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1.
Clin Radiol ; 74(8): 650.e13-650.e18, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31014571

RESUMO

AIM: To compare perfusion computed tomography (CT) with reconstructed image from source data using low-dose contrast agent and conventional 320-row CT for the evaluation of renal tumours. MATERIALS AND METHODS: Twenty-eight patients underwent conventional CT (C-CT) and 26 patients underwent perfusion CT with low-dose (40 ml) contrast agent. Image noise, arterial visualisation, the sharpness of the corticomedullary junction (CMJ), and overall image quality were each assessed using a four-point scale. The tumour detection rate for lesions <4 cm (n=66) was also evaluated. Quantitative image parameters including image noise and the contrast-to-noise ratios (CNRs) of the renal artery and CMJ were measured. The volume CT dose index (CTDI), dose-length product (DLP), and size-specific dose estimate (SSDE) were also recorded. RESULTS: Although the image noise of perfusion CT was higher than that of C-CT and the overall image quality of perfusion CT was lower than that of C-CT, the arterial visualisation score of perfusion CT was significantly higher than that of C-CT. The CMJ sharpness scores of the two techniques were equivalent. Sensitivity and positive predictive values were also equivalent with respect to tumour detection. The CNRs of both the left and right renal arteries were significantly higher on perfusion CT than on C-CT. The CTDI, DLP, and SSDE of perfusion CT were significantly lower than those of C-CT. CONCLUSION: Perfusion CT using low-dose contrast agent preserved arterial visualisation and the tumour detection rate and achieved a low radiation dose despite image quality degradation and image noise.


Assuntos
Meios de Contraste , Neoplasias Renais/diagnóstico por imagem , Doses de Radiação , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Imagem de Perfusão/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos
2.
Leukemia ; 32(3): 616-625, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28904384

RESUMO

Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with either refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinase that regulates a variety of fundamental cellular processes. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD) that plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in a patient-derived xenograft murine model of B-ALL. Interestingly, although KPT-9274 is a dual PAK4/NAMPT inhibitor, B-ALL cell growth inhibition by KPT-9274 was largely abolished with nicotinic acid supplementation, indicating that the inhibitory effects on B-ALL cells are mainly exerted by NAD+ depletion through NAMPT inhibition. Moreover, we have found that the extreme susceptibility of B-ALL cells to NAMPT inhibition is related to the reduced cellular NAD+ reserve. NAD+ depletion may be a promising alternative approach to treating patients with B-ALL.


Assuntos
NAD/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Acrilamidas/química , Acrilamidas/farmacologia , Aminopiridinas/química , Aminopiridinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Ativadas por p21/antagonistas & inibidores
3.
Leukemia ; 31(1): 1-10, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27389053

RESUMO

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Proliferação de Células/genética , Células Clonais , Exoma , Humanos , Taxa de Mutação , Nucleofosmina , Sequências de Repetição em Tandem , Fatores de Tempo
5.
J Laryngol Otol ; 128(10): 926-31, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25230256

RESUMO

OBJECTIVE: This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion. METHODS: A case-control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated. RESULTS: RESULTS for HMGB1 were dichotomised into positive staining scores (score, 5-7) and negative scores (0-4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6-26.5) after adjusting for other factors. CONCLUSION: In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína HMGB1/biossíntese , Neoplasias da Língua/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Proteína HMGB1/genética , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias da Língua/genética , Neoplasias da Língua/patologia
6.
Breast Cancer Res Treat ; 147(3): 513-25, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25200445

RESUMO

Several trials have confirmed that the pathological complete response (pCR) rates after neoadjuvant chemotherapy (NAC) are significantly lower in HER2-positive/ER-positive patients than in HER2-positive/ER-negative patients. To understand this phenomenon, we investigated the association between NAC resistance and CCND1, which is frequently overexpressed in ER-positive tumors. Pretreatment formalin-fixed tumor tissues were collected from 75 HER2-positive patients receiving NAC comprised anthracyclines, taxanes, and trastuzumab. Seventeen gene transcripts along with PIK3CA mutations were detected using MassARRAY (Sequenom, San Diego, CA). The gene expression levels were dichotomized according to the median values. The immunohistochemical expression of ER, PTEN, BCL-2, and cyclin D1 was scored. The relationship between the variables was assessed using the Spearman correlation. A logistic regression analysis was performed to detect predictors of pCR, which was defined as no invasive tumor in the breast or axilla. Forty-seven percent of the cases were ER-positive and 52 % (40/63 % in ER-positive/ER-negative) achieved a pCR. Among the ER-positive patients, the CCND1 gene expression level was 2.1 times higher than that in ER-negative patients and was significantly correlated with the expression of cyclin D1 protein. In a univariate analysis, a pCR was associated with high mRNA levels of ESR1, PGR, LMTK3, HER2, IGF1R, INPP4B, PDL-1, BCL-2, and CCND1 (P ≤ 0.05). In contrast, none of these genes were significantly correlated with a pCR among the ER-negative tumors and only EGFR was significantly correlated with a pCR. PIK3CA mutations or PTEN loss were not associated with a pCR in either group. After excluding ESR1 (r = 0.58), PGR (r = 0.64), and IGF1R (r = 0.59), the expressions of which were correlated with CCND1, a multivariate analysis revealed that CCND1 [P = 0.043; OR, 0.16] and HER2 [P = 0.012; OR, 11.2] retained its predictive value for pCR among ER-positive patients, but not among ER-negative patients. A High Level of CCND1 gene expression is a poor predictor of a pCR and provides a rationale for evaluating CDK4/6 inhibitors in HER2-positive/ER-positive breast cancer patients.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Ciclina D1/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Idoso , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/cirurgia , Classe I de Fosfatidilinositol 3-Quinases , Ciclina D1/genética , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Fosfatidilinositol 3-Quinases/genética , Valor Preditivo dos Testes , Trastuzumab , Resultado do Tratamento
7.
Breast Cancer Res Treat ; 145(1): 143-53, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24682674

RESUMO

We investigated the disease-free survival (DFS) of HER2-positive primary breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well as predictive factors for DFS and pathologic response. Data from 829 female patients treated between 2001 and 2010 were collected from 38 institutions in Japan. Predictive factors were evaluated using multivariate analyses. The 3-year DFS rate was 87 % [95 % confidence interval (CI) 85-90]. The pathologic complete response (pCR: ypT0/is + ypN0) rate was 51 %. The pCR rate was higher in the ER/PgR-negative patients than in the ER/PgR-positive patients (64 vs. 36 %, P < 0.001). Patients with pCR showed a higher DFS rate than patients without pCR (93 vs. 82 %, P < 0.001). Multivariate analysis revealed three independent predictors for poorer DFS: advanced nodal stage [hazard ratio (HR) 2.63, 95 % CI 1.36-5.21, P = 0.004 for cN2-3 vs. cN0], histological/nuclear grade 3 (HR 1.81, 95 % CI 1.15-2.91, P = 0.011), and non-pCR (HR 1.98, 95 % CI 1.22-3.24, P = 0.005). In the ER/PgR-negative dataset, non-pCR (HR 2.63, 95 % CI 1.43-4.90, P = 0.002) and clinical tumor stage (HR 2.20, 95 % CI 1.16-4.20, P = 0.017 for cT3-4 vs. cT1-2) were independent predictors for DFS, and in the ER/PgR-positive dataset, histological grade of 3 (HR 3.09, 95 % CI 1.48-6.62, P = 0.003), clinical nodal stage (HR 4.26, 95 % CI 1.53-13.14, P = 0.005 for cN2-3 vs. cN0), and young age (HR 2.40, 95 % CI 1.12-4.94, P = 0.026 for ≤40 vs. >40) were negative predictors for DFS. Strict pCR (ypT0 + ypN0) was an independent predictor for DFS in both the ER/PgR-negative and -positive datasets (HR 2.66, 95 % CI 1.31-5.97, P = 0.006 and HR 3.86, 95 % CI 1.13-24.21, P = 0.029, respectively). These results may help assure a more accurate prognosis and personalized treatment for HER2-positive breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Trastuzumab
9.
Oncogene ; 32(39): 4614-21, 2013 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-23108411

RESUMO

Pancreatic cancer is one of the most lethal malignancies due to its aggressive growth and rapid development of distant metastases. In this context, mucin 1 (MUC1) overexpression and hypoxia are frequently observed events. However, their functional relationship remains largely unknown. This study provides evidence that MUC1 is overexpressed by hypoxia and contributes to hypoxia-driven angiogenesis. Using the conditioned medium obtained from hypoxia-stressed AsPC1 cells treated with MUC1 siRNAs, we demonstrated that MUC1 enhanced the endothelial tube formation, proliferation and migration ability, which induced by hypoxia-conditioned medium (HCM). In addition, MUC1 was significantly induced by hypoxia, especially in the pancreatic cancer cells derived from metastatic tumors (AsPC1, HPAF2 or Capan1), and MUC1-cytoplasmic tail (MUC1-CT) accumulated in the nucleus under hypoxia. As noted in a previous report, MUC1-CT was recruited to genomic regions upstream of the connective tissue growth factor (CTGF) accompanied with ß-catenin and p53, resulting in the hypoxic induction of CTGF. Moreover, hypoxia-induced MUC1 partially regulated two other hypoxia-inducible proangiogenic factors including vascular endothelial growth factor-A and platelet-derived growth factor-B. The neutralization assay revealed that endothelial tube formation induced by HCM was clearly suppressed by antibodies against these three factors, suggesting the importance of these factors in hypoxia-driven angiogenesis. In summary, this is the first report demonstrating a pivotal role of MUC1 in controlling the hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors in pancreatic cancer. Our findings provide the novel insights into the understanding of complex interactions between pancreatic cancer cells and tumor microenvironments.


Assuntos
Proteínas Angiogênicas/biossíntese , Carcinoma/irrigação sanguínea , Hipóxia Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Mucina-1/fisiologia , Proteínas de Neoplasias/fisiologia , Neovascularização Patológica/fisiopatologia , Neoplasias Pancreáticas/irrigação sanguínea , Proteínas Angiogênicas/genética , Carcinoma/patologia , Carcinoma/fisiopatologia , Carcinoma/secundário , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Meios de Cultivo Condicionados/farmacologia , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Metástase Neoplásica , Estresse Oxidativo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/fisiopatologia , Fragmentos de Peptídeos/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-sis/biossíntese , Proteínas Proto-Oncogênicas c-sis/genética , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
10.
Med Phys ; 39(6Part6): 3661-3662, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517566

RESUMO

PURPOSE: In the real-time tumor-tracking radiotherapy system, fiducial markers are detected by X-ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. METHODS: A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. RESULTS: In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. CONCLUSIONS: The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy.

11.
Med Phys ; 39(6Part21): 3872, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28518247

RESUMO

PURPOSE: In spot scanning proton therapy, accurate patient positioning before and during treatment is essential. A small gold ball marker is suitable as a fiducial for prostate treatment. However, it has been pointed out that the marker causes dose shadowing because the protons are scattered with their energy quickly diminished. In this research we explore the possibility that the biological effect of dose shadowing can be mitigated with a limited number of fields. METHODS: The proton dose distribution in prostate was simulated using Geant4. The simulations include the Hokkaido University spot scanning nozzle and a water phantom positioned isocentrically. The PTV was delineated at the center of the phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV. The plan was created by single-field optimization and each of the following beam arrangements was investigated; (1) single lateral field (2) two lateral fields (3) two lateral + one anterior fields (4) four-field box. The dose prescription was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP) were compared for the four beam arrangements. RESULTS: For (1)-(4), the minimum dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The reduction of the TCP values from those in the absence of the gold marker were 50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al. (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the biological parameters in Levegrûn et al. (Int.J.RadiatOncol.Biol.Phys. 51, 2001), respectively. CONCLUSIONS: Although dose shadowing by the gold marker is locally non-negligible, the size of the affected domain is tiny. It was found that with a minimum number of fields, the TCP nearly recovers to the value without the gold marker.

12.
Med Phys ; 39(6Part18): 3821-3822, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28518493

RESUMO

PURPOSE: To investigate the possibility of using a single spot scanning proton beam to treat superficial lesions. METHODS: A cylindrical phantom with a simulated superficial target (it seated 0.5-4cm depth from the surface, volume: 270cm3 ) was created in Eclipse treatment planning system. Three proton plans were generated: (a) a single AP uniform scanning beam with aperture and range compensator; (b) a single AP spot scanning beam with a pre-absorber. The location and thickness of the pre-absorber were calculated using Geant4 to Monte Carlo code to make use of the available spot scanning beams to get a conformal plan. (c) a five-beam spot scanning beam plan using multi-field optimization. The prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target. The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to normal tissue (phantom-target) and skin (2mm from the surface) were evaluated and compared for three plans. RESULTS: The mean doses to the target are comparable within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04 and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to 20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that of plan (a) and (b). CONCLUSIONS: Each plan provides good coverage of target. And in this study, it showed that, with a properly designed pre-absorber, it is possible to use a single spot scanning beam to treat superficial lesion. The plan provides good target coverage and maintains normal tissue sparing in the mean time.

13.
Br J Cancer ; 98(8): 1389-97, 2008 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-18349830

RESUMO

Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P=0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P=0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P=0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.


Assuntos
Antígenos CD/análise , Glicoproteínas/análise , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologia , Peptídeos/análise , Fator C de Crescimento do Endotélio Vascular/análise , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Antígeno Ki-67/análise , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/mortalidade , Prognóstico , Receptores CXCR4/análise
14.
Br J Cancer ; 97(3): 405-11, 2007 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-17622248

RESUMO

Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P=0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.


Assuntos
Citocinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Midkina , Neoplasias Pancreáticas/patologia , Prognóstico , Análise de Sobrevida , Taxa de Sobrevida
15.
Br J Cancer ; 96(9): 1353-7, 2007 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-17437021

RESUMO

In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy x 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m(-2) day(-1) on days 1-7 and 15-21 (level 1), 1-14 (level 2), and 1-21 (level 3a) and 80 mg m(-2) day(-1) on days 1-21 (level 3b) and 1-28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19-9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m(-2) day(-1) given on days 1-21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Ácido Oxônico/toxicidade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Radioterapia/métodos , Tegafur/toxicidade , Adulto , Idoso , Terapia Combinada , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Análise de Sobrevida
16.
Arch Virol ; 151(12): 2511-7, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16847553

RESUMO

We have studied the prevalence of the subgenus F adenoviruses and the molecular characteristics of adenovirus type 41 in Hiroshima Prefecture, Japan, as a limited area during the period of 1997-2004. Subgenus F adenoviruses were detected in 30 (3.4%) of 892 fecal specimens by enzyme immunoassay (EIA), and 80.0% (24 of 30) of positive patients were <36 months old. One (3.3%) and 29 (96.7%) of the 30 EIA-positive specimens were adenoviruses type 40 (Ad40) and 41 (Ad41), respectively. The genomes of Ad41 strains amplified by PCR were divided into two genomic type clusters (GTC1 and GTC2) based on the hexon gene as described by Li et al. (J Clin Microbiol 42: 4032-4039, 2004.). Twenty-one (95.5%) of 22 Ad41 strains detected between 2000 and 2004 belonged to GTC1, whereas all seven strains detected between 1997 and 1999 belonged to GTC2. These genomic typings were the same for the hexon and fiber genes except for one strain. This strain contained a hexon gene belonging to GTC1 and a fiber gene belonging to GTC2 and was considered to be a recombinant between adenoviruses of these types.


Assuntos
Infecções por Adenoviridae/epidemiologia , Adenoviridae/genética , Gastroenterite/epidemiologia , Gastroenterite/virologia , Adenoviridae/classificação , Infecções por Adenoviridae/genética , Sequência de Bases , Criança , Primers do DNA , Gastroenterite/genética , Humanos , Incidência , Japão/epidemiologia , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia
18.
J Clin Pathol ; 58(8): 845-52, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16049287

RESUMO

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Mucinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/secundário , Progressão da Doença , Feminino , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucina-4 , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Pâncreas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Fatores de Risco , Análise de Sobrevida
19.
Br J Cancer ; 92(2): 284-9, 2005 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-15655547

RESUMO

The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological, respectively). Furthermore, in p53-negative tumours, CRT was more effective in tumours with p53R2 negative expression than those with p53R2 positive expression (P=0.0014). We demonstrated that the negative expression of p53 and p53R2 expression was closely related to the effect of CRT and should predict the CRT outcome in patients with ESCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Idoso , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
20.
Acta Radiol ; 44(5): 464-71, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14510751

RESUMO

PURPOSE: To compare the effectiveness of thin-section helical CT and MR imaging with gadolinium-enhanced dynamic technique and MR cholangiopancreatography (MRCP) in the examination of patients with intraductal papillary mucinous tumors. MATERIAL AND METHODS: Helical CT, dynamic MR imaging, and MRCP of 25 intraductal papillary mucinous tumors were compared with ERCP and surgical findings. RESULTS: The duodenal papilla was identified by helical CT and dynamic MR imaging in 11 (44%) and 20 (80%) of the 25 patients, respectively (p<0.05). The main pancreatic duct was visualized on helical CT, dynamic MR imaging, and MRCP in all patients (100%): 25 (96.2%), 24 (92.3%), and 26 (100%) cystic lesions were depicted, respectively. A communicating duct between the main pancreatic duct and the cystic lesion was visualized on helical CT, dynamic MR imaging, and MRCP in 14 (53.8%), 11 (42.3%), and 15 (55.7%) lesions, respectively. The papillary projections corresponding to 3 mm or larger papillary neoplasms were depicted on helical CT and MR imaging in 7 patients (25%). CONCLUSION: MR imaging was equal or slightly superior to thin-section helical CT in the evaluation of intraductal papillary mucinous tumors.


Assuntos
Cistadenoma Mucinoso/diagnóstico por imagem , Cistadenoma Mucinoso/patologia , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada Espiral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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