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1.
DNA Res ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677568

RESUMO

Cyanobacteria are a diverse group of Gram-negative prokaryotes that perform oxygenic photosynthesis. Cyanobacteria have been used for research on photosynthesis and have attracted attention as a platform for biomaterial/biofuel production. Cyanobacteria are also present in almost all habitats on Earth and have extensive impacts on global ecosystems. Given their biological, economical, and ecological importance, the number of high-quality genome sequences for Cyanobacteria strains is limited. Here, we performed genome sequencing of Cyanobacteria strains in the National Institute for Environmental Studies microbial culture collection in Japan. We sequenced 28 strains that can form a heterocyst, a morphologically distinct cell that is specialized for fixing nitrogen, and 3 non-heterocystous strains. Using Illumina sequencing of paired-end and mate pair libraries with in silico finishing, we constructed highly contiguous assemblies. We determined the phylogenetic relationship of the sequenced genome assemblies and found potential difficulties in the classification of certain heterocystous clades based on morphological observation. We also revealed a bias on the sequenced strains by the phylogenetic analysis of the 16S rRNA gene including unsequenced strains. Genome sequencing of Cyanobacteria strains deposited in worldwide culture collections will contribute to understanding the enormous genetic and phenotypic diversity within the phylum Cyanobacteria.

2.
J Phys Ther Sci ; 33(3): 246-249, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33814712

RESUMO

[Purpose] To quantitatively evaluate smoothness during standing and sitting motion analysis using an accelerometer and to clarify the relationship between indices. [Participants and Methods] Seventeen healthy males participated in this study. We attached a 9-axis motion sensor to the spinous process of the third lumbar spine and measured the acceleration of standing and sitting motions under normal and unstable conditions. We estimated and compared the root mean square and entropy in the lateral, vertical, longitudinal, and triaxial composite directions. [Results] On comparing both conditions, the unstable condition indices were significantly high, except for the lateral direction of entropy. The root mean square was significantly negatively correlated with entropy under normal conditions. [Conclusion] The study results suggested that the acceleration index quantitatively evaluates motion smoothness. Since each index had different characteristics, the motion-specific index was observed to be significant.

3.
Jpn J Infect Dis ; 74(5): 465-472, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33642428

RESUMO

Soon after the 2019 outbreak of coronavirus disease 2019 in Wuhan, China, a protocol for real-time RT-PCR assay detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) was established by the National Institute of Infectious Diseases (NIID) in Japan. The protocol used Charité's nucleocapsid (Sarbeco-N) and NIID nucleocapsid (NIID-N2) assays. During the following months, SARS-CoV-2 spread and caused a global pandemic, and various SARS-CoV-2 sequences were registered in public databases, such as the Global Initiative on Sharing All Influenza Data (GISAID). In this study, we evaluated the S2 assay (NIID-S2) that was newly developed to replace the Sarbeco-N assay and the performance of the NIID-N2 and NIID-S2 assays, referring to mismatches in the primer/probe targeted region. We found that the analytical sensitivity and specificity of the NIID-S2 set were comparable to those of the NIID-N2 assay, and the detection rate for clinical specimens was identical to that of the NIID-N2 assay. Furthermore, among the available sequences (approximately 192,000), the NIID-N2 and NIID-S2 sets had 2.6% and 1.2% mismatched sequences, respectively, although most of these mismatches did not affect the amplification efficiency, except the 3' end of the NIID-N2 forward primer. These findings indicate that the previously developed NIID-N2 assay is suitable for the detection of SARS-CoV-2 with support from the newly developed NIID-S2 set.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Proteínas do Nucleocapsídeo de Coronavírus/genética , Primers do DNA/genética , Humanos , Japão , Fosfoproteínas/genética , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2/genética , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/genética
4.
Gland Surg ; 10(1): 83-89, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33633965

RESUMO

Background: Remote-access thyroidectomy and its cosmetic merit have been widely accepted, but remote-access parathyroidectomy has not become common. There are few reports about the risks and effectiveness of a remote-access endoscopic parathyroidectomy. Herein, we evaluated the risks and benefits of total endoscopic parathyroidectomy (TEP) for patients with primary hyperparathyroidism (PHPT). We retrospectively compared the surgical outcomes of TEP and open minimally invasive parathyroidectomy (MIP). Methods: We analyzed the cases of 28 patients with PHPT who were scheduled to undergo a MIP at Mita Hospital (Tokyo) during the period from April 2015 to March 2019, all of whom were presumed preoperatively to have a single adenoma. Results: Eleven of the patients underwent a TEP (10 females, one male; mean age 54.2 years). The other 17 patients underwent an open MIP (11 females, 6 males; mean age 63.5 years). The younger patients and the females tended to select endoscopic surgery as their treatment. The operation time was significantly longer in the TEP group compared to the open MIP group (106 vs. 50 min; P<0.001). Common postoperative complications (such as recurrent laryngeal nerve paralysis and seroma) did not occur in this series. For the TEP patients who did not undergo a partial thyroidectomy, the mean amount of drainage on the first postoperative day was only 19±10 mL. The operative cure rate of the minimally invasive parathyroidectomies was 96.4%. Conclusions: TEP is a good surgical procedure for hyperparathyroidism caused by a single adenoma, and it achieves superior cosmetic results without increasing the rate of complications.

5.
Plant Dis ; 105(4): 1072-1079, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32897153

RESUMO

We developed a loop-mediated isothermal amplification (LAMP) assay for detecting Fusarium oxysporum f. sp. fragariae, the causal agent of wilt in strawberry plants. This assay was based on genomic regions between the portions of transposable elements Han and Skippy of the fungus. The LAMP assay allowed the efficient detection of F. oxysporum f. sp. fragariae DNA by visual inspection, without requiring gel electrophoresis. The detection limit was 100 pg of genomic DNA, which is comparable to that of PCR. The LAMP primers successfully discriminated F. oxysporum f. sp. fragariae strains from nonpathogenic F. oxysporum strains and other fungi. The LAMP assay at 63°C, which was found to be the optimal treatment temperature, for 1.5 h successfully detected F. oxysporum f. sp. fragariae California strains GL1270 and GL1385. When the assay was performed using a Genelyzer FIII portable fluorometer, these California strains were successfully detected in 1 h. The assay facilitated the detection of conidia in soil samples after they were precultured on a selective medium for F. oxysporum (FoG2) as well as latent infection in strawberry plants after preculturing. The LAMP assay for visual inspection of DNA required only a heating block and an incubator, reducing the cost of this assay. Thus, it could be suitable for the detection of F. oxysporum f. sp. fragariae strains in centers that store prefoundation and foundation stocks of strawberry, including plant nurseries.


Assuntos
Fusarium , Fusarium/genética , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Doenças das Plantas
6.
Gan To Kagaku Ryoho ; 47(9): 1387-1389, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130707

RESUMO

A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy( CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Ductal , Carcinoma Intraductal não Infiltrante , Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Criança , Feminino , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/cirurgia , Humanos , Mastectomia
7.
Microbiol Immunol ; 64(9): 635-639, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579258

RESUMO

In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.


Assuntos
Antivirais/farmacologia , Benzamidas/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Ácido Micofenólico/farmacologia , Pneumonia Viral/tratamento farmacológico , Animais , COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Vírus da Dengue/efeitos dos fármacos , Humanos , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Células Vero , Replicação Viral/efeitos dos fármacos
8.
Proc Natl Acad Sci U S A ; 117(13): 7001-7003, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32165541

RESUMO

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many countries globally. Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Serina Endopeptidases/metabolismo , Animais , COVID-19 , Linhagem Celular , Chlorocebus aethiops , Surtos de Doenças , Humanos , Pandemias , RNA Viral/metabolismo , SARS-CoV-2 , Células Vero , Cultura de Vírus
9.
J Phys Ther Sci ; 32(1): 48-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32082028

RESUMO

[Purpose] This study investigated spine kinematics during normal sitting and flexion sitting with lateral reaching using a three-dimensional motion analysis system. [Participants and Methods] Nineteen healthy young adult males participated in this study. While seated, each participant was asked to reach toward the right using his right hand. Spine angles were defined as T1, T4, T8, L1, and L5 segments. Kinematic data were calculated using the Euler angle and compared to normal sitting and flexion sitting. During flexion sitting, each participant wore a trunk flexion brace. [Results] In the frontal plane, the angle of the T8 segment during flexion sitting was significantly less than during normal sitting. In the axial plane, there were significant differences among the T4, L1, and L5 segments. [Conclusion] Changes in spinal alignment decrease spinal movement and change the movement strategy during lateral reaching while seated.

10.
Jpn J Infect Dis ; 73(4): 304-307, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32074516

RESUMO

During the emergence of novel coronavirus 2019 (nCoV) outbreak in Wuhan city, China at the end of 2019, there was movement of many airline travelers between Wuhan and Japan, suggesting that the Japanese population was at high risk of infection by the virus. Hence, we urgently developed diagnostic systems for detection of 2019 nCoV. Two nested RT-PCR and two real-time RT-PCR assays were adapted for use in Japan. As of February 8, 2020, these assays have successfully detected 25 positive cases of infection in Japan.


Assuntos
Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , RNA Viral/análise , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Humanos , Japão , Pandemias , Poliproteínas , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais/genética
11.
J Surg Res ; 246: 535-543, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31711613

RESUMO

BACKGROUND: A growing body of evidences shows that systemic inflammatory responses are involved in patient prognosis in multiple cancers. Combinations of peripheral leukocyte fractions have been shown to be useful markers for the inflammatory responses. However, significance of such systemic inflammatory responses is still unknown in thyroid cancer. Accordingly, we aimed to clarify clinical impact of peripheral leukocyte fractions in papillary thyroid cancer (PTC). METHODS: Clinicopathological analyses were performed including preoperative leukocyte fractions in 570 patients with curatively resected PTC. Receiver operating characteristic curves were used to determine cutoffs of leukocyte fraction or inflammation indexes such as lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio. A Kaplan-Meier analysis and a Cox's proportional hazard model were used to conduct prognostic analysis. A multivariable logistic regression analysis was performed for correlation assay. RESULTS: Preoperative low LMR predicted recurrence with high sensitivity (63.3%) and specificity (68.7%) (P = 0.002). The multivariable prognostic analyses revealed that preoperative low LMR (P = 0.025), pathological N1b (P = 0.019), high metastatic lymph node ratio (node density) (P = 0.014), and high thyroglobulin level (P = 0.002) independently predicted worse prognosis. The combination of these independent parameters clearly enriched high-risk patients (P < 0.001). Of note, low LMR was dramatically associated with recurrence especially in patients with advanced PTC. CONCLUSIONS: Preoperative low LMR dramatically predicts high-risk patients for recurrences. The results in this study give rational to focusing on immune cell profiles to tackle advanced PTC.


Assuntos
Linfócitos , Monócitos , Recidiva Local de Neoplasia/diagnóstico , Câncer Papilífero da Tireoide/sangue , Neoplasias da Glândula Tireoide/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
12.
J Surg Res ; 245: 552-563, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472311

RESUMO

BACKGROUND: It is elusive which subtypes of immune cells are pivotal in cancer progression and prognosis in gastric cancer (GC). The aim of this study is to clarify clinical impact of immature myeloid-derived immune cells in patients with GC who underwent curative gastrectomy with curative lymphadenectomy and treated with S-1 (tegafur/gimeracil/oteracil) postoperatively. METHODS: The prognostic impact of recruited CD33+ immature myeloid-derived cells were clinicopathologically analyzed in curatively resected stage II and III GC. Correlation of preoperative peripheral leukocyte fractions with recruited CD33+ immature cells was also assessed. RESULTS: Patients with high CD33+ cell counts in primary tumor showed dramatically worse prognosis (5-y recurrence-free survival 29.0%) than that of the counterparts (79.4%). High CD33+ cell counts independently predicted poor prognosis in stage II/III (hazard ratio, 4.34; P < 0.001). In analyses of each stage, high CD33+ cell count was pivotally associated with poor prognosis in both stages. There was no significant correlation of each peripheral leukocyte fraction with CD33+ cell recruitment. Of note, high CD33+ cell count was significantly correlated with hematogenous recurrence. CONCLUSIONS: Recruitment of CD33+ immature myeloid cells critically predict hematogenous recurrences in curatively resected advanced GC. These results give rational to focusing on CD33+ myeloid-derived cells as a novel approach to tackle advanced GC.


Assuntos
Células Supressoras Mieloides/imunologia , Recidiva Local de Neoplasia/diagnóstico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Neoplasias Gástricas/terapia , Estômago/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/imunologia , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Prognóstico , Estômago/citologia , Estômago/cirurgia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem
13.
Biomed Rep ; 11(6): 253-256, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798870

RESUMO

Palbociclib is a first-in-class potent oral inhibitor of cyclin-dependent kinase (CDK)4/6 that was approved in the USA in 2015 and in Japan in 2017. Next-generation abemaciclib was approved in the USA and Japan in 2018. The use of palbociclib results in a high frequency of bone marrow suppression, whereas abemaciclib induces a low frequency of bone marrow suppression, but a high incidence of diarrhea. However, the most appropriate uses for these CDK4/6 inhibitors remain unclear. In this study, we analyzed the efficacy and side-effects associated with the use of palbociclib at our hospital and examined the suitability of palbociclib or abemaciclib. Among 35 patients who used palbociclib at our hospital from December, 2017 to December, 2018, the mean age was 39-83 years. The patients receiving treatment with palbociclib with a combination of drugs included 20 patients (57%) receiving fulvestrant, 8 patients (23%) receiving letrozole, and 7 patients (20%) receiving fulvestrant + LH-RH (leuprorelin). Fourteen patients (40%) had a history of receiving chemotherapy, and 21 patients (60%) had no history of receiving chemotherapy. The number of prior treatment regimens was 0-11 (mean, 2.9). The initial dose of palbociclib was 125 mg for 29 patients (83%) and 100 mg for 6 patients (17%). Partial response, stable disease and progressive disease were achieved in 6 (17%), 19 cases (54%) and 10 cases (29%), respectively. Leukocytopenia was observed in 24 cases, neutropenia was observed in 26 cases, anemia was observed in 13 cases, thrombocytopenia was observed in 15 cases, fatigue was observed in 3 cases and itchy skin was observed in 1 case. When the number of neutrophils prior to palbociclib introduction was <3,000, neutropenia of grade 3 or higher was observed in all cases following palbociclib introduction. Thus, in order to avoid grade 3 or higher neutropenia and to maintain relative dose intensity, abemaciclib treatment may be considered for cases with neutrophils of <3,000 prior to the introduction of a CDK4/6 inhibitor.

14.
Oncotarget ; 10(57): 5906-5918, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31666923

RESUMO

HOPX is involved in multiple organ development and acts as a tumor suppressor in various cancers. Epigenetic silencing of HOPX via its promoter methylation has been shown frequent and cancer-specific in human cancers. The proliferation of thyroid cancer cells and cancer progression are strongly influenced by epigenetic alterations as well as genetic changes. Papillary thyroid cancer (PTC) comprises the vast majority of thyroid cancers and exhibits slow progression. However, ~10% of patients still show disease recurrence and refractoriness to treatment. Accordingly, it is important approach to research epigenetic mechanisms in PTC progression to find useful biomarkers. Here, we aimed to seek into the roles and clinical impact of epigenetic silencing of HOPX in PTC. The promoter methylation of HOPX was observed in five of six human thyroid cancer cell lines. Down-regulation of HOPX was seen in three cell lines including PTC line K1, and demethylating agents restored HOPX expression. The promoter methylation was observed with high sensitivity and specificity in human PTC tissues. HOPX promoter methylation independently predicted disease recurrence in PTC patients. Epigenetic silencing of HOPX was associated with Ki-67 expression. Of note, HOPX promoter methylation was dramatically associated with worse prognosis especially in patients with stage I PTC. Forced HOPX expression suppressed cell proliferation, invasive activities, and anchorage-independent growth in vitro. HOPX promoter methylation is frequent and cancer-specific event, leading to aggressive phenotype in PTC. Epigenetic silencing of HOPX may be a clue to tackle cancer progression and have clinical impact as a novel biomarker in PTC.

15.
J Phys Ther Sci ; 31(10): 776-779, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31645805

RESUMO

[Purpose] In clinical settings, patients with knee osteoarthritis often complain of pain at gait initiation. In the present study, we aimed to determine the differences in the center of foot pressure and lower extremity muscle activity at gait initiation in healthy volunteers compared to patients with medial knee osteoarthritis. [Participants and Methods] The study comprised of 10 females without medial knee osteoarthritis (healthy group) and 10 females with medial knee osteoarthritis (medial knee osteoarthritis group). We measured the center of foot pressure trajectory and muscle activity onset times of the tibialis anterior and internal gastrocnemius at gait initiation. Moreover, we examined the effects of insole use in the medial knee osteoarthritis group. [Results] The posterior center of foot pressure displacement was significantly smaller in the medial knee osteoarthritis group (barefoot and insole) than in the healthy group. The anterior center of foot pressure displacement significantly improved with insole use. The muscle activity onset time of the tibialis anterior was significantly delayed in the medial knee osteoarthritis group (barefoot) than in the healthy group. [Conclusion] Postural control decreased at gait initiation in the medial knee osteoarthritis group.

16.
J Virol ; 93(22)2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31484751

RESUMO

Two viral nonstructural proteins, p150 and p90, are expressed in rubella virus (RUBV)-infected cells and mediate viral genome replication, presumably using various host machineries. Molecular chaperones are critical host factors for the maintenance of cellular proteostasis, and certain viral proteins use this chaperone system. The RUBV p150 and p90 proteins are generated from a precursor polyprotein, p200, via processing by the protease activity of its p150 region. This processing is essential for RUBV genome replication. Here we show that heat shock protein 90 (HSP90), a molecular chaperone, is an important host factor for RUBV genome replication. The treatment of RUBV-infected cells with the HSP90 inhibitors 17-allylamino-17-desmethoxygeldanamycin (17-AAG) and ganetespib suppressed RUBV genome replication. HSP90α physically interacted with p150, but not p90. Further analyses into the mechanism of action of the HSP90 inhibitors revealed that HSP90 activity contributes to p150 functional integrity and promotes p200 processing. Collectively, our data demonstrate that RUBV p150 is a client of the HSP90 molecular chaperone and that HSP90 functions as a key host factor for RUBV replication.IMPORTANCE Accumulating evidence indicates that RNA viruses use numerous host factors during replication of their genomes. However, the host factors involved in rubella virus (RUBV) genome replication are largely unknown. In this study, we demonstrate that the HSP90 molecular chaperone is needed for the efficient replication of the RUBV genome. Further, we reveal that HSP90 interacts with RUBV nonstructural protein p150 and its precursor polyprotein, p200. HSP90 contributes to the stability of p150 and the processing of p200 via its protease domain in the p150 region. We conclude that the cellular molecular chaperone HSP90 is a key host factor for functional maturation of nonstructural proteins for RUBV genome replication. These findings provide novel insight into this host-virus interaction.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Vírus da Rubéola/metabolismo , Proteínas não Estruturais Virais/metabolismo , Células A549 , Animais , Linhagem Celular , Chlorocebus aethiops , Células HEK293 , Proteínas de Choque Térmico HSP90/fisiologia , Humanos , Chaperonas Moleculares/metabolismo , Proteólise , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Rubéola (Sarampo Alemão)/virologia , Células Vero , Proteínas não Estruturais Virais/genética , Replicação Viral/genética , Replicação Viral/fisiologia
17.
Ann Surg Oncol ; 26(13): 4814-4825, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529309

RESUMO

BACKGROUND: OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. METHODS: OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). RESULTS: OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. CONCLUSION: Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC.


Assuntos
Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Marcadores Genéticos , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Idoso , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Seguimentos , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Peptídeos Cíclicos/farmacologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
18.
Cancer Sci ; 110(9): 2846-2855, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325200

RESUMO

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation-specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound-fine needle aspiration (EUS-FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS-FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS-FNA cytology.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Cisteína Dioxigenase/genética , Metilação de DNA , Neoplasias Pancreáticas/diagnóstico , Idoso , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Cisteína Dioxigenase/metabolismo , Progressão da Doença , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Suco Pancreático/metabolismo , Neoplasias Pancreáticas/patologia , Projetos Piloto , Prognóstico , Regiões Promotoras Genéticas , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Anticancer Res ; 39(5): 2289-2298, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092420

RESUMO

BACKGROUND/AIM: We previously identified that promoter DNA methylation of cysteine dioxygenase type 1 (CDO1) and homeobox only protein homeobox (HOPX) were both cancer specific, and have a clinical potential as prognostic biomarkers in breast cancer (BC). The present study compared the differential prognostic relevance of methylation status of the CDO1 and HOPX genes in BC. MATERIALS AND METHODS: Methylation levels (TaqMethVs) were quantified in 7 BC cell lines and 133 BC patients by TaqMan methylation-specific PCR and functional traits were explored for CDO1. RESULTS: TaqMethVs were associated between CDO1 and HOPX (r2=0.072, p=0.002). Multivariate Cox proportional hazards model could identify CDO1 hypermethylation as well as Ki-67 as independent prognostic factors related to disease-specific survival (p=0.016, p<0.001). Overexpression of CDO1 decreased the anchorage-independent growth capacity in BC cell lines. CONCLUSION: CDO1 is a definite tumor suppressor gene, while its prognostic relevance was more than expected in the context of its functional relevance.


Assuntos
Neoplasias da Mama/genética , Cisteína Dioxigenase/genética , Metilação de DNA/genética , Proteínas de Homeodomínio/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Modelos de Riscos Proporcionais
20.
PLoS Pathog ; 15(5): e1007749, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31121004

RESUMO

The regulation of paramyxovirus RNA synthesis by host proteins is poorly understood. Here, we identified a novel regulation mechanism of paramyxovirus RNA synthesis by the Hsp90 co-chaperone R2TP complex. We showed that the R2TP complex interacted with the paramyxovirus polymerase L protein and that silencing of the R2TP complex led to uncontrolled upregulation of mumps virus (MuV) gene transcription but not genome replication. Regulation by the R2TP complex was critical for MuV replication and evasion of host innate immune responses. The R2TP complex also regulated measles virus (MeV) RNA synthesis, but its function was inhibitory and not beneficial to MeV, as MeV evaded host innate immune responses in the absence of the R2TP complex. The identification of the R2TP complex as a critical host factor sheds new light on the regulation of paramyxovirus RNA synthesis.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Interações Hospedeiro-Patógeno , Vírus da Caxumba/genética , Caxumba/genética , RNA Viral/biossíntese , Proteínas Virais/metabolismo , Replicação Viral , Células A549 , Proteínas de Choque Térmico HSP90/genética , Humanos , Caxumba/virologia , Proteínas Virais/genética
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