Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 107.069
Filtrar
1.
Braz. j. biol ; 83: e248746, 2023. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339351

RESUMO

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.


Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.


Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Quercetina/farmacologia , Ciclo Celular , Anexina A5 , Linhagem Celular Tumoral , Proliferação de Células
2.
Ann R Coll Surg Engl ; 104(4): 257-260, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34939845

RESUMO

INTRODUCTION: The aim of this study was to assess faecal immunochemical test (FIT) negativity in terms of its effect on cancer risk in the local symptomatic two-week wait (2WW) population. FIT was introduced to the colorectal 2WW pathway at the start of the pandemic. This study analyses the FIT-negative (<10µg Hb/g) cohort and calculates the relative risk and odds ratio associated with a negative FIT test. METHODS: FIT tests were sent to symptomatic 2WW patients without rectal bleeding, iron-deficient anaemia or palpable mass. Where FIT was <10µg Hb/g investigations were moved to a radiology protocol. RESULTS: The test return rate was 91% with a FIT-negative (<10µg Hb/g) rate of 82%. The FIT-negative group in the symptomatic referral pathway in Cornwall have a low (1.4%) risk of colon cancer but a significant risk (6.6%) when all cancer types are considered. The impact of a negative quantitative FIT changes the odds ratio of a patient having a luminal cancer by 0.26. The odds ratio for 'all cancer' risk was affected by 0.83. CONCLUSION: A negative FIT test within the local NG12 symptomatic patient group signifies a low risk of colon cancer and identifies patients who can be initially investigated with cross-sectional imaging. However, when all cancer types are considered, cancer prevalence in this group remains above 6%. In relative risk terms a negative FIT represents a small change in overall risk and this patient group still qualify for investigation through 2WW pathways.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Fezes , Humanos , Sangue Oculto , Reto , Encaminhamento e Consulta
3.
Clin. transl. oncol. (Print) ; 24(10): 1881–1889, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207944

RESUMO

All phases of carcinogenesis are affected by inflammation. Activation of the inflammasome is a crucial signaling mechanism that leads to acute and chronic inflammation. When specific nucleotide-binding domains, leucine-rich repeat-containing proteins (NLRs) are activated, inflammasomes are formed. The NLRP3 is one of the NLR family members with the most functional characterization. NLRP3 can modulate the immune systems, apoptosis, growth, and/or the gut microbiome to impact cancer development. Colorectal cancer (CRC) is one of the most common cancers, and it begins as a tissue overgrowth on the internal part of the rectum or colon. In vivo and in vitro studies showed that the NLRP3 inflammasome has a role in CRC development due to its broad activity in shaping immune responses. Here, onwards, we focus on the NLRP3 inflammasome role in CRC development, as well as the therapeutic prospective of modifying NLRP3 inflammasome in the context of anti-cancer therapy. (AU)


Assuntos
Humanos , Neoplasias Colorretais , Inflamassomos , Inflamação , Fagocitose
4.
Clin. transl. oncol. (Print) ; 24(10): 1924–1931, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207948

RESUMO

BackgroundCell-free DNA analysis (cfDNA) holds promise for residual disease or tumor burden quantification in colorectal cancer, with reduced costs and diagnostic equipment compared to gold standard-specific tumor DNA (ctDNA) analysis.MethodsThis prospective case–control study included 46 colorectal cancer patients and healthy controls to perform cfDNA quantification by fluorometry using Quantus Fluorometer (Promega, Madison, WI) and using cell-free DNA ScreenTape assay (Agilent) and 4200 TapeStation instrument (Agilent Technologies, Inc., Santa Clara, CA, USA). cfDNA quantification results were correlated with stage, clinical and histopathological features.Results33 localized (8 stage I, 12 stage II, and 13 stage III) and 13 advanced colorectal cancer patients were included. No differences in cfDNA quantification by fluorometry were demonstrated depending on stage or histopathological features in localized disease patients. Differences in cfDNA quantification by fluorometry could be demonstrated in patients with advanced disease depending on the presence of liver metastases and synchronous or metachronous metastatic disease. Differences in cfDNA quantification by fluorometry could be demonstrated between advanced colorectal cancer patients and both localized disease patients and healthy controls. Secondary cfDNA analysis by electrophoresis, although showing more specificity to measure ctDNA in cfDNA values, could not improve the capacity to detect differences between analyzed a groups beyond previously achieved with fluorometry.ConclusionThis exploratory analysis of cfDNA based on fluorometry and electrophoresis methods showed promising results discriminating colorectal cancer and non-cancer patients, as well as different colorectal cancer stages and disease profiles. Further studies are needed to increase our knowledge and to help to overcome barriers to broader implementation and applications. (AU)


Assuntos
Humanos , Biomarcadores Tumorais , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias Colorretais , Estudos de Casos e Controles
5.
Clin. transl. oncol. (Print) ; 24(10): 1940–1953, octubre 2022. tab, graf
Artigo em Inglês | IBECS | ID: ibc-207950

RESUMO

Purpose: Distal metastases are a major cause of poor prognosis in colorectal cancer patients. Approximately 95% of metastatic colorectal cancers are defined as DNA mismatch repair proficient (pMMR). Our previous study found that miR-6511b-5p was downregulated in pMMR colorectal cancer. However, the mechanism of miR-6511b-5p in pMMR colorectal cancer metastases remain unclear.MethodsWe first used quantitative real-time PCR to evaluate the role of miR-6511b-5p in colorectal cancer. Second, we conducted invasion assays and wound healing assays to investigate the role of miR-6511b-5p and CD44 in colorectal cancer cells metastases. Third, luciferase reporter assay, in situ hybridization (ISH), and immunohistochemistry assays were performed to study the relationship between miR-6511b-5p and BRG1. Finally, real-time quantitative PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) assays were performed to analyze the relationship between BRG1 and CD44 in colorectal cancer.ResultsWe found that lower expression of miR-6511b-5p appeared more often in pMMR colorectal cancer patients compared with dMMR (mismatch repair deficient) cases, and was positively correlated with metastases. In vitro, overexpression of miR-6511b-5p inhibited metastasis by decreasing CD44 expression via directly targeting BRG1 in colorectal cancer. Furthermore, BRG1 knockdown decreased the expression of CD44 by promoting CD44 methylation in colorectal cancer cells.ConclusionOur data suggest that miR-6511b-5p may act as a promising biomarker and treatment target for pMMR colorectal cancer, particularly in metastatic patients. Mechanistically, miR-6511b-5p suppresses invasion and migration of colorectal cancer cells through methylation of CD44 via directly targeting BRG1. (AU)


Assuntos
Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Metilação , MicroRNAs
6.
Clin. transl. oncol. (Print) ; 24(10): 1964–1974, octubre 2022.
Artigo em Inglês | IBECS | ID: ibc-207952

RESUMO

Purpose: Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy.Materials and methodsThe expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as “positive”, and the top 10% genes with “positive rate” were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients.ResultsEighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro.ConclusionOur findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients. (AU)


Assuntos
Humanos , Biomarcadores Tumorais , Proliferação de Células , Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intercelular , Prognóstico
7.
Cir. Esp. (Ed. impr.) ; 100(10): 635-640, oct. 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-208275

RESUMO

Introduction Endoscopic resection offers advantages over surgical resection for early colorectal cancer (ECC). However, there might be a presumed risk of recurrence. We aimed to determine the risk of recurrence after endoscopic removal of ECC. Methods A single-centre series of endoscopic resections for ECC. Patients were stratified according to four risk factors: positive resection margins, Haggitt 4, lymphatic/vascular invasion and tumour budding. Results We included 127 patients. Haggitt classification was grade 4 in 54.0%. Positive margins were found in 43 (33.9%), 16 (12.6%) had lymphatic or vascular invasion, and 5 (4.0%) had high grade budding. In 82 (64.5%) endoscopic excision was the definitive treatment, 45 (35.4%) underwent surgery. Six patients (13.3%) had residual tumour on specimen and/or node metastases. Postoperative complications occurred in ten (22.2%). At a median follow-up of 63 months, none of the 82 patients treated with endoscopic resection alone had recurrence. After stratifying patients according to risk factors, those who had residual tumour also had ≥2 risk factors. Conclusions Endoscopic follow up might be a valid option for patients with ECC. A risk-adjusted management seems prudent (AU)


Introducción La resección endoscópica ofrece claras ventajas frente a la cirugía en el tratamiento del cáncer de colon inicial (ECC). Sin embargo, existe un riesgo de recurrencia tanto a nivel del lecho de polipectomía como a nivel ganglionar. El objetivo del estudio es determinar el riesgo de recurrencia tras la resección endoscópica del ECC. Métodos Serie retrospectiva unicéntrica de resecciones endoscópicas de ECC. Se analizaron cuatro factores de riesgo en la pieza de polipectomía: el margen de resección afecto, Haggitt 4, invasión linfovascular y la presencia de budding tumoral. Resultados Se incluyeron 127 pacientes: Haggitt 4 en el 54%, margen de resección afecto en el 33,9%, infiltración linfática o vascular en el 12,6% y budding tumoral de alto grado en el 4%. En 82 pacientes (64,5%), la resección endoscópica fue el tratamiento definitivo. En 45 (35,4%) se realizó una colectomía oncológica. Seis pacientes (13,3%) presentaron tumor residual en el lecho de la polipectomía y/o a nivel de los ganglios linfáticos. La morbilidad postoperatoria fue del 22% y la mortalidad del 0%. Tras un seguimiento medio de 63 meses, ninguno de los 82 pacientes del grupo de polipectomía presentó recurrencia tumoral. Tras dividir a los pacientes según el número de factores de riesgo presentes, aquellos que presentaron tumor residual en la pieza de colectomía presentaban a su vez ≥ 2 factores de riesgo. Conclusiones El seguimiento endoscópico puede ser una opción válida en los pacientes con ECC. El manejo de estos pacientes debe ajustarse al riesgo individual, en función del número de factores de riesgo (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico por imagem , Endoscopia , Estudos Retrospectivos , Estudos Longitudinais , Seguimentos , Fatores de Risco
8.
Medicine (Baltimore) ; 101(37): e30619, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36123948

RESUMO

Colorectal cancer (CRC) is known to display a high risk of metastasis and recurrence. The main objective of our investigation was to shed more light on CRC pathogenesis by screening CRC datasets for the identification of key genes and signaling pathways, possibly leading to new approaches for the diagnosis and treatment of CRC. We downloaded the colorectal cancer datasets from the Gene Expression Omnibus (GEO) database site. We used GEO2R to screen for differentially expressed genes (DEGs) of which those with a fold change >1 were considered as up-regulated and those with a fold change <-1 were considered as down-regulated on the basis of a P < .05. "Gene ontology (GO)" and "Kyoto Encyclopedia of Genes and Genomes (KEGG)" data were analyzed by the "DAVID" software. The online search tool "STRING" was used to search for interacting genes or proteins and we used Cytoscape (v3.8.0) to generate a PPI network map and to identify key genes. Finally, survival analysis and stage mapping of key genes were performed using "GEPIA" with the aim of elucidating their potential impact on CRC. Our study revealed 120 intersecting genes of which 55 were up- and 65 were downregulated, respectively. GO analysis revealed that these genes were involved in cell proliferation, exosome secretion, G2/M transition, cytosol, protein binding, and protein kinase activity. KEGG pathway analysis showed that these genes were involved in cell cycle and mineral absorption. The Cytoscape PPI map showed 17 nodes and 262 edges, and 10 hub genes were identified by top 10 degrees. Survival analysis demonstrated that the AURKA, CCNB1, and CCNA2 genes were strongly associated with the survival rate of CRC patients. In addition, CCNB1, CCNA2, CDK1, CKS2, MAD2L1, and DLGAP5 could be correlated to pathological CRC staging. In this research, we identified key genes that may explain the molecular mechanism of occurrence and progression of CRC but may also contribute to an improvement in the clinical staging and prognosis of CRC patients.


Assuntos
Quinases relacionadas a CDC2 e CDC28 , Neoplasias Colorretais , Aurora Quinase A , Proteínas de Ciclo Celular , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Humanos , Prognóstico
9.
PLoS One ; 17(9): e0274918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36126088

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) affected cancer care in Japan, but the detailed impact on cancer diagnosis and treatment is not well-understood. We aimed to assess the impact of COVID-19 on digestive cancer care in Osaka Prefecture, which has a population of 8.8 million. METHODS: We conducted a multi-center cohort study, using hospital-based cancer registry (HBCR) data linked to administrative data from 66 designated cancer care hospitals in Osaka. Records of patients diagnosed with cancer of the stomach, colorectum, esophagus, liver, gallbladder or pancreas were extracted from the HBCR data. Baseline characteristics, such as the number of diagnoses, routes to diagnosis and clinical stage, were compared between patients diagnosed in 2019 and those in 2020. We also compared treatment patterns such as the number of treatments (operations, endoscopic surgeries, chemotherapies, radiotherapies), pathological stage and time to treatment for each digestive cancer. RESULTS: In total, 62,609 eligible records were identified. The number of diagnoses decreased in 2020, ranging from -1.9% for pancreatic cancer to -12.7% for stomach cancer. Screen-detected cases decreased in stomach and colorectal cancer. The percentage of clinical stage III slightly increased across different cancers, although it was only significant for colorectal cancer. Among 52,741 records analyzed for treatment patterns, the relative decrease in radiotherapy was larger than for other treatments. The median time from diagnosis to operation was shortened by 2-5 days, which coincided with the decrease in operations. CONCLUSION: The impact of COVID-19 on cancer care in 2020 was relatively mild compared with other countries but was apparent in Osaka. Further investigation is needed to determine the most affected populations.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Gástricas , COVID-19/epidemiologia , Teste para COVID-19 , Estudos de Coortes , Humanos , Japão/epidemiologia , Sistema de Registros
10.
Cell Death Dis ; 13(9): 804, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127319

RESUMO

Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis.


Assuntos
Neoplasias Colorretais , MicroRNAs , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Proteína 4 Homóloga a Disks-Large/genética , Regulação Neoplásica da Expressão Gênica , Glucose , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Via de Pentose Fosfato/genética , RNA Circular/genética
11.
PLoS One ; 17(9): e0274555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129915

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. MATERIALS AND METHOD: The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. RESULTS: 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways.


Assuntos
Neoplasias Colorretais , Proteína Supressora de Tumor p53 , Proteína Axina/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Crizotinibe , Receptores ErbB/metabolismo , Humanos , RNA , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Transdução de Sinais , Trombospondinas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Tirosina
12.
PLoS One ; 17(9): e0274942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129954

RESUMO

BACKGROUND: Linear and parallel are the two leading models of metastatic progression. In this study we propose a simple way to differentiate between them. While the linear model predicts accumulation of genetic and epigenetic alterations within the primary tumor by founder cells before spreading as waves of metastases, the parallel model suggests preclinical distribution of less advanced disseminated tumor cells with independent selection and expansion at the ectopic sites. Due to identical clonal origin and time of dispatching, linear metastases are expected to have comparable diameters in any specific organ while parallel metastases are expected to appear in variable sizes. METHODS AND FINDINGS: Retrospective revision of chest CT of oncological patients with lung metastases was performed. Metastasis number and largest diameters were recorded. The sum number of metastases with a similar diameter (c) and those without (i) was counted and the linear/parallel ratio (LPR) was calculated for each patient using the formula (∑c-∑i)/(∑c+∑i). A LPR ratio of 1 implies pure linear progression pattern and -1 pure parallel. 12,887 metastases were measured in 503 patients with nine malignancy types. The median LPR of the entire group was 0.71 (IQR 0.14-0.93). In carcinomas of the pancreas, prostate, and thyroid the median LPR was 1. Median LPRs were 0.91, 0.65, 0.60, 0.58, 0.50 and 0.43 in renal cell carcinomas, melanomas, colorectal, breast, bladder, and sarcomas, respectively. CONCLUSIONS: Metastatic spread of thyroid, pancreas, and prostate tumors is almost exclusively by a linear route. The spread of kidney, melanoma, colorectal, breast, bladder and sarcoma is both linear and parallel with increasing dominance of the parallel route in this order. These findings can explain and predict the clinical and genomic features of these tumors and can potentially be used for evaluation of metastatic origin in the individual patient.


Assuntos
Carcinoma de Células Renais , Neoplasias Colorretais , Neoplasias Renais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Neoplasias Renais/patologia , Masculino , Estudos Retrospectivos , Sarcoma/patologia
13.
Sci Rep ; 12(1): 15727, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130977

RESUMO

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality. We aim to map out differences in CRC incidence and survival between first-generation traditional labour immigrants of Italian, Turkish and Moroccan descent and native Belgians; and assess the contribution of socioeconomic position (SEP) to these differences. Individually-linked data of the 2001 Belgian Census, the Crossroads Bank for Social Security and the Belgian Cancer Registry are used. Age-standardized incidence rates and incidence rate ratios are calculated by country of origin, with and without adjusting for SEP. For CRC patients, 5-year relative survival rates and the relative excess risk for dying within five years after diagnosis are calculated by migrant origin. Lower CRC incidence was observed among immigrants compared to native Belgians, in particular among non-Western immigrants, which could not be explained by SEP. Survival inequalities were less clear, yet, after adjusting for age and stage at diagnosis and educational attainment, we observed a survival advantage among Turkish and Italian immigrant men. Health gains can be made for the native population by adapting lifestyle. The later stage at diagnosis for immigrants is of concern. Barriers regarding screening as perceived by the vulnerable groups should be identified.


Assuntos
Neoplasias Colorretais , Emigrantes e Imigrantes , Migrantes , Bélgica/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Incidência , Masculino
14.
Cell Commun Signal ; 20(1): 150, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131281

RESUMO

Anti-epidermal-growth-factor-receptor (EGFR) monoclonal antibodies (mAbs) are of great significance for RAS and BRAF wild-type metastatic colorectal cancer (mCRC) patients. However, the generation of primary and secondary resistance to anti-EGFR mAbs has become an important factor restricting its efficacy. Recent studies have revealed that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are implicated in anti-EGFR antibodies resistance, affecting the sensitivity of CRC cells to Cetuximab and Panitumumab. This paper briefly reviewed the research advance of the expression, signaling network and functional mechanism of ncRNAs related to anti-EGFR mAbs resistance in CRC, as well as their relationship with clinical prognosis and the possibility of therapeutic targets. In addition, some ncRNAs that are involved in the regulation of signaling pathways or genes related to anti-EGFR resistance, but need to be further verified by resistance experiments were also included in this review, thereby providing more ideas and basis for ncRNAs as CRC prognostic markers and anti-EGFR therapy sensitizers. Video Abstract.


Assuntos
Antineoplásicos , Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Cetuximab/genética , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , MicroRNAs/genética , Mutação , Panitumumabe/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , RNA Circular , RNA não Traduzido/genética
15.
Curr Oncol ; 29(9): 6091-6114, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36135048

RESUMO

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Quimioprevenção/efeitos adversos , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Humanos , Prognóstico
16.
Curr Oncol ; 29(9): 6226-6235, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36135058

RESUMO

(1) Background: The coronavirus 2019 pandemic has resulted in an abrupt transition to virtual oncology care worldwide. This study's objective is to evaluate chemotherapy delivery and clinical outcomes in patients on systemic treatment for colorectal cancer before and during the pandemic. (2) Methods: Clinical data was collected on patients with colorectal cancer receiving intravenous chemotherapy at The Ottawa Hospital from June 2019 to March 2021. Patients were stratified by whether they were started on chemotherapy pre-pandemic (June 2019-January 2020) or intra-pandemic (February 2020-March 2021). Multiple regression analysis was used to compare outcomes between pandemic periods; (3) Results: There were 220 patients included in this study. The proportion of virtual consultations (1.2% to 64.4%) and follow-up visits (5.2% to 83.3%) increased during the pandemic. There was no difference in the incidence of treatment delays (OR = 1.01, p = 0.78), chemotherapy dose reductions (OR = 0.99, p = 0.69), emergency department visits (OR = 1.23, p = 0.37) or hospitalizations (OR = 0.73, p = 0.43) between pandemic periods. A subgroup analysis revealed no difference in outcomes independent of the presence of metastases; (4) Conclusion: These findings serve as an important quality-care indicator and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Serviço Hospitalar de Emergência , Humanos , Pandemias , Tempo para o Tratamento
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(8): 1191-1197, 2022 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-36073218

RESUMO

OBJECTIVE: To investigate whether miR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote metastasis of colorectal cancer cells. METHODS: We detected the differential expression of miR-372-5p using RT-qRCR in colorectal cancer and adjacent tissues, colorectal cancer cells and normal intestinal epithelial cells. Bioinformatic analysis and double luciferase assay were performed for verification of the targeting relationship between miR-372-5p and PTEN. Western blotting was used to assess the effects of transfection with miR-372-5p inhibitor and miR-372-5p mimics alone, co-transfection with miR-372-5p inhibitor and si-PTEN, and co-transfection with miR-372-5p mimics and PI3K inhibitor on the expressions of PTEN and CXCL12 and the activation of PI3K/AKT signal pathway; Transwell assay and scratch assay were used to examine the changes in the migration ability of the transfected cells, the cells co-transfected with miR-372-5p mimics and si-CXCL12, and the cells treated with conditioned medium from HCT116 cells transfected with miR-372-5p mimics. RESULTS: The expression of miR-372-5p was significantly higher in colorectal cancer tissues than in adjacent tissues, and higher in HCT116 and SW620 cells than in NCM460 cells (P < 0.01). Double luciferase assay confirmed that PTEN was a potential target gene of miR-372-5p (P < 0.05). Transfection of HCT116 cells with miR-372-5p mimics obviously decreased PTEN protein expression, increase CXCL12 expression and the phosphorylation level of AKT, and lowered the cell migration ability, while transfection with miR-372-5p inhibitor produced the opposite effects (P < 0.05); si-PTEN obviously neutralized the effect of miR-372-5p inhibitor (P < 0.01). PI3K inhibitor significantly decreased CXCL12 expression and inhibited the cell migration (P < 0.05), and this effect was mitigated by miR-372-5p mimics (P < 0.01). Treatment with the conditioned medium from HCT116 cells transfected with miR-372-5p mimics significantly enhanced the migration ability of NCM460 cells, and this effect was suppressed by transfection with si-CXCL12 (P < 0.01). CONCLUSION: MiR-372-5p activates PI3K/AKT signaling pathway by targeting PTEN and up-regulates CXCL12 expression to promoting metastasis of colorectal cancer cells.


Assuntos
Neoplasias Colorretais , MicroRNAs , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/patologia , Meios de Cultivo Condicionados , Humanos , MicroRNAs/metabolismo , Metástase Neoplásica , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(8): 1198-1204, 2022 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-36073219

RESUMO

OBJECTIVE: To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients. METHODS: We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay. RESULTS: The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ2=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells. CONCLUSION: CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.


Assuntos
Neoplasias Colorretais , Centrômero/metabolismo , Centrômero/patologia , Neoplasias Colorretais/patologia , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos
19.
Chem Res Toxicol ; 35(9): 1533-1540, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36074022

RESUMO

Nonylphenol (NP) is a widely used chemical, which has been considered a kind of endocrine-disrupting chemical and is involved in the occurrence and development of many types of cancers. Our recent studies demonstrated that NP exposure is related to colorectal cancer (CRC) progression. In this study, we also found epithelial-mesenchymal transition (EMT) promoted by NP treatment in CRC cells. However, the mechanism of NP on tumor metastasis is still unclear. In this study, we focused on the effect of the regulator of cell cycle (RGCC) induced by NP treatment. The cancer genome atlas (TCGA) analysis suggested that the expression of RGCC increased in CRC tissues, and our clinical samples showed that the expression of RGCC in tumor tissues is positively correlated with the serum level of NP in CRC patients. Further studies revealed that overexpression of RGCC could enhance the NP-induced EMT process in CRC cells and activate ERK signaling pathways. Inhibiting ERK signaling by ERK inhibitors or the knockdown of RGCC could attenuate the NP-induced EMT process. In addition, both RGCC overexpression and NP treatment could activate ERK pathways and attenuate the effect of ERK inhibitors on the EMT process in CRC cells. Altogether, this study demonstrated that NP could induce cell invasion and migration by increasing the expression of RGCC to enhance the EMT process, which might be through the activation of ERK signaling pathways. This finding supported a potential target for studying NP exposure-related colorectal cancers.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Fenóis/farmacologia
20.
Front Immunol ; 13: 1008975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119074

RESUMO

Colorectal cancer (CRC) is the third most common form of cancer, and the incidence of sporadic young-onset colorectal cancer (yCRC) has been increasing. Microbiota residing in the tumor microenvironment are emerging tumor components. The colonic microbiome differs between patients with CRC and healthy controls; however, few studies have investigated the role of the tumor microbiota in disease diagnosis and tumorigenesis of yCRC. We performed 16S rRNA sequencing analysis to identify the microbiome in CRC and found that tumor microbial diversity decreased in yCRC. Proteobacteria and Firmicutes were the most abundant phyla in all CRC samples, and Actinomyces and Schaalia cardiffensis were the key microbiota in the yCRC group. Correlation analysis revealed that Actinomyces co-occurred with various pro-tumor microbial taxa, including Bacteroidia, Gammaproteobacteria, and Pseudomonas. An independent cohort was used to validate the results. The Actinomyces in CRC was co-localized with cancer-associated fibroblasts and activated the TLR2/NF-κB pathway and reduces CD8+ T lymphocyte infiltration in CRC microenvironment. This study suggests that tumoral microbiota plays an important role in promoting tumorigenesis and therefore has potential as a promising non-invasive tool and intervention target for anti-tumor therapy.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Microbiota , Actinomyces/genética , Fibroblastos Associados a Câncer/patologia , Carcinogênese , Transformação Celular Neoplásica , Neoplasias Colorretais/patologia , Disbiose/microbiologia , Humanos , NF-kappa B , RNA Ribossômico 16S/genética , Receptor 2 Toll-Like , Microambiente Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...