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1.
Hepatol Res ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804859

RESUMO

AIM: Measurement of O-glycosylated middle hepatitis B surface antigen (HBsAg glycan isomer, HBsAgGi) has been developed to quantify hepatitis B virus (HBV) infectious virions and distinguish them from subviral particles. This study aimed to evaluate the association between serum HBsAg seroclearance and serum HBV virions measured by HBsAgGi in patients with chronic hepatitis B (CHB). METHODS: Serum HBsAgGi levels were quantified in 232 treatment-naïve patients with CHB genotype C. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) for factors associated with HBsAg seroclearance. RESULTS: Baseline HBsAgGi levels showed significant differences among HBV phenotypes. During a median follow-up period of 7.4 years, 22 of the 232 patients achieved HBsAg seroclearance. Multivariate analysis demonstrated that quantitative HBsAg, nucleoside/nucleotide analog therapy during the follow-up period, and HBsAgGi levels were independent predictors of seroclearance. The adjusted HR indicated that the HBsAg seroclearance probability in patients with low HBsAgGi (≤3.5log ng/mL) was over five times higher than that in patients with high HBsAgGi. Kaplan-Meier analysis indicated that the 10-year probabilities of HBsAg seroclearance were 21.0% and 3.0% in patients with low and high HBsAgGi levels, respectively (p < 0.001), and that patients with high HBsAgGi levels showed low seroclearance probabilities irrespective of the other predictors. CONCLUSION: Serum HBV infectious virion levels, measured using HBsAgGi, may be a novel predictor of HBsAg seroclearance.

2.
Int J Clin Oncol ; 29(1): 72-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38055097

RESUMO

BACKGROUND: The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. METHODS: Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. RESULTS: The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. CONCLUSION: The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic.


Assuntos
COVID-19 , Neoplasias do Colo do Útero , Feminino , Humanos , Estudos de Coortes , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Japão/epidemiologia , Pandemias , COVID-19/epidemiologia , COVID-19/patologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38839079

RESUMO

Cervical cancer affects women worldwide and is the most common human papillomavirus (HPV)-associated cancer. Carcinogenesis caused by HPV results in specific cancer behavior because of the underlying viral infection. The mechanism and timing of the transformation from viral infection to cancer cells have been elucidated in detail. Treatments for this cancer are based on its characteristics and are being implemented. Moreover, HPV infection is widespread worldwide and is transmitted through sexual activity. Although the HPV vaccination is the most effective strategy of preventing cervical cancer, it is not feasible to vaccinate the entire human population especially in low- and middle-income countries. In order to consider the next step for HPV vaccination, we need to understand the characteristics of HPV carcinogenesis and cervical cancer. Additionally, treatment aimed at preservation of reproductive function in patients with cervical cancer is often required, as the cervix is a reproductive organ and because the disease is more prevalent in the adolescent and young adult generation. Thus, there are still many challenges in the diagnosis, treatment, and prevention of cervical cancer.

4.
Inorg Chem ; 62(40): 16329-16342, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37756217

RESUMO

We report on a nonoxidative topochemical route for the synthesis of a novel indate-based oxyfluoride, LaBaInO3F2, using a low-temperature reaction of Ruddlesden-Popper-type LaBaInO4 with polyvinylidene difluoride as a fluorinating agent. The reaction involves the replacement of oxide ions with fluoride ions as well as the insertion of fluoride ions into the interstitial sites. From the characterization via powder X-ray diffraction (PXRD) and Rietveld analysis as well as automated electron diffraction tomography (ADT), it is deduced that the fluorination results in a symmetry lowering from I4/mmm (139) to monoclinic C2/c (15) with an expansion perpendicular to the perovskite layers and a strong tilting of the octahedra in the ab plane. Disorder of the anions on the apical and interstitial sites seems to be favored. The most stable configuration for the anion ordering is estimated based on an evaluation of bond distances from the ADT measurements via bond valence sums (BVSs). The observed disordering of the anions in the oxyfluoride results in changes in the optical properties and thus shows that the topochemical anion modification can present a viable route to alter the optical properties. Partial densities of states (PDOSs) obtained from ab initio density functional theory (DFT) calculations reveal a bandgap modification upon fluoride-ion introduction which originates from the presence of the oxide anions on the interstitial sites. The photocatalytic performance of the oxide and oxyfluoride shows that both materials are photocatalytically active for hydrogen (H2) evolution.

5.
Appl Opt ; 62(31): 8434-8441, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38037949

RESUMO

Utilizing microlasers and microwaves, our study examined the impact of microwaves on the expansion of air plasma. We applied microwaves to the air plasma generated by a microlaser, visualized its growth using a phone camera, and recorded plasma emissions using a high-resolution spectrometer. Software tools were then used to analyze these emissions for temperature changes and electron density. Notably, we noticed a 400-fold increase in plasma volume due to microwave enhancement, even though the microlaser operated at a modest energy level of 1 mJ. Simultaneously, we recorded an increase in temperature and a decrease in electron density when the plasma was subjected to microwaves, indicative of nonequilibrium plasmas. Further, a minor shift in electron temperature during microwave exposure pointed toward the ability of microwaves to sustain plasma characteristics over time. These findings suggest that the microwave application potentially improves the analytical performance of laser-induced breakdown spectroscopy.

6.
Appl Opt ; 62(11): 2827-2834, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37133125

RESUMO

Although a reflective optical system can theoretically realize ideal optical designs, it is not always the optimal choice compared with a refractive one because of the difficulty in achieving high wavefront accuracy. A promising solution is to build reflective optical systems by mechanically assembling all the optical and structural components made of cordierite, which is a ceramic with a very low thermal expansion coefficient. Interferometric evaluations of an experimental product demonstrated that diffraction-limited performance in the visible wavelength was achieved and maintained even after cooling to 80 K. This new technique may be the most cost-effective method for utilizing reflective optical systems, especially for cryogenic applications.

7.
J Am Chem Soc ; 144(16): 7096-7110, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35417653

RESUMO

From reaction of excess lithium with tin, we isolate well-crystallized Li5Sn and solve the crystal structure from single-crystal X-ray diffraction data. The orthorhombic structure (space group Cmcm) features the same coordination polyhedra around tin and lithium as previously predicted by electronic structure calculations for this composition, however differently arranged. An extensive ab initio analysis, including thermodynamic integration using Langevin dynamics in combination with a machine-learning potential (moment tensor potential), is conducted to understand the thermodynamic stability of this Cmcm Li5Sn structure observed in our experiments. Among the 108 Li5Sn structures systematically derived using the structure enumeration algorithm, including the experimental Cmcm structure and those obtained in previous ab initio studies, another new structure with the space group Immm is found to be energetically most stable at 0 K. This computationally discovered Immm structure is also found to be thermodynamically more stable than the Cmcm structure at finite temperatures, indicating that the Cmcm Li5Sn structure observed in our experiments is favored likely due to kinetic reasons rather than thermodynamics.

8.
Opt Express ; 30(17): 29868-29884, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36242102

RESUMO

A semiconductor microwave device that generates a series of burst microwaves at a sub-microsecond duration has been successfully used in a breakdown plasma spectrometer in atmospheric conditions. Microwave delivery has been changed to couple the microwave with laser sparks and electric sparks which are typical plasma ignition sources in laser-induced breakdown spectroscopy (LIBS) and spark-induced breakdown spectroscopy (SIBS). A helical antenna was used for the laser spark, while a coaxial antenna was considered more appropriate for the electric spark. The weak and transient sparks in LIBS and SIBS are enlarged by the microwaves which are stably sustained in the air. The microwave's output power and pulse duration are easily controllable, resulting in tunable plasma intensity and sustained production of hydroxyl radicals (OH radicals). Even in continuous-wave operation by microwave, the low-energy system prevented the formation of high-temperature thermal plasma (>10,000 K) without any mechanical cooling system. The microwave-enhanced LIBS (MW-LIBS) and microwave-enhanced SIBS (MW-SIBS) could be applied to optical emission spectroscopy analyses. In analytical applications, MW-SIBS produces no shockwave in contrast with MW-LIBS which is a great advantage in powdered samples. The MW-SIBS successfully analyzed the direct introduction of copper metal powders.

9.
Opt Express ; 30(19): 33756-33766, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36242403

RESUMO

This paper investigated how microwaves affect the temperature of laser-generated air plasma. The air breakdown threshold was experimentally characterized by focusing the 1064 nm YAG laser on varied condensing lens focal lengths. Increase in focal lengths increases the focused spot diameter of the laser and decreases the laser fluence. Large spot diameter required large amount of laser fluence for breakdown. However, the plasma generated with small spot sizes found to absorb higher laser energy in compared to the plasma generated with large spot size condition. In terms of energy density, the experimental threshold breakdown was generated between 2.6∼4.9 × 1011 W/cm2. The plasma formation was then observed under a high-speed camera. The area of intensity distribution increased with the input of microwaves owing to re-excitation and microwave absorption. This led to emission intensity measurements of the elusive stable electronically excited molecular nitrogen (N2 2nd positive system) and hydroxyl radical (OH). Without the input of microwave, these molecular and radical emissions were not observed. The OH and N2 2nd positive system emission intensities were then used to measure the rovibrational temperature using the synthetic spectrum method by SPECAIR. The rotational and vibrational temperatures were not found to be equal indicating non-equilibrium plasma. The nonequilibrium and nonthermal plasma was observed from after the initial laser air breakdown using the 2.6 × 1011 W/cm2, 1.0 kW microwave power, and 1.0 ms microwave pulse width. The microwaves were not found to affect the temporal changes in the rotational temperatures, demonstrating that the intensity enhancements and plasma sustainment were caused by re-excitation and not by microwave absorption.

10.
BMC Gastroenterol ; 22(1): 478, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411436

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is usually asymptomatic and lacks a specific biomarker; therefore, many individuals might remain undiagnosed even with advanced liver fibrosis. The aim of this study was to clarify the prevalence and clinical features of subjects with a high risk of advanced liver fibrosis in the general population, using the Fibrosis-4 (FIB-4) index. METHODS: We retrospectively investigated 6,087 subjects without known liver disease who had participated in an annual health checkup examination. We analyzed the factors associated with high FIB-4 index (≥ 2.67) using a logistic regression analysis. RESULTS: Among the 6,087 subjects, 76 (1.2%) had high FIB-4 index. Multivariate analysis identified hypertension (odds ratio [OR]; 9.040; 95% confidence interval [CI], 4.081-20.024; P < 0.001) and diabetes mellitus (OR = 4.251; 95% CI, 1.773-10.193; P = 0.001) as important risk factors for high FIB-4 index. The rates of hypertension and diabetes mellitus in subjects with high FIB-4 index were 78.9% and 23.7%, respectively. No significant association was observed between obesity or large waist circumference and high FIB-4 index. A history of cardiovascular disease was significantly more common in subjects with high FIB-4 index. These results were also observed in subjects with normal liver function test. CONCLUSIONS: The present study revealed that approximately 1% of the general Japanese population has a high risk of advanced liver fibrosis. Many of these patients had hypertension and/or diabetes mellitus. Our findings suggest that there are many undiagnosed patients NAFLD with risk of advanced liver fibrosis in the general population.


Assuntos
Diabetes Mellitus , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hipertensão/epidemiologia , Hipertensão/complicações
11.
Appl Opt ; 61(36): 10707-10716, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36606930

RESUMO

A microwave discharge igniter (MDI) with a resonating cavity was developed and optimized for practical applications in an internal combustion engine. In contrast to the typical microwave ignition, the resonating cavity of the MDI induces a discharge through dielectric resonance. Its source of microwave (MW) is a 2.45 GHz semiconductor oscillator that is capable of numerous oscillation patterns. To verify and demonstrate the optimum ignition performance and combustion, we varied the oscillation parameters (signal factors) of the MW to optimize the performance of the MDI using the Taguchi method. Plasma spectroscopy was used for ignition condition analysis. Two sets of microwave pulses, a first pulse followed by a second set of pulse bursts, were used to ignite a propane-air fuel. The flame kernel growth rate and O I species generation were used as the response outputs, which were obtained, respectively from Schlieren imaging and emission spectroscopy experiments. The extended pulse periods and higher MW pulse numbers of the second set of pulses improved the response outputs of the MDI. To further analyze the effect of MW oscillation patterns on plasma properties and performance, measurements were done on MW superimposed operation with the high-voltage ignition from spark plugs. The MW transmission on a typical spark plug enhanced the air plasma ignition. Higher input MW energy and more extended MW pulse widths results in increased spectral intensity and radical generation of OH, O, and N 2. An inverse relation between the temperature and spectral intensity functions of the MW pulse width was observed, which was attributed to the cutoff density of the MW-enhanced plasma.

12.
Chemistry ; 27(38): 9763-9767, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-33908660

RESUMO

A new vacancy ordered, anion deficient perovskite modification with composition of BaCoO2.67 (Ba3 Co3 O8 □1 ) has been prepared via a two-step heating process. Combined Rietveld analysis of neutron and X-ray powder diffraction data shows a novel ordering of oxygen vacancies not known before for barium cobaltates. A combination of neutron powder diffraction, magnetic measurements, and density functional theory (DFT) studies confirms G-type antiferromagnetic ordering. From impedance measurements, the electronic conductivity of the order of 10-4  S cm-1 is determined. Remarkably, the bifunctional catalytic activity for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is found to be comparable to that of Ba0.5 Sr0.5 Co0.8 Fe0.2 O3-y , confirming that charge-ordered anion deficient non-cubic perovskites can be highly efficient catalysts.

13.
Inorg Chem ; 60(15): 10923-10933, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34240868

RESUMO

A vacancy-ordered perovskite-type compound Ba3Fe3O8 (BaFeO2.667) was prepared by oxidizing BaFeO2.5 (P21/c) with the latter compound obtained by a spray pyrolysis technique. The structure of Ba3Fe3O8 was found to be isotypic to Ba3Fe3O7F (P21/m) and can be written as Ba3Fe3+2Fe4+1O8. Mössbauer spectroscopy and ab initio calculations were used to confirm mixed iron oxidation states, showing allocation of the tetravalent iron species on the tetrahedral site, and octahedral as well as square pyramidal coordination for the trivalent species within a G-type antiferromagnetic ordering. The uptake and release of oxygen were investigated over a broad temperature range from room temperature to 1100 °C under pure oxygen and ambient atmosphere via a combination of DTA/TG and variable temperature diffraction measurements. The compound exhibited a strong lattice enthalpy driven reduction to monoclinic and cubic BaFeO2.5 at elevated temperatures.

14.
Hepatol Res ; 51(7): 786-795, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33964118

RESUMO

AIM: Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. METHODS: This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation. RESULTS: Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p = 0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p < 0.001). CONCLUSIONS: Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.

15.
Hepatol Res ; 50(2): 214-223, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31652380

RESUMO

AIM: Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. METHODS: A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis. RESULTS: Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 µmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P < 0.001). Kaplan-Meier analysis showed that the 5-year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10-year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001). CONCLUSION: Elevation of serum tyrosine concentration indicates a high risk of liver-related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.

16.
J Obstet Gynaecol Res ; 46(2): 328-336, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958879

RESUMO

AIM: Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. METHODS: Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. RESULTS: Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. CONCLUSION: Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.


Assuntos
Complicações Pós-Operatórias/prevenção & controle , Traquelectomia/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Adulto , Constrição Patológica/etiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gravidez , Taxa de Gravidez , Traquelectomia/métodos
17.
Gynecol Oncol ; 155(2): 331-339, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31493899

RESUMO

INTRODUCTION: PI3K pathway signaling has received attention as a molecular target in clear cell ovarian carcinoma (CCOC). MDM2 is one of the AKT effectors in the PI3K pathway, which binds to and degrades p53. In this study, we aimed to clarify the prognostic significance of PIK3CA and MDM2 expression, and potential therapeutic effect of a dual inhibition of the PI3K pathway and MDM2. MATERIALS AND METHODS: cDNA expression was evaluated by using microarray data using 75 samples of CCOC. DS-7423 (dual inhibitor of pan-PI3K and mTOR) and RG7112 (MDM2 inhibitor) were used on CCOC cell lines to evaluate cell proliferation, expression level of MDM2 related proteins, and apoptosis by MTT assay, western blotting, and flow cytometry. DS-7423 (3 mg/kg) and/or RG7112 (50 mg/kg) were orally administrated every day for three weeks, and the anti-tumor effect was evaluated using tumor xenografts, along with immunohistochemistry. RESULTS: Tumors with high expression of both PIK3CA and MDM2 showed significantly worse prognosis in expression array of 71 CCOCs (P = 0.013). Dual inhibition of the PI3K pathway by DS-7423 and MDM2 by RG7112 showed synergistic anti-proliferative effect in 4 CCOC cell lines without TP53 mutations. The combination therapy more robustly induced pro-apoptotic proteins (PUMA and cleaved PARP) with increase of sub G1 population and apoptotic cells, compared with either single agent alone. The combination therapy significantly reduced tumor volume in mice (P < 0.001 in OVISE, and P = 0.038 in RMG-I) without severe body weight loss. Immunohistochemistry from the xenograft tumors showed that the combination treatment significantly reduced vascularity and cell proliferation, with an increase of apoptotic cell death. CONCLUSION: A combination therapy targeting the PI3K pathway and MDM2 might be a promising therapeutic strategy in CCOC.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Adenina/análogos & derivados , Adenina/farmacologia , Adenocarcinoma de Células Claras , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , DNA Complementar/metabolismo , Feminino , Xenoenxertos , Imidazolinas/farmacologia , Camundongos Nus , Transplante de Neoplasias/fisiologia , Neoplasias Ovarianas/metabolismo , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Distribuição Aleatória
18.
Jpn J Clin Oncol ; 49(9): 877-880, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613356

RESUMO

We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.


Assuntos
Papillomavirus Humano 16 , Imunoterapia , Proteínas E7 de Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/terapia , Adulto , Método Duplo-Cego , Feminino , Humanos , Imunidade nas Mucosas , Lactobacillus/genética , Pessoa de Meia-Idade , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia
19.
Digestion ; 100(4): 247-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30540999

RESUMO

BACKGROUND: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. METHODS: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. RESULTS: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. CONCLUSIONS: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age.


Assuntos
Colite Ulcerativa/terapia , Leucaférese , Leucócitos/imunologia , Indução de Remissão/métodos , Prevenção Secundária/métodos , Adulto , Fatores Etários , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Ann Vasc Surg ; 61: 466.e7-466.e11, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31349055

RESUMO

A radiocephalic arteriovenous fistula (AVF) in the anatomical snuffbox is the most distal site of AVF in the upper limb. When the cephalic vein distal to the wrist is in poor condition or thrombosed, creating the typical radiocephalic AVF in the distal forearm just proximal to the wrist will likely be considered. However, we have adopted an operative technique for creating a transposed radial artery-dorsal metacarpal vein AVF (RDAVF) in the anatomical snuffbox when possible in such cases. RDAVF is AVF using the most peripheral autologous vein in the upper limb. To our knowledge, the creation of an RDAVF has not been previously reported. We herein describe the steps of the technique and report the successful treatment of a hemodialysis patient who developed occlusion of a radiocephalic AVF in the anatomical snuffbox.


Assuntos
Derivação Arteriovenosa Cirúrgica , Mãos/irrigação sanguínea , Falência Renal Crônica/terapia , Artéria Radial/cirurgia , Diálise Renal , Veias/cirurgia , Idoso , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Artéria Radial/diagnóstico por imagem , Resultado do Tratamento , Veias/diagnóstico por imagem
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