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1.
J Virol ; 98(3): e0127823, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38345384

RESUMEN

Cytomegalovirus (CMV), a type of herpes virus, is the predominant cause of congenital anomalies due to intrauterine infections in humans. Adverse outcomes related to intrauterine infections with human cytomegalovirus (HCMV) vary widely, depending on factors such as fetal infection timing, infection route, and viral virulence. The precise mechanism underlying HCMV susceptibility remains unclear. In this study, we compared the susceptibility of neonatal human dermal fibroblast cells (NHDFCs) and human induced pluripotent stem cells (hiPSCs) derived from NHDFCs, which are genetically identical to HCMV, using immunostaining, microarray, in situ hybridization, quantitative PCR, and scanning electron microscopy. These cells were previously used to compare CMV susceptibility, but the underlying mechanisms were not fully elucidated. HCMV susceptibility of hiPSCs was significantly lower in the earliest phase. No shared gene ontologies were observed immediately post-infection between the two cell types using microarray analysis. Early-stage expression of HCMV antigens and the HCMV genome was minimal in immunostaining and in in situ hybridization in hiPSCs. This strongly suggests that HCMV does not readily bind to hiPSC surfaces. Scanning electron microscopy performed using the NanoSuit method confirmed the scarcity of HCMV particles on hiPSC surfaces. The zeta potential and charge mapping of the charged surface in NHDFCs and hiPSCs exhibited minimal differences when assessed using zeta potential analyzer and scanning ion conductance microscopy; however, the expression of heparan sulfate (HS) was significantly lower in hiPSCs compared with that in NHDFCs. Thus, HS expression could be a primary determinant of HCMV resistance in hiPSCs at the attachment level. IMPORTANCE: Numerous factors such as attachment, virus particle entry, transcription, and virus particle egress can affect viral susceptibility. Since 1984, pluripotent cells are known to be CMV resistant; however, the exact mechanism underlying this resistance remains elusive. Some researchers suggest inhibition in the initial phase of HCMV binding, while others have suggested the possibility of a sufficient amount of HCMV entering the cells to establish latency. This study demonstrates that HCMV particles rarely attach to the surfaces of hiPSCs. This is not due to limitations in the electrostatic interactions between the surface of hiPSCs and HCMV particles, but due to HS expression. Therefore, HS expression should be recognized as a key factor in determining the susceptibility of HCMV in congenital infection in vitro and in vivo. In the future, drugs targeting HS may become crucial for the treatment of congenital CMV infections. Thus, further research in this area is warranted.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Heparitina Sulfato , Células Madre Pluripotentes Inducidas , Humanos , Recién Nacido , Membrana Celular/química , Membrana Celular/metabolismo , Citomegalovirus/fisiología , Heparitina Sulfato/análisis , Heparitina Sulfato/metabolismo , Infecciones por Herpesviridae , Células Madre Pluripotentes Inducidas/química , Células Madre Pluripotentes Inducidas/metabolismo , Fibroblastos/química , Fibroblastos/metabolismo , Fibroblastos/virología , Piel/citología
2.
Sci Adv ; 9(11): eadf4166, 2023 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-36921046

RESUMEN

The potato cyst nematode (PCN) causes extensive crop losses worldwide. Because the hatching of PCN requires host-derived molecules known as hatching factors (HFs), regulating HF production in host plants may help to control this harmful pest. Solanoeclepin A (SEA), isolated from potato, is the most active HF for PCN; however, its biosynthesis is completely unknown. We discovered a HF called solanoeclepin B (SEB) from potato and tomato root exudates and showed that SEB was biosynthesized in the plant and converted to SEA outside the plant by biotic agents. Moreover, we identified five SEB biosynthetic genes encoding three 2-oxoglutarate-dependent dioxygenases and two cytochrome P450 monooxygenases in tomato. Exudates from tomato hairy roots in which each of the genes was disrupted contained no SEB and had low hatch-stimulating activity for PCN. These findings will help to breed crops with a lower risk of PCN infection.


Asunto(s)
Nematodos , Solanum lycopersicum , Solanum tuberosum , Animales , Solanum tuberosum/genética , Raíces de Plantas/genética , Fitomejoramiento , Solanum lycopersicum/genética , Nematodos/fisiología
3.
Hinyokika Kiyo ; 68(9): 295-300, 2022 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-36199208

RESUMEN

Immune checkpoint inhibitors (ICIs) provide excellent benefits to the treatment of various cancer types, including urothelial carcinoma. Conversely, they can cause immune-related adverse events (irAEs), and some of them are severe or fatal. Furthermore, evidence on the safety and effectiveness of the readministration of ICIs after the occurrence of irAEs is limited. In this case report, a 78-year-old man who suffered from metastatic right renal pelvic cancer was treated with pembrolizumab. He had a partial response to pembrolizumab, but he developed grade 3 myasthenia gravis. The myasthenia gravis symptoms were immediately relieved by corticosteroids and intravenous immunoglobulin therapy. When the disease rapidly progressed, he was treated again with pembrolizumab. After 5 days, a chest radiograph showed shrinkage of pulmonary metastases. Unfortunately, he died of multiple brain infarctions 7 days after the readministration. We report this case with a literature review on the efficacy and safety of the readministration of ICIs after the occurrence irAEs including myasthenia gravis.


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Células Transicionales , Neoplasias Renales , Miastenia Gravis , Neoplasias de la Vejiga Urinaria , Anciano , Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Células Transicionales/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoglobulinas Intravenosas/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Masculino , Miastenia Gravis/inducido químicamente , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
4.
Rev Sci Instrum ; 93(8): 084905, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050116

RESUMEN

A new temperature measurement method-the dual two-color method-was developed to accurately measure the temperature over an ultra-wide temperature range (200-3600 °C) for ITER divertor infrared thermography. This novel method introduces a third wavelength filter to the conventional two-color method by replacing the shorter single wavelength bandpass filter with a customized dual-bandpass filter having two transmission bands, without having to add a third infrared camera. The dominant wavelength band of the total radiance through the dual-band filter changes automatically as the temperature increases and, consequently, either the shorter or longer wavelength band of the dual-bandpass filter is used to establish the two-color combination at both low and high temperatures. The dual two-color method increased the acceptable measurement error of the two-color radiance ratio for the temperature measurement requirement of the ITER divertor infrared thermography to 9.45% from that of 4.3% when using the conventional two-color method.

5.
Cancer Genet ; 266-267: 28-32, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35691222

RESUMEN

Birt-Hogg-Dubé syndrome is an autosomal dominant disease caused by germline mutations in the folliculin gene (FLCN), characterized by skin fibrofolliculomas, pulmonary cysts, and multiple renal tumors. We report the case of a 51-year-old woman with multiple bilateral renal tumors resected by bilateral open partial nephrectomy. Following pathological diagnosis of hybrid oncocytic/chromophobe tumors, targeted next-generation sequencing of FLCN of the patient's blood revealed a novel missense mutation (c.602A>C, p.Gln201Pro) in exon 6. Sanger sequencing revealed that this mutation was heterozygous. In silico prediction programs consistently indicated the mutation as pathogenic. Western blot analysis and immunohistochemistry revealed suppressed FLCN expression and the upregulation of glycoprotein nonmetastatic B, a downstream target negatively regulated by FLCN, in the tumor tissue, suggesting that the mutation resulted in reduction of functional FLCN expression. Whole-genome sequencing of one of the tumors identified another frameshift mutation in exon 4, suggesting a "second hit" leading to tumorigenesis. We recommend that gene sequencing should be considered in patients with multiple renal tumors to identify their genetic predisposition to renal tumors.


Asunto(s)
Síndrome de Birt-Hogg-Dubé , Neoplasias Renales , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Birt-Hogg-Dubé/patología , Humanos , Neoplasias Renales/genética , Mutación , Mutación Missense , Fenotipo
6.
J Ocul Pharmacol Ther ; 38(5): 354-358, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35613407

RESUMEN

Purpose: To retrospectively evaluate the 1-year efficacy and safety of single-agent of omidenepag isopropyl in patients with normal-tension glaucoma (NTG). Methods: One hundred patients (100 eyes) newly administered omidenepag isopropyl were enrolled. Intraocular pressure (IOP) was compared at baseline and 3, 6, 9, and 12 months after administration. The mean deviation values at baseline and 12 months measured using the Humphrey visual field test (30-2 Swedish Interactive Threshold Algorithm standard) were compared. Adverse reactions and dropouts were observed. Results: IOP significantly decreased from 15.5 ± 2.7 mmHg at baseline to 13.3 ± 2.5 mmHg after 3 months, 13.7 ± 2.3 mmHg after 6 months, 13.9 ± 2.4 mmHg after 9 months, and 13.7 ± 2.3 mmHg after 12 months (P < 0.0001). There was no significant difference in the mean deviation values at baseline (-3.66 ± 3.49 dB) and after 12 months (-3.41 ± 3.80 dB). Adverse reactions occurred in 9 patients (9.0%): conjunctival hyperemia (n = 6), eye pain (n = 1), iritis (n = 1), and blepharitis (n = 1). Twenty-one patients (21.0%) discontinued administration because of changes in medication (n = 7), interruption of visits (n = 5), adverse reactions (n = 4), and others. Conclusions: After administering omidenepag isopropyl, the IOP in patients with NTG decreased within 1 year, visual fields were maintained, and safety was satisfactory. Omidenepag isopropyl can be used as the first-line medication for patients with NTG.


Asunto(s)
Glaucoma de Baja Tensión , Glicina/análogos & derivados , Humanos , Presión Intraocular , Glaucoma de Baja Tensión/tratamiento farmacológico , Pirazoles , Piridinas , Estudios Retrospectivos , Tonometría Ocular
7.
Artículo en Inglés | MEDLINE | ID: mdl-35487690

RESUMEN

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2 Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Resección Transuretral de la Próstata , Anticuerpos Monoclonales Humanizados , Humanos , Masculino , Inestabilidad de Microsatélites , Proteína 2 Homóloga a MutS/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética
8.
IJU Case Rep ; 5(1): 32-35, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35005467

RESUMEN

INTRODUCTION: Mucin-producing adenocarcinoma of the prostate is a rare disease that includes prostate adenocarcinoma with mucus production, secondary adenocarcinoma from the bladder or colorectum, and adenocarcinoma from the urothelium of the prostatic urethra. We describe prostate-specific antigen-negative mucin-producing urothelial-type adenocarcinoma of the prostate. CASE PRESENTATION: The patient had urinary retention and a serum prostate-specific antigen level of 0.74 ng/mL. Computed tomography and magnetic resonance imaging revealed a prostate tumor with a mucous component. We diagnosed adenocarcinoma by prostate biopsy and subsequently performed robot-assisted radical prostatectomy. Mucin-producing urothelial-type adenocarcinoma of the prostate was diagnosed by pathological examinations. Lung metastasis, developing within 3 months after surgery, was treated using chemotherapy. CONCLUSION: Endocrine therapy is ineffective for mucin-producing urothelial-type adenocarcinoma of the prostate. Mucin-producing urothelial-type adenocarcinoma of the prostate diagnosis requires pathological and immunohistochemical analyses. It is important to surgically remove the primary lesion, and robot-assisted radical prostatectomy may provide an effective approach. Multimodal therapy is essential to treat for mucin-producing urothelial-type adenocarcinoma of the prostate.

9.
Colloids Surf B Biointerfaces ; 211: 112286, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34929484

RESUMEN

Dehydrin is an intrinsically disordered protein involved in the cold tolerance of plants. Although dehydrins have been thought to protect biomembranes under cold conditions, the underlying protective mechanism has not been confirmed. Here we report that Arabidopsis dehydrin AtHIRD11 inhibited the aggregation of phospholipid liposomes after freezing and thawing. AtHIRD11 showed significantly greater cryoaggregation-prevention activity than cryoprotective agents such as trehalose, proline, and polyethylene glycols. Amino acid sequence segmentation analysis indicated that the K-segment of AtHIRD11 inhibited the cryoaggregation of phosphatidylcholine (PC) liposomes but other segments did not. This showed that K-segments conserved in all dehydrins were likely to be the cryoprotective sites of dehydrins. Amino acid replacement for a typical K-segment (TypK for short) sequence demonstrated that both hydrophobic and charged amino acids were required for the cryoaggregation-prevention activity of PC liposomes. The amino acid shuffling of TypK remarkably reduced cryoprotective activity. Although TypK did not bind to PC liposomes in solution, the addition of liposomes reduced its disordered content under crowded conditions. Together, these results suggested that dehydrins protected biomembranes via conserved K-segments whose sequences were optimized for cryoprotective activities.


Asunto(s)
Arabidopsis , Proteínas Intrínsecamente Desordenadas , Secuencia de Aminoácidos , Arabidopsis/química , Proteínas Intrínsecamente Desordenadas/química , Liposomas , Fosfolípidos , Proteínas de Plantas/química
10.
Am J Ophthalmol ; 237: 114-121, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34942112

RESUMEN

PURPOSE: To investigate the periocular adverse reactions to omidenepag isopropyl (OMDI). DESIGN: Nonrandomized comparative clinical study. METHODS: We enrolled 100 patients (100 eyes) with primary open-angle glaucoma or ocular hypertension who received initial treatment with OMDI or tafluprost in only 1 eye for ≥6 months. Photographs of the eyelids were taken on the day of the participants' visit after ≥6 months of prescription. Subsequently, 3 ophthalmologists individually determined the occurrence of eyelid pigmentation, eyelash growth, and deepening of the upper eyelid sulcus (DUES). Additionally, a questionnaire on the subjective symptoms was administered. Multivariate analysis of baseline data was performed to investigate the factors involved in adverse reactions. RESULTS: The mean duration of drug administration was 10.2 ± 3.8 and 10.8 ± 4.1 months in the OMDI and tafluprost groups, respectively. The frequencies of eyelid pigmentation, eyelash growth, and DUES were 0.0%, 0.0%, and 2.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 4.0%, 32.0%, and 12.0%. The only significant difference was that the OMDI group showed fewer patients with eyelash growth than in the tafluprost group (P < .0001). In the questionnaire, the subjective symptoms of eyelid pigmentation, eyelash growth, and DUES were 8.0%, 2.0%, and 4.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 12.0%, 40.0%, and 4.0%, respectively. Multivariate analysis revealed a correlation between the type of drug administered and these adverse reactions (R = 0.38, P = .005). CONCLUSIONS: The frequencies of periocular adverse reactions to OMDI, ranging from 0% to 2.0%, were lower than those to tafluprost.


Asunto(s)
Glaucoma de Ángulo Abierto , Hipertensión Ocular , Antihipertensivos/efectos adversos , Glicina/análogos & derivados , Humanos , Presión Intraocular , Pirazoles/uso terapéutico , Piridinas
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7178-7181, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892756

RESUMEN

The walking distance estimated from the coordinate position information of the center of mass obtained via Xsens MTw Awinda were validated from 5 adult volunteers and the accuracy was shown significantly high. (Average absolute error of -1.22% with a standard deviation of 2.26%).


Asunto(s)
Caminata , Dispositivos Electrónicos Vestibles , Adulto , Recolección de Datos , Humanos , Voluntarios
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7276-7279, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892778

RESUMEN

Full body motion tracking system was used to obtain accurate posture information under free-living condition and the accuracy of posture prediction by ActiGraph was verified. ActiGraph tends to detect people as standing when they are actually sitting. By combining a prediction model that detects posture change, lying posture, and walking from raw acceleration data obtained by ActiGraph, we were able to predict posture information with higher accuracy.Clinical Relevance- By combining model for predicting posture changes, lying posture, and walking from raw acceleration data obtained by ActiGraph, it is possible to obtain more accurate posture information.


Asunto(s)
Acelerometría , Postura , Aceleración , Humanos , Posición de Pie , Caminata
13.
Int J Urol ; 28(12): 1261-1267, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34545627

RESUMEN

OBJECTIVES: To investigate the impact of the number of cycles and objective response to chemotherapy on overall survival in patients with metastatic urothelial carcinoma treated with pembrolizumab. METHODS: This multicenter, retrospective study included 755 patients from 59 institutions with advanced, chemoresistant urothelial carcinoma who received pembrolizumab. The associations of the overall survival with the number of cycles and best objective response were investigated using Cox multiple regression analysis. RESULTS: Overall, 391 patients received standard first-line chemotherapy and pembrolizumab as a second-line treatment, and were included in the final analysis. Of the 391 patients, 185 received less than four cycles, 134 received four to six cycles and 72 received more than six cycles of first-line chemotherapy. An objective response (complete or partial response) to chemotherapy was observed in 145 patients (37.1%). Univariate analysis showed that the overall survival of patients who received more than six cycles or responded to chemotherapy (complete or partial response) was significantly longer than that of patients who received less than four cycles or did not respond to chemotherapy (stable or progressive disease). At multivariate levels, no correlations were observed between overall survival and the number of cycles of or the response to chemotherapy. CONCLUSIONS: Therapeutic benefit of pembrolizumab can be expected irrespective of the objective response to and number of cycles of platinum-based first-line chemotherapy.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Humanos , Platino (Metal)/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
14.
Case Rep Urol ; 2021: 7822422, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34327035

RESUMEN

Lymphorrhea can develop after various types of surgeries. Surgical closure of the lymphatic leakage point is an effective treatment option. However, it is difficult to identify the leakage point sometimes. Here, we report a case of pelvic lymphorrhea after radical cystectomy for bladder cancer. Identification of the leakage point was difficult during laparoscopic surgical repair of lymphorrhea. Intranodal lymphangiography was performed via the inguinal lymph node by injection of lipiodol, followed by injection of indigo carmine. Laparoscopy revealed extravasation of lipiodol and indigo carmine from the pelvic wall. The leakage point was successfully cauterized using an electric scalpel. Lymphorrhea improved after the surgical repair. This case suggests that intranodal lymphangiography may be useful for detecting the site of lymphatic leakage during the surgical repair of lymphorrhea.

15.
Biosci Biotechnol Biochem ; 85(8): 1789-1797, 2021 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-34057172

RESUMEN

Headspace solid-phase microextraction combined with gas chromatography/mass spectrometry is one of the strongest tools for comprehensive analysis of volatile compounds and has been used to analyze aromatic components of mango and investigate its varietal characteristics. In this study, profiling of aroma compounds in 17 mango cultivars, grown in the same green house to exclude the effect of environmental factors, was conducted and the patterns were subjected to principal component analysis (PCA) to identify the relationship between the aroma components and cultivars. Fifty-nine different volatile constituents were detected from the blends of these 17 mango cultivars. The cultivars were divided into 4 clusters using PCA based on the volatile components determined in the study. Aiko was found to mainly contain δ-3-carene and showed a composition more similar to its pollen parent, Irwin, than to its seed parent, Chiin Hwang No. 1.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Mangifera/química , Compuestos Orgánicos Volátiles/análisis , Análisis de Componente Principal , Microextracción en Fase Sólida/métodos
16.
J Control Release ; 335: 389-397, 2021 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-34033858

RESUMEN

As current treatments for multiple sclerosis (MS) remain chemotherapeutic ones directed toward symptoms, the development of a curative treatment is urgently required. Herein, we show an autoreactive immune cell-targetable approach using autoantigen-modified liposomes for the curative treatment of MS. In these experiments, experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic myelin oligodendrocyte glycoprotein (MOG) peptide was used as a model of primary progressive MS, and MOG-modified liposomes encapsulating doxorubicin (MOG-LipDOX) were used as a therapeutic drug. The results showed that the progression of encephalomyelitis symptoms was significantly suppressed by MOG-LipDOX injection, whereas the other samples failed to show any effect. Additionally, invasion of inflammatory immune cells into the spinal cord and demyelination of neurons were clearly suppressed in the MOG-LipDOX-treated mice. FACS analysis revealed that the number of both MOG-recognizable CD4+ T cells in the spleen was obviously decreased after MOG-LipDOX treatment. Furthermore, the number of effector Th17 cells in the spleen was significantly decreased and that of regulatory Treg cells was concomitantly increased. Finally, we demonstrated that myelin proteolipid protein (PLP)-modified liposomes encapsulating DOX (PLP-LipDOX) also showed the therapeutic effect on relapsing-remitting EAE. These findings indicate that autoantigen-modified liposomal drug produced a highly therapeutic effect on EAE by delivering the encapsulated drug to autoantigen-recognizable CD4+ T cells and thus suppressing autoreactive immune responses. The present study suggests that the use of these autoantigen-modified liposomes promises to be a suitable therapeutic approach for the cure of MS.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Autoantígenos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Liposomas , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/tratamiento farmacológico , Glicoproteína Mielina-Oligodendrócito
17.
Cancer Med ; 10(10): 3188-3196, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33931987

RESUMEN

BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Urológicas/tratamiento farmacológico , Urotelio/efectos de los fármacos , Anciano , Pueblo Asiatico , Carcinoma/patología , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Urológicas/patología , Urotelio/patología
18.
Oncol Rep ; 44(6): 2735-2745, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33125156

RESUMEN

Yes­associated protein (YAP) is a transcription­coupling factor that plays a central role in the Hippo pathway, and its activation regulates cell proliferation and carcinogenesis. YAP activation has been reported in various malignancies, conferring tumors with migratory and invasive abilities. Several studies have suggested that YAP expression is closely associated with prostate cancer. Furthermore, YAP has been revealed to regulate destabilization of F­actin associated with the cytoskeleton via Rho GTPase­activating protein 29 (ARHGAP29), suggesting that ARHGAP29 is associated with cancer metastasis. In the present study, the functions of ARHGAP29 were examined in four prostate cancer cell lines (22Rv1, LNCaP, DU145 and PC­3) and it was revealed that upregulation of ARHGAP29 in LNCaP and DU145 cells with the lowest expression of ARHGAP29 promoted cell proliferation and invasion. Conversely, ARHGAP29 knockdown in PC­3 cells with its highest expression level significantly reduced cell proliferation and invasion. In addition, immunohistochemistry of specimens from 133 patients who underwent radical prostatectomy was performed to investigate the clinical association between ARHGAP29 expression and prognosis in prostate cancer patients. Multivariate analysis demonstrated that ARHGAP29 was an independent prognostic factor for biochemical progression­free survival (P=0.0123). These findings indicated that ARHGAP29 in prostate cancer may be a potential prognostic biomarker and therapeutic target.


Asunto(s)
Biomarcadores de Tumor/genética , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Próstata/patología , Neoplasias de la Próstata/genética , Anciano , Biomarcadores de Tumor/análisis , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Conjuntos de Datos como Asunto , Proteínas Activadoras de GTPasa/análisis , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Supervivencia sin Progresión , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/cirugía , Regulación hacia Arriba
19.
Clin Ophthalmol ; 14: 2943-2949, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33061280

RESUMEN

PURPOSE: To retrospectively evaluate the short-term efficacy of omidenepag isopropyl (EYBELIS 0.002%) by assessing its intraocular pressure (IOP)-lowering capability and safety in patients with normal-tension glaucoma (NTG). PATIENTS AND METHODS: Fifty-four NTG patients (54 eyes) who were newly administrated with omidenepag isopropyl were enrolled in the study. The subjects comprised 22 men and 32 women, and the mean age of the subjects was 55.0 ± 14.1 years. The mean deviation value using the Humphrey visual field test program (30-2 SITA Standard) was -5.03 ± 3.38 dB. The following data were retrieved from the medical records and used for retrospective analyses: IOP at baseline 1-2 months and 3-4 months after administration. The frequency of non-responder patients who had less than 10% IOP reduction was evaluated. Patients were observed for adverse reactions and dropouts at each time point. RESULTS: IOP at baseline, after 1-2 months and after 3-4 months was 15.7 ± 2.6 mmHg, 13.5 ± 2.3 mmHg, and 13.6 ± 2.4 mmHg, respectively. There was a significant decrease in IOP after administration (p<0.0001). Eleven patients (22.4%) were non-responders. Adverse reactions occurred in 4 patients (7.4%), including conjunctival hyperemia in 3 patients (after 1 week, 2 weeks, and 1 month, respectively) and eye pain in 1 patient (after 1 month). Five patients (9.3%) dropped out of the study because of an adverse reaction in 3 patients, insufficient IOP reduction in 1 patient, and discontinuation of follow-up of 1 patient at our institution. CONCLUSION: After administration of omidenepag isopropyl, IOP in patients with NTG was significantly decreased. However, adverse reactions occurred in 7.4% of patients.

20.
Plant Biotechnol (Tokyo) ; 37(3): 319-325, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-33088195

RESUMEN

Cyst nematodes (Globodera spp. and Heterodera spp.) are highly evolved sedentary endoparasites that are considered as harmful pests worldwide. The hatching of the dormant eggs of cyst nematodes occurs in response to hatching factors (HFs), which are compounds that are secreted from the roots of host plants. Solanoeclepin A (SEA), a triterpene compound, has been isolated as HF for potato cyst nematode (PCN) eggs, whereas other compounds, such as steroidal glycoalkaloids (SGAs), are also known to show weak hatching stimulation (HS) activity. However, the structures of both compounds are different and the HF-mediated hatching mechanism is still largely unknown. In the present study, we observed specific hatching of PCN eggs stimulated by the hairy root culture media of potato and tomato, revealing the biosynthesis and secretion of HFs. SGAs, such as α-solanine, α-chaconine, and α-tomatine, showed significant HS activity, despite being remarkably less activities than that of SEA. Then, we evaluated the contribution of SGAs on the HS activities of the hairy root culture media. The estimated SGAs content in the hairy root culture media were low and nonconcordant with the HS activity of those, suggesting that the HS activity of SGAs did not contribute much. The analysis of structure-activity relationship revealed that the structural requirements of the HS activity of SGAs are dependent on the sugar moieties attached at the C3-hydoroxyl group and the alkaloid property of their aglycones. The stereochemistry in the EF rings of their aglycone also affected the strength of the HS activity.

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