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1.
Reprod Sci ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124395

RESUMO

HSP60 is a mitochondrial chaperone protein that is associated with decreased overall survival of ovarian cancer patients. We determined whether targeting HSP60 with its monoclonal antibody would induce cytotoxicity in sensitive and chemoresistant ovarian cancer cells and whether it is synergistic when combined with chemotherapeutic drugs. Epithelial ovarian cancer (EOC) cells and their docetaxel- or cisplatin-resistant counterparts were utilized. HSP60 mRNA levels were determined by real-time RT-PCR. Cytotoxicity of HSP60 antibody (0.5 or 1.5 µg/ml) alone and in combination with chemotherapy were assessed by MTT Cell Proliferation Assay. Unpaired t tests were used to compare groups for real-time RT-PCR. One-way ANOVA followed by Tukey's post hoc tests with Bonferroni correction was performed for cytotoxicity comparisons. Significant synergistic effects of the antibody combined with chemotherapy were determined by the CompuSyn Software. Basal HSP60 mRNA levels were increased in chemoresistant EOC cells as compared with their sensitive counterparts (p < 0.05). There was no significant difference in cytotoxicity between EOC cell types; however, treatment with the HSP60 antibody for 24 h showed a dose response (0.5 and 1.5 µg/ml) cytotoxic effect to both sensitive and chemoresistant EOC cells as compared with the isotype control (p < 0.05). Importantly, treatment with both doses of HSP60 antibody was not cytotoxic to normal macrophages. Combination of the HSP60 antibody with docetaxel or cisplatin was significantly synergistic in both sensitive and chemoresistant EOC cells. Here, we identify a novel target that may serve not only for ovarian cancer treatment but also for sensitization of patients to chemotherapy. The cytotoxic effect of HSP60 monoclonal antibody and its synergism with chemotherapeutic agents highlight HSP60 as a promising target for therapy and chemosensitization in ovarian cancer treatment.

2.
J Infect Dis ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211776

RESUMO

BACKGROUND: Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining HBV RNA and hepatitis B core-related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. METHODS: The evaluation cohort included 127 HBeAg-positive patients from a multi-centre prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA<50 IU/mL for >48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analysed. RESULTS: At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg <4 log10 U/mL at EOT (low-risk group), whereas 46.8% patients with positive HBV RNA and HBcrAg ≥4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year post-treatment follow-up (P <0.001); the corresponding incidences in the validation cohort were 0% and 69.4% (P <0.001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs. 1.3%, P =0.002). CONCLUSION: Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive CHB patients.

3.
J Zhejiang Univ Sci B ; 21(3): 204-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133798

RESUMO

Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.

4.
Turk J Gastroenterol ; 31(1): 30-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32009611

RESUMO

BACKGROUND/AIMS: To determine the characteristics of small bowel tumors (SBTs) in patients underwent double balloon endoscopy (DBE) and to compare the clinical value of DBE with other diagnostic tools. MATERIALS AND METHODS: A retrospective study was conducted in patients underwent DBE procedures from March 2008 to April 2017.The demographic, clinical and pathological characteristics of patients with SBTs were recorded, while the diagnosis of SBTs was achieved either by DBE biopsy or surgical specimens. RESULTS: One thousand one hundred and two patients (761 males, range 3-85 years) were enrolled in this study, with 1140 procedures completed in total. 99/1102 patients (9.0%) had SBTs, including benign polyps (20, 20.2%), gastrointestinal stromal tumors (GISTs) (24, 24.2%), lymphomas (13, 13.1%), adenocarcinoma (39, 39.4%), and neuroendocrine tumors (3, 3.0%). The most common clinical symptom for benign polyps was obscure gastrointestinal bleeding (OGIB) (75.0%). But among patients with malignant SBTs, the main indication for DBE was chronic abdominal pain (43.8%), followed by OGIB (36.3%), vomit (10.0%), abnormal images (6.3%) and diarrhea (3.8%) (P<0.001). Moreover, SBTs were primarily located in the jejunum alone (40/99, 40.4%). DBE had better sensitivity (89.2%), specificity (95.2%), positive predictive value (PPV) (90.0%), and negative predictive value (NPV) (94.8%) than other tools for suspected SBTs. CONCLUSION: Small bowel tumor is mainly located in jejunum and with OGIB and abdominal pain as major complaints. DBE is a reliable method for the diagnosis of SBTs compared with other diagnostic tools.

5.
Biomed Pharmacother ; 125: 109931, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32066040

RESUMO

κ-opioid receptor (κ-OR) plays a key role in preventing hypoxic pulmonary hypertension (HPH) development after activated by exogenous agonist U50,488H. Calcium sensing receptor (CaSR) activation induces HPH by promoting vasoconstriction and vascular remodeling. The activated κ-OR is reported to inhibit the expression of CaSR in pulmonary artery smooth muscle cells (PASMCs). Thus, in this study, we aimed to explore the effect of activated κ-OR on the role of CaSR in preventing HPH development. An HPH rat model was constructed using Sprague-Dawley rats. Changes in mean pulmonary arterial pressure (mPAP) and right ventricular pressure (RVP) mediated by κ-OR agonist U50,488H and CaSR inhibitor NPS2143 were observed. The effects of CaSR agonist spermine and inhibitor NPS2143 on pulmonary artery tension were tested. The expression and localization of κ-OR and CaSR were measured in isolated PASMCs. A cell-counting kit-8 assay was performed to evaluate the effect of spermine in PASMC proliferation. Expression of proliferating cell nuclear antigen (PCNA), Erk, and p-Erk was evaluated by western blot analysis. Results showed that κ-OR and CaSR were co-expressed and colocalized in PASMCs under normoxic and hypoxic conditions. Interactions between κ-OR and CaSR were also observed. Spermine improved vasoconstriction in the pulmonary artery in HPH rats, which was abolished by U50,488H. RVP and mPAP were significantly increased in HPH rats under CaSR stimulation, but were significantly reduced when the rats were pretreated with U50,488H and NPS2143 (P < 0.01). Spermine treatment significantly promoted PASMC proliferation, which was significantly inhibited by U50,488H, p38 inhibitor SB203580, JNK inhibitor SP600125, Erk inhibitor SCH772984, and MEK inhibitor U0126, especially Erk inhibitor (P < 0.01). Spermine significantly increased PCNA and P-Erk expression in hypoxic conditions, which was inhibited by U50,488H and NPS2143. κ-OR stimulation prevented HPH development via the CaSR/MAPK signaling pathway.

6.
J Cell Mol Med ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048816

RESUMO

High-fat diet (HFD) leads to obesity, type II diabetes mellitus (T2DM) and increases the coincidence of cardiovascular diseases and cancer. Insulin resistance (IR) is considered as the 'common soil' of those diseases. Furthermore, people on HFD showed restrained glycolysis and enhanced fatty acid oxidation, which is the so-called metabolic reprogramming. However, the relationship between metabolic reprogramming and IR induced by HFD is still unclear. Here, we demonstrate that PANK1 and miR-107 were up-regulated in the liver tissue of mice on HFD for 16 weeks and involved in metabolic reprogramming induced by palmitate acid (PA) incubation. Importantly, miR-107 within an intron of PANK1 gene facilitated IR by targeting caveolin-1 in AML12 cells upon PA incubation. Moreover, we identify that HFD enhanced P53 expression, and activation of P53 with nutlin-3a induced PANK1 and miR-107 expression simultaneously in transcriptional level, leading to metabolic reprogramming and IR, respectively. Consistently, inhibition of P53 with pifithrin-α hydrobromide ameliorated PA-induced metabolic reprogramming and IR. Thus, our results revealing a new mechanism by which P53 regulate metabolism. In addition, the results distinguished the different roles of PANK1 and its intron miR-107 in metabolic regulation, which will provide more accurate intervention targets for the treatment of metabolic diseases.

7.
Ir J Med Sci ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064546

RESUMO

BACKGROUND: Recent study reported that microRNA-142 (miR-142) were up-regulated in the atherosclerotic plaques, which may be responsible for pathogenesis of atherosclerosis. However, whether it associates with presence of acute myocardial infarction (AMI), and its prognostic value is still unknown. We, therefore, investigated the association between miR-142 expression and presence of AMI, and its prognostic value in AMI patients. METHODS: We included 300 AMI patients and 100 subjects as the control group. MiR-142 content was detected by quantitative real-time polymerase chain reaction. MiR-142 level was identified in all subjects. The multivariate logistic regression analysis were performed to evaluate the risk factors of AMI. The Kaplan-Meier analysis was performed to determine the major adverse cardiovascular and cerebrovascular events (MACCE)-free survival. RESULTS: AMI group had significantly higher miR-142 level in comparison to the controls [4.10 (2.03-7.43) vs. 1.92 (0.91-2.91), p < 0.001], moreover, miR-142 content was significantly associated with cardiac troponin I (cTnI) level (r = 0.707, p < 0.001). The MACCE-free survival was significantly lower over 24-month for patients in miR-142 high expression group (72.4% ± 5.6% vs. 76.4% ± 5.1%) (p = 0.022). After adjusting for the traditional risk factors, the odds ratios of miR-142 was 14.74 (95% CI, 2.15-101.24). The multivariate logistic regression analysis revealed that miR-142 level significantly associated with presence of AMI (p < 0.001). CONCLUSION: The serum level of miR-142 was increased in AMI patients when compared with health population. Furthermore, use of this marker may allow a certain predictor of the MACCE in AMI patients.

8.
Eur J Pharmacol ; 874: 172987, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032598

RESUMO

Mitochondrial dynamics, determining mitochondrial morphology, quality and abundance, have recently been implicated in myocardial ischemia and reperfusion (MI/R) injury. The roles of κ-opioid receptor activation in cardioprotection have been confirmed in our previous studies, while the underlying mechanism associated with mitochondrial dynamics remains unclear. This study aims to investigate the effect of κ-opioid receptor activation on the pathogenesis of MI/R and its underlying mechanisms. MI/R mouse model and hypoxia-reoxygenation cardiomyocyte model were established in this study. Mitochondrial dynamics were analyzed with transmission electron microscopy in vivo and confocal microscopy in vitro. STAT3 phosphorylation and OPA1 expression were detected by Western blotting. We show here that κ-opioid receptor activation with its selective receptor agonist U50,488H promoted mitochondrial fusion and enhanced myocardial resistance to MI/R injury, while these protective effects were blockaded by nor-BNI, a selective κ-opioid receptor antagonist. In addition, κ-opioid receptor activation increased STAT3 phosphorylation and OPA1 expression, which were blockaded by nor-BNI. Furthermore, inhibition of STAT3 phosphorylation by stattic, a specific STAT3 inhibitor, repressed the effects of κ-opioid receptor activation on promoting OPA1 expression and mitochondrial fusion, as well as inhibiting cell apoptosis and oxidative stress both in vivo and in vitro during MI/R injury. Overall, our data for the first time provide evidence that κ-opioid receptor activation promotes mitochondrial fusion and enhances myocardial resistance to MI/R injury via STAT3-OPA1 pathway. Targeting the pathway regulated by κ-opioid receptor activation may be a potential therapeutic strategy for MI/R injury.

9.
Chemistry ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037581

RESUMO

Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.

10.
Eur J Radiol ; 123: 108745, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899061

RESUMO

PURPOSE: To investigate the relationship between intravoxel incoherent motion (IVIM) parameters and histological parameters of vascularity and cellularity in marrow of hyperplasia disease and compare the difference between benign and malignant marrow disorders. METHODS: From August 2016 to March 2017, 43 newly diagnosed patients were recruited, which included 15 anemia patients (benign hemopathy) and 28 patients with acute leukemia (AL) (malignant hemopathy). All patients underwent IVIM in the lumbar marrow and the D, D*, f values were measured. The microvessel density (MVD) and cellularity of marrow were calculated from the sample of iliac crest biopsy. Pearson correlation analysis was used to study the relationship between IVIM-derived and histology-derived parameters. We performed unpaired t test to analyze the differences of all parameters between AL and anemia. RESULT: The MVD was positively correlated with f in patients with AL, anemia and both of them (r = 0.692, P < 0.001; r = 0.595, P = 0.019; r = 0.673, P < 0.001, respectively). But there was no correlation between D* and MVD in three groups. D was not related to bone marrow cellularity (BMC) in all groups. In addition, the f and MVD were higher in AL than anemia (t = 3.546, P = 0.001; t = 6.695, P < 0.001, respectively). The BMC was significantly higher in AL than in anemia (t = 3.330, P = 0.004), but D and D* value had no significant difference between the two groups. CONCLUSION: The blood volume fraction f was positively correlated with the histological features of marrow in hematological disorders, while f can show the difference of vascularity between benign and malignant marrow disease.

11.
Arch Microbiol ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894392

RESUMO

The bacterial community in mammalian gastrointestinal tract is abundant and complex. To date, little is known about the gut microbiota of wild boar. This study aimed to investigate the fecal bacterial diversity of wild boar and compare with commercial pig and domestic native pig. The diet composition showed that the diets of wild boar, commercial pig and domestic native pig were different from each other. More than 1,760,000 quality-filtered sequences were obtained, and the results revealed distinct compositions and diversity of fecal microbiota in three groups. PCoA and NMDS analyses showed that fecal bacterial communities of wild boar, commercial pig and domestic native pig formed distinctly different clusters. Although the three groups shared a large size of OTUs comprising a core microbiota community, a strong distinction existed at family and genus levels. Ruminococcaceae, Prevotellaceae and Christensenellaceae were more abundant in the feces of wild boar than in domestic native pig and commercial pig. At the genus level, the proportion of unidentified Christensenellaceae was remarkably higher in wild boar group, while commercial pig and domestic native pig group had a higher abundance of Streptococcus and Lactobacillus. Tax4Fun predictions of metagenome function showed statistically significant differences in the functions of fecal microbiota in three groups. There were more bacteria genes with amino acid metabolism, cell growth and death, cell motility, energy metabolism, immune system and environmental adaptation observed in wild boar feces, while commercial pig feces contained more bacteria genes with carbohydrate metabolism, drug resistance, aging, infectious diseases, lipid metabolism, endocrine and metabolic diseases. These results indicated that the fecal microbial ecosystem of the wild boar is significantly different from that of domestic native pig and commercial pig, suggesting that diet is an important factor leading to differences in bacterial abundance and diversity in feces.

12.
Nutrients ; 12(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947716

RESUMO

Supplementation with n-3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT). Agricultural products that are biofortified with α-linolenic acid (ALA), the precursor of n-3 LC PUFA, have been launched to the market, but their impact on BAT function is unknown. This study aimed to evaluate the effects of ALA-biofortified butter on lipid metabolism and thermogenic functions in the BAT. C57BL/6 mice were fed a high-fat diet containing ALA-biofortified butter (n3Bu, 45% calorie from fat) for ten weeks in comparison with the isocaloric high-fat diets prepared from conventional butter or margarine. The intake of n3Bu significantly reduced the whitening of BAT and increased the thermogenesis in response to acute-cold treatment. Also, n3Bu supplementation is linked with the remodeling of BAT by promoting bioconversion into n-3 LC PUFA, FA elongation and desaturation, and mitochondrial biogenesis. Taken together, our results support that ALA-biofortified butter is a novel source of n-3 PUFA, which potentiates the BAT thermogenic function.

14.
BMJ Open ; 10(1): e034290, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31911525

RESUMO

INTRODUCTION: Migraine is the second-leading cause of years lived with disability worldwide. The high prevalence of migraine-related emotional disorders is often overlooked. Acupuncture is often used to treat both migraine and emotional disorders. This systematic review protocol aims to analyse whether acupuncture is effective for treating emotional disorders in patients with migraine. METHODS AND ANALYSIS: Nine databases will be searched from inception to may 2019: cochrane central register of controlled trials, medline, embase, allied and complementary medicine database, cinahl, china national knowledge infrastructure, chinese biomedical literature database, vip database and wanfang database. Randomised controlled trials (rcts) of acupuncture therapy for migraine with emotional functioning outcomes, which were reported in chinese or english, will be included. The primary outcome is the change in emotional functioning. Study selection, data extraction and assessment of the risk of bias will be performed independently by two or more reviewers. Revman software (v.5.3) will be used to perform the assessment of the risk of bias and data synthesis. ETHICS AND DISSEMINATION: Ethics approval is not be needed because the data will not contain individual patient data, and there are no concerns about privacy. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal or relevant conference. TRIAL REGISTRATION NUMBER: CRD42019139433.

15.
Aliment Pharmacol Ther ; 51(4): 469-478, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943297

RESUMO

BACKGROUND: To date, 14 single-nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). AIM: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. METHODS: We performed a retrospective analysis of 1623 Han Chinese HBeAg-positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow-up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase-IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. RESULTS: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα-treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one-third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P-trend = 4.000 × 10-4 ) and HBsAg loss (P-trend = 0.010) in PegIFNα-treated patients. However, none of the SNPs were associated with treatment response in NUCs-treated patients. CONCLUSIONS: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg-positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31967446

RESUMO

All-solid-state lithium metal batteries are highly attractive because of their high energy density and inherent safety. However, it is still a great challenge to design the solid electrolytes with high ionic conductivity at room temperature and good electrode/electrolyte interfacial compatibility simultaneously in a facile and scalable way. In this work, for the first time, the combination of salt affluent Poly(ethylene oxide) with Li6.75La3Zr1.75Ta0.25O12 nanofibers was designed and intensively evaluated. The synergistic effect of each component in the electrolyte enhances the ionic conductivity to 2.13 × 10-4 S cm-1 at 25 °C and exhibits a high transference number of 0.57. The composite electrolyte possesses superior interfacial stability against Li metal for over 680 h in Li symmetric cells even at a relatively high current density of 2 mA cm-2. The all-solid-state batteries employing the solid electrolytes exhibit excellent cycling stability at room temperature and superior safety performance. This work proposes a brand-new strategy to design and fabricate solid electrolytes in a versatile way for room-temperature all-solid-state batteries.

17.
J Food Prot ; : 204-210, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917614

RESUMO

The milk bar is an emerging style of retail business that mainly produces pasteurized milk (PM) and other dairy products on-site in many large cities of the People's Republic of China. To date, no data about veterinary drug residues in PM samples produced from milk bars have been reported. The objective of this study was to investigate the safety of PM from a total of 182 PM samples collected from milk bars from 10 provincial capital cities and to analyze the residues of seven classes of 61 veterinary drugs. First, the chemical components were screened with test kits, and then the positive samples were further confirmed by ultraperformance liquid chromatography-tandem mass spectrometry. The results showed that 15 (8.24%) samples were screened positive for veterinary drugs, and six drugs in 11 (6.04%) samples were confirmed. The veterinary drugs detected were penicillin G (2.20%), tetracycline (1.10%), tylosin (1.10%), amoxicillin (0.55%), oxytetracycline (0.55%), and gentamicin (0.55%), with maximum residue levels of 3.4, 11.9, 28.2, 3.0, 26.9, and 63.5 µg kg-1, respectively. Veterinary drug residues were detected as positive in 7 of 10 cities, with the highest detection rate as 14.29% in Urumqi. No positive samples were found in the cities of Nanjing, Tianjin, and Nanning. All detected drug levels were far below the maximum residue levels regulated by China, the European Union, and the Codex Alimentarius Commission. This suggests that the overall veterinary drug residues in PM in milk bars reached the safety code of the country. However, potential risks still exist, and continuous attention should be paid to guarantee the safety of this milk product in the future.

18.
Pediatr Blood Cancer ; 67(2): e28018, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710168

RESUMO

BACKGROUND:  Extraskeletal osteosarcoma is an extremely rare disease, comprising less than 0.1% of all cancers diagnosed in the United States, of which less than 5% occur in the upper extremities. The management of two cases of pediatric upper extremity extraskeletal osteosarcoma is discussed. CASE DESCRIPTION: Two children initially noticed painless left upper extremity masses at the ages of 16 and 13, respectively. Following a period of several months, both lesions became symptomatic, necessitating operative intervention, which revealed giant cell-rich extraskeletal osteosarcoma; PET staging following gross total resection revealed no residual or metastatic disease in either patient. After extensive discussion with the patients and family, adjuvant chemotherapy was initiated for one patient, and adjuvant radiation therapy was initiated in both patients. CONCLUSIONS: Despite the rarity of these tumors, the importance of radiation therapy has been established by current and ongoing studies such as the Children's Oncology Group study ARST0332. Radiation therapy remains an important component of the multimodality therapy comprising optimal treatment of this disease, despite the relative paucity of long-term outcome data derived from level I evidence.

19.
J Nutr Biochem ; 76: 108285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760228

RESUMO

α-Linolenic acid (ALA) is an essential fatty acid and the precursor for long-chain n-3 PUFA. However, biosynthesis of n-3 PUFA is limited in a Western diet likely due to an overabundance of n-6 PUFA. We hypothesized that dietary reduction of n-6/n-3 PUFA ratio is sufficient to promote the biosynthesis of long-chain n-3 PUFA, leading to an attenuation of high fat (HF) diet-induced obesity and inflammation. C57BL/6 J mice were fed a HF diet from ALA-enriched butter (n3Bu, n-6/n-3=1) in comparison with isocaloric HF diets from either conventional butter lacking both ALA and LA (Bu, n-6/n-3=6), or margarine containing a similar amount of ALA and abundant LA (Ma, n-6/n-3=6). Targeted lipidomic analyses revealed that n3Bu feeding promoted the bioconversion of long-chain n-3 PUFA and their oxygenated metabolites (oxylipins) derived from ALA and EPA. The n3Bu supplementation attenuated hepatic TG accumulation and adipose tissue inflammation, resulting in improved insulin sensitivity. Decreased inflammation by n3Bu feeding was attributed to the suppression of NF-κB activation and M1 macrophage polarization. Collectively, our work suggests that dietary reduction of the n-6/n-3 PUFA ratio, as well as total n-3 PUFA consumed, is a crucial determinant that facilitates n-3 PUFA biosynthesis and subsequent lipidomic modifications, thereby conferring metabolic benefits against obesity-induced inflammation and insulin resistance.

20.
Clin Gastroenterol Hepatol ; 18(3): 719-727.e7, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31362119

RESUMO

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

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