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1.
Life (Basel) ; 10(9)2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32878005

ABSTRACT

LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. In the present study, we aimed to analyze the clinical value of lincRNA-p21 in 177 resected stage I-III colorectal cancer (CRC) patients. Tumor and normal paired tissue and plasma samples from tumor-draining mesenteric veins and paired peripheral veins were analyzed. LincRNA-p21 expression was determined by RTqPCR and correlated with disease-free (DFS) and overall survival (OS). LincRNA-p21 was downregulated in tumor versus normal tissue (p = 0.0012). CRC patients with high lincRNA-p21 expression had shorter DFS (p = 0.0372) and shorter OS (p = 0.0465). Of note, the major prognostic impact was observed in the subset of rectal cancer patients where patients with high lincRNA-p21 levels had worse DFS (p = 0.0226) and OS (p = 0.0457). Interestingly, rectal cancer patients with high lincRNA-p21 benefited from post-operative chemoradiotherapy, as indicated by a longer OS in the group of high lincRNA-p21 patients receiving post-operative chemoradiotherapy (p = 0.04). Finally, patients with high lincRNA-p21 levels in mesenteric vein (MV) had shorter OS (p = 0.0329). LincRNA-p21 is a marker of advanced disease and worse outcome in CRC. Moreover, rectal cancer patients with high lincRNA-p21 levels could benefit from post-operative chemoradiotherapy, and plasmatic-lincRNA-p21 is a promising liquid biopsy biomarker.

2.
Int J Colorectal Dis ; 35(5): 805-813, 2020 May.
Article in English | MEDLINE | ID: mdl-32088737

ABSTRACT

PURPOSE: In colorectal cancer (CRC), circulating tumor cells (CTCs) are released into the mesenteric veins (MV). We chose to determine whether KRAS mutations detected in CTCs from blood obtained at the time of surgery could be a marker of survival. METHODS: From 52 surgically resected CRC patients who later relapsed, samples of tumor tissue, normal tissue, and blood from the peripheral vein (PV) and MV were obtained from each patient at the time of surgery. KRAS mutations were assessed by Sanger sequencing and digital PCR (DGPCR) in tissue samples and by DGPCR in CTCs. Mutant KRAS copy number was assessed in CTCs. Results were correlated with overall survival (OS). RESULTS: Sanger sequencing detected KRAS mutations in ten tumor samples (19.2%), while DGPCR detected mutations in 30 (58%). Mutations were detected in CTCs in 21 MV samples (40.4%) and 18 PV samples (34.6%). Patients with G13D mutations in CTCs from the MV had shorter OS than those with G12D mutations (28.1 vs 54.6 months; p = 0.025). Patients with a high mutant KRAS copy number in CTCs had shorter OS than those with a low mutant KRAS copy number (MV: 20.5 vs 43.7 months; p = 0.002; PV: 15.1 vs 38.2 months; p = 0.027). CONCLUSION: DGPCR is more efficient than Sanger sequencing for detecting KRAS mutations. KRAS G13D mutations and high mutant KRAS copy number are associated with shorter OS. The analysis of KRAS mutations in CTCs from blood obtained at the time of surgery can identify patients with a higher risk of relapse.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/surgery , Mesenteric Veins/pathology , Mutation/genetics , Neoplasm, Residual/pathology , Neoplastic Cells, Circulating/pathology , Polymerase Chain Reaction/methods , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Aged, 80 and over , Cell Separation , Colorectal Neoplasms/pathology , Female , Gene Dosage , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual/genetics , Survival Analysis
3.
Oncology ; 95(5): 309-318, 2018.
Article in English | MEDLINE | ID: mdl-30138915

ABSTRACT

OBJECTIVE: To evaluate the prognostic potential of expression levels of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429, miR-141) in plasma and exosomes from the tumor-draining vein (mesenteric vein [MV]) and peripheral vein (PV) of colon cancer (CC) patients. METHODS: We analyzed the expression of miR-200 family members in matched samples of MV and PV plasma from 50 resected patients with CC and correlated our findings with overall survival (OS). We also examined the content of these microRNAs in MV and PV exosomes. RESULTS: Expression levels were higher in MV than in PV (miR-200a, p < 0.001; miR-200b, p < 0.001; miR-429, p = 0.01; miR-200c, p = 0.05; miR-141, p = 0.05). Low levels of both miR-200c and miR-141 in MV plasma were associated with longer OS (p = 0.02). This association was maintained for the MV exosome cargo of miR-200c and miR-141 (p = 0.02). CONCLUSION: Our findings provide the first indication that expression levels of miR-200c and miR-141 in MV plasma can identify CC patients with poor prognosis. In addition, our results lend further support to the premise that tumor-draining veins constitute a better source of biomarkers than do PVs.


Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , Colonic Neoplasms/blood , Colonic Neoplasms/blood supply , Exosomes/metabolism , MicroRNAs/blood , Aged , Biomarkers, Tumor/genetics , Circulating MicroRNA/genetics , Colectomy , Colonic Neoplasms/genetics , Colonic Neoplasms/surgery , Exosomes/genetics , Exosomes/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Mesenteric Veins , MicroRNAs/genetics , Neoplasm Staging , Time Factors , Treatment Outcome
7.
Clin Colorectal Cancer ; 15(4): e175-e182, 2016 12.
Article in English | MEDLINE | ID: mdl-27247088

ABSTRACT

BACKGROUND: The potential benefit of adjuvant chemotherapy in surgically resected patients with stage II colorectal cancer is controversial. The current guidelines, which are based solely on clinical factors, have limited usefulness, and a clear need exists for biomarkers to supplement the clinical information. MicroRNAs (miRNAs) have previously been shown to be useful cancer biomarkers. In the present study, we assessed the usefulness of a miRNA score to help identify the subset of high-risk patients likely to benefit from adjuvant chemotherapy. PATIENTS AND METHODS: Six miRNAs previously identified as prognostic markers in Asian patients (miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215) were studied in tumor samples from 71 white patients with stage II colon cancer. RESULTS: Three miRNAs (miR-103a-3p, miR-143-5p, and miR-215) emerged as independent prognostic markers on multivariate analysis and were used to construct a miRNA-based score that classified patients into high- and low-risk groups. The patients in the high-risk group had significantly shorter disease-free survival compared with their low-risk counterparts (P = .003). The time-dependent receiver operating characteristic curve analysis showed that our 3-miRNA score improved the prediction of outcome when added to the clinical features (P = .023). CONCLUSION: Our 3-miRNA score added valuable prognostic information to the clinical features in stage II colon cancer. Further research in this field could provide useful tools to determine whether adjuvant chemotherapy would benefit patients with stage II colon cancer after surgery.


Subject(s)
Biomarkers, Tumor/genetics , Colonic Neoplasms/pathology , MicroRNAs/biosynthesis , Adult , Aged , Area Under Curve , Colonic Neoplasms/genetics , Colonic Neoplasms/mortality , Disease-Free Survival , Female , Gene Expression Profiling , History, 16th Century , History, 17th Century , Humans , Kaplan-Meier Estimate , Male , MicroRNAs/analysis , Middle Aged , Prognosis , ROC Curve , Risk Factors , Sensitivity and Specificity
8.
Medicine (Baltimore) ; 94(1): e145, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25569638

ABSTRACT

Findings on the role of plasma miR-21 expression in colorectal cancer are contradictory. Before reaching a peripheral vein (PV), microRNAs released by the tumor are dispersed throughout the body. We hypothesized that blood drawn from the mesenteric vein (MV) near the site of the primary tumor could provide more homogeneous information than blood drawn from the PV.We have analyzed miR-21 expression in matched samples of tumor tissue, normal tissue, MV plasma, and PV plasma in 57 surgically resected patients with colon cancer and correlated our findings with clinical characteristics and disease-free survival (DFS).miR-21 expression was higher in MV than PV plasma (P = 0.014) and in tumor than in normal tissue (P < 0.001). Patients with high levels of miR-21 in MV plasma had shorter DFS (P = 0.05) than those with low levels, and those with high levels in both MV and PV plasma had shorter DFS than all other patients (P = 0.01).Our findings suggest that the primary tumor in colon cancer releases high concentrations of miR-21 in the MV but that these concentrations are later diluted in the circulatory system. MV expression of miR-21 may be a stronger prognostic marker than PV expression.


Subject(s)
Colonic Neoplasms/blood , MicroRNAs/blood , Aged , Colonic Neoplasms/therapy , Disease-Free Survival , Female , Humans , Male , Mesenteric Veins , Neoplasm Metastasis
11.
Cir Esp ; 84(5): 262-6, 2008 Nov.
Article in Spanish | MEDLINE | ID: mdl-19080911

ABSTRACT

INTRODUCTION: Outpatient laparoscopic cholecystectomy (CL) has not been generalised due to the fear of complications by the surgeon and preference of patients for hospitalisation. This situation could be changed by setting up strict selection criteria and providing hospital home care. The aims of this study are to find out what percentage of our population fulfil these criteria, confirm their validity and find out if the surgical process should be improved before being introduced. MATERIAL AND METHOD: A retrospective analysis was carried out on the first 200 elective CL cases dating from January 2006. The exclusion criteria were as follows: pre-operative criteria (social causes, age $ 70 years, unstable ASA III or ASA IV, an associated pathology or admission due to biliopancreatic patho-logy), intra-operative criteria (conversion, surgical time lasting longer than 90 minutes, non-identification or bleeding of the cystic artery, application of haemostatic material, haemorrhaging in the entrance ports, intra-abdominal bile spillage, drainage, difficulties in removing the gallbladder, anaesthetic and/or surgical complications) and post-operative (haemodynamic instability, excessive pain, nausea, and /or vomiting). RESULTS: Out of the 200 cases, 53 (26.5%) patients fulfilled the criteria. The outpatient system was preferred predominantly by females and by those younger in age. Post-operative incidents occurred in 9.4% of the cases and these were dealt with by the hospital home care team. CONCLUSIONS: Ambulatory CL procedure is safe. Patients of advanced age or with associated pathologies limit the inclusion. Hospital home care can solve any possible complications and contribute to the speedy discharge in those patients without criteria.


Subject(s)
Ambulatory Surgical Procedures , Cholecystectomy, Laparoscopic , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Young Adult
12.
Cir. Esp. (Ed. impr.) ; 84(5): 262-266, nov. 2008. ilus, tab
Article in Es | IBECS | ID: ibc-69215

ABSTRACT

Introducción. La colecistectomía laparoscópica(CL) ambulatoria no se ha generalizado por temor del cirujano a las potenciales complicaciones postoperatorias y preferencia del paciente a la hospitalización. El establecimiento de criterios selectivos estrictos y la hospitalización a domicilio podrían cambiar esta predisposición. Los objetivos de este estudio son averiguar qué porcentaje de nuestra población con colelitiasis cumple dichos criterios, confirmar su validez y descubrir si debe mejorarse el proceso quirúrgico antes de implementarse. Material y método. Se analizan prospectivamente los primeros 200 casos de CL electiva desde enero de 2006. Los criterios de exclusión son: preoperatorios(causas sociales, edad >= 70 años, ASA III inestable o ASA IV, enfermedad concomitante que precisa control hospitalario, ingreso previo por afección biliopancreática), intraoperatorios (conversión a laparotomía, tiempo quirúrgico >= 90 min, sin identificació no sangrado de la arteria cística, aplicación de material hemostático, hemorragia en puertas de entrada, vertido de bilis intraabdominal, drenajes, extracción dificultosa de vesícula, complicaciones anestésicas y/o quirúrgicas) y postoperatorios (inestabilidad hemodinámica, dolor excesivo, náuseas y/o vómitos en la sala de reanimación).Resultados. Cumplieron criterios 53 (26,5%) pacientes. El sexo femenino y la menor edad favorecen el proceso ambulatorio. Se presentaron incidencias postoperatorias en el 9,4% que podrían asumirse por el equipo de hospitalización a domicilio. Conclusiones. La CL en régimen ambulatorio es segura. La edad avanzada y la enfermedad concomitante limitan la inclusión. La hospitalización a domicilio puede solucionar las posibles complicaciones y facilitar el alta precoz de los pacientes sin criterios de CL ambulatoria (AU)


Introduction. Outpatient laparoscopic cholecystectomy (CL) has not been generalised due to the fear of complications by the surgeon and preference of patients for hospitalisation. This situation could be changed by setting up strict selection criteria and providing hospital home care. The aims of this study are to find out what percentage of our population fulfil these criteria, confirm their validity and find out if the surgical process should be improved before being introduced. Material and method. A retrospective analysis was carried out on the first 200 elective CL cases dating from January 2006. The exclusion criteria were as follows: pre-operative criteria (social causes, age $ 70 years, unstable ASA III or ASA IV, an associated pathology or admission due to biliopancreatic patho-logy), intra-operative criteria (conversion, surgical time lasting longer than 90 minutes, non-identification or bleeding of the cystic artery, application of haemostatic material, haemorrhaging in the entrance ports, intra-abdominal bile spillage, drainage, difficulties in removing the gallbladder, anaesthetic and/or surgical complications) and post-operative (haemodynamic instability, excessive pain, nausea, and /or vomiting). Results. Out of the 200 cases, 53 (26.5%) patients fulfilled the criteria. The outpatient system was preferred predominantly by females and by those younger in age. Post-operative incidents occurred in 9.4% of the cases and these were dealt with by the hospital home care team. Conclusions. Ambulatory CL procedure is safe. Patients of advanced age or with associated pathologies limit the inclusion. Hospital home care can solve any possible complications and contribute to the speedy discharge in those patients without criteria (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Cholecystectomy, Laparoscopic/methods , Cholecystectomy, Laparoscopic/trends , Cholelithiasis/pathology , Cholelithiasis/surgery , Monitoring, Ambulatory/instrumentation , Ambulatory Surgical Procedures/methods , Ambulatory Surgical Procedures/trends , Home Care Services , Home Nursing/organization & administration , Prospective Studies , Body Mass Index , Postoperative Complications/pathology , Postoperative Complications/surgery
14.
Clin Colorectal Cancer ; 6(9): 634-40, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17945035

ABSTRACT

PURPOSE: Phase II/III studies have shown XELOX to be as effective as FOLFOX in patients with advanced colorectal cancer (CRC). The study was designed to evaluate the activity and tolerability of XELOX in CRC. In August 2002, we began a prospective study of XELOX as first-line therapy for patients with metastatic CRC. Twenty-two patients were enrolled between November 2002 and August 2003 (series I). An interim analysis performed in August 2003 revealed that 32% of patients required a dose reduction of oxaliplatin because of toxicity. From August 2003 to April 2005, an additional 20 patients were included (series II). This second group of patients received oxaliplatin at a lower dose. PATIENTS AND METHODS: The first 22 patients (series I) included received oxaliplatin 130 mg/m(2) on day 1 plus capecitabine 2000 mg/m(2) daily on days 1-15 (3-week cycle). The second set of 20 patients (series II) received oxaliplatin 85 mg/m(2) on day 1; the dose of capecitabine and the frequency of administration were not modified. RESULTS: Patient characteristics were well balanced in the 2 series. Overall response (series I vs. II): 41% vs. 65%; median time to progression was similar: 10.51 vs. 10.92 (log-rank test, P = .79). Median survival was similar in the 2 series: 19.55 vs. 21.18 months (log-rank test, P = .61). Grade 3/4 toxicity (series I vs. II): peripheral neuropathy, 14% vs. 0 (P = .23). CONCLUSION: In patients with advanced CRC, in combination with capecitabine, oxaliplatin 85 mg/m(2) is as effective with lower toxicity when compared with oxaliplatin 130 mg/m(2).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Capecitabine , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Combinations , Drug-Related Side Effects and Adverse Reactions , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/pharmacology , Humans , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/pharmacology , Oxaloacetates , Survival Analysis
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