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1.
Opt Express ; 27(5): 6030-6036, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876196

RESUMO

Ultrafast time-resolved x-ray absorption near edge spectroscopy (XANES) experiment was performed on a magnetite (Fe3O4) film using a femtosecond laser plasma x-ray source delivering Bremsstrahlung radiation. Ultrafast temporal evolution of the XANES of Fe3O4 following an excitation by an infra-red (IR) laser pulse was observed in a pump-probe scheme. The Fe K x-ray absorption edge shifts towards low energy upon IR excitation as much as 12 eV, which is mainly attributed to the charge transfer between the Fe ions. The shift in the absorption edge occurred within about 150 fs, typical time of non-thermal electronic redistribution. The charge transfer also causes an ultrafast increase in the IR transmission in the similar time scale.

2.
Osteoporos Int ; 28(4): 1413-1422, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28083668

RESUMO

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. INTRODUCTION: AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. METHODS: We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >-2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. RESULTS: BMD significantly decreased from baseline to 5 years at the lumbar spine (-6.15%), femur neck (-7.12%), and total hip (-6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (-2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P < 0.001); these changes were independent of total hip BMD. CONCLUSIONS: Long-term adjuvant AI treatment negatively influenced bone quality in addition to BMD in patients with breast cancer. This study suggests that early monitoring and management are needed in non-osteoporotic patients with breast cancer who are starting AIs.


Assuntos
Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Absorciometria de Fóton , Idoso , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Articulação do Quadril/efeitos dos fármacos , Articulação do Quadril/patologia , Articulação do Quadril/fisiopatologia , Humanos , Estudos Longitudinais , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/induzido quimicamente , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/fisiopatologia , Estudos Retrospectivos
3.
Ann Oncol ; 27(5): 828-33, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26823524

RESUMO

BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.


Assuntos
Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer , Prognóstico , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Antígeno Ki-67/genética , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores de Progesterona/genética
4.
Ann Oncol ; 26(9): 1974-1980, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26116430

RESUMO

BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.


Assuntos
Comunicação , Conflito Psicológico , Tomada de Decisões , Relações Médico-Paciente , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Educação de Pacientes como Assunto , Qualidade de Vida , Fatores Socioeconômicos , Inquéritos e Questionários
5.
Br J Cancer ; 110(4): 1088-100, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24548884

RESUMO

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Estudos de Casos e Controles , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genética
6.
Ann Oncol ; 24(9): 2298-304, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23704201

RESUMO

BACKGROUND: In this study, the prognostic impact of the presence of the multifocal or multicentric tumor (MMT) and its association with molecular subtypes were investigated. PATIENTS AND METHODS: We investigated the breast cancer metastasis and survival in patients with multifocal or multicentric invasive foci in the same breast. The study population includes 2882 patients in the Seoul National University Hospital Breast Care Center (SNUHBCC) dataset and 41 179 patients in Korean Breast Cancer Registry (KBCR) dataset. RESULTS: From SNUHBCC dataset, we observed a significant role of MMT in developing distant metastasis and death when the tumors were triple-negative subtype. This subtype-specific prognostic importance of MMT in overall survival was also seen in KBCR dataset (HR, 1.32; 95% CI, 1.02-1.69). In tumors <2 cm, the hazard ratios (HRs) for node metastasis and death were similar along the tumor size change in triple-negative subtype, while other subtypes showed a stepwise increment, suggesting the biologic importance of small invasive foci in this subtype. CONCLUSIONS: Our results demonstrate the prognostic importance of MMT in patients with triple-negative breast cancers. Small additional invasive foci in triple-negative breast cancer patients should be considered as clinically relevant tumor deposits.


Assuntos
Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Invasividade Neoplásica , República da Coreia/epidemiologia , Sobrevida , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/cirurgia
7.
Ann Oncol ; 23(8): 1992-1998, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22700992

RESUMO

BACKGROUND: Cancer patients are at high risk for skin problems because rapidly proliferating skin cells are susceptible to anticancer therapies. However, the effects of daily skin care habits on development of skin problems in cancer patients have rarely been studied. PATIENTS AND METHODS: We conducted a survey of daily skin care habits and the presence of skin problems in 866 cancer patients. RESULTS: Hot water bath>1 h significantly increased the risk of definite eruptions [odds ratio (OR) 4.09] and the risk of itching or pain on the skin (OR 1.73). Diligent use of moisturizers did not decrease the risk of definite eruptions and symptoms, and daily bathing, scrubbing off the skin while bathing, and sun protection did not influence the risk of definite eruptions and symptoms. Subgroup analysis of 183 breast cancer patients showed results similar to the total results, including that hot water bath>1 h significantly increased the risk of definite eruptions (OR 3.41). CONCLUSIONS: Being a cross-sectional study, our study could not prove causality. However, at the present stage of knowledge, avoidance of hot water baths of protracted duration should be first emphasized in patient education to prevent skin problems in cancer patients.


Assuntos
Neoplasias/terapia , Higiene da Pele/métodos , Dermatopatias/prevenção & controle , Antineoplásicos/efeitos adversos , Banhos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Educação de Pacientes como Assunto/métodos , Dermatopatias/induzido quimicamente , Dermatopatias/etiologia , Inquéritos e Questionários
8.
Ann Oncol ; 23(10): 2731-2737, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22553194

RESUMO

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.


Assuntos
Neoplasias/cirurgia , Taxa de Sobrevida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Listas de Espera , Adulto Jovem
9.
J Synchrotron Radiat ; 18(Pt 2): 143-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21335899

RESUMO

Focused hard X-ray microbeams for use in X-ray nanolithography have been investigated. A 7.5 keV X-ray beam generated at an undulator was focused to about 3 µm using a Fresnel zone plate fabricated on silicon. The focused X-ray beam retains a high degree of collimation owing to the long focal length of the zone plate, which greatly facilitates hard X-ray nanoscale lithography. The focused X-ray microbeam was successfully utilized to fabricate patterns with features as small as 100 nm on a photoresist.

10.
Opt Express ; 18(7): 7253-62, 2010 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-20389746

RESUMO

We present a reflection based coherent diffraction imaging method which can be used to reconstruct a non periodic surface image from a diffraction amplitude measured in reflection geometry. Using a He-Ne laser, we demonstrated that a surface image can be reconstructed solely from the reflected intensity from a surface without relying on any prior knowledge of the sample object or the object support. The reconstructed phase image of the exit wave is particularly interesting since it can be used to obtain quantitative information of the surface depth profile or the phase change during the reflection process. We believe that this work will broaden the application areas of coherent diffraction imaging techniques using light sources with limited penetration depth.


Assuntos
Processamento de Imagem Assistida por Computador , Óptica e Fotônica , Algoritmos , Simulação por Computador , Desenho de Equipamento , Ouro/química , Imageamento Tridimensional , Lasers , Silício/química , Propriedades de Superfície , Raios Ultravioleta , Raios X
11.
Sci Rep ; 10(1): 15445, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963275

RESUMO

We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.


Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Carga Tumoral , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida , Adulto Jovem
12.
Ann Oncol ; 20(4): 636-41, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19179551

RESUMO

BACKGROUND: Although recent studies suggest high accuracy of breast magnetic resonance imaging (MRI) in predicting residual tumor extent after neo-adjuvant systemic treatment (NST), its use is still controversial. In this study, we aimed to identify predictive factors of MRI accuracy after NST to determine a subgroup of patients in whom the use of MRI provides best additional benefit. MATERIALS AND METHODS: Clinicopathologic and molecular profiles of breast cancer patients were investigated and their relationships with MRI accuracy were analyzed. RESULTS: From January 2006 to February 2008, 195 patients received NST and preoperative MRI. In overall, MRI predicted residual tumor extent with higher accuracy than ultrasonography. Triple-negative (TN) tumors showed highest correlation between MRI-measured and pathologic tumor size (r = 0.781) when compared with other subtypes. Multivariate analysis showed age and HER2 expression status as independent factors predicting MRI accuracy. When patients were classified based on their age and HER2 status, relatively older patients (>45) with HER2-negative tumors showed highest MRI accuracy. This finding was further validated using an independent cohort of 63 consecutive patients. CONCLUSION: Age and HER2 status independently affected MRI accuracy after NST. This observation may guide more tailored approach in using MRI in breast cancer patients undergoing NST.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Genes erbB-2 , Imageamento por Ressonância Magnética/normas , Adulto , Fatores Etários , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Análise Multivariada
13.
Clin Genet ; 76(2): 152-60, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19656164

RESUMO

The BRCA1 and BRCA2 genes are the strongest susceptibility genes identified for breast cancer worldwide. However, BRCA1/BRCA2 have been incompletely investigated due to their large size and the genomic rearrangements that occasionally occur within them. Here we performed a comprehensive mutational analysis for BRCA1/BRCA2 in 206 Korean patients with breast cancer. We analyzed all exons and flanking regions of BRCA1/BRCA2 by direct sequencing and screened deletions or duplications involving BRCA1/BRCA2 by multiplex ligation-dependent probe amplification. We reconstructed haplotypes using intragenic single nucleotide polymorphisms (SNPs) to investigate the possibility of a founder effect among recurrent mutations. In our series, 38 patients (18.4%) had one or more BRCA1/BRCA2 mutations including 10 novel ones. Three additional patients carried novel distinct unclassified variants with potentially harmful effects. No large deletions or duplications involving BRCA1/BRCA2 were identified in our series. Haplotype analyses and allele separation suggested that the most frequent mutation in Koreans, BRCA2:c.7480C>T, might have originated from a common ancestor. BRCA1/BRCA2 mutations were more frequent in a group with family history, bilateral cancer or multiple site cancer than in a group without the risk factors described or an unknown risk group. In contrast, mutation frequencies in the early-onset cancer group were not higher than in the unknown risk group. Our results will be helpful to understand the mutation spectrum in BRCA1/BRCA2 genes and establish a genetic screening strategy. In addition, this study suggests the possibility of the first true founder mutation of BRCA1/BRCA2 identified in the Korean population.


Assuntos
Povo Asiático/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Efeito Fundador , Mutação/genética , Sequência de Aminoácidos , Proteína BRCA1/química , Proteína BRCA2/química , Sequência de Bases , Sequência Conservada , Análise Mutacional de DNA , Feminino , Haplótipos/genética , Humanos , Coreia (Geográfico) , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência
14.
Cancer Res ; 57(24): 5465-8, 1997 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9407951

RESUMO

Phospholipase C-gamma1 (PLC-gamma1) mediates signals from various extracellular origins to evoke cellular events such as mitogenesis. Previously, we reported that PLC-gamma1 was highly expressed in colorectal cancer and familial adenomatous polyposis, suggesting that PLC-gamma1 might be oncogenic. In this study, we have established rat 3Y1 fibroblasts that overexpress whole PLC-gamma1 and src homology 2 (SH2)-SH2-SH3 domain of PLC-gamma1. These cells showed a transformed phenotype and were tumorigenic when transplanted into nude mice. These results indicate that overexpression of PLC-gamma1 could transform rat fibroblasts, and the transformation is mediated by SH2-SH2-SH3 domain of PLC-gamma1.


Assuntos
Transformação Celular Neoplásica , Fibroblastos/citologia , Fibroblastos/enzimologia , Isoenzimas/fisiologia , Fosfolipases Tipo C/fisiologia , Animais , Células Cultivadas , Isoenzimas/biossíntese , Camundongos , Camundongos Nus , Fosfolipase C gama , Ratos , Transfecção , Fosfolipases Tipo C/biossíntese , Domínios de Homologia de src
15.
Cancer Res ; 54(8): 2240-4, 1994 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-8174133

RESUMO

Phosphoinositide-specific phospholipase C (PLC) isozymes occupy a central role in the signal transduction system by regulating various cellular processes including proliferation and differentiation. In the present study, we examined the contents of PLCs in colorectal adenomas, carcinomas, and normal mucosa obtained from 4 familial adenomatous polyposis patients to find out whether this enzyme plays any role in the pathogenesis of adenomas and/or carcinomas in familial adenomatous polyposis. Radioimmunoassay and immunoblot analysis revealed that in contrast to little difference in PLC-beta 1 and PLC-delta 1 content, a considerably higher level of PLC-gamma 1 was detected in 3 of 4 cases for adenoma and in all cases for carcinoma as compared to normal mucosa. The level of PLC-gamma 1 expression increased from normal mucosa to adenoma, and finally to carcinoma progressively. Immunohistochemical findings also confirmed this observation. Likewise, activity of PLC-gamma 1 was considerably higher in adenomas and carcinomas than in normal mucosa. These results suggest that PLC-gamma 1-mediated signal transduction may play a significant role in the progression of colorectal tumors in patients with familial adenomatous polyposis.


Assuntos
Polipose Adenomatosa do Colo/enzimologia , Mucosa Intestinal/enzimologia , Isoenzimas/biossíntese , Fosfolipases Tipo C/biossíntese , Adenoma/enzimologia , Adenoma/patologia , Adenoma/cirurgia , Polipose Adenomatosa do Colo/patologia , Polipose Adenomatosa do Colo/cirurgia , Adulto , Carcinoma/enzimologia , Carcinoma/patologia , Carcinoma/cirurgia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Isoenzimas/análise , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Fosfolipases Tipo C/análise
16.
Eur J Surg Oncol ; 42(8): 1169-75, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27296727

RESUMO

PURPOSE: Previously, we reported a nomogram for the prediction of positive resection margin (RM) after breast conserving surgery (BCS). This study was conducted to evaluate the clinical usefulness of the nomogram. METHODS: Prospective patients who underwent operations using the nomogram between July 2012 and August 2013 (nomogram group; N = 260) were compared with past control patients who underwent operations between July 2010 and October 2011 and underwent frozen section biopsy (FSB) without use of the nomogram (N = 266). In the nomogram group, an intraoperative assessment of RM using FSB was only performed when the nomogram score was higher than predefined cut-off (>80). In addition, we conducted retrospective analysis of additional 181 patients who received BCS in another institute (Kyoto University Hospital). These patients did not undergo FSBs for RMs. RESULTS: Of 260 patients, 161 (61.9%) presented low nomogram scores and avoided FSB. The surgical decision to use the nomogram did not significantly increase reoperation rate due to positive RM compared with the control FSB group (4.6% vs. 3.8%, p = 0.47). The surgery time was significantly reduced by 18.1% (mean 14.7 min) in nomogram group (p < 0.001). Of 99 nomogram high-score patients, 14 presented with positive RM on FSB and 11 of them avoided reoperation. In the Kyoto cohort, the reoperation rate was significantly lower in low-score patients than in high-score patients (2.7% vs. 11.4%, p < 0.001). CONCLUSIONS: We showed that our nomogram is useful to reduce FSBs without increasing reoperation rate for surgeons who perform routine FSBs. For most surgeons, it can give useful information about the possibility of tumor-positive RMs.


Assuntos
Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/cirurgia , Mastectomia Segmentar/métodos , Nomogramas , Densidade da Mama , Calcinose/diagnóstico por imagem , Calcinose/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Estudos de Casos e Controles , Feminino , Secções Congeladas , Humanos , Imageamento por Ressonância Magnética , Margens de Excisão , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Ultrassonografia Mamária
17.
Biochim Biophys Acta ; 1242(2): 99-113, 1995 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-7492569

RESUMO

The importance of PLC activation in cell proliferation is evident from the fact that the hydrolysis of PtdIns(4,5)P2 is one of the early events that follow the interaction of many growth factors and mitogens with their respective receptors. However, the importance of PLC activation is not restricted to proliferation; it is one of the most common transmembrane signaling events elicited by receptors that regulate many other cellular processes, including differentiation, metabolism, secretion, contraction, and sensory perception. It is also clear that cell proliferation signaling does not always require PLC, as indicated by the fact that growth factors such as insulin and CSF-1 do not appear to elicit the hydrolysis of PtdIns(4,5)P2, even though the intracellular domains of their receptors carry a PTK domain and the receptors show topologies very similar to those of the PLC-activating growth factors PDGF, EGF, and FGF. The growth factor-dependent activation of PLC is initiated by the formation of a complex between the receptor PTK and PLC-gamma; the formation of this complex is mediated by a specific interaction between a tyrosine phosphate residue on the intracellular domain of PTK and the SH2 domain of PLC-gamma. The receptor PTK subsequently phosphorylates PLC-gamma, of which two distinct isozymes, PLC-gamma 1 and PLC-gamma 2, have been identified. Proliferation of T cells and B cells in response to the aggregation of their respective cell surface receptors is also accompanied by the activation of PLC-gamma isozymes at an early stage. Unlike growth factor receptors, the T cell and B cell receptors lack intrinsic PTK activity but associate with several non-receptor PTKs of the Src and Syk families. Although the specific kinases are not known, one or more of these enzymes phosphorylate and activate PLC-gamma 1 and PLC-gamma 2. Transduction of growth signals by G protein-coupled receptors such as those for thrombin or bombesin also requires PtdIns(4,5)P2 hydrolysis, which, in this instance, is mediated by PLC-beta isozymes. The PLC-beta subfamily consists of four distinct members: PLC-beta 1, PLC-beta 2, PLC-beta 3, and PLC-beta 4. Agonist interaction with specific G protein-coupled receptors causes the dissociation of Gq proteins into G alpha and G beta gamma subunits and the exchange of GDP bound to G alpha for GTP. The resulting GTP-bound G alpha subunit then activates PLC-beta isoforms by binding to the carboxyl-terminal region of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Mitose , Diester Fosfórico Hidrolases/fisiologia , Transdução de Sinais , Fosfolipases Tipo C/fisiologia , Animais , Ciclo Celular , Membrana Celular/química , Núcleo Celular/fisiologia , Ativação Enzimática , Proteínas de Ligação ao GTP/fisiologia , Humanos , Isoenzimas/fisiologia , Fosfatidilinositol Diacilglicerol-Liase , Receptores de Superfície Celular/fisiologia
18.
J Mol Med (Berl) ; 79(11): 648-55, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11715068

RESUMO

The main reason for the recent interest in p53 is that almost 50% of human cancers contain p53 gene mutations. The majority of studies on p53 alterations in breast cancer have been limited to the isolated cases of ductal carcinoma in situ and infiltrating ductal carcinoma. The aims of this study were to determine the status and timing of p53 mutation in the progression from atypical ductal hyperplasia to invasive cancer, and to evaluate the patterns of p53 mutations in noninvasive and invasive lesions. Available lesions of invasive (n=88) and noninvasive (n=76) lesions were microdissected in 107 paraffin-embedded tissues (19 ductal carcinomas in situ, 57 invasive carcinomas with intraductal components, and 31 pure invasive carcinomas) and double-strand DNA sequencing was performed in exon 4-9 of the p53 gene. Among in situ cancers without invasive disease 36.8% had p53 mutations whereas in situ cancer with concurrent invasive disease showed p53 mutations in 33.3% of cases. In particular, two of seven atypical ductal hyperplasias harbored p53 alterations (one insertion and one missense mutation) in exon 8. The invasive component harbored p53 mutations in 30 of 88 cases (34.1%). We also discovered a novel deletion of 14 bp in exon 6 of two invasive lesions. The invasive component (1.33+/-0.13) carried a greater number of p53 mutations than its counterparts (1.19+/-0.10) and demonstrated more frequent multiple mutations (23.3% vs. 15.4%), but without statistical significance. Moreover, no statistical significance could be attached to the mutation frequency in the zinc-binding domains (26.7% vs. 15.4%), the directly DNA contact region (13.3% vs. 15.4%) and the missense mutation of p53 (50.0% vs. 57.7%) of the two groups. Based on our results, in spite of the small number of the lesions investigated, p53 mutation can occur at the stage of atypical ductal hyperplasia. The hypermutability and the specific p53 mutations involving the biologically functional domain (e.g., zinc binding domain or DNA contact region) have an insignificant influence on invasive progression in the breast cancer.


Assuntos
Neoplasias da Mama/genética , Genes p53/genética , Hiperplasia/genética , Mutação , Lesões Pré-Cancerosas/genética , Sequência de Bases , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Códon , Progressão da Doença , Éxons , Feminino , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Fatores de Tempo
19.
Cell Death Differ ; 22(4): 665-76, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25342465

RESUMO

Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.


Assuntos
Membrana Celular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Queratina-19/metabolismo , Receptor ErbB-2/metabolismo , Animais , Anticorpos/imunologia , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Queratina-19/antagonistas & inibidores , Queratina-19/imunologia , Sistema de Sinalização das MAP Quinases , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos Transgênicos , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/química , Transcrição Gênica/efeitos dos fármacos
20.
Eur J Surg Oncol ; 41(3): 426-32, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25578249

RESUMO

PURPOSE: Studies regarding the effects of aesthetic outcomes after breast cancer surgery on quality of life (QoL) have yielded inconsistent results. This study analyzed the aesthetic outcomes and QoL of women who underwent breast conserving surgery (BCS) or total mastectomy with immediate reconstruction (TMIR) using objective and validated methods. PATIENTS AND METHODS: QoL questionnaires (EORTC QLQ-C30, BR23, and HADs) were administered at least 1 year after surgery and adjuvant therapy to 485 patients who underwent BCS, 46 who underwent TMIR, and 87 who underwent total mastectomy (TM) without reconstruction. Aesthetic results were evaluated using BCCT.core software and by a panel of physicians. Patients' body image perception was assessed using the body image scale (BIS). RESULTS: QoL outcomes, including for social and role functioning, fatigue, pain, body image, and arm symptoms, were significantly better in the BCS and TMIR groups than in the TM group (p<0.05 each). BIS was significantly better in the BCS than in the TM or TMIR group (p<0.001 each). In the BCS and TMIR groups, general QoL factors were not significantly associated with objective cosmetic outcomes, except for body image in the QLQ-BR23. In contrast, patients with poorer BIS score reported lower QoL in almost all items of the QLQ-C30, BR23, and HADS (p<0.05 each). CONCLUSION: In conclusion, BCS and TMIR enhanced QoL compared with TM. Among BCS and TMIR patients, objectively measured cosmetic results did not affect general QoL. Self-perception of body image seems to be more important for QoL after breast cancer surgery.


Assuntos
Imagem Corporal/psicologia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Mastectomia Simples/métodos , Qualidade de Vida/psicologia , Adulto , Neoplasias da Mama/psicologia , Feminino , Humanos , Mamoplastia/psicologia , Mastectomia Segmentar/psicologia , Mastectomia Simples/psicologia , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento
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