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1.
Risk Anal ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664225

RESUMO

A comparative assessment of the risks of the three current wastewater effluent disposal options and three other potential options was conducted for Southeast Florida communities. The question was how the risk to humans from the use of potable reuse compares to the other five available wastewater disposal alternatives. The need for this type of risk assessment is due to the potential to use potable reuse as a water supply and the potential resistance from the public as a result of such a proposal. Water quality data relevant to disposal of wastewater treatment plant effluent from South Florida utilities along with water quality data on the receiving waters and drinking water standards were obtained for the project. The comparison of the public health risks associated with these disposal alternatives indicated that health risks associated with deep wells and direct potable reuse were generally lower than those of the other alternatives.

2.
Phys Rev Lett ; 130(11): 111801, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-37001070

RESUMO

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

3.
Neuropathol Appl Neurobiol ; 46(2): 111-124, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31179566

RESUMO

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/imunologia , Linhagem da Célula/imunologia , Germinoma/diagnóstico , Germinoma/imunologia , Neoplasias Encefálicas/metabolismo , Perfilação da Expressão Gênica , Germinoma/metabolismo , Humanos , Prognóstico , Transcriptoma , Microambiente Tumoral/imunologia
4.
Ann Oncol ; 29(4): 992-997, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29401241

RESUMO

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Glote/patologia , Neoplasias Laríngeas/radioterapia , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
J Clin Pharm Ther ; 43(5): 633-639, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29981285

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. METHODS: This was an open-label, randomized, two-period, two-sequence crossover study in non-elderly healthy adult males. Subjects randomized to Group 1 received roxadustat alone during Period 1 and roxadustat concomitantly with lanthanum carbonate during Period 2; subjects randomized to Group 2 received roxadustat concomitantly with lanthanum carbonate during Period 1 and roxadustat alone during Period 2. All subjects received a single oral dose of 100 mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750 mg lanthanum carbonate three times daily on Days 1 and 2. Pharmacokinetic assessments were conducted on Days 1-4 in both periods. The primary study outcomes were the area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf ), and maximum concentration (Cmax ); the geometric least squares mean ratio (GMR; roxadustat + lanthanum carbonate/roxadustat alone) and corresponding 90% confidence interval (CI) was calculated for AUCinf and Cmax . Safety was assessed by the occurrence of treatment-emergent adverse events (TEAEs), laboratory test results, vital signs and standard 12-lead electrocardiogram. RESULTS AND DISCUSSION: A total of 18 subjects were enrolled (Group 1, n = 9; Group 2, n = 9); no subjects discontinued from the study. Roxadustat was rapidly absorbed, reaching maximum plasma concentration between 1 and 4 hours. The GMRs for AUCinf and Cmax were 88.00% (90% CI: 84.01, 92.17) and 98.58% (90% CI: 92.92, 104.58), respectively. The 90% CIs for both parameters were within the no-effect boundaries of 80% and 125%, indicating a lack of effect of lanthanum carbonate on roxadustat absorption. No deaths or serious TEAEs occurred. WHAT IS NEW AND CONCLUSIONS: Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg lanthanum carbonate three times daily did not impact the AUCinf or Cmax of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.


Assuntos
Glicina/análogos & derivados , Isoquinolinas/farmacocinética , Lantânio/efeitos adversos , Administração Oral , Adulto , Anemia/tratamento farmacológico , Anemia/etiologia , Área Sob a Curva , Estudos Cross-Over , Glicina/farmacocinética , Glicina/uso terapêutico , Humanos , Isoquinolinas/uso terapêutico , Masculino , Insuficiência Renal Crônica/complicações , Adulto Jovem
6.
Diabet Med ; 34(12): 1788-1791, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29044634

RESUMO

BACKGROUND: Type B insulin resistance syndrome is a rare disease characterized by refractory transient hyperglycaemia and severe insulin resistance associated with circulating anti-insulin receptor antibodies. A standardized treatment regimen for type B insulin resistance syndrome has yet to be established. CASE REPORT: We report the case of a 64-year-old man undergoing haemodialysis for antineutrophil cytoplasmic antibody-associated vasculitis and diabetic nephropathy, who developed rapid onset of hyperglycaemia (glycated albumin 52.1%). Type B insulin resistance syndrome was diagnosed, on the basis of positivity for anti-insulin receptor antibodies and the man's autoimmune history of antineutrophil cytoplasmic antibody-associated vasculitis and idiopathic thrombocytopenic purpura. Although severe hyperglycaemia persisted in spite of corticosteroids and high-dose insulin therapy, rituximab treatment resulted in remarkable improvement of the man's severe insulin resistance and disappearance of anti-insulin receptor antibodies without any adverse effects. CONCLUSIONS: According to a literature review of 11 cases in addition to the present case, rituximab appears to be a safe and effective strategy for the treatment of corticosteroid-resistant type B insulin resistance syndrome.


Assuntos
Síndrome Metabólica/tratamento farmacológico , Rituximab/uso terapêutico , Doenças Autoimunes/classificação , Doenças Autoimunes/tratamento farmacológico , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/classificação , Pessoa de Meia-Idade
7.
Org Biomol Chem ; 15(17): 3568-3570, 2017 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-28345721

RESUMO

The structural basis for the intracellular delivery of OSW-1 is investigated using fluorescent derivatives of OSW-1 and its closely related congeners. Despite the large differences in activity, all the fluorescent probes are found to translocate across the plasma membrane to the ER and Golgi apparatus. This observation suggests that the glycosylated cholestane moiety plays an important role in the cell internalization and intracellular localization property of OSW-1.


Assuntos
Colestenonas/química , Colestenonas/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Espaço Intracelular/metabolismo , Saponinas/química , Saponinas/metabolismo , Transporte Biológico , Células HeLa , Humanos
8.
J Fish Dis ; 40(2): 157-168, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27150547

RESUMO

Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus-2 (CyHV-2), has affected the commercial production of the goldfish Carassius auratus and gibelio carp Carassius auratus gibelio. High water temperature treatments are reported to reduce the mortality rate of infected goldfish and elicit immunity in the survivors. To define the mechanism by which this intervention induces resistance, clonal ginbuna Carassius auratus langsdorfii, which is closely related to both species and has been used in fish immunology, may represent a promising model species. In this study, we investigated the susceptibility of clonal ginbuna strains to CyHV-2 and the effect of high water temperature treatment on infected ginbuna and goldfish. Experimental intraperitoneal infection with CyHV-2 at 25 °C caused 100% mortality in ginbuna strains, which was accompanied by histopathological changes typical of HVHN. Both infected ginbuna S3n strain and goldfish, exposed to high temperature for 6 days [shifting from 25 °C (permissive) to 34 °C (non-permissive)], showed reduced mortalities after the 1st inoculation, and subsequent 2nd virus challenge to 0%, indicating induction of immunity. It was concluded that ginbuna showed a similar susceptibility and disease development in CyHV-2 infection compared to goldfish, suggesting that ginbuna can be a useful fish model for the study of CyHV-2 infection and immunity.


Assuntos
Infecções por Vírus de DNA/veterinária , Vírus de DNA/fisiologia , Doenças dos Peixes/virologia , Carpa Dourada , Temperatura Alta/efeitos adversos , Animais , Linhagem Celular , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/mortalidade , Infecções por Vírus de DNA/virologia , Resistência à Doença , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/mortalidade , Suscetibilidade a Doenças/veterinária , Suscetibilidade a Doenças/virologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/mortalidade , Necrose/imunologia , Necrose/mortalidade , Necrose/veterinária , Necrose/virologia , Água
9.
Gene Ther ; 23(6): 479-88, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26905369

RESUMO

Oncolytic herpes simplex virus (HSV) vectors have attracted increasing attention as novel anti-cancer agents. HSV entry is triggered by the binding of glycoprotein D (gD) to its receptors, such as herpesvirus entry mediator or nectin-1. We have recently reported the construction of a fully retargeted HSV platform that incorporates single-chain antibodies (scFv) into gD to mediate entry exclusively via tumor-associated antigens. In this study, we created an scFv directed against epithelial cell adhesion molecule (EpCAM), a recognized carcinoma-associated antigen, and inserted it into the retargeted HSV platform that is ablated for gD recognition of its canonical receptors and contains the entry-enhancing mutations in gB we previously identified. We observed that both initial entry and subsequent cell-to-cell spread of the retargeted virus were stringently dependent on cellular EpCAM expression. Interestingly, the retargeted virus developed larger plaques on some of the human tumor lines tested than the control virus bearing wild-type gD. Intratumoral injection of the retargeted virus revealed antitumor activity in a mouse xenograft model. These observations illustrate the versatility of our retargeted HSV platform as it allows expansion of the oncolytic virus toolbox for the treatment of diverse cancers.


Assuntos
Molécula de Adesão da Célula Epitelial/genética , Vetores Genéticos/genética , Herpesvirus Humano 1/genética , Neoplasias/terapia , Neoplasias/virologia , Terapia Viral Oncolítica/métodos , Animais , Células CHO , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Chlorocebus aethiops/imunologia , Cricetulus , Molécula de Adesão da Célula Epitelial/imunologia , Feminino , Vetores Genéticos/metabolismo , Células Hep G2 , Herpesvirus Humano 1/metabolismo , Humanos , Camundongos , Nectinas , Distribuição Aleatória , Receptores Virais/metabolismo , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Transfecção/métodos , Células Vero , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Internalização do Vírus , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Clin Exp Dermatol ; 41(5): 480-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27135282

RESUMO

BACKGROUND: Tranexamic acid (TA) has been suggested as an effective treatment for melasma. AIM: To investigate the effects and mechanism of action of topical TA in the treatment of melasma. METHODS: In this study, 23 participants with melasma applied a 2% TA formulation to the whole face for 12 weeks. Clinical effects were evaluated using the modified Melasma Area and Severity Index (mMASI) and a chromameter. Skin biopsies were obtained from 10 participants to evaluate pigmentation, vascularity and the expression levels of possible paracrine factors contributing to the effect of TA. RESULTS: Most of the participants had mild melasma, with mMASI of < 5. The mMASI scores significantly improved in 22 of 23 participants after application. The L* values were increased and the a* values were decreased in both lesional and perilesional normal skin. Fontana-Masson staining showed a significant decrease in melanin content in the epidermis. The number of CD31-positive vessels and the expression of the vascular endothelial growth factor both tended to decrease. Endothelin (ET)-1 was found to be downregulated with TA. CONCLUSIONS: Topical TA is effective for melasma. This immunohistochemical study found that suppression of ET-1 could be one of the mechanisms of action of TA on melasma.


Assuntos
Antifibrinolíticos/uso terapêutico , Melanose/tratamento farmacológico , Ácido Tranexâmico/uso terapêutico , Adulto , Biomarcadores/metabolismo , Endotelina-1/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Melanose/metabolismo , Melanose/patologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
J Radiol Prot ; 36(3): 456-473, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27355162

RESUMO

Measured neutron energy distribution emitted from a thick stopping target of natural carbon at 0°, 30°, 60° and 90° from nuclear reactions caused by 12 MeV amu-1 incident 12C5+ ions were converted to energy differential and total neutron absorbed dose as well as ambient dose equivalent H *(10) using the fluence-to-dose conversion coefficients provided by the ICRP. Theoretical estimates were obtained using the Monte Carlo nuclear reaction model code PACE and a few existing empirical formulations for comparison. Results from the PACE code showed an underestimation of the high-energy part of energy differential dose distributions at forward angles whereas the empirical formulation by Clapier and Zaidins (1983 Nucl. Instrum. Methods 217 489-94) approximated the energy integrated angular distribution of H *(10) satisfactorily. Using the measured data, the neutron doses received by some vital human organs were estimated for anterior-posterior exposure. The estimated energy-averaged quality factors were found to vary for different organs from about 7 to about 13. Emitted neutrons having energies above 20 MeV were found to contribute about 20% of the total dose at 0° while at 90° the contribution was reduced to about 2%.


Assuntos
Carbono/química , Nêutrons , Doses de Radiação , Radiometria/métodos , Ciclotrons , Íons Pesados , Humanos , Modelos Teóricos , Método de Monte Carlo , Física Nuclear , Espalhamento de Radiação
12.
Org Biomol Chem ; 13(40): 10117-21, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26369435

RESUMO

We synthesised a novel membrane-insertable amphiphilic DNA. The amphiphilic DNA had a nine-nucleotide hydrophobic region at one end consisting of octyl phosphotriester linkages. The amphiphilic DNA bound to the lipid membrane by inserting the hydrophobic region; this process was facilitated by the presence of the complementary DNA strand.


Assuntos
DNA/síntese química , Lipídeos/química , Tensoativos/síntese química , DNA/química , Ésteres/química , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Estrutura Molecular , Tensoativos/química
13.
Ann Oncol ; 25(6): 1192-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24669010

RESUMO

BACKGROUND: This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. PATIENTS AND METHODS: Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm. RESULTS: Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC. CONCLUSIONS: This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment. UMIN CLINICAL TRIALS REGISTRY IDENTIFIER: C000000093.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cistectomia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos
14.
Water Sci Technol ; 70(3): 430-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25098871

RESUMO

Odaiba seaside park is one of the most popular waterfronts in Tokyo Bay, but is easily affected by wet weather pollutant loads through combined sewer overflows (CSOs). The monitoring data of Escherichia coli clearly showed high faecal contamination after a rainfall event on 9-11 November 2007. We estimated the amounts of discharge volume and E. coli pollutant loads of urban rivers receiving CSO from rainfall chambers as well as pumping stations and primary effluent discharge. The result suggested that Sumida River and Meguro River were more influential to the Odaiba coastal area than other sources including the nearest wastewater treatment plant. Subsequently, we simulated the dynamic behaviour of E. coli by a three-dimensional (3D) hydro-dynamic and water quality model. The model simulation reproduced that E. coli concentration after the rainfall event increased rapidly at first and later gradually decreased. The simulations with and without inflow pollutant loads from urban rivers suggested that the E. coli concentration can be influenced by the Meguro River just after the rainfall event and Sumida River about 1 week later. From the spatial and temporal distribution of surface E. coli concentration, after at least 6 days from the rainfall event, high faecal contamination spread to the whole of the coastal area.


Assuntos
Fezes , Modelos Teóricos , Esgotos , Movimentos da Água , Monitoramento Ambiental/métodos , Escherichia coli/isolamento & purificação , Rios , Urbanização , Microbiologia da Água , Qualidade da Água
15.
Br J Cancer ; 108(10): 1957-63, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23640393

RESUMO

BACKGROUND: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. METHODS: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1-5, vincristine 0.7 mg m(-2) day 5, mitomycin 7 mg m(-2) day 5, cisplatin 14 mg m(-2) days 1-5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. RESULTS: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80%; P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). CONCLUSION: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Braquiterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada , Feminino , Humanos , Histerectomia/métodos , Japão , Oncologia/organização & administração , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/uso terapêutico , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
16.
Ann Oncol ; 24(10): 2594-2600, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23899839

RESUMO

BACKGROUND: Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established. PATIENTS AND METHODS: The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung. RESULTS: Amplification (an increase in the copy number by ≥ 2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10(-5), Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients. CONCLUSIONS: Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.


Assuntos
Actinina/genética , Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Variações do Número de Cópias de DNA/genética , Dosagem de Genes/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma de Pulmão , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Movimento Celular/genética , Receptores ErbB/genética , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Sobrevida , Análise Serial de Tecidos , Proteínas ras/genética
17.
Intervirology ; 56(5): 302-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24008863

RESUMO

JTK-853 is a novel, non-nucleoside, palm site-binding hepatitis C virus (HCV) polymerase inhibitor that has demonstrated antiviral activity in HCV-infected patients during 3 days of treatment. To estimate the genetic barrier of JTK-853 to resistance in vitro, colony formation assays were conducted using HCV replicon cells (genotypes 1a and 1b). The colony formation assays revealed that the numbers of resistant colonies for JTK-853 were much lower than those for other direct-acting antivirals, including palm site- or thumb pocket-binding non-nucleoside HCV polymerase inhibitors (NNIs), an NS5A inhibitor (NS5Ai), and a protease inhibitor (PI). Furthermore, the numbers of resistant colonies for JTK-853 in combination with the NS5Ai or PI were lower than those for other combinations of NS5Ai + NNI, and NS5Ai + PI. Our findings demonstrate that JTK-853 has a high genetic barrier to resistance, and suggest that its combination therapies will be potent in suppressing the emergence of drug resistance in HCV-infected patients.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Taxa de Mutação , Piperazinas/farmacologia , Linhagem Celular , Sinergismo Farmacológico , Hepatócitos/virologia , Humanos , Virologia/métodos
18.
Eur Surg Res ; 51(3-4): 129-37, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24280661

RESUMO

BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.


Assuntos
Embolização Terapêutica , Hepatectomia/métodos , Fígado/patologia , Veia Porta , Cuidados Pré-Operatórios , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hipertrofia , Fígado/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos
19.
Nat Genet ; 10(3): 261-8, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7670463

RESUMO

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VI (270 kb) has revealed that it contains 129 predicted or known genes (300 bp or longer). Thirty-seven (28%) of which have been identified previously. Among the 92 novel genes, 39 are highly homologous to previously identified genes. Local sequence motifs were compared to active ARS regions and inactive loci with perfect ARS core sequences to examine the relationship between these motifs and ARS activity. Additional ARS sequences were predominantly observed in 3' flanking sequences of active ARS loci.


Assuntos
Cromossomos Fúngicos , Saccharomyces cerevisiae/genética , Composição de Bases , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , Sequência Consenso , Replicação do DNA/genética , DNA Fúngico/biossíntese , DNA Fúngico/química , DNA Fúngico/genética , Genes Fúngicos , Dados de Sequência Molecular , Fases de Leitura Aberta , Saccharomyces cerevisiae/metabolismo
20.
Sci Total Environ ; 901: 165836, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37517729

RESUMO

Beach sand harbors a diverse group of microbial organisms that may be of public health concern. Nonetheless, little is known about the presence and distribution of viruses in beach sand. In this study, the first objective was to evaluate the presence of seven viruses (Aichi virus, enterovirus, hepatitis A virus, human adenovirus, norovirus, rotavirus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) in sands collected at public beaches. The second objective was to assess the spatial distribution of enteric viruses in beach sand. To that end, 27 beach sand samples from different beaches in Portugal were collected between November 2018 and August 2020 and analyzed for the presence of viruses. At seven beaches, samples were collected in the supratidal and intertidal zones. Results show that viruses were detected in 89 % (24/27) of the sand samples. Aichi virus was the most prevalent (74 %). Noroviruses were present in 19 % of the samples (norovirus GI - 15 %, norovirus GII - 4 %). Human adenovirus and enterovirus were detected in 48 % and 22 % of the samples, respectively. Hepatitis A virus and rotavirus were not detected. Similarly, SARS-CoV-2 in beach sand collected during the initial stages of the pandemic was also not detected. The detection of three or more viruses occurred in 15 % of the samples. Concentrations of viruses were as high as 7.2 log copies (cp)/g of sand. Enteric viruses were found in higher prevalence in sand collected from the supratidal zone compared to the intertidal zone. Human adenovirus was detected in 43 % of the supratidal and 14 % in the intertidal samples and Aichi virus in 57 % and 86 % of the intertidal and supratidal areas, respectively. Our findings suggest that beach sand can be a reservoir of enteric viruses, suggesting that it might be a vehicle for disease transmission, particularly for children, the elderly, and immunocompromised users.


Assuntos
Adenovírus Humanos , COVID-19 , Enterovirus , Norovirus , Rotavirus , Criança , Humanos , Idoso , SARS-CoV-2 , Areia , COVID-19/epidemiologia
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