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1. Faecal Immunochemical Test Impact on Prognosis of Colorectal Cancer Detected in Symptomatic Patients

Author

Jesús Daniel Fernández de Castro, Franco Baiocchi Ureta, Raquel Fernández González, Noel Pin Vieito, and Joaquín Cubiella Fernández

Subjects
colorectal cancer, diagnosis, FIT, symptomatic, Medicine (General), R5-920
Abstract

The use of the faecal immunochemical test (FIT) to stratify the risk of colorectal cancer (CRC) in symptomatic patients in primary healthcare enables improved referrals to colonoscopy. However, its effect on diagnostic delays or the prognosis of patients has been poorly evaluated in this setting. We performed a retrospective cohort study that included symptomatic patients with outpatient CRC diagnosis between 2009 and 2017. We identified whether FIT had been analysed between initial healthcare contact and diagnostic confirmation. We included 589 patients (male = 65%, 71.7 ± 11.6 years, TNM IV = 17.1%) in the analysis. FIT was performed in 411 (69.8%) patients with a positive result (≥10 µg/g of faeces) in 96.4% of the evaluated patients. The use of FIT was associated with increased diagnostic delay (yes = 159 ± 277 days, no = 111 ± 172 days; p = 0.01). At five years follow up, 193 (32.8%) patients died (151 due to CRC). Mean survival was not modified by the use of FIT or its result (not performed = 46.8 ± 1.5 months, FIT+ = 48.9 ± 1 months, FIT− = 45.6 ± 5.5 months; p = 0.5) in Kaplan–Meier analysis, and was confirmed later in multivariate Cox regression analysis. In conclusion, FIT determination in symptomatic patients in primary healthcare did not modify CRC prognosis.

Published
2022
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2. Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort

Author

Noel Pin-Vieito, María José Iglesias, David Remedios, Victoria Álvarez-Sánchez, Fernando Fernández-Bañares, Jaume Boadas, Eva Martínez-Bauer, Rafael Campo, Luis Bujanda, Ángel Ferrández, Virginia Piñol, Daniel Rodríguez-Alcalde, Martín Menéndez-Rodríguez, Natalia García-Morales, Cristina Pérez-Mosquera, and Joaquín Cubiella

Subjects
biochemical diagnosis, carcinoembryonic antigen, colonoscopy, early cancer, gastrointestinal cancer, symptoms, Medicine (General), R5-920
Abstract

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3–3.1), CRC (HR 4.4, 95% CI 1.1–17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0–2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3–5.8), rectal bleeding (OR 0.3, 95% CI 0.1–0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7–7.1). However, CEA was increased only in 31.8% (95% CI, 16.4–52.7%) and 50% (95% CI, 25.4–74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.

Published
2020
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3. Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas

Author

Eduardo Albéniz, María Pellisé, Antonio-Z. Gimeno-García, Alfredo-José Lucendo, Pedro-A. Alonso-Aguirre, Alberto Herreros-de-Tejada, Marco-Antonio Álvarez, María Fraile, Maite Herráiz-Bayod, Leopoldo López-Rosés, David Martínez-Ares, Akiko Ono, Adolfo Parra-Blanco, Eduardo Redondo, Andrés Sánchez-Yagüe, Santiago Soto, José Díaz-Tasende, Marta Montes-Díaz, Manuel Rodríguez-Téllez, Orlando García, Alba Zuñiga-Ripa, Marta Hernández-Conde, Fernando Alberca-de-las-Parras, Carla Gargallo, Esteban Saperas, Miguel Muñoz-Navas, Javier Gordillo, Felipe Ramos-Zabala, José-Manuel Echevarría, Marco Bustamante, Mariano González-Haba, Ferrán González-Huix, Begoña González-Suárez, Juan-José Vila-Costas, Carlos Guarner-Argente, Fernando Múgica, Julyssa Cobián, Joaquín Rodríguez-Sánchez, Bartolomé López-Viedma, Noel Pin, José-Carlos Marín-Gabriel, Óscar Nogales, Joaquín de-la-Peña, Francisco-Javier Navajas-León, Helena León-Brito, David Remedios, José-Miguel Esteban, David Barquero, Juan-Gabriel Martínez-Cara, Felipe Martínez-Alcalá, Ignacio Fernández-Urién, and Eduardo Valdivielso

Subjects
Endoscopic mucosal resection, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

RESUMEN Este documento resume el contenido de la Guía de resección mucosa endoscópica elaborada por el grupo de trabajo de la Sociedad Española de Endoscopia Digestiva (GSEED de Resección Endoscópica) y expone las recomendaciones sobre el manejo endoscópico de las lesiones neoplásicas colorrectales superficiales.

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4. Inadequate social support decreases survival in decompensated liver cirrhosis patients

Author

Natalia García Morales, Margarita Fernández de la Varga, Javier Pumares Pérez, Martín Menéndez Rodríguez, Sagrario Gutiérrez Morato, Carmen Castillo Cejas, Victoria Aguilera, Salvador Benlloch, Luis Menéndez Rodríguez, Teresa Seoane Pillado, Noel Pin Vieito, and Joaquín Cubiella

Subjects
Análisis de supervivencia, Hepatology, Liver cirrhosis, Mortalidad, Gastroenterology, Cirrosis hepática, Mortality, Preventive health services, Survival analysis, Actividades preventivas
Abstract

[Abstract] Introduction: Inadequate social support is associated with higher mortality both in the general population and in patients with chronic diseases. There are no studies that have described social support in liver cirrhosis and its impact on prognosis. Objectives: To analyze the impact social support has in the survival of patients with decompensated cirrhosis. Methods: Prospective multicentric cohort study (2016-2019). Patients with decompensated liver cirrhosis were included. Epidemiological, clinical and social variables were collected, using the validated Medical Outcomes Study Social Support Survey, with a 12-month follow-up. Results: A total of 127 patients were included, of which 79.5% were men. The most common etiology of cirrhosis was alcohol (74.8%), mean age was 60 years (SD 10.29), mean MELD was 15.6 (SD 6.3) and most of the patients had a Child-Pugh B (53.5%) or C (35.4%). In the assessment of social support, we observed that most of the patients (92.2%) had adequate global support. At the end of the follow-up (median 314 days), 70.1% of the patients survived. The 1-year survival rate in patients with inadequate global social support was 30%, compared to 73.5% in the presence of social support. In multivariate Cox regression analysis, inadequate social support predicted survival with an adjusted HR of 5.5 (95% CI 2,3-13,4) independently of MELD (HR 1.1, 95% CI 1-1.2), age (HR 1, 95% CI 1-1.1) and hepatocarcinoma (HR 10.6, 95% CI 4.1-27.4). Conclusion: Adequate social support improves survival in liver cirrhosis, independently of clinical variables. Social intervention strategies should be considered for their management. [Resumen] Introducción. El apoyo social se asocia a mortalidad en población general y en pacientes con enfermedades crónicas. No hay estudios que hayan descrito el apoyo social en cirrosis hepática y su impacto sobre el pronóstico. Objetivo. Analizar el impacto del apoyo social en la supervivencia en cirrosis hepática descompensada. Material y métodos. Estudio multicéntrico prospectivo de cohortes (2016–2019). Se incluyeron pacientes con cirrosis hepática descompensada. Se recogieron variables epidemiológicas, clínicas y sociales mediante la escala validada Medical Outcomes Study Social Support Survey (MOS), realizando un seguimiento de 12 meses. Resultados. Se incluyeron 127 pacientes, el 79,5% eran hombres. La causa más común de la cirrosis hepática fue alcohol (74,8%), la edad media 60 años (DE: 10,29), la media de MELD 15,6 (DE: 6,3) y la mayoría tenían Child-Pugh B (53,5%) o C (35,4%). Se observó que la mayoría de pacientes (92,2%) tenían un apoyo social adecuado (MOS global > 56). Al finalizar el seguimiento (mediana 314 días), el 70,1% de los pacientes sobrevivieron. La supervivencia al año en falta de apoyo social fue del 30%, comparado con el 73,5% en los que el apoyo social era adecuado. En el análisis de regresión multivariante el apoyo social predijo la supervivencia con un HR ajustado de 5,5 (IC 95%: 2,3-13,4) independientemente del MELD (HR: 1,1; IC 95%: 1-1,2), edad (HR: 1; IC 95%: 1-1,1) y hepatocarcinoma (HR: 10,6; IC 95%: 4,1-27,4). Conclusión. El apoyo social inadecuado en pacientes con CH disminuye la supervivencia, independientemente de las variables clínicas. Se deberían plantear estrategias de intervención social para su manejo.

Published
2023

6. Surgical complications in a population-based colorectal cancer screening program: Incidence and associated factors

Author

Cristina Alejandra, Sánchez Gómez, Coral, Tejido Sandoval, Natalia, de Vicente Bielza, Noel, Pin Vieito, Antía, González, Raquel, Almazán, Elena, Rodríguez-Camacho, Juana, Fontenla Rodiles, Carmen, Domínguez Ferreiro, Isabel, Peña-Rey Lorenzo, Raquel, Zubizarreta, and Joaquín, Cubiella

Subjects
Male, Postoperative Complications, Incidence, Humans, General Medicine, Middle Aged, Colorectal Neoplasms, Early Detection of Cancer, Digestive System Surgical Procedures, Retrospective Studies
Abstract

Colorectal cancer (CRC) screening programs produce risks, including those derived from colorectal surgeries. The objective of this analysis is to evaluate the complications associated with the surgery.Retrospective analysis including patients who required colorectal surgery within the population-based CRC screening program in Galicia (May 2013-June 2019). We analyzed the indication for surgery and the rate of in-hospital (mildI-II, severeIII-V, Clavien-Dindo classification) and at discharge complications. We performed a multivariate analysis to determine the variables independently associated.In the analyzed period, 1092 patients underwent surgery (benign lesion 16.5%, pT1 CRC 18.2%, rest of CRC 64.6%) laparoscopic approach in 69.8% of the cases. In-hospital complications were detected in 19.2% of patients (mild: 13.4%; severe: 5.9%; deaths: 0.2%) and at discharge in 159 (14.6%) patients. Male sex was associated with in-hospital complications (OR: 2.0; 95%CI: 1.3-3.0). The variables associated with severe complications were: male sex (OR: 2.6; 95%CI: 1.2-5.5), tertiary hospital (OR: 0.5; 95%CI: 0.2-0.9) and ECOGI (OR: 0.2; 95%CI: 0.05-0.6). The factors associated with complications after discharge were age ≥60years (OR: 1.5; 95%CI: 1.0-2.3), rectal location (OR: 1.6; 95%CI: 1.1-2.3) and in-hospital complications (OR: 2.2; 95%CI: 1.5-3.2).Surgery is the main cause of morbidity and mortality associated with a CRC screening program. These results must be taken into account in the decision making of lesions that are candidates for endoscopic resection.

Published
2022

7. Barreras y beneficios percibidos en la participación en el cribado de cáncer de colon mediante test de sangre oculta en heces

Author

Martín Menéndez Rodríguez, Natalia García-Morales, Teresa Seoane Pillado, Jorge Garau Ramírez, Alba Traver Salvador, Yésica Hervás Jiménez, Noel Pin Vieito, Luis Menéndez Rodríguez, and Joaquín Cubiella

Subjects
Hepatology, Mortalidad, Gastroenterology, Cribado poblacional, Modelo de Creencias en Salud, Cáncer colorrectal, General Medicine, Mass screening, Mortality, Atención primaria, Colorectal neoplasms, Health Belief Model, Primary health care
Abstract

[Abstract] Background: Colorectal cancer is the second cancer-related cause of death in the world. Tumour stage at diagnosis is the principal prognosis factor of survival. However, the participation in the programme is around 50%. The aim of the study was to identify the benefits and barriers perceived by the population when participating in a colorectal cancer screening programme with faecal occult blood test. Methods: We carried out a cases-controls study with 408 participants. We analyzed epidemiological and social variables associated with lifestyle and behavioural factors based in the Health Belief Model. We conducted a descriptive analysis, and identified variables associated to adherence by a logistic regression. Results: Variables independently associated with the participation in a colorectal cancer screening programme were age (OR 1.06; 95% CI: 1.01-1.11), having a stable partner (OR 1.96; 95% CI: 1.20-3.18), the level of education (OR 1.59; 95% CI: 1.02-2.47) and two of the barriers to participate in the faecal occult blood test screening: "you don't know how to do one" (OR=0.46; 95% CI: 0.23-0.93) and "it is not that important right now" (OR=0.43; 95% CI: 0.24-0.78). Conclusion: The existing barriers for screening with faecal occult blood test are the best factor predicting. This is relevant when designing the intervention programmes, as they should focus on reducing perceived barriers to increase the participation in colorectal cancer screening, thereby reducing colorectal cancer mortality. [Resumen] Antecedentes. El cáncer colorrectal constituye la segunda causa de muerte por cáncer en el mundo. El estadio del tumor al diagnóstico es el principal factor pronóstico de supervivencia. Sin embargo, la participación en el programa está en torno al 50%. El objetivo de este estudio fue identificar los beneficios y las barreras percibidos por la población al participar en un programa de cribado de cáncer de colon mediante el test de sangre oculta en heces. Métodos. Estudio de casos y controles con 408 participantes en el que analizamos variables sociodemográficas, variables asociadas al estilo de vida y factores conductuales basados en el Modelo de Creencias en Salud. Realizamos un análisis descriptivo y, para identificar las variables asociadas a la adhesión al programa de cribado de cáncer colorrectal, una regresión logística. Resultados. Las variables que se asociaron de forma independiente a la participación en el programa fueron la edad (OR 1,06; IC 95% 1,01-1,11), tener pareja estable (OR 1,96; IC 95% 1,20-3,18), el nivel de estudios (OR 1,59; IC 95% 1,02-2,47) y 2 de las barreras para participar en el cribado mediante test de sangre oculta en heces: «no sabe cómo hacerlo» (OR 0,46; IC 95% 0,23-0,93) y «no es un problema importante en el momento actual» (OR 0,3; IC 95% 0,24-0,78). Conclusión. Las barreras existentes para el cribado mediante test de sangre oculta en heces son el mejor factor predictivo de participación. Esto es importante a la hora de diseñar los programas de cribado de cáncer colorrectal, ya que la reducción de las barreras percibidas aumentará la participación en los mismos, reduciendo así la mortalidad por cáncer de colon.

Published
2023

8. Validación al castellano del cuestionario Rawl de cribado de cáncer colorrectal con sangre oculta en heces

Author

M.M. Martín Rodríguez, Pablo Vega Villaamil, Jorge Garau Ramírez, Yésica Hervás Jiménez, Joaquín Cubiella, Natalia García Morales, Alba Traver Salvador, Noel Pin Vieito, Agustín Montes Martinez, and Teresa Seoane Pillado

Subjects
03 medical and health sciences, 0302 clinical medicine, Hepatology, business.industry, 030220 oncology & carcinogenesis, Gastroenterology, Medicine, 030212 general & internal medicine, business, Humanities
Abstract

Resumen Introduccion La supervivencia del cancer colorrectal es del 57% a los 5 anos, en parte debido a un diagnostico tardio por una baja participacion en los programas de cribado. Son necesarios instrumentos que analicen las causas de participacion. Objetivo Comprobar la validez y consistencia interna de la version en castellano del cuestionario de Rawl para el cribado de cancer colorrectal con sangre oculta en heces. Tipo de estudio Metodologia de validacion de cuestionarios. Localizacion Tres centros de salud de Valencia. Variables Edad, sexo, estado civil, nivel de estudios, clase social, consumo de tabaco, alcohol, indice de masa corporal, antecedentes personales y familiares de cancer. Resultados Se estudiaron 408 individuos (237 casos y 171 controles). La edad media fue de 59,45 (DE 5,17) anos. La consistencia interna de todas las variables alcanzo una alfa de Cronbach de 0,796. El alfa de Cronbach de la dimension beneficios del cribado fue de de 0,871 y para la dimension barreras al cribado fue de 0,817. Los coeficientes de correlacion intraclase del test-retest para la dimension de los beneficios del cribado fue de 0,809 (IC 95% 0,606-0,913) y de 0,499 (IC 95% 0,126-0,750) para las barreras. Conclusion La version en castellano del cuestionario Rawl es valido, fiable y reproducible. Con lo que disponemos de un elemento validado en Espana con el que objetivar barreras y beneficios percibidos en un programa de cribado poblacional.

Published
2022

9. Quantitative brain T1 maps derived from T1-weighted MRI acquisitions: a proof-of-concept study

Author

Audrey Lavielle, Noël Pinaud, Bei Zhang, and Yannick Crémillieux

Subjects
Brain, Brain neoplasms, Contrast media, Magnetic resonance imaging, T1 mapping, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Background Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences. Methods A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps. Results Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI− 1.11 (R 2 = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd3+ concentration value in brain metastases was 94.7 ± 30.0 μM. Conclusion The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions. Relevance statement High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions. Key Points Quantitative T1 mapping adds significant value to MRI diagnostics. T1 measurement sequences are rarely included in routine protocols. T1 mapping and concentration of contrast agents can be derived from routine standard scans. The diagnostic value of MRI can be improved without additional scan time. Graphical Abstract

Published
2024
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10. Design, Synthesis, and In Vitro Antimalarial Evaluation of New 1,3,5-Tris[(4-(Substituted-Aminomethyl)Phenoxy)Methyl]Benzenes

Author

Sandra Albenque-Rubio, Jean Guillon, Patrice Agnamey, Céline Damiani, Solène Savrimoutou, Romain Mustière, Noël Pinaud, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Mathieu Marchivie, Serge Moukha, Pascale Dozolme, Pascal Sonnet, and Anita Cohen

Subjects
antimalarial activity, 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene, G-quadruplexes, synthesis, Pharmacy and materia medica, RS1-441, Chemistry, QD1-999
Abstract

By taking into account our previously described series of 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds, we have now designed, prepared, and evaluated in vitro against Plasmodium falciparum a novel series of structural analogues of these molecules, i.e., the 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivatives. The pharmacological data showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new nitrogen polyphenoxymethylbenzene compounds was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivative 1m was found as one of the most potent and promising antimalarial candidates with favorable cytotoxic to antiprotozoal properties in the P. falciparum strains W2 and 3D7. In conclusion, this 1,3,5-tris[(4-(pyridin-3-ylmethylaminomethyl)phenoxyl)methyl]benzene 1m (IC50 = 0.07 μM on W2, 0.06 μM on 3D7, and 62.11 μM on HepG2) was identified as the most promising antimalarial derivative with selectivity indexes (SI) of 887.29 on the W2 P. falciparum chloroquine-resistant strain, and of 1035.17 on the chloroquine-sensitive and mefloquine decreased sensitivity strain 3D7. It has been previously described that the telomeres of P. falciparum could represent potential targets for these types of polyaromatic compounds; therefore, the capacity of our novel derivatives to stabilize the parasitic telomeric G-quadruplexes was assessed using a FRET melting assay. However, with regard to the stabilization of the protozoal G-quadruplex, we observed that the best substituted derivatives 1, which exhibited some interesting stabilization profiles, were not the most active antimalarial compounds against the two Plasmodium strains. Thus, there were no correlations between their antimalarial activities and selectivities of their respective binding to G-quadruplexes.

Published
2024
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11. Optimal diagnostic accuracy of quantitative faecal immunochemical test positivity thresholds for colorectal cancer detection in primary health care: A community‐based cohort study

Author

Joaquín Cubiella, Luis Bujanda, María A. Gutierrez-Stampa, Vanessa Aguilar-Gama, Isabel Portillo, Laura García Nimo, Noel Pin-Vieito, and Begona Román Alonso

Subjects
Male, medicine.medical_specialty, Colorectal cancer, Colon, faecal haemoglobin, Primary health care, Colonoscopy, Diagnostic accuracy, colorectal cancer, Sensitivity and Specificity, 03 medical and health sciences, Feces, Hemoglobins, 0302 clinical medicine, diagnostic performance, Internal medicine, Primary health, medicine, Humans, faecal biomarkers, 3207.03 Carcinogénesis, Early Detection of Cancer, Aged, Retrospective Studies, Community based, Aged, 80 and over, medicine.diagnostic_test, Primary Health Care, business.industry, 2302.16 Inmunoquímica, Gastroenterology, Middle Aged, medicine.disease, faecal immunochemical test, Immunohistochemistry, 3212 Salud Publica, Test (assessment), Oncology, Spain, 030220 oncology & carcinogenesis, Occult Blood, 030211 gastroenterology & hepatology, Original Article, Female, business, Colorectal Neoplasms, Cohort study
Abstract

Background Optimizing colonoscopy resources is challenging, and information regarding performing diagnostic quantitative faecal immunochemical test (FIT) in daily clinical practice in primary health care is still limited. This study aimed to assess the sensitivity, specificity, positive predictive value and negative predictive value of varying FIT positivity thresholds on colorectal cancer (CRC) detection in primary health care. Methods A retrospective cohort study of 38,675 asymptomatic and symptomatic patients with a FIT (OC-Sensor™) performed between 2012 and 2016 in a primary health-care setting, using a clinical laboratory database of two Spanish areas linked with the National Health System's Hospital Discharge Records Database. The primary outcome was 2-year CRC incidence. Results The mean age of the participants was 63.2 years; 17,792 (46.0%) were male. CRC prevalence was 1.7% (650/38,675). The percentage of patients with a FIT result above the threshold was 20.7% and 14.6% for 10 μg Hb/g faeces and 20 μg Hb/g faeces thresholds, respectively. Sensitivity was 90.5% (95% confidence interval 88.0%–92.5%) at a 10 μg Hb/g faeces threshold, and this decreased by 3.1% when a 20 μg Hb/g faeces threshold was used. The negative predictive value for CRC was at least 99.2% in any subgroup analysed. At a 20 μg Hb/g faeces threshold, less than one additional CRC would be missed per 1000 patients investigated, while approximately 1.3 times more colonoscopy examinations were needed to identify an incidence of CRC using the lowest threshold for any situation analysed. Conclusions In primary health care, a quantitative FIT threshold should be tailored to colonoscopy capacity and CRC prevalence in specific populations. Instituto de Salud Carlos III, España | Ref. PI17/00837

Published
2021

12. Validación al castellano del cuestionario Rawl de cribado de cáncer colorrectal con sangre oculta en heces

Author

Martín, Menéndez Rodríguez, Jorge, Garau Ramírez, Alba, Traver Salvador, Yésica, Hervás Jiménez, Natalia, García Morales, Teresa, Seoane Pillado, Noel, Pin Vieito, Pablo, Vega Villaamil, Agustín, Montes Martínez, and Joaquín, Cubiella

Subjects
Questionnaire, Age Factors, Validación de cuestionarios, Modelo de creencias en salud, General Medicine, Middle Aged, Primary care, Atención primaria, Colorectal cancer screening, Sex Factors, Health belief model, Case-Control Studies, Occult Blood, Validation, Educational Status, Humans, Translations, Cribado cáncer colorrectal, Colorectal Neoplasms, Aged, Language
Abstract

[Abstract] Introduction: Colorectal cancer 5-years-survival is 57%, partway due to a low rate of participation in screening programmes. Instruments analyzing causes of low adherence are needed. Objective: To evaluate the validity and internal consistency of the Spanish version of Rawl's Questionnaire for the screening of colorectal cancer by faecal occult blood testing. Type of study: Questionnaire validation methodology. Location: Three Primary Care Centres in Valencia. Variables: Age, sex, civil status, educational level, social class, smoking, alcohol consumption, body mass index, personal and family history of cancer. Results: We analyzed 408 individuals (237 cases and 171 controls). Mean age was 59.45 years (SD 5.17). Internal consistency of all variables reached a Cronbach's alfa of 0.796. The Cronbach's alfa benefit dimension of the screening was 0.871 and for the barrier dimension of the screening it was 0.817. Intraclass correlation coefficients of the test-retest for the benefit dimension of the screening was 0.809 (CI 95% 0.606-0.913) and 0.499 (CI 95% 0.126-0.750) for the barrier dimension. Conclusion: The Spanish version of Rawl's Questionnaire is valid, reliable and reproducible, so we have this validated instrument with which to identify barriers and benefits in a colorectal screening programme in Spain. [Abstract] Introducción. La supervivencia del cáncer colorrectal es del 57% a los 5 años, en parte debido a un diagnóstico tardío por una baja participación en los programas de cribado. Son necesarios instrumentos que analicen las causas de participación. Objetivo. Comprobar la validez y consistencia interna de la versión en castellano del cuestionario de Rawl para el cribado de cáncer colorrectal con sangre oculta en heces. Tipo de estudio. Metodología de validación de cuestionarios. Localización. Tres centros de salud de Valencia. Variables. Edad, sexo, estado civil, nivel de estudios, clase social, consumo de tabaco, alcohol, índice de masa corporal, antecedentes personales y familiares de cáncer. Resultados. Se estudiaron 408 individuos (237 casos y 171 controles). La edad media fue de 59.45 (DE 5.17) años. La consistencia interna de todas las variables alcanzó una alfa de Cronbach de 0.796. El alfa de Cronbach de la dimensión beneficios del cribado fue de de 0.871 y para la dimensión barreras al cribado fue de 0.817. Los coeficientes de correlación intraclase del test-retest para la dimensión de los beneficios del cribado fue de 0.809 (IC 95% 0.606−0.913) y de 0.499 (IC 95% 0.126−0.750) para las barreras. Conclusión. La versión en castellano del cuestionario Rawl es válido, fiable y reproducible. Con lo que disponemos de un elemento validado en España con el que objetivar barreras y beneficios percibidos en un programa de cribado poblacional.

Published
2022

13. The effect of delay on the prognosis of colorectal cancer

Author

Jesús Daniel Fernández-de Castro, Franco Baiocchi Ureta, Joaquín Cubiella Fernández, Noel Pin Vieito, and Raquel Fernández González

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Medicine, 030211 gastroenterology & hepatology, Primary care, business
Abstract

Resumen Objetivo Analizar el efecto de la demora atribuible al sistema sanitario en una cohorte consecutiva de pacientes diagnosticados de forma ambulatoria de cancer colorrectal (CCR) en el area sanitaria de Ourense. Pacientes y metodos Estudio observacional de cohortes retrospectivo en el que se incluyeron los pacientes diagnosticados entre 2009 y 2017. Se definio la demora atribuible al sistema sanitario como el tiempo entre la primera consulta por sintomas y la confirmacion diagnostica. Se determino si existia una relacion independiente entre la demora diagnostica y el CCR estadio IV mediante una regresion logistica. Finalmente, realizamos una regresion de riesgos proporcionales para determinar que variables se asociaban con la mortalidad global y por CCR. Resultados Se incluyeron 575 pacientes (hombres 64.5%, edad 71.9 ± 11.5 anos) con una demora atribuible al sistema sanitario de 115 ± 153 dias. Ninguna de las variables analizadas se asocio con el estadio tumoral al diagnostico. Durante un seguimiento de 30.6 ± 21 meses fallecieron 121 pacientes (79.3% en relacion al CCR). Las variables asociadas de forma independiente con la mortalidad atribuible al CCR fueron el estadio IV al diagnostico (HR 50.65, IC 95% 12.28-209), la edad (HR 1.04, IC 95% 1.02-1.05) y la solicitud de la colonoscopia desde Atencion Primaria (HR 0.55, IC 95% 0.37-0.88). Conclusiones La demora diagnostica atribuible al sistema sanitario no se relaciono ni con el estadio ni con el pronostico del CCR. Sin embargo, la solicitud de la colonoscopia desde Atencion Primaria se asocio a una reduccion en el riesgo de mortalidad.

Published
2019

14. Efecto de la demora atribuible al sistema sanitario en el pronóstico del cáncer colorrectal

Author

Franco Baiocchi Ureta, Noel Pin Vieito, Raquel Fernández González, Jesús Daniel Fernández-de Castro, and Joaquín Cubiella Fernández

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Hepatology, business.industry, 030220 oncology & carcinogenesis, Gastroenterology, medicine, 030211 gastroenterology & hepatology, business
Abstract

Resumen Objetivo Analizar el efecto de la demora atribuible al sistema sanitario en una cohorte consecutiva de pacientes diagnosticados de forma ambulatoria de cancer colorrectal (CCR) en el area sanitaria de Ourense. Pacientes y metodos Estudio observacional de cohortes retrospectivo en el que se incluyeron los pacientes diagnosticados entre 2009 y 2017. Se definio la demora atribuible al sistema sanitario como el tiempo entre la primera consulta por sintomas y la confirmacion diagnostica. Se determino si existia una relacion independiente entre la demora diagnostica y el CCR estadio IV mediante una regresion logistica. Finalmente, realizamos una regresion de riesgos proporcionales para determinar que variables se asociaban con la mortalidad global y por CCR. Resultados Se incluyeron 575 pacientes (hombres 64,5%, edad 71,9 ± 11,5 anos) con una demora atribuible al sistema sanitario de 115 ± 153 dias. Ninguna de las variables analizadas se asocio con el estadio tumoral al diagnostico. Durante un seguimiento de 30,6 ± 21 meses fallecieron 121 pacientes (79,3% en relacion al CCR). Las variables asociadas de forma independiente con la mortalidad atribuible al CCR fueron el estadio IV al diagnostico (HR 50,65; IC 95% 12,28-209), la edad (HR 1,04; IC 95% 1,02-1,05) y la solicitud de la colonoscopia desde Atencion Primaria (HR 0,55; IC 95% 0,37-0,88). Conclusiones La demora diagnostica atribuible al sistema sanitario no se relaciono ni con el estadio ni con el pronostico del CCR. Sin embargo, la solicitud de la colonoscopia desde Atencion Primaria se asocio a una reduccion en el riesgo de mortalidad.

Published
2019

16. Implantable theranostic device for in vivo real-time NMR evaluation of drug impact in brain tumors

Author

Justine Deborne, Imad Benkhaled, Véronique Bouchaud, Noël Pinaud, and Yannick Crémillieux

Subjects
Medicine, Science
Abstract

Abstract The evaluation of the efficacy of a drug is a fundamental step in the development of new treatments or in personalized therapeutic strategies and patient management. Ideally, this evaluation should be rapid, possibly in real time, easy to perform and reliable. In addition, it should be associated with as few adverse effects as possible for the patient. In this study, we present a device designed to meet these goals for assessing therapeutic response. This theranostic device is based on the use of magnetic resonance imaging and spectroscopy for the diagnostic aspect and on the application of the convection-enhanced delivery technique for the therapeutic aspect. The miniaturized device is implantable and can be used in vivo in a target tissue. In this study, the device was applied to rodent glioma models with local administration of choline kinase inhibitor and acquisition of magnetic resonance images and spectra at 7 Tesla. The variations in the concentration of key metabolites measured by the device during the administration of the molecules demonstrate the relevance of the approach and the potential of the device.

Published
2024
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17. High-risk symptoms and quantitative faecal immunochemical test accuracy: Systematic review and meta-analysis

Author

Joaquín Cubiella, Sara Zarraquiños, and Noel Pin Vieito

Subjects
medicine.medical_specialty, Colorectal cancer, Diagnostic accuracy, Sensitivity and Specificity, Inflammatory bowel disease, Gastroenterology, Hemoglobins, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Internal medicine, Prevalence, medicine, Faecal haemoglobin, Humans, Mass Screening, 3207.03 Carcinogénesis, Referral and Consultation, Faecal occult blood test, Early Detection of Cancer, Faecal immunochemical test, Primary Health Care, Significant colonic lesion, business.industry, 2302.16 Inmunoquímica, Immunochemistry, digestive, oral, and skin physiology, General Medicine, medicine.disease, Test (assessment), Occult Blood, 030220 oncology & carcinogenesis, Meta-analysis, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, 3205.03 Gastroenterología, Colorectal Neoplasms, business, Bowel disease, Meta-Analysis
Abstract

BACKGROUND The quantitative faecal immunochemical test for haemoglobin (FIT) has been revealed to be highly accurate for colorectal cancer (CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 µg Hb/g faeces threshold. Nevertheless, it is unknown whether FIT´s accuracy remains stable throughout the broad spectrum of possible symptoms. AIM To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings. METHODS A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand, threshold of faecal haemoglobin concentration for a positive test result, percentage of reported symptoms (solely symptomatic, mixed cohorts) and CRC prevalence (< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT´s accuracy to detect CRC. RESULTS Fifteen cohorts including 13073 patients (CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 µg Hb/g faeces threshold (n = 10400) was 89.6% [95% confidence interval (CI): 82.7% to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients (n = 4035) and mixed cohorts (n = 6365) were 94.1% (95%CI: 90.0% to 96.6%) and 85.5% (95%CI: 76.5% to 91.4%) respectively (P < 0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5% (84.9%, 95%CI: 73.4% to 92.0%) and ≥ 2.5% (91.7%, 95%CI: 83.3% to 96.1%) (P = 0.25). At the same threshold, OC-Sensor® sensitivity to rule out any significant colonic lesion was 78.6% (95%CI: 75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity. CONCLUSION The results of this meta-analysis confirm that, regardless of CRC prevalence, quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.

Published
2019

18. Faecal immunochemical test outside colorectal cancer screening?

Author

Noel Pin-Vieito, Daniel Fernández-de-Castro, Manuel Puga, and Joaquín Cubiella

Subjects
Adenoma, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Colorectal cancer, Faecal biomarkers, Colonoscopy, Sensitivity and Specificity, Feces, Hemoglobins, Health care, Pandemic, medicine, Humans, Mass Screening, Faecal haemoglobin, Intensive care medicine, Mass screening, Early Detection of Cancer, medicine.diagnostic_test, Faecal immunochemical test, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, Minireviews, General Medicine, medicine.disease, digestive system diseases, Test (assessment), Occult Blood, Biomarker (medicine), Diagnostic performance, business, Colorectal Neoplasms, Primary healthcare
Abstract

Faecal immunochemical tests (FITs) are the most widely colorectal cancer (CRC) diagnostic biomarker available. Many population screening programmes are based on this biomarker, with the goal of reducing CRC mortality. Moreover, in recent years, a large amount of evidence has been produced on the use of FIT to detect CRC in patients with abdominal symptoms in primary healthcare as well as in surveillance after adenoma resection. The aim of this review is to highlight the available evidence on these two topics. We will summarize the evidence on diagnostic yield in symptomatic patients with CRC and significant colonic lesion and the different options to use this (thresholds, brands, number of determinations, prediction models and combinations). We will include recommendations on FIT strategies in primary healthcare proposed by regulatory bodies and scientific societies and their potential effects on healthcare resources and CRC prognosis. Finally, we will show information regarding FIT-based surveillance as an alternative to endoscopic surveillance after high-risk polyp resection. To conclude, due to the coronavirus disease 2019 pandemic, FIT-based strategies have become extremely relevant since they enable a reduction of colonoscopy demand and access to the healthcare system by selecting individuals with the highest risk of CRC.

Published
2021

19. Faecal immunochemical tests safely enhance rational use of resources during the assessment of suspected symptomatic colorectal cancer in primary care: systematic review and meta-analysis

Author

Noel Pin-Vieito, Joaquín Cubiella, Cristina Sánchez-Gómez, Coral Tejido-Sandoval, and Natalia de Vicente-Bielza

Subjects
Adult, medicine.medical_specialty, Colorectal cancer, MEDLINE, Colonoscopy, Primary care, Rational use, Sensitivity and Specificity, 03 medical and health sciences, Feces, Hemoglobins, 0302 clinical medicine, Internal medicine, medicine, Humans, Early Detection of Cancer, medicine.diagnostic_test, Primary Health Care, business.industry, Gastroenterology, medicine.disease, Triage, Systematic review, 030220 oncology & carcinogenesis, Meta-analysis, Occult Blood, 030211 gastroenterology & hepatology, business, Colorectal Neoplasms
Abstract

ObjectiveImplementation of faecal immunochemical tests (FIT) as a triage test in primary healthcare may improve the efficiency of referrals without missing cases of colorectal cancer (CRC). We aim to summarise the performance characteristics of FITs for CRC in symptomatic patients presenting to primary healthcare.DesignWe performed a systematic literature review of Medline and EMBASE databases from May 2018 to November 2020. Previous related systematic searches were also adapted to this aim and completed with reference screening. We identified studies performed on adult patients consulting for abdominal symptoms in primary care which reported data such that the FIT diagnostic performance parameters for CRC could be obtained. Bivariate models were used to synthesise available evidence. Meta-regression analysis was performed to evaluate the causes of heterogeneity.ResultsTwenty-three studies (69 536 participants) were included (CRC prevalence 0.3%–6.2%). Six studies (n=34 691) assessed FIT as rule in test (threshold of ≥150 µg Hb/g faeces) showing a sensitivity of 64.1% (95% CI 57.8% to 69.9%) and a specificity of 95.0% (95% CI 91.2% to 97.2%). A threshold of 10 µg/g (15 studies; n=48 872) resulted in a sensitivity of 87.2% (95% CI 81.0% to 91.6%) and a specificity of 84.4% (95% CI 79.4% to 88.3%) for CRC. At a 20 µg Hb/g faeces threshold (five studies; n=24 187) less than one additional CRC would be missed per 1000 patients investigated compared with 10 µg Hb/g faeces threshold (CRC prevalence 2%).ConclusionFIT is the test of choice to evaluate patients with new-onset lower gastrointestinal symptoms in primary healthcare.

Published
2021

20. Crystal Structure of Bis(1-butyl-1-methypyrrolidinium) Perthiodicarbonate Complex

Author

Noël Pinaud, Yann Danten, Mathieu Marchivie, Marcel Besnard, Isabel Cabaço, and Jean Guillon

Subjects
bis(1-butyl-1-methypyrrolidinium) perthiodicarbonate, ionic liquid, single-crystal X-ray diffraction analysis, Inorganic chemistry, QD146-197
Abstract

Bis(1-butyl-1-methypyrrolidinium) perthiodicarbonate was obtained by the reaction of carbon disulfide with 1-butyl-1-methypyrrolidinium acetate ([BmPyrro][Ac]) in the liquid phase. Structural characterization of this original complex was achieved by single-crystal X-ray diffraction (SCXRD) analysis. The asymmetric unit of the title compound, C2S6·2C9H20N, consisted of two crystallographically 1-methyl-1-butyl pyrrolidinium cations and one perthiodicarbonate anion. The complex C2S6·2C9H20N crystallized in the monoclinic space group, C 2/c, and possessed the following cell parameters: a = 16.0970(10) Å, b = 14.7140(9) Å, c = 12.3280(8) Å, α = 90°, β = 112.3730(12)°, γ = 90°, V = 2700.11 Å3, and Z = 8, Z’ = 0.5.

Published
2024
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21. Effect of Health Belief Model on the Participation in FOBT CRC Screening Programme: Case/Control Study

Author

Luis Menéndez Rodríguez, Natalia García-Morales, Noel Pin Vieito, M.M. Martín Rodríguez, Alba Traver Salvador, Teresa Seoane Pillado, Joaquín Cubiella, Yésica Hervás Jiménez, and Jorge Garau Ramírez

Subjects
medicine.medical_specialty, History, Polymers and Plastics, Crc screening, business.industry, Family medicine, Case-control study, medicine, Health belief model, Business and International Management, business, Industrial and Manufacturing Engineering
Abstract

BackgroundColorectal cancer is the second cancer-related cause of death in the world. Tumor stage at diagnosis is the principal prognosis factor of survival. However, the participation in the program is around 50%. The aim of the study was to identify the benefits and barriers perceived by the population when participating in a colorectal cancer screening program with faecal occult blood test.MethodsWe carried out a cases-controls study with 408 participants. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors based in the Health Belief Model. We conducted a descriptive analysis, and identified variables associated to adherence by a logistic regression. ResultsVariables independently associated with the participation in a colorectal cancer screening program were age (OR 1.06; 95% CI: 1.01-1.11), having a stable partner (OR 1.96; 95% CI: 1.20-3.18), the level of education (OR 1.59; 95% CI:1.02-2.47) and two of the barriers to participate in the faecal occult blood test screening: “not to know how to do it” (OR=0.46; 95% CI: 0.23-0.93) and “to take the test is currently not a major problem” (OR=0.43; 95% CI: 0.24-0.78).Conclusion The existing barriers for screening with faecal occult blood test are the best factor predicting. This is relevant when designing the intervention programs, as they should focus on reducing perceived barriers to increase the participation in colorectal cancer screening, thereby reducing colorectal cancer mortality.

Published
2021

22. Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort

Author

David Remedios, Rafael Campo, Victoria Álvarez-Sánchez, Daniel Rodríguez-Alcalde, Luis Bujanda, María José Iglesias, Noel Pin-Vieito, Martín Menéndez-Rodríguez, Eva Martínez-Bauer, Cristina Pérez-Mosquera, Angel Ferrandez, Virginia Piñol, Jaume Boadas, Natalia García-Morales, Fernando Fernández-Bañares, and Joaquín Cubiella

Subjects
medicine.medical_specialty, Colorectal cancer, Anemia, gastrointestinal cancer, Clinical Biochemistry, Colonoscopy, 2412.01 Antígenos, 3210 Medicina Preventiva, Malignancy, Gastroenterology, biochemical diagnosis, Article, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, colonoscopy, Internal medicine, medicine, Gastrointestinal cancer, 3207.03 Carcinogénesis, lcsh:R5-920, medicine.diagnostic_test, biology, business.industry, carcinoembryonic antigen, Cancer, medicine.disease, digestive system diseases, 030220 oncology & carcinogenesis, early cancer, tumor biomarkers, Cohort, biology.protein, symptoms, 030211 gastroenterology & hepatology, business, lcsh:Medicine (General)
Abstract

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 &plusmn, 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3&ndash, 3.1), CRC (HR 4.4, 95% CI 1.1&ndash, 17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0&ndash, 2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3&ndash, 5.8), rectal bleeding (OR 0.3, 95% CI 0.1&ndash, 0.7) and CEA level &gt, 3 ng/mL (OR 3.4, 95% CI 1.7&ndash, 7.1). However, CEA was increased only in 31.8% (95% CI, 16.4&ndash, 52.7%) and 50% (95% CI, 25.4&ndash, 74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.

Published
2020

24. Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions

Author

Felipe Martínez Alcalá, Santiago Soto, Antonio Z. Gimeno-García, Alfredo J. Lucendo, Joaquín Rodríguez Sánchez, Ferrán González-Huix, Óscar Nogales, Eduardo Redondo, Javier Gordillo, José Manuel Echevarría, Esteban Saperas, Felipe Ramos Zabala, Ignacio Fernandez-Urien, Maite Herráiz Bayod, Manuel Rodríguez-Téllez, José Miguel Esteban, Francisco Javier Navajas León, Carlos Guarner Argente, Alberto Herreros de Tejada, Maria Pellise, Eduardo Albéniz, O. Garcia, Fernando Alberca de Las Parras, Alba Zuñiga Ripa, Juan José Vila Costas, Mariano González-Haba, David Barquero, Miguel Muñoz Navas, Pedro Alonso-Aguirre, José Carlos Marín Gabriel, M.H. Conde, Noel Pin, David Remedios, Helena León Brito, Adolfo Parra Blanco, Juan Gabriel Martínez Cara, Bartolomé López Viedma, Leopoldo López Rosés, David Martínez Ares, Joaquín de la Peña, Marco Antonio Álvarez, José Díaz-Tasende, María Fraile, Eduardo Valdivielso, Fernando Múgica, Marta Montes Díaz, Andres Sanchez-Yague, Julyssa Cobian, Marco Bustamante, Akiko Ono, Begoña González-Suárez, and Carla J. Gargallo

Subjects
medicine.medical_specialty, Endoscopic Mucosal Resection, MEDLINE, Endoscopic mucosal resection, Endoscopic management, Endoscopy, Gastrointestinal, 03 medical and health sciences, Digestive endoscopy, Colonic Diseases, 0302 clinical medicine, medicine, Humans, Endoscopic resection, Intestinal Mucosa, medicine.diagnostic_test, business.industry, Resección mucosa endoscópica, General surgery, Gastroenterology, General Medicine, Guideline, Endoscopy, Rectal Diseases, Còlon -- Càncer, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Colorectal Neoplasms, Colorectal Surgery, Gastroscòpia
Abstract

RESUMEN Este documento resume el contenido de la Guía de resección mucosa endoscópica elaborada por el grupo de trabajo de la Sociedad Española de Endoscopia Digestiva (GSEED de Resección Endoscópica) y expone las recomendaciones sobre el manejo endoscópico de las lesiones neoplásicas colorrectales superficiales. ABSTRACT This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Published
2018

25. Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas

Author

Carlos Guarner Argente, José Miguel Esteban, Joaquin De La Peña, Andres Sanchez Yague, David Barquero, Adolfo Parra Blanco, Maite Herráiz Bayod, Miguel Muñoz Navas, Fernando Alberca de Las Parras, Pedro Alonso Aguirre, Bartolomé López Viedma, Joaquín Rodríguez Sánchez, M.H. Conde, Francisco Leon, Felipe Martínez Alcalá, Manuel Rodríguez Téllez, José Carlos Marín Gabriel, Eduardo Redondo, Leopoldo López Rosés, David Martínez Ares, Marta Montes Díaz, Noel Pin, Juan José Vila Costas, Maria Pellise, David Remedios, Julyssa Cobian, Eduardo Albéniz, Marco Antonio Álvarez, Felipe Ramos Zabala, Ignacio Fernández Urién, Alba Zuñiga Ripa, José Díaz Tasende, Mariano González Haba, Juan Gabriel Martínez Cara, Óscar Nogales, Alfredo J. Lucendo, O. Garcia, Begoña González Suárez, Alberto Herreros de Tejada, Fernando Múgica, María Fraile, Antonio Z. Gimeno García, Javier Gordillo, Marco Bustamante, Akiko Ono, Ferran González Huix, José Manuel Echevarría, Esteban Saperas, Helena León Brito, Carla J. Gargallo, Santiago Soto, and Eduardo Valdivielso

Subjects
Gynecology, medicine.medical_specialty, Hepatology, business.industry, Resección mucosa endoscópica, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endoscopic mucosal resection, 030220 oncology & carcinogenesis, Medicine, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, lcsh:RC799-869, business
Abstract

Resumen Este documento resume el contenido de la Guia de reseccion mucosa endoscopica elaborada por el grupo de trabajo de la Sociedad Espanola de Endoscopia Digestiva (GSEED de Reseccion Endoscopica) y expone las recomendaciones sobre el manejo endoscopico de las lesiones neoplasicas colorrectales superficiales.

Published
2018

27. Potassium 6-Oxo-7,13,16,22-tetraazatetracyclo[12.6.2.18,12.017,21]tricosa-1(20),8(23),9,11,14,16,18,21-octaen-2-yne-15-carboxylate

Author

Camille Blouet, Stéphanie Letast, Thomas Robert, Stéphane Bach, Noël Pinaud, Nicolas Joubert, Marie-Claude Viaud-Massuard, Jean Guillon, Cédric Logé, and Caroline Denevault-Sabourin

Subjects
macrocycle, quinoxaline, Pim kinases, kinase inhibitor, Inorganic chemistry, QD146-197
Abstract

Potassium 6-oxo-7,13,16,22-tetraazatetracyclo[12.6.2.18,12.017,21]tricosa-1(20),8(23),9,11,14,16,18,21-octaen-2-yne-15-carboxylate was synthesized through a multi-step pathway, starting from commercially available 3-iodo-1,2-phenylenediamine. Structure characterization of this new substituted macrocyclic quinoxaline compound was achieved using 1H NMR, 13C NMR, and HRMS spectral analysis. This new macrocyclic derivative demonstrated submicromolar potency on both Pim-1 and Pim-2 isoforms, with an interesting selectivity profile against a selected panel of human kinases.

Published
2023
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29. Synthesis, Crystal Structure and Anti-Leukemic Activity of (E)-Pyrrolo[1,2-a]quinoxalin-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one

Author

Jean Guillon, Solène Savrimoutou, Sandra Albenque-Rubio, Noël Pinaud, Nina Fillová, Stéphane Moreau, Virginie Baylot, and Vanessa Desplat

Subjects
pyrrolo[1,2-a]quinoxaline derivative, leukemia, antiproliferative activity, Inorganic chemistry, QD146-197
Abstract

(E)-Pyrrolo[1,2-a]quinoxalin-4-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one was designed then synthesized using a multi-step pathway starting from commercially available 2-nitroaniline. Structure characterization of this original substituted pyrrolo[1,2-a]quinoxaline compound was achieved by using FT-IR, 1H-NMR, 13C-NMR, X-Ray and HRMS spectral analysis. This new pyrroloquinoxaline shows interesting cytotoxic potential against different human leukemia cell lines (MV4-11, K562, MOLM14 and Jurkat cells).

Published
2023
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30. New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex

Author

Jean Guillon, Marc Le Borgne, Vittoria Milano, Aurore Guédin-Beaurepaire, Stéphane Moreau, Noël Pinaud, Luisa Ronga, Solène Savrimoutou, Sandra Albenque-Rubio, Mathieu Marchivie, Haouraa Kalout, Charley Walker, Louise Chevallier, Corinne Buré, Eric Largy, Valérie Gabelica, Jean-Louis Mergny, Virginie Baylot, Jacky Ferrer, Yamina Idrissi, Edith Chevret, David Cappellen, Vanessa Desplat, Zsuzsanna Schelz, and István Zupkó

Subjects
antiproliferative activities, 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline, 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline, G-quadruplex, G4 ligands, FRET-melting, Medicine, Pharmacy and materia medica, RS1-441
Abstract

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line.

Published
2023
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31. Neonatal alveolar rhabdomyosarcoma with skin and brain metastases

Author

Bhaskar N. Rao, Carlos Rodriguez-Galindo, Larry E. Kun, Onynye Onyekwere, Alberto S. Pappo, Victor M. Santana, Noel Pin, D. Ashley Hill, and Fredric A. Hoffer

Subjects
Cancer Research, Pathology, medicine.medical_specialty, genetic structures, business.industry, Cancer, Histology, musculoskeletal system, medicine.disease, Metastasis, Central nervous system disease, Oncology, medicine, Alveolar rhabdomyosarcoma, Sarcoma, business, Rhabdomyosarcoma, Brain metastasis
Abstract

BACKGROUND Approximately 5–10% of patients with rhabdomyosarcomas (RMS) are diagnosed during the first year of life, and their clinical characteristics have been well documented. However, because RMS rarely occurs during the neonatal period, little is known about neonatal RMS. METHODS Four patients with neonatal RMS were treated at St. Jude Children's Research Hospital between 1962 and 1999. The authors report the results of a review of these patients and of cases described in the literature. Clinical, radiologic, and pathologic features of these patients and their outcomes were evaluated. RESULTS One patient with embryonal RMS was treated successfully with a combination of systemic chemotherapy and local control measures. The other three patients had alveolar RMS. Two of them had multiple skin and subcutaneous metastatic nodules at the time of diagnosis and developed brain metastases early in their course. In one of these patients, the PAX3-FKHR fusion transcript was detected. Three other similar cases of neonatal alveolar RMS with metastases to the skin and brain have been reported in the literature. CONCLUSIONS A distinct syndrome of neonatal RMS is described. This syndrome is characterized by alveolar histology, multiple skin and subcutaneous metastases, and fatal outcome as the result of early brain metastasis. Cancer 2001;92:1613–20. © 2001 American Cancer Society.

Published
2001

32. Sa1585 Morphological and Histological Characteristics of Colonic Laterally Spreading Tumors. East/WEST Comparative Study

Author

Felipe Martinez-Alcala, Akiko Ono, María Fraile, Santiago Soto, Francisco Pérez-Roldán, Bartolomé López Viedma, José Santiago García, David R. Remedios Espino, Hiroaki Ikematsu, Carlos Guarner-Argente, Helena León-Brito, Javier Eguaras, Pedro Alonso, Alberto Herreros de Tejada, Oscar Nogales Rincon, Noel Pin, Joaquin De La Peña, Juan Gabriel martinez-cara, Patricia Huelin, Shozo Osera, David Martínez-Ares, Marco Antonio Alvarez-Gonzalez, Joaquín Rodríguez-Sánchez, Eduardo Redondo Cerezo, Kazuhiro Kaneko, Fernando Múgica, Carol J. Cobián, Carla J. Gargallo, Antonio Pueyo, Javier Jiménez-Pérez, Manuel Rodríguez-Téllez, Eduardo Albéniz, Leopoldo López-Rosés, Felipe Ramos Zabala, and Victoria Alejandra Jiménez-García

Subjects
business.industry, East west, Gastroenterology, Medicine, Radiology, Nuclear Medicine and imaging, Anatomy, business
Published
2015

33. 332 Delayed Bleeding Risk Score for Colorectal Endoscopic Mucosal Resection

Author

Manuel Rodríguez-Téllez, Felipe Ramos Zabala, María López-Cerón, O. Garcia, Oscar Nogales Rincon, Francisco Pérez-Roldán, Akiko Ono, Carol J. Cobián, Carlos Guarner-Argente, Eduardo Redondo Cerezo, David R. Remedios Espino, Javier Eguaras, Joaquin De La Peña, Alberto Herreros de Tejada, Noel Pin, Bartolomé López Viedma, Victoria A. Jimenez-Garcia, Antonio Pueyo, Joaquín Cubiella, Santiago Soto, Carla J. Gargallo, Mariano Gonzalez-Haba Ruiz, Javier Jiménez-Pérez, Eduardo Albéniz, Fernando Múgica, Leopoldo López-Rosés, Helena León-Brito, Esteban Saperas, Marco Antonio Alvarez-Gonzalez, Joaquín Rodríguez-Sánchez, José Santiago García, María Fraile, David Martínez-Ares, Pedro Alonso, and Felipe Martinez-Alcala

Subjects
medicine.medical_specialty, Framingham Risk Score, business.industry, Gastroenterology, medicine, Radiology, Nuclear Medicine and imaging, Endoscopic mucosal resection, business, Surgery
Published
2015

34. Tu1455 Delayed Bleeding After Endoscopic Mucosal Resection of Large Colorectal Lesions. a Prospective Multicenter Spanish Study

Author

O. Garcia, J Rodríguez-Sánchez, Javier Jiménez-Pérez, Helena León-Brito, Eduardo Albéniz, Leopoldo López-Rosés, Antonio Pueyo, Esteban Saperas, Carlos Guarner-Argente, Joaquin De La Peña, Felipe Martinez-Alcala, David Martínez-Ares, Pedro Alonso, Anna Baiges, María Fraile, Javier Eguaras, Noel Pin, María López-Cerón, and Joaquín Cubiella

Subjects
medicine.medical_specialty, business.industry, Gastroenterology, Medicine, Radiology, Nuclear Medicine and imaging, Endoscopic mucosal resection, business, Surgery
Published
2014

35. Partnering to Reduce Colon Cancer Health Disparities Among the American Indian Population in Michigan

Author

Noel Pingatore, Angela Lewis Precht, Georgetta Alverson, Glenn Copeland, Betty Jahnke, Andrea Dwyer, and Robey B. Champine

Subjects
American Indian, colon cancer, health disparities, quality improvement, Education, Communities. Classes. Races, HT51-1595
Abstract

American Indian and Alaska Native people experience higher rates of several cancers, including lung, colorectal, liver, stomach, and kidney cancers, compared to non-Hispanic White people in the United States. Cancer disparities are also prominent among the American Indian population and vary by region. Disproportionately high rates of colon cancer were identified among three tribal communities in Michigan by linking each tribe’s enrollment roster to the state cancer registry. In response, in 2015 the Inter-Tribal Council of Michigan received funding from the Office of Minority Health within the U.S. Department of Health and Human Services to work with the three tribes to develop and implement the Tribal Colon Cancer Collaborative Project. The project used a community-based participatory research approach and a learning collaborative model to implement a multipronged initiative intended to improve colon cancer screening rates and outcomes among the three tribal communities. Local tribal coordinators were trained in the use of evidence-based interventions, including patient navigation and quality improvement processes, and implemented activities within their respective tribal health settings. Preliminary findings indicated increased colon cancer screening rates and improved rates of early stage cancer diagnoses. This paper describes the processes involved in implementing the project in collaboration with local tribal coordinators and the details of their journey toward improved colon cancer health outcomes.

Published
2022
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36. Synthesis, Crystal Structure and Anti-Leukemic Activity of 1,3-Dihydro-1-{1-[4-(4-phenylpyrrolo[1,2-a]quinoxalin-3-yl)benzyl]piperidin-4-yl}-2H-benzimidazol-2-one

Author

Jean Guillon, Solène Savrimoutou, Sandra Albenque-Rubio, Noël Pinaud, Stéphane Moreau, and Vanessa Desplat

Subjects
pyrrolo[1,2-a]quinoxaline derivative, leukemia, antiproliferative activity, Inorganic chemistry, QD146-197
Abstract

1,3-Dihydro-1-{1-[4-(4-phenylpyrrolo[1,2-a]quinoxalin-3-yl)benzyl]piperidin-4-yl}-2H-benzimidazol-2-one has been synthesized through a multi-step pathway starting from commercially available 2-nitroaniline. A structure characterization of this new substituted pyrrolo[1,2-a]quinoxaline compound was achieved by using FT-IR, 1H-NMR, 13C-NMR, X-Ray and HRMS spectral analysis. This new pyrroloquinoxaline derivative shows an interesting cytotoxic potential against several human leukemia cell lines (HL60, K562 and U937 cells).

Published
2022
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37. P0482 HOSPITAL READMISSION PATTERN IN PATIENTS WITH HEART FAILURE

Author

M. Teresa V. Rigueiro, Fátima Paz, E. Casariego, J.M. Cerqueiro, Nuria Domínguez, Francisco Terrón, and Noel Pin

Subjects
medicine.medical_specialty, Hospital readmission, business.industry, Heart failure, Emergency medicine, Internal Medicine, medicine, In patient, Medical emergency, medicine.disease, business
Published
2009

38. 1-Phenyl-8-[[4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]methyl]-1,3,8-triazaspiro[4.5]decan-4-one: Synthesis, Crystal Structure and Anti-Leukemic Activity

Author

Jean Guillon, Solène Savrimoutou, Sandra Rubio, Stéphane Moreau, Noël Pinaud, Mathieu Marchivie, and Vanessa Desplat

Subjects
pyrrolo[1,2-a]quinoxaline derivative, leukemia, antiproliferative activity, Inorganic chemistry, QD146-197
Abstract

1-Phenyl-8-[[4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenyl]methyl]-1,3,8-triazaspiro[4.5]decan-4-one has been successfully synthesized via a multi-step pathway starting from 2-nitroaniline. Structure characterization of this original pyrrolo[1,2-a]quinoxaline derivative was achieved by FT-IR, 1H-NMR, 13C-NMR, X-Ray and HRMS spectral analysis. This title compound shows interesting cytotoxic potential against several human leukemia cell lines (K562, HL60, and U937 cells).

Published
2020
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39. Online Quantification of Lactate Concentration in Microdialysate During Cerebral Activation Using 1H-MRS and Sensitive NMR Microcoil

Author

Yannick Crémillieux, Ursule Dumont, Leslie Mazuel, Roberto Salvati, Vanessa Zhendre, Silvia Rizzitelli, Jordy Blanc, Hélène Roumes, Noël Pinaud, and Anne-Karine Bouzier-Sore

Subjects
barrel cortex, lactate, microdialysis, 1H-MRS, NMR microcoil, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The dynamic in vivo profiling of lactate is of uppermost importance in both neuroenergetics and neuroprotection fields, considering its central suspected role as a metabolic and signaling molecule. For this purpose, we implemented proton magnetic resonance spectroscopy (1H-MRS) directly on brain microdialysate to monitor online the fluctuation of lactate contents during neuronal stimulation. Brain activation was obtained by right whisker stimulation of rats, which leads to the activation of the left barrel cortex area in which the microdialysis probe was implanted. The experimental protocol relies on the use of dedicated and sensitive home-made NMR microcoil able to perform lactate NMR profiling at submillimolar concentration. The MRS measurements of extracellular lactate concentration were performed inside a pre-clinical MRI scanner allowing simultaneous visualization of the correct location of the microprobe by MRI and detection of metabolites contained in the microdialysis by MRS. A 40% increase in lactate concentration was measured during whisker stimulation in the corresponding barrel cortex. This combination of microdialysis with online MRS/MRI provides a new approach to follow in vivo lactate fluctuations, and can be further implemented in physio-pathological conditions to get new insights on the role of lactate in brain metabolism and signaling.

Published
2019
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40. Implantable NMR Microcoils in Rats: A New Tool for Exploring Tumor Metabolism at Sub-Microliter Scale?

Author

Justine Deborne, Noël Pinaud, and Yannick Crémillieux

Subjects
magnetic resonance spectroscopy (MRS), metabolic imaging, implantable microcoil, brain spectroscopy, tumor metabolism, Microbiology, QR1-502
Abstract

The aim of this study was to evaluate the potential of a miniaturized implantable nuclear magnetic resonance (NMR) coil to acquire in vivo proton NMR spectra in sub-microliter regions of interest and to obtain metabolic information using magnetic resonance spectroscopy (MRS) in these small volumes. For this purpose, the NMR microcoils were implanted in the right cortex of healthy rats and in C6 glioma-bearing rats. The dimensions of the microcoil were 450 micrometers wide and 3 mm long. The MRS acquisitions were performed at 7 Tesla using volume coil for RF excitation and microcoil for signal reception. The detection volume of the microcoil was measured equal to 450 nL. A gain in sensitivity equal to 76 was found in favor of implanted microcoil as compared to external surface coil. Nine resonances from metabolites were assigned in the spectra acquired in healthy rats (n = 5) and in glioma-bearing rat (n = 1). The differences in relative amplitude of choline, lactate and creatine resonances observed in glioma-bearing animal were in agreement with published findings on this tumor model. In conclusion, the designed implantable microcoil is suitable for in vivo MRS and can be used for probing the metabolism in localized and very small regions of interest in a tumor.

Published
2021
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41. New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

Author

Bruno Oyallon, Marie Brachet-Botineau, Cédric Logé, Thomas Robert, Stéphane Bach, Sajida Ibrahim, William Raoul, Cécile Croix, Pascal Berthelot, Jean Guillon, Noël Pinaud, Fabrice Gouilleux, Marie-Claude Viaud-Massuard, and Caroline Denevault-Sabourin

Subjects
quinoxaline, Pim kinases, kinase inhibitor, anticancer targeted therapy, Organic chemistry, QD241-441
Abstract

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.

Published
2021
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42. Inadequate social support decreases survival in decompensated liver cirrhosis patients

Author

Morales, Natalia García, de la Varga, Margarita Fernández, Pérez, Javier Pumares, Rodríguez, Martín Menéndez, Morato, Sagrario Gutiérrez, Cejas, Carmen Castillo, Aguilera, Victoria, Benlloch, Salvador, Rodríguez, Luis Menéndez, Pillado, Teresa Seoane, Vieito, Noel Pin, and Cubiella, Joaquín

Abstract

Introduction: Inadequate social support is associated with higher mortality both in the general population and in patients with chronic diseases. There are no studies that have described social support in liver cirrhosis and its impact on prognosis.

Published
2022
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43. Perceived Barriers And Benefits In The Participation In Faecal Occult Blood Test Colorectal Cancer Screening Programme

Author

Rodríguez, Martín Menéndez, García-Morales, Natalia, Pillado, Teresa Seoane, Ramírez, Jorge Garau, Salvador, Alba Traver, Jiménez, Yésica Hervás, Vieito, Noel Pin, Rodríguez, Luis Menéndez, and Cubiella, Joaquín

Abstract

Background: Colorectal cancer is the second cancer-related cause of death in the world. Tumor stage at diagnosis is the principal prognosis factor of survival. However, the participation in the program is around 50%. The aim of the study was to identify the benefits and barriers perceived by the population when participating in a colorectal cancer screening program with faecal occult blood test.

Published
2022
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44. Synthesis, Biological Evaluation and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors of Human Protein Kinase CK2

Author

Faten Alchab, Laurent Ettouati, Zouhair Bouaziz, Andre Bollacke, Jean-Guy Delcros, Christoph G.W. Gertzen, Holger Gohlke, Noël Pinaud, Mathieu Marchivie, Jean Guillon, Bernard Fenet, Joachim Jose, and Marc Le Borgne

Subjects
indeno[1,2-b]indoles, synthesis, protein kinase CK2, inhibitory activity, molecular modeling, cytotoxicity, Medicine, Pharmacy and materia medica, RS1-441
Abstract

Due to their system of annulated 6-5-5-6-membered rings, indenoindoles have sparked great interest for the design of ATP-competitive inhibitors of human CK2. In the present study, we prepared twenty-one indeno[1,2-b]indole derivatives, all of which were tested in vitro on human CK2. The indenoindolones 5a and 5b inhibited human CK2 with an IC50 of 0.17 and 0.61 µM, respectively. The indeno[1,2-b]indoloquinone 7a also showed inhibitory activity on CK2 at a submicromolar range (IC50 = 0.43 µM). Additionally, a large number of indenoindole derivatives was evaluated for their cytotoxic activities against the cell lines 3T3, WI-38, HEK293T and MEF.

Published
2015
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45. tert-Butyl N-{[5-(5-oxohexanamido)pyridin-2-yl]amino}carbamate

Author

Luisa Ronga, Noel Pinaud, Charlotte Rimbault, Mathieu Marchivie, and Jean Guillon

Subjects
Crystallography, QD901-999
Abstract

In the crystal structure of the title compound, C16H24N4O4, molecules are linked by N—H...O hydrogen bonds between the carbonyl groups of the carbamoyl and amido functional groups and the amino groups, and by N—H...N hydrogen bonds between the amino group and the pyridine ring, forming two-dimensional networks parallel to the ab plane.

Published
2013
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