%), wall motion (mm) and wall thickening (%) were determined automatically using quantitative gated SPECT (QGS) software. The wall motion score was defined visually using a four-point scale (0, normal; 3, akinesis), and segments with severe asynergy (score of 2 or 3) with patent grafts were assessed. Of 77 segments with severe asynergy, 56 segments showed improved wall motion and 21 segments did not improve after CABG. The area under the receiver operating characteristic curve of wall thickening for the prediction of functional recovery was significantly higher (0.92) than that of the percentage uptake (0.77, P<0.017) or wall motion (0.60, P<0.0001). When each analysis used the optimal threshold, the wall thickening analysis (>or=10%) had a sensitivity of 95% and a specificity of 81%. These values tended to be higher than those of the percentage uptake (sensitivity, 86%; specificity, 67%). The wall motion analysis (>or=1.5 mm) had a significantly lower sensitivity of 75% and specificity of 43% than the wall thickening analysis (P=0.0038 and P=0.011, respectively). The results indicate that wall thickening, calculated by QGS software, may be more useful than regional perfusion or wall motion analysis for the prediction of functional recovery after CABG. The areas of asynergy with relatively preserved wall thickening may have the potential for improved function despite severely decreased perfusion.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Imagem do Acúmulo Cardíaco de Comporta/métodos , Interpretação de Imagem Assistida por Computador/métodos , Compostos Organofosforados , Compostos de Organotecnécio , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/cirurgia
20.
Mol Genet Genomics ; 268(4): 434-45, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12471441

RESUMO

The entire mitochondrial genome of rice (Oryza sativa L.), a monocot plant, has been sequenced. It was found to comprise 490,520 bp, with an average G+C content of 43.8%. Three rRNA genes, 17 tRNA genes and five pseudo tRNA sequences were identified. In addition, eleven ribosomal protein genes and two pseudo ribosomal protein genes were found, which are homologous to 13 of the 16 genes for ribosomal proteins in the mitochondrial genome of the liverwort (Marchantia polymorpha). A greater degree of variation in terms of presence/absence and integrity of genes was observed among the ribosomal protein genes and tRNA genes of rice, Arabidopsis and sugar beet. Transcription and post-transcriptional modification (RNA editing) in the rice mitochondrial sequence were also examined. In all, 491 Cs in the genomic DNA were converted to Ts in cDNA. The frequency of RNA editing differed markedly depending upon the ORF considered. Sequences derived from plastid and nuclear genomes make up 6.3% and 13.4% of the mitochondrial genome, respectively. The degree of conservation of plastid sequences in the mitochondrial genome ranged from 61% to 100%, suggesting that sequence migration has occurred very frequently. Three plastid DNA fragments that were incorporated into the mitochondrial genome were subsequently transferred to the nuclear genome. Nineteen fragments that were similar to transposon or retrotransposon sequences, but different from those found in the mitochondrial genomes of dicots, were identified. The results indicate frequent and independent DNA sequence flow to and from the mitochondrial genome during the evolution of flowering plants, and this may account for the range of genetic variation observed between the mitochondrial genomes of higher plants.


Assuntos
DNA Mitocondrial/genética , Genes de Plantas/genética , Mitocôndrias/genética , Oryza/genética , Evolução Biológica , Núcleo Celular/genética , Elementos de DNA Transponíveis , Topos Floridos/genética , Genoma de Planta , Dados de Sequência Molecular , Plastídeos/genética , Edição de RNA , RNA de Transferência/genética , Recombinação Genética , Retroelementos
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