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2.
Medicine (Baltimore) ; 99(5): e18924, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000405

RESUMO

Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.


Assuntos
Dor do Câncer/genética , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único , Receptores de Adiponectina/genética , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Feminino , Estudos de Associação Genética , Humanos , Inflamação/genética , Laparotomia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico
3.
Adv Exp Med Biol ; 1226: 1-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32030672

RESUMO

The tumour microenvironment (TME) of intestinal tumours is highly complex and comprises a network of stromal cells, tumour cells, immune cells and fibroblasts, as well as microorganisms. The tumour location, environmental factors and the tumour cells themselves influence the cells within the TME. Immune cells can destroy tumour cells and are associated with better patient prognosis and response to therapy; however, immune cells are highly plastic and easily influenced to instead promote tumour growth. The interaction between local immune cells and the microbiome can lead to progression or regression of intestinal tumours. In this chapter, we will discuss how tumour development and progression can influence, and be influenced by, the microenvironment surrounding it, focusing on immune and fibroblastic cells, and the intestinal microbiota, particularly in the context of colorectal cancer.


Assuntos
Neoplasias Intestinais , Microambiente Tumoral , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Neoplasias Intestinais/imunologia , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia
4.
Lancet ; 395(10221): 350-360, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007170

RESUMO

BACKGROUND: Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. METHODS: More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. FINDINGS: 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72-5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07-4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. INTERPRETATION: A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes. FUNDING: The Research Council of Norway.


Assuntos
Neoplasias Colorretais/diagnóstico , Aprendizado Profundo , Idoso , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Detecção Precoce de Câncer/métodos , Amarelo de Eosina-(YS)/metabolismo , Feminino , Hematoxilina/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
5.
J Biomed Nanotechnol ; 16(1): 54-64, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996285

RESUMO

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.


Assuntos
Neoplasias Colorretais , Neoplasias Peritoneais , Linhagem Celular Tumoral , Humanos , Luteolina , Micelas
6.
Lancet ; 395(10218): 123-131, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31929014

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC. METHODS: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account. FINDINGS: During follow-up, we observed 1336 incident CRCs in the UC cohort (1·29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0·82 per 1000 person-years; HR 1·66, 95% CI 1·57-1·76). In the UC cohort, 639 patients died from CRC (0·55 per 1000 person-years), compared with 4451 reference individuals (0·38 per 1000 person-years; HR 1·59, 95% CI 1·46-1·72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0·0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1·54, 95% CI 1·33-1·78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1·38 (95% CI 1·20-1·60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1·25 (95% CI 1·03-1·51, or one additional case per 3041 patients with UC per 5 years). INTERPRETATION: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines. FUNDING: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation.


Assuntos
Colite Ulcerativa/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/mortalidade , Neoplasias Colorretais/mortalidade , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
7.
Isr Med Assoc J ; 22(1): 32-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927803

RESUMO

BACKGROUND: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency. OBJECTIVES: To identify a unique heterogeneity pattern that is associated with true MMR loss. METHODS: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing. RESULTS: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases. CONCLUSIONS: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.


Assuntos
Reparo de Erro de Pareamento de DNA/genética , Proteínas MutS/genética , Adenoma/genética , Adenoma/patologia , Adulto , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Corantes , Heterogeneidade Genética , Humanos , Masculino
8.
Anticancer Res ; 40(1): 1-7, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892548

RESUMO

BACKGROUND/AIM: The treatment of colorectal liver metastases is challenging and requires multidisciplinary strategies. Unfortunately, only 25% of patients with colorectal liver metastases are eligible for liver resection. Due to the variety of therapeutic approaches, this percentage has increased; however, at the same time, the definition of resectability has become complex. The aim of this review was to provide an overview of current surgical therapies for colorectal liver metastases. MATERIALS AND METHODS: Relevant studies published before June 2019 were identified using PubMed. A comprehensive review of the current literature regarding the impact of and innovations in the therapy of colorectal liver metastases was carried out. RESULTS: The major advances in the resectability of colorectal liver metastases were effective chemotherapy regimens and preoperative liver volume modulation techniques. In addition, health professionals face rapid technical developments in interventional local therapies, minimally invasive surgery, robot-assisted surgery and even liver transplantation. CONCLUSION: Currently, liver metastases from colorectal cancer are considered a chronic disease. In cases of advanced colorectal liver metastases, the definition of resectability and the indications for surgical treatment should be exclusively determined by experienced hepatobiliary surgeons.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Doença Crônica , Neoplasias Colorretais/epidemiologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Resultado do Tratamento
9.
Anticancer Res ; 40(1): 101-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892558

RESUMO

BACKGROUND: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer. MATERIALS AND METHODS: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared. RESULTS: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC. CONCLUSION: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.


Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Neoplasias Colorretais/etiologia , Genes Mitocondriais , Polimorfismo Genético , Transformação Celular Neoplásica/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Suscetibilidade a Doenças , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Mutação
10.
Anticancer Res ; 40(1): 169-176, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892565

RESUMO

BACKGROUND/AIM: Cancer stem cells (CSCs) are considered to be one of the causes of tumor recurrence after chemotherapy. The purpose of our study was to isolate CSCs from human colorectal cancer cell (CRC) lines. MATERIALS AND METHODS: Nine CRC lines were screened based on the expression level of potential CSC markers to identify putative CSCs. Tumor formation capacity in immunodeficient mice was compared with that of their counterparts. Stemness, differentiation potency and sensitivity to 5-fluorouracil (5-FU), in vitro, were also assessed. Microarray analysis was used to characterize the features of the putative CSCs. RESULTS: COLO 201 cells were separated into two populations based on CD44 expression. CD44 positive (CD44+) cells showed significantly higher tumor formation capacity than CD44- cells in immunodeficient mice. CD44+ cells also possessed stemness properties and lower sensitivity to 5-FU in vitro. Moreover, cancer stemness and chemoresistance-related genes were highly up-regulated in CD44+ cells. CONCLUSION: CD44+ COLO 201 cells possessed the features of CSCs; therefore, the present CSC model could serve as a valuable tool to accelerate CSC research.


Assuntos
Receptores de Hialuronatos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Citometria de Fluxo , Fluoruracila/farmacologia , Xenoenxertos , Humanos , Receptores de Hialuronatos/genética , Camundongos
11.
Anticancer Res ; 40(1): 177-190, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892566

RESUMO

BACKGROUND/AIM: The chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) regulates cancer cell proliferation and invasion via complex molecular mechanisms. We aimed to investigate whether COUP-TFII modulates proliferation and invasion of the colorectal adenocarcinoma cell line HT-29. MATERIALS AND METHODS: HT-29 cells were stably tranfected with COUP-TFII shRNA plasmid to knock-down COUP-TFII (COUP-TFII shRNA-HT-29 cells). Cell proliferation, colony formation assay, invasion assay, microarray assays and western blot analyses were performed. RESULTS: Cell proliferation and invasion were significantly enhanced in COUP-TFII shRNA-HT-29 cells. The protein levels of forkhead box C1 (FOXC1), p-Akt, p-glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin, which are known to be involved in cell proliferation and invasion, were significantly increased in COUP-TFII shRNA-HT-29 cells. Akt inhibitor IV and dominant negative (DN)-Akt expression vector transfection reversed the increased proliferation and invasion, which was accompanied by decreased protein levels of p-Akt, p-GSK-3ß, ß-catenin and FOXC1. CONCLUSION: COUP-TFII knock-down promoted proliferation and invasion via activation of Akt/GSK-3ß/ß-catenin and up-regulation of FOXC1. Further studies on the molecular mechanism of interaction between ß-catenin and FOXC1 expression may reveal novel target molecules for metastatic colorectal cancer therapy.


Assuntos
Fator II de Transcrição COUP/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator II de Transcrição COUP/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , RNA Interferente Pequeno/genética
15.
Anticancer Res ; 40(1): 287-291, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892578

RESUMO

BACKGROUND/AIM: Estimating survival is important for treatment personalization in patients with metastatic cancer. In this study, we aimed to develop a survival score for patients irradiated for bone metastases from colorectal cancer. PATIENTS AND METHODS: Eleven factors were retrospectively analyzed in 25 patients, including age, gender, Eastern Cooperative Oncology Group performance score, tumor site, time between diagnosis of colorectal cancer and irradiation, visceral or other bone metastases, type and number of irradiated sites, upfront surgery and previous systemic treatment. RESULTS: On multivariate analysis, performance score (p=0.005) and previous systemic treatment (p=0.007) were significantly associated with survival and used for the score. One point (performance score 0-1 or no previous systemic treatment) or 0 points (performance score ≥2 or previous systemic treatment) were assigned resulting in 0, 1 or 2 points. Six-month survival rates of these groups were 0%, 64% and 100%, respectively. CONCLUSION: This new survival score can support physicians during personalization of treatment for patients with bone metastases from colorectal cancer.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Colorretais/patologia , Idoso , Humanos , Estimativa de Kaplan-Meier , Prognóstico
16.
Anticancer Res ; 40(1): 299-304, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892580

RESUMO

BACKGROUND/AIM: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. PATIENTS AND METHODS: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. RESULTS: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). CONCLUSION: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Rim/fisiopatologia , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/metabolismo , Feminino , Humanos , Incidência , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fatores de Risco , Adulto Jovem
17.
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
18.
Medicine (Baltimore) ; 99(1): e18575, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895803

RESUMO

This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Alho , Adulto , Idoso , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Medicine (Baltimore) ; 99(2): e18623, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914042

RESUMO

BACKGROUND: The surgical management of acute malignant left-sided bowel obstruction is associated with high morbidity and mortality. Recently, transanal drainage tubes (DTs) and metallic stents (MSs) used as a "bridge to surgery" have become widely used decompression methods compared with emergency surgery. This study aims to evaluate the efficacy and safety of DTs and MSs for the decompression of acute left-sided malignant colorectal obstruction. METHODS: All studies were acquired from PubMed, Medline, Embase, CNKI and the Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed with RevMan5.3. Mean differences (MDs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Cochrane Collaboration's risk of bias tool and the Newcastle-Ottawa scale were used to assess the risk of bias. RESULTS: Eleven studies, which included three randomized controlled trials (RCTs) and 8 observational studies, were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of the technical success rate showed that the difference was not statistically significant between the2 devises. The differences in clinical success rate, operative time and complications were statistically significant between MSs and DTs, and MSs were associated with a better clinical success rate, increased operative time and fewer complications. Sensitivity analysis proved the stability of the pooled results, and the publication bias was low. CONCLUSION: MS insertion for acute left-sided malignant bowel obstruction is effective and safe with a better technical success rate and with fewer complications than decompression using a DT, and MS insertion can avoid stoma formation. Moreover, MS insertion appears to be a useful treatment strategy for malignant colonic obstruction even if the lesion is located in the right colon. More large-sample, multicenter, high-quality RCTs are needed to verify the outcomes of this meta-analysis.


Assuntos
Neoplasias Colorretais/complicações , Drenagem/instrumentação , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia
20.
Life Sci ; 244: 117300, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953162

RESUMO

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear ß-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear ß-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the ß-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas F-Box/metabolismo , MicroRNAs/genética , Animais , Apoptose/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Proteínas F-Box/genética , Proteína Forkhead Box M1/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
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