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1.
Water Res ; 168: 115157, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614235

RESUMO

Hemodialysis is one of the therapies for patients with kidney failure. Hemodialysis requires large amounts of pure water, and is one of the most water-hungry medical procedures, and thus represents a clear opportunity where improvements should be made concerning the consumption and wastage of water. In this paper, we explored the potential of forward osmosis (FO) membrane for recycling the spent dialysate using the dialysis concentrate as the draw solution. Partially diluted dialysis concentrate could be further diluted with pure water to form dialysate for further dialysis process. Using commercial cellulose triacetate (CTA) FO membranes, the water recovery of approximately 64% was achieved and the final volume of the partially diluted dialysis concentrate was about four times the initial volume. Flux decline of the FO process was observed, mainly due to concentration of synthetic spent dialysate and dilution of dialysis concentrate, while membrane scaling had little impact on the flux decline. The urea rejection was found to be relatively low owing to the small size and electroneutral nature of the urea molecule. Obvious membrane scaling was observed after three FO cycles. The energy dispersive spectroscopy analysis of the scaling layer indicated that the scalants were phosphates and carbonates. The scaling was removed via osmotic backwash and almost completely recovery of FO flux was obtained. Economic analysis showed that the centralized treatment of spent dialysate in a dialysis center using the proposed osmotic dilution process could greatly save water resources and cost. Improving the urea rejection of FO membrane was identified as an important research focus for future research on the potential application of FO technology for recycling the spent dialysate in hemodialysis.


Assuntos
Purificação da Água , Análise Custo-Benefício , Soluções para Diálise , Estudos de Viabilidade , Membranas Artificiais , Osmose
2.
Front Biosci (Landmark Ed) ; 25: 536-548, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585902

RESUMO

Hyperhomocysteinemia induces stress response in endoplasmic reticulum (ERS). Here, we tested whether blockage of homocysteine (Hcy) induced ERS and subsequent apoptosis in vascular smooth muscle cells can be inhibited by  blockage of PERK/eIF2α/ATF4/CHOP signaling. Short-term exposure of vascular smooth muscle cells to Hcy led to the phosphorylation of PERK (pPERK), which in turn, phosphorylated eIF2 alpha (peIF2a) and inhibited the unfolded protein response. Long-term Hcy exposure, however, increased the expression of ATF-4 and CHOP and led to apoptosis. Treatment of cells with salubrinal, a specific inhibitor for eIF2a decreased the expression of ATF-4 and CHOP, and prevented apoptosis. Together, the results show that PERK pathway is involved in Hcy-induced vascular smooth muscle cell apoptosis and that blocking the PERK pathway protects against this injury.

3.
Acta Trop ; 201: 105184, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31542374

RESUMO

Schistosomiasis is a chronic parasitic disease caused by the genus Schistosoma and poses a great threat to human and animal health. Identification of effective biomarkers would facilitate evaluation of drug efficacy and recognition of infected hosts, which are crucial for effective schistosomiasis control. Extracellular vesicle (EV) proteins are considered ideal biomarkers for developing invasive diagnostic tools. In this study, we evaluated the potential of Schistosoma japonicum EV (SjEV) proteins as biomarkers for diagnosing schistosomiasis. Several SjEV proteins were subject to epitope prediction using DNASTAR software, and the diagnostic potential of selected peptides was evaluated using enzyme-linked immunosorbent assay (ELISA). The results indicated that the sera showed detectable antibody levels against the two antigens in mice, rabbits, and humans infected with S. japonicum. Further analysis of the combined epitope protein demonstrated a modest sensitivity for detection of Schistosomiasis japonica. Our preliminary study suggests that S. japonicum EV proteins could serve as potential biomarkers for developing diagnostic tools for schistosomiasis.

4.
Cells ; 8(11)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683603

RESUMO

Tumor suppressor HOXA9 has been identified to promote apoptosis in cutaneous squamous cell carcinoma (cSCC). However, the mechanism of such pro-apoptotic role of HOXA9 remains obscure. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data showed that NF-κB, apoptosis and autophagy pathways are significantly regulated after HOXA9 knockdown. HOXA9 transcriptionally regulates RELA, the p65 subunit of NF-κB. Loss of HOXA9 in cSCC significantly upregulates RELA expression and thus enhances NF-κB pathway. Interestingly, RELA transcriptionally promotes not only anti-apoptotic factor BCL-XL but also autophagic genes including ATG1, ATG3, and ATG12. Our results reveal an enhanced NF-κB signaling network regulated by HOXA9, which contributes to repressed apoptosis and activated autophagy in cSCC development and may represent an intervention target for cSCC therapy.

5.
J Membr Biol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712855

RESUMO

Many natural products could induce apoptosis through mitochondrial pathways. However, direct interactions between natural products and mitochondria have rarely been reported. In this work, the effects and regulatory mechanisms of Jaceosidin on the isolated rat liver mitochondria have been studied. The results of the experiments which by introducing exogenous Ca2+ illustrated that Jaceosidin has the protective effects on the structure and function of the isolated mitochondria. These protective effects were related to the chelation of Ca2+ with Jaceosidin. Besides, Jaceosidin could scavenge reactive oxygen species produced during electron transport, and weaken the mitochondrial lipid peroxidation rate, which may be attributed to the antioxidant effect of phenolic hydroxyl groups of Jaceosidin. In addition, Jaceosidin has some damage effects on mitochondrial function, such as the inhibition of mitochondrial respiration and the increase of mitochondrial membrane fluidity. These results of this work provided comprehensive information to clarify the mechanisms of Jaceosidin on mitochondria, which may be the bidirectional regulatory mechanisms.

6.
Sci Rep ; 9(1): 15973, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685957

RESUMO

Jatropha curcas, an economically important biofuel feedstock with oil-rich seeds, has attracted considerable attention among researchers in recent years. Nevertheless, valuable information on the yield component of this plant, particularly regarding ovule development, remains scarce. In this study, transcriptome profiles of anther and ovule development were established to investigate the ovule development mechanism of J. curcas. In total, 64,325 unigenes with annotation were obtained, and 1723 differentially expressed genes (DEGs) were identified between different stages. The DEG analysis showed the participation of five transcription factor families (bHLH, WRKY, MYB, NAC and ERF), five hormone signaling pathways (auxin, gibberellic acid (GA), cytokinin, brassinosteroids (BR) and jasmonic acid (JA)), five MADS-box genes (AGAMOUS-2, AGAMOUS-1, AGL1, AGL11, and AGL14), SUP and SLK3 in ovule development. The role of GA and JA in ovule development was evident with increases in flower buds during ovule development: GA was increased approximately twofold, and JA was increased approximately sevenfold. In addition, the expression pattern analysis using qRT-PCR revealed that CRABS CLAW and AGAMOUS-2 were also involved in ovule development. The upregulation of BR signaling genes during ovule development might have been regulated by other phytohormone signaling pathways through crosstalk. This study provides a valuable framework for investigating the regulatory networks of ovule development in J. curcas.

7.
Sci Rep ; 9(1): 15998, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690787

RESUMO

Our aim is to assess the optimal cutoff value of fasting plasma glucose (FPG) in Chinese women at 24-28 weeks' gestation by performing oral glucose tolerance test (OGTT) to improve diagnostic rate of gestational diabetes mellitus (GDM). Data were derived from the Medical Birth Registry of Xiamen. A FPG cutoff value of 5.1 mmol/L confirmed the diagnosis of GDM in 4,794 (6.10%) pregnant women. However, a FPG cutoff value of 4.5 mmol/L should rule out the diagnosis of GDM in 35,932 (45.73%) pregnant women. If we use this cutoff value, the diagnosis of GDM to about 27.3% of pregnant women will be missed. Additionally, a 75-g OGTT was performed in pregnant women with FPG values between 4.5 and 5.1 mmol/L, avoiding the performance of formal 75-g OGTT in about 50.37% pregnant women. Meanwhile, according to maternal age and pre-pregnancy BMI categories, with FPG values between 4.5 mmol/L and 5.1 mmol/L, which had high sensitivity, to improve the diagnostic rate of GDM in all groups. Further researches are needed to present stronger evidences for the screening value of FPG in establishing the diagnosis of GDM in pregnant women.

8.
Life Sci ; : 116927, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672577

RESUMO

AIM: Aortic dissection (AD) is a devastating disease with rapid progression and high mortality, while the initiation mechanism of AD is far from clear. MAIN METHODS: AD was established by feeding mice with ß-aminopropionitrile in the diet and usage of angiotensin II (AngII) to trigger the rupture of aorta. LysMiDTR mice were constructed by crossing of LysM-Cre mice with ROSA26iDTR mice and characterized by diphtheria toxin receptor (DTR) expression in monocytes/macrophages specifically. Then, monocyte/macrophage depletion in LysMiDTR mice was conducted to evaluate the function of monocyte/macrophage in AD. Finally, the underlying mechanism was elucidated by proteomics, Western blot analysis, immunofluorescence staining and bioinformatics analysis. KEY FINDINGS: First, we detected T lymphocytes, macrophages and neutrophils infiltrated into the aorta simultaneously when AD occurred, and macrophages were the most abundant cell type. Then, targeted depletion of monocyte/macrophage in LysMiDTR mice considerably inhibited the occurrence of AD and infiltration of T lymphocytes and neutrophils. Furthermore, monocyte transfusion into LysMiDTR mice augmented the rupture of aorta, jointly supporting the key roles of monocytes/macrophages in AD development. Mechanistically, a total of 347 proteins exhibited significant differences in intensity after monocyte/macrophage depletion according to quantitative mass spectrometry. Specifically, increased matrix metalloprotein-9 (MMP-9) level in AD may be of concern due to its functions in vascular remodeling. The infiltration of macrophages considerably up-regulated MMP-9, and MMP-9 co-localized with macrophages at the tearing area of aorta. SIGNIFICANCE: Macrophages infiltrated into the tear sites of the aortic wall, regulated extracellular remodeling pathway, functioned as initiators to switch on the occurrence of AD.

9.
BMC Gastroenterol ; 19(1): 180, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711420

RESUMO

BACKGROUND: A validated histopathological tool to precisely evaluate bowel fibrosis in patients with Crohn's disease is lacking. We attempted to establish a new index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis. METHODS: We analyzed the histopathological data of 31 patients with Crohn's disease strictures undergoing surgical resection. The most representative sections of resected strictured segments were stained with Masson trichrome to manifest bowel fibrosis. The collagen area fraction and histological fibrosis score were simultaneously calculated for the same section to evaluate the severity of bowel fibrosis. RESULTS: Collagen area fraction strongly correlated with histological fibrosis scores (r = 0.733, P < 0.001). It showed a stronger correlation (r = 0.561, P < 0.001) with the degree of bowel strictures than the histological fibrosis score did (r = 0.468, P < 0.001). It was also shown to be more accurate for diagnosing Crohn's disease strictures (area under the receiver operating characteristic curve = 0.815, P < 0.001) compared with the histological fibrosis score (area under the curve = 0.771, P < 0.001). High repeatability was observed for the collagen area fraction, with an intraclass correlation coefficient of 0.915 (P < 0.001). CONCLUSIONS: Collagen area fraction is a simple and reliable index to quantify the severity of bowel fibrosis in patients with Crohn's disease-associated fibrostenosis.

10.
Neurosci Lett ; : 134618, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711978

RESUMO

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders, and studies have shown BDNF aberrations in major psychiatric diseases including schizophrenia (SCZ) and major depressive disorder (MDD). However, data from clinical studies were inconsistent. In this study, we recruited 34 patients with MDD, 77 patients with SCZ and 65 healthy control (HC) subjects to clarify the circulating BDNF levels in MDD and SCZ patients, and to assess whether serum BDNF levels were associated with the disease severity. Our results showed that serum BDNF levels were significantly decreased in the patients with SCZ (Mean difference = -4.517, 95%CI of difference = -7.854 to -1.180, p < 0.01) and MDD (Mean difference = -5.699, 95%CI of difference = -9.892 to -1.506, p < 0.01) when compared with HC subjects. Sub-group analyses suggested that BDNF levels were significantly reduced in the female SCZ (Mean difference = -5.700, 95%CI of difference = -10.21 to -1.189, p < 0.01) and MDD (Mean difference = -5.840, 95%CI of difference = -10.66 to -1.019, p < 0.05) patients, but not in male patients. Further analyses indicated that serum BDNF levels were not correlated with disease severity of MDD and SCZ. In addition, the transcriptional expression of TrkB was significantly down-regulated in the blood of MDD patients, but not in SCZ patients. However, there was no significant correlation between BDNF concentrations and TrkB mRNA levels. Taken together, our results revealed differential changes of BDNF-TrkB signaling in MDD and SCZ patients, therefore contributed to a better understanding of MDD and SCZ pathophysiology.

11.
Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756484

RESUMO

In this study, an endophytic actinobacterium Glutamicibacter halophytocola KLBMP 5180, was investigated for the production and antioxidant activity of exopolysaccharides (EPSs). First, the suitable fermentation time, temperature, inoculation volume, pH value, and the carbon and nitrogen sources for EPSs production were obtained using the one variable at a time method (OVAT). Then, a central composition design was used for fermentation conditions optimization to obtain the maximum EPS yield. The optimal medium and condition were as follows: 100 mL broth in 250 mL Erlenmeyer flasks, including 3.65 g/L maltose, 9.88 g/L malt extract, 3.40 g/L yeast extract, 1.41 g/L MnCl2, pH 7.5, culture temperature 28 °C, and 200 rpm for 7 days, which increased the yield of EPSs to 2.89 g/L. Two purified EPSs, 5180EPS-1 (MW 58.9 kDa) and 5180EPS-2 (10.5 kDa), comprising rhamnose, galacturonic acid, glucose, glucuronic acid, xylose, and arabinose, were obtained for chemical analysis and antioxidant evaluation. The scavenging ability and reducing power of the superoxide anion and hydroxyl radicals demonstrated the moderate in vitro antioxidant activities of the two EPSs, thus indicating their potential to be a new source of natural antioxidants. However, further structure elucidation and functional studies need to be continued.

12.
Infect Genet Evol ; 78: 104116, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730824

RESUMO

Porcine circovirus type 3 (PCV3) is a newly identified virus, which is associated with PDNS-like clinical signs, reproductive failure, cardiac and multiorgan inflammation. However, the genotype of PCV3 is still controversial. Here, we reconstructed the phylogenies of 194 complete coding sequences of PCV3 using five different phylogenetic methods. The results showed five trees reconstructed using different methods displayed similar phylogenies, indicating genotyping based on complete coding sequences of PCV3 is stable and accurate.

13.
Cell Death Dis ; 10(12): 875, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748541

RESUMO

Efficient repair of injured epithelium by airway progenitor cells could prevent acute inflammation from progressing into chronic phase in lung. Here, we used small molecules, genetic loss-of-function, organoid cultures, and in vivo lung-injury models to show that autophagy is essential for maintaining the pool of airway stem-like vClub cells by promoting their proliferation during ovalbumin-induced acute inflammation. Mechanistically, impaired autophagy disrupted glucose uptake in vClub progenitor cells, and either reduced accessibility to glucose or partial inhibition of glycolysis promoted the proliferative capacity of vClub progenitor cells and their daughter Club cells. However, glucose deprivation or glycolysis blockade abrogated the proliferative capacity of airway vClub cells and Club cells but promoted ciliated and goblet cell differentiation. Deficiency of glucose transporter-1 suppressed the proliferative capacity of airway progenitor cells after ovalbumin challenge. These findings suggested that autophagy and glucose metabolism are essential for the maintenance of airway epithelium at steady state and during allergic inflammation.

14.
ChemMedChem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31765517

RESUMO

Nanomedicine recently emerge as a novel strategy to improve the performance of radiotherapy. Here we report the first application of an intrinsic radioenhancer, nanoscale metal-organic frameworks (nanoMOFs), loaded with an anticancer drug (Gemcitabine-monophosphate, Gem-MP), a highly effective radiosensitizer for cancer treatment. Iron trimesate nanoMOFs possess a regular porous structure with oxocentered Fe trimers separated by distances of around 5 Š(trimesate linkers). This peculiar configuration is favorable to diffuse in surrounding water the electrons emitted from nanoMOFs due to activation by γ radiation. The hydroxyl radicals generated by electron water-induced radiolysis lead to nanoscale damages. Finally, non-toxic nanoMOFs are shown to efficiently improve γ-ray efficacy for cancer cells eradication. On top of this effect, nanoMOFs act as "Trojan horses" significantly penetrating inside cancer cells, carrying their Gem-MP cargo to interfere with DNA repair. By displaying different mechanisms of action, both nanoMOFs and incorporated Gem-MP synergistically contribute to improve radiation efficacy. The radiation enhancement factor of Gem-MP loaded nanoMOFs reaches 1.8, which is to the best of our knowledge, the highest value ever reported. These results pave the way towards the design of engineered nanoparticles in which each component synergistically plays a role in cancer treatment by radiotherapy.

15.
Dalton Trans ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746879

RESUMO

Rechargeable Mg batteries are considered as low-cost and reliable candidates for efficient energy storage, but their development is blocked by the lack of suitable cathode materials. In this work, Sb2Se3 nanowires and Bi2Se3 nanosheets are fabricated by facile one-step hydrothermal methods and their Mg-storage performances are systematically investigated. The results show that the Bi2Se3 nanosheets with stable hierarchical 2D structure exhibit a better performance. Because of its thin nanosheet structure, Bi2Se3 provides a high Mg-storage capacity of 144 mA h g-1 and a remarkable rate capability with 65 mA h g-1 delivered at 1000 mA g-1. Bi2Se3 also exhibits an outstanding cyclability over 350 cycles owing to its hierarchical structure. Furthermore, this study reveals that the electrochemical charge/discharge cycling is a typical conversion reaction occurring between Bi3+ and metallic Bi0. Kinetic investigation suggests that the high performance of Bi2Se3 is attributed to both its intrinsic nature and its thin nanosheet structure facilitating solid-state Mg2+ diffusion. The present work highlights the selection principle of conversion cathodes for rechargeable Mg batteries, namely matching a soft anion with a quasi-soft metal cation. Moreover, the facile synthesis approach is also used for low-dimensional main-group VI metal chalcogenides to improve the Mg-storage performance.

17.
J Asian Nat Prod Res ; : 1-9, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680547

RESUMO

Phytochemical investigation on the rhizomes of Matteuccia intermedia C.Chr. led to the isolation of three new compounds, named matteuinterins A-C (1-3), together with seven known compounds (4-10). Their structures were elucidated by extensive NMR analyses and chemical derivatization. Compounds 5-10 were evaluated for their anti-inflammatory activities on PGE2 release in LPS-stimulated RAW 264.7 murine macrophages. Compounds 5 and 10 exhibited inhibitory effect on PGE2 production in LPS-activated murine macrophages with IC50 values of 17.8 ± 1.5 and 30.3 ± 2.1 µM, respectively.

18.
Physiol Genomics ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682178

RESUMO

Long non-coding RNAs have been implicated in the development and progression of atherosclerosis. However, the expression and mechanism of action of lncRNAs in atherosclerosis are still unclear. We implemented microarray analysis in human advanced atherosclerotic plaques and normal arterial intimae to detect the lncRNA and mRNA expression profile. Gene Ontology functional enrichment and pathway analyses were applied to explore the potential functions and pathways involved in the pathogenesis of atherosclerosis. A total of 236 lncRNAs and 488 mRNAs were selected for further Ingenuity Pathway Analysis. Moreover, qRT-PCR tests of most selected lncRNAs and mRNAs with high fold changes were consistent with the microarray data. We also performed ELISA to investigate the corresponding proteins levels of selected genes and showed that serum levels of SPP1, CD36, ATP6V0D2, CHI3L1, MYH11 and BDNF were differentially expressed in patients with coronary heart disease compared with healthy subjects.These proteins correlated with some biochemical parameters used in the diagnosis of cardiovascular diseases. Furthermore, receiver operating characteristic analysis showed a favorable diagnostic performance.The microarray profiling analysis and validation of differentially-expressed lncRNAs and mRNAs in atherosclerosis not only provide new insights into the pathogenesis of this disease, but may also reveal new biomarkers for its diagnosis and treatment.

19.
New Phytol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31667846

RESUMO

Basic helix-loop-helix (bHLH) proteins are involved in transcriptional networks controlling a number of biological processes in plants. However, little is known on the roles of bHLH proteins in cotton fiber development so far. Here, we show that a cotton bHLH protein (GhFP1) positively regulates fiber elongation. GhFP1 transgenic cotton and Arabidopsis plants were generated to study how GhFP1 regulates fiber cell elongation. Fiber length of the transgenic cotton overexpressing GhFP1 was significantly longer than that of wild type, whereas suppression of GhFP1 expression hindered fiber elongation. Furthermore, overexpression of GhFP1 in Arabidopsis promoted trichome development. Expressions of the brassinosteroid (BR)-related genes were remarkably up-regulated in fibers of GhFP1 overexpression cotton, but down-regulated in GhFP1-silenced fibers. BR content in the transgenic fibers was significantly altered, relative to that in wild type. Moreover, GhFP1 protein could directly bind to the promoters of GhDWF4 and GhCPD to activate expressions of these BR-related genes. Thus, our data suggest that GhFP1 as a positive regulator participates in controlling fiber elongation by activating BR biosynthesis and signaling. Additionally, homodimerization of GhFP1 may be essential for its function, and interaction between GhFP1 and other cotton bHLH proteins may interfere with its DNA-binding activity.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31669564

RESUMO

PURPOSE: To compare toxicity and biochemical control in post-prostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiotherapy. METHODS: Patients who had stage pT3-4, positive surgical margins, or rising PSA ≥ 0.2 ng/mL following radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these two cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic (HT) toxicities between these two cohorts. bPFS was estimated by the Kaplan-Meier method and toxicities were compared using the χ2 test. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range: 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs. 82.6%; P = 0.299). However, in patients with a higher Gleason score (GS; 8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs. 55.7%; P = 0.049). Toxicity analysis showed no difference in ≥2 acute or late GI or GU toxicities between these two cohorts. A total of 48 patients were scored as urinary incontinence before RT, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, while only 9 (18.8%) patients reported worsening. There was no difference between the two cohorts in urinary incontinence either at baseline or at 1-year follow-up. CONCLUSION: Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities, and did not increase urinary incontinence.

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