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1.
Nucleic Acids Res ; 52(9): 5209-5225, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38636948

RESUMEN

RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.


Asunto(s)
Apoptosis , Caspasas , Proteínas de Unión al ARN , Humanos , Caspasas/metabolismo , Línea Celular , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/genética , Estrés del Retículo Endoplásmico/genética , Células HEK293 , Células HeLa , Interferón Tipo I/metabolismo , Interferón Tipo I/genética , MicroARNs/metabolismo , MicroARNs/genética , Ribonucleasa III/metabolismo , Ribonucleasa III/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal , Virosis/genética , Virosis/metabolismo
2.
Biochem Biophys Res Commun ; 658: 122-127, 2023 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-37030066

RESUMEN

Viral infection induces diverse cellular immune responses. Some viruses induce the production of antiviral cytokines, alterations of endogenous gene expression, and apoptosis; however, other viruses replicate without inducing such responses, enabling them to persistently infect cells. Infection by Borna disease virus type 1 (BoDV-1) can result in fatal immune-mediated encephalitis, including in humans, yet infection of cells in vitro is generally persistent. The regulatory mechanisms underlying this persistent infection remain unclear. Here, we show that an enhancer of RNA-silencing, TRBP, positively regulates BoDV RNA level in human cells. Knockdown of TRBP decreased BoDV RNA levels in persistently-infected cells, whereas overexpression of TRBP increased BoDV RNA levels. To investigate the mechanism underlying this phenomenon, we performed immunoprecipitation assays and found that TRBP interacts with BoDV RNA. Furthermore, we performed cell fractionation, which revealed that persistent infection with BoDV does not alter the localization of TRBP and other RNA silencing factors in cells. Our results showed the regulation of persistent BoDV infection by RNA-silencing factors in human cells.


Asunto(s)
Enfermedad de Borna , Virus de la Enfermedad de Borna , Animales , Humanos , Virus de la Enfermedad de Borna/genética , Enfermedad de Borna/genética , Enfermedad de Borna/metabolismo , Interferencia de ARN , Infección Persistente , ARN
3.
Nihon Shokakibyo Gakkai Zasshi ; 120(10): 837-844, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-37821373

RESUMEN

This study aimed to investigate the significance of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor by reporting 21 patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev) as the first line of treatment. The optimal cut-off value of NLR was 2.25 with Atezo/Bev, and patients with NLR of ≥2.25 had a shorter progression free survival (PFS) (199 vs. 393 days, p=0.009) compared to patients with NLR of <2.25. NLR was positively correlated with C-reactive protein (r=0.525, p=0.016). The high NLR group demonstrated a shorter PFS than the low NLR group. NLR may be a useful predictive biomarker of the first-line Atezo/Bev treatment for unresectable HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab , Neutrófilos , Neoplasias Hepáticas/tratamiento farmacológico , Linfocitos
4.
Nihon Shokakibyo Gakkai Zasshi ; 119(5): 476-485, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-35545547

RESUMEN

The subject was a man in his late 70s who was seeing a family physician for diabetes and dyslipidemia on an outpatient basis. A routine medical checkup revealed liver dysfunction, prompting an abdominal ultrasound. As a result, a large hepatic tumor was discovered, prompting a thorough examination. The patient was diagnosed with hepatocellular carcinoma and multiple liver metastases, as well as tumor shadows that could indicate pulmonary metastases, after a thorough examination at our hospital. Due to the patient not having viral hepatitis or any drinking history and had formerly been confirmed as having fatty liver, a diagnosis of cirrhosis and hepatocellular carcinoma caused by NASH (nonalcoholic steatohepatitis) was given. A Child-Pugh score of 5 (A) and modified albumin-bilirubin (mALBI) grade 2 were used to maintain liver function. As a result, a 12-mg/day Lenvatinib treatment regimen was initiated. From the 6th day of the start of oral administration, the patient developed right hypochondralgia and loss of appetite. Blood samples showed increased levels of liver enzymes and inflammatory reaction, requiring hospitalization for closer examination. Intratumoral hemorrhage from hepatocellular carcinoma was discovered by dynamic CT scans. The patient's general condition was stable, and an angiogram was performed on the 3rd day of admission. As a result, persistent extravasation was discovered, necessitating transcatheter arterial embolization (TAE) treatment of the lesion for tumor vessel embolization. Thereafter, transient deterioration of the liver function occurred but an immediate improvement was seen. The patient was discharged without a recurrence of hemorrhage. An outpatient follow-up was performed, with blood test results indicating that liver function was maintained with a Child-Pugh score of 6 (A), and a dynamic CT showing that intratumoral hemorrhage was under control, allowing for readministration. Readministration of Lenvatinib was started at 4mg/day, one level lower, because the patient's body weight had dropped below 60kg. There are few reports on Lenvatinib-induced intratumoral hemorrhage, and this is a unique case worthy of reporting, with previous literary references, in which the entire process from intratumoral hemorrhage to readministration of Lenvatinib after embolization treatment has been documented.


Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Embolización Terapéutica/efectos adversos , Hemorragia/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Compuestos de Fenilurea , Quinolinas
5.
World J Surg Oncol ; 19(1): 269, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34479591

RESUMEN

BACKGROUND: Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. CASE PRESENTATION: A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 µm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. CONCLUSIONS: Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.


Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Adenocarcinoma/cirugía , Adulto , Colonoscopía , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Recurrencia Local de Neoplasia , Pronóstico
6.
Surg Today ; 51(4): 582-588, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33037476

RESUMEN

PURPOSE: Anatomical pulmonary resection, such as lobectomy, is a common procedure. Staplers play an important role in dividing an incomplete interlobular fissure, especially in thoracoscopic surgery. This study evaluates the effectiveness of a powered stapler for reducing the need for intraoperative fibrin glue and the incidence of air leakage after radical pulmonary resection. METHODS: The subjects of this retrospective study were 478 patients who underwent radical pulmonary resection. Propensity score analysis generated two matched pairs of 177 patients treated using powered and manual staplers, respectively. RESULTS: The need for fibrin glue intraoperatively during radical pulmonary resection was significantly less in the powered-stapler group (47.5%) than in the manual-stapler group (58.8%, p = 0.033). The incidence of postoperative air leakage following radical pulmonary resection was also significantly lower in the powered-stapler group (2.8%) than in the manual-stapler group (10.7%, p = 0.003). Logistic regression analysis identified use of the powered stapler as a factor independently associated with both non-use of fibrin glue intraoperatively (odds ratio, 0.63; p = 0.040) and no postoperative air leakage (odds ratio, 0.26; p = 0.010). CONCLUSION: Using a powered stapler to divide the incomplete interlobular fissure decreased the need for additional intraoperative management using fibrin glue and reduced postoperative air leakage in radical pulmonary resection.


Asunto(s)
Fuga Anastomótica/prevención & control , Neumonectomía/instrumentación , Complicaciones Posoperatorias/prevención & control , Puntaje de Propensión , Engrapadoras Quirúrgicas , Aire , Fuga Anastomótica/epidemiología , Utilización de Medicamentos/estadística & datos numéricos , Suministros de Energía Eléctrica , Femenino , Adhesivo de Tejido de Fibrina , Humanos , Incidencia , Cuidados Intraoperatorios/estadística & datos numéricos , Masculino , Neumonectomía/métodos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Toracoscopía/instrumentación , Toracoscopía/métodos
7.
J Cutan Pathol ; 47(7): 584-591, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32125018

RESUMEN

BACKGROUND: Sarcoidosis is a chronic and systemic inflammatory disease, in which patients present with noncaseating epithelioid granulomas. Cutaneous lesions of sarcoidosis develop in 9% to 35% of all sarcoidosis patients and comprise various clinical subtypes. It usually affects multiple organs and has a variable clinical course; this is called systemic sarcoidosis (SS). However, occasionally, it only affects the skin and is then called cutaneous sarcoidosis (CS). Recent observations suggest that serum levels of soluble CD163 correlate with immune cell activity in sarcoidosis patients; however, the contribution of M1 and M2 macrophages toward disease progression remains unclear. METHODS: We evaluated macrophage phenotypes histopathologically using skin biopsy samples obtained from patients with CS (n = 8) and SS (n = 31) and performed immunostaining with CD68, iNOS (M1 macrophages), PD-L1, and CD163 (M2 macrophages). RESULTS: The density of CD163-positive cells in the SS group was significantly higher than that in the CS group. There was no significant correlation between the CD163 (+) cell density and serum angiotensin-converting enzyme level, serum calcium, or tuberculin reaction. CONCLUSIONS: Immunostaining for CD163 may be a novel and useful marker to predict systemic involvement in patients with cutaneous lesions of epithelioid granulomas.


Asunto(s)
Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Macrófagos/inmunología , Receptores de Superficie Celular/inmunología , Sarcoidosis/inmunología , Sarcoidosis/patología , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piel/patología
8.
Surg Today ; 49(7): 580-586, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30684049

RESUMEN

PURPOSE: In recent years, several reports have noted that the specific coagulation mode called "soft coagulation" with modern electrosurgical tools offers superior hemostasis. The "suction ball coagulation" (SBC) device, which can achieve hemostasis using a soft coagulation mode and simultaneous suction, has been developed as a next step. This study aimed to evaluate the hemostatic effects of SBC in comparison to a conventional soft coagulation device (non-SBC) in video-assisted thoracoscopic surgery (VATS) for patients with non-small cell lung cancer (NSCLC). METHODS: This study retrospectively analyzed 351 patients who underwent complete VATS lobectomy for NSCLC. A propensity score analysis generated matched pairs from the patients in the SBC and non-SBC groups (119 patients each). RESULTS: After propensity score matching, the bleeding volume during surgery in the SBC group (27.0 g) was significantly less than that in the non-SBC group (42.0 g, p < 0.001). No significant difference was seen in the frequency of postoperative complications. A logistic regression analysis identified the non-use of SBC as an independent risk factor for greater intraoperative blood loss during complete VATS lobectomy (odds ratio 3.14, p < 0.001). CONCLUSIONS: SBC was safe for complete VATS lobectomy in patients with NSCLC, and the use of this device was associated with significantly decreased intraoperative blood loss.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Electrocoagulación/instrumentación , Hemostasis Quirúrgica/instrumentación , Neoplasias Pulmonares/cirugía , Neumonectomía/instrumentación , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Anciano , Electrocoagulación/métodos , Femenino , Hemostasis Quirúrgica/métodos , Humanos , Modelos Logísticos , Masculino , Puntaje de Propensión , Estudios Retrospectivos , Resultado del Tratamiento
9.
World J Surg Oncol ; 15(1): 112, 2017 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-28566093

RESUMEN

BACKGROUND: Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus, Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. METHODS: We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages III-IV or clinical node stages 0-III. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m2/day, days 1-14 and 29-42) plus LV (75 mg/day, days 1-14 and 29-42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. RESULTS: The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). CONCLUSIONS: Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.


Asunto(s)
Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/mortalidad , Neoplasias del Recto/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Japón , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Preoperatorios , Pronóstico , Neoplasias del Recto/terapia , Estudios Retrospectivos , Tasa de Supervivencia , Tegafur/administración & dosificación
10.
BMC Cancer ; 16: 366, 2016 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-27296289

RESUMEN

BACKGROUND: Several recent studies have reported that patients with metastatic colorectal cancer (CRC) whose primary tumor is located in left side of the colon have more favorable responses to anti-epidermal growth factor receptor (EGFR) antibody therapy than those with right-sided tumors. However, the mechanism for this phenomenon is unknown. METHODS: Fifty-two cases of primary CRC with liver metastases were analyzed in this retrospective study. The mRNA levels of 19 signal transduction genes in both primary tumor and liver metastases were measured by real-time reverse transcription polymerase chain reaction. The purposes of this study were (1) to determine the correspondence between signal transduction gene expressions in primary tumors and corresponding liver metastases, and (2) to determine whether expression levels of these genes differ by primary tumor location. RESULTS: mRNA expression levels of 14 of 19 signal transduction genes, including PTEN, ERBB2, MET, HGF, AREG, and EREG, showed significant correlations between the primary tumor and corresponding liver metastases. When the mRNA levels of the primary tumors were compared by tumor location, only PTEN mRNA expression differed significantly between left and right-sided CRC (median PTEN expression: left 1.00 vs. right 1.68; p = 0.017). When rectal cancers were separated from left-sided colon cancers, PTEN mRNA levels increased progressively from rectum to right-sided colon (median; rectum 0.84, left colon 1.23, right colon 1.68, p = 0.013). PTEN mRNA expression in liver metastases also differed significantly according to primary tumor location (median; left 0.92 vs. right 1.27, p = 0.048). There was no difference in overall survival between patients with high versus low levels of PTEN mRNA (p = 0.59). CONCLUSIONS: Our data suggest that the PIK3/AKT/mTOR pathway is more active in left- than right-sided CRC, which provides a possible explanation for the fact that efficacy of anti-EGFR therapy differs by location of primary tumor.


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfohidrolasa PTEN/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Femenino , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estudios Retrospectivos
11.
Bioorg Med Chem Lett ; 25(5): 1110-6, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25619637

RESUMEN

The combination of cysteine-specific modifiers, iodoacetanilide (IAA) and (13)C7-labeled iodoacetanilide ((13)C7-IAA), has been applied to absolute quantification of proteins. The selected reaction monitoring (SRM) with the use of nano liquid chromatography/nanoelectrospray ionization ion trap mass spectrometry (nano LC/nano-ESI-IT-MS) analysis was applied to precise quantification of three commercial proteins. Good correlation was observed between the theoretical ratios and observed ratios for all these proteins both in a simple buffer solution and in a complex protein environment. Due to efficient tagging, this method does not require separate synthesis of isotope-labeled peptides for the SRM studies. Therefore, this method is expected to be a useful tool for proteomics research.


Asunto(s)
Acetanilidas/química , Proteínas/análisis , Animales , Isótopos de Carbono/química , Bovinos , Cromatografía Liquida/métodos , Marcaje Isotópico/métodos , Lactalbúmina/análisis , Ovalbúmina/análisis , Péptidos/análisis , Proteómica/métodos , Albúmina Sérica Bovina/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos
12.
FASEB J ; 27(6): 2301-15, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23430976

RESUMEN

The role of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in glucose metabolism is unknown. Here, we generated DDAH2 transgenic (Tg) mice. These mice had lower plasma glucose levels (60 min: 298±32 vs. 418±35 mg/dl; 120 min: 205±15 vs. 284±20 mg/dl) and higher insulin levels (15 min: 2.1±0.2 vs. 1.5±0.1 ng/ml; 30 min: 1.8±0.1 vs. 1.5±0.1 ng/ml) during intraperitoneal glucose tolerance tests when fed a high-fat diet (HFD) compared with HFD-fed wild-type (WT) mice. Glucose-stimulated insulin secretion (GSIS) was increased in Tg islets by 33%. Pancreatic asymmetrical dimethylarginine, nitric oxide, and oxidative stress levels were not correlated with improvements in insulin secretion in Tg mice. Secretagogin, an insulin vesicle docking protein, was up-regulated by 2.7-fold in Tg mice and in pancreatic MIN-6 cells overexpressing DDAH2. GSIS in MIN-6 cells was dependent on DDAH2-induced secretagogin expression. Pancreatic Sirt1, DDAH2, and secretagogin were down-regulated in HFD-fed WT mice by 70, 75, and 85%, respectively. Overexpression of Sirt1 overexpression by 3.9-fold increased DDAH2 and secretagogin expression in MIN-6 cells by 3.2- and 2.5-fold, respectively. DDAH2 overexpression improved GSIS in pancreas-specific Sirt1-deficient mice. In summary, the Sirt1/DDAH2/secretagogin pathway is a novel regulator of GSIS.


Asunto(s)
Amidohidrolasas/fisiología , Proteínas de Unión al Calcio/genética , Insulina/metabolismo , Páncreas/fisiología , Sirtuina 1/fisiología , Regulación hacia Arriba/fisiología , Amidohidrolasas/genética , Animales , Glucemia/fisiología , Línea Celular , Femenino , Resistencia a la Insulina/genética , Resistencia a la Insulina/fisiología , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Páncreas/metabolismo , Secretagoginas , Transducción de Señal/fisiología , Sirtuina 1/deficiencia , Sirtuina 1/genética
13.
Cell Biochem Funct ; 32(5): 429-37, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24578328

RESUMEN

Prechondrogenic condensation is a critical step for skeletal pattern formation. Our previous study showed that ATP oscillations play an essential role in prechondrogenic condensation because they induce oscillatory secretion. However, the molecular mechanisms that underlie ATP oscillations remain poorly understood. We examined how differential changes in proteins are implicated in ATP oscillations during chondrogenesis by using liquid chromatography/mass spectrometry. Our analysis showed that a number of proteins involved in ATP synthesis/consumption, catabolic/anabolic processes, actin dynamics, cell migration and adhesion were detected at either the peak or the trough of ATP oscillations, which implies that these proteins have oscillatory expression patterns that are coupled to ATP oscillations. On the basis of the results, we suggest that (1) the oscillatory expression of proteins involved in ATP synthesis/consumption and catabolic/anabolic processes can contribute to the generation or maintenance of ATP oscillations and that (2) the oscillatory expression of proteins involved in actin dynamics, cell migration and adhesion plays key roles in prechondrogenic condensation by inducing collective adhesion and migration in cooperation with ATP oscillations.


Asunto(s)
Adenosina Trifosfato/farmacología , Diferenciación Celular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Proteoma/análisis , Espectrometría de Masa por Ionización de Electrospray , Línea Celular , Condrocitos/citología , Condrocitos/metabolismo , Humanos
14.
Int J Clin Oncol ; 19(1): 113-20, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23299277

RESUMEN

BACKGROUND: KRAS mutation is widely accepted as a strong, negative predictive marker for anti-epidermal growth factor receptor antibodies, including cetuximab and panitumumab. Previous reports demonstrated approximately 100 % concordance of KRAS status between primary colorectal cancer and liver metastases; however, mismatched KRAS status still occurs. METHODS: KRAS status was evaluated in 105 pairs of formalin-fixed primary colorectal cancer and corresponding liver metastases specimens by direct sequencing. DNA quality of patients displaying mismatched KRAS status between primary tumors and metastases was assessed using a Bioanalyzer. RESULTS: KRAS status was successfully analyzed in 90/105 patients (85.7 %). The concordance rate between primary tumors and metastases was 88.2 % in synchronous metastases (n = 76) and 100 % in metachronous metastases (n = 14). Discordance in KRAS status was observed in nine patients. Independent method validation revealed only five samples showed the same KRAS status between the two methods. DNA quality assessment by a Bioanalyzer revealed that the median length of DNA samples in the peak concentration of the mismatched group was significantly shorter than those in the control group (153.5 vs 276.5 bp, P = 0.0059). In addition, the median value of the percentage of degraded DNA (0-200 bp) in each sample in the mismatched group was significantly higher than the control group (35.5 vs 22 %, P = 0.020). These data suggest that the discordant results for these nine patients (18 samples) were due to low quality DNA, which may obscure polymerase chain reaction analysis, affecting sequencing reliability. CONCLUSION: Quality control and assurance of KRAS genotyping is critical, and standardization of the methodology is warranted.


Asunto(s)
Neoplasias Colorrectales/genética , ADN de Neoplasias/genética , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Femenino , Genotipo , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Control de Calidad , Proteínas ras/metabolismo
15.
Biol Open ; 13(6)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875000

RESUMEN

Viral infectivity depends on multiple factors. Recent studies showed that the interaction between viral RNAs and endogenous microRNAs (miRNAs) regulates viral infectivity; viral RNAs function as a sponge of endogenous miRNAs and result in upregulation of its original target genes, while endogenous miRNAs target viral RNAs directly and result in repression of viral gene expression. In this study, we analyzed the possible interaction between parainfluenza virus RNA and endogenous miRNAs in human and mouse lungs. We showed that the parainfluenza virus can form base pairs with human miRNAs abundantly than mouse miRNAs. Furthermore, we analyzed that the sponge effect of endogenous miRNAs on viral RNAs may induce the upregulation of transcription regulatory factors. Then, we performed RNA-sequence analysis and observed the upregulation of transcription regulatory factors in the early stages of parainfluenza virus infection. Our studies showed how the differential expression of endogenous miRNAs in lungs could contribute to respiratory virus infection and species- or tissue-specific mechanisms and common mechanisms could be conserved in humans and mice and regulated by miRNAs during viral infection.


Asunto(s)
Pulmón , MicroARNs , Animales , MicroARNs/genética , Ratones , Humanos , Pulmón/virología , Pulmón/inmunología , Pulmón/metabolismo , ARN Viral/genética , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Regulación de la Expresión Génica , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/genética , Infecciones por Respirovirus/inmunología
16.
Thorac Cancer ; 15(3): 209-214, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38083973

RESUMEN

BACKGROUND: Histopathology by pathologists is essential in the diagnosis of non-small cell lung cancer (NSCLC). However, auxiliary diagnostic procedures for malignant tumor have continued to evolve. Despite the poor prognosis of patients with NSCLC, the application of the latest procedures and technologies to the field of lung cancer has lagged. Mass spectrometry was used to detect trace amounts of peptides in human tissue with high accuracy. The aim of this study was to establish a method for diagnostic mass spectrometry to identify lymph node metastasis by detecting cytokeratin (CK)19, a useful biomarker in lung cancer. METHODS: We collected 81 lymph nodes with positive expression of CK19 in patients who underwent radical surgical resection in the Department of Thoracic Surgery at Iwate Medical University between May 2020 and December 2022. An X500R instrument was used for sample analysis. A positive result for lymph node metastasis as the detection at least two product ions (FGPGVAFR and ILGATIENSR) from CK19 was defined. RESULTS: Our study indicated a high diagnostic efficiency for mass spectrometry, with 87.5% sensitivity and 91.2% specificity. The mutual concordance of mass spectrometry methods and histopathological diagnosis was 90.1%. CONCLUSIONS: Mass spectrometry offers high diagnostic accuracy and can be clinically applied to auxiliary diagnostic procedures for lymph node metastasis from NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Metástasis Linfática/patología , Ganglios Linfáticos/patología , Queratina-19
17.
Bioorg Med Chem Lett ; 23(10): 3111-8, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23562245

RESUMEN

We have developed a methodology for quantitative analysis and concurrent identification of proteins by the modification of cysteine residues with a combination of iodoacetanilide (IAA, 1) and (13)C7-labeled iodoacetanilide ((13)C7-IAA, 2), or N-ethylmaleimide (NEM, 3) and d5-labeled N-ethylmaleimide (d5-NEM, 4), followed by mass spectrometric analysis using nano liquid chromatography/nanoelectrospray ionization ion trap mass spectrometry (nano LC/nano-ESI-IT-MS). The combinations of these stable isotope-labeled and unlabeled modifiers coupled with LC separation and ESI mass spectrometric analysis allow accurate quantitative analysis and identification of proteins, and therefore are expected to be a useful tool for proteomics research.


Asunto(s)
Acetanilidas/química , Etilmaleimida/química , Lactalbúmina/análisis , Nanotecnología , Ovalbúmina/análisis , Albúmina Sérica Bovina/análisis , Animales , Isótopos de Carbono , Bovinos , Cromatografía Liquida , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray
18.
MicroPubl Biol ; 20232023.
Artículo en Inglés | MEDLINE | ID: mdl-37497181

RESUMEN

MicroRNAs (miRNAs) are approximately 22 nucleotide-long non-coding RNAs that are encoded in the genome. miRNAs form base pairs with target mRNAs in the RNA-induced silencing complex and repress their expression through a mechanism called RNA silencing. Expression profiles of miRNAs differ between cells and tissues. In this study, we performed cytosine ß-D-arabinofuranoside (AraC)-induced neuron-like differentiation of human NTERA2/D1 (NT2) cells and quantified endogenous miRNA levels using quantitative RT-PCR. In conclusion, pre-mir-106b and pre-mir-19b levels were decreased after AraC-induced neuron-like differentiation of NT2 cells, indicating the functional relevance of miRNAs in the differentiation of mammalian cells.

19.
Thorac Cancer ; 14(3): 304-308, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36495037

RESUMEN

BACKGROUND: Segmentectomy with curative intention is occasionally performed for early non-small cell lung cancer (NSCLC). However, a major problem has been pointed out, in that the rate of locoregional recurrence is higher after segmentectomy than after lobectomy. This study aimed to investigate differences in rates of lymph node metastasis between segment 6 and basal segment NSCLC as potential candidates for segmentectomy and to explore factors associated with locoregional recurrence of segmentectomy. METHODS: We retrospectively analyzed 461 patients with lower lobe NSCLC who underwent segmentectomy or lobectomy with mediastinal lymph node dissection between 2011 and 2021. Among these, 122 patients with clinical N0 NSCLC, diameter ≤ 20 mm, and consolidation tumor ratio >0.5 were analyzed. RESULTS: The 122 patients were divided into a segment 6 group (n = 51) and a basal segment group (n = 71). Frequency of lymph node metastasis was significantly higher in the segment 6 group (17.7%) than in the basal segment group (4.2%; p = 0.01). Metastases to lymph node station 7 were seen in five of 122 patients (4.1%). Hilar lymph node metastasis occurred in nine of 122 patients (7.4%). Notably, metastases to station 11, 11i and 11 s lymph nodes were the most frequent patterns for hilar lymph nodes (41.7%). CONCLUSIONS: Station 11 lymph nodes are adjacent to the remaining lung segment or pulmonary artery in S6 segmentectomy or basal segmentectomy. Part of the NSCLC in segment 6 patients may thus be considered for lobectomy owing to the difficulty of complete dissection of station 11 lymph nodes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Metástasis Linfática , Estudios Retrospectivos , Estadificación de Neoplasias , Neumonectomía , Recurrencia Local de Neoplasia/patología , Escisión del Ganglio Linfático
20.
Artículo en Inglés | MEDLINE | ID: mdl-37294842

RESUMEN

OBJECTIVES: Postoperative pulmonary complications (PPCs) provoke an extended hospital stay and increased postoperative mortality. Although several factors can cause PPCs, smoking is the only factor that can be adjusted within a short period of time preoperatively. However, the optimal period of smoking cessation to reduce the risk of PPCs remains unclear. METHODS: A total of 1260 patients with primary lung cancer who underwent radical pulmonary resection between January 2010 and December 2021 were analysed retrospectively. RESULTS: We classified patients into 2 groups: non-smokers (patients who had never smoked) and smokers (patients who had ever smoked). The frequency of PPCs was 3.3% in non-smokers and 9.7% in smokers. PPCs were significantly less frequent in non-smokers than in smokers (P < 0.001). When smokers were classified according to the duration of smoking cessation, the frequency of PPCs was significantly lower for a duration of 6 weeks or more than for <6 weeks (P < 0.001). In a propensity score analysis performed for 6 or >6 and <6 weeks' smoking cessation in smokers, the frequency of PPCs was significantly lower for smokers with 6 or more weeks' smoking cessation than for smokers with <6 weeks' smoking cessation (P = 0.002). A multivariable analysis identified <6 weeks' smoking cessation as a significant predictor of PPCs for smokers (odds ratio: 4.55, P < 0.001). CONCLUSIONS: Smoking cessation for 6 or more weeks preoperatively significantly reduced the frequency of PPCs.

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