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1.
Braz. j. biol ; 83: e248746, 2023. graf
Article in English | LILACS, VETINDEX | ID: biblio-1339351

ABSTRACT

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


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


Subject(s)
Humans , Colorectal Neoplasms/drug therapy , Catechin/analogs & derivatives , Catechin/pharmacology , Quercetin/pharmacology , Cell Cycle , Annexin A5 , Cell Line, Tumor , Cell Proliferation
2.
Rev. cir. (Impr.) ; 74(4): 376-383, ago. 2022. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1407939

ABSTRACT

Resumen Objetivo: El objetivo de este estudio es comparar los resultados perioperatorios del abordaje abierto (AA) con el abordaje laparoscópico (AL) para la reconstitución de tránsito (RT), y determinar factores de riesgo asociados a morbilidad posoperatoria. Material y Métodos: Se estudiaron pacientes consecutivos sometidos a RT entre enero de 2007 y diciembre de 2016 en nuestro centro. Se excluyeron aquellos con grandes hernias incisionales que requirieran reparación abierta simultánea. Se consignaron variables demográficas y perioperatorias, y se compararon ambos grupos. Además, se realizó una regresión logística para la identificación de factores de riesgo asociados a morbilidad posoperatoria en la serie. Resultados: Se realizaron 101 RT en el período. Se excluyeron 14 casos por hernia incisional, por lo que se analizaron 87 casos (46 AA y 41 AL). Diez pacientes en el grupo AL (24,4%) requirieron conversión, principalmente por adherencias. La morbilidad total de la serie fue de 36,8%, siendo mayor en el AA (50% vs 21,9%, p = 0,007). Hubo una filtración anastomótica en cada grupo. La estadía posoperatoria fue de 5 (3-52) días para el AL y 7 (4-36) días para el AA (p < 0,001). En la regresión logística, sólo el AA fue un factor de riesgo independientemente asociado a morbilidad posoperatoria (OR 2,89, IC 95% 1,11-7,49; p = 0,029). Conclusión: El abordaje laparoscópico se asocia a menor morbilidad y estadía posoperatoria que el abordaje abierto para la reconstitución del tránsito pos-Hartmann. En nuestra serie, el abordaje abierto fue el único factor independientemente asociado a morbilidad posoperatoria.


Introduction: Hartmann's reversal (HR) is considered a technically demanding procedure and is associated with high morbidity rates. Aim: The aim of this study is to compare the perioperative results of the open approach (OA) with the laparoscopic approach (LA) for HR, and to determine the risk factors associated with postoperative morbidity. Material and Methods: Consecutive patients undergoing HR between January 2007 and December 2016 at a university hospital were included. Patients with large incisional hernias that required an open approach a priori were excluded from the analysis. Demographic and perioperative variables were recorded. Analytical statistics were carried out to compare both groups, and a logistic regression was performed to identify risk factors associated with postoperative morbidity in the series. Results: A hundred and one HR were performed during the study period. Fourteen cases were excluded due to large incisional hernias, so 87 cases (46 OA and 41 LA) were analyzed. Ten patients in the LA group (24.4%) required conversion, mainly due to adhesions. The total morbidity of the series was 36.8%, being higher in the OA group (50% vs. 21.9%, p = 0.007). There was one case of anastomotic leakage in each group. The length of stay was 5 (3-52) days for LA and 7 (4-36) days for OA (p < 0.001). In the logistic regression, the OA was the only independent risk factor associated with postoperative morbidity in HR (OR 2.89, IC 95% 1.11-7.49; p = 0.029). Conclusion: A laparoscopic approach is associated with less morbidity and a shorter length of stay compared to the open approach for Hartmann's reversal. An open approach was the only factor independently associated with postoperative morbidity in our series.


Subject(s)
Humans , Postoperative Complications/epidemiology , Colorectal Neoplasms/surgery , Laparoscopy/methods , Colorectal Surgery/methods , Laparotomy/methods , Postoperative Complications/physiopathology , Anastomosis, Surgical/methods , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Chi-Square Distribution , Survival Analysis , Laparoscopy/adverse effects , Colorectal Surgery/adverse effects , Laparotomy/adverse effects
3.
rev.cuid. (Bucaramanga. 2010) ; 13(3): 1-14, 20220831.
Article in Portuguese | LILACS, BDENF, COLNAL | ID: biblio-1402491

ABSTRACT

Objetivo: Conhecer o acesso e aguardo pela estomização de pessoas adoecidas por câncer colorretal no nível terciário do Sistema Único de Saúde. Materiais e Métodos: Estudo etnográfico fundamentado na Sociologia da Saúde, com 8 familiares e 14 adoecidos em Centro de Alta Complexidade em Oncologia, Brasil. Os dados foram coletados entre outubro de 2018 a março de 2019, com observação participante e não participante, registro em diário de campo e entrevista semiestruturada. Os depoimentos e notas etnográficas após triangulação foram submetidos a análise indutiva de conteúdo em seis etapas. Resultados: Apreenderam-se "A história do adoecimento entrecortada pelas dificuldades" e "As perdas no processo de paciência-resiliência no percurso". Discussão: Em busca de validações biomédicas foram reportados três tipos de acesso ao sistema médico, assim como os subsentidos "paguei no particular" e atraso diagnóstico mobilizaram via oficial e não oficial no Sistema Único de Saúde. O capital social foi analisado como premente no adoecimento, uma rede de contatos sem a qual o acesso dos usuários é impactado. No nível terciário enquanto aguardam pela estomização desvelou-se a resiliência não como recurso heroico, mas como recurso pessoal e coletivo diante do percurso dificultoso e da semi-reclusão na instituição total onde vivenciam medos, fadiga e dores. Conclusão:O acesso contou com mobilização relacional e uma gama de vias até a internação com parte do percurso na saúde suplementar, já o aguardo pela estomização mitiga a paciência ao passo que torna a resiliência um recurso benéfico na espera pela programação cirúrgica.


Introduction: The access of people with colorectal cancer to surgical treatment with stomization implies a difficult itinerary through the network of care, and when accessing the tertiary level in an apprehensive preoperative waiting. Objetive: To know the access and waiting for stomization of people sick with colorectal cancer at the tertiary level of the Brazilian Unified Health System. Materials and Methods:Ethnographic study based on the Sociology of Health, with 8 relatives and 14 patients in a High Complexity Oncology Center, Brazil. Data were collected between October 2018 to March 2019, with participant and non-participant observation, field diary recording, and semi-structured interview. Statements and ethnographic notes after triangulation were subjected to inductive content analysis in six steps. Results:"The history of illness interspersed with difficulties" and "The losses in the process of patience-resilience along the way" were apprehended. Discussion: Three types of access were reported, as well as the sub-meanings "I paid privately" and the diagnostic delay mobilized by official and unofficial means in the Unified Health System. Social capital is pressing, a network without which users' access is impacted. At the tertiary level while waiting for stomization, resilience was unveiled not as a heroic resource, but as a personal and collective resource. Conclusion: The access counted on relational mobilization and a range of paths to hospitalization with part of the journey in supplementary health, while the waiting for stomization mitigates patience making resilience a beneficial resource in the wait for surgical programming.


Introducción: El acceso de las personas con cáncer colorrectal al tratamiento quirúrgico con estomización implica un difícil itinerario a través de la red asistencial, y al acceder al nivel terciario en una aprensiva espera preoperatoria. Objetivo: Conocer el acceso y el aguante de las personas afectadas por el cáncer colorrectal en el nivel terciario del Sistema Único de Salud. Materiales y Métodos: Estudio etnográfico basado en la Sociología de la Salud, con 8 familiares y 14 pacientes en Centro Oncológico de Alta Complejidad, Brasil. Los datos se recogieron entre octubre de 2018 y marzo de 2019, con observación participante y no participante, registro de diario de campo y entrevista semiestructurada. Los testimonios y las notas etnográficas, tras la triangulación, se sometieron a un análisis de contenido inductivo en seis etapas. Resultados: Se aprende "La historia del adoctrinamiento entrecortado por las dificultades" y "Las pérdidas en el proceso de pacificación-resiliencia en el curso". Discusión: Se reportaron tres tipos de acceso, así como los subsentidos "pagué en el privado" y el atraso diagnóstico se movilizaron vía oficial y no oficial en el Sistema Único de Salud. El capital social es apremiante, una red de contactos sin la cual el acceso de los usuarios se ve afectado. En el nivel terciario, mientras aguantan por la estomatología, la resistencia se revela no como un recurso heroico, sino como un recurso personal y colectivo. Conclusión: El acceso a la movilización relacional y a una gama de vías hasta la internación con parte del curso en la salud suplementaria, ya que la espera por la estomización mitiga la pacificación haciendo de la resiliencia un recurso benéfico en la espera por el programa quirúrgico.


Subject(s)
Sociology, Medical , Unified Health System , Colorectal Neoplasms , Medicalization , Health Services Accessibility
4.
Oncología (Ecuador) ; 32(2)2 de Agosto del 2022.
Article in Spanish | LILACS | ID: biblio-1391906

ABSTRACT

In troducción: El cáncer colorrectal (CCR) es la afección maligna más frecuente del tubo digestivo. El tratamiento se basa en la administración de fármacos antineoplásicos, como el 5­fluoro uracilo (5-FU), perteneciente al grupo farmacológico de las fluoro pirimidinas. Sin embargo, se ha demostrado que existe toxicidad asociada con polimorfismos genéticos en pacientes tratados con 5-FU que incluyen síntomas gastrointestinales, mielo supresión y neurotoxicidad. Se estudiaron las variaciones genéticas de cuatro genes ABCB1, DPYD, MTHFR y TYMS Metodología: Revisión bibliográfica basada en revistas digitales, la cual inicia con la búsqueda exhaustiva de información acerca del uso del 5-fluorouracilo como tratamiento en pacientes con cáncer colorrectal, reacciones adversas, polimorfismos y toxicidad. Las bases de datos empleadas son PubMed, Science-Direct y Scielo; cuyas publicaciones corresponden a los últimos 10 años. Se incluyen artículos científicos, estudios realizados en pacientes mayores a 18 años de edad, revistas en español e inglés y artículos visibles a texto completo. Adicionalmente se analizaron los polimorfismos en la base de datos NCBI (National Center for Biotechnology Information), de donde se obtuvo las frecuencias alélicas a nivel global y latinoamericano 2.Resultados: Se revisaron un total de 11 artículos, de los cuales se pudo obtener datos sobre polimorfismos genéticos que se presentan en pacientes con cáncer colorrectal que reciben tratamiento con 5-fluorouracilo. Los genes que se analizaron son ABCB1, DPYD, MTHFR y TYMS. Se estableció que los polimorfismos desencadenan en una toxicidad que se manifiesta de diferentes formas: diarrea, estoma-titis, mucositis, neutropenia, etc


In troduction:Colorectal cancer is the most common malignancy of the digestive tract. The treatment is based basically on administering antitumor medications, like 5-fluorouracil (5-FU), which belongs to the antimetabolites, antineoplastic agents. However, it has been shown that there is toxicity related to ge-netic polymorphism in patients treated with 5-FU, including gastrointestinal symptoms, myelosuppres-sion, and neurotoxicity. The genetic variations of four genes have been studied, including ABCB1, DPYD, MTHFR, and TYMS. Met hodology: Bibliographic review based on digital articles, starting with the research of information about 5-fluorouracil as treatment of patients with colorectal cancer, its adverse reactions, polymor-phisms, and toxicity. The database used is PubMed, ScienceDirect, and Scielo, published within the last ten years. It included scientific articles and studies on patients older than 18. Publications in Spanish and English as well as full-text articles. Additionally, the polymorphisms were analyzed in the NCBI (National Center for Biotechnology Information) database, from which the allelic frequencies at the global and Latin American levels were obtained. R esults: A total of 11 articles were reviewed, from where we obtained data about polymorphism that developed in patients with colorectal cancer who receive treatment with 5-fluorouracil. The analyzed genes are ABCB1, DPYD, MTHFR, and TYMS. It was established that the polymorphisms trigger toxicity that manifests in different forms: diarrhea, stomatitis, mucositis, and neutropenia


Subject(s)
Colorectal Neoplasms
5.
J. coloproctol. (Rio J., Impr.) ; 42(2): 131-139, Apr.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1394418

ABSTRACT

Background: The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective: To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods: We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results: The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Colorectal Neoplasms/therapy , Lymphatic Metastasis/diagnosis , Prognosis , Recurrence , Colorectal Neoplasms/surgery , Survival Rate , Prospective Studies , Treatment Outcome , Lymphatic Metastasis/pathology , Neoplasm Staging
6.
J. coloproctol. (Rio J., Impr.) ; 42(2): 120-125, Apr.-June 2022. tab, ilus
Article in English | LILACS | ID: biblio-1394416

ABSTRACT

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Colorectal Neoplasms/diagnosis , Biomarkers, Tumor , WT1 Proteins/genetics , Carbonic Anhydrase IX/genetics , Antigens, Neoplasm/genetics , Prognosis , Case-Control Studies , Gene Expression , Prospective Studies , Reverse Transcriptase Polymerase Chain Reaction
7.
J. coloproctol. (Rio J., Impr.) ; 42(2): 146-151, Apr.-June 2022. tab
Article in English | LILACS | ID: biblio-1394414

ABSTRACT

Objective: Colonoscopy is increasingly performed in octogenarians for the detection of colorectal cancer (CRC), but its benefits may be outweighed by its risks. The aim of the present study was to identify the risk factors for CRC in octogenarians presenting for colonoscopy to help stratify the need for this procedure. Methods: A retrospective analysis of 434 patients aged ≥ 80 years referred for a colonoscopy between January 2018 and December 2019. Comparisons were made between those with and without CRC and advanced adenoma (AA). The primary endpoint was to identify the clinical variables predictive of CRC and AA, and the secondary endpoints were complications and death 30 days after the procedure. Results: Colonoscopy was performed in 434 octogenarians, predominantly for symptoms, with CRC in 65 (15.0%) patients. Iron deficiency was associated with a higher risk of having CRC identified on colonoscopy (odds ratio [OR]: 2.33; 95% confidence interval [95%CI] = 1.36-4.00), but not symptoms such as bleeding, weight loss, or diarrhea. A colonoscopy in the last 10 years was protective, with a lower risk of CRC (OR: 0.45; 95% CI = 0.22-0.93). Patients with both normal iron stores and a colonoscopy within 10 years had a 92.5% chance of not having CRC. No variables were predictive of AA. Patients with complications, including death, were older and more likely to have underlying cardiorespiratory disease. Conclusion: Iron status and colonoscopy within 10 years can be used to predict the risk of CRC in octogenarians. Those with low predicted risk, especially if older and with cardiorespiratory disease, should be considered for non-invasive tests, such as computed tomography (CT) colonography, over colonoscopy. (AU)


Subject(s)
Humans , Male , Female , Aged, 80 and over , Colorectal Neoplasms/diagnosis , Colonoscopy/adverse effects , Octogenarians , Comorbidity , Retrospective Studies , Risk Factors
8.
J. coloproctol. (Rio J., Impr.) ; 42(2): 107-114, Apr.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1394411

ABSTRACT

Background: Peritoneal carcinomatosis (PC) is a lethal regional progression in patients with colorectal cancer (CRC). Treatment with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves better local control than systemic palliative chemotherapy. Objectives: To assess the efficacy on the prognosis of CRS and HIPEC compared with CRS only and to identify possible clinicopathological factors associated with the recurrence of PC. Methods: The present retrospective study included all colorectal carcinoma cases with PC subjected to CRS with or without HIPC from January 2009 to June 2018 at the National Cancer Institute (NCI), Cairo University, Cairo, Egypt. The outcome is evaluated in terms of recurrence-free survival (RFS) and its predictors. Results: Out of the 61 patients, 45 patients (73.8%) underwent CRS plus HIPEC, and 16 (26.2%) underwent CRS alone. The 1-year RFS was 55.7%, with a median of 12 months. The risk factors for recurrence identified in the univariate analysis were T4 primary tumor, high-grade, positive lymphovascular invasion (LVI), positive extracapsular nodal spread, and patients treated with CRS only, without HIPEC. In the multivariate analysis, the independent risk factors for recurrence were high grade and patients treated with CRS only. Conclusion: T4 primary tumor, high grade, positive LVI, and positive extracapsular nodal spread seemed to be important predictors of recurrence following the treatment of PC. Our study also demonstrated that the addition of HIPEC to CRS improved the RFS. (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Peritoneal Neoplasms/diagnosis , Colorectal Neoplasms , Cytoreduction Surgical Procedures/methods , Recurrence , Hyperthermic Intraperitoneal Chemotherapy , Neoplasm Staging
9.
Rev. colomb. gastroenterol ; 37(2): 187-191, Jan.-June 2022. tab
Article in English, Spanish | LILACS | ID: biblio-1394947

ABSTRACT

Abstract Aim: To locate and characterize colorectal adenomas endoscopically and histologically in a cohort of patients undergoing colonoscopy in Medellín, Colombia. Materials and methods: Descriptive cross-sectional study. We included patients older than 18 years who underwent colonoscopy between February and July 2020 at a specialized center in Medellín, Colombia. We determined the incidence of adenomas, their location in different segments of the colon, their endoscopic and histological characteristics, and cases of colorectal cancer (CRC) and high-grade dysplasia (HGD). Results: 992 colonoscopies were performed, finding colorectal polyps in 266 patients, of which 208 had adenomas. We resected 461 polyps, of which 336 were adenomas (72 %). The histological type with the highest representation was tubular (78 %). The location of adenomas was 37 % in the right colon, 25 % in the transverse colon, and 38 % in the left colon. CRC cases were nine per 1,000 patients, including advanced carcinoma and carcinoma in situ (HGD). Conclusions: Given the incidence of adenomas in the right and transverse colon, rectosigmoidoscopy is discouraged as a screening study for CRC. Tubular adenomas, sessile in appearance and tiny, predominated in the population studied. We recommend screening in the population over 40 years of age and the search for precursor lesions as strategies to reduce morbidity and mortality rates due to CRC.


Resumen Objetivo: localización y caracterización endoscópica e histológica de los adenomas colorrectales en una cohorte de pacientes sometidos a colonoscopia en Medellín, Colombia. Materiales y métodos: estudio descriptivo de corte transversal. Se incluyeron pacientes mayores de 18 años sometidos a colonoscopia entre febrero y julio de 2020 en un centro especializado de Medellín, Colombia. Se determinó la incidencia de adenomas, su localización en los diferentes segmentos del colon, sus características endoscópicas e histológicas, así como también los casos de cáncer colorrectal (CCR) y displasia de alto grado. Resultados: se realizaron 992 colonoscopias y se encontraron pólipos colorrectales en 266 pacientes, de los cuales 208 tenían adenomas. En total se resecaron 461 pólipos, de los cuales 336 fueron adenomas (72 %). El tipo histológico con mayor representación fue el tubular (78 %). La localización de adenomas fue del 37 % en el colon derecho, 25 % en el transverso y 38 % en el colon izquierdo. La cantidad de casos de CCR fue de 9 por 1000 pacientes, que incluyen carcinoma avanzado y carcinoma in situ (DAG). Conclusiones: dada la incidencia de adenomas en el colon derecho y transverso, no se recomienda la rectosigmoidoscopia como estudio de tamizaje para CCR. En la población estudiada fueron predominantes los adenomas tubulares, de aspecto sésil y tamaño diminuto. Se recomienda el tamizaje en la población mayor de 40 años y la búsqueda de lesiones precursoras como estrategias para disminuir las tasas de morbimortalidad por CCR.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Colorectal Neoplasms , Adenoma , Colonoscopy , Colon , Patients , Polyps , Carcinoma , Indicators of Morbidity and Mortality , Cross-Sectional Studies , Methods
10.
Rev. cir. (Impr.) ; 74(3): 276-282, jun. 2022. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1407922

ABSTRACT

Resumen Introducción: El cáncer colorrectal (CCR) es el segundo tipo más frecuente de cáncer en el mundo. La cirugía es la intervención terapéutica más común y se asocia con la reducción de 20-40% en la capacidad fisiológica y funcional. Un programa de prehabilitación podría mejorar la condición funcional basal de los pacientes previo a la cirugía. Objetivo: Describir los resultados funcionales de un programa de prehabilitación en personas adultas candidatos a cirugía electiva de CCR. Materiales y Método: Estudio descriptivo, longitudinal y retrospectivo. Se registraron los antecedentes sociodemográficos, clínicos y las variables funcionales como capacidad cardiorrespiratoria, fuerza de presión manual, fatiga, independencia en actividades de la vida diaria (AVDs) y equilibrio dinámico de 50 personas que ingresaron a un programa de prehabilitación entre mayo 2019 y febrero de 2020. Los datos fueron analizados con estadística descriptiva y pruebas de diferencia entre tiempo de evaluación, previo y posterior a la prehabilitación. Resultados: Posterior al programa de prehabilitación, los pacientes mejoraron la capacidad cardiorrespiratoria, fatiga, equilibrio dinámico y fuerza prensil (p 0,05; tamaño de efecto: 0,01). Conclusión: Un programa estructurado de prehabilitación para pacientes candidatos a cirugía electiva de CCR basado en ejercicios y educación, logró cambios significativos en los resultados funcionales en un período de 3 a 4 semanas previo a la cirugía.


Introduction: Colorectal cancer (CRC) is the second most frequent type of cancer in the world. Surgery is the most common therapeutic intervention and is associated with a 20-40% reduction in physiological and functional capacity. A prehabilitation program could improve the baseline functional condition of patients prior to surgery. Aim: To describe the functional results of a prehabilitation program in adults who will undergo elective surgery CCR. Materials and Method: Descriptive, longitudinal and retrospective study. The sociodemographic, clinical and functional variables such as cardiorespiratory capacity, manual pressure force, fatigue, independence in activities of daily living and dynamic balance of 50 people who entered a pre-rehabilitation program between may 2019 and february 2020 were compiled. Data were analyzed with descriptive statistics and difference tests between evaluation time, before and after prehabilitation. Results: After the prehabilitation program, the patients improved cardiorespiratory capacity, fatigue, dynamic balance and grip strength (p 0.05; effect size: 0.01). Conclusión: A structured prehabilitation program for patients who are candidates for elective colorectal cancer surgery based on exercises and education, achieved significant changes in functional results in a period of 3 to 4 weeks prior to surgery.


Subject(s)
Humans , Male , Female , Aged , Colorectal Neoplasms/surgery , Preoperative Exercise , Epidemiology, Descriptive , Retrospective Studies , Sample Size , Fatigue
11.
Article in English | LILACS | ID: biblio-1410587

ABSTRACT

Intestinal obstruction is the most frequent clinical manifestation of colon tumors, most of which are located in the descending and recto-sigmoid colon. Emergency bowel obstruction surgery is associated with high mortality and morbidity risks and the ideal approach remains controversial. Multi-stage procedures and the use of stents as bridges for surgery are promising options. A case of a 61-year-old patient with an acute obstructive abdomen secondary to colorectal neoplasm is presented, with emphasis on its diagnosis and treatmen (AU)


Obstrução intestinal é a manifestação clínica mais frequente de tumores de cólon sendo esses, em sua maioria, localizados no cólon descendente e reto-sigmoide. A cirurgia de emergência para obstrução intestinal é associada a altos riscos de mortalidade e de morbidade e a abordagem ideal permanece controversa. Procedimentos em vários estágios e o uso de stents como ponte para cirurgia são opções promissoras. É apresentado um caso de paciente de 61 anos, com abdome agudo obstrutivo secundário à neoplasia colorretal, com ênfase em seu diagnóstico e tratamento (AU)


Subject(s)
Humans , Female , Middle Aged , Colorectal Neoplasms/surgery , Colorectal Neoplasms/diagnosis , Colectomy , Abdomen, Acute/diagnosis , Intestinal Obstruction/therapy
12.
Biomédica (Bogotá) ; 42(supl.1): 154-171, mayo 2022. tab, graf
Article in Spanish | LILACS | ID: biblio-1394003

ABSTRACT

Introducción. El cáncer colorrectal tiene una alta incidencia en la población mundial. Diversas vías moleculares están involucradas en su desarrollo, entre ellas, la inestabilidad cromosómica, la inestabilidad microsatelital y la epigenética. Objetivo. Hacer la caracterización molecular de 44 individuos con cáncer colorrectal esporádico. Materiales y métodos. El análisis de mutaciones en los genes APC, KRAS, TP53 y BRAF se hizo mediante secuenciación de Sanger; la inestabilidad microsatelital se determinó mediante electroforesis capilar utilizando cinco marcadores de repetición corta en tándem (Short Tandem Repeat) y el estado de metilación del promotor del gen MLH1 se hizo con la técnica MS-PCR (Methylation-Specific PCR). Resultados. La frecuencia de mutación de los genes APC, KRAS y TP53 fue del 18,1, 25 y 4,5 %, respectivamente; las mutaciones detectadas se localizaron con mayor frecuencia en el colon derecho. La frecuencia de inestabilidad microsatelital fue del 27,2 % y el 73,1 % en los tumores con metilación en el gen MHL1, y el 91,6 % de los tumores con inestabilidad microsatelital presentaba metilación en el gen MLH1. En el grupo de tumores con estabilidad microsatelital, las mutaciones en los genes APC, KRAS y TP53 fueron más frecuentes que en el grupo de tumores con inestabilidad microsatelital. La metilación del gen MLH1 fue la alteración más predominante. Conclusiones. En los pacientes con cáncer colorrectal evaluados se demostró la presencia de alteraciones moleculares en las diferentes vías genéticas, las cuales son comunes en su carcinogénesis. Los pacientes presentaron un perfil de mutaciones diferente al de otras poblaciones. Los hallazgos obtenidos en este estudio confirman la heterogeneidad molecular descrita en el desarrollo del cáncer colorrectal.


Introduction: Colorectal cancer has a high incidence in the world population. Different molecular pathways, such as chromosomal instability, microsatellite instability, and epigenetics are involved in its development. Objective: To perform molecular characterization in 44 individuals with sporadic colorectal cancer. Materials and methods: We conducted mutation analyses of the APC, KRAS, TP53 y BRAF genes using Sanger sequencing techniques; microsatellite instability was determined by capillary electrophoresis with five STR genetic markers while the methylation status of the MHL1 promotor gene was analyzed using methylation-specific PCR. Results: APC, KRAS, and TP53 genes mutation frequency was 18.1%, 25%, and 4.5%, respectively; the somatic mutations detected were located more frequently in the right colon. The frequency of microsatellite instability was 27.2% and 73.1% of the tumors had the MHL1 gene methylated while 91.6% of microsatellite instability-positive tumors had the methylated MLH1 gene. The mutation profile of microsatellite stability tumors APC, KRAS, and TP53 genes was more frequent than in the microsatellite instability-positive tumors. The methylation of the MLH1 gene was the most predominant molecular alteration. Conclusions: We identified molecular alterations in different genetic pathways of the colorectal cancer patients evaluated, which are common in the carcinogenesis of this cancer. These patients showed a different mutational profile compared to other populations. Our findings confirm the molecular heterogeneity described in the development of colorectal cancer.


Subject(s)
Colorectal Neoplasms/genetics , Oncogenes , Genes, Tumor Suppressor , Genetic Heterogeneity , Microsatellite Instability , Epigenomics
13.
Rev. colomb. gastroenterol ; 37(1): 48-56, Jan.-Mar. 2022. tab
Article in English | LILACS | ID: biblio-1376905

ABSTRACT

Abstract Introduction: Inflammatory bowel disease (IBD) is an immune-mediated disease whose incidence in Latin America has increased in recent years. Aim: To analyze the demographic and clinical characteristics of patients with IBD treated in a university hospital and present the epidemiological data compared to other centers in Colombia. Patients and methods: Descriptive study of patients with IBD (1996-2019) at the Hospital Universitario Fundación Santa Fe de Bogotá. Analysis of data from centers in Medellín, Cali, Bogotá, and Cartagena. Results: Of 386 patients, 277 presented with ulcerative colitis (UC), 102 with Crohn's disease (CD), and seven with unclassifiable colitis. IBD was more frequent in women (53 %). Mortality was less than 1 %. The involvement of UC was mainly pancolitis (42.6 %). The greater the extent of the disease, the higher the hospitalization and surgery rates (OR 3.70, P < 0.01). Thirteen percent of patients with UC received biologics. Compromise due to CD was mainly ileocolonic (43.6 %) and ileal (43.6 %). The predominant clinical pattern of CD was structuring (50%). Forty-five percent received biologicals and 56 % surgery. Primary sclerosing cholangitis (PSC) was found in 4 % of patients (n = 15). Two patients with PSC developed colorectal cancer (OR 4.18; p 0.008), while 13 patients with UC developed colon cancer and seven dysplastic changes. Three patients with CD developed colon cancer. Conclusions: The results were compared to other reference centers. We found similar trends in the clinical behavior and treatment of IBD, with higher hospitalization and surgery rates in our cases.


Resumen Introducción: la enfermedad inflamatoria intestinal (EII) es una enfermedad inmunomediada, cuya incidencia en Latinoamérica ha aumentado en los últimos años. Objetivo: analizar las características demográficas y clínicas de los pacientes con EII tratados en un hospital universitario y presentar los datos epidemiológicos con respecto a otros centros en Colombia. Pacientes y métodos: estudio descriptivo de pacientes con EII (1996-2019) en el Hospital Universitario Fundación Santa Fe de Bogotá. Análisis de datos de centros de Medellín, Cali, Bogotá y Cartagena. Resultados: de 386 pacientes, 277 presentaron colitis ulcerativa (CU), 102 enfermedad de Crohn (EC) y 7 colitis no clasificable. La EII fue más frecuente en mujeres (53 %). La mortalidad fue menor de 1 %. El compromiso de la CU fue principalmente la pancolitis (42,6 %). Entre mayor la extensión de la enfermedad, más alta fue la tasa de hospitalización y cirugías (OR 3,70; p < 0,01). El 13 % de los pacientes con CU recibió biológicos. El compromiso por la EC fue principalmente ileocolónico (43,6 %) e ileal (43,6 %). El patrón clínico predominante de la EC fue estenosante (50%). El 45 % recibió biológicos y 56% cirugía. La colangitis esclerosante primaria (CEP) se encontró en 4 % de los pacientes (n = 15). Dos pacientes con CEP desarrollaron cáncer colorrectal (OR 4,18; p 0,008), mientras que 13 pacientes con CU desarrollaron cáncer de colon y 7 cambios displásicos. 3 pacientes con EC desarrollaron cáncer de colon. Conclusiones: se compararon los resultados en relación con otros centros de referencia. Encontramos tendencias similares en el comportamiento clínico y en el tratamiento de la EII, con mayores tazas de hospitalizaciones y cirugías en nuestros casos.


Subject(s)
Humans , Male , Female , Inflammatory Bowel Diseases , Colitis, Ulcerative , Colitis , Data Analysis , Patients , Behavior , Colorectal Neoplasms , Crohn Disease , Incidence , Hospitals
14.
J. coloproctol. (Rio J., Impr.) ; 42(1): 14-19, Jan.-Mar. 2022. tab
Article in English | LILACS | ID: biblio-1375763

ABSTRACT

Objective: To determine the impact of the quality of colonoscopy examination for colorectal cancer screening. Methods: Retrospective observational study ofmedical records from patients treated at the endoscopy and colonoscopy service of Hospital Universitário Evangélico Mackenzie (Curitiba, PR, Brazil) from January 2019 to January 2020. Results: The analysis was based on 337 medical records from patients with adenomas identified during colonoscopy, and 1,385 medical records from patients without adenomas. The estimated occurrence rate of diagnosis of adenoma during colonoscopy in the target population of the study was of 19.6%, with a 95% confidence interval ranging from 17.7 to 21.5%. Of the 337 patients with adenoma, 136 (40.4%) presented the advanced form. Statistical analysis indicated a significant association between the quality of colonoscopy preparation and test completion. Conclusion: The quality of colonoscopy images is a critical factor for colorectal cancer screening, as it leads to higher rates of adenoma detection and test completion. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Polyps , Colorectal Neoplasms/diagnosis , Adenoma , Mass Screening , Sensitivity and Specificity , Colonoscopy , Endoscopy
15.
Säo Paulo med. j ; 140(2): 244-249, Jan.-Feb. 2022. tab
Article in English | LILACS | ID: biblio-1366048

ABSTRACT

ABSTRACT BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic has changed the course of diseases that require emergency surgery. OBJECTIVE: To evaluate the effect of the COVID-19 pandemic on colorectal cancer disease stage. DESIGN AND SETTING: Retrospective analysis in the city of Rize, Turkey. METHODS: This was a comparative analysis on two groups of patients with various symptoms who underwent surgical colorectal cancer treatment. Group 1 comprised patients operated between March 11, 2019, and December 31, 2019; while group 2 comprised patients at the same time of the year during the COVID-19 pandemic. RESULTS: Groups 1 and 2 included 56 and 48 patients, respectively. The rate of presentation to the emergency service was higher in Group 2 (P < 0.02). The stage of the pathological lymph nodes and the rate of liver metastasis was higher in Group 2 (P < 0.004 and P < 0.041, respectively). The disease stage was found to be more advanced in Group 2 (P < 0.005). The rate of postoperative complications was higher in Group 2 (P < 0.014). CONCLUSION: The presentation of patients with suspicious findings to the hospital was delayed, due both to the fear of catching COVID-19 and to the pandemic precautions that were proposed and implemented by healthcare authorities worldwide. Among the patients who presented to the hospital with emergency complaints and in whom colorectal cancer was detected, their disease was at a more advanced stage and thus a higher number of emergency oncological surgical procedures were performed on those patients.


Subject(s)
Humans , Colorectal Neoplasms/surgery , COVID-19/surgery , Retrospective Studies , Pandemics , SARS-CoV-2
16.
Article in Portuguese | LILACS | ID: biblio-1369019

ABSTRACT

RESUMO: Obstrução intestinal é a manifestação clínica mais frequente de tumores de cólon sendo esses, em sua maioria, localizados no cólon descendente e reto-sigmoide. A cirurgia de emergência para obstrução intestinal é associada a altos riscos de mortalidade e de morbidade e a abordagem ideal permanece controversa. Procedimentos em vários estágios e o uso de stents como ponte para cirurgia são opções promissoras. É apresentado um caso de paciente de 61 anos, com abdome agudo obstrutivo secundário à neoplasia colorretal, com ênfase em seu diagnóstico e tratamento. (AU)


ABSTRACT: Intestinal obstruction is the most frequent clinical manifestation of colon tumors, most of which are located in the descending and recto-sigmoid colon. Emergency bowel obstruction surgery is associated with high mortality and morbidity risks and the ideal approach remains controversial. Multi-stage procedures and the use of stents as bridges for surgery are promising options. A case of a 61-year-old patient with an acute obstructive abdomen secondary to colorectal neoplasm is presented, with emphasis on its diagnosis and treatment. (AU)


Subject(s)
Humans , Female , Middle Aged , Colorectal Neoplasms , Colectomy , Abdomen, Acute , Intestinal Obstruction/surgery , Megacolon/diagnosis
17.
Rev. argent. salud publica ; 14: 1-4, 20 de Enero del 2022.
Article in Spanish | LILACS, BINACIS, ARGMSAL | ID: biblio-1370109

ABSTRACT

NTRODUCCIÓN: El cáncer colorrectal (CCR) es una causa frecuente de mortalidad en adultos. El objetivo de este estudio fue mostrar resultados de la implementación del Programa de Rastreo de Cáncer Colorrectal (PRCCR) en la provincia del Neuquén, Argentina. MÉTODOS: Se realizó un estudio retrospectivo con análisis de resultados de sangre oculta en materia fecal (SOMF) y videocolonoscopía (VCC) en personas de 50-75 años, en efectores del sistema de salud pública en 2015-2019. Se determinó porcentaje de participación, resultados de SOMF, realización de colonoscopía en pacientes con SOMF positiva y sus hallazgos, y valor predictivo positivo (VPP) para detección de lesiones y de CCR. RESULTADOS: Se analizaron 11 189 SOMF. La participación promedio fue 6,52% de la población objetivo. Tuvieron SOMF positiva el 24,6% de los participantes; de ellos, realizaron la VCC un 24%. Se encontró lesión significativa en el 24,8% (pólipos adenomatosos 21,9%, cáncer 2,9%), con un VPP para la detección de lesiones del 34,3%. Tuvieron adenomas avanzados el 7,4%. Repitieron la SOMF tras un resultado negativo (segunda o tercera ronda) el 17,6% de los pacientes, y realizaron una VCC de control tras el hallazgo de un pólipo adenomatoso el 13,7%. DISCUSIÓN: El PRCCR en Neuquén muestra algunos indicadores que deben mejorarse (cobertura, realización de VCC) y otros adecuados (frecuencia de lesiones). Ante las dificultades se pueden plantear medidas más focalizadas, como la aplicación de escalas de riesgo de CCR, rastreo bianual, etc.


Subject(s)
Colorectal Neoplasms , Mass Screening , Colonoscopy , Outcome Assessment, Health Care , Occult Blood
18.
Acta sci., Health sci ; 44: e56960, Jan. 14, 2022.
Article in English | LILACS | ID: biblio-1367539

ABSTRACT

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.


Subject(s)
In Vitro Techniques/methods , DNA/analysis , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/therapy , Colonic Neoplasms/diagnosis , Early Diagnosis , Azacitidine/analysis , Azacitidine/antagonists & inhibitors , Biomarkers , Colorectal Neoplasms/mortality , Cell Line/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/therapy , Epigenomics , RNA, Long Noncoding , RNA, Long Noncoding/drug effects , Genes
19.
São Paulo; s.n; s.n; 2022. 130 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396955

ABSTRACT

O câncer colorretal (CCR) é o terceiro câncer mais diagnosticado em humanos. O CCR causou mais de 900.000 mortes em 2020 e foi estimado, para o período entre 2020 - 2025, um incremento de 13.5 % no número de casos novos de acordo com a plataforma Web Global Cancer Observatory. A Terapia Fotodinâmica (PDT) é uma alternativa terapêutica promissora. Conhecer as vias de sinalização de morte celular, assim como, as respostas associadas com a resistência ao dano foto-oxidativo, são relevantes para incrementar a eficiência da PDT. Neste trabalho, investigamos como as células de adenocarcinoma colorretal HT 29 respondem ao dano fotoinduzido gerado pelo fotossensibilizador (FS) meso-tetrafenilporfirina dissulfônado (TPPS2a), uma molécula que é ativada pela irradiação com luz em 522 nm. Como esperado, após irradiação (2.1 J cm-2) foi verificado que com o incremento do TPPS2a houve diminuição da viabilidade celular. A concentração do FS escolhida para darmos seguimento ao estudo foi a necessária para reduzir em 30 % a sobrevida celular (DL30; 148 nM). Abordagens moleculares nos permitiram identificar que nas células fotossensibilizadas a redução na maturação da catepsina D (CTSD, 55 %) e da catepsina B (CTSB, 52 %) contribuem com a disfunção endolisossomal. Além disso, comprovamos que as células fotossensibilizadas tiveram, pela menor quantidade de CTSD ativa, o processamento da prosaposina (PSAP) significativamente afetado. Células coletadas após 24 horas de irradiação expressaram 7 vezes mais PSAP do que as amostras dos grupos controle, sugerindo que as reações de oxidação causadas pelo TPPS2a podem ocasionar o acúmulo de glicoesfingolipídios nos endossomos e nos lisossomos, mimetizando o fenótipo observado em doenças de armazenamento lisossomal. Imagens de células HT 29 com expressão estável da proteína LGALS3 fusionada ao marcador EFGP mostraram que, após 24 horas de irradiação, as células não ativaram a lisofagia para remover os endossomos e os lisossomos danificados. A ausência do recrutamento da LGALS3 também apontou que as membranas dos endossomos e dos lisossomos não apresentam rupturas permanentes que permitam a passagem de uma molécula de 26 kDa. Experimentos complementares de análise da expressão proteica dos marcadores autofágicos LC3-II e p62/SQSTM1 (referida como p62) confirmaram o bloqueio do fluxo autofágico nas células fotosenssibilizadas. Pelo envolvimento do sistema endolisossomal no tráfego de membranas e no fluxo de lipídios, o aumento da transcrição da Hidroximetilglutaril-CoA reductase (HMGCR) (≈ 1.6 vezes) uma enzima envolvida na síntese de novo do colesterol - sugeriu que a disfunção dos endossomos e dos lisossomos altera a distribuição de colesterol. Não obstante, para manter a homeostase lipídica nas células fotossensibilizadas este não foi o único mecanismocompensatório acionado, uma vez que houve um incremento sutil; porém, significativo (1.2 vezes) na transcrição da ceramidase ácida (ASAH1). Em conjunto, nossos dados apontam que a fotossensibilização com TPPS2a constitui uma ferramenta promissora para causar dano no sistema endolisossomal, inibindo a autofagia e permitindo o estudo das respostas metabólicas em células expostas a estresse oxidativo


Colorectal cancer (CRC) is the third most commonly diagnosed cancer in humans. CRC caused more than 900,000 deaths in 2020 and it was estimated for the period 2020 - 2025, an increase of 13.5 % in the number of new cases according to the Global Cancer Observatory Web platform. Photodynamic Therapy (PDT) is a promising therapeutic alternative. Understandings of cell death signaling pathways as well as the adaptive responses associated with resistance to photo-oxidative damage are relevant to optimize the effectiveness of PDT. For this purpose, in this research, we investigated how HT-29 colorectal adenocarcinoma cells respond to photosensitization reactions generated by TPPS2a, a molecule activated by irradiation with light at 522 nm. PS concentrations displayed increased inhibitory effect on cell viability after irradiation (2.1 J cm-2). The lethal dose selected to photosensibilize cells was the TPPS2a concentration able to reduce 30 % of cell survival (LD30; 148 nM). By molecular methods, we observed a reduction in cathepsin D (CTSD, 55 %) and cathepsin B (CTSB, 52 %) maturation, depletion that may contribute to endo-lysosomal dysfunction in photosensitized cells. It is widely known that endo-lysosomal cathepsins are crucial in protein turnover and degradation. Thus, we focused on the consequence of CTSD reduction. Literature data indicate that CTSD plays a key role in prosaposin (PSAP) processing to the four saposins (SAPs) that are required in glycosphingolipids breakdown. In fact, our results in photosensitized cells showed that, due to the lower amount of active CTSD, PSAP processing was significantly affected. Cells collected after irradiation expressed 7 times more PSAP than cells from the control groups. This data suggest that oxidative photodamage induced by TPPS2a may result in glycosphingolipid-accumulating endosomes and lysosomes, phenotype which mimics lysosomal storage diseases. Furthermore, we monitored by fluorescence microscopy a form of selective autophagy which detects and removes damaged endosomes and lysosomes known as lysophagy. Images of HT-29 cells expressing Galectin 3/LGALS3 fused to EFGP showed that photosensitized cells did not activate lysophagy. The absence of LGALS3 recruitment also indicated that the membranes of endosomes and lysosomes do not present ruptures which allow the passage of proteins with a molecular weight up to at least 26 kDa. Protein expression analysis of the autophagic markers LC3-II and p62/SQSTM1 (referred as p62) confirmed autophagic flux blockade in cells challenged with photoactivated TPPS2a. The endo-lysosomal system plays a key role in membrane trafficking and lipid flux. At the transcriptional level, 1.6-fold increase in gene expression of Hydroxymethylglutaryl-CoA reductase (HMGCR) - an enzyme involved in the synthesis de novo of cholesterol - indicated that endosomes and lysosomes dysfunction alters the distribution of cholesterol in cellschallenged with photoactivated TPPS2a. However, to maintain lipid homeostasis in photosensitized cells, this was not the only compensatory mechanism triggered, since there was a slightly increase (1.2-fold) in the transcription of acid ceramidase (ASAH1). Taken together, our data showed that photosensitization with TPPS2a constitutes a promising tool to damage the endolysosomal system, to inhibit autophagy and to study metabolic responses in cells exposed to oxidative stress


Subject(s)
Autophagy , Colorectal Neoplasms/pathology , Cathepsins/chemistry , Photochemotherapy , Gene Expression , Cholesterol/adverse effects , Lysosomal Storage Diseases , Oxidative Stress , HT29 Cells/metabolism
20.
Braz. J. Pharm. Sci. (Online) ; 58: e19400, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403750

ABSTRACT

Abstract This study highlights the cytotoxic effect of three L. casei strains on colorectal cell lines in invitro conditions. Different concentrations of live, heat killed (HK) and cell free supernatant (CFS) of three L.casei strains were subjected to CaCo2 and MRC5 cell lines. The viability of the treated and untreated cells was determined after 72 hrs by MTT assay, and IC50 estimated. Apoptosis was evaluated by Annexin V-propidium iodide method using flow cytometry. The live, HK and CFS of the L. casei strains showed cytotoxic effects on colorectal cell lines with significant differences. The cytotoxicity effects of live cells on CaCo2 cells were significantly higher (p˂0.01) than the HK cells. A dose dependent response was observed, as higher concentrations resulted in enhanced cytotoxicity effects. Live L.casei 1296-2cells inhibited 91% of CaCo2 cell growth, with IC50 of less than 108 cfu/ml. MRS medium and concentrations of CFS at above 20% v/v, were cytotoxic to the normal cell lines. Flow cytometry analyses of L. casei 1296-2 indicated that cytotoxicity effects on CaCo2 cells is related to apoptotic induction. Invitro studies indicate that Live and CFS of L. casei 1296-2 might be promising candidate for the control of colorectal cancers


Subject(s)
Propidium/analysis , Colonic Neoplasms/pathology , Probiotics/analysis , Lactobacillus casei/metabolism , Colorectal Neoplasms , Cells/immunology , Apoptosis , Inhibitory Concentration 50 , Flow Cytometry/methods
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