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1.
Am J Med Sci ; 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32376002

RESUMO

BACKGROUND: Diabetes carries a known risk of bone fracture despite high bone mineral density (BMD). The fracture risk assessment tool (FRAX) predicts the 10-year major osteoporotic fracture risk and hip fracture risk. We investigated the effects of clinical parameters on the FRAX score and evaluated the validity of FRAX for evaluating current bone fragility in diabetes subjects. MATERIALS AND METHODS: Forty-seven thousand, three hundred eighty-nine Japanese women participated in the Chiba bone survey, a population-based, multicenter, cross-sectional study of postmenopausal osteoporosis; we estimated FRAX scores without BMD and compared scores between subjects with and without type 2 diabetes. RESULTS: Mean FRAX major osteoporotic fracture risk was significantly higher in the diabetes group. A multiple regression model demonstrated some clinical parameters that affected the FRAX score and, after adjusting for such parameters, the FRAX score was not significantly different between the diabetes and nondiabetes groups, although the type 2 diabetes rate was significantly higher in subjects with a fracture in the past 5 years, which reflected current bone fragility. After adjusting for clinical parameters, the diabetes rate remained significantly higher in subjects with a fracture in the past 5 years, confirming that type 2 diabetes influences current bone fragility. Our study demonstrated that type 2 diabetes truly carries a risk of bone fracture, but adjusted FRAX major osteoporotic fracture risk is not significantly different between subjects with and without type 2 diabetes. CONCLUSIONS: The FRAX major osteoporotic fracture risk without BMD does not correctly indicate current bone fragility in Japanese middle-aged women with type 2 diabetes.

2.
Endocr J ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32378529

RESUMO

This phase 2, single-arm, open-label, dose-titration, multicenter study evaluated osilodrostat (11ß-hydroxylase inhibitor) in Japanese patients with endogenous Cushing's syndrome (CS) caused by adrenal tumor/hyperplasia or ectopic adrenocorticotropic hormone syndrome. The primary endpoint was percent change from baseline to week 12 in mean urinary free cortisol (mUFC) at the individual patient level. Of the nine patients enrolled in the study, seven completed the 12-week core treatment period and two discontinued at or prior to week 12 due to adverse events (AEs). Of the seven patients who completed 12 weeks of study treatment, two completed 48 weeks of study treatment. Median osilodrostat exposure was 12 weeks. Median (range) average dose including dose interruption (0 mg/day) was 2.143 (1.16-7.54) mg/day. Median (range, population) percentage change in mUFC was -94.47% (-99.0% to -52.6%, n = 7) at week 12. At week 12, 6/9 patients were complete responders (mUFC ≤ upper limit of normal [ULN]) and 1/9 was a partial responder (mUFC > ULN but decreased by ≥50% from baseline). Most frequent AEs were adrenal insufficiency (n = 7), gamma-glutamyl transferase increase, malaise, and nasopharyngitis (n = 3 each). Serious AEs were seen in four patients. No deaths occurred in this study. In conclusion, osilodrostat treatment led to a reduction in mUFC in all nine patients with endogenous CS other than Cushing's disease (CD), regardless of disease type, with >80% reduction seen in 6/7 patients at week 12. The safety profile was consistent with previous reports in CD patients, and the reported AEs were manageable.

3.
J Clin Endocrinol Metab ; 105(2)2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614366

RESUMO

CONTEXT: Hashimoto's thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto's thyroiditis. CASE DESCRIPTION: The patient whose case we report had a history of Hashimoto's thyroiditis, immune thrombocytopenia, and refractory hypertension, with varying treatment resistance to the oral medications prescribed for each condition. In order to establish or exclude a genetic basis for her illness, we examined the patient's gene expression profiles using peripheral blood leukocytes, and found that ABCG2/BCRPexpression was significantly high compared with healthy volunteers. Also, the increased daunomycin efflux capacity of our patient's lymphocytes was successfully inhibited by fumitremorgin C, a specific ABCG2/BCRP inhibitor, and the patient's level of thyroid-stimulating hormone increased by 248.6% after administration of intact levothyroxine tablets but decreased by 45.1% when tablets were crushed. Her average blood pressure decreased from 166.3/108.5 mmHg to 125.9/78.8 mmHg when switching from intact to crushed losartan tablets. CONCLUSIONS: High expression and accelerated efflux transporter activity of ABCG2/BCRP in the small intestine are expected to contribute to the ineffectiveness of orally administered intact tablets in cases with treatment-resistant Hashimoto's thyroiditis, and crushed tablets can be more effective for some of these patients.

4.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628466

RESUMO

OBJECTIVE: Accurate assessment and localization of aldosterone-producing adenomas (APAs) are essential for the treatment of primary aldosteronism (PA). Although adrenal venous sampling (AVS) is the standard method of reference for subtype diagnosis in PA, controversy exists concerning the criteria for its interpretation. This study aims to determine better indicators that can reliably predict subtypes of PA. METHOD: Retrospective, single-cohort analysis including 209 patients with PA who were subjected to AVS. Eighty-two patients whose plasma aldosterone concentrations (PAC) were normalized after surgery were histopathologically or genetically diagnosed with APA. The accuracy of image findings was compared to AVS results. Receiver operating characteristic (ROC) curve analysis between the operated and the no-apparent laterality groups was performed using AVS parameters and loading test for diagnosis of PA. RESULT: Agreement between image findings and AVS results was 56.3%. ROC curve analysis revealed that the lateralization index (LI) after adrenocorticotropin stimulation cutoff was 2.40, with 98.8% sensitivity and 97.1% specificity. The contralateral suppression index (CSI) cutoff value was 1.19, with 98.0% sensitivity and 93.9% specificity. All patients over the LI and CSI cutoff values exhibited unilateral subtypes. Among the loading test, the best classification accuracy was achieved using the PAC reduction rate after a saline infusion test (SIT) >33.8%, which yielded 87.2% sensitivity or a PAC after a SIT <87.9 pg/mL with 86.2% specificity for predicting bilateral PA. CONCLUSION: The combined criteria of the PAC reduction rate and PAC after the SIT can determine which subset of patients with APA who should be performed AVS for validation.

5.
Int J Urol ; 27(1): 30-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31522462

RESUMO

This review summarizes the latest insights on ABO-incompatible living-donor renal transplantation. Desensitization protocols and clinical outcomes were investigated, and a comparison was made with kidney-paired donation, which is not permitted in Japan for ethical reasons. Although renal transplantation is greatly beneficial for most patients with end-stage kidney disease, many of these patients must remain on dialysis therapy for extended periods due to the scarcity of organs from deceased donors. ABO blood type incompatibility was once believed to be a contraindication to renal transplantation due to the increased risk for antibody-mediated rejection and early graft loss attributable to isoagglutinins. Recently, pretransplant desensitization strategies, such as removal of isoagglutinins and antibody-producing cells, have achieved successful outcomes, although it remains unclear whether graft survival and patient morbidity are equivalent to those for ABO-compatible renal transplantation. The present review suggested that ABO-incompatible living-donor renal transplantation might be a favorable radical renal replacement therapy for patients with end-stage kidney disease.

7.
J Exp Med ; 217(1)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31653691

RESUMO

The zinc finger transcription factor, Bcl11b, is expressed in T cells and group 2 innate lymphoid cells (ILC2s) among hematopoietic cells. In early T-lineage cells, Bcl11b directly binds and represses the gene encoding the E protein antagonist, Id2, preventing pro-T cells from adopting innate-like fates. In contrast, ILC2s co-express both Bcl11b and Id2. To address this contradiction, we have directly compared Bcl11b action mechanisms in pro-T cells and ILC2s. We found that Bcl11b binding to regions across the genome shows distinct cell type-specific motif preferences. Bcl11b occupies functionally different sites in lineage-specific patterns and controls totally different sets of target genes in these cell types. In addition, Bcl11b bears cell type-specific post-translational modifications and organizes different cell type-specific protein complexes. However, both cell types use the same distal enhancer region to control timing of Bcl11b activation. Therefore, although pro-T cells and ILC2s both need Bcl11b for optimal development and function, Bcl11b works substantially differently in these two cell types.

8.
Sci Rep ; 9(1): 17411, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31757988

RESUMO

Next-generation sequencing (NGS) is a revolutionary sequencing technology for analyzing genomes. However, preprocessing methods for mitochondrial DNA (mtDNA) sequencing remain complex, and it is required to develop an authenticated preprocessing method. Here, we developed a simple and easy preprocessing method based on isothermal rolling circle mtDNA amplification using commercially available reagents. Isothermal amplification of mtDNA was successfully performed using both nanoliter quantities of plasma directly and 25 ng of total DNA extracted from blood or tissue samples. Prior to mtDNA amplification, it was necessary to treat the extracted total DNA with Exonuclease V, but it was not required to treat plasma. The NGS libraries generated from the amplified mtDNA provided sequencing coverage of the entire human mitochondrial genome. Furthermore, the sequencing results successfully detected heteroplasmy in patient samples, with called mutations and variants matching those from previous, independent, Sanger sequencing analysis. Additionally, a novel single nucleotide variant was detected in a healthy volunteer. The successful analysis of mtDNA using very small samples from patients is likely to be valuable in clinical medicine, as it could reduce patient discomfort by reducing sampling-associated damage to tissues. Overall, the simple and convenient preprocessing method described herein may facilitate the future development of NGS-based clinical and forensic mtDNA tests.

9.
Endocr J ; 66(12): 1063-1072, 2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31511435

RESUMO

We recently conducted an open-label phase I/II study to evaluate the efficacy and safety of preoperative and chronic treatment with metyrosine (an inhibitor of catecholamine synthesis) in pheochromocytoma/paraganglioma (PPGL) in Japan. We compared creatinine-corrected metanephrine fractions in spot urine and 24-hour urine samples (the current standard for the screening and diagnosis of PPGLs) from 16 patients to assess the therapeutic effect of metyrosine. Percent changes from baseline in urinary metanephrine (uMN) or normetanephrine (uNMN) were compared between spot and 24-hour urine samples. Mean percent changes in uMN or uNMN in spot and 24-hour urine were -26.36% and -29.27%, respectively. The difference in the percent change from baseline between uMN or uNMN in spot and 24-hour urine was small (-2.90%). The correlation coefficient was 0.87 for percent changes from baseline between uMN or uNMN measured in spot and 24-hour urine. The area under the receiver operator characteristic (ROC) curve of uMN or uNMN measured in spot urine vs. 24-hour urine (reference standard) to assess the efficacy of metyrosine treatment was 0.93. Correlations and ROCs between 24-hour urinary vanillylmandelic acid, adrenaline, and noradrenaline and 24-hour uMN or uNMN were similar to those between spot uMN or uNMN and 24-hour uMN or uNMN. No large difference was observed between spot and 24-hour urine for the assessment of metyrosine treatment by quantifying uMN or uNMN in Japanese patients with PPGLs. These results suggest that spot urine samples may be useful in assessing the therapeutic effect of metyrosine.

10.
Aging Male ; : 1-7, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469340

RESUMO

Purpose: To investigate the relationship between urodynamic study (UDS) data and recovery of urinary incontinence (UI) in elderly patients who underwent robot-assisted radical prostatectomy (RARP). Materials and methods: Seventy-five prostate cancer (PCa) patients received UDS before and at 3 months after RARP. They were divided into two groups; a younger group (<70 years old, n = 47) and older group (≥70 years, n = 28), and each was classified according to urinary continence (UC) or UI at 3 months post-RARP. Continence was defined as being pad-free or 1-safety pad usage per day. Results: In the older group, preoperative maximum urethral closure pressure (MUCP) in the UI group was significantly lower than that in the UC group. Detrusor overactivity (DO) rate was significantly higher in the older UI group than in the older UC group at both pre- and 3 months post-RARP. Persistent DO rate pre- and post-RARP was significantly higher in the older group than in the younger group. Regardless of age, postoperative DO was an independent predictor of UI 6 months post-RARP. Conclusions: In elderly patients, low preoperative MUCP and both pre- and postoperative DO are associated with postoperative UI.

11.
Plast Reconstr Surg ; 144(3): 644-655, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31461020

RESUMO

BACKGROUND: Adipose-derived stem cells and ceiling culture-derived preadipocytes can be harvested from subcutaneous adipose tissue. Little is known about the epigenetic differences, which may contribute to differences in osteogenic potential, between these cell types. The purpose of this study was to address the osteogenic potential and underlying epigenetic status of adipose-derived stem cells and ceiling culture-derived preadipocytes. METHODS: Adipose-derived stem cells and ceiling culture-derived preadipocytes were cultured from abdominal subcutaneous fat tissues of four metabolically healthy, lean female patients. After 7 weeks of culture, cellular responses to osteogenic differentiation media were examined. To evaluate the osteogenic potentials of undifferentiated adipose-derived stem cells and ceiling culture-derived preadipocytes, two types of epigenetic assessment were performed using next-generation sequencing: DNA methylation assays with the Human Methylation 450K BeadChip, and chromatin immunoprecipitation assays for trimethylation of histone H3 at lysine 4. RESULTS: Human ceiling culture-derived preadipocytes showed greater osteogenic differentiation ability than did adipose-derived stem cells. In an epigenetic survey of the promoters of four osteogenic regulator genes (RUNX2, SP7, ATF4, and BGLAP), the authors found a general trend toward decreased CpG methylation and increased trimethylation of histone H3 at lysine 4 levels in ceiling culture-derived preadipocytes as compared to adipose-derived stem cells, indicating that these genes were more likely to be highly expressed in ceiling culture-derived preadipocytes. CONCLUSIONS: The surveyed epigenetic differences between adipose-derived stem cells and ceiling culture-derived preadipocytes were consistent with the observed differences in osteogenic potential. These results enhance the authors' understanding of these cells and will facilitate their further application in regenerative medicine.


Assuntos
Adipócitos/citologia , Adipócitos/fisiologia , Epigênese Genética/fisiologia , Osteogênese/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Gordura Subcutânea/citologia , Adulto , Células Cultivadas , Feminino , Humanos , Pessoa de Meia-Idade
12.
Sci Rep ; 9(1): 10009, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292513

RESUMO

Statins have been reported to increase the plasma concentration of arachidonic acid (AA), an omega-6 long chain polyunsaturated fatty acid (LCPUFA) in several clinical studies indicating that statins affect the endogenous synthesis of LCUFAs. In the present study, we investigated the roles of the intrinsic mevalonate cascade and Rho-dependent pathway in LCPUFA synthesis, especially focusing on fatty acid desaturases (Fads) 2, using the human hepatocellular carcinoma cell line HepG2. Cell number and the activity of caspase-3 and 7 (caspase-3/7) was measured using a commercial kit. Gene expression was analyzed by quantitative real-time PCR. Protein expression was detected by Western blot analysis. Atorvastatin decreased cell viability and increased caspase-3/7 activity in a dose-dependent manner. At lower concentrations, atorvastatin stimulated both mRNA and protein expression of Fads2, and increased mRNA expression of FADS1 and ELVOL5. Both mevalonate and geranylgeranyl-pyrophosphate (GGPP), but not cholesterol, fully reversed atorvastatin-induced upregulation of Fads2, and mevalonate-effected reversal was inhibited by treatment with the Rho-associated protein kinase inhibitor Y-27632. These data clearly demonstrated that in human HepG2 cells, statins affect the endogenous synthesis of LCPUFAs by regulation of not only Fads2, but also Fads1 and Elovl5, through the GGPP-dependent Rho kinase pathway.

13.
Reprod Toxicol ; 88: 39-47, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288075

RESUMO

Effects of endocrine disrupting chemicals (EDCs) on reproduction have not been fully explained comprehensively. In this study, we tried to validate the common effect of Bisphenol A (BPA) and Nonylphenol (NP) on the differentiation of embryonic stem (ES) cells and found that they modify the expression of germ cell specific genes. To elucidate functional significance on biological process, we performed Gene Ontology (GO)-based microarray analysis comparing with published GeneChip data of primordial germ cell development in vivo. Cluster analysis of gene expression profile revealed that EDC treatment and primordial germ cell (PGC) development shared characteristic cluster consists of GO terms related to "germ cell development" and "reproduction". In the GO term "reproduction", meiosis related genes showed high expression level by EDC exposure. These results suggest that BPA and NP affect not only some of the germ cell specific genes, but functionally interferes germ cell development and reproduction.


Assuntos
Compostos Benzidrílicos/toxicidade , Células-Tronco Embrionárias/efeitos dos fármacos , Perfilação da Expressão Gênica , Fenóis/toxicidade , Animais , Células Cultivadas , Células Germinativas/efeitos dos fármacos , Células Germinativas/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos ICR , Análise de Sequência com Séries de Oligonucleotídeos , Reprodução/efeitos dos fármacos
14.
Geriatr Gerontol Int ; 19(8): 834-837, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31270946

RESUMO

AIM: This study aimed to establish and validate a quantitative evaluation method for pelvic floor muscles using magnetic resonance images (MRI) and to examine the morphological change of pelvic floor muscles with aging. METHODS: Data from 369 consecutive patients (163 men, 206 women; median age 58 years; range 17-92 years) who underwent coronal T2-weighted pelvic MRI at Osaka General Hospital between January 2016 and December 2016 were retrospectively examined. MRI of the levator ani muscle was evaluated. The MRI image blinded the patient information and was evaluated by a radiology specialist with 22 years of experience. In coronal T2-weighted MRI of the pelvis, the levator ani muscle was evaluated using the slice; it showed the most upward and downward convexity. We measured the thickness of the levator ani muscle, and the distance at the most convex part from a straight line connecting the origin and insertion of the levator ani muscle on both the left and right sides. Upward and downward convexity was recorded in positive and negative values, respectively. RESULTS: The levator ani muscle was able to be evaluated quantitatively in all cases. Both men and women showed thinning (men: mean 3.316 mm, r = -0.388, P < 0.0001; women: mean 3.947 mm, r = -0.359, P < 0.0001) and concavity (men: mean 1.412 mm, r = -0.362, P < 0.0001; women: mean 4.979 mm, r = -0.630, P < 0.0001) of the levator ani muscle with aging. CONCLUSIONS: A quantitative evaluation method for pelvic floor muscles using MRI was established. Aging was associated with morphological changes in the pelvic floor muscles in both men and women. Geriatr Gerontol Int 2019; 19: 834-837.


Assuntos
Envelhecimento/patologia , Diafragma da Pelve , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Correlação de Dados , Precisão da Medição Dimensional , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/patologia , Fatores Sexuais
15.
Environ Sci Technol ; 53(16): 9636-9645, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31347357

RESUMO

California methane (CH4) emissions are quantified for three years from two tower networks and one aircraft campaign. We used backward trajectory simulations and a mesoscale Bayesian inverse model, initialized by three inventories, to achieve the emission quantification. Results show total statewide CH4 emissions of 2.05 ± 0.26 (at 95% confidence) Tg/yr, which is 1.14 to 1.47 times greater than the anthropogenic emission estimates by California Air Resource Board (CARB). Some of differences could be biogenic emissions, superemitter point sources, and other episodic emissions which may not be completely included in the CARB inventory. San Joaquin Valley (SJV) has the largest CH4 emissions (0.94 ± 0.18 Tg/yr), followed by the South Coast Air Basin, the Sacramento Valley, and the San Francisco Bay Area at 0.39 ± 0.18, 0.21 ± 0.04, and 0.16 ± 0.05 Tg/yr, respectively. The dairy and oil/gas production sources in the SJV contribute 0.44 ± 0.36 and 0.22 ± 0.23 Tg CH4/yr, respectively. This study has important policy implications for regulatory programs, as it provides a thorough multiyear evaluation of the emissions inventory using independent atmospheric measurements and investigates the utility of a complementary multiplatform approach in understanding the spatial and temporal patterns of CH4 emissions in the state and identifies opportunities for the expansion and applications of the monitoring network.


Assuntos
Poluentes Atmosféricos , Metano , Aeronaves , Teorema de Bayes , California , São Francisco
16.
Cancer Res ; 79(15): 3903-3915, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31189648

RESUMO

Cancer cell-intrinsic properties caused by oncogenic mutations have been well characterized; however, how specific oncogenes and tumor suppressors impact the tumor microenvironment (TME) is not well understood. Here, we present a novel non-cell-autonomous function of the retinoblastoma (RB) tumor suppressor in controlling the TME. RB inactivation stimulated tumor growth and neoangiogenesis in a syngeneic and orthotropic murine soft-tissue sarcoma model, which was associated with recruitment of tumor-associated macrophages (TAM) and immunosuppressive cells such as Gr1+CD11b+ myeloid-derived suppressor cells (MDSC) or Foxp3+ regulatory T cells (Treg). Gene expression profiling and analysis of genetically engineered mouse models revealed that RB inactivation increased secretion of the chemoattractant CCL2. Furthermore, activation of the CCL2-CCR2 axis in the TME promoted tumor angiogenesis and recruitment of TAMs and MDSCs into the TME in several tumor types including sarcoma and breast cancer. Loss of RB increased fatty acid oxidation (FAO) by activating AMP-activated protein kinase that led to inactivation of acetyl-CoA carboxylase, which suppresses FAO. This promoted mitochondrial superoxide production and JNK activation, which enhanced CCL2 expression. These findings indicate that the CCL2-CCR2 axis could be an effective therapeutic target in RB-deficient tumors. SIGNIFICANCE: These findings demonstrate the cell-nonautonomous role of the tumor suppressor retinoblastoma in the tumor microenvironment, linking retinoblastoma loss to immunosuppression.

17.
Plast Reconstr Surg ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31181041

RESUMO

BACKGROUND: Adipose-derived stem cells (ASCs) and ceiling culture-derived preadipocytes (ccdPAs) can be harvested from subcutaneous adipose tissue. Little is known about the epigenetic differences, which may contribute to differences in osteogenic potential, between these cell types. PURPOSE: The purpose of this study was to address the osteogenic potential and underlying epigenetic status of ASCs and ccdPAs. MATERIALS AND METHODS: ASCs and ccdPAs were cultured from abdominal subcutaneous fat tissues of four metabolically healthy, lean females. After seven weeks of culture, cellular responses to osteogenic differentiation media were examined. To evaluate the osteogenic potentials of undifferentiated ASCs and ccdPAs, two types of epigenetic assessment were performed using next generation sequencing: DNA methylation assays with a 450K BeadChip; and chromatin immunoprecipitation assays (ChIP-Seq) for trimethylation of histone H3 at lysine 4 (H3K4me3). RESULTS: Human ccdPAs showed greater osteogenic differentiation ability than did ASCs. In an epigenetic survey of the promoters of four osteogenic regulator genes (RUNX2, SP7, ATF4, and BGLAP), we found a general trend toward decreased CpG methylation and increased H3K4me3 levels in ccdPAs as compared to ASCs, indicating that these genes were more likely to be highly expressed in ccdPAs. CONCLUSION: The surveyed epigenetic differences between ASCs and ccdPAs were consistent with the observed differences in osteogenic potential. These results enhance our understanding of these cells and will facilitate their further application in regenerative medicine.

18.
Endocr J ; 66(6): 485-496, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31105124

RESUMO

The tumor suppressor gene p53 is mutated in approximately more than 50% of human cancers. p53 is also referred to as the "cellular gatekeeper" or "guardian of the genome" because it protects the body from spreading mutated genome induced by various stress. When the cells receives stimuli such as DNA damage, oncogene activation, oxidative stress or undernutrition, p53 gives rise to a number of cellular responses, including cell cycle arrest, apoptosis, cellular senescence and metabolic adaptation. Related to energy metabolisms, it has been reported that p53 reduces glycolysis and enhances mitochondrial respiration. p53 is also involved in the regulation of other cellular metabolism and energy production systems: amino acid metabolism, fatty acid metabolism, nucleic acid metabolism, anti-oxidation, mitochondrial quality control, and autophagy. Moreover, recent studies have shown that p53 gene polymorphisms affect life expectancy and lifestyle-related disease such as type 2 diabetes, suggesting that there is a certain relationship between p53 function and metabolic disorders. In addition, mutant p53 protein does not only lose the tumor suppressor function, but it also gains novel oncogenic function and contributes to tumor development, involving cellular metabolism modification. Therefore, the importance of multifunctionality of p53, particularly with regard to intracellular metabolisms, arouses therapeutic interest and calls attention as the key molecule among cancer, lifestyle-related diseases and life expectancy.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/fisiologia , Neoplasias/metabolismo , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Diabetes Mellitus Tipo 2/genética , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Neoplasias/genética , Proteína Supressora de Tumor p53/genética
19.
Int J Urol ; 26(9): 860-867, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31083787

RESUMO

Hyperbaric oxygen therapy is a promising medical technology that delivers oxygen to targeted tissues at high pressure to increase the amount of dissolved oxygen in the blood. Over the past three decades, hyperbaric oxygen has been used in a variety of conditions, including radiation-induced tissue injuries, non-healing states with ischemia and malignant neoplasms. In the field of urology, hyperbaric oxygen has also been applied to some pathological conditions (e.g. radiation-induced hemorrhagic cystitis, Fournier gangrene, interstitial cystitis, male infertility, acute kidney injury and urological cancers). In normal and injured tissues, hyperoxia from hyperbaric oxygen therapy contributes to anti-inflammation, angiogenesis through endothelial proliferation, enhanced fibroblastic activity, increased lymphocyte and macrophage activity, and bactericidal effects with the aim of wound repair. In cancerous tissues, the enhanced supply of oxygen into the hypoxic cancer cells can exert inhibitory effects on factors that contribute to their aggressiveness (e.g. cell survival, escape from apoptosis, epithelial-to-mesenchymal transition and tumor immunotolerance), and sensitize the tumor to radiation therapy and chemotherapy. However, further research, including multicenter clinical studies, is essential for determining the role of hyperbaric oxygen therapy in refractory urological diseases that are resistant to conventional therapies.

20.
J Med Case Rep ; 13(1): 13, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30646927

RESUMO

BACKGROUND: Panitumumab is the first human combinatorial antibody for the treatment of metastatic colorectal carcinoma. Dermatologic toxicity of all grades occurs in more than 90% of patients. However, there are few reports of purpura induced by anti-epidermal growth factor receptor antibody. Renal failure is also uncommon as an adverse event of anti-epidermal growth factor receptor antibody. CASE PRESENTATION: A 67-year-old Japanese man with advanced colon cancer received monotherapy with panitumumab. General malaise, bilateral edema of his legs, and bilateral purpura of his forearms developed 2 days after the second cycle of panitumumab. A skin biopsy was performed to evaluate the purpuric lesions on his left leg and leukocytoclastic vasculitis was diagnosed. Blood tests showed grade III acute renal failure with a blood urea nitrogen level of 33.8 mg/dL and a creatinine level of 3.10 mg/dL. CONCLUSIONS: This is the first reported case of leukocytoclastic vasculitis followed by purpura and acute renal failure associated with panitumumab.


Assuntos
Lesão Renal Aguda/patologia , Neoplasias do Colo/tratamento farmacológico , Perna (Membro)/patologia , Neoplasias Hepáticas/tratamento farmacológico , Panitumumabe/uso terapêutico , Púrpura/patologia , Vasculite Leucocitoclástica Cutânea/patologia , Lesão Renal Aguda/induzido quimicamente , Idoso , Neoplasias do Colo/patologia , Progressão da Doença , Evolução Fatal , Humanos , Neoplasias Hepáticas/secundário , Masculino , Panitumumabe/efeitos adversos , Púrpura/induzido quimicamente , Vasculite Leucocitoclástica Cutânea/induzido quimicamente
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