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1.
Molecules ; 22(12)2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29261152

RESUMO

The aim of the research was to determine the impact of fermentation with Pleurotus ostreatus on kidney beans, black beans, and oats. The results indicate that the fungus has a positive effect on the substrates when compared to the controls. The antioxidant activity (39.5% on kidney beans and 225% on oats in relation to the controls) and content of total polyphenols (kidney beans three times higher regarding the controls) increased significantly by the presence of the fungus mycelium, even after simulated digestion. There was a significant increase in protein digestibility (from 39.99 to 48.13% in black beans, 44.06 to 69.01% in kidney beans, and 63.25 to 70.01% in oats) and a decrease of antinutrient tannins (from 65.21 to 22.07 mg in black beans, 35.54 to 23.37 in kidney beans, and 55.67 to 28.11 in oats) as well as an increase in the contents of some essential amino acids. Overall, this fermentation treatment with Pleurotus ostreatus improved the nutritional quality of cereals and legumes, making them potential ingredients for the elaboration and/or fortification of foods for human nutrition.


Assuntos
Antioxidantes/química , Avena/química , Proteínas Alimentares/química , Phaseolus/química , Pleurotus/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Avena/metabolismo , Carboidratos/química , Proteínas Alimentares/metabolismo , Fermentação , Humanos , Micélio/metabolismo , Valor Nutritivo , Phaseolus/metabolismo , Polifenóis/química , Polifenóis/metabolismo , Sementes/química , Sementes/metabolismo , Taninos/química , Taninos/metabolismo
2.
Magn Reson Med ; 71(4): 1592-602, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23661583

RESUMO

PURPOSE: The purpose of this pilot study is to determine (1) if early changes in both semiquantitative and quantitative DCE-MRI parameters, observed after the first cycle of neoadjuvant chemotherapy in breast cancer patients, show significant difference between responders and nonresponders and (2) if these parameters can be used as a prognostic indicator of the eventual response. METHODS: Twenty-eight patients were examined using DCE-MRI pre-, post-one cycle, and just prior to surgery. The semiquantitative parameters included longest dimension, tumor volume, initial area under the curve, and signal enhancement ratio related parameters, while quantitative parameters included K(trans), v(e), k(ep), v(p), and τ(i) estimated using the standard Tofts-Kety, extended Tofts-Kety, and fast exchange regime models. RESULTS: Our preliminary results indicated that the signal enhancement ratio washout volume and k(ep) were significantly different between pathologic complete responders from nonresponders (P < 0.05) after a single cycle of chemotherapy. Receiver operator characteristic analysis showed that the AUC of the signal enhancement ratio washout volume was 0.75, and the AUCs of k(ep) estimated by three models were 0.78, 0.76, and 0.73, respectively. CONCLUSION: In summary, the signal enhancement ratio washout volume and k(ep) appear to predict breast cancer response after one cycle of neoadjuvant chemotherapy. This observation should be confirmed with additional prospective studies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Aumento da Imagem/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Projetos Piloto , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
3.
J Behav Med ; 36(3): 328-39, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22569774

RESUMO

Women with a personal or maternal history of breast cancer experience psychological stress in relation to breast cancer risk, and adolescent and young adult daughters are particularly at risk for experiencing stress related to their mothers' history of breast cancer. The current study examined interpersonal and biological stress responses during a laboratory-based communication task about breast cancer risk in 32 mother-daughter dyads and explores whether certain communication styles between mothers and daughters are associated with increased stress reactivity during the task. Five saliva samples were collected from each participant to determine cortisol baseline levels, reactivity to, and recovery from the task. Negative maternal communication was associated with higher cortisol levels in daughters. In addition, maternal sadness was correlated with lower levels of daughters' cortisol at all time points with the exception of baseline measures. Implications for understanding the psychobiology of stress in women at risk for breast cancer are highlighted.


Assuntos
Nível de Alerta/fisiologia , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Comunicação , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Educação em Saúde , Hidrocortisona/sangue , Relações Mãe-Filho , Estresse Psicológico/complicações , Adolescente , Adulto , Afeto/fisiologia , Fatores Etários , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Saliva/química , Adulto Jovem
4.
Magn Reson Med ; 68(1): 261-71, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22127821

RESUMO

By fitting dynamic contrast-enhanced MRI data to an appropriate pharmacokinetic model, quantitative physiological parameters can be estimated. In this study, we compare four different models by applying four statistical measures to assess their ability to describe dynamic contrast-enhanced MRI data obtained in 28 human breast cancer patient sets: the chi-square test (χ(2)), Durbin-Watson statistic, Akaike information criterion, and Bayesian information criterion. The pharmacokinetic models include the fast exchange limit model with (FXL_v(p)) and without (FXL) a plasma component, and the fast and slow exchange regime models (FXR and SXR, respectively). The results show that the FXL_v(p) and FXR models yielded the smallest χ(2) in 45.64 and 47.53% of the voxels, respectively; they also had the smallest number of voxels showing serial correlation with 0.71 and 2.33%, respectively. The Akaike information criterion indicated that the FXL_v(p) and FXR models were preferred in 42.84 and 46.59% of the voxels, respectively. The Bayesian information criterion also indicated the FXL_v(p) and FXR models were preferred in 39.39 and 45.25% of the voxels, respectively. Thus, these four metrics indicate that the FXL_v(p) and the FXR models provide the most complete statistical description of dynamic contrast-enhanced MRI time courses for the patients selected in this study.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Gadolínio DTPA/farmacocinética , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Simulação por Computador , Meios de Contraste/farmacocinética , Interpretação Estatística de Dados , Feminino , Humanos , Aumento da Imagem/métodos , Modelos Estatísticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Appl Environ Microbiol ; 78(6): 1644-51, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22210213

RESUMO

Rhizobium rhizogenes strain K84 is a commercial biocontrol agent used worldwide to control crown gall disease. The organism binds tightly to polypropylene substrate and efficiently colonizes root surfaces as complex, multilayered biofilms. A genetic screen identified two mutants in which these surface interactions were affected. One of these mutants failed to attach and form biofilms on the abiotic surface although, interestingly, it exhibited normal biofilm formation on the biological root tip surface. This mutant is disrupted in a wcbD ortholog gene, which is part of a large locus predicted to encode functions for the biosynthesis and export of a group II capsular polysaccharide (CPS). Expression of a functional copy of wcbD in the mutant background restored the ability of the bacteria to attach and form normal biofilms on the abiotic surface. The second identified mutant attached and formed visibly denser biofilms on both abiotic and root tip surfaces. This mutant is disrupted in the rkpK gene, which is predicted to encode a UDP-glucose 6-dehydrogenase required for O-antigen lipopolysaccharide (LPS) and K-antigen capsular polysaccharide (KPS) biosynthesis in rhizobia. The rkpK mutant from strain K84 was deficient in O-antigen synthesis and exclusively produced rough LPS. We also show that strain K84 does not synthesize the KPS typical of some other rhizobia strains. In addition, we identified a putative type II CPS, distinct from KPS, that mediates cell-surface interactions, and we show that O antigen of strain K84 is necessary for normal cell-cell interactions in the biofilms.


Assuntos
Aderência Bacteriana , Biofilmes/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Polissacarídeos Bacterianos/metabolismo , Rhizobium/fisiologia , Antígenos de Bactérias/biossíntese , Antígenos de Superfície/biossíntese , Deleção de Genes , Teste de Complementação Genética , Antígenos O/biossíntese , Rhizobium/metabolismo
6.
J Magn Reson Imaging ; 33(5): 1063-70, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21509862

RESUMO

PURPOSE: To provide a quantitative assessment of motion and distortion correction of diffusion-weighted images (DWIs) of the breast and to evaluate the effects of registration on the mean apparent diffusion coefficient (mADC). MATERIALS AND METHODS: Eight datasets from four patients with breast cancer and eight datasets from six healthy controls were acquired on a 3T scanner. A 3D affine registration was used to align each set of images and principal component analysis was used to assess the results. Variance in tumor ADC measurements, tumor mADC values, and voxel-wise tumor mADC values were compared before and after registration for each patient. RESULTS: Image registration significantly (P = 0.008) improved image alignment for both groups and significantly (P < 0.001) reduced the variance across individual tumor ADC measurements. While misalignment led to potential under- and overestimation of mADC values for individual voxels, average tumor mADC values did not significantly change (P > 0.09) after registration. CONCLUSION: 3D affine registration improved the alignment of DWIs of the breast and reduced the variance between ADC measurements. Although the reduced variance did not significantly change tumor region-of-interest measures of mADC, it may have a significant impact on voxel-based analyses.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Algoritmos , Artefatos , Neoplasias da Mama/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Modelos Estatísticos , Movimento (Física) , Análise de Componente Principal
7.
Breast Cancer Res Treat ; 112(2): 335-41, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18075785

RESUMO

INTRODUCTION: Studies investigating the prognostic effect of circulating TGF-beta-1 in breast cancer have given inconsistent findings. The purpose of this study is to evaluate whether circulating transforming growth factor beta 1 (TGF-beta-1) is associated with overall and disease-free survival in a cohort of recently diagnosed breast cancer patients. METHODS: We measured TGF-beta-1 levels in plasma samples of breast cancer patients in the Shanghai Breast Cancer Study, a population-based case-control study. We evaluated the relationship between TGF-beta-1 levels and overall and disease-free survival. The median follow up time was 7.2 years. RESULTS: We observed that, compared with the patients with the lowest quartile of plasma TGF-beta-1, patients with the highest quartile of plasma TGF-beta-1 had significantly worse overall survival with hazards ratio (HR) = 2.78, with 95% confidence interval (CI): 1.34-5.79 and disease-free survival with HR = 2.49, 95% CI: 1.15-5.41, while the patients with the second and third quartiles of plasma TGF-beta-1 did not have significantly different overall and disease-free breast cancer survival. The shape of association between plasma TGF-beta-1 levels and breast cancer survival appears to be non-linear. Stratified analysis by stage of disease did not appreciably change the association pattern. CONCLUSIONS: We conclude that the relationship between circulating levels of TGF-beta-1 and prognosis in breast cancer is complex and non-linear. High levels of TGF-beta-1 are associated with worse survival independent of stage of disease.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Fator de Crescimento Transformador beta1/sangue , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , China , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Isoformas de Proteínas , Resultado do Tratamento
8.
Cell Signal ; 18(7): 1041-50, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16288847

RESUMO

Nuclear factor kappa B (NF-kappaB) has been implicated in cancer cell survival. We explored the role of the TGF-beta pathway in the regulation of NF-kappaB in colon cancer cells. TGF-beta-1 treatment of the colon adenocarcinoma cell line FET-1, results in an early increase in IkappaB-alpha phosphorylation that precedes NF-kappaB nuclear translocation and DNA binding activity. Activation of the TGF-beta type I receptor is required for the TGF-beta-mediated activation of NF-kappaB. No activation of NF-kappaB is observed in a Smad4 null cell line, SW480, even though TGF-beta does result in IkappaB-alpha phosphorylation in these cells. Smad4 restores the TGF-beta-1-mediated NF-kappaB activation in SW480 cells. TGF-beta-1 treatment fails to activate NF-kappaB or phosphorylate IkappaB-alpha in FET-1 cells expressing the inhibitory Smad, Smad7. Taken together, these results suggest a role for Smad4 in the transcriptional activation of NF-kappaB, and a direct effect of Smad 7 inhibiting IkappaB-alpha phosphorylation rather than through the well-established inhibition of Smad2/3 phosphorylation with subsequent inhibition of the TGF-beta pathway.


Assuntos
NF-kappa B/metabolismo , Proteína Smad4/fisiologia , Proteína Smad7/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Transporte Ativo do Núcleo Celular , Receptores de Ativinas Tipo I/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Neoplasias do Colo , DNA/metabolismo , Ativação Enzimática , Células Epiteliais/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Proteína Smad7/biossíntese , Proteína Smad7/genética , Ativação Transcricional , Fator de Crescimento Transformador beta1
9.
J Gastrointest Surg ; 11(12): 1752-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17634764

RESUMO

A 42-year-old male was admitted with recurrent gastrointestinal bleeding and new-onset jaundice. Computed tomography showed a persistent gastroduodenal artery pseudoaneurysm and dilated intrahepatic and extrahepatic ducts consistent with obstructive jaundice. This patient had two previous coil embolizations, which failed to prevent recurrent bleeding. The patient underwent pancreaticoduodenectomy for definitive treatment of his pseudoaneurysm. We report this case and review the literature.


Assuntos
Falso Aneurisma/complicações , Duodeno/irrigação sanguínea , Hemorragia Gastrointestinal/etiologia , Icterícia Obstrutiva/complicações , Ductos Pancreáticos , Estômago/irrigação sanguínea , Adulto , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/patologia , Dilatação Patológica , Embolização Terapêutica , Humanos , Masculino , Pancreaticoduodenectomia , Recidiva
10.
Clin Cancer Res ; 12(5): 1570-6, 2006 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16533783

RESUMO

PURPOSE: The aim of this study was to determine the safety and pathologic response rates following neoadjuvant paclitaxel and radiation in patients with stage II/III breast cancer and to evaluate the use of sequential biopsies to allow an in vivo assessment of biological markers as potential predictive markers of response to this regimen. PATIENTS AND METHODS: Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel 175 mg/m2 every 3 weeks, followed by twice-weekly paclitaxel 30 mg/m2 and concurrent radiation. Core biopsies were obtained at baseline and 24 to 72 hours after the first cycle of paclitaxel. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary end point was pathologic complete response, which is defined as the absence of any invasive cancer at surgery. Potential markers of therapeutic response were evaluated including markers of proliferation, apoptosis, p21, HER2, estrogen receptor, and progesterone receptor status. RESULTS: Of the 38 patients enrolled, 13 (34%) had a pathologic complete response. There was no significant difference in baseline Ki-67 between responders (35%) and nonresponders (28%; P = 0.45). There was also no significant change in Ki-67 following paclitaxel administration. Despite this lack of immunohistologic change in proliferative activity, baseline mitotic index was higher for patients with pathologic complete response over nonresponders (27 versus 10, P = 0.003). Moreover, the increase in mitotic index following paclitaxel administration was associated with pathologic complete response. CONCLUSIONS: Neoadjuvant paclitaxel/radiation is effective and well tolerated. Tumor proliferation at baseline and response to chemotherapy as measured by mitotic activity may serve as an important indicator of pathologic response to neoadjuvant paclitaxel/radiation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Raios gama , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica
11.
Lymphat Res Biol ; 15(1): 45-56, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28323572

RESUMO

BACKGROUND: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD). METHODS AND RESULTS: Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages. CONCLUSION: Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.


Assuntos
Linfedema Relacionado a Câncer de Mama/fisiopatologia , Linfedema Relacionado a Câncer de Mama/terapia , Vasos Linfáticos/fisiopatologia , Massagem/métodos , Adulto , Axila , Linfedema Relacionado a Câncer de Mama/diagnóstico , Linfedema Relacionado a Câncer de Mama/etiologia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Estudos de Casos e Controles , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Clin Cancer Res ; 23(15): 4035-4045, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28270498

RESUMO

Purpose: Because of inherent disease heterogeneity, targeted therapies have eluded triple-negative breast cancer (TNBC), and biomarkers predictive of treatment response have not yet been identified. This study was designed to determine whether the mTOR inhibitor everolimus with cisplatin and paclitaxel would provide synergistic antitumor effects in TNBC.Methods: Patients with stage II/III TNBC were enrolled in a randomized phase II trial of preoperative weekly cisplatin, paclitaxel and daily everolimus or placebo for 12 weeks, until definitive surgery. Tumor specimens were obtained at baseline, cycle 1, and surgery. Primary endpoint was pathologic complete response (pCR); secondary endpoints included clinical responses, breast conservation rate, safety, and discovery of molecular features associated with outcome.Results: Between 2009 and 2013, 145 patients were accrued; 36% of patients in the everolimus arm and 49% of patients in the placebo arm achieved pCR; in each arm, 50% of patients achieved complete responses by imaging. Higher rates of neutropenia, mucositis, and transaminase elevation were seen with everolimus. Clinical response to therapy and long-term outcome correlated with increased frequency of DNA damage response (DDR) gene mutations, Basal-like1 and Mesenchymal TNBC-subtypes, AR-negative status, and high Ki67, but not with tumor-infiltrating lymphocytes.Conclusions: The paclitaxel/cisplatin combination was well tolerated and active, but addition of everolimus was associated with more adverse events without improvement in pCR or clinical response. However, discoveries made from correlative studies could lead to predictive TNBC biomarkers that may impact clinical decision-making and provide new avenues for mechanistic exploration that could lead to clinical utility. Clin Cancer Res; 23(15); 4035-45. ©2017 AACR.


Assuntos
Cisplatino/administração & dosagem , Everolimo/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Cisplatino/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Everolimo/efeitos adversos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Antígeno Ki-67/genética , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Receptores Androgênicos/genética , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
13.
J Gastrointest Surg ; 10(3): 428-33, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16504891

RESUMO

We discuss the case of a Jehovah's Witness patient who presented with a bleeding endocrine periampullary mass. Transduodenal excision of the ampullary mass was successfully performed as a bridge to pancreaticoduodenectomy in this critically ill patient. The roles of pancreaticoduodenectomy and alternatives to pancreaticoduodenectomy in the emergency setting are reviewed, in particular, for patients who decline transfusion of blood products. The surgical approach to surgery and perioperative anemia in Jehovah's Witness patients is described. Finally, we reviewed the role of transduodenal excision in the management of ampullary tumors and describe its use as a bridge to pancreaticoduodenectomy in a patient with a malignant neoplasm of the ampulla.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/cirurgia , Testemunhas de Jeová , Pancreaticoduodenectomia/métodos , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Neoplasias do Ducto Colédoco/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Recusa do Paciente ao Tratamento
14.
Clin Cancer Res ; 8(11): 3628-38, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12429655

RESUMO

PURPOSE: The tumor suppressor gene Smad4/DPC4, a key transcription factorin transforming growth factor beta (TGF-beta) signaling cascades,is inactivated in 50% of pancreatic adenocarcinomas. We seek to determine the role of Smad4/DPC4 in the suppression of tumor cell growth and in the regulation of TGF-beta-mediated expression of cell-cycle regulatory genes p15(ink4b) and p21(waf1). EXPERIMENTAL DESIGN: Smad4/DPC4 is overexpressed by adenoviral infection in CFPac-1 pancreatic cancer cells, in which the Smad4/DPC4 is homozygously deleted, and in Capan-1 pancreatic cancer cells, in which Smad4/DPC4 is not expressed. Expression of the TGF-beta downstream target gene p21(waf1), regulation of the p15(ink4b) promoter, anchorage-independent growth, and tumorigenesis were examined. RESULTS: We demonstrate that expression of Smad4/DPC4 in Capan-1 cells reduced anchorage-independent growth by more than 50%, and inhibited xenograft tumor growth. However, overexpression of Smad4/DPC4 did not inhibit CFPac-1 cell growth. Interestingly, Smad4/DPC4 induced expression of p15(ink4b), p21(waf1), and TGF-beta-responsive reporter gene in Capan-1 but not in CFPac-1 cells. Furthermore, we found a previously unidentified Smad4 binding element (SBE) located in the region between -356 and -329 bp of the p15(ink4b) promoter. The p15(ink4b) promoter reporter gene assays revealed that Smad4-dependent transcriptional activation is mediated by this SBE, which indicates that p15(ink4b) is one of the downstream target genes regulated by Smad/DPC4. CONCLUSION: These results explain the role of Smad4/DPC4 in TGF-beta-mediated inhibition of cell proliferation in vitro and in vivo. Moreover, these results suggest that Smad4/DPC4-mediated tumor suppression and induction of TGF-beta-regulated cell-cycle-inhibitory genes may depend on additional factors that are absent in CFPac-1 cells.


Assuntos
Proteínas de Ciclo Celular/farmacologia , Inibidor p16 de Quinase Dependente de Ciclina/farmacologia , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pancreáticas/metabolismo , Transativadores/metabolismo , Proteínas Supressoras de Tumor , Adenoviridae/genética , Animais , Northern Blotting , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Deleção de Genes , Genes Reporter , Homozigoto , Humanos , Immunoblotting , Luciferases/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Regiões Promotoras Genéticas , Transdução de Sinais , Proteína Smad4 , Fatores de Tempo , Ativação Transcricional , Transfecção , Fator de Crescimento Transformador beta/metabolismo , Células Tumorais Cultivadas
15.
Am Surg ; 71(2): 164-70, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16022018

RESUMO

Black women have the highest mortality for breast cancer. Our hypothesis is that racial disparities in breast cancer survival persist after controlling for stage of disease and treatment at both a city hospital as well as at a university hospital. Data from tumor registries of breast cancer patients at a city hospital and a university center were analyzed for overall and disease-specific survival, controlling for stage and treatment. Black patients presented with more advanced stages and had significantly worse survival compared with whites. After controlling for stage of disease and treatment, a difference in survival persisted for stage II patients, with blacks doing worse than whites at both institutions. Although there were socioeconomic differences, race was an independent prognostic factor, with black patients having the worse prognosis. The lower survival of black women with breast cancer is only partially explained by their advanced stage at diagnosis. Black women with potentially curable stage II cancer had a lower survival that is not explained by the variables measured.


Assuntos
População Negra/estatística & dados numéricos , Neoplasias da Mama/mortalidade , População Branca/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Seguimentos , Hospitais Universitários/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Estudos Longitudinais , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Classe Social , Taxa de Sobrevida , Tennessee/epidemiologia , Resultado do Tratamento
16.
Invest Radiol ; 50(4): 195-204, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25360603

RESUMO

OBJECTIVES: The purpose of this study was to determine whether multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI), obtained before and after the first cycle of neoadjuvant chemotherapy (NAC), is superior to single-parameter measurements for predicting pathologic complete response (pCR) in patients with breast cancer. MATERIALS AND METHODS: Patients with stage II/III breast cancer were enrolled in an institutional review board-approved study in which 3-T DCE-MRI and DWI data were acquired before (n = 42) and after 1 cycle (n = 36) of NAC. Estimates of the volume transfer rate (K), extravascular extracellular volume fraction (ve), blood plasma volume fraction (vp), and the efflux rate constant (kep = K/ve) were generated from the DCE-MRI data using the Extended Tofts-Kety model. The apparent diffusion coefficient (ADC) was estimated from the DWI data. The derived parameter kep/ADC was compared with single-parameter measurements for its ability to predict pCR after the first cycle of NAC. RESULTS: The kep/ADC after the first cycle of NAC discriminated patients who went on to achieve a pCR (P < 0.001) and achieved a sensitivity, specificity, positive predictive value, and area under the receiver operator curve (AUC) of 0.92, 0.78, 0.69, and 0.88, respectively. These values were superior to the single parameters kep (AUC, 0.76) and ADC (AUC, 0.82). The AUCs between kep/ADC and kep were significantly different on the basis of the bootstrapped 95% confidence intervals (0.018-0.23), whereas the AUCs between kep/ADC and ADC trended toward significance (-0.11 to 0.24). CONCLUSIONS: The multiparametric analysis of DCE-MRI and DWI was superior to the single-parameter measurements for predicting pCR after the first cycle of NAC.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Imageamento por Ressonância Magnética , Terapia Neoadjuvante/métodos , Adulto , Idoso , Área Sob a Curva , Mama/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Aumento da Imagem , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
17.
Surg Oncol ; 12(1): 27-37, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12689668

RESUMO

Cystosarcoma phyllodes constitutes only 0.3-0.9% of all breast tumors. The term "sarcoma" was initially used because of its fleshy appearance, a more modern term is Phyllodes tumor (PT). The behavior of PT constitutes a spectrum from benign and locally recurrent to malignant and metastatic. In a general surgical series, 6.2% of the tumors were malignant. The microscopic appearance of PT is that of epithelial elements and connective tissue stroma. Malignancy is determined by characteristics of the stroma. The metastatic spread of malignant PT is mainly hematogenous to lung, with infrequent lymphatic involvement. Wide local excision with 2 cm margins is the treatment of choice. In 20% of both benign and malignant cases, PT will locally recur. There is no proven benefit of radiation or chemotherapy, although radiotherapy may be useful in selected cases. We present a case of a sarcomatous overgrowth in a malignant phyllodes tumor involving multiple histologic types.


Assuntos
Neoplasias da Mama/cirurgia , Tumor Filoide/cirurgia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Tumor Filoide/epidemiologia , Tumor Filoide/patologia , Resultado do Tratamento
18.
J Gastrointest Surg ; 7(1): 118-128, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12559193

RESUMO

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of the pancreas allows the diagnosis of pancreatic cancer to be established without exploratory surgery. We reviewed our recent experience with EUS-FNA in patients with presumed pancreatic cancer and report the diagnostic accuracy and complications of this procedure. Data were reviewed from all patients who presented with CT evidence of a pancreatic mass or a malignant biliary stricture and underwent EUS-FNA at our institution between November 1, 1999, and October 1, 2001. Based on the findings of contrast-enhanced, multislice CT scanning, patients were categorized as having resectable, locally advanced, or metastatic disease. EUS-FNA was performed in 233 patients. A final diagnosis of cancer was established in 216 patients (93%), 15 patients (6%) were found to have benign disease, and the final diagnosis remains unknown in two patients (1%). The sensitivity, specificity, and accuracy of EUS-FNA for diagnosis of a pancreatic malignancy were 91%, 100%, and 92%, respectively. For the 216 patients subsequently proven to have cancer, the results of EUS-FNA were diagnostic in 197 (91%); 96 (90%) of 107 patients with resectable disease, 62 (97%) of 64 with locally advanced disease, and 39 (87%) of 45 with metastatic disease. Four patients (2%) developed a clinically apparent complication that required hospital admission, including two patients who required surgery for duodenal perforation. There were no EUS-related deaths. We conclude that EUS-FNA can safely and accurately establish a cytologic diagnosis in patients with both early-stage and advanced pancreatic cancer. This enables consideration of all treatment options including protocol-based therapy.


Assuntos
Biópsia por Agulha , Endossonografia , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
19.
J Pediatr Surg ; 47(10): 1930-3, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23084210

RESUMO

We describe a case of a 15-year-old girl who presented with 2 painful masses in her right breast. Ultrasound confirmed the presence of 2 lesions, both of which appeared noncharacteristic for fibroadenomas. Both lesions were surgically resected. One was found to be a fibroadenoma and the other a granular cell tumor, both benign upon further histologic evaluation. Breast masses are rare in the pediatric population. The finding of a concurrent fibroadenoma and granular cell tumor is unique and has not been previously reported. Granular cell tumors of the breast are relatively uncommon. Often, they are mistaken for a breast malignancy. The concerning clinical and radiographic findings in this patient warranted operative excision.


Assuntos
Neoplasias da Mama/patologia , Fibroadenoma/patologia , Tumor de Células Granulares/patologia , Neoplasias Primárias Múltiplas/patologia , Adolescente , Feminino , Humanos
20.
Phys Med Biol ; 56(17): 5753-69, 2011 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-21841212

RESUMO

Quantitative analysis of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data requires the accurate determination of the arterial input function (AIF). A novel method for obtaining the AIF is presented here and pharmacokinetic parameters derived from individual and population-based AIFs are then compared. A Philips 3.0 T Achieva MR scanner was used to obtain 20 DCE-MRI data sets from ten breast cancer patients prior to and after one cycle of chemotherapy. Using a semi-automated method to estimate the AIF from the axillary artery, we obtain the AIF for each patient, AIF(ind), and compute a population-averaged AIF, AIF(pop). The extended standard model is used to estimate the physiological parameters using the two types of AIFs. The mean concordance correlation coefficient (CCC) for the AIFs segmented manually and by the proposed AIF tracking approach is 0.96, indicating accurate and automatic tracking of an AIF in DCE-MRI data of the breast is possible. Regarding the kinetic parameters, the CCC values for K(trans), v(p) and v(e) as estimated by AIF(ind) and AIF(pop) are 0.65, 0.74 and 0.31, respectively, based on the region of interest analysis. The average CCC values for the voxel-by-voxel analysis are 0.76, 0.84 and 0.68 for K(trans), v(p) and v(e), respectively. This work indicates that K(trans) and v(p) show good agreement between AIF(pop) and AIF(ind) while there is a weak agreement on v(e).


Assuntos
Artéria Axilar/fisiopatologia , Neoplasias da Mama/irrigação sanguínea , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Imagem de Perfusão/métodos , Algoritmos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Simulação por Computador , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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