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1.
Phys Rev Lett ; 127(23): 237801, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34936791

RESUMO

The swelling dynamics of polymer gels are characterized by the (collective) diffusion coefficient D of the polymer network. Here, we measure the temperature dependence of D of polymer gels with controlled homogeneous network structures using dynamic light scattering. An evaluation of the diffusion coefficient at the gelation point D_{gel} and the increase therein as the gelation proceeds ΔD≡D-D_{gel} indicates that ΔD is a linear function of the absolute temperature with a significantly large negative constant term. This feature is formally identical to the recently discovered "negative energy elasticity" [Y. Yoshikawa et al. Phys. Rev. X 11, 011045 (2021)PRXHAE2160-330810.1103/PhysRevX.11.011045], demonstrating a nontrivial similarity between the statics and dynamics of polymer networks.

2.
Case Rep Nephrol Dial ; 11(3): 286-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722647

RESUMO

With an increase in the number of older adults worldwide, the oldest-old population, defined as individuals over the age of 90, is also growing. Japan is now facing the problem of a "super-aged society" in which over 21% of the population is aged over 65. The oldest-old constituted 1.8% (2.31 million) of the Japanese population in 2019. Such individuals have special health-care needs. In cases of acute or chronic (or both) renal failure in the oldest-old, it becomes difficult to decide whether dialysis should be initiated. The issue is controversial, and there is some debate on whether dialysis should be avoided in elderly people because of their frailty or if it should be initiated to enable them to spend their remaining years with their families by improving their quality of life. Herein, we describe our experience in 4 cases of hemodialysis initiated in patients over the age of 90. In our experience, dialysis enabled them to spend the rest of their lives with their families, which could not have been possible without it. Although further studies are needed, we concluded that oldest-old individuals in good general health could be eligible for and benefit from hemodialysis.

3.
Int J Antimicrob Agents ; 58(6): 106446, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34610457

RESUMO

Improving prudent use of antibiotics is one way to limit the spread of antimicrobial resistance (AMR). The objective of this systematic review was to assess the effects of financial strategies targeting healthcare providers on the prudent use of antibiotics. A systematic review of the literature was conducted searching PubMed, Embase and Cochrane databases, and the grey literature. Search terms related to antibacterial agents, drug resistance, financial strategies, and healthcare providers and/or prescribers. Twenty-two articles were included in the review, reporting on capitation and salary reimbursement, cost containment interventions, pay-for-performance initiatives, penalties, and a one-off bonus payment. There was substantial variation in the reported outcomes describing prescribing behaviours, including proportion of patients prescribed antibiotics, antibiotic prescriptions per patient, and number of cases treated with recommended antibiotic therapy. All financial strategies were associated with improvements in the appropriate prescription of antibiotics in the short-term, although the magnitude of observed effects varied across financial strategies. Financial penalties were associated with the greatest decreases in inappropriate antibiotic prescriptions, followed by capitation models and pay-for-performance schemes that paid bonuses upon achievement of performance targets. However, the risk of bias across studies must be noted. Findings point to the viability of financial strategies to promote the prudent use of antibiotics. Measuring the downstream impact of prescriber behaviour changes is key to estimating the true value of such interventions to tackle AMR. Research efforts should continue to build the evidence on causal mechanisms driving provider prescribing patterns for antibiotics and the long-term impact on antibiotic prescriptions.

4.
Sci Rep ; 11(1): 18508, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531474

RESUMO

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.


Assuntos
Endoscopia/efeitos adversos , Hidrogéis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Mucosa Gástrica/patologia , Projetos Piloto , Ratos , Úlcera Gástrica/etiologia , Úlcera Gástrica/patologia
5.
Oncogene ; 40(43): 6210-6222, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34545188

RESUMO

There has been accumulating evidence for the clinical benefit of chemoradiation therapy (CRT), whereas mechanisms in CRT-recurrent clones derived from the primary tumor are still elusive. Herein, we identified an aberrant BUB1B/BUBR1 expression in CRT-recurrent clones in bladder cancer (BC) by comprehensive proteomic analysis. CRT-recurrent BC cells exhibited a cell-cycle-independent upregulation of BUB1B/BUBR1 expression rendering an enhanced DNA repair activity in response to DNA double-strand breaks (DSBs). With DNA repair analyses employing the CRISPR/cas9 system, we revealed that cells with aberrant BUB1B/BUBR1 expression dominantly exploit mutagenic nonhomologous end joining (NHEJ). We further found that phosphorylated ATM interacts with BUB1B/BUBR1 after ionizing radiation (IR) treatment, and the resistance to DSBs by increased BUB1B/BUBR1 depends on the functional ATM. In vivo, tumor growth of CRT-resistant T24R cells was abrogated by ATM inhibition using AZD0156. A dataset analysis identified FOXM1 as a putative BUB1B/BUBR1-targeting transcription factor causing its increased expression. These data collectively suggest a redundant role of BUB1B/BUBR1 underlying mutagenic NHEJ in an ATM-dependent manner, aside from the canonical activity of BUB1B/BUBR1 on the G2/M checkpoint, and offer novel clues to overcome CRT resistance.

6.
Microorganisms ; 9(8)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34442729

RESUMO

Proline is a pivotal and multifunctional amino acid that is used not only as a nitrogen source but also as a stress protectant and energy source. Therefore, proline metabolism is known to be important in maintaining cellular homeostasis. Here, we discovered that proline oxidation, catalyzed by the proline oxidase Put1, a mitochondrial flavin-dependent enzyme converting proline into ∆1-pyrroline-5-carboxylate, controls the chronological lifespan of the yeast Saccharomyces cerevisiae. Intriguingly, the yeast strain with PUT1 deletion showed a reduced chronological lifespan compared with the wild-type strain. The addition of proline to the culture medium significantly increased the longevity of wild-type cells but not that of PUT1-deleted cells. We next found that induction of the transcriptional factor Put3-dependent PUT1 and degradation of proline occur during the aging of yeast cells. Additionally, the lifespan of the PUT3-deleted strain, which is deficient in PUT1 induction, was shorter than that of the wild-type strain. More importantly, the oxidation of proline by Put1 helped maintain the mitochondrial membrane potential and ATP production through the aging period. These results indicate that mitochondrial energy metabolism is maintained through oxidative degradation of proline and that this process is important in regulating the longevity of yeast cells.

7.
Clin J Gastroenterol ; 14(5): 1517-1524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34291386

RESUMO

The overall survival of patients with advanced hepatocellular carcinoma with tumor thrombosis of the main trunk or bilobar branches of the portal vein is extremely poor. Moreover, there is no standard treatment established for the condition. Herein, we present the case of a 65-year-old man who were treated the patient with hepatic arterial infusion chemotherapy, radiation therapy for tumor thrombosis, portal vein stent placement, lenvatinib administration, and renal venous shunt embolization. A complete response was observed according to mRECIST and the patient has been alive for 14 months since treatment initiation with no tumor recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Recidiva Local de Neoplasia , Veia Porta , Trombose/etiologia , Trombose/terapia
8.
Cancers (Basel) ; 13(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298768

RESUMO

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan-Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

9.
JAMA Netw Open ; 4(7): e2117060, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259847

RESUMO

Importance: Socioeconomic factors in the disparities in COVID-19 outcomes have been reported in studies from the US and other Western countries. However, no studies have documented national- or subnational-level outcome disparities in Asian countries. Objective: To assess the association between regional COVID-19 outcome disparities and socioeconomic characteristics in Japan. Design, Setting, and Participants: This cross-sectional study collected and analyzed confirmed COVID-19 cases and deaths (through February 13, 2021) as well as population and socioeconomic data in all 47 prefectures in Japan. The data sources were government surveys for which prefecture-level data were available. Exposures: Prefectural socioeconomic characteristics included mean annual household income, Gini coefficient, proportion of the population receiving public assistance, educational attainment, unemployment rate, employment in industries with frequent close contacts with the public, household crowding, smoking rate, and obesity rate. Main Outcomes and Measures: Rate ratios (RRs) of COVID-19 incidence and mortality by prefecture-level socioeconomic characteristics. Results: All 47 prefectures in Japan (with a total population of 126.2 million) were included in this analysis. A total of 412 126 confirmed COVID-19 cases (326.7 per 100 000 people) and 6910 deaths (5.5 per 100 000 people) were reported as of February 13, 2021. Elevated adjusted incidence and mortality RRs of COVID-19 were observed in prefectures with the lowest household income (incidence RR: 1.45 [95% CI, 1.43-1.48] and mortality RR: 1.81 [95% CI, 1.59-2.07]); highest proportion of the population receiving public assistance (1.55 [95% CI, 1.52-1.58] and 1.51 [95% CI, 1.35-1.69]); highest unemployment rate (1.56 [95% CI, 1.53-1.59] and 1.85 [95% CI, 1.65-2.09]); highest percentage of workers in retail industry (1.36 [95% CI, 1.34-1.38] and 1.45 [95% CI, 1.31-1.61]), transportation and postal industries (1.61 [95% CI, 1.57-1.64] and 2.55 [95% CI, 2.21-2.94]), and restaurant industry (2.61 [95% CI, 2.54-2.68] and 4.17 [95% CI, 3.48-5.03]); most household crowding (1.35 [95% CI, 1.31-1.38] and 1.04 [95% CI, 0.87-1.24]); highest smoking rate (1.63 [95% CI, 1.60-1.66] and 1.54 [95% CI, 1.33-1.78]); and highest obesity rate (0.93 [95% CI, 0.91-0.95] and 1.17 [95% CI, 1.01-1.34]) compared with prefectures with the most social advantages. Among potential mediating variables, higher smoking rate (RR, 1.54; 95% CI, 1.33-1.78) and obesity rate (RR, 1.17; 95% CI, 1.01-1.34) were associated with higher mortality RRs, even after adjusting for prefecture-level covariates and other socioeconomic variables. Conclusions and Relevance: This cross-sectional study found a pattern of socioeconomic disparities in COVID-19 outcomes in Japan that was similar to that observed in the US and Europe. National policy in Japan could consider prioritizing populations in socially disadvantaged regions in the COVID-19 response, such as vaccination planning, to address this pattern.


Assuntos
COVID-19 , Disparidades nos Níveis de Saúde , Classe Social , Adulto , Idoso , COVID-19/epidemiologia , Estudos Transversais , Aglomeração , Escolaridade , Emprego , Características da Família , Feminino , Humanos , Renda , Japão , Masculino , Pessoa de Meia-Idade , Obesidade , Ocupações , Pandemias , Assistência Pública , SARS-CoV-2 , Fumar , Fatores Socioeconômicos , Adulto Jovem
10.
Genes Cells ; 26(10): 823-829, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34245655

RESUMO

Nitric oxide (NO) is a ubiquitous signaling molecule in various organisms. In the yeast Saccharomyces cerevisiae, NO functions in both cell protection and cell death, depending on its concentration. Thus, it is important for yeast cells to strictly regulate NO concentration. The transcription factor Fzf1, containing five zinc fingers, is reportedly important for NO homeostasis by regulating the expression of the YHB1 gene, which encodes NO dioxygenase. However, the mechanism by which NO activates Fzf1 is still unclear. In this study, we showed that NO activated Fzf1 specifically at the protein level by RT-qPCR and Western blotting. Our further transcriptional analyses indicated that cysteine residues in the fourth zinc finger (ZF4) are required for the NO-responsive activation of Fzf1. Additionally, the present results suggest that ZF4 is important for the protein stability of Fzf1. From these results, we proposed possible mechanisms underlying Fzf1 activation.

11.
Biosci Biotechnol Biochem ; 85(9): 2084-2088, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34169967

RESUMO

We showed that the isobutanol sensitivity in glucose-6-phosphate dehydrogenase-deficient cells of the yeast Saccharomyces cerevisiae was rescued by an alternative NADPH producer, acetaldehyde dehydrogenase, but not in the cells lacking 6-phosphogluconate dehydrogenase. This phenotype correlated with the intracellular NADPH/NADP+ ratio in yeast strains. Our findings indicate the importance of NADPH for the isobutanol tolerance of yeast cells.

12.
Oncology ; 99(8): 507-517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33946070

RESUMO

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Pontuação de Propensão , Quinolinas/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
13.
Liver Cancer ; 10(2): 151-160, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33977091

RESUMO

Background: Overall survival of patients with advanced hepatocellular carcinoma (HCC) with Vp4 (tumor thrombosis of the main trunk or bilobar of the portal vein) is extremely poor. Purpose: The purpose of this study is to clarify the prognosis of hepatic arterial infusion chemotherapy (HAIC) combined with radiation therapy (RT) for advanced HCC with Vp4 and to analyze the factors that contribute to the prognosis. Methods: In this retrospective cohort study, 51 HCC patients who were treated with HAIC and RT for portal vein tumor thrombosis and met the following criteria were enrolled: (i) with Vp4; (ii) Child-Pugh score of 5-7; (iii) Eastern Cooperative Oncology Group performance status of 0 or 1; (iv) no history of systemic therapy; and (v) from September 2004 to April 2019. Results: Median overall survival and median progression-free survival were 12.1 and 4.2 months, respectively. Multivariate analysis showed >50% of relative tumor volume in the liver (HR, 3.027; p = 0.008) and extrahepatic spread with (HR, 3.773; p = 0.040) as significant and independent factors of OS. The total overall response rate (ORR) was 19.6%; ORR in main tumor was 13.7%; and ORR in Vp4 was 51.0%. None of the patients who received HAIC combined with RT for advanced HCC with Vp4 developed hepatic failure. This combination therapy of HAIC with RT was safe and well tolerated in all cases. Conclusion: Combination therapies of HAIC and RT might be good therapy for advanced HCC with Vp4.

14.
Oncology ; 99(8): 491-498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34000725

RESUMO

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
15.
BMC Fam Pract ; 22(1): 59, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789572

RESUMO

BACKGROUND: There is limited quantitative research on the effect of physician attire on patient-physician relationships. This study aimed to measure the influence of Japanese family physicians' attire on the "human" aspects of medical care in terms of patient-perceived relational empathy. METHODS: This was a multicenter, prospective, controlled trial conducted in primary clinics in Japan. We explored the effects of family physician attire (white coat vs. casual attire) on patient-perceived empathy. Family physicians were allocated to alternate weeks of wearing a white coat or casual attire during consultations. Patients' perceptions of physician empathy were evaluated using the self-rated Japanese Consultation and Relational Empathy (CARE) Measure. We used a linear mixed model to analyze the CARE Measure scores, adjusting for cluster effects of patients nested within doctor, age, and sex of patients, and doctors' sex and years of clinical experience. We used the same method with Bonferroni adjustment to analyze patient sex differences in perceived empathy. RESULTS: A total of 632 patients of seven family physicians were allocated to white coat-wearing consultations (n = 328), and casual attire-wearing consultations (n = 304). There was no difference in CARE Measure scores between white coat and casual primary care consultations overall (p = 0.162). Subgroup analysis of patient sex showed that CARE Measure scores of male patients were significantly higher in the Casual group than in the White coat group (adjusted p-value = 0.044). There was no difference in female patient scores between White coat and Casual groups (adjusted p-value = 1.000). CONCLUSIONS: This study demonstrated that physician attire (white coat or casual attire) in a primary care setting did not affect patient-perceived relational empathy overall. However, male patients of physicians wearing casual attire reported higher physician empathy. Although empathy cannot be reduced to simple variables such as attire, white coats may have a negative effect on patients, depending on the context. Family physicians should choose their attire carefully. TRIAL REGISTRATION: Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000037687 (Registered August 14, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042749 ). The study was prospectively registered.


Assuntos
Empatia , Médicos , Vestuário , Feminino , Humanos , Japão , Masculino , Preferência do Paciente , Percepção , Relações Médico-Paciente , Atenção Primária à Saúde , Estudos Prospectivos , Inquéritos e Questionários
16.
Yeast ; 38(7): 414-423, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33648021

RESUMO

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), which is required for various redox systems involving antioxidative stress enzymes, is thus important for stress tolerance mechanisms. Here, we analyzed the stress response of the NADPH-depleted cells of Saccharomyces cerevisiae. A cell viability assay showed that the NADPH depletion induced by disruption of the ZWF1 gene encoding glucose-6-phosphate dehydrogenase, which is the major determinant of the intracellular NADPH/NADP+ ratio, enhanced the tolerance of S. cerevisiae to both oxidative and nitrosative stresses. The subsequent analyses demonstrated that the antioxidative transcriptional factor Yap1 was activated and the cytosolic catalase Ctt1, whose expression is regulated by Yap1, was upregulated in zwf1Δ cells irrespective of the presence or absence of stress stimuli. Moreover, deletion of the YAP1 or CTT1 gene inhibited the increased stress tolerance of zwf1Δ cells, indicating that Ctt1 dominantly contributed to the higher stress tolerance of zwf1Δ cells. Our findings suggest that an NADPH-independent mechanism enhances oxidative and nitrosative stress tolerance in ZWF1-lacking yeast cells.


Assuntos
NADP/metabolismo , Estresse Nitrosativo , Estresse Oxidativo , Saccharomyces cerevisiae/enzimologia , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Oncology ; 99(5): 327-335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33677453

RESUMO

INTRODUCTION: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. METHODS: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. RESULTS: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. CONCLUSION: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Quinolinas/administração & dosagem , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Taxa de Sobrevida
18.
IDCases ; 23: e01059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552903

RESUMO

Background: Multi-virus real-time polymerase chain reaction (PCR) system is able to simultaneously detect 163 viruses using a multiplex Taqman real-time PCR system. We present a case of acute liver failure (ALF) of unknown etiology diagnosed with echovirus 30 infection via multi-virus real-time PCR. Case presentation: A previously healthy 66-year-old man had a persistent fever and developed ALF of unclear etiology. Although viral infection was suspected, serological screening showed no evidence of acute viral infections such as hepatitis A, B, C and E, Epstein-Barr virus, herpes simplex virus, and varicella zoster virus. Multi-virus real-time PCR revealed the presence of enterovirus and echovirus 30 genomes, and reverse transcription-PCR using enterovirus-specific primers confirmed the presence of enterovirus genome in serum samples at the time of admission. Anti-echovirus antibody titers showed an increase in paired sera. In spite of multimodality treatment, the patient died due to multiple organ failure. Histological analysis in autopsy revealed extensive coagulative necrosis of the hepatocytes and immunohistochemical analysis showed the expression of enterovirus antigens in necrotic hepatocytes. Conclusions: We present here a case of echovirus 30 associated with ALF. Multi-virus real-time PCR is useful for detection of virus for patients with ALF of unknown etiology suspected of harboring a viral infection.

19.
BMC Cancer ; 21(1): 201, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639880

RESUMO

BACKGROUND: We assessed the prognostic value of body mass index (BMI) in Asian patients with localized RCC who underwent nephrectomy. METHODS: A total of 665 patients who underwent nephrectomy for localized RCC were enrolled in the present study and divided into the two BMI groups: i.e., BMI < 25 in 463 (69.6%) and BMI > 25 in 202 (30.4%) patients. RESULTS: In total, there were 482 (72.5%) males and 183 (27.5%) females. Five-year cancer-specific survival (CSS) rates were significantly higher in increased BMI than the lower BMI group (97.1 and 92.5%: P = 0.007). When stratified by sex, significantly longer CSS in higher BMI was confirmed in males (5-year CSS of 92.7% in BMI < 25 and 98.1% in BMI > 25, p = 0.005), while there was no difference in CSS between BMI groups for female patients. Multivariable analysis exhibited that higher BMI was an independent predictor for favorable CSS in male (cox model: p = 0.041, Fine & Gray regression model: p = 0.014), but not in the female. Subgroup analysis for CSS revealed that favorable CSS with higher BMI was observed in patient subgroups of age < 65 (p = 0.019), clear cell histology (p = 0.018), and tumor size > 4 cm, p = 0.020) as well as male (p = 0.020). CONCLUSION: Our findings collected from the multi-institutional Japanese dataset demonstrated longer survival in patients with higher BMI than lower BMI for non-metastatic RCC treated with nephrectomy. Intriguingly, this finding was restricted to males, but not to females.


Assuntos
Índice de Massa Corporal , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia , Fatores Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
20.
Cancers (Basel) ; 13(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573172

RESUMO

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks-particularly in patients with a modest effect of ADT and poor performance status.

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