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1.
JCO Clin Cancer Inform ; 6: e2100180, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025670

RESUMO

PURPOSE: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Social media platforms such as Twitter are extensively used to communicate about cancer care, yet little is known about the role of these online platforms in promoting early detection or sharing the lived experiences of patients with CRC. This study tracked Twitter discussions about CRC and characterized participating users to better understand public communication and perceptions of CRC during the COVID-19 pandemic. METHODS: Tweets containing references to CRC were collected from January 2020 to April 2021 using Twitter's Application Programming Interface. Account metadata was used to predict user demographic information and classify users as either organizations, individuals, clinicians, or influencers. We compared the number of impressions across users and analyzed the content of tweets using natural language processing models to identify prominent topics of discussion. RESULTS: There were 72,229 unique CRC-related tweets by 31,170 users. Most users were male (66%) and older than 40 years (57%). Individuals accounted for most users (44%); organizations (35%); clinicians (19%); and influencers (2%). Influencers made the most median impressions (35,853). Organizations made the most overall impressions (1,067,189,613). Tweets contained the following topics: bereavement (20%), appeals for early detection (20%), research (17%), National Colorectal Cancer Awareness Month (15%), screening access (14%), and risk factors (14%). CONCLUSION: Discussions about CRC largely focused on bereavement and early detection. Online coverage of National Colorectal Cancer Awareness Month and personal experiences with CRC effectively stimulated goal-oriented tweets about early detection. Our findings suggest that although Twitter is commonly used for communicating about CRC, partnering with influencers may be an effective strategy for improving communication of future public health recommendations related to CRC.


Assuntos
COVID-19 , Neoplasias Colorretais , Mídias Sociais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Masculino , Pandemias , SARS-CoV-2
2.
World J Surg Oncol ; 20(1): 18, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033097

RESUMO

BACKGROUND: Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC. METHODS: Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method. RESULTS: At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719-0.791) vs. 0.663 (0.629-0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001). CONCLUSIONS: The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.


Assuntos
Neoplasias Colorretais , Nomogramas , Colesterol , Neoplasias Colorretais/cirurgia , Humanos , Linfócitos , Prognóstico , Estudos Retrospectivos
3.
J Cardiothorac Surg ; 17(1): 9, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034630

RESUMO

A comparison of the relative merits of video-assisted pulmonary metastasectomy versus thoracotomy is predicated on the assumption that removal of asymptomatic lung metastases favourably influences survival and that it does so by a large degree. Recently published but long-awaited evidence from a prospective cohort study and a randomised trial of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) challenges that assumption.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Metastasectomia , Estudos de Coortes , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Estudos Prospectivos
4.
Oncol Rep ; 47(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35029289

RESUMO

Zinc finger proteins (ZNFs) serve key roles in tumor formation and progression; however, the functions and underlying mechanisms of dysregulated ZNF384 in colorectal cancer (CRC) are yet to be fully elucidated. Therefore, the present study initially aimed to investigate the expression levels of ZNF384 in CRC samples. Moreover, lentiviral ZNF384 overexpression and ZNF384 knockdown models were established in CRC cells. Transwell, wound healing and in vivo tail vein metastasis assays were carried out to evaluate the effects of ZNF384 on CRC cell metastasis. Furthermore, reverse transcription­quantitative PCR, western blotting, serial deletion, site­directed mutagenesis, dual­luciferase reporter and chromatin immunoprecipitation assays were conducted to investigate the potential underlying mechanisms. The results of the present study demonstrated that ZNF384 expression was markedly increased in CRC samples and this was associated with a poor prognosis. Notably, ZNF384 overexpression increased the levels of CRC cell invasion and migration, whereas ZNF384 knockdown inhibited CRC development. Moreover, the results of the present study demonstrated that ZNF384 mediated the expression of MMP2. MMP2 knockdown inhibited ZNF384­mediated CRC cell invasion and migration, whereas MMP2 overexpression ameliorated ZNF384 knockdown­induced inhibition of CRC progression. In addition, the results of the present study demonstrated that hypoxia­inducible factor 1α (HIF­1α) had the ability to bind to the ZNF384 promoter, thereby initiating ZNF384 expression. In human­derived CRC samples, the expression levels of ZNF384 were positively correlated with both MMP2 and HIF­1α expression. Collectively, these findings highlighted that ZNF384 may act as a prognostic marker and regulator of CRC metastasis.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metaloproteinase 2 da Matriz/metabolismo , Transativadores/genética , Dedos de Zinco/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Regulação para Cima
5.
Artigo em Inglês | MEDLINE | ID: mdl-35046092

RESUMO

OBJECTIVE: To describe a conceptual framework that provides understanding of the challenges encountered and the adaptive approaches taken by organised colorectal cancer (CRC) screening programmes during the initial phase of the COVID-19 pandemic. DESIGN: This was a qualitative case study of international CRC screening programmes. Semi-structured interviews were conducted with programme managers/leaders and programme experts, researchers and clinical leaders of large, population-based screening programmes. Data analysis, using elements of grounded theory, as well as cross-cases analysis was conducted by two experienced qualitative researchers. RESULTS: 19 participants were interviewed from seven programmes in North America, Europe and Australasia. A conceptual framework ('Nimble Approach') was the key outcome of the analysis. Four concepts constitute this approach to managing CRC screening programmes during COVID-19: Fast (meeting the need to make decisions and communicate quickly), Adapting (flexibly and creatively managing testing/colonoscopy capacity, access and backlogs), Calculating (modelling and actively monitoring programmes to inform decision-making and support programme quality) and Ethically Mindful (considering ethical conundrums emerging from programme responses). Highly integrated programmes, those with highly integrated communication networks, and that managed greater portions of the screening process seemed best positioned to respond to the crisis. CONCLUSIONS: The Nimble Approach has potentially broad applications; it can be deployed to effectively respond to programme-specific challenges or manage CRC programmes during future pandemics, other health crises or emergencies.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Humanos , Pandemias , SARS-CoV-2
6.
Medicina (Kaunas) ; 58(1)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35056408

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has brought significant challenges to many aspects of healthcare delivery since the first reported case in early December 2019. Once in the body, SARS-CoV-2 can spread to other digestive organs, such as the liver, because of the presence of ACE2 receptors. Colorectal cancer (CRC) remains the second-leading cause of death in the United States (US). Therefore, individuals are routinely screened using either endoscopic methods (i.e., flexible sigmoidoscopy and colonoscopy) or stool-based tests, as per the published guidelines. At the beginning of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS) recommended that all non-urgent surgical and medical procedures, including screening colonoscopies, be delayed until the pandemic stabilization. This article aims to review the impact of COVID-19 on CRC screening.


Assuntos
COVID-19 , Neoplasias Colorretais , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Humanos , Medicare , Pandemias , SARS-CoV-2 , Estados Unidos/epidemiologia
7.
Clin Epigenetics ; 14(1): 3, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991708

RESUMO

BACKGROUND: DNA mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is not responsive to pembrolizumab monotherapy. DNA methyltransferase inhibitors can promote antitumor immune responses. This clinical trial investigated whether concurrent treatment with azacitidine enhances the antitumor activity of pembrolizumab in mCRC. METHODS: We conducted a phase 2 single-arm trial evaluating activity and tolerability of pembrolizumab plus azacitidine in patients with chemotherapy-refractory mCRC (NCT02260440). Patients received pembrolizumab 200 mg IV on day 1 and azacitidine 100 mg SQ on days 1-5, every 3 weeks. A low fixed dose of azacitidine was chosen in order to reduce the possibility of a direct cytotoxic effect of the drug, since the main focus of this study was to investigate its potential immunomodulatory effect. The primary endpoint of this study was overall response rate (ORR) using RECIST v1.1., and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Tumor tissue was collected pre- and on-treatment for correlative studies. RESULTS: Thirty chemotherapy-refractory patients received a median of three cycles of therapy. One patient achieved partial response (PR), and one patient had stable disease (SD) as best confirmed response. The ORR was 3%, median PFS was 1.9 months, and median OS was 6.3 months. The combination regimen was well-tolerated, and 96% of treatment-related adverse events (TRAEs) were grade 1/2. This trial was terminated prior to the accrual target of 40 patients due to lack of clinical efficacy. DNA methylation on-treatment as compared to pre-treatment decreased genome wide in 10 of 15 patients with paired biopsies and was significantly lower in gene promoter regions after treatment. These promoter demethylated genes represented a higher proportion of upregulated genes, including several immune gene sets, endogenous retroviral elements, and cancer-testis antigens. CD8+ TIL density trended higher on-treatment compared to pre-treatment. Higher CD8+ TIL density at baseline was associated with greater likelihood of benefit from treatment. On-treatment tumor demethylation correlated with the increases in tumor CD8+ TIL density. CONCLUSIONS: The combination of pembrolizumab and azacitidine is safe and tolerable with modest clinical activity in the treatment for chemotherapy-refractory mCRC. Correlative studies suggest that tumor DNA demethylation and immunomodulation occurs. An association between tumor DNA demethylation and tumor-immune modulation suggests immune modulation and may result from treatment with azacitidine. Trial registration ClinicalTrials.gov, NCT02260440. Registered 9 October 2014, https://clinicaltrials.gov/ct2/show/NCT02260440 .


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Azacitidina/uso terapêutico , Biomarcadores/sangue , Neoplasias Colorretais/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Adulto , Idoso , Epigenômica , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade
8.
BMC Gastroenterol ; 22(1): 17, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012456

RESUMO

BACKGROUND: We report the first case of a patient affected by peritoneal metastases from colon cancer, arising in the context of Lynch syndrome with pathological complete response. The patient was treated with immunotherapy and cytoreductive surgery. This paper discusses the implications of these novel therapies for the management of PM. CASE PRESENTATION: A 50-year-old man affected by Lynch syndrome was referred to our institution for metachronous peritoneal recurrence of ascending colon adenocarcinoma. As a second-line treatment, he received Nivolumab therapy with stable disease. Patient underwent cytoreductive surgery with residual disease and a pathological complete response. Flow cytometry described a particular immune sub-population response. There was no evidence of disease progression after nine months. CONCLUSION: This is the first report of a Lynch patient affected by peritoneal metastases of colorectal cancer, treated with cytoreductive surgery (CRS) and resulting in a pathological complete response after immune checkpoint inhibitors treatment (ICIs). This case report may suggest that patients with peculiar immunological features could benefit from a tailored approach, since "classical" CRS paradigms may not effectively predict the clinical outcome. Further large-scale studies are needed to determine the correct operative management of such patients (tailored or "standard" CRS), defining the correct surgical timing and eventual discontinuation of ICI therapy after surgery.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/terapia , Taxa de Sobrevida
9.
Trials ; 23(1): 31, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022080

RESUMO

BACKGROUND: Increasing participation in the Australian National Bowel Cancer Screening Program (NBCSP) is the most efficient and cost-effective way of reducing mortality associated with colorectal cancer by detecting and treating early-stage disease. Currently, only 44% of Australians aged 50-74 years complete the NBCSP. This efficacy trial aims to test whether this SMS intervention is an effective method for increasing participation in the NBCSP. Furthermore, a process evaluation will explore the barriers and facilitators to sending the SMS from general practice. METHODS: We will recruit 20 general practices in the western region of Victoria, Australia to participate in a cluster randomised controlled trial. General practices will be randomly allocated with a 1:1 ratio to either a control or intervention group. Established general practice software will be used to identify patients aged 50 to 60 years old who are due to receive a NBCSP kit in the next month. The SMS intervention includes GP endorsement and links to narrative messages about the benefits of and instructions on how to complete the NBCSP kit. It will be sent from intervention general practices to eligible patients prior to receiving the NBCSP kit. We require 1400 eligible patients to provide 80% power with a two-sided 5% significance level to detect a 10% increase in CRC screening participation in the intervention group compared to the control group. Our primary outcome is the difference in the proportion of eligible patients who completed a faecal occult blood test (FOBT) between the intervention and control group for up to 12 months after the SMS was sent, as recorded in their electronic medical record (EMR). A process evaluation using interview data collected from general practice staff (GP, practice managers, nurses) and patients will explore the feasibility and acceptability of sending and receiving a SMS to prompt completing a NBCSP kit. DISCUSSION: This efficacy trial will provide initial trial evidence of the utility of an SMS narrative intervention to increase participation in the NBCSP. The results will inform decisions about the need for and design of a larger, multi-state trial of this SMS intervention to determine its cost-effectiveness and future implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001020976 . Registered on 17 October 2020.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Sangue Oculto , Vitória
10.
In Vivo ; 36(1): 180-188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972713

RESUMO

BACKGROUND/AIM: The role of irisin, the extracellular part of fibronectin type III domain containing 5 (FNDC5), in colorectal cancer (CRC) is unclear. The aim of this study was to investigate immunohistochemical (IHC) expression level of irisin and correlations with clinicopathological factors in patients with CRC. MATERIALS AND METHODS: We collected 222 archived CRC samples and 26 control samples from autopsies conducted at the Department of Forensic Medicine. They were used to perform IHC reactions detecting irisin, Ki-67, minichromosome maintenance protein complex component 3 (MCM3), and urine diphosphate-galactose ceramide galactosyltransferase (UGT3) expression. The correlations with Ki-67, MCM3, and UGT3 were analyzed. Irisin expression was also evaluated in cancer cell lines by immunofluorescence reaction and western blot. RESULTS: Irisin expression was higher in cancer cells compared to the control tissues (p<0.0001). Irisin expression was significantly higher in stage I than in stage III (p=0.013) and IV CRC (p=0.05). CONCLUSION: The correlation between higher expression of irisin and cancer stages indicates its potential usefulness as a marker in CRC.


Assuntos
Neoplasias Colorretais , Fibronectinas , Linhagem Celular , Neoplasias Colorretais/genética , Fibronectinas/genética , Humanos , Fatores de Transcrição
11.
In Vivo ; 36(1): 450-457, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34972748

RESUMO

AIM: It has been shown that nutritional status and inflammation correlate with survival in patients with various cancer types. In this study, we evaluated several kinds of nutritional and inflammation parameters in preoperative blood samples and constructed new risk model predicting survival in patients with colorectal cancer. PATIENTS AND METHODS: We retrospectively examined 286 patients with stage I-III colorectal cancer who had undergone curative resection at Teikyo University Hospital. The association between overall survival (OS) and nutritional status and inflammation factors were examined using Kaplan-Meier curves and log-rank tests. RESULTS: Serum albumin, cholesterol and C-reactive protein concentration, neutrophil count and platelet count were shown to be correlated with OS. We constructed a new risk model (nutrition inflammation status, NIS) using these factors, and compared it with other nutrition and inflammation models. CONCLUSION: NIS was useful as a new model for predicting OS in patients undergoing curative resection for colorectal cancer, compared with known models.


Assuntos
Neoplasias Colorretais , Avaliação Nutricional , Neoplasias Colorretais/cirurgia , Humanos , Inflamação , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos
12.
World J Surg Oncol ; 20(1): 21, 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35065650

RESUMO

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.


Assuntos
Neoplasias Colorretais , Metilação de DNA , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Sequência de DNA
13.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(1): 22-29, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35067030

RESUMO

In recent years, with the wide application of immune score and liquid biopsy to guide the accurate diagnosis and precise treatment of colorectal cancer, colorectal surgery develops more rationally and scientifically. The strategy of organ function protection in colorectal surgery gradually attracts more and more attention. The continuous development of comprehensive treatments, such as targeted therapy and immunotherapy, provides more choices for colorectal cancer patients. Several significant progress in surgical strategies for benign colorectal diseases challenges the traditional concepts as well. The advances in medical science and the innovation of concepts and ideas set high new standards for the development of colorectal surgery in China. Efforts are required to improve the standardization of diagnosis and treatment of colorectal disease. There is still a long way to go to explore patient-centered new technologies, new concepts and new fields of accurate diagnosis and precise treatment in colorectal surgery.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , China , Neoplasias Colorretais/cirurgia , Humanos
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(1): 36-39, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35067032

RESUMO

The judgment of surgical resection margins is an important factor affecting local recurrence and distant metastasis of colorectal cancer, which is crucial to the prognosis of patients. How to select a standard and ideal surgical resection margin is a challenge for colorectal cancer surgeons. Surgical resection margins for colorectal cancer include longitudinal resection margin (LRM) and circumferential resection margin (CRM), and the distance of safe resection margins varies according to different guidelines. Surgical resection margins are mainly evaluated by preoperative imaging, operative experience, operative type, hyperspectral imaging (HPI) and fluorescence angiography (FA), and postoperative pathology. It is the constant pursuit of colorectal cancer surgeons to pay attention to the safe resection margins in colorectal cancer surgery to reduce local recurrence and distant metastasis.


Assuntos
Neoplasias Colorretais , Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Retais , Neoplasias Colorretais/cirurgia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia , Prognóstico
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(1): 56-62, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35067035

RESUMO

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Estudos de Casos e Controles , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
16.
Saudi Med J ; 43(1): 37-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35022282

RESUMO

OBJECTIVES: To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC). METHODS: In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity. RESULTS: After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm. CONCLUSION: Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC.Clinicaltrial.gov ID:NCT03645187.


Assuntos
Neoplasias Colorretais , Fator A de Crescimento do Endotélio Vascular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Celecoxib/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila , Humanos , Leucovorina
18.
Nat Commun ; 13(1): 136, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013263

RESUMO

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial ß-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Carcinógenos/antagonistas & inibidores , Colite/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Glucuronidase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Triclosan/antagonistas & inibidores , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/metabolismo , Anti-Infecciosos Locais/toxicidade , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Biotransformação , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinógenos/química , Carcinógenos/metabolismo , Carcinógenos/toxicidade , Colite/induzido quimicamente , Colite/enzimologia , Colite/microbiologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Expressão Gênica , Glucuronidase/química , Glucuronidase/genética , Glucuronidase/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triclosan/química , Triclosan/metabolismo , Triclosan/toxicidade
19.
Medicina (Kaunas) ; 58(1)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35056404

RESUMO

Background and Objectives: To assess the periostin level and the concentrations of pro-inflammatory cytokines: TNFα, IFN-γ, IL-1ß and IL-17 in tumor and marginal tissues of CRC and to investigate the influence of periostin on angiogenesis by MVD (microvessel density) and concentration of VEGF-A in relation to clinicopathological parameters of patients. Materials and Methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of periostin, VEGF-A, TNFα, IFNγ, IL-1ß and IL-17, we used the commercially available enzyme- linked immunosorbent assay kit. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope Results: We found significantly higher concentrations of periostin, VEGF-A, IFN-γ, IL-1 ß, IL-17 and TNFα in the tumor samples compared with surgical tissue margins. The tumor concentrations of periostin were correlated with tumor levels of VEGF-A, IFN-γ, IL-1ß and TNFα. We observed significant correlation between margin periostin and VEGF-A, IFN-γ, IL-17 and TNFα in tumor and margin specimens. Additionally, we found a significantly negative correlation between periostin tumor concentration and microvessel density at the invasive front. Tumor periostin levels were also correlated positively with tumor budding. Conclusions: Periostin activity may be associated with pro-inflammatory cytokine levels: TNFα, IFN-γ, IL-1ß and IL-17. Our results also suggest the role of periostin in angiogenesis in CRC and its upregulation in poorly vascularized tumors. Further research on the regulations between periostin and cytokines are necessary to understand the interactions between tumor and immune tumor microenvironment, which could be helpful in the development of new targeted therapy.


Assuntos
Moléculas de Adesão Celular/sangue , Neoplasias Colorretais/diagnóstico , Citocinas , Inflamação , Citocinas/sangue , Testes Diagnósticos de Rotina , Ensaio de Imunoadsorção Enzimática , Humanos , Interferon gama
20.
Stud Health Technol Inform ; 289: 489-490, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35062198

RESUMO

This study analyzes samples of intestinal microbiome and metabolites, from healthy individuals (HE) and patients with adenomas (AD) or colorectal carcinomas (CRC). A network analysis (NetAn) method was applied to the data, to identify the metabolites and microbial genera associated with the 3 classes and then 7 classification models were used. The models were initially trained with classic feature selection vs features resulting from NetAn. The distinction of HE and AD is successful, while CRC distinction presented lower success.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Humanos , Aprendizado de Máquina , Metabolômica
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