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1.
Mol Oncol ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33694305

RESUMO

Screening for early-stage disease is vital for reducing colorectal cancer (CRC)-related mortality. Methylation of circulating tumor DNA has been previously used for various types of cancer screening. A novel cell-free DNA (cfDNA) methylation-based model which can improve the early detection of CRC is warranted. For our study, we collected 313 tissue and 577 plasma samples from patients with CRC, advanced adenoma (AA), non-AA and healthy controls. After quality control, 187 tissue DNA samples (91 non-malignant tissue from CRC patients, 26 AA and 70 CRC) and 489 plasma cfDNA samples were selected for targeted DNA methylation sequencing. We further developed a cfDNA methylation model based on 11 methylation biomarkers for CRC detection in the training cohort (area under curve [AUC] = 0.90 (0.85-0.94]) and verified the model in the validation cohort (AUC = 0.92 [0.88-0.96]). The cfDNA methylation model robustly detected patients pre-diagnosed with early-stage CRC (AUC = 0.90 [0.86-0.95]) or AA (AUC = 0.85 [0.78-0.91]). Here we established and validated a non-invasive cfDNA methylation model based on 11 DNA methylation biomarkers for the detection of early-stage CRC and AA. The utilization of the model in clinical practice may contribute to the early diagnosis of CRC.

2.
BMC Med ; 19(1): 18, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33504335

RESUMO

BACKGROUND: Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. METHODS: We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend = 0.03, respectively). CONCLUSIONS: The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

3.
Int J Biol Sci ; 17(1): 368-378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390856

RESUMO

Traumatic brain injury (TBI) is recognized as the disease with high morbidity and disability around world in spite of the work ongoing in neural protection. Due to heterogeneity among the patients, it's still hard to acquire satisfying achievements in clinic. Neuroinflammation, which exists since primary injury occurs, with elusive duality, appear to be of significance from recovery of injury to neurogenesis. In recent years, studied have revealed that communication in neurogenic niche is more than "cell to cell" communication, and study on NSCs represent it as central role in the progress of neural regeneration. Hence, the neuroinflammation-affecting crosstalk after TBI, and clarifying definitive role of NSCs in the course of regeneration is a promising subject for researchers, for its great potential in overcoming the frustrating status quo in clinic, promoting welfare of TBI patient.

4.
Int J Cancer ; 148(1): 57-66, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32638350

RESUMO

The influence of polyunsaturated fatty acids (PUFAs) on risk of colorectal cancer precursors remains largely unknown. We examined the associations of erythrocyte PUFAs, including n-3 and n-6 PUFAs, with risk of colorectal conventional adenomas and serrated polyps in 4517 participants from three US prospective cohorts who had provided a blood sample and undergone at least one endoscopic examination. We calculated the multivariable odds ratios (ORs) per 1 SD increment in individual PUFAs and the ratio of n-6/n-3 PUFAs. We considered P < .005 statistically significant to account for multiple testing. During a median of 20 years of follow-up, we documented 493 conventional adenomas and 316 serrated polyps. After adjusting for various CRC risk factors, no associations for PUFAs achieved the stringent statistical significance for either conventional adenomas or serrated polyps (ORs per 1 SD ranged from 0.90 to 1.14). Some associations achieved nominal significance (P < .05), including the association of dihomogammalinolenic acid (DGLA) (20:3, n-6) with lower risk of conventional adenomas (OR = 0.91; 95% confidence interval [CI] = 0.83-1.00), total n-6 PUFAs with higher risk of proximal serrated polyps (OR = 1.32; 95% CI = 1.01-1.74) and eicosadienoic acid (20:2, n-6) and DGLA with lower risk of advanced adenomas (OR = 0.83; 95% CI = 0.71-0.97 and OR = 0.84; 95% CI = 0.72-0.98, respectively). Our findings indicate that erythrocyte PUFAs in a typical American diet are unlikely to have a substantial influence on risk of colorectal cancer precursors. The subgroup associations require further confirmation.

5.
Neural Plast ; 2020: 9814978, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879625

RESUMO

It was not clear how and whether neural stem cells (NSCs) responded to toll-like receptor 2 (TLR2) in the inflammatory environment after traumatic brain injury (TBI). The current study investigated the correlation of TLR2 and NSC proliferation in the dentate gyrus (DG) using the TBI model of rats. Immunofluorescence (IF) was used to observe the expression of BrdU, nestin, and TLR2 in the DG in morphology. Proliferating cells in the DG were labelled by thymidine analog 5-bromo-2-deoxyuridine (BrdU). Three-labelled BrdU, nestin, and DAPI was used for the identification of newly generated NSCs. Western blotting and real-time polymerase chain reaction (PCR) were used to observe the expression of TLR2 from the level of protein and mRNA. We observed that BrdU+/nestin+/DAPI+ cells accounted for 84.30% ± 6.54% among BrdU+ cells; BrdU+ and nestin+ cells in the DG were also TLR2+ cells. BrdU+ cells and the expression of TLR2 (both protein and mRNA levels) both elevated immediately at 6 hours (h), 24 h, 3 days (d), and 7 d posttrauma and peaked in 3 d. Results indicated that TLR2 was expressed on proliferating cells in the DG (NSCs possibly) and there was a potential correlation between increased TLR2 and proliferated NSCs after TBI. Taken together, these findings suggested that TLR2 was involved in endogenous neurogenesis in the DG after TBI.

6.
Cell Death Dis ; 11(8): 668, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820151

RESUMO

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

7.
Diabetes Care ; 43(10): 2588-2596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32788283

RESUMO

OBJECTIVE: Coffee may protect against multiple chronic diseases, particularly type 2 diabetes, but the mechanisms remain unclear. RESEARCH DESIGN AND METHODS: Leveraging dietary and metabolomic data in two large cohorts of women (the Nurses' Health Study [NHS] and NHSII), we identified and validated plasma metabolites associated with coffee intake in 1,595 women. We then evaluated the prospective association of coffee-related metabolites with diabetes risk and the added predictivity of these metabolites for diabetes in two nested case-control studies (n = 457 case and 1,371 control subjects). RESULTS: Of 461 metabolites, 34 were identified and validated to be associated with total coffee intake, including 13 positive associations (primarily trigonelline, polyphenol metabolites, and caffeine metabolites) and 21 inverse associations (primarily triacylglycerols [TAGs] and diacylglycerols [DAGs]). These associations were generally consistent for caffeinated and decaffeinated coffee, except for caffeine and its metabolites that were only associated with caffeinated coffee intake. The three cholesteryl esters positively associated with coffee intake showed inverse associations with diabetes risk, whereas the 12 metabolites negatively associated with coffee (5 DAGs and 7 TAGs) showed positive associations with diabetes. Adding the 15 diabetes-associated metabolites to a classical risk factor-based prediction model increased the C-statistic from 0.79 (95% CI 0.76, 0.83) to 0.83 (95% CI 0.80, 0.86) (P < 0.001). Similar improvement was observed in the validation set. CONCLUSIONS: Coffee consumption is associated with widespread metabolic changes, among which lipid metabolites may be critical for the antidiabetes benefit of coffee. Coffee-related metabolites might help improve prediction of diabetes, but further validation studies are needed.

8.
Gastroenterol Rep (Oxf) ; 8(3): 167-174, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32661490

RESUMO

Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.

9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(1): 49-55, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32314724

RESUMO

Objective To explore the change of the expression of microRNA-124-3p (miR-124-3p) in injured hippocampus of rats and investigate the role of miR-124-3p in neuranagenesis after traumatic brain injury (TBI). Methods The healthy male rats were randomly divided into a sham-operated group, TBI group, miR-124-3p agomir group and miR-124-3p antagomir group. TBI models were constructed by controlled cortical injury (CCI) device for all the groups except for the sham-operated group. The miR-124-3p agomir (1 nmol) was given to the miR-124-3p agomir group and miR-124-3p antagomir (1 nmol) to the miR-124-3p antagomir group via lateral ventricular injection, and equivalent solvent was given to the sham-operated group and TBI group after injury. The injured hippocampus of rats was collected at 12 hours, 1 day, 3, 7 days after injury. The real-time PCR and Western blot analysis were used to examine the expression of miR-124-3p and Delta-like 1 (DLL1) in the injured hippocampus. Immunofluorescence histochemistry was used to examine the expression levels of 5-bromodeoxyuridine (BrdU), neuronal nuclear antigen (NeuN) and nestin in the injured hippocampus. Bioinformatics software was used to predict and dual luciferase reporter assay to validate the regulatory relationship between miR-124-3p and DLL1. Results The miR-124-3p and DLL1 expression in the TBI group were significantly higher than those in the sham-operated group; compared with the TBI group, the miR-124-3p agomir group had significantly increased expression of miR-124-3p and significantly decreased expression of DLL1 in the injured hippocampus, and miR-124-3p antagomir group had significantly decreased expression of miR-124-3p and significantly increased expression of DLL1. Compared with the sham-operated group, the BrdU+NeuN+ cells and BrdU+nestin+ cells in the hippocampus significantly increased in the TBI group at 7 days after injury. The miR-124-3p agomir treatment increased the number of the BrdU+NeuN+ cells and BrdU+nestin+ cells, while the miR-124-3p antagomir treatment decreased the number of the BrdU+NeuN+ cells and BrdU+nestin+ cells. Bioinformatics analysis confirmed that DLL1 was a target of miR-124-3p. Conclusion High expression of miR-124-3p in the trauma region promotes the proliferation and differentiation of neural stem cells by targeting and inhibiting DLL1.


Assuntos
Lesões Encefálicas Traumáticas/genética , Proteínas de Membrana/antagonistas & inibidores , MicroRNAs/genética , Células-Tronco Neurais/citologia , Receptores Notch/genética , Animais , Lesões Encefálicas Traumáticas/patologia , Diferenciação Celular , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
10.
Gastroenterology ; 159(1): 241-256.e13, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32247020

RESUMO

BACKGROUND & AIMS: The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum. METHODS: We collected data from the Nurses' Health Study, Nurses' Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum. RESULTS: We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer. CONCLUSIONS: In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.

11.
Int J Cancer ; 147(7): 1831-1844, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32150293

RESUMO

Serrated polyps (SPs) and conventional adenomas represent 2 distinct groups of colorectal premalignancy. The influence of early life adiposity on risk of these precursors remains unclear. Within the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study, we assessed body fatness during childhood using 9-level somatotype and obtained weight and body mass index (BMI) in adulthood. We used multivariable-adjusted logistic regression to examine the association of SPs and conventional adenomas with body fatness in early childhood (age 5), late childhood (age 10), early adulthood (age 18/21) and middle adulthood (baseline) and weight change during early-to-middle adulthood. During 18-20 years of follow-up, we documented 8,697 SPs and 10,219 conventional adenomas in 132,514 women; 2,403 SPs and 4,495 conventional adenomas in 29,207 men. We found a modest positive association of adiposity in early and late childhood with risk of SPs and conventional adenomas, with odds ratios ranging from 1.12 to 1.18 for comparison of extreme somatotypes groups. The associations were attenuated after adjusting for adulthood BMI but remained significant for conventional adenomas. No association with early life body fatness was found in men. Adulthood body fatness and weight change during early-to-middle adulthood showed positive relationships with SPs and conventional adenomas in both women and men, with stronger associations observed for SPs (pheterogeneity < 0.0001). Our findings indicated a potential role in development of colorectal cancer precursors of childhood body fatness in women, and early-to-middle adulthood weight gain and attained adiposity in both sexes.

12.
Gastroenterol Rep (Oxf) ; 8(1): 56-65, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32104586

RESUMO

Background: The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer. Low-dose cyclophosphamide (CTX) is widely believed to be involved in the modulation of the immune system. However, the underlying mechanism of low-dose CTX remains unknown. This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis. Methods: Thirty mice were randomly divided into five groups. After liver metastasis was established in colon-cancer models, mice in the treatment groups were injected with low-dose CTX (20 mg/kg) at different time points. Liver and spleen tissues were examined for T-cell markers via flow cytometry. Interleukin (IL)-10 and transforming growth factor (TGF)-ß1 expression levels in liver tissues were analysed by immunohistochemistry. Serum interferon (IFN)-γ and IL-10 levels were detected by enzyme-linked immunosorbent assay. An additional 20 mice were randomly allocated into two groups and the survival times were recorded. Results: The expression levels of CD4+ T cells, CD8+ T cells, and IFN-γ were down-regulated, whereas those of IL-10 and TGF-ß1 were up-regulated in liver metastasis from colon cancer in mice. Furthermore, the local and systemic microenvironments of the liver were altered, which led to reduced antitumor immune responses and subsequently liver metastasis. However, treatment with low-dose CTX reversed these effects. The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups. Conclusions: Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation in mice. CTX could be used as a drug to prevent and treat liver metastasis from colon cancer.

13.
Int J Epidemiol ; 49(1): 259-269, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31038671

RESUMO

BACKGROUND: Increasing evidence suggests that conventional adenomas (CAs) and serrated polyps (SPs) represent two distinct groups of precursor lesions for colorectal cancer (CRC). The influence of common genetic variants on risk of CAs and SPs remain largely unknown. METHODS: Among 27 426 participants within three prospective cohort studies, we created a weighted genetic risk score (GRS) based on 40 CRC-related single nucleotide polymorphisms (SNPs) identified in previous genome-wide association studies; and we examined the association of GRS (per one standard deviation increment) with risk of CAs, SPs and synchronous CAs and SPs, by multivariable logistic regression. We also analysed individual variants in the secondary analysis. RESULTS: During 18-20 years of follow-up, we documented 2952 CAs, 1585 SPs and 794 synchronous CAs and SPs. Higher GRS was associated with increased risk of CAs [odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.12-1.21] and SPs (OR = 1.09, 95% CI: 1.03-1.14), with a stronger association for CAs than SPs (Pheterogeneity=0.01). An even stronger association was found for patients with synchronous CAs and SPs (OR = 1.32), advanced CAs (OR = 1.22) and multiple CAs (OR = 1.25). Different sets of variants were associated with CAs and SPs, with a Spearman correlation coefficient of 0.02 between the ORs associating the 40 SNPs with the two lesions. After correcting for multiple testing, three variants were associated with CAs (rs3802842, rs6983267 and rs7136702) and two with SPs (rs16892766 and rs4779584). CONCLUSIONS: Common genetic variants play a potential role in the conventional and serrated pathways of CRC. Different sets of variants are identified for the two pathways, further supporting the aetiological heterogeneity of CRC.


Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Pólipos/genética , Idoso , Estudos de Coortes , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Seguimentos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Pólipos/patologia , Estudos Prospectivos , Fatores de Risco
15.
Gastroenterology ; 158(4): 852-861.e4, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31302144

RESUMO

BACKGROUND & AIMS: Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance. METHODS: We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors. RESULTS: After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38). CONCLUSIONS: These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.


Assuntos
Adenoma/cirurgia , Pólipos do Colo/cirurgia , Neoplasias Colorretais/epidemiologia , Programas de Rastreamento/estatística & dados numéricos , Lesões Pré-Cancerosas/cirurgia , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Pólipos do Colo/patologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Masculino , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Inoculação de Neoplasia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sigmoidoscopia/normas , Sigmoidoscopia/estatística & dados numéricos , Fatores de Tempo
17.
Ann Transl Med ; 7(20): 543, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807525

RESUMO

Background: Currently, reliable approaches for accurate assessment of lymph node metastases (LNM), which is an important indication of preoperative chemoradiotherapy (CRT), are not available for clinically node-negative rectal cancer patients. This study aims to identify clinical factors associated with LNM and to establish a nomogram for LNM prediction in clinically node-negative rectal cancer patients. Methods: The least absolute shrinkage and selection operator (LASSO) aggression and multivariate logistic regression analyses were applied to identify clinical factors associated with LNM. A nomogram was established to predict the probability of LNM in clinically node-negative rectal cancer patients based on the multivariate logistic regression model. Results: Six potential risk factors were selected on the basis of LASSO aggression analysis, and five of them were identified as independent risk factors for LNM based on multivariate analysis, including MRI-reported tumor location, clinical T classification, MRI-reported tumor diameter, white blood cell count (WBC), and preoperative elevated tumor markers. A nomogram consisting of the five clinical factors was established and showed good discrimination. Decision curve analysis demonstrated that the established nomogram was reliable and accurate for LNM prediction in clinically node-negative rectal cancer patients. Conclusions: A nomogram based on five clinical factors, including MRI-reported tumor location, clinical T classification, MRI-reported tumor diameter, WBC, and preoperative elevated tumor markers, are useful for assessing LNM in clinically node-negative rectal cancer patients, which is important for preoperative CRT regimens.

18.
Int J Colorectal Dis ; 34(12): 2201-2204, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31735986

RESUMO

BACKGROUND: The incidence of colorectal cancer, especially located in distal colorectum, is rising markedly in young patients. Conventional adenomas and serrated polyps have been widely recognized as precursors of colorectal cancer. AIM: To investigate the correlation of polyp feature with polyp location in patients under age 50. METHOD: Patients under age 50 who had received colonoscopy were included from 2010 to 2018. Clinical data including number, location, size, and histopathology of polyps were collected. Odd ratios and 95% confidence interval of adenomas with their location were calculated. RESULT: In total, 25,636 patients aged 18-49 were enrolled, among which 4485 patients had polyps, with polyp detection rate of 17.5%. A total of 2484 and 2387 patients had conventional adenomas and serrated polyps, respectively. 76.0% advanced adenomas and 69.5% ≥ 10-mm serrated polyps were located in the distal colorectum. The detection rate of advanced adenomas was higher in patients aged 45-49. Patients with adenomas especially advanced adenomas in the distal colorectum were more likely to have advanced adenoma in the proximal colon. CONCLUSION: Among patients under age 50, advanced adenomas and ≥ 10-mm serrated polyps were predominantly in the distal colorectum. Advanced adenomas tended to be found in patients aged 45-49. Our results might explain the rising trend of distal colorectal cancer and emphasize the necessity for colonoscopy screening among these populations.


Assuntos
Pólipos Adenomatosos/patologia , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Pólipos Adenomatosos/epidemiologia , Adolescente , Adulto , Distribuição por Idade , China/epidemiologia , Pólipos do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
19.
Gastroenterol Rep (Oxf) ; 7(4): 283-290, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31413836

RESUMO

Background and objective: Neoadjuvant chemoradiation therapy (NCRT) followed by radical resection has been a common practice for patients with locally advanced rectal cancer. This study aimed to analyse the association of tumor differentiation and prognosis in rectal-cancer patients undergoing NCRT. Methods: Patients with locally advanced, non-mucinous rectal cancer who underwent NCRT followed by radical resection between 2007 and 2017 were identified from an electronic health record system at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Multivariable logistic regression and multivariate Cox regression were performed to analyse the association of response to NCRT and survival with clinicopathological characteristics of all these patients. Results: We identified 325 patients (241 males and 84 females; mean age, 54.4 ± 11.2 years) who underwent NCRT followed by radical resection, including 26 (8.0%) with poorly-differentiated rectal cancer, 182 (56.0%) with moderately-differentiated cancer and 117 (36.0%) with well differentiated cancer. Propensity score matching analysis and multivariable logistic regression analysis results showed that tumor differentiation was significantly associated with response to NCRT. In the poor differentiation and non-poor differentiation groups, the 3-year overall survival (OS) rates were 74.6 and 93.5%, respectively, whereas the 3-year local recurrence rates were 18.6 and 3.7%, respectively. Multivariable Cox regression analyses revealed that poor differentiation was an independent risk factor for local recurrence and OS. Conclusions: Among the patients with locally advanced, non-mucinous rectal cancer, the patients with poorly-differentiated cancer who underwent NCRT had a worse response to NCRT and poorer prognosis than those with moderately- and well-differentiated diseases.

20.
Neurochem Res ; 44(9): 2113-2122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31372925

RESUMO

To investigate the role and mechanism of microRNA-124-3p (miR-124-3p) and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) in neuronal apoptosis induced by mechanical injury. Transient transfection was used to modify the expression of miR-124-3p and SPTLC2. After transfection, neuronal apoptosis was evaluated in an in vitro injury model of primary neurons using TUNEL staining and western blot. The correlation between miR-124-3p and SPTLC2 was identified through a dual luciferase reporter assay in HEK293 cells. A rescue experiment in primary neurons was performed to further confirm the result. To explore the downstream mechanisms, co-immunoprecipitation was performed to identify proteins that interact with SPTLC2 in toll-like receptor 4 (TLR4) signalling pathway. Subsequently, the relative expression levels of TLR4 pathway molecules were measured by western blot. Our results showed that increased miR-124-3p can inhibit neuronal apoptosis, which is opposite to the effect of SPTLC2. In addition, miR-124-3p was proved to negatively regulate SPTLC2 expression and suppress the apoptosis-promoting effect of SPTLC2 via the TLR4 signalling pathway.


Assuntos
Apoptose/fisiologia , MicroRNAs/fisiologia , Neurônios/fisiologia , Serina C-Palmitoiltransferase/fisiologia , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/fisiologia , Animais , Córtex Cerebral/fisiologia , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Serina C-Palmitoiltransferase/metabolismo , Traumatismos do Sistema Nervoso/fisiopatologia
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