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1.
Sci Rep ; 14(1): 3330, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336918

RESUMO

Strain engineering for gallium nitride has been studied by many researchers to improve the performance of various devices (i.e., light-emitting diodes, laser diodes, power devices, high electron mobility transistors, and so on). Further miniaturization of gallium nitride devices will clearly continue in the future, and therefore an accurate understanding of the strain state in the devices is essential. However, a measurement technique for axially resolved evaluation of the strain in microareas has not yet been established. In this study, we revealed that the anisotropic strain state induced in c-plane growth gallium nitride is linked to the split state of Raman peaks, which were measured with [Formula: see text] and [Formula: see text] polarized configurations. The anisotropic strain state in c-plane gallium nitride was induced in the 3D-structure by epitaxial lateral overgrowth, which enabled successful performance of our work. This result allowed us to axially decompose the strain in c-plane gallium nitride through Raman spectroscopy and establish a measurement technique for axially resolving the strain. This measurement technique is feasible using a conventional Raman spectrometer. Furthermore, the method was indicated to be applicable to all wurtzite-type crystals, including gallium nitride, silicon carbide, and aluminum nitride. Our work provides a new perspective for understanding the complex strain state in microareas for wurtzite materials. Comprehending the strain state, which strongly affects device performance, will help promote the research and development of III-V semiconductor devices.

2.
Palliat Med Rep ; 5(1): 43-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38249830

RESUMO

Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75-2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale "disease progression" score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p = 0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale "harmful effects" (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids.Clinical Trial Registration Number UMIN000042443.

3.
Biochem Biophys Res Commun ; 684: 149145, 2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-37913587

RESUMO

Mechanical stimuli serve as crucial regulators of bone mass, promoting bone formation. However, the molecular mechanisms governing how mesenchymal stem cells (MSCs) respond to mechanical cues during their differentiation into osteogenic cells remain elusive. In this study, we found that cyclic stretching enhances MSC proliferation but does not increase the expression of osteoblast-related genes. We further revealed that this proliferative effect is mediated by fibroblast growth factor 2 (FGF-2), synthesized by MSCs in response to mechanical stress. Cell proliferation induced by cyclic stretching was inhibited upon the addition of either U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK), or early growth response 1 (EGR1)-targeting small-hairpin RNA (shRNA), indicating the involvement of the extracellular signal-regulated kinase (ERK)/EGR1 signaling pathway. Osteoblast differentiation, evaluated through ALP activity, osteoblast-related gene expression, and mineralization, was stimulated by recombinant human FGF-2 (rhFGF-2) when applied during the proliferation phase, but not when applied during the differentiation stage alone. Our results suggest that FGF-2 indirectly promotes osteoblast differentiation as a downstream effect of stimulating cell proliferation. For the first time, we demonstrate that cyclic stretching induces MSCs to produce FGF-2, which in turn encourages cell proliferation through an autocrine/paracrine mechanism, consequently leading to osteoblast differentiation.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Estresse Mecânico , Diferenciação Celular , Proliferação de Células , Osteoblastos/metabolismo
4.
PLoS One ; 18(5): e0283155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37163537

RESUMO

Cancer tissues reflect a greater number of pathological characteristics of cancer compared to cancer cells, so the evaluation of cancer tissues can be effective in determining cancer treatment strategies. Mass spectrometry imaging (MSI) can evaluate cancer tissues and even identify molecules while preserving spatial information. Cluster analysis of cancer tissues' MSI data is currently used to evaluate the phenotype heterogeneity of the tissues. Interestingly, it has been reported that phenotype heterogeneity does not always coincide with genotype heterogeneity in HER2-positive breast cancer. We thus investigated the phenotype heterogeneity of luminal breast cancer, which is generally known to have few gene mutations. As a result, we identified phenotype heterogeneity based on lipidomics in luminal breast cancer tissues. Clusters were composed of phosphatidylcholine (PC), triglycerides (TG), phosphatidylethanolamine, sphingomyelin, and ceramide. It was found that mainly the proportion of PC and TG correlated with the proportion of cancer and stroma on HE images. Furthermore, the number of carbons in these lipid class varied from cluster to cluster. This was consistent with the fact that enzymes that synthesize long-chain fatty acids are increased through cancer metabolism. It was then thought that clusters containing PCs with high carbon counts might reflect high malignancy. These results indicate that lipidomics-based phenotype heterogeneity could potentially be used to classify cancer for which genetic analysis alone is insufficient for classification.


Assuntos
Lipidômica , Neoplasias , Lipidômica/métodos , Espectrometria de Massas , Análise por Conglomerados , Triglicerídeos
5.
Sci Rep ; 12(1): 20955, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470963

RESUMO

Laser-induced periodic surface structure (LIPSS), which has a period smaller than the laser wavelength, is expected to become a potential technique for fine surface processing. We report the microscopic and macroscopic observations of the crystallinity of LIPSSs, where the characteristics such as defects generation and residual strain were analyzed, respectively. The LIPSSs were formed on a Si substrate using two different femtosecond pulses from Ti:Sapphire laser with near-infrared wavelength (0.8 µm) and free-electron laser (FEL) with mid-infrared wavelength (11.4 µm). The photon energies of the former and latter lasers used here are higher and lower than the Si bandgap energies, respectively. These LIPSSs exhibit different crystalline states, where LIPSS induced by Ti:Sapphire laser show residual strain while having a stable crystallinity; in contrast, FEL-LIPSS generates defects without residual strain. This multiple analysis (microscopic and macroscopic observations) provides such previously-unknown structural characteristics with high spatial resolution. To obtain LIPSS with suitable properties and characteristics based on each application it is paramount to identify the laser sources that can achieve such properties. Therefore, identifying the structural information of the LIPSS generated by each specific laser is of great importance.

6.
J Biomed Opt ; 27(10)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36229894

RESUMO

Significance: The water and lipid content of normal breast tissue showed mammary gland characteristics with less influence from the chest wall using six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) in a reflectance geometry. Aim: To determine the depth sensitivity of a six-wavelength TD-DOS system and evaluate whether the optical parameters in normal breast tissue can distinguish dense breasts from non-dense breasts. Approach: Measurements were performed in normal breast tissue of 37 breast cancer patients. We employed a six-wavelength TD-DOS system to measure the water and lipid content in addition to the hemoglobin concentration. The breast density in mammography and optical parameters were then compared. Results: The depth sensitivity of the system for water and lipid content was estimated to be ∼15 mm. Our findings suggest that the influence of the chest wall on the water content is weaker than that on the total hemoglobin concentration. In data with evaluation conditions, the water content was significantly higher (p < 0.001) and the lipid content was significantly lower (p < 0.001) in dense breast tissue. The water and lipid content exhibited a high sensitivity and specificity to distinguish dense from non-dense breasts in receiver-operating-characteristic curve analysis. Conclusions: With less influence from the chest wall, the water and lipid content of normal breast tissue measured by a reflectance six-wavelength TD-DOS system, together with ultrasonography, can be applied to distinguish dense from non-dense breasts.


Assuntos
Neoplasias da Mama , Água , Neoplasias da Mama/diagnóstico por imagem , Feminino , Hemoglobinas , Humanos , Lipídeos , Mamografia , Sensibilidade e Especificidade , Análise Espectral
7.
BMJ Open ; 12(3): e054914, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361645

RESUMO

INTRODUCTION: Opioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer. METHODS AND ANALYSIS: This ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting. TRIAL REGISTRATION NUMBER: UMIN000042443.


Assuntos
Analgésicos Opioides , Neoplasias , Adulto , Analgésicos Opioides/efeitos adversos , Doença Crônica , Estudos de Coortes , Humanos , Estudos Multicêntricos como Assunto , Neoplasias/complicações , Estudos Observacionais como Assunto , Dor/etiologia , Adulto Jovem
8.
Surg Case Rep ; 7(1): 16, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433770

RESUMO

BACKGROUND: Fibromatosis-like metaplastic carcinoma (FLMCa), classified as a metaplastic carcinoma of the breast, is a very rare type of metaplastic carcinoma. We report a case of FLMCa that was difficult to diagnose. CASE PRESENTATION: The patient was a 56-year-old postmenopausal woman who presented with a left-sided breast mass. A 1.3-cm irregular mass was found in the lower outer quadrant of the left breast on breast ultrasonography. She underwent core needle biopsy and vacuum-assisted biopsy, but the pathological findings only revealed inflammatory cell infiltration and a high level of fibrosis, with no malignant findings. At 3 months follow-up, she underwent a repeat breast ultrasonography, which revealed an increase in the size of the mass to 1.8 cm, and a repeat core needle biopsy, which showed a few spindle cells and squamous cells positive for cytokeratin (CK)5/6 and AE1/AE3, leading to the suspicion of FLMCa. Since the amount of tissue was insufficient to establish a definitive diagnosis, she underwent a lumpectomy. We found low-grade and slightly atypical spindle cells and partly atypical spindle cell carcinoma and squamous cell carcinoma. CK5/6 and α-SMA were positive, thus confirming FLMCa. Because the margins on the edge of the nipple side and anterior side were "ink on tumor", she underwent a mastectomy and sentinel lymph node biopsy. After the surgery, she received adjuvant chemotherapy. At 3 years and 8 months of follow-up, no recurrent or metastatic lesions were identified in her body. CONCLUSIONS: FLMCa should be considered in the differential diagnosis when collagenous fibers are proliferating and malignancy is clinically suspected. Immunohistochemical analysis may be helpful in confirming this diagnosis.

9.
Breast Cancer ; 27(5): 819-827, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32144735

RESUMO

PURPOSE: Luminal B-like breast cancer is sensitive to both chemotherapy and endocrine therapy. We aimed to assess the safety and efficacy of concomitant chemotherapy and endocrine therapy compared with chemotherapy alone in the preoperative setting in luminal B-like breast cancer. METHODS: This two-arm randomized clinical trial enrolled patients with luminal B-like human epithelial growth factor 2-negative breast cancer, who were randomly assigned at a 1:1 ratio to receive preoperative chemotherapy alone or preoperative endocrine therapy concurrent with chemotherapy for 24 weeks before surgery. The primary endpoint was the pathological complete response (pCR) rate. The secondary endpoints included the clinical response rate, toxicity, and health-related quality of life (HRQOL). RESULTS: Overall, 70 patients were randomly assigned to the chemotherapy and chemo-endocrine therapy groups. The pCR rates were 9.7% and 3.0% (P = 0.319), and the clinical complete response rates were 5.9% and 5.6% (P = 0.745) in the chemotherapy and chemo-endocrine therapy groups, respectively. There were no clear differences in treatment-related adverse events or HRQOL between the two groups. CONCLUSIONS: In patients with luminal B-like breast cancer, the pCR, clinical response rate, toxicity, and HRQOL with the concomitant administration of endocrine therapy and chemotherapy were not superior to chemotherapy alone in the preoperative setting.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Mama/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Qualidade de Vida , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Resultado do Tratamento , Adulto Jovem
10.
Technol Cancer Res Treat ; 18: 1533033819830411, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30764728

RESUMO

We measured total hemoglobin concentrations in breast tumors by near-infrared time-resolved spectroscopy. Muscles interfere with measurement when the probe is close to the chest wall. Since the target area of measurement depends on the distance between the light source and probe detector, we inferred that this issue could be solved by reducing the source-detector distance. The purpose of this study was to examine the effects of the source-detector distance on the measurement of total hemoglobin concentration in the breast. We examined 26 patients with breast tumors. Total hemoglobin concentration was measured in tumors and the contralateral normal breasts at source-detector distances of 20 and 30 mm. The difference in total hemoglobin concentration between each tumor and the contralateral breast was calculated. The normal breast total hemoglobin concentration was significantly smaller for the source-detector distance of 20 mm than for the source-detector distance of 30 mm. Differences in source-detector distance did not significantly affect tumor total hemoglobin. The difference in total hemoglobin concentration between the tumor and the contralateral breast obtained at the source-detector distance of 20 mm was significantly higher than that obtained at the source-detector distance of 30 mm. From these results, we considered that measurement with a source-detector distance of 20 mm is less affected by the chest wall than with a source-detector distance of 30 mm and that the difference in total hemoglobin concentration between the tumor and the contralateral breast at a source-detector distance of 20 mm can better reflect the net total hemoglobin concentrations of the breast tumors. In conclusion, using a probe with a source-detector distance of 20 mm can more accurately evaluate the total hemoglobin concentration in breast tumors.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Hemoglobinas/análise , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Parede Torácica/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
11.
Biomed Opt Express ; 9(11): 5792-5808, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30460162

RESUMO

We introduced a method for producing solid phantoms with various water-to-lipid ratios that can simulate the absorption, and to some extent the scattering characteristics of human breast tissue. We also achieved phantom stability for a minimum of one month by solidifying the emulsion phantoms. The characteristics of the phantoms were evaluated using the six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) system we developed to measure water and lipid contents and hemoglobin concentration. The TD-DOS measurements were validated with a magnetic resonance imaging system.

12.
J Biomed Opt ; 23(2): 1-6, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29488362

RESUMO

The purpose of this study was to evaluate the effects of the thickness and depth of tumors on hemoglobin measurements in breast cancer by optical spectroscopy and to demonstrate tissue oxygen saturation (SO2) and reduced scattering coefficient (µs') in breast tissue and breast cancer in relation to the skin-to-chest wall distance. We examined 53 tumors from 44 patients. Total hemoglobin concentration (tHb), SO2, and µs' were measured by time-resolved spectroscopy (TRS). The skin-to-chest wall distance and the size and depth of tumors were measured by ultrasonography. There was a positive correlation between tHb and tumor thickness, and a negative correlation between tHb and tumor depth. SO2 in breast tissue decreased when the skin-to-chest wall distance decreased, and SO2 in tumors tended to be lower than in breast tissue. In breast tissue, there was a negative correlation between µs' and the skin-to-chest wall distance, and µs' in tumors was higher than in breast tissue. Measurement of tHb in breast cancer by TRS was influenced by tumor thickness and depth. Although SO2 seemed lower and µs' was higher in breast cancer than in breast tissue, the skin-to-chest wall distance may have affected the measurements.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Feminino , Hemoglobinas/análise , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Oxigênio/sangue , Processamento de Sinais Assistido por Computador , Ultrassonografia
14.
Cancer Chemother Pharmacol ; 81(5): 923-933, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29594360

RESUMO

PURPOSE: Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. MATERIALS AND METHODS: We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). RESULTS: A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1-53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95% CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients. CONCLUSIONS: Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Furanos/administração & dosagem , Cetonas/administração & dosagem , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia , Intervalo Livre de Progressão , Qualidade de Vida , Receptor ErbB-2/metabolismo
15.
PLoS One ; 12(8): e0183724, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28832678

RESUMO

Triple-negative breast cancer (TNBC) is one of the breast cancer subtype that displays a high risk of early recurrence and short overall survival. Improvement of the prognosis of patients with TNBC requires identifying a predictive factor of recurrence, which would make it possible to provide beneficial personalized treatment. However, no clinically reliable predictive factor is currently known. In this study, we investigated the predictive factor of recurrence in TNBC using matrix-assisted laser desorption/ionization-imaging mass spectrometry for lipid profiling of breast cancer specimens obtained from three and six patients with recurrent and non-recurrent TNBC, respectively. The signal for phosphatidylcholine (PC) (32:1) at m/z 732.5 was significantly higher in the recurrence group compared to the non-recurrence group (P = 0.024). PC (32:1) was more abundant in the cancer epithelial area than it was in the surrounding stroma, suggesting that abnormal lipid metabolism was associated with malignant transformation. Our results indicate PC (32:1) as a candidate predictive factor of TNBC recurrence. A future prospective study investigating whether personalized therapy based on PC (32:1) intensity improves the prognosis of patients with TNBC is recommended.


Assuntos
Fosfatidilcolinas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Recidiva , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias de Mama Triplo Negativas/patologia
16.
J Nucl Med ; 57(8): 1189-95, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26940765

RESUMO

UNLABELLED: Diffuse optical spectroscopic imaging (DOSI) is used as an indicator of tumor blood volume quantified by tissue hemoglobin concentrations. We aimed to determine whether early changes in tumor total hemoglobin (tHb) concentration can predict a pathologic complete response (pCR) to neoadjuvant chemotherapy in patients with operable breast cancer, and we compared the predictive value of pCR between DOSI and (18)F-FDG PET combined with CT. METHODS: Of the 100 patients enrolled, 84 patients were prospectively evaluated for primary objective analysis. Sixty-four of the patients underwent both sequential DOSI scans at baseline after their first and second chemotherapy courses and (18)F-FDG PET/CT at baseline and after their second chemotherapy course. The mean tHb (tHbmean) concentration and SUVmax of the lesion were measured using DOSI and (18)F-FDG PET/CT, respectively, and the percentage change in tHbmean (∆tHbmean) and change in SUVmax (∆SUVmax) were calculated. We compared the diagnostic performances of DOSI and (18)F-FDG PET/CT for predicting pCR via the analysis of the receiver-operating-characteristic curves. RESULTS: pCR was achieved in 16 patients, and neoadjuvant chemotherapy caused a significant reduction of ∆tHbmean in pCR compared with non-pCR after the 2 chemotherapy courses. When the tentative ∆tHbmean cutoff values after the first and second courses were used, the ability to predict pCR was as follows: 81.2% sensitivity/47.0% specificity and 93.7% sensitivity/47.7% specificity, respectively. Comparison of the diagnostic performances of DOSI and (18)F-FDG PET/CT revealed areas under the curve of 0.69 and 0.75 of ∆tHbmean after the first and second courses, respectively, which were lower than those of ∆SUVmax (0.90). CONCLUSION: DOSI predicted pCR in patients with breast cancer with moderate accuracy. The diagnostic performance of DOSI was inferior to that of the early metabolic response as monitored by (18)F-FDG PET/CT.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Hemoglobinas/análise , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Tomografia Óptica/métodos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Quimioterapia Adjuvante/métodos , Monitoramento de Medicamentos/métodos , Detecção Precoce de Câncer , Feminino , Fluordesoxiglucose F18 , Humanos , Pessoa de Meia-Idade , Imagem Molecular , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
17.
Mol Cell Biol ; 36(3): 394-406, 2016 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-26572825

RESUMO

Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone acetyltransferase for forming the prereplicative complex (pre-RC) at the replication origin. Pre-RC formation is completed by loading of the MCM2-7 heterohexameric complex, which functions as a helicase in DNA replication. HBO1 recruited to the replication origin by CDT1 acetylates histone H4 to relax the chromatin conformation and facilitates loading of the MCM complex onto replication origins. However, the acetylation status and mechanism of regulation of histone H3 at replication origins remain elusive. HBO1 positively regulates cell proliferation under normal cell growth conditions. Whether HBO1 regulates proliferation in response to DNA damage is poorly understood. In this study, we demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were phosphorylated in an ATM/ATR DNA damage sensor-dependent manner after UV treatment. ATM/ATR-dependently phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4(DDB2). Replacement of endogenous HBO1 in Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV irradiation. Our findings demonstrate that HBO1 is one of the targets in the DNA damage checkpoint. These results show that ubiquitin-dependent control of the HBO1 protein contributes to cell survival during UV irradiation.


Assuntos
Proliferação de Células/efeitos da radiação , Dano ao DNA/efeitos da radiação , Proteínas de Ligação a DNA/metabolismo , Histona Acetiltransferases/metabolismo , Fosforilação/efeitos da radiação , Ubiquitina-Proteína Ligases/metabolismo , Acetilação/efeitos da radiação , Células HEK293 , Células HeLa , Histona Acetiltransferases/química , Histona Acetiltransferases/genética , Histonas/metabolismo , Humanos , Mutação Puntual , Mapas de Interação de Proteínas , Estabilidade Proteica/efeitos da radiação , Proteólise , Ubiquitina/metabolismo , Ubiquitinação/efeitos da radiação , Raios Ultravioleta
18.
Breast Cancer ; 23(6): 844-850, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26474784

RESUMO

BACKGROUND: Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. METHODS: We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. RESULTS: The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. CONCLUSIONS: The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Hemoglobinas/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Feminino , Humanos , Glândulas Mamárias Humanas/irrigação sanguínea , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Valores de Referência , Parede Torácica/anatomia & histologia , Parede Torácica/diagnóstico por imagem
19.
Int J Clin Exp Med ; 8(9): 16914-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26629243

RESUMO

A 53-year-old woman with breast cancer received FEC treatment (5FU: 500 mg/m(2), epirubicin: 100 mg/m(2), and cyclophosphamide: 500 mg/m(2)) every 3 weeks as preoperative chemotherapy. Fifteen days after her third cycle of FEC, she developed a cold. Diplopia occurred 4 days after developing the cold, and progressive paresthesia of the hands and weakness of the limbs occurred. She had ophthalmoplegia, ataxia, and are flexia and was diagnosed with Miller Fisher Syndrome (MFS). The cause of MFS during chemotherapy is believed to be caused by an immunological response to infection, or drug neurotoxicity. In our case, since the patient underwent an antecedent upper respiratory infection in the period of myelosuppression, her MFS was probably induced by the immunoreaction associated with this infection. Our patient underwent intravenous immunoglobulin therapy. After initiation of the treatment, her neurological symptoms improved, then, she received a fourth cycle of FEC and her remaining neurological symptoms did not worsen. Thus, we report a rare case of MFS developed in immunosuppression by chemotherapy and remind physicians of the alarming triad of MFS symptoms.

20.
Jpn J Radiol ; 33(2): 107-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25544028

RESUMO

The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Renais/secundário , Segunda Neoplasia Primária/diagnóstico por imagem , Veias Renais/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Vasculares/secundário , Adulto , Evolução Fatal , Feminino , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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