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1.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542258

RESUMO

As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.


Assuntos
Quebras de DNA de Cadeia Dupla , Células-Tronco Embrionárias Murinas , Animais , Camundongos , Reparo do DNA , Reparo do DNA por Junção de Extremidades , Análise de Sequência de RNA , Perfilação da Expressão Gênica
2.
Keio J Med ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38403636

RESUMO

Radiation-induced nausea and vomiting (RINV) is a frequent adverse event that occurs in patients undergoing radiotherapy. However, research on RINV is underrepresented. This prospective single-institution exploratory pilot study investigated the incidence of RINV according to the irradiation site and observed the efficacy of symptomatic antiemetic treatment in controlling symptoms of RINV. The primary outcomes were the proportions of emesis-free days and nausea-free days. The secondary endpoints included the time to the first episode of RINV, frequency of vomiting, and severity of nausea, including its impact on eating habits and weight loss. Fifteen patients were enrolled in each group (minimal, low, and moderate emetogenic risk). All patients received greater than 20 Gy in five fractions. Evaluation was based on weekly questionnaires completed by patients during routine clinic visits. Nausea and vomiting occurred in 11 and 0 patients, respectively. Six of 15 patients in the minimal-risk group, 1 in the low-risk group, and 4 in the moderate-risk group experienced nausea. Although all 11 symptomatic patients were offered antiemetics, only 3 used them, who reported satisfactory control of nausea. The percentage of emesis-free days for all patients was 100% and the percentage of nausea-free days for the 11 patients who developed RINV was 38%. An unexpectedly high percentage of patients in the minimal-risk group experienced nausea; all had breast cancer. Future studies should investigate factors beyond the irradiation site, including the characteristics of the patient and the treatment, to better predict an individual's risk of RINV.

3.
Br J Radiol ; 96(1151): 20230351, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37750858

RESUMO

OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.


Assuntos
Neoplasias Ósseas , Qualidade de Vida , Humanos , Estudos Transversais , Estudos Prospectivos , Analgésicos Opioides , Neoplasias Ósseas/patologia , Cuidados Paliativos , Inquéritos e Questionários
4.
J Radiat Res ; 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37154504

RESUMO

We investigated dose perturbations caused by 125I seeds in patients undergoing supplemental external beam radiotherapy (EBRT) for prostate cancer. We examined two types of nonradioactive seed models: model 6711 and model STM1251. All experiments were performed using a water-equivalent phantom. Radiochromic film was used to measure the dose distributions adjacent to the seeds upstream and downstream of the external beam source. Single and clusters of multiple seeds were placed in slots in a solid water (SW) slab to measure dose perturbations with separate versus dense seed placement at beam energies of 6 or 10 MV. Monte Carlo simulations (MCSs) were also performed to include the theoretical basis against film dosimetry. Distinct patterns of dose enhancement (buildup [BU]) were upstream, and dose reduction (builddown [BD]) were downstream of the radiation source. Model 6711 with lower photon beam energies produced larger dose perturbations of BU and BD than the model STM1251. The results showed the same tendency with different seed placements and beam energies. However, these differences were not observed in the rotational irradiation measurement, which replicated a clinical plan. Dose perturbations around seeds result in dose enhancement and dose reduction with varying impact depending on the photon beam energy and seed type. This has the potential to cancel out these perturbations using multiple beam direction fields.

5.
Adv Radiat Oncol ; 8(4): 101205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077179

RESUMO

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

6.
Oral Dis ; 29(8): 3688-3697, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36266256

RESUMO

OBJECTIVE: Porphyromonas gingivalis (Pg) is thought to be involved in the progression of Alzheimer's disease (AD). Whether Pg or its contents can reach the brain and directly affect neuropathology is, however, unknown. Here, we investigated whether outer membrane vesicles (OMVs) of Pg translocate to the brain and induce the pathogenic features of AD. MATERIAL AND METHODS: Pg OMVs were injected into the abdominal cavity of mice for 12 weeks. Pg OMV translocation to the brain was detected by immunohistochemistry using an anti-gingipain antibody. Tau protein and microglial activation in the mouse brain were examined by western blotting and immunohistochemistry. The effect of gingipains on inflammation was assessed by real-time polymerase chain reaction using human microglial HMC3 cells. RESULTS: Gingipains were detected in the region around cerebral ventricles, choroid plexus, and ventricular ependymal cells in Pg OMV-administered mice. Tau and phosphorylated Tau protein increased and microglia were activated. Pg OMVs also increased the gene expression of proinflammatory cytokines in HMC3 cells in a gingipain-dependent manner. CONCLUSION: Pg OMVs, including gingipains, can reach the cerebral ventricle and induce neuroinflammation by activating microglia. Pg OMVs may provide a better understanding of the implications of periodontal diseases in neurodegenerative conditions such as AD.


Assuntos
Doença de Alzheimer , Microglia , Humanos , Animais , Camundongos , Cisteína Endopeptidases Gingipaínas , Proteínas tau , Porphyromonas gingivalis , Ventrículos Cerebrais
7.
Heliyon ; 8(8): e10266, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36061033

RESUMO

Nowadays, ordinary people can travel in space, and the possibility of extended durations in an environment such as moon of the Earth and Mars with higher space radiation exposures compared to past missions, is increasing. Until now, the physical doses of space radiation have been measured, but measurement of direct biological effects has been hampered by its low dose and low dose-rate effect. To assess the biological effects of space radiation, we launched and kept frozen mouse embryonic stem (ES) cells in minus eighty degree Celsius freezer in ISS (MELFI) on the International Space Station (ISS) for a maximum of 1,584 days. The passive dosimeter for life science experiments in space (PADLES) was attached on the surface of the sample case of the ES cells. The physical dosimeter measured the absorbed dose in water. After return, the frozen cells were thawed and cultured and their chromosome aberrations were analyzed. Comparative experiments with proton and iron ion irradiation were performed at particle accelerators on Earth. The wild-type ES cells showed no differences in chromosomal aberrations between the ground control and ISS exposures. However, we detected an increase of chromosome aberrations in radio-sensitized histone H2AX heterozygous-deficient mouse ES cells and found that the rate of increase against the absorbed dose was 1.54-fold of proton irradiation at an accelerator. On the other hand, we estimated the quality factor of space radiation as 1.48 ± 0.2. using formulas of International Commission of Radiation Protection (ICRP) 60. The relative biological effectiveness (RBE) observed from our experiments (1.54-fold of proton) was almost equal (1.04-fold) to the physical estimation (1.48 ± 0.2). It should be important to clarify the relation between biological effect and physical estimates of space radiation. This comparative study paves a way to reveal the complex radiation environments to reduce the uncertainty for risk assessment of human stay in space.

8.
Development ; 149(3)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35029658

RESUMO

Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.


Assuntos
Tecido Adiposo/metabolismo , Galectina 3/metabolismo , Músculo Esquelético/fisiologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Actinas/genética , Actinas/metabolismo , Adipogenia , Tecido Adiposo/citologia , Animais , Cardiotoxinas/farmacologia , Diferenciação Celular , Senescência Celular/genética , Dieta Hiperlipídica , Feminino , Galectina 3/deficiência , Galectina 3/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/deficiência , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Regeneração , Transdução de Sinais/genética
9.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166236, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389473

RESUMO

Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such as Porphyromonas gingivalis (Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term "periodontal medicine" is used to describe how periodontal infection/inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived from Pg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected with Pg. We observed that EVs from Pg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice. Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. The Pg-inf EVs or the recombinant histone H3 activated the NF-κB pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.


Assuntos
Vesículas Extracelulares/imunologia , Lesão Pulmonar/imunologia , Macrófagos/imunologia , Periodontite/complicações , Porphyromonas gingivalis/imunologia , Células A549 , Animais , Infecções por Bacteroidaceae , Modelos Animais de Doenças , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Lesão Pulmonar/patologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Periodontite/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Células THP-1
10.
Sci Rep ; 11(1): 14943, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294795

RESUMO

The ability of cancer cells to undergo partial-epithelial mesenchymal transition (p-EMT), rather than complete EMT, poses a higher metastatic risk. Although Fusobacterium nucleatum mainly inhabits in oral cavity, attention has been focused on the F. nucleatum involvement in colorectal cancer development. Here we examined the p-EMT regulation by F. nucleatum in oral squamous cell carcinoma (OSCC) cells. We cultured OSCC cells with epithelial, p-EMT or EMT phenotype with live or heat-inactivated F. nucleatum. Expression of the genes involved in epithelial differentiation, p-EMT and EMT were examined in OSCC cells after co-culture with F. nucleatum by qPCR. Cell growth and invasion of OSCC cells were also examined. Both live and heat-inactivated F. nucleatum upregulated the expression of p-EMT-related genes in OSCC cells with epithelial phenotype, but not with p-EMT or EMT phenotype. Moreover, F. nucleatum promoted invasion of OSCC cells with epithelial phenotype. Co-culture with other strains of bacteria other than Porphyromonas gingivalis did not alter p-EMT-related genes in OSCC cells with epithelial phenotype. F. nucleatum infection may convert epithelial to p-EMT phenotype via altering gene expression in OSCC. Oral hygiene managements against F. nucleatum infection may contribute to reduce the risk for an increase in metastatic ability of OSCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/virologia , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/patogenicidade , Neoplasias Bucais/virologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Infecções por Fusobacterium/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , Metástase Neoplásica , Higiene Bucal
11.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165731, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088316

RESUMO

Outer membrane vesicles (OMVs) are nanosized particles derived from the outer membrane of gram-negative bacteria. Oral bacterium Porphyromonas gingivalis (Pg) is known to be a major pathogen of periodontitis that contributes to the progression of periodontal disease by releasing OMVs. The effect of Pg OMVs on systemic diseases is still unknown. To verify whether Pg OMVs affect the progress of diabetes mellitus, we analyzed the cargo proteins of vesicles and evaluated their effect on hepatic glucose metabolism. Here, we show that Pg OMVs were equipped with Pg-derived proteases gingipains and translocated to the liver in mice. In these mice, the hepatic glycogen synthesis in response to insulin was decreased, and thus high blood glucose levels were maintained. Pg OMVs also attenuated the insulin-induced Akt/glycogen synthase kinase-3 ß (GSK-3ß) signaling in a gingipain-dependent fashion in hepatic HepG2 cells. These results suggest that the delivery of gingipains mediated by Pg OMV elicits changes in glucose metabolisms in the liver and contributes to the progression of diabetes mellitus.


Assuntos
Membrana Externa Bacteriana/metabolismo , Cisteína Endopeptidases Gingipaínas/genética , Periodontite/genética , Porphyromonas gingivalis/genética , Animais , Membrana Externa Bacteriana/patologia , Modelos Animais de Doenças , Cisteína Endopeptidases Gingipaínas/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Resistência à Insulina/genética , Fígado/metabolismo , Fígado/microbiologia , Camundongos , Periodontite/microbiologia , Periodontite/patologia , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/patogenicidade , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética
12.
World J Surg ; 43(8): 2006-2015, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30972432

RESUMO

BACKGROUND: Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory long-term prognosis. Moreover, CRT can lead to esophageal fistula, perforation, and strictures. Therefore, strong induction chemotherapeutic treatments are necessary to reduce the tumor volume for subsequent radical esophagectomy. This study aimed to determine the oncological utility of docetaxel plus cisplatin and 5-fluorouracil (DCF) and the technical feasibility of subsequent esophagectomy for locally advanced esophageal cancer. METHODS: Eighty-seven patients with clinical borderline unresectable T3 and T4 esophageal squamous cell carcinoma without distant metastases were included in this study. There were 44 patients in primary DCF group and 43 patients in definitive CRT group, and perioperative and long-term oncological outcomes were compared between the two groups. RESULTS: Twenty-two patients (50%) achieved R0 resection in the DCF group. Albeit not significant, the rate of curative treatment was higher in the DCF group than the definitive CRT group (p = 0.099). The overall survival (OS) and progression-free survival (PFS) were better with DCF than with definitive CRT (median OS, 29 vs. 17 months, p = 0.206; median PFS, 10 vs. 6 months, p = 0.020). Specifically, the OS of patients with a Charlson score of less than 3 among the DCF-treated patients tended to be better than those among the definitive CRT-treated patients. CONCLUSION: DCF and subsequent esophagectomy achieved R0 resection in 50% of the patients and was associated with better long-term oncological outcomes in patients with initially unresectable esophageal cancer if their systemic status is acceptable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Quimioterapia de Indução/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Segunda Neoplasia Primária , Intervalo Livre de Progressão
13.
J Gastrointest Surg ; 22(11): 1881-1889, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29980971

RESUMO

BACKGROUND OR PURPOSE: As we previously indicated, postoperative pneumonia has a negative impact on the overall survival after planned esophagectomy. However, the impact of postoperative pneumonia after salvage esophagectomy on long-term oncologic outcomes still remains unclear. This study aimed to indicate the association between postoperative pneumonia and long-term outcomes of definitive chemoradiotherapy followed by salvage esophagectomy. Furthermore, we determined a prediction model for overall survival (OS) and disease-free survival (DFS) using a survival classification and regression tree (CART). METHODS: Ninety-three patients who underwent CRT followed by esophagectomy for thoracic esophageal cancer were identified for this study. Forty-nine patients and 44 patients were included in the salvage and neoadjuvant groups, respectively. We investigated the association between postoperative pneumonia and long-term oncologic outcomes following salvage esophagectomy. RESULTS: Patients from the salvage group tended to have a lower OS compared to neoadjuvant group (median survival: salvage, 24 months vs neoadjuvant, 43 months, p = 0.117). Multivariate analyses revealed that postoperative pneumonia adversely affected both OS (p < 0.001) and DFS (p = 0.044) after salvage esophagectomy. We generated the prediction model for OS and DFS in the salvage group using survival CART. Postoperative pneumonia was the most important parameter for predicting the OS. DISCUSSION: The present study demonstrates the long-term outcomes and risk factors for mortality of salvage esophagectomy. To improve OS after salvage surgery, the development of a means of decreasing pulmonary complications is needed.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomia/efeitos adversos , Pneumonia/etiologia , Terapia de Salvação/efeitos adversos , Idoso , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Complicações Pós-Operatórias/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
14.
Gastrointest Endosc ; 88(3): 456-465, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29750982

RESUMO

BACKGROUND AND AIMS: Active use of endoscopic resection (ER) for cM3-SM2 esophageal cancer may enable sufficient extent of esophageal resection and help determine the need for lymph node dissection based on histopathologic findings. However, ER preceding esophagectomy may have an adverse impact on outcomes. This study was designed to determine the technical feasibility and oncologic safety of diagnostic ER. METHODS: A single-institution retrospective cohort study was performed between July 2008 and June 2014. During this period, 135 consecutive patients with clinical T1a-M3N0M0, T1b-SM1N0M0, and T1b-SM2N0M0 primary esophageal cancer were referred to our division. Eight patients who underwent chemoradiotherapy as primary treatment were excluded because of inadequate pathologic findings. Based on oncologic and physical factors, we categorized the remaining 127 patients into 2 groups: primary esophagectomy (n = 54) and primary ER (n = 73). RESULTS: In all 127 patients, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 95.7% and 87.6%, respectively. No adverse event requiring surgical intervention was observed after ER. Diagnostic ER had no negative impact on surgical outcomes, DFS, and OS after esophagectomy. Fourteen patients (19.2%) of those who received primary ER underwent curative resection, whereas 11 (20.4%) who had pT1a disease, no lymphovascular invasion, and no pathologic lymph node metastasis underwent primary esophagectomy. CONCLUSIONS: Diagnostic ER for cM3-SM2 esophageal cancer with or without subsequent esophagectomy was feasible and safe, not only from a surgical perspective but also an oncologic perspective. Approximately 20% of cM3-SM2N0M0 patients can potentially avoid undergoing additional treatment including esophagectomy using diagnostic ER.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Esofagectomia , Esofagoscopia/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Brachytherapy ; 15(6): 768-773, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27592130

RESUMO

PURPOSE: To evaluate the effectiveness of the single-energy metal artifact reduction (SEMAR) technique for improving the accuracy of I-125 seed identification in postimplant computed tomography (CT) after prostate brachytherapy. METHODS AND MATERIALS: Postimplant CT images of 40 patients treated with I-125 prostate brachytherapy were acquired. For all patients, 2 data sets were reconstructed, 1 with SEMAR algorithms (SEMAR image), and the other without SEMAR algorithms (non-SEMAR image). Seed locations are automatically detected by the automatic seed finder tool, and their locations were compared between the SEMAR and non-SEMAR images. Dosimetric parameters using seed locations as detected were compared. RESULTS: The true-positive fraction of properly detected seeds on the SEMAR image as determined from a reference seed distribution defined by one investigator was significantly higher than the true-positive fraction on the non-SEMAR image (p = 0.011). The variabilities in D90 (p = 0.001), V100 (p = 0.007), and V150 (p = 0.007) were significantly reduced for seed location on the SEMAR image as compared with non-SEMAR image. CONCLUSIONS: Prostate postimplant CT with SEMAR improved the accuracy of seed localization and postimplant dosimetric parameters.


Assuntos
Artefatos , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Algoritmos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Radioisótopos do Iodo/uso terapêutico , Masculino , Metais , Neoplasias da Próstata/diagnóstico por imagem , Radiometria/métodos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X/métodos
16.
Environ Sci Pollut Res Int ; 22(22): 18252-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26206128

RESUMO

A high-throughput test of cell growth inhibition was performed using mouse embryonic stem (ES) cells to assess chemical toxicities. We herein demonstrated using a 96-well culture plate approach and the MTT assay that this method was suitable for prioritization of chemicals for their cytotoxic properties. In order to categorize chemicals, we used p53 gene-modified mouse ES cells as well as wild-type ES cells. The p53 gene is a well-known tumor suppressor and controls programmed cell death (apoptosis) and cellular senescence that is triggered by DNA-damaging agents such as alkylating agents and radiation. In the present study, p53-deficient ES cells were found to be more resistant to a tumor initiator, diethylnitrosamine (DEN), than wild-type ES cells, suggesting the inhibition of apoptosis or senescence by a dysfunction in p53. Chromosome aberrations were more frequently detected in p53-deficient ES cells than in wild-type cells, indicating genomic instability due to the deletion of p53. Other tumor initiators, methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (NMU), did not reveal apparent differences in cytotoxicity between wild-type and p53-deficient ES cells. Thus, ES test system using gene-modified ES cells may be used to categorize chemicals by detecting their characteristic effects on apoptosis, genotoxic potentials as well as general cytotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Células-Tronco Embrionárias/efeitos dos fármacos , Testes de Toxicidade/métodos , Proteína Supressora de Tumor p53/genética , Animais , Células Cultivadas , Dano ao DNA , Dietilnitrosamina/toxicidade , Camundongos
17.
Neonatology ; 105(3): 166-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24458138

RESUMO

BACKGROUND: Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing. OBJECTIVES: To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan. METHODS: Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011. RESULTS: One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications. CONCLUSIONS: Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Hiperinsulinismo Congênito/tratamento farmacológico , Diazóxido/efeitos adversos , Recém-Nascido Prematuro , Peso ao Nascer , Hiperinsulinismo Congênito/epidemiologia , Permeabilidade do Canal Arterial/epidemiologia , Permeabilidade do Canal Arterial/fisiopatologia , Permeabilidade do Canal Arterial/terapia , Edema/induzido quimicamente , Edema/epidemiologia , Edema/fisiopatologia , Feminino , Idade Gestacional , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Japão/epidemiologia , Masculino , Oligúria/induzido quimicamente , Oligúria/epidemiologia , Oligúria/fisiopatologia , Prevalência , Recidiva , Fatores de Risco , Inquéritos e Questionários
18.
Int J Clin Oncol ; 19(5): 940-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24170247

RESUMO

BACKGROUND: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with (125)I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0-3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation. RESULTS: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy. CONCLUSIONS: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.


Assuntos
Braquiterapia/efeitos adversos , Radioisótopos do Iodo/efeitos adversos , Próstata/efeitos da radiação , Neoplasias da Próstata/radioterapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ereção Peniana/fisiologia , Ereção Peniana/efeitos da radiação , Próstata/patologia , Neoplasias da Próstata/patologia , Inquéritos e Questionários
19.
Gan To Kagaku Ryoho ; 41(12): 2010-2, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731405

RESUMO

Herein, we report the treatment outcomes of patients with limited cervical lymph node recurrence after esophagectomy for esophageal cancer. Between April 2010 and December 2013, 8 patients with cervical lymph nodes recurrence were diagnosed and treated in our department. All patients were detected with recurrent disease by using positron emission tomography computed tomography(PET-CT), and among these, 5 patients had solitary node recurrence. Initial treatments were irradiation therapy in 5 patients and lymphadenectomy in 3 patients. Four of 5 patients underwent irradiation therapy and lymphadenectomy. Four of 5 patients with solitary node recurrence are still alive without relapse of disease. In conclusion, PET-CT can be useful for early detection of recurrent disease after esophagectomy. Appropriate therapy for patients with solitary cervical lymph node recurrence is associated with long-term survival after recurrence.


Assuntos
Neoplasias Esofágicas/patologia , Pescoço/patologia , Idoso , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Pescoço/cirurgia , Tomografia por Emissão de Pósitrons , Recidiva , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
World J Gastrointest Surg ; 5(4): 129-34, 2013 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-23717746

RESUMO

Primary histiocytic sarcoma of the spleen is a rare but potentially lethal condition. It can remain asymptomatic or only mildly symptomatic for a long time. An 81-year-old woman presented with an extremely enlarged spleen. She suffered from progressive anemia and required a red blood cell transfusion once a month. Although computed tomography, ultrasonography, and magnetic resonance imaging were performed for diagnosis, a confirmed diagnosis was not obtained. Her enlarged spleen compressed her stomach, and she suffered from gastritis and a sense of gastric fullness just after meals. She underwent laparoscopic splenectomy for therapeutic and diagnostic purposes. Her post-operative course was uneventful. After surgery, her red blood cell and platelet counts increased markedly. The tumor was diagnosed as splenic histiocytic sarcoma. Post-surgical chemotherapy was not performed, and the patient died of liver failure due to liver metastasis 5 mo after surgery. Laparoscopic splenectomy is minimally invasive and useful for the relief of symptoms related to hematological disorders. However, in cases of an enlarged spleen, optimal views and working space are limited. In such cases, splenic artery ligation can markedly reduce the size of the spleen, thus facilitating the procedure. The case reported herein suggests that laparoscopic splenectomy may be useful for the treatment of splenic malignancy.

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