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The safety and efficacy of hemoglobin vesicles (HbVs) as artificial oxygen carriers encapsulating a purified and concentrated Hb solution in liposomes have been studied extensively. The HbV surface, modified with PEG by incorporating a PEG-conjugated phospholipid, is beneficial for storage and biocompatibility. However, it might be possible that interaction of PEG and the pre-existing anti-PEG antibody in the bloodstream causes acute adverse reaction. This study used two sets of experiments with rats and guinea pigs to ascertain whether the anti-PEG antibody generated by the PEG-modified HbV injection can induce anaphylactic reactions. SD rats received repeated intravenous injection of HbV at a dose rate of 16 or 32 mL/kg three times. Not anti-PEG IgG but anti-PEG IgM was detected. Nevertheless, no anaphylactic reaction occurred. Guinea pigs were used to study the presence of active systemic anaphylaxis further after injections of the PEG-modified liposomes used for HbV. The animals were sensitized by three repeated subcutaneous injections of PEG-modified liposomes (PEG-liposome) along with adjuvant at 1 week intervals. For comparison, unmodified liposomes (liposome) and 10 times excessively PEG-modified liposomes with ionizable lipid (10PEG-DODAP-liposome) were used. Inclusion of PEG modification induced not only anti-PEG IgM but also anti-PEG IgG. Three weeks after the final injection, intravenous injection of both PEG-liposome and liposome (1 mL/kg) induced no anaphylactic reaction. However, the injection of 10PEG-DODAP-liposome showed one lethal anaphylaxis case and one mild anaphylaxis case. Antisera obtained from the animal sensitized as described above were inoculated (0.05 mL) intradermally into fresh guinea pigs. The presence of passive cutaneous anaphylaxis was evaluated after intravenous injections (1 mL/kg) of three liposomes with Evans blue. No dye leakage was detected at any inoculated skin point for PEG-liposome or liposome, but a slight leakage was detected in one inoculated skin point for 10PEG-DODAP-liposome. These results indicate the absence of acute allergic reactions at repeated injections of HbVs despite the anti-PEG antibody induction. Not all the PEG-modified liposomes show anaphylaxis, and it may depend on the amount of PEGylated phospholipid and lipid composition of PEG-modified liposomes.
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We report the outcome of photoselective vaporizaion of the prostate (PVP) with the 180W GreenLight XPS™ system (180 W-XPS) for large benign prostatic hyperplasia (BPH) with a prostate volume of ≥100 ml, in comparison with that with the 120 W GreenLight HPS™ system (120 W-HPS). We studied the outcomes of 86 patients who underwent PVP with 180 W-XPS for BPH with a prostate volume of ≥100 ml between February 2019 and October 2021, in comparison with those of 86 patients who underwent PVP with 120 W-HPS. 180 W-XPS significantly improved postoperative international prostate specific score, quality of life score, overactive bladder symptom score, Qmax, and residual urine volume. The operative time was significantly shorter in 180 W-XPS {100.5 min (150-175)}, than in 120 W-HPS {117.5 min (18-189)}, pï¼ 0.05), the laser irradiation time was significantly shorter in 180 W-XPS {63.0 min (35-83)}, than in 120 WHPS : {79. 0 min (24-102)} (p ï¼0. 05), and the laser fluence was significantly higher in 180 W-XPS {633647J (291991-805011)}, than in 120 W-HPS {396832J (40000-481842)} (pï¼0. 05). At 3 and 12 months postoperatively, the prostate volume reduction rates were 59.8 and 66.7%, respectively, for the 180 W-XPS patients which were rates significantly higher than those for the 120 W-HPS patients, 49.5 and 45.0%, respectively. The PSA reduction rates were 58.1 and 53.2ï¼ , respectively, which were significantly higher rates than those for the 120 W-HPS patients, 41.3 and 25.7ï¼ , respectively. The 180 W-XPS system was considered to be a more effective and efficient treatment than the 120 W-HPS.
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Terapia por Láser , Hiperplasia Prostática , Masculino , Humanos , Próstata/cirugía , Hiperplasia Prostática/cirugía , Calidad de Vida , Resultado del Tratamiento , Terapia por Láser/efectos adversosRESUMEN
We analyzed the perioperative parameters, postoperative urinary status, and complications of 200 patients who underwent photoselective vaporization of the prostate (PVP) with the 180W-X-ray photoelectron spectroscopy (XPS) for benign prostatic hyperplasia at our hospital. In addition, we compared perioperative parameters and complications, as well as the rate of decrease in prostate-specific antigen (PSA) and prostate volume at 3 and 12 months after surgery, with those of the last 200 patients who underwent PVP with the 120W-high-performance system (HPS). The results showed significant differences between methods in operative time (XPS: 67.9±29.0 minutes, HPS: 95.2±32.1 minutes, pï¼0.05), laser exposure time (XPS: 41.4±17.8 minutes, HPS: 60.1±19.7 minutes, pï¼0.05), and laser dose (XPS: 385,937±180,872, HPS: 300,316±105,528, pï¼0.05). In addition, there were significant differences in the rates of decrease in PSA and prostate volume in the 180W-XPS group compared with the 120W-HPS group. The transpiration efficiency of the 180W-XPS was higher than that of the 120W-HPS.
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Hiperplasia Prostática , Humanos , Masculino , Espectroscopía de Fotoelectrones , Próstata/cirugía , Antígeno Prostático Específico , Hiperplasia Prostática/cirugía , Resultado del Tratamiento , VolatilizaciónRESUMEN
In order to identify genes involved in the pathogenesis of clear cell carcinoma of the ovary (CCC), functional screening using a cDNA expression library was performed. We extracted mRNA from a CCC cell line (RMG-1), established a cDNA library using a retroviral vector, transfected that library into mouse NIH3T3 cells and sequenced the resultant foci. The tissue-type specific expression of isolated genes and their transforming activities were evaluated. Seven genes were isolated. Of these genes, the mRNA expression of SEC61B and DVL1 is significantly stronger in CCC than in other histological types (p < .05). Immunohistochemical staining reveals the stronger expression of SEC61B and C1ORF38 than normal ovarian tissues (p < .05). Focus formation is confirmed by the transfection of SEC61B, C1ORF38, and DVL1 into NIH3T3 cells. The present study identified novel genes including SEC61B, C1ORF38, and DVL1, involved in the pathogenesis of CCC. These genes may be additional therapeutic targets for CCC.Impact statementWhat is already known on this subject? Several important genetic abnormalities, including ARID1A and PIK3CA mutations, have been reported in ovarian clear cell carcinoma (CCC).What the results of this study add? SEC61B, C1ORF38, and DVL1 were newly detected as candidate genes involved in ovarian clear cell carcinogenesis.What the implications are of these findings for clinical practice and/or further research? Functional screening using a cDNA expression library may be a useful technique to identify functional genes for pathogenesis. The information obtained using this technique may provide new therapeutic targets of CCC.
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Adenocarcinoma de Células Claras/genética , Carcinogénesis/genética , Neoplasias Ováricas/genética , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proteínas Dishevelled/metabolismo , Femenino , Biblioteca de Genes , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Células 3T3 NIH , Ovario/metabolismo , Canales de Translocación SEC/metabolismoRESUMEN
Objective Although a number of studies have shown that both short and long sleep durations were associated with the risk of metabolic disorders related to obesity, the underlying mechanism is still not fully understood. In this study, we analyzed the association of sleep duration with metabolic, anthropometric, and lifestyle factors in patients with type 2 diabetes. Methods The subjects were 279 patients with type 2 diabetes 63 (52-70) years old (median and interquartile range) with a body mass index of 25.0 (22.2-28.3) kg/m2 and HbA1c levels of 8.7% (7.6-10.3%). Patients with advanced complications were excluded from the study. Diets were evaluated by registered dietitians using a software program. Body composition was assessed by the multifrequency bioelectrical impedance method. Results The mean self-reported nightly sleep duration was 6.4 hours with no marked gender difference. Sleep duration was inversely correlated with the HbA1c levels, total energy intake, and intakes of carbohydrate, protein, and fat. The body fat ratio and skeletal muscle mass were correlated positively and negatively, respectively, with sleep duration. When the subjects were divided into three groups based on sleep duration, the intakes of total energy, carbohydrates, and fat tended to be high in those with <5.5 hours of sleep, and the percentage of patients who had habitual physical activities was lower in those with >7 hours of sleep. Conclusion The observation that sleep duration is distinctly associated with excessive eating and a sedentary lifestyle may provide a basis for effective lifestyle management of patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Ingestión de Energía , Humanos , Persona de Mediana Edad , Obesidad/epidemiología , SueñoRESUMEN
BACKGROUND: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive histology of immune-complex-type glomerulonephritis has been reported. However, the clinical relevance and etiologic mechanisms remain unknown. CASE PRESENTATION: A 5-year-old child presented with steroid-resistant nephrotic range proteinuria. Initial renal biopsy revealed predominant diffuse mesangial proliferation with a double-contour and coexisting milder changes of focal segmental glomerulosclerosis. Immunofluorescence and electron microscopy revealed a full-house-pattern deposition of immune complexes in the subendothelial and paramesangial areas. Serial biopsies at 6 and 8 years of age revealed that more remarkable changes of focal segmental glomerulosclerosis had developed on top of the initial proliferative glomerulonephritis. Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. CONCLUSIONS: Our findings, together with those of others, point to the importance of heterogeneity in clinicopathological phenotypes caused by Wilms tumor 1 mutations and suggest that immune-complex-mediated membranoproliferative glomerulopathy should be considered as a histological variant.
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Complejo Antígeno-Anticuerpo , Síndrome de Frasier/patología , Glomerulonefritis Membranoproliferativa/patología , Glomeruloesclerosis Focal y Segmentaria/patología , Riñón/patología , Niño , Preescolar , Progresión de la Enfermedad , Síndrome de Frasier/genética , Humanos , Masculino , Proteínas WT1/genéticaRESUMEN
INTRODUCTION: Photoselective vaporization of the prostate (PVP) does not provide prostate tissue for pathologic analysis. Here, we carried out early monitoring for prostate cancer by measuring prostate-specific antigen (PSA) levels and assessing clinicopathological features after PVP. MATERIALS AND METHODS: Patients (n = 800) who underwent PVP and were followed-up for more than 12 months were analyzed retrospectively. After PVP, PSA levels were measured at 3 and 12 months and each year thereafter. Prostate biopsies were performed when PSA levels increased continuously. We assessed the characteristics of patients diagnosed with prostate cancer. RESULTS: The mean follow-up period was 49 months. After PVP, 54 patients underwent biopsies, and 23 patients were diagnosed with prostate cancer. Overall, 10, 10, and 3 patients had clinical stage T1c, T2a, and T2b disease, respectively, and there were no cases of stage T2c disease or greater. CONCLUSIONS: We found that it was possible to diagnose prostate cancer at a localized stage under our optimal PSA monitoring schedule before and after PVP.
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In order to understand the role of gene mutations in endometrial carcinogenesis, whole exome sequencing via laser microdissection was performed in the normal endometrium, atypical endometrial hyperplasia and endometrial carcinoma in the same patient. A total of 4046 and 5746 mutations with amino acid substitution were detected in endometrial hyperplasia and endometrial carcinoma, respectively; 2252 were common in both tissues and might play crucial roles in early carcinogenesis. These common mutations included polymerase epsilon (POLE) and DNA mismatch repair (MMR) genes, indicating that an ultra-mutated phenotype, and also included PTEN and PIK3CA. The mutation-prone environment evoked by mutations in the POLE and MMR genes associated with the activated phosphatidylinositol-3 kinase pathway played a pivotal role in this case.
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Fosfatidilinositol 3-Quinasa Clase I/genética , ADN Polimerasa Dirigida por ADN/genética , Hiperplasia Endometrial/genética , Neoplasias Endometriales/genética , Secuenciación del Exoma/métodos , Transducción de Señal/genética , Adulto , Femenino , Humanos , MutaciónRESUMEN
â¢Pure-type ovarian squamous cell carcinoma (POSCC) is extremely rare.â¢This is the first report of G-CSF-producing POSCC.â¢This case was successfully treated with primary surgery and standard chemotherapy.â¢A tumor with uninfected neutrophilia may be a G-CSF-producing tumor.â¢18F-FDG-PET/CT and MRI may be useful for diagnosing G-CSF-producing tumors.
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BACKGROUND: SIRT1 is a longevity gene that forestalls aging and age-related diseases including cancer, and has recently attracted widespread attention due to its overexpression in some cancers. We previously identified the overexpression of SIRT1 in ovarian carcinoma (OvCa) as a poor prognostic factor. However, mechanistic insights into the function of SIRT1 in OvCa have yet to be elucidated. METHODS: Quantitative real-time reverse PCR (qRT-PCR) and Western blotting were employed to examine the expression of SIRT1 in a panel of human OvCa cell lines. si-RNA or sh-RNA and cDNA technologies were utilized to knockdown or overexpress SIRT1, respectively. The effects of SIRT1 on proliferation and chemoresistance were examined using a WST-1 assay, and the underlying mechanisms were confirmed using an apoptotic assay, and the quantification of glutathione (GSH), and reactive oxygen species (ROS). The aggressiveness of SIRT1 was analyzed using in vitro invasion and migration assays. RESULTS: SIRT1 was more strongly expressed in OvCa cell lines than in the immortalized ovarian epithelium at the gene and protein levels. Stress up-regulated the expression of SIRT1 in dose- and time-dependent manners. SIRT1 significantly enhanced the proliferation (P<.05), chemoresistance (P<.05), and aggressiveness of OvCa cells by up-regulating multiple antioxidant pathways to inhibit oxidative stress. Further study into the overexpression of SIRT1 demonstrated the up-regulation of several stemness-associated genes and enrichment of CD44v9 via an as-yet-unidentified pathway. CONCLUSIONS: Our results suggest that SIRT1 plays a role in the acquisition of aggressiveness and chemoresistance by OvCa, and has potential as a therapeutic target for OvCa.
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Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target.
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Neoplasias Ováricas/patología , Sirtuina 1/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the long-term outcomes and safety photoselective vaporization of the prostate (PVP). PATIENTS AND METHODS: From April 2005 to December 2015, a total of 1154 patients with benign prostatic hyperplasia underwent PVP. The type of Green Light laser was an 80 W potassium-titanyl-phosphate laser and later a 120 W lithium triborate laser. Before and after surgery, the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), post-voiding volume of residual urine (PVR), prostate-specific antigen (PSA) level, and prostate volume were assessed regularly. After surgery, events such as second PVP, transurethral incision, and permanent urethral catheterization were defined as retreatment. RESULTS: The mean and median periods of follow-up after PVP were 35.4 and 24.0 months, respectively. The maximum duration of follow-up was 125 months. Compared with before surgery, the IPSS, quality of life score, and PSA concentration improved significantly, even at 10 years after PVP; however, Qmax and PVR were not improved at 10 years. The retreatment-free survival rate was 93.9% at 5 years and 79.0% at 10 years. Prostate cancer was found in 27 cases after PVP, and all patients who were found to have prostate cancer remained alive. Prostate cancer-free survival after PVP was 96.7% at 5 years and 89.4% at 10 years. CONCLUSION: Our data suggest that the efficacy of PVP was maintained for 10 years; however, it may decrease after more than 10 years. PVP also did not promote the progression of or worsen the prognosis of prostate cancer.
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Láseres de Estado Sólido/uso terapéutico , Hiperplasia Prostática/cirugía , Neoplasias de la Próstata/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Terapia por Láser , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/cirugía , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , Cateterismo Urinario , Retención Urinaria/cirugía , VolatilizaciónRESUMEN
Ectopic molar pregnancy is extremely rare, and preoperative diagnosis is difficult. Our literature search found only one report of molar pregnancy diagnosed preoperatively. Moreover, there is no English literature depicting magnetic resonance image (MRI) findings of ectopic molar pregnancy. We report a case of ectopic molar pregnancy preoperatively diagnosed using MRI. A literature review of 31 cases of ectopic molar pregnancy demonstrated that lesions have been found in the fallopian tube (19 cases, 61%), ovary (5 cases, 16%), cornu (3 cases, 10%), peritoneum (2 cases, 6%), uterine cervix (1 case, 3%), and cesarean scar (1 case, 3%). Abdominal pain and abnormal vaginal bleeding were reported in 70% and 61% of the patients, respectively. Twenty-one cases (67%) presented with rupture and hemoperitoneum. All patients underwent surgical resection or dilatation and curettage. Methotrexate therapy was performed in one case because residual trophoblastic tissue was suspected. A second operation was performed in one case of ovarian molar pregnancy because serum hCG levels increased again after primary focal ovarian resection. No patients developed metastatic disease or relapsed. These findings suggest the prognosis of ectopic molar pregnancy to be favorable.
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Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall.
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Antioxidantes/uso terapéutico , Condicionamiento Psicológico/efectos de los fármacos , Miedo/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Quercetina/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico por imagen , Compuestos de Anilina , Animales , Benzotiazoles/farmacocinética , Femenino , Humanos , Yofetamina/farmacocinética , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/etiología , Recuerdo Mental/efectos de los fármacos , Pruebas de Estado Mental y Demencia , Ratones , Ratones Endogámicos C57BL , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , TiazolesRESUMEN
PURPOSE: Lipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear. METHODS: The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively. RESULTS: LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing. CONCLUSIONS: These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Células Epiteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Lipocalina 2/genética , Fosfatidilinositol 3-Quinasas/genética , Proteína p53 Supresora de Tumor/genética , Antineoplásicos/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Cisplatino/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Resistencia a Antineoplásicos/genética , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Endometrio/efectos de la radiación , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Células Epiteliales/efectos de la radiación , Femenino , Humanos , Lipocalina 2/antagonistas & inhibidores , Lipocalina 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Rayos UltravioletaRESUMEN
Ovarian clear cell carcinoma (CCC) arises from ovarian endometriosis. Intra-cystic fluid contains abundant amounts of free iron, which causes persistent oxidative stress, a factor that has been suggested to induce malignant transformation. However, the mechanisms linking oxidative stress and carcinogenesis in CCC currently remain unclear. Lipocalin 2 (LCN2), a multifunctional secretory protein, functions as an iron transporter as well as an antioxidant. Therefore, we herein examined the roles of LCN2 in the regulation of intracellular iron concentrations, oxidative stress, DNA damage, and antioxidative functions using LCN2-overexpressing (ES2), and LCN2-silenced (RMG-1) CCC cell lines. The results of calcein staining indicated that the up-regulated expression of LCN2 correlated with increases in intracellular iron concentrations. However, a DCFH-DA assay and 8OHdG staining revealed that LCN2 reduced intracellular levels of reactive oxygen species and DNA damage. Furthermore, the expression of LCN2 suppressed hydrogen peroxide-induced apoptosis and prolonged cell survival, suggesting an antioxidative role for LCN2. The expression of mRNAs and proteins for various oxidative stress-catalyzing enzymes, such as heme oxygenase (HO), superoxide dismutase (SOD), and glutathione peroxidase, was not affected by LCN2, whereas the intracellular concentration of the potent antioxidant, glutathione (GSH), was increased by LCN2. Furthermore, the expression of xCT, a cystine transporter protein, and CD44 variant 8-10 (CD44v), a stem cell marker, was up-regulated by LCN2. Although LCN2 increased intracellular iron concentrations, LCN2-induced GSH may catalyze and override oxidative stress via CD44v and xCT, and subsequently enhance the survival of CCC cells in oxidative stress-rich endometriosis.
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Células Epiteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Receptores de Hialuranos/genética , Hierro/metabolismo , Lipocalina 2/genética , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Línea Celular Tumoral , Supervivencia Celular/genética , Células Epiteliales/patología , Femenino , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Hemo Oxigenasa (Desciclizante)/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Humanos , Receptores de Hialuranos/metabolismo , Lipocalina 2/metabolismo , Ovario/metabolismo , Ovario/patología , Estrés Oxidativo , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (P<0.05), and its overexpression was associated with a shorter survival (P<0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy.
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Carbazoles/uso terapéutico , Carcinoma Endometrioide/metabolismo , Cisplatino , Resistencia a Antineoplásicos , Neoplasias Endometriales/metabolismo , Sirtuina 1/metabolismo , Animales , Carbazoles/farmacología , Carcinoma Endometrioide/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Neoplasias Endometriales/tratamiento farmacológico , Endometrio/metabolismo , Femenino , Humanos , Inmunohistoquímica , Ratones Endogámicos BALB C , Ratones Desnudos , Sirtuina 1/antagonistas & inhibidores , Estrés Fisiológico , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A 51-year-old woman received an ABO blood type-incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no 'storiform' fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4-positive plasma cells, most of which expressed kappa-type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4-related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow-up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4-positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4-positive plasma cell-rich tubulointerstitial nephritis mimicking IgG4-related kidney disease after kidney transplantation.
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Inmunoglobulina G/inmunología , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/patología , Nefritis Intersticial/patología , Células Plasmáticas/patología , Diagnóstico Diferencial , Femenino , Humanos , Cadenas kappa de Inmunoglobulina/inmunología , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/inmunología , Persona de Mediana Edad , Nefritis Intersticial/etiología , Nefritis Intersticial/inmunología , Células Plasmáticas/inmunología , Esteroides/uso terapéutico , Trasplante HomólogoRESUMEN
A 20-year-old unmarried Ghanaian man complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Abdominal ultrasound revealed a hyper echoic lesion in the entire bladder wall. Computed tomography showed a calcification of the whole bladder wall and of the left lower ureter. Flexible cystoscopy revealed many nodular masses, so-called 'bilharzial tubercles', at the trigone and posterior wall of the urinary bladder, and there was partial bleeding. Pathological examination revealed granuloma with many calcified eggs of schistosome haematobium. He was diagnosed with Bilharzial schistosomiasis and was treated with 1,500 mg of praziquantel for two days. However the therapeutic effect was insufficient. Therefore, he was treated with 2,400 mg of praziquantel for two days, and the symptoms disappeared.
Asunto(s)
Esquistosomiasis Urinaria/diagnóstico , Adulto , Antihelmínticos/uso terapéutico , Ghana/etnología , Humanos , Masculino , Praziquantel/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológicoRESUMEN
Polypoid endometriosis is a rare type of endometriosis. We report a case of polypoid endometriosis of the ovary mimicking ovarian carcinoma with peritoneal dissemination. Computed tomography and magnetic resonance imaging showed a left ovarian endometriotic cyst containing several nodules in the cystic wall that displayed enhancement, and pelvic nodules on the right ovary. A preoperative or intraoperative diagnosis to avoid the unnecessary extended operation is important for such disease. Retrospective magnetic resonance imaging analysis identified a peculiar finding for polypoid endometriosis: all solid nodules had a round and smooth shape and displayed a low-signal-intense marginal edge on T2-weighted images, suggesting that this is an important finding for differentiating polypoid endometriosis from ovarian carcinoma arising from endometriosis.