Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Medicine (Baltimore) ; 99(1): e18530, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895788

RESUMO

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14-1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.


Assuntos
Neoplasias Colorretais/epidemiologia , Dermatite Atópica/complicações , Adulto , Neoplasias Colorretais/etiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
2.
Sleep Med ; 66: 15-20, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-31785565

RESUMO

BACKGROUND: Epidemiological studies on the obstructive sleep apnea (OSA) and cancer relationship in humans are inconsistent. Furthermore, there are limited prospective studies on the association between OSA and the risk of colorectal cancer (CRC). This retrospective cohort study examined the longitudinal relationship between OSA and CRC in a nationwide population-based cohort. METHODS: We identified 4180 individuals newly diagnosed with OSA (the exposed cohort) and randomly selected 16,720 age- and sex-matched subjects without OSA (the nonexposed cohort) between 2000 and 2008 from Taiwan's National Health Insurance Research Database (NHIRD). The Kaplan-Meier method was used for calculating the cumulative incidence of CRC in each cohort. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and the accompanying 95% confidence intervals (CIs) for the association between OSA and CRC. RESULTS: After adjusting for potential confounders, patients with OSA were associated with a significantly higher risk of CRC than those without OSA (adjusted HR, 1.80; 95% CI, 1.28-2.52). The cumulative incidence of CRC was significantly higher in the OSA cohort than in the comparison cohort (log-rank test, p < 0.001). Furthermore, the association between OSA and CRC appeared to be enhanced with increasing frequency of OSA medical visits (adjusted HR [95% CI] was 1.61 [0.97-2.66] and 1.86 [1.26-2.75] for one visit and two or more visits, respectively). CONCLUSION: This population-based cohort study demonstrated that OSA was associated with an increased risk of CRC. Further large-scale prospective studies are needed to confirm our results.

3.
Sci Rep ; 9(1): 19283, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848368

RESUMO

Our study aims to estimate the incidence of metachronous second primary lung cancer(SPLC) in initial primary lung cancer(IPLC) survivors and to determine whether radiotherapy affects the risk of metachronous SPLC in the first five years after the diagnosis of lung cancer. Incidence data of IPLC individuals who survived ≥2 years were obtained from SEER-18 database in 2004-2007. Joinpoint regression analysis and competing risk analysis were used to calculate the incidence of metachronous SPLC. Propensity score matching and decision analysis were available to estimate the effect of radiotherapy on metachronous SPLC. 264 of 11657 IPLC survivors with radiotherapy and 1090 of 24499 IPLC survivors without radiotherapy developed metachronous SPLC during 5-year follow-up, respectively. In joinpoint regression analysis, the 5-year incidence of metachronous SPLC in the radiotherapy group was lower than that in the nonradiotherapy group(2385 per 100,000 vs 4748 per 100,000, HR = 0.43,95% CI:0.39-0.47). Competing risk analysis showed that the survivors with radiotherapy were associated with the lower 5 year incidence of metachronous SPLC compared with those without radiotherapy(2.28% vs 4.47%, HR = 0.49,95% CI:0.43-0.57). Through propensity score matching, 4077 pairs of survivors were available to further study that radiotherapy potentially decreased the risk of developing metachronous SPLC with the adjustment of various factors(2.5% vs 3.3%, HR = 0.72, 95% CI:0.55-0.96). Decision analysis suggested that radiotherapy was a negative independent risk factor of metachronous SPLC with clinical net benefit in a range of risk thresholds (2% to 5%). Survivors of IPLC with radiotherapy likely had a low risk of metachronous SPLC during the first five years follow-up, especially non-small cell lung cancer.

4.
BMC Cancer ; 19(1): 1120, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733644

RESUMO

BACKGROUND: Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort. METHODS: We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan's National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan-Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients. RESULTS: The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P < 0.001). After adjusting for potential confounders, the exposed cohort exhibited a significantly increased risk of CRC compared with the non-exposed cohort (adjusted HR, 1.34; 95% CI, 1.11-1.62). CONCLUSIONS: Hemodialysis patients undergoing KT have a significantly higher risk of CRC than those not undergoing KT. Cancer should continue to be a primary focus of prevention during KT.

5.
EBioMedicine ; 43: 270-281, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982765

RESUMO

BACKGROUND: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. METHODS: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR. Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. FINDINGS: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. INTERPRETATION: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. FUND: NCKU Hospital, Taiwan, Ministry of Science and Technology, Taiwan.


Assuntos
Autofagia/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
6.
7.
Drug Des Devel Ther ; 13: 405-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774306

RESUMO

Background: Previous clinical studies reported inconsistent results on the associations of statins with the mortality and survival of lung cancer patients. This review and meta-analysis summarized the impact of statins on mortality and survival of lung cancer patients. Materials and methods: Eligible papers of this meta-analysis were searched by using PubMed, EMBASE, and Cochrane until July 2017. Primary end points were the mortality (all-cause mortality and cancer-specific mortality) and survival (progression-free survival and overall survival) of patients with statin use. Secondary end points were overall response rate and safety. The random-effects model was used to calculate pooled HRs and 95% CIs. Results: Seventeen studies involving 98,445 patients were included in the meta-analysis. In observational studies, the pooled HR indicated that statins potentially decreased the cancer-specific mortality and promoted the overall survival of lung cancer patients. Statins showed an association with decreased all-cause mortality in cohort studies (HR =0.77, 95% CI: 0.59-0.99), but not in case-control studies (HR =0.75, 95% CI: 0.50-1.10). However, statin use showed no impact on mortality and overall survival in randomized controlled trials. Meanwhile, this meta-analysis indicated that statin use did not affect the progression-free survival of lung cancer patients in observational studies and randomized controlled trials. In addition, statins potentially enhanced the effects of tyrosine kinase inhibitors (HR=0.86, 95% CI: 0.76-0.98) and chemotherapy (HR=0.86, 95% CI: 0.81-0.91) on the overall survival of patients with non-small-cell lung cancer, but did not increase overall response rate and toxicity. Conclusion: Statins were potentially associated with the decreasing risk of mortality and the improvement of overall survival in observational studies but not in randomized controlled trials.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Estudos Observacionais como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
8.
APMIS ; 127(4): 170-180, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803053

RESUMO

The objective of this study was to examine the expression level of cytochrome P450 4B1 (CYP4B1) protein and its clinical significance in specimens from patients with urothelial carcinomas (UC) including upper tract urothelial carcinoma (UTUC, n = 340) and urinary bladder urothelial carcinoma (UBUC, n = 295). Data mining on public domains identified five potential candidate transcripts which were downregulated in advanced UBUCs, indicating that it might implicate in UC progression. Immunohistochemistry was performed to analyze the CYP4B1 protein levels on 635 tissues from UC patients retrospectively. Immunoexpression of CYP4B1 was further estimated using the H-score method. Correlations between CYP4B1 H-score and important clinicopathological factors, as well as the significance of CYP4B1 expression level for disease-specific and metastasis-free survivals were evaluated. In UTUCs and UBUCs, 118 (34.7%) and 92 (31.2%) patients, respectively, were identified to be of CYP4B1 downregulation. The CYP4B1 expression level was found to be associated with several clinicopathological factors and patient survivals. Downregulation of CYP4B1 protein was correlated to advanced primary tumor (p < 0.001), nodal metastasis (p < 0.001), high histological grade (p = 0.001), vascular invasion (p < 0.001), perineural invasion (p = 0.017) and mitotic rate (p = 0.036) in UTUCs and/or UBUCs. Low CYP4B1 protein level independently predicted inferior disease-specific (p = 0.009; p < 0.001) and metastasis-free (p = 0.035; p < 0.001) survivals in UTUC and UBUC patients. Our findings showed that downregulation of CYP4B1 protein level is an independent unfavorable prognosticator. Loss of the CYP4B1 gene expression may play an important role in UC progression.


Assuntos
Hidrocarboneto de Aril Hidroxilases/análise , Carcinoma/diagnóstico , Carcinoma/patologia , Regulação para Baixo , Sistema Urinário/patologia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
9.
Oncol Lett ; 17(2): 1551-1558, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675212

RESUMO

The aim of the present study was to investigate the prognostic value of cytoplasmic (-C) and nuclear epidermal growth factor receptor (EGFR-N) expression in rectal cancer patients following neoadjuvant concurrent chemoradiotherapy (CCRT). A total of 172 newly diagnosed rectal cancer patients post-neoadjuvant CCRT and curative surgery, treated between January 1998 to December 2008, were included. Pathological tissues used for evaluation were biopsy specimens obtained prior to CCRT, and specimens collected at surgery. EGFR expression in the nucleus and cytoplasm was assessed by immunohistochemistry tests. An intensity of 3+ EGFR reactivity in the cytoplasm (and/or membrane) of tumor cells was defined as overexpression of EGFR-C. The cutoff percentage of immunoreactive tumor cells for EGFR-N overexpression was 50%. Expression levels of EGFR-C and EGFR-N were further analyzed by clinicopathological features for 5-year survival disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). The results revealed that 20.9 and 23.3% of the cohort had high EGFR-N and EGFR-C expression, respectively. EGFR-N overexpression was significantly associated with advanced pre-treatment tumor stage (T3 and 4; P=0.017) and post-treatment tumor stage (T3 and 4; P<0.001). In univariate analysis, EGFR-N overexpression was significantly associated with poorer DSS (P=0.0005), MeFS (P=0.0182), and LRFS (P=0.0014). Furthermore, it remained an independent prognosticator of worse DSS [P=0.007, hazard ratio (HR)=2.755] and LRFS (P=0.0164, HR=3.026) in multivariate analysis. Overexpression of EGFR-N, and not EGFR-C, may help identify rectal cancer patients who have an increased risk of local recurrence and poor survival following neoadjuvant CCRT.

10.
Urol Oncol ; 37(5): 299.e7-299.e18, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660494

RESUMO

BACKGROUND: Metabolic adaptation in cancer cells is important for cancer cell survival. Alternation in cellular metabolism getting more energy to support cell proliferation played a critical role in disease progression. We initially analyzed the public transcriptome of urothelial carcinoma in Gene Expression Omnibus database (GSE31684) with particular focus on genes associated with carbohydrate metabolism, and found that Chitinase 3-like-1 (CHI3L1) was a significantly up-regulated gene associated with advanced disease status. This study was aimed to evaluate the expression and prognostic significance of CHI3L1 in upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC). MATERIALS AND METHODS: We performed immunohistochemical study to evaluate CHI3L1 expression in 2 well-defined cohorts of urothelial carcinoma, including UTUC (n = 340) and UBUC (n = 295). CHI3L1 expression level was determined by H-score method. The associations between CHI3L1 expression and clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MFS) were analyzed. RESULTS: High expression of CHI3L1 was significantly associated with adverse clinicopathological features in UTUC or UBUC, including advanced tumor status (pT), nodal metastasis, high histological grade, vascular invasion, perineural invasion, and high mitotic activity (all P < 0.05). Kaplan-Meier survival analysis revealed that patients with high CHI3L1 expression had shorter DSS and MFS in both UTUC and UBUC (all P < 0.05). In multivariate survival analyses, high expression of CHI3L1 acted as an independent prognostic factor for worse DSS (P < 0.001 in UTUC and P = 0.036 in UBUC) and MFS (P = 0.002 in UTUC and P = 0.003 in UBUC) in both UTUC and UBUC groups. CONCLUSIONS: High expression of CHI3L1 was significantly associated with aggressive clinicopathological features and acted as an independent prognostic factor for worse outcome in urothelial carcinoma.

11.
Med Sci Monit ; 24: 8096-8104, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30417859

RESUMO

BACKGROUND Several clinical conditions can cause hepatic ischemia/reperfusion (I/R) injury. This study aimed to determine the mechanism of the protective effect of hyperbaric oxygen preconditioning (HBO2P) on hepatic ischemia/reperfusion (I/R) injury in a rat model, and to investigate the effects on HBO2P and I/R injury of blocking HSP70 using antibody (Ab) pretreatment. MATERIAL AND METHODS Male Sprague-Dawley rats underwent HBO2P for 60 min at 2.0 atmosphere absolute (ATA) pressure for five consecutive days before surgical hepatic I/R injury, performed by clamping the portal vein and hepatic lobe. Four groups studied included: the non-HBO2P+ non-I/R group, which underwent sham surgery (N=10); the non-HBO2P + I/R group (N=10); the HBO2P + I/R group (N=10); and the HBO2P + HSP70-Ab + I/R group (N=10) received one dose of HSP70 antibody one day before hepatic I/R injury. Serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) and myeloperoxidase (MPO) were measured biochemically. Rat liver tissues were examined histologically. RESULTS In rats with hepatic I/R injury without HSP70 antibody pre-treatment, HBO2P significantly reduced hepatic injury and levels of LDH, AST, ALT, TNF-α, IL-6, MDA, and MPO levels; in comparison, the group pre-treated with an antibody to inhibit HSP70 (the HBO2P + HSP70-Ab + I/R group) showed significant reversal of the beneficial effects of HBO2P on hepatic I/R injury (p<0.05). CONCLUSIONS In a rat model of hepatic I/R injury with HBO2P, HSP70 reduced hepatic inflammatory and oxidative damage.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Oxigenação Hiperbárica/métodos , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Imuno-Histoquímica , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Hepatopatias/prevenção & controle , Masculino , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/sangue
12.
Chin J Physiol ; 61(5): 266-279, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30384400

RESUMO

Regulated upon activation, normal T cell expressed, and secreted (RANTES), also known as chemokine ligand 5 (CCL5), has been reported to facilitate macrophage migration, which plays a crucial role in tissue inflammation. The aim of this study is to investigate the characteristics and underlying mechanism of RANTES on macrophage chemotaxis under physiological and pathological conditions. The study was conducted on macrophage RAW264.7 cell and bone marrow-derived macrophages (BMDM) isolated from CCL receptor 5 (CCR5) knockout mice. The macrophage migration and glucose uptake was assessed in time and dose dependent manners. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to characterize mRNA and protein level related to the underlying mechanism. The present result showed that the maraviroc, a selective CCR5 inhibitor, dose-dependently suppressed RANTES-induced rapid increases in glucose uptake and cell migration in RAW264.7 cells. Similar effects were observed in the BMDM isolated from CCR5 knockout mice compared with wild type control. RANTES treatment promptly enhanced membrane glucose transporter 1 (GLUT1) expression, glucose uptake as well as phosphorylation of AKT on Thr308, Ser473 within min and has prolonged effect on phosphorylation of AMP-activated protein kinase (AMPK) on Thr172, which were abrogated by maraviroc, CCR5 siRNA or phospholipase C (PLC) inhibitor in RAW264.7 cells. Inhibition of PI3K and AMPK by LY294002 and Compound C significantly suppress RANTES-stimulated macrophage glucose uptake and migration, respectively. RANTES has biphasic effect on activating PLC signaling including prompt action on PI3K/AKT phosphorylation and prolong action on AMPK phosphorylation via CCR5 which leads to increased GLUT1-mediated glucose uptake and macrophage migration under physiopathological states.


Assuntos
Quimiocina CCL5 , Macrófagos , Animais , Quimiotaxia , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores CCR5 , Transdução de Sinais , Linfócitos T , Fosfolipases Tipo C
13.
Am J Cancer Res ; 8(9): 1812-1822, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323973

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, which is characterized by its high invasiveness, rapid progression, and profound resistance to therapy. Gemcitabine is the first-line treatment option for pancreatic cancer patients, but the overall survival is quite low. Therefore, it is an urgent issue to identify new molecules for improved therapies, with better efficacy and less toxicity. Our previous data indicated that Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) functions as a therapeutic target to override GEM resistance and promote metastasis in the treatment of pancreatic cancer. Here, we screened a small-molecule library of 143 protein kinase inhibitors, to verify cytotoxicity of different inhibitors in EHMT2-depleted cells. We determined that the EHMT2 plays a promising modulating role for targeted PI3K/mTOR inhibition. Our data revealed that EHMT2 down-regulates p27 expression, and this contributes to tumor growth. The depletion of EHMT2, ectopic expression of methyltransferase-dead EHMT2, or treatment with an EHMT2 inhibitor decreases H3K9 methylation of p27 promoter and induces G1 arrest in PANC-1 pancreatic cancer cells. Consistent with these findings, in vivo tumor xenograft models, primary tumors, and the Oncomine database utilizing bioinformatics approaches, also show a negative correlation between EHMT2 and p27. We further demonstrated that low EHMT2 elevated BEZ235 sensitivity through up-regulation of p27 in PDAC cells; high levels of SKP2 decrease BEZ235 responsiveness in PDAC cells. Altogether, our results suggest the EHMT2-p27 axis as a potential marker to modulate cell response to dual PI3K/mTOR inhibition, which might provide a strategy in personalized therapeutics for PDAC patients.

14.
BMC Nephrol ; 19(1): 234, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223782

RESUMO

BACKGROUND: Kidney transplantation is the preferred renal replacement therapy for patients with end-stage renal disease, but the waiting list for kidneys continues to grow because of a shortage of donor organs. The reuse of transplanted kidneys would seem to be a good approach to expand the pool of available organs. Here, we describe the reuse of a kidney 9 years after the initial transplantation. At 4-year follow-up, the second recipient is showing good renal function. CASE PRESENTATION: In 2005, a kidney was transplanted from a 40-year-old man, who suffered brain death due to an intracranial hemorrhage, into a 45-year-old man. Nine years later, the recipient suffered a ruptured cerebral aneurysm, resulting in brain death. The kidney was re-transplanted into a 40-year-old man with diabetic nephropathy who had received hemodialysis for 5 years. During 4 years of follow-up, the graft has functioned well. CONCLUSIONS: This case demonstrates the successful regrafting of a transplanted kidney. We believe this is the longest period for reuse of kidney after initial transplantation. The outcome suggests that a well-functioning transplanted kidney can be reused years after transplantation.


Assuntos
Sobrevivência de Enxerto/fisiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Transplantados , Transplantes/fisiologia , Transplantes/transplante , Adulto , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
15.
Int J Med Sci ; 15(11): 1171-1178, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123054

RESUMO

Background: Concurrent chemoradiotherapy (CCRT) has now become the standard of treatments for advanced rectal cancer before surgery. To search the biological molecules with prognostic and therapeutic potential of CCRT could be beneficial for these patients. Recently, aberrant expression of chloride channels has been linked to radio-resistance in glioblastoma; however, its clinical implication has not been well-studied in rectal cancers. Therefore, we examined the clinical significance of targetable drivers associated with chloride channel activity in patients with rectal cancer receiving CCRT. Methods: After datamining from a published transcriptome of rectal cancers, upregulation of CLCA1 gene was recognized to be significantly correlated with non-responders of CCRT. In validation cohort of rectal cancers, the expression levels of CLCA1 were accessed by using immunohistochemistry assays in 172 tumor specimens that were obtained before any treatment. Expression levels of CLCA1 were statistically analyzed with principal clinicopathological features and survival outcomes in this substantial cohort. Results: In validation cohort, high expression of CLCA1 was significantly associated with higher pre-treatment tumor nodal stages (P=0.032), vascular invasion (P=0.028), and inferior tumor regression grade (P=0.042). In survival evaluations, high expression of CLCA1 was significantly correlated with worse local recurrence-free survival (LRFS; P=0.0012), metastasis-free survival (MeFS; P =0.0114), and disease-specific survival (DSS; P=0.0041). Furthermore, high expression of CLCA1 remained an independent prognosticator of shorter LRFS (P=0.029, hazard ratio=2.555), MeFS (P=0.044, hazard ratio=2.125) and DSS (P=0.044, hazard ratio=2.172). Conclusions: High expression of CLCA1 is significantly associated with poor therapeutic response and survival outcomes in rectal cancer patients with CCRT treatment before surgery. With the development of specific inhibitors, our findings indicate not only prognostic but also therapeutic potential of CLCA1 in rectal cancers.


Assuntos
Quimiorradioterapia , Canais de Cloreto/metabolismo , Neoplasias Retais/terapia , Idoso , Biomarcadores Tumorais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Prognóstico , Neoplasias Retais/metabolismo , Regulação para Cima
16.
Clin Sci (Lond) ; 132(14): 1581-1596, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-29773671

RESUMO

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Ciclo-Oxigenase 2/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Antígenos de Diferenciação de Linfócitos B/genética , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina/genética , Ativação de Macrófagos , Fatores Inibidores da Migração de Macrófagos/genética , Macrófagos/classificação , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Interferência de RNA , Células THP-1
17.
World Neurosurg ; 115: e299-e304, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29660548

RESUMO

OBJECTIVE: Dealing with the empty space after organ removal for transplantation has not been investigated. METHODS: From January 28, 2005, to November 21, 2017, 111 organ donors were enrolled in this study. They were divided into 3 groups: no replacement, replaced with paper printed with organ graphics, or replaced with 3-dimensional (3D) printed simulated organs. The organs were removed at different periods. The donor's age, gender, etiology of admission, characteristics, clinical pictures, time interval between admission and date of donation, and time interval between donor coordinator consultations were evaluated. RESULTS: A total of 82 men and 29 women with mean age of 43 ± 15.1 years were enrolled. Overall, 329 organs and 126 corneas were transplanted. The major causes of brain death were traumatic brain injury (44.1%) and cerebrovascular disease (32.4%). Twelve donors initially presented with out-of-hospital cardiac arrest. Ten patients with solid cancers and 3 with septic shock donated both of their corneas. The mean time interval between donor coordinator and social worker consultation to organ donation was 3 (2-5 days) (median [interquartile range]). Periods I and II averaged 7-8 donors per year. Fourteen donors and 41 organs were replaced with 3D-printed simulated organs at the families' request in 1 year. CONCLUSIONS: This is the first study to provide a replacement method dealing with the empty space after organ removal. We used 3D-printed simulated organs in addition to providing grief assistance and spiritual support. It also has the potential effect of increasing the organ donation rate.


Assuntos
Transplante de Órgãos/métodos , Impressão Tridimensional , Centros de Atenção Terciária , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/tendências , Impressão Tridimensional/tendências , Estudos Retrospectivos , Centros de Atenção Terciária/tendências
18.
Int J Colorectal Dis ; 33(3): 349-352, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29397431

RESUMO

BACKGROUND: Periodontal disease (PD) and colorectal cancer (CRC) were associated with chronic inflammation. This retrospective cohort study examined the association between PD severity and CRC in a large-scale, population-based Chinese cohort. METHODS: A total of approximately 106,487 individuals with newly diagnosed PD and 106,487 age-matched and sex-matched patients without PD from 2000 to 2002 were identified from Taiwan's National Health Insurance Research Database (NHIRD). RESULTS: The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in patients with PD than in those without PD (log-rank test, P < 0.001). After adjustment for age, sex, and comorbidities, patients with PD were associated with a significantly higher risk of CRC compared with those without PD (adjusted HR = 1.64, 95% CI = 1.50-1.80). Further, the risk of CRC appeared to increase with increasing frequency of PD medical visits [adjusted HR (95% CI) was 1.78 (1.58-2.02) and 1.53 (1.35-1.74) for annual visits > 10 and < 4, respectively]. CONCLUSION: Based on our study, PD severity was associated with an increase in the risk of CRC. Further mechanistic research is needed.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Doenças Periodontais/complicações , Doenças Periodontais/patologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Fatores de Risco
19.
Int J Med Sci ; 14(13): 1327-1334, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200946

RESUMO

Background: Clinical assessment reveals that patients after surgery of cardiopulmonary bypass or coronary bypass experience postoperative cognitive dysfunction. This study aimed to investigate whether resuscitation after a hemorrhagic shock (HS) and/or mild cerebral ischemia caused by a unilateral common carotid artery occlusion (UCCAO) can cause brain injury and concomitant neurological dysfunction, and explore the potential mechanisms. Methods: Blood withdrawal (6 mL/100 g body weight) for 60 min through the right jugular vein catheter-induced an HS. Immediately after the termination of HS, we reinfused the initially shed blood volumes to restore and maintain the mean arterial blood pressure (MABP) to the original value during the 30-min resuscitation. A cooling water blanket used to induce whole body cooling for 30 min after the end of resuscitation. Results: An UCCAO caused a slight cerebral ischemia (cerebral blood flow [CBF] 70%) without hypotension (MABP 85 mmHg), systemic inflammation, multiple organs injuries, or neurological injury. An HS caused a moderate cerebral ischemia (52% of the original CBF levels), a moderate hypotension (MABP downed to 22 mmHg), systemic inflammation, and peripheral organs injuries. However, combined an UCCAO and an HS caused a severe cerebral ischemia (18% of the original CBF levels), a moderate hypotension (MABP downed to 17 mmHg), systemic inflammation, peripheral organs damage, and neurological injury, which can be attenuated by whole body cooling. Conclusions: When combined with an HS, an UCCAO is associated with ischemic neuronal injury in the ipsilateral hemisphere of adult rat brain, which can be attenuated by therapeutic hypothermia. A resuscitation from an HS regards as a reperfusion insult which may induce neurological injury in patients with an UCCAO disease.


Assuntos
Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Hipotensão/fisiopatologia , Animais , Pressão Sanguínea , Lesões Encefálicas/etiologia , Isquemia Encefálica/complicações , Ponte Cardiopulmonar/efeitos adversos , Artéria Carótida Primitiva/fisiopatologia , Artéria Carótida Primitiva/cirurgia , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/fisiopatologia , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Humanos , Hipotensão/etiologia , Complicações Pós-Operatórias , Ratos , Ressuscitação/efeitos adversos , Choque Hemorrágico/complicações , Choque Hemorrágico/fisiopatologia
20.
Cell Physiol Biochem ; 44(5): 1726-1740, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29227981

RESUMO

BACKGROUND/AIMS: In response to traumatic brain injury (TBI), activated microglia exhibit changes in their morphology from the resting ramified phenotype toward the activated hypertrophic or amoeboid phenotype. Here, we provide the first description of the mechanism underlying the neuroprotective effects of γ-secretase inhibitors on TBI outcomes in rats. METHODS: The neuroprotective effects of γ-secretase inhibitors such as LY411575 or CHF5074 on TBI-induced neurotoxicity were analysed using a neurological motor function evaluation, cerebral contusion assay, immunohistochemical staining for microglia phenotypes, lung injury score and Evans Blue dye extravasation assay of brain and lung oedema. RESULTS: Hypertrophic or amoeboid microglia accumulated in the injured cortex, the blood-brain-barrier was disrupted and neurological deficits and acute lung injury were observed 4 days after TBI in adult rats. However, a subcutaneous injection of LY411575 (5 mg/kg) or CHF5074 (30 mg/kg) immediately after TBI and once daily for 3 consecutive days post-TBI significantly attenutaed the accumulation of hypertrophic microglia in the injured brain, neurological injury, and neurogenic acute lung injury. CONCLUSION: Gamma-secretase inhibitors attenuated neurotrauma and neurogenic acute lung injury in rats by reducing the accumulation of hypertrophic microglia in the vicinity of the lesion.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Lesões Encefálicas Traumáticas/prevenção & controle , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Alanina/análogos & derivados , Alanina/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Azepinas/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/patologia , Lesões Encefálicas Traumáticas/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Córtex Cerebral/fisiopatologia , Ciclopropanos/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Flurbiprofeno/análogos & derivados , Flurbiprofeno/farmacologia , Pulmão/patologia , Masculino , Microglia/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA