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1.
Gene ; 723: 144120, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589964

RESUMO

PURPOSE: Matrix Gla protein (MGP) is a vitamin K-dependent, γ-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcifications in cartilage, lungs, brain and vascular system. MGP was recently implicated in tumorigenic processes such as angiogenesis and shown to be abnormally regulated in several tumors, including cervical, ovarian, urogenital and breast. This fact has triggered our interest in analyzing the expression of MGP and of its regulator, the transcription factor runt related transcription factor 2 (RUNX2), in colorectal cancer (CRC). METHODS: MGP and RUNX2 expression were analyzed in cancer and non-tumor biopsies samples from 33 CRC patients and 9 healthy controls by RT-qPCR. Consequently, statistical analyses were performed to evaluate the clinical-pathological significance of MGP and RUNX2 in CRC. MGP protein was also detected by immunohistochemical analysis. RESULTS: Showed an overall overexpression of MGP in the tumor mucosa of patients at mRNA level when compared to adjacent normal mucosa and healthy control tissues. In addition, analysis of the expression of RUNX2 mRNA demonstrated an overexpression in CRC tissue samples and a positive correlation with MGP expression (Pearson correlation coefficient 0.636; p ≤ 0.01) in tumor mucosa. However correlations between MGP gene expression and clinical-pathological characteristics, such as gender, age and pathology classification did not provide relevant information that may shed light towards the differences of MGP expression observed between normal and malignant tissue. CONCLUSIONS: We were able to associate the high levels of MGP mRNA expression with a worse prognosis and survival rate lower than five years. These results contributed to improve our understanding of the molecular mechanism underlying MGP deregulation in cancer.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Neoplasias Colorretais/patologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(10): 997-1000, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31630499

RESUMO

Indocyanine green (ICG) fluorescence imaging has been widely used in surgery. In colorectal surgery specifically, more and more studies have shown that intraoperative fluorescence imaging is a safe and feasible method to assess anastomotic perfusion, and its use may decrease the incidence of anastomotic leakage. Meanwhile, indocyanine green can also be used to mark the location of lesion, identify sentinel lymph nodes, protect the ureter, and so on. It can also provide detection and guidance in the operation of peritoneal metastasis and liver metastasis of colorectal cancer. The application of indocyanine green fluorescence imaging can offer great value for surgery through improving the accuracy and outcomes of oncological resections. According to existing studies, we are still at an early application stage of indocyanine green fluorescence imaging technology in colorectal surgery. Lacking prospective randomized controlled studies, neither standards nor guidelines for injection dosage, site and observation period are satisfactory. Therefore, deep researches and establishment of standardized operational procedure are required to enhance the safety and accuracy of tumor resection and improve outcomes.


Assuntos
Colo/cirurgia , Neoplasias Colorretais/diagnóstico , Corantes Fluorescentes/administração & dosagem , Verde de Indocianina/administração & dosagem , Reto/cirurgia , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Colo/irrigação sanguínea , Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Reto/irrigação sanguínea , Reto/patologia
3.
Zhonghua Zhong Liu Za Zhi ; 41(10): 734-741, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648494

RESUMO

Microsatellite instability (MSI) which resulted from the deficiency of DNA mismatch repair (MMR), is an important clinical significance in the related solid tumors, such as colorectal cancer and endometrial cancer. There are several methods to detect MSI status, including immunohistochemistry for MMR protein, multiplex fluorescent polymerase chain reaction (PCR) for microsatellite site and MSI algorithm based on next generation sequencing (NGS). The consensus elaborates the definition and clinical significance of MSI as well as the advantages and disadvantages of the three detection methods. Through this expert consensus, we hope to promote the screening which based on MSI status in malignant tumors and improve the acknowledge of clinicians about various testing methods. Thereby, they could interpret the results more accurately and provide better clinical services to patients.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/genética , Consenso , Assistência à Saúde/normas , Instabilidade de Microssatélites , Guias de Prática Clínica como Assunto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , China , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Sequência de DNA Instável , Neoplasias do Endométrio , Feminino , Humanos , Imuno-Histoquímica , Repetições de Microssatélites , Microscopia de Fluorescência , Reação em Cadeia da Polimerase
4.
Zhonghua Zhong Liu Za Zhi ; 41(10): 796-800, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648505

RESUMO

Objective: To discuss the role of enhanced recovery after surgery (ERAS) in patients with colorectal carcinoma after natural orifce specimen extraction surgery (NOSES). Methods: From March 2017 to May 2018, 86 patients diagnosed with colorectal carcinoma and received NOSES at Tangshan Gongren Hospital were randomized to the control group and the observation group. Doctors utilized traditional interventions in the control group. In the observation group were orally administered with electrolyte solution for 12 hours before surgery, without gastrointestinal decompression tube routinely. Patients were fasting for 6 hours before surgery, 2 hours of water inhalation, and oral administration of 10% glucose 3 hours before surgery. During surgery, patients received intraoperative warming and controlled infusion volume. After operation, no drainage tube was placed, and multi-mode analgesia was used. The patient was given a fluid diet on the first day after surgery, and gradually transitioned to a normal diet. The intraoperative blood loss, number of lymph node dissection, operation time, hospitalization time, hospitalization expenses, first drinking time after surgery, diet time, exhaust time, time to get out of bed, pre-and post-operative self-rating anxiety scale (SAS) and self-rating depression scale (SDS) score, postoperative Barthel index and complication were compared between the two groups. Results: The intraoperative blood loss, number of lymph node dissection, and operation time were almost the same between the two groups (all P>0.05). The hospitalization time (6.8±1.2 d versus 8.5±1.5 d) and expenses (58±10 thousand Yuan versus 69±12 thousand Yuan) were significantly reduced in The first drinking time after surgery(1.31±0.35 d versus 2.28±0.24 d), diet time(1.8±0.4 d versus 3.0±0.4 d), exhaust time(2.4±0.5 d versus 2.9±0.6 d), and time to get out of bed (12.0±2.4 d versus 16.8±2.5 d) were all earlier in the observation group (all P<0.05). The SAS and SDS score before the operation were similar between the two groups (all P>0.05), while post-operative SAS (57±7 versus 69±8) and SDS (57±4 versus 62±9) score were significantly decreased in the observation group (all P<0.05). The incidence rates of complication after surgery was 7.0%(3/43) in the observation group, which was significantly lower than the control group (27.9%, 12/43, P=0.011). Conclusion: The combination of NOSES and EARS could reduce stress response, complications, recovery time and expense after surgery, while improving the quality of life in these patients.


Assuntos
Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Cirurgia Endoscópica por Orifício Natural , Qualidade de Vida , Perda Sanguínea Cirúrgica , Neoplasias Colorretais/patologia , Neoplasias Colorretais/psicologia , Humanos , Duração da Cirurgia , Recuperação de Função Fisiológica , Resultado do Tratamento
5.
Acta Gastroenterol Belg ; 82(3): 375-378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31566324

RESUMO

BACKGROUND: Colorectal recurrent lesions after endoscopic mucosal resection (EMR) often contain severe fibrosis. In such lesions, repeat EMR is often difficult and endoscopic piecemeal mucosal resection (EPMR) has a high risk of repeated recurrence, while surgery is considered overtreatment. Whether ESD can be used safely and reliably to treat such difficult lesions has not been adequately verified. We analyzed the treatment outcomes of ESD for recurrent lesions after EMR. METHODS: Among 653 colorectal ESD conducted in our institution between April 2012 and August 2017, 27 consecutive patients underwent the procedure for recurrent lesions after EMR. Treatment outcomes including en bloc resection rate, R0 resection rate, and curative resection rate; complications were analyzed. RESULTS: Treatment outcomes of the 27 patients were as follows: en bloc resection rate 81.5%, R0 resection rate 74.1%, curative resection rate 74.1%, median procedure time 47 min (range 10‒210 min), perforation rate 0%, and delayed bleeding rate 3.7%. The corresponding rates for 626 patients who underwent colorectal ESD during the same period for lesions other than recurrence after EMR were 97.2%, 95.5%, 88.7%, 37 min (7-225 min), 0.5%, and 2.8%. There were no differences in complication rates. Treatment outcomes including en bloc resection rate were inferior in the recurrence group compared to non-recurrent group, but no local recurrence was found in all patients. CONCLUSIONS: Colorectal ESD is feasible for recurrent colorectal lesions after EMR. The procedure is safe and achieves good treatment outcomes with no local recurrence.


Assuntos
Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Mucosa Intestinal/cirurgia , Recidiva Local de Neoplasia/cirurgia , Colonoscopia , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Humanos , Mucosa Intestinal/patologia , Resultado do Tratamento
6.
Medicine (Baltimore) ; 98(39): e17221, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574832

RESUMO

To investigate the clinicopathological features and prognostic impact of Fusobacterium nucleatum (F nucleatum) status in patients with colorectal cancer (CRC) and its relationships with microsatellite instability (MSI) status.Retrospective analysis of consecutive 91 CRC tissues from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery in Wuhan Union Hospital from January, 2017 to January, 2019 was conducted. F nucleatum DNA was quantitatively measured and classified into 1 of the 2 categories: F nucleatum-high, or F nucleatum-low/negative. The Cox risk ratio model analysis was performed to identify independent risk factors of F nucleatum. F nucleatum-high group was compared with the F nucleatum-low/negative group with respect to clinicopathological features and their relationships with MSI status. Kaplan-Meier method and log-rank test were used for univariate analysis of prognostic factors in patients with CRC.The number of total lymph node acquisition and positive lymph nodes, neurological invasion, vascular tumor thrombus were higher in F nucleatum-high group (27.44 ±â€Š25.213 vs 20.70 ±â€Š10.141; P = .018; 3.80 ±â€Š7.974 vs 1.74 ±â€Š3.531; P = .001; 68.0% vs 33.3%; P = .003; 60.0% vs 25.8%; P = .002). Moreover, microsatellite mutations were more frequent in patients with F nucleatum-high (84.0% vs 60.6%; P = .034). A higher abundance of F nucleatum in CRC is associated with a shorter survival time. The F nucleatum status, peripheral nerve invasion, vascular tumor thrombus, lymph node metastasis, and TNM staging were related factors affecting the prognosis of patients with CRC. The Cox risk ratio model analysis showed that the F nucleatum (odds ratio [OR] 2.094, 95% confidence interval [CI] 1.178-8.122, P = .032) and MSI status (OR 2.243, 95% CI 1.136-5.865, P = 0.039) were independent prognostic factors.Intratumoral F nucleatum load has a poor prognostic effect of CRC by increasing nerve invasion, vascular tumor thrombus, and microsatellite mutation.


Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/mortalidade , Fusobacterium nucleatum , Idoso , Carga Bacteriana , Neoplasias Colorretais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/microbiologia , Linfonodos/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
7.
Medicine (Baltimore) ; 98(39): e17384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574891

RESUMO

BACKGROUND: Irinotecan (IRI)-based and oxaliplatin (OXA)-based regimens are available for the treatment of metastatic colorectal cancer (mCRC). Several studies have published inconsistent results in their comparisons of the efficacy and toxicity of IRI ±â€Šbevacizumab and OXA ±â€Šbevacizumab. This meta-analysis was performed to evaluate the efficacy and safety of these 2 regimens in patients with mCRC. METHODS: We searched several databases to identify relevant studies, including PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary comparisons were overall response rate (ORR) and toxicity. In addition, the hazard ratio (HR) or risk ratio (RR) values with their corresponding 95% confidence intervals (CIs) were extracted from these studies. RESULTS: Pooled data of 13 studies demonstrated no significant differences in OS (HR = 0.96, 95% CI: 0.86-1.08, P = .53) and TTP (HR = 0.88, 95% CI: 0.72-1.08, P = .24) between the 2 groups. However, the ORR (RR = 0.87, 95% CI: 0.78-0.97, P = .02) was clearly improved in the OXA ±â€Šbevacizumab arm. Higher incidences of grade 3/4 nausea (RR = 1.63, 95% CI: 1.28-2.07, P < .001), vomiting (RR = 1.40, 95% CI: 1.09-1.81, P = .01), diarrhea (RR = 1.44, 95% CI: 1.23-1.70, P < .001), and anemia (RR = 4.13, 95% CI: 2.75-6.22, P < .001) were observed in the IRI group. However, the incidences of grade 3/4 neutropenia (RR = 0.75, 95% CI: 0.68-0.83, P < .001), thrombocytopenia (RR = 0.43, 95% CI: 0.26-0.73, P = .002), and paresthesia/neurological disturbances (RR = 0.04, 95% CI: 0.02-0.07, P < .001) were higher in the OXA group. CONCLUSION: This meta-analysis confirmed that the OXA ±â€Šbevacizumab regimen as a maintenance therapy significantly improved the ORR in patients with mCRC. Exhibiting strong efficacy and safety, the OXA and OXA plus bevacizumab regimens are preferred as first-line treatments for mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Irinotecano/administração & dosagem , Oxaliplatina/administração & dosagem , Adulto , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(42): e17570, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626124

RESUMO

Perineural invasion (PNI) is a prognostic factor in patients with colorectal cancer. Neurotrophic factors, molecular determinants of PNI, are altered in their expression levels in patients with ulcerative colitis. In this study, we evaluated the frequency of PNI in colitis-associated cancer (CAC) and sporadic cancer.We retrospectively reviewed 778 colorectal cancers with pathological T3-T4 in 761 patients all of whom were surgically resected without preoperative treatment. The lesions were classified into either CAC or sporadic cancer based on the clinical information. Clinicopathological findings including PNI were compared between CACs and sporadic cancers. Moreover, we analyzed the risk factors for positive PNI by multivariate analysis using a logistic regression model.Ten of the cancers (1.3%) were diagnosed as CACs, and the remaining 768 as sporadic cancers. CACs were characterized by being nonobstructive and predominantly located in the rectum. The CACs had a larger size and more frequent undifferentiated histology than sporadic cancers. PNI was observed more frequently in CACs (90%) than in sporadic cancers without obstruction (45%, P = .007). On multivariate analysis, CAC was one of the significant factors associated with PNI (odds ratio: 9.05, P = .040).Our results suggest that CAC was more likely to exhibit PNI than sporadic colorectal cancer.


Assuntos
Adenocarcinoma/patologia , Colite Ulcerativa/complicações , Neoplasias Colorretais/patologia , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso Periférico/patologia , Reto/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias do Sistema Nervoso Periférico/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
9.
Anticancer Res ; 39(10): 5645-5652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570462

RESUMO

BACKGROUND/AIM: The aim of our study was to assess the predictive role of primary tumour sidedness (PTS) in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS and treated with targeted agents. PATIENTS AND METHODS: The cohort included 178 patients treated with first-line chemotherapy plus cetuximab, panitumumab or bevacizumab. RESULTS: We observed longer progression-free survival (PFS) and overall survival (OS) in patients with left-sided (L-CRC) compared to right-sided tumours (R-CRC) treated with anti-EGFR mAbs (p=0.0033 and p=0.0037), while there was no difference in patients treated with bevacizumab (p=0.076 and p=0.56). Finally, we observed longer PFS and OS in patients with L-CRC treated with anti-EGFR mAbs and those with R-CRC treated with bevacizumab compared to the reverse combination (p=0.0002 and p=0.011). CONCLUSION: PTS is a predictive factor for anti-EGFR mAbs, not for bevacizumab. Superior survival was observed when anti-EGFR mAbs were used for L-CRC and bevacizumab for R-CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Idoso , Anticorpos Monoclonais/administração & dosagem , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Genes ras/genética , Humanos , Masculino , Panitumumabe/administração & dosagem
10.
Anticancer Res ; 39(10): 5721-5724, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570473

RESUMO

BACKGROUND/AIM: This study aimed to identify risk factors for recurrence of patients with stage III colorectal cancer by assessing clinicopathological features. PATIENTS AND METHODS: The study included 231 patients with stage III colorectal cancer who underwent curative resection between 2006 and 2012 at the Department of Surgery of the Jikei University Hospital, Tokyo, Japan. Clinicopathological data of the patients were retrospectively evaluated. RESULTS: The recurrence rate was 27.7% (64/231) in the study group. The univariate analysis for recurrence identified five risk factors: site of primary tumor (rectal cancer), surgical procedure (open surgery), preoperative serum CEA level (>5 ng/ml), preoperative serum CA19-9 level (>37 U/ml), and number of metastatic lymph nodes (over three metastases). The multivariate analysis for recurrence identified three risk factors: rectal cancer, preoperative serum CEA level >5.0 ng/ml 95%, and more than three metastatic lymph nodes. CONCLUSION: The risk factors for stage III colorectal cancer recurrence seem to be rectal cancer, preoperative serum CEA level >5.0 ng/ml, and more than three metastatic lymph nodes.


Assuntos
Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Japão , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
11.
Zhonghua Wai Ke Za Zhi ; 57(9): 666-672, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31474058

RESUMO

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , China , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Hipertermia Induzida , Laparoscopia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Rev Port Cir Cardiotorac Vasc ; 26(2): 117-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476811

RESUMO

INTRODUCTION: Colorectal cancer is the third most common malignancy, being associated with metastatic disease in 50% of cases. The lung is the second organ most affected by metastasis in colorectal cancer. In this study, we aim to review the cases submitted to resection of pulmonary colorectal metastasis at Hospital Pulido Valente, comprised in the period from the 1st of January to the 31st of December 2017. METHODS: Retrospective analysis. Data were collected from clinical records. RESULTS: There were 21 patients operated during this period, with a total of 22 surgeries performed, all with curative intent. Data were collected regarding age, gender, site of primary tumour, number of resected lesions, surgical approach, performed procedure, disease-free interval, presence of bilateral disease and existence of extra-pulmonary metastasis. CONCLUSION: Lung metastases are frequent in colorectal cancer. Pulmonary metastasectomy is currently accepted as a potentially curative therapy as part of a multimodal approach to metastatic colorectal cancer.


Assuntos
Neoplasias Pulmonares/cirurgia , Metastasectomia , Pneumonectomia , Neoplasias Colorretais/patologia , Humanos , Neoplasias Pulmonares/secundário , Prognóstico , Estudos Retrospectivos
13.
J Clin Pathol ; 72(11): 736-740, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471468

RESUMO

Evaluating peritoneal elastic laminal invasion (ELI) has been proposed as an additional assessment for pT3 colorectal cancers (CRC). Its clinical significance has not yet been established. We performed a meta-analysis to investigate the prognostic impact of ELI assessment for subcategorisation of pT3 CRC. We performed a search in three electronic databases. HR and its 95% CI for overall survival (OS) and disease-free survival (DFS) were calculated using the random effects model weighted by the inverse variance method. We identified six studies that met inclusion criteria out of an original 703 studies found with our database search terms. Our meta-analysis included 1925 patients with pT3 and pT4a CRCs. The presence of ELI in pT3 CRC was associated with shortened OS compared with ELI negative pT3 CRC (HR=1.76; 95% CI 1.21 to 2.55); whereas the DFS was not statistically significant (HR=1.79; 95% CI 0.91 to 3.52). Furthermore, pT4a patients' OS (HR=1.84; 95% CI 1.41 to 2.40) and DFS (HR=1.88; 95% CI 1.17 to 3.04) were even worse than the OS and DFS of pT3 ELI (+) patients. ELI is a useful marker for stratifying patients with pT3 or pT4a CRCs into three prognostically distinct groups. We recommend the subcategorisation of pT3 CRC by ELI for better prognostic assessment and treatment strategy of patients with CRC.


Assuntos
Neoplasias Colorretais/patologia , Tecido Elástico/patologia , Peritônio/patologia , Idoso , Biópsia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo
14.
Tumour Biol ; 41(9): 1010428319863627, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500540

RESUMO

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade (p = 0.008), tumor invasion (p = 0.01), and distant metastasis (p = 0.04). Kaplan-Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression (p = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker (p = 0.02). However, nuclear SPP1 expression did not show any prognostic value (p = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes' assessment is highly recommended toward precision oncology.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Osteopontina/genética , Idoso , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Medicina de Precisão , Prognóstico , Arábia Saudita/epidemiologia
17.
Life Sci ; 235: 116799, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472144

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies in the world. Emerging evidence has shown that dysregulation of tripartite motif (TRIM) family proteins is strongly correlated with the tumorigenesis of CRC. Here, we evaluated the biological roles of TRIM66, a member of TRIM family, in the progression of CRC. The results demonstrated that TRIM66 was markedly up-regulated in both CRC tissues and cell lines. To further investigate the functions of TRIM66 in CRC, CRC cells were infected with lentivirus expressing anti-TRIM66 shRNA (sh-TRIM66) or control lentivirus (sh-con). We found that knockdown of TRIM66 significantly inhibited cell proliferation, migration, invasion of CRC cells. TRIM66 knockdown also suppressed epithelial-mesenchymal transition (EMT), as proved by the increased E-cadherin expression and decreased expressions of N-cadherin and vimentin. Furthermore, TRIM66 knockdown markedly inhibited tumor growth in a mouse xenograft model. Knockdown of TRIM66 reduced the activation of JAK2/STAT3 signaling pathway in CRC cells. Treatment with AG490, an inhibitor of JAK2/STAT3 signaling pathway, enhanced the inhibitory effects of TRIM66 knockdown on cell proliferation, migration and invasion. These findings suggested that knockdown of TRIM66 exhibited anti-tumor activity through inhibiting the JAK2/STAT3 signaling pathway in CRC cells.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Janus Quinase 2/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Anticancer Res ; 39(9): 4659-4666, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519564

RESUMO

BACKGROUND/AIM: Short-chain fatty acids (SCFAs) inhibit human colorectal cancer cell growth and tumorigenicity. We investigated the mechanism of the anti-proliferative effects of SCFAs on human colorectal cancer cells by examining their effects on gene expression. MATERIALS AND METHODS: The DLD-1 cell line was cultured with different SCFAs. Gene groups whose expression levels decreased to <50% or increased >50% compared to untreated cells and the signalling pathways responsible for DLD-1 cell growth inhibition were identified and analyzed. RESULTS: Genes whose expression levels decreased to ≤50% (791 genes) showed remarkable changes in gene function compared to genes whose expression levels increased ≥50%. These genes encode proteins involved in DNA replication and cell cycle/proliferation that contribute to major pathways responsible for suppression of colorectal carcinogenesis pathways. CONCLUSION: SCFAs inhibited the expression of genes encoding proteins involved in DNA replication and cell cycle/proliferation of human colorectal cancer cells and exerted antiproliferative activity via different pathways.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ácidos Graxos Voláteis/metabolismo , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Ácidos Graxos Voláteis/farmacologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Transdução de Sinais
19.
Anticancer Res ; 39(9): 4667-4671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519565

RESUMO

BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Anticancer Res ; 39(9): 4729-4736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519572

RESUMO

BACKGROUND/AIM: Amphiregulin (AREG) and epiregulin (EREG) mRNA expression levels are predictors of response to anti-EGFR antibody therapy. Left-sided colon cancer is more sensitive to anti-EGFR antibodies than right-sided, although the mechanism is unclear. The aim of this study was to determine the relationship between AREG, EREG mRNA expression levels and tumor location as well as the efficacy of anti-EGFR antibody agents. MATERIALS AND METHODS: Real-time PCR was used to assess AREG and EREG mRNA expression in metastatic colorectal cancer (CRC) samples from 153 patients. RESULTS: Among KRASwt samples, high AREG expression (AREGHigh) was significantly more common in left-sided tumors than in right-sided. Among patients who received anti-EGFR antibody, response rates were significantly higher in AREGHigh than in AREGLow In the left-sided tumor group, overall survival was significantly longer in patients with high EREG levels than with low levels, whereas the right-sided tumor group showed no survival difference between them. CONCLUSION: AREG and EREG mRNA expression levels in left-sided CRC were higher than in right-sided tumors. This may help explain why left-sided CRC is more responsive to anti-EGFR antibodies.


Assuntos
Anfirregulina/genética , Neoplasias Colorretais/genética , Epirregulina/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Especificidade de Órgãos/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
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