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Bol. latinoam. Caribe plantas med. aromát ; 21(1): 66-80, ene. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1372378


Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.

Animals , Rats , Plant Extracts/administration & dosage , Anticarcinogenic Agents/administration & dosage , Colonic Neoplasms/drug therapy , Melastomataceae/chemistry , Organ Size/drug effects , Body Weight/drug effects , Chromatography, High Pressure Liquid , Rats, Sprague-Dawley , Colon/pathology , Plant Leaves , Methanol , Phenolic Compounds , Aberrant Crypt Foci , Carcinogenesis/drug effects , Antioxidants
Acta Pharmaceutica Sinica B ; (6): 246-261, 2022.
Article in English | WPRIM | ID: wpr-929291


The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.

Article in Chinese | WPRIM | ID: wpr-927924


Astragali Radix-Curcumae Rhizoma(AR-CR) is a combination commonly used in the clinical treatment of tumors. Based on the T helper 17(Th17)/regulatory T cell(Treg) balance, the present study explored the possible mechanism of AR-CR combined with 5-fluorouracil(5-FU) on the tumor growth of orthotopic xenograft model mice of colorectal carcinoma. Ninety male BALB/c mice were randomly divided into nine groups, i.e., a blank group, a model group, a 5-FU group, high-, medium-, and low-dose AR-CR(2∶1) groups, and high-, medium-, and low-dose AR-CR+5-FU groups, with 10 mice in each group. The orthotopic xenograft model of CT26.WT colorectal carcinoma was induced in mice except those in the blank group. Twenty-four hours after the ope-ration, mice in the blank group and the model group received normal saline by gavage(10 mL·kg~(-1), once per day), and those in the 5-FU group received 5-FU by intraperitoneal injection(25 mg·kg~(-1), once every other day). Mice in the AR-CR groups received AR and CR decoctions by gavage(12, 6, and 3 g·kg~(-1), once a day) and those in the combination groups received AR and CR decoctions and 5-FU(doses and administration methods were the same as above). After intervention for three weeks, all mice were sacrificed and tumor tissues were collected. The tumor mass was weighed and the average tumor weight was calculated. The changing trend of Th17/Treg(%) in the CD4~+T lymphocytes of the spleen tissues of the mice in each group was detected. The mRNA expression in the blood and protein expression in the tumor tissues of transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α), interferon-γ(IFN-γ), Smad4, N-cadherin, matrix metalloproteinase-7(MMP-7) were detected. The experimental results revealed that compared with the model group, the groups with drug intervention showed reduced tumor mass(P<0.01), decreased CD4~+IL-17~+ in the spleen tissues to varying degrees(P<0.001), and increased proportion of CD4~+Foxp3~+(P<0.001 or P<0.05), indicating that Th17/Treg maintained dynamic balance, and the effect of the combination groups was predominant. Additionally, the mRNA expression in the blood and protein expression in the tumor tissues of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 declined to varying degrees in a dose-dependent manner(P<0.01 or P<0.001). The AR-CR combined with 5-FU can inhibit the tumor growth of orthotopic xenograft model mice of CT26.WT colorectal carcinoma. The mechanism may be related to maintenance of Th17/Treg dynamic balance in the body and down-regulation of TGF-β, TNF-α, IFN-γ, Smad4, N-cadherin, and MMP-7 expression.

Animals , Colorectal Neoplasms/genetics , Drugs, Chinese Herbal/pharmacology , Fluorouracil/pharmacology , Heterografts , Humans , Male , Mice , Mice, Inbred BALB C , RNA, Messenger/metabolism , T-Lymphocytes, Regulatory , Th17 Cells
Braz. J. Pharm. Sci. (Online) ; 58: e19381, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374533


Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.

Rev. cuba. cir ; 60(3): e1150, 2021. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1347387


Introducción: La metástasis hepática del cáncer de colon es una entidad frecuente. Objetivo: Identificar los factores asociados a la supervivencia en pacientes intervenidos de cáncer de colon con metástasis hepática sincrónica. Métodos: Se realizó un estudio observacional, descriptivo y transversal a 34 pacientes operados con este diagnóstico, en el servicio de Cirugía General del Hospital Provincial Docente "Saturnino Lora" de Santiago de Cuba, desde 2010 hasta 2019. Fue estimada la supervivencia global y por diferentes periodos de tiempo en la cohorte, según el método de Kaplan-Meier. La comparación de las curvas de supervivencia para las covariables seleccionadas se realizó mediante la prueba de igualdad de distribuciones (Log-Rank de Mantel y Cox). Resultados: La supervivencia global a los seis meses y al año del diagnóstico fue de 66,5 por ciento y 66,2 por ciento, respectivamente, con mediana de dos años (IC 95 por ciento: 0,97-3,02). La supervivencia fue superior si el paciente presentó una metástasis versus dos o más, así como la de ambos lóbulos marca la menor probabilidad de supervivencia. Los tumores bien y moderadamente diferenciados mostraron mayor probabilidad de supervivencia al año que los pocos diferenciados, sin diferencias significativas. Conclusiones: La cirugía permite mejorar la sobrevida global y libre de enfermedad, aunque el uso de las distintas opciones terapéuticas para el cáncer colónico con metástasis hepática sincrónica continúa controvertido. La supervivencia de estos enfermos está condicionada por la estadificación, diferenciación histológica del tumor, localización y número de metástasis, entre otros factores(AU)

Introduction: Liver metastasis from colon cancer is a frequent entity. Objective: To identify the factors associated with survival in patients operated on for colon cancer with synchronic liver metastasis. Methods: An observational, descriptive and cross-sectional study was carried out, from 2010 to 2019, with 34 patients with this diagnosis operated on in the general surgery service of Saturnino Lora Provincial Teaching Hospital of Santiago de Cuba. Overall survival was estimated, as well as by different time periods in the cohort, using the Kaplan-Meier method. The comparison of the survival curves for the selected covariates was carried out using the test of equality of distributions (log-rank or Mantel-Cox test). Results: Overall survival six months and one year after diagnosis was 66.5 percent and 66.2 percent, respectively, with a median of two years (95 percent CI: 0.97-3.02). Survival was higher if the patient had one metastasis versus two or more, while metastasis in both lobules represents the lowest probability of survival. Well and moderately differentiated tumors showed higher probability of survival at one year than the little differentiated ones, without significant differences. Conclusions: Surgery improves overall and disease-free survival, although the use of different therapeutic options for colon cancer with synchronic liver metastases remains controversial. The survival of these patients is conditioned by staging, histological differentiation of the tumor, location and number of metastases, among other factors(AU)

Humans , Male , Female , Adult , Colonic Neoplasms/surgery , Survivorship , Neoplasm Metastasis/diagnostic imaging , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Studies as Topic
Electron. j. biotechnol ; 52: 76-84, July. 2021. graf, ilus
Article in English | LILACS | ID: biblio-1283597


BACKGROUND: Butyrate is a histone deacetylase inhibitor that induces apoptosis and inhibits cell proliferation of colorectal cancer cells. To improve its anticancer activity, butyrate has been evaluated mixed with drugs and different molecules. Plant antimicrobial peptides are attractive anticancer alternative molecules because they show selective cytotoxic activity against different cancer cell lines. In this work, we explore if the plant defensin c-thionin (Capsicum chinense) can improve butyrate activity on Caco-2 cell line and we also determined the mechanism of death activated. RESULTS: The combined treatment of c-thionin (3.5 mM) and butyrate (50 mM) showed higher cytotoxicity on Caco-2 cells with respect to single treatments. Also, the combined treatment reduced cell proliferation and exhibited a higher rate of apoptosis than single treatments. Combined treatment induced caspases 8 and 9 activation to an extent comparable with that of butyrate while c-thionin did not activate caspases. Additionally, reactive oxygen species generation preceded the onset of apoptosis, and superoxide anion production was higher in cells treated with the combined treatment. CONCLUSIONS: The c-thionin from Habanero chili pepper improved the butyrate cytotoxicity on Caco-2 cells. This effect occurred through apoptosis induction associated with reactive oxygen species production. Therefore, the combination of butyrate with cytotoxic antimicrobial peptides could be an attractive strategy for cancer therapy.

Humans , Butyrates , Capsicum/chemistry , Adenocarcinoma , Colonic Neoplasms , Cell Cycle , Reactive Oxygen Species , Apoptosis , Caco-2 Cells , Defensins , Thionins
J. coloproctol. (Rio J., Impr.) ; 41(3): 249-256, July-Sept. 2021. tab, graf
Article in English | LILACS | ID: biblio-1346430


Background: Globally, 1,096,601, 704,376, and 48,541 new colon, rectum, and anus cancer cases were recorded in 2018, respectively. Besides, 551,269, 310,394 and 19,129 cases of colon, rectum, and anus cancer deaths occurred in the same year. As a result, these cancers ranked in the third level of cancer incidence, and in the second level of cancer mortality. As it is known, all cancer patients are subjected to cancerinduced and therapy-induced nutritional deficiencies (mainly of proteins and calories). The present study aimed to assess proteins level in colorectal cancer (CRC) patients who underwent surgery and chemotherapy. Methods: A combined retrospective and prospective study was performed. The present study enrolled 100 CRC patients with their data on surgical procedures and chemotherapy management. Assessments of the studied samples were conducted as a baseline before receiving chemotherapy and preoperatively as P0, while the period after that was termed as P1. The serum samples were collected to measure protein concentration. Total Protein Kit, Micro was used. Results: The mean age of the patients was 50.7±12.88 years old. Only 8% had a positive CRC family history. Rectosigmoid cancer represented the most frequent site, figured in 41% of the cases, followed by rectum cancer. Multiple sites of CRC metastasis were recorded in 15% of the patients. All patients received chemoradiation. Folinic acid (leucovorin), 5-FU, and oxaliplatin (FOLFOX) was the most used regimen, administered in 40% of the patients. Oxaliplatin and capecitabine (also called Xeloda) (XELOX) were administered in 14% of the patients. Folinic acid (leucovorin), 5-FU, oxaliplatin, and irinotecan (FOLFOXIRI) were administered in 16% of the patients. Single-agent oxaliplatin or carboplatin were administered in 6% of the patients, each. 5-FU plus leucovorin was administered to 12% of the patients. Three patients received irinotecan, and oxaliplatin (IROX). One patient received folinic acid (leucovorin), 5-FU and irinotecan (FOLFIRI). Also, Gemzar was administered to two patients only. A total of 80% of the patients underwent several surgical procedures. Anterior perineal resection (APR) and total mesorectal excision (TME) were the most common two surgeries, performed in 20 and in 30% of the patients, respectively. In P0 status, 44% of the patients suffered from low protein levels, and 13% of the patients were within the normal level. These findings were statistically different (p=0.03). After CRC management (i.e., P1 status), 70% of the patients had protein deficiency. These results have strong significant differences (p=0.000). The mean of protein concentration declined gradually after management, from 8.82±0.9 μg/L to 6.210.78 μg/L, with a strong association between a reduction in proteins levels towards deficiency and surgical procedures and chemotherapy protocols (p=0.000). Conclusion: The incidence of CRC is increasing annually, and the chance of being diagnosed with this type of cancer has risen in recent years. In the present study, the male to female ratio was 1:1.5, and the 5th decade of life was themost common age for the diagnosis of CRC. A negative family history and bowel inflammatory diseases (IBD) history did not exclude people from exposure to the incidence of CRC. Colorectal cancer with localized and moderately differentiated adenocarcinoma were the most common types in the present work. Tumor distance from the anal verge seems to be very important and plays a significant role in the choosing of surgical intervention types and chemoradiation protocols. Colorectal cancer acts as a complex condition and, in addition to its management, nutritional state influences it in different mechanisms. Most patients suffered from hypoproteinemia after surgery and chemoradiation. As a result, alteration in the treatment outcomes, delaying in wound healing, and an increase in postoperative complications may occur. (AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Protein Deficiency , Colorectal Neoplasms/therapy , Chemoradiotherapy/statistics & numerical data
Rev. cuba. cir ; 60(2): e989,
Article in Spanish | LILACS, CUMED | ID: biblio-1280220


Introducción: El cáncer de colon constituye un grave problema sanitario debido a su alta incidencia y mortalidad. Objetivo: Describir algunos aspectos epidemiológicos, etiopatogénicos, diagnósticos, terapéuticos y evolutivos del cáncer de colon con metástasis hepáticas. Métodos: Revisión documental en bases de datos bibliográficos biomédicas sobre el tema durante el período 2015-2020. Se seleccionaron 31 artículos relacionados con el objetivo propuesto. Desarrollo: Los pacientes con cáncer de colon con metástasis hepáticas sincrónicas son tratados mediante tres estrategias: la tradicional o clásica consiste en la resección quirúrgica del tumor primario y posteriormente, quimioterapia, radioterapia o ambas, para proceder a la resección de las lesiones hepáticas tres a seis meses después; la simultánea, consistente en la resección de la lesión tumoral primaria y de las metástasis hepáticas en un mismo acto quirúrgico, seguida de quimioterapia, radioterapia o ambas y la inversa, que administra de tres a seis ciclos de quimioterapia sistémica, seguidos por la resección de las metástasis hepáticas y en un segundo tiempo resecar el tumor primario, todo esto con quimioterapia durante el intervalo entre ambas cirugías. Conclusiones: El único tratamiento con potencial curativo en los pacientes con metástasis hepáticas debe ser la resección de todo el volumen tumoral hepático con márgenes adecuados y la suficiente preservación del parénquima sano (25 - 30 por ciento), según criterios oncológicos y anatómicos establecidos, lo que incide en la calidad de vida y la supervivencia de estos enfermos(AU)

Introduction: Colon cancer is a serious health concern due to its high incidence and mortality. Objective: To describe some epidemiological, etiopathogenic, diagnostic, therapeutic and evolutionary aspects of colon cancer with hepatic metastases. Methods: Documentary review about the subject carried out in biomedical bibliographic databases, during the period 2015-2020. Thirty-one articles related to the proposed objective were selected. Development: Colon cancer patients with synchronous hepatic metastases are treated using three strategies: the traditional, or classic, strategy consists in surgical resection of primary tumor and, subsequently, chemotherapy, radiotherapy or both, before proceeding then to resection of liver lesions three to three six months later; the simultaneous strategy consists in resection of primary tumor lesion and hepatic metastases in the same surgical procedure, followed by chemotherapy, radiotherapy or both; and the reverse strategy, in which three to six cycles of systemic chemotherapy are administered, followed by resection of hepatic metastases and, in a second stage, resection of primary tumor, all this with chemotherapy during the interval between both surgeries. Conclusions: The only treatment with curative potential in patients with hepatic metastases should be the resection of the entire hepatic tumor volume with adequate margins and sufficient preservation of the healthy parenchyma (25-30 percent), according to established oncological and anatomical criteria, which has an incidence on the quality of life and survival of these patients(AU)

Humans , Quality of Life , Databases, Bibliographic , Colonic Neoplasms/surgery , Colonic Neoplasms/epidemiology , Neoplasm Metastasis/therapy , Survivorship , Liver/injuries
Rev. cuba. cir ; 60(2): e1049, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1280215


Introducción: El cáncer de colon mantiene un importante impacto social y una alta morbilidad a pesar de programas de detección precoz existentes. Ocupa el cuarto lugar entre los tumores malignos y un número importante de pacientes son operados de urgencia por las complicaciones de esta enfermedad, muchas veces desconocida hasta el momento de la cirugía. Objetivo: Caracterizar la cirugía de urgencia realizada a los pacientes con diagnóstico de cáncer de colon complicado. Método: Se realizó un estudio observacional, descriptivo, de corte transversal entre enero de 2014 y diciembre de 2016, en el Servicio de Cirugía General. La muestra fue de 96 pacientes portadores de esta entidad en el Hospital Universitario "General Calixto García". Resultados: Se analizó la incidencia según sexo, relación sexo/localización, relación localización/complicación, estadificación y mortalidad. Prevalecieron los tumores de colon en el sexo femenino y por ende fueron más frecuente las pacientes con complicaciones quirúrgicas por esta entidad en nuestro centro. Predominó la localización derecha globalmente, con predominio femenino. La oclusión intestinal fue la complicación más frecuente. Sobresalió el estadio II según TNM con un 37,5 por ciento y una mortalidad postoperatoria del 31 por ciento. Conclusiones: Nuestros datos coinciden con la tendencia nacional sobre la mayor incidencia del cáncer de colon en pacientes femeninas, son estas las que mayor tasa de morbilidad y mortalidad reportan. Seguir perfeccionando el programa de prevención y detección temprana de la entidad y su tratamiento oportuno causará la reducción de los índices que hoy se exhiben(AU)

Introduction: Colon cancer still has an important social impact and high morbidity despite existing early detection programs. It ranks fourth among malignant tumors, while a significant number of patients undergo emergency surgery for complications of this disease, many times unknown until the time of surgery. Objective: To characterize the emergency surgery performed to patients with a diagnosis of complicated colon cancer. Method: An observational, descriptive, cross-sectional study was carried out, between January 2014 and December 2016, in the general surgery service. The sample consisted of 96 patients with this entity and from General Calixto García University Hospital. Results: The incidence was analyzed according to sex, sex/location relationship, location/complication relationship, staging and mortality. Colon tumors prevailed in the female sex and, therefore, patients with surgical complications from this entity were more frequent in our center. There right location predominated globally, with a predominance in the female sex. Intestinal obstruction was the most frequent complication. Stage two, according to the TNM classification, stood out, accounting for 37.5 percent, together with a postoperative mortality of 31 percent. Conclusions: Our data coincide with the national trend on the highest incidence of colon cancer in female patients, who account for the highest morbidity and mortality rates. Continuing to improve the entity's prevention and early detection program, as well as its timely treatment, will bring about a reduction in the rates nowadays reported(AU)

Humans , Male , Female , Colonic Neoplasms/diagnosis , Emergencies , Intestinal Obstruction/complications , Neoplasm Staging/methods , Epidemiology, Descriptive , Cross-Sectional Studies , Colonic Neoplasms/epidemiology , Observational Studies as Topic
Rev. cuba. cir ; 60(1): e1020, ene.-mar. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289371


Introducción: El cáncer de colon se erige como la neoplasia del tubo digestivo más frecuente en la presente centuria. Objetivo: Identificar algunos factores clínicos, epidemiológicos y diagnósticos en pacientes operados de cáncer de colon con metástasis hepática sincrónica. Métodos: Se realizó un estudio observacional, descriptivo y transversal de una muestra de 31 pacientes operados con diagnóstico definitivo de cáncer de colon con metástasis hepática sincrónica, en el servicio de Cirugía General del Hospital Provincial Docente "Saturnino Lora" de Santiago de Cuba durante el periodo comprendido entre 2010 y 2019. Resultados: La edad promedio fue de 63,2 años. Existió predominio de la enfermedad inflamatoria intestinal como antecedente patológico personal, y del alcoholismo como factor de riesgo. La sintomatología predominante fue dolor abdominal y cambios del hábito intestinal, así como el tumor palpable al examen físico del abdomen. La ecografía abdominal y el colon por enema fueron los procederes de diagnóstico más utilizados. Prevalecieron los tumores en el colon izquierdo a nivel del descendente. Todos los tumores malignos fueron adenocarcinomas a predominio de los moderadamente diferenciados. Conclusiones: Las edades avanzadas de la vida, así como la presencia de tabaquismo y alcoholismo son factores epidemiológicos característicos de la población de enfermos aquejados de cáncer de colon con metástasis hepática. Los elementos clínicos identificados constituyeron los habitualmente descritos en la literatura médica, aunque los estudios imaginológicos utilizados preoperatoriamente resultaron limitados para el diagnóstico del cáncer de colon con metástasis hepática sincrónica, precisándose el hallazgo de las lesiones metastásicas durante la intervención quirúrgica(AU)

Introduction: Colon cancer is the most frequent digestive-tract neoplasm in the present century. Objective: To identify some clinical, epidemiological and diagnostic factors in patients operated on for colon cancer and synchronic hepatic metastasis. Methods: An observational, descriptive and cross-sectional study was carried out in a sample of 31 patients operated on with a definitive diagnosis of colon cancer and synchronic hepatic metastasis, in the general surgery service of Saturnino Provincial Teaching Hospital in Santiago de Cuba, during the period between 2010 and 2019. Results: The average age was 63.2 years. There was a predominance of inflammatory intestinal disease as a personal pathological antecedent, as well as alcoholism as a risk factor. The predominant symptoms were abdominal pain and changes in intestinal habits, as well as a tumor palpable on physical abdominal examination. Abdominal ultrasound and lower barium enema were the most used diagnostic procedures. Tumors prevailed at the level of the left descending colon. All malignant tumors were adenocarcinomas, predominantly moderately differentiated ones. Conclusions: Advanced ages of life, as well as smoking and alcoholism are characteristic epidemiological factors among the population of patients suffering from colon cancer with hepatic metastases. The clinical elements identified were those usually described in the medical literature, although the imaging studies used preoperatively were limited for the diagnosis of colon cancer with synchronic hepatic metastasis, a fact that required finding metastatic lesions during surgery(AU)

Humans , Male , Female , Middle Aged , Surgical Procedures, Operative/methods , Abdominal Pain/etiology , Colonic Neoplasms/diagnosis , Neoplasm Metastasis/diagnostic imaging , Epidemiologic Factors , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Studies as Topic
J. coloproctol. (Rio J., Impr.) ; 41(1): 87-95, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1286967


Abstract Objective This metanalysis aimed to evaluate the sensitivity and specificity of computed tomography colonography in colorectal polyp detection. Methods A literature search was performed in the PubMed and Web of Science databases. Results A total of 1,872 patients (males 57.2%, females 42.8%) aged 49 to 82 years old (mean age 59.7 ± 5.3 years) were included in this metanalysis. The estimated sensitivity of computed tomography colonography was 88.4% (46.3-95.7%, coefficient of variation [CV]=28.5%) and the estimated specificity was 73.6% (47.4-100.0%, CV=37.5%). For lesions up to 9mm, the sensitivity was 82.5% (62.0-99.9%, CV =25.1%) and the specificity was 79.2% (32.0-98.0%, CV=22.9%). For lesions>9mm, the sensitivity was 90.2% (64.0-100.0%, CV=7.4%) and the specificity was 94.7% (80.0-100.0%, CV=6.2%). No statistically significant differences in sensitivity according to the size of the lesion were found (p=0.0958); however, the specificity was higher for lesions>9mm (p<0.0001). Conclusions Most of the studies analyzed in the present work were conducted before 2010, which is about a decade after computed tomography colonography started being indicated as a screening method by European and American guidelines. Therefore, more studies aimed at analyzing the technique after further technological advancements are necessary, which could lead to the development of more modern devices.

Resumo Objetivo Esta meta-análise teve como objetivo avaliar a sensibilidade e especificidade da colonografia por tomografia computadorizada na detecção de pólipos colorretais. Métodos Foi realizada uma pesquisa bibliográfica nas bases de dados da PubMed e da Web of Science. Resultados Um total de 1.872 pacientes, 57,2% homens e 42,8% mulheres, com idades entre 49 a 82 anos de idade (média de 59,7 ± 5,3 anos) foram incluídos nesta meta análise. A sensibilidade da colonografia por tomografia computadorizada foi estimada em 88,4% (46,3-95,7%; coeficiente de variância [CV]=28,5%) e a especificidade em 73,6% (47,4%-100,0%; CV=37,5%). Para lesões de até 9mm, a sensibilidade foi de 82,5% (62,0-99,9%; CV=25,1%) e a especificidade de 79,2% (32,0-98,0%; CV=22,9%). Para lesõesmaiores que 9mm, a sensibilidade foi de 90,2% (64,0-100,0%; CV=7,4%) e a especificidade de 94,7% (80,0-100,0%; CV=6,2%). Não houve diferença estatisticamente significante entre as sensibilidades por tamanho da lesão (p=0,0958), porém a especificidade foi maior em lesões acima de 9mm (p<0,0001). Conclusão A maioria dos estudos analisados no presente trabalho foi realizada antes de 2010, cerca de uma década depois que a colonografia por tomografia computadorizada passou a ser indicada como método de triagem pelas diretrizes europeias e americanas. Portanto, são necessários mais estudos com o objetivo de analisar a técnica apósmaiores avanços tecnológicos, o que poderia levar ao desenvolvimento de dispositivos mais modernos.

Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Colorectal Neoplasms/diagnosis , Adenocarcinoma/diagnosis , Colonography, Computed Tomographic/statistics & numerical data
Article in Chinese | WPRIM | ID: wpr-909334


Objective:To explore the effect of nurse-led multi-disciplinary team management on postoperative gastrointestinal function and nutritional status in elderly colon cancer inpatients.Methods:A total of 75 elderly inpatients after colon cancer operation who met eligibility criteria and signed informed consent form were randomized into study (n=37) or control group (n=38), receiving nurse-led multi-disciplinary team management or routine nursing for 6 months, respectively. The gastrointestinal function, days of postoperative hospital stay, body weight, body composition and dietary intake were compared between the two groups.Result:Compared to the control group, time to defecation (t=14.79, P<0.01), time to initiation of liquid diet intake (t=6.80, P<0.01), time to initiation of semi-liquid diet intake (t=10.78, P<0.01) and days of postoperative hospital stay (t=8.76, P<0.01) in the study group were significantly shortened; and body weight [(59.44±6.12)kg vs. (62.54±6.41)kg, P=0.004], BMI [(19.02±4.13)kg/m 2 vs. (19.98±3.98)kg/m 2, P=0.025], body fat percentage [(20.03±3.55)% vs. (21.34±3.68)%, P<0.01], lean body mass [(19.63±3.44)kg vs. (21.45±3.16)kg, P<0.01], grip strength [(21.65 ± 3.56) kg vs. (22.48 ± 3.81) kg, P=0.011], attainment rate of 75% target energy intake (65.8% vs. 86.5%, P=0.036) and attainment rate of 75% target protein intake (57.9% vs. 83.8%, P=0.014) were significantly improved in study group 6 months after operation. Conclusion:The nurse-led multi-disciplinary team management can effectively improve the postoperative recovery of gastrointestinal function and the long-term nutritional status in elderly patients with colon cancer.

International Journal of Surgery ; (12): 755-759, 2021.
Article in Chinese | WPRIM | ID: wpr-907518


Objective:To investigate the incidence of adhesive intestinal obstruction after resection of colon cancer and analyze its risk factors.Methods:Three hundred and sixty-three colon cancer patients who underwent colon cancer resection in Affiliated Hospital of Weifang Medical University from March 2016 to September 2019 were selected as the research objects, including 189 male and 174 female, aged from 45 to 75 years old, with the average of (62.36±10.69) years. Postoperative outpatient follow-up for 6 months to record the incidence of adhesive intestinal obstruction in patients after colon cancer resection. According to the occurrence of adhesive intestinal obstruction, they were divided into occurrence group and non-occurring group. The general data, laboratory data and pathological data of the two groups of patients were compared. Logistic regression was used to analyze the risk factors of adhesive intestinal obstruction after colon cancer resection.Results:As of the last follow-up time on March 23, 2020, a total of 13 patients were lost to follow-up due to different reasons. A total of 350 patients completed the follow-up, and 350 patients were finally included. The incidence of adhesive intestinal obstruction after colon cancer resection was 22.29% (78/350), these 78 patients were defined as the occurrence group, and the other 272 patients without adhesive intestinal obstruction were regarded as the non-occurrence group. There were statistically significant differences in age, comorbid diabetes, surgical methods, operation time, tumor differentiation, and lymphatic metastasis between the occurrence group and the non-occurring group ( χ2=275.397, P<0.001; χ2=52.574, P<0.001; χ2=137.931, P<0.001; χ2=48.419, P<0.001; χ2=2.099, P=0.036; χ2=36.073, P<0.001); multivariate logistic regression analysis showed that age>60 years old ( OR=41.113), complicated with diabetes ( OR=0.055), open surgery ( OR=21.913), long operation time ( OR=25.069), high degree of tumor differentiation ( OR=0.109), lymphatic metastasis ( OR=0.068) are the adhesive bowel after colon cancer resection Risk factors for obstruction. Conclusions:The incidence of bowel function after colon cancer resection was 22.29%. Age, operation method, operation time, comorbidities, tumor differentiation degree, and lymphatic metastasis are the influencing factors of adhesive intestinal obstruction after colon cancer resection, and should be treated in the treatment process. Focus on preventing the occurrence of adhesive intestinal obstruction after colon cancer resection.

Article in Chinese | WPRIM | ID: wpr-906208


Objective:To explore the anti-hepatoma effect of compound <italic>Phylanthus urinaria</italic> Ⅱ ( CPU Ⅱ) by inhibiting the expression of the long non-coding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) and restoring the expression of microRNA let-7a. Method:Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the expression of lncRNA CCAT1 in normal liver cells (LO2 cells) and hepatocellular carcinoma HepG2 cells, and the differences in expression between these two types of cells were compared. The methylthiazolyl tetrazolium(MTT) assay was used to detect the proliferation of HepG2 cells after treatment with different concentrations of CPU Ⅱ and 5-fluorouracil(5-FU) for 24, 48 and 72 h. Hepatocellular carcinoma HepG2 cells were cultured <italic>in vitro </italic>and set into three gropes: cell control group, CPU Ⅱ low-dose group (0.8 g·L<sup>-1</sup>) and high-dose group (1.6 g·L<sup>-1</sup>). Real-time PCR was used to detect the mRNA expression of lncRNA CCAT1, microRNA let-7a and its target genes high mobility group protein A2(HMGA2), and N-RAS in each grope. Western blot was used to detect the protein expression of HMGA2, and Cyclin D<sub>1</sub> in each grope. Result:As compared with LO2 cells, expression of lncRNA CCAT1 in HepG2 cells was significantly up-regulated (<italic>P</italic><0.05). Results of MTT assay showed that the 50% inhibiting concentration(IC<sub>50</sub>)<sub> </sub>of CPU Ⅱ and 5-FU on hepatocellular carcinoma HepG2 cells was 1.649, 0.044 648 g·L<sup>-1 </sup>respectively. As compared with the control group, CPU Ⅱ high-and low-dose groups (1.6, 0.8 g·L<sup>-1</sup>) significantly inhibited the proliferation of HepG2 cells (<italic>P</italic><0.05), and the effect was most remarkable in CPU Ⅱ high-dose group (<italic>P</italic><0.05). The results of Real-time PCR showed that as compared with control group, the expression of lncRNA CCAT1 mRNA was significantly inhibited in CPU Ⅱ high-and low-dose groups (<italic>P</italic><0.05), and the expression of microRNA let-7a mRNA was obviously up-regulated in high-dose group (<italic>P</italic><0.05), but the expression of HMGA2 mRNA in CPU Ⅱ high-and low-dose groups as well as the expression of N-RAS mRNA in CPU Ⅱ low-dose group were down-regulated (<italic>P</italic><0.05). Western blot results showed that as compared with the cell control group, the protein expression of HMGA2 and Cyclin D<sub>1</sub> in CPU Ⅱ high-and low-dose groups (1.6, 0.8 g·L<sup>-1</sup>) was significantly down-regulated (<italic>P</italic><0.05). Conclusion:CPU Ⅱ can inhibit the expression of lncRNA CCAT1, recover the expression of microRNA let-7a, and suppress the mRNA and protein expression of related downstream target genes in hepatoma cells line HepG2, thereby inhibiting the proliferation of hepatocellular carcinoma cells and exerting anti-hepatocellular carcinoma effect.

Article in Chinese | WPRIM | ID: wpr-905962


Objective:To explore whether palmatine interferes with the proliferation and apoptosis of colon cancer HCT116 cells by binding to G-quadruplex in the promoter region of MYC proto-oncogene and its possible molecular mechanism. Method:Fluorescence spectrum was used to analyze the binding ability of palmatine to MYC G-quadruplex. Circular dichroism analysis was conducted to confirm the effect of palmatine on the configuration of MYC G-quadruplex, followed by the prediction of their binding mode based on molecular docking and the localization analysis of palmatine in HCT116 cells under a fluorescence microscope. The effects of palmatine on MYC gene transcription and MYC protein expression were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. The effects of palmatine on the viability and apoptosis of HCT116 cells were further assayed by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry. Result:As revealed by fluorescence spectrum and molecular docking analysis, palmatine might bind to G-quadruplex of MYC gene through stacking. Circular dichroism analysis showed that palmatine could maintain the parallel configuration of MYC<italic> </italic>G-quadruplex. It was discovered in fluorescence imaging that palmatine was distributed in the nucleus and bond to G-quadruplex of MYC gene. In addition, palmatine inhibited MYC gene transcription, MYC protein expression, as well as the viability of HCT116 cells, and promoted the apoptosis of HCT116 cells. Conclusion:Palmatine is able to bind to MYC G-quadruplex to further inhibit the expression of MYC gene and protein expression, which may be one of the molecular mechanisms of palmatine in suppressing the proliferation of colon cancer HCT116 cells and facilitating their apoptosis.

Article in Chinese | WPRIM | ID: wpr-905958


Objective:To explore the possible mechanism of Astragali Radix-Curcumae Rhizoma (AC) in inhibiting tumor growth in the orthotopic transplantation model of colon cancer in mice. Method:The molecular docking technology was used to predict the intermolecular interaction between the main active components of AC and the pathway target proteins, such as stromal cell-derived factor-1 (SDF-1), C-X-C motif chemokine receptor 4 (CXCR4), and nuclear factor kappa-B p65 (NF-<italic>κ</italic>B p65). The orthotopic transplantation model of CT26.WT colon cancer was established in mice for <italic>in vivo</italic> experimental verification. Sixty BALB/c male mice were randomly divided into a sham operation group, a model group, a 5-fluorouracil (5-Fu, 30 mg·kg<sup>-1</sup>) group,and low- (0.32 g·kg<sup>-1</sup>), medium- (0.64 g·kg<sup>-1</sup>), and high-dose (1.28 g·kg<sup>-1</sup>) AC groups, with 10 mice in each group. The sham operation group and the model group received normal saline by gavage. The corresponding drugs were administered by gavage in the 5-Fu group and by intraperitoneal injection in the AC groups. After intervention for 15 days, the tumor <italic>in situ</italic> was completely stripped, and the colon tissues 5-6 cm in length adjacent to the tumor were taken. The tumor volume was measured and calculated. The pathological changes of tumor tissues and colon tissues were observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression of SDF-1, CXCR4, p-NF-<italic>κ</italic>B p65 in colon tissues. Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect SDF-1, CXCR4, NF-<italic>κ</italic>B p65, Cyclin D<sub>1</sub>, oncogene c-Myc protein and mRNA expression in tumor tissues. Result:Compared with the model group, 5-Fu and AC groups showed reduced tumor volumes <italic>in situ</italic> (<italic>P</italic><0.05, <italic>P</italic><0.01), with the tumor inhibition rate in the 5-Fu group as high as (61.38±2.34)%. The tumor-inhibiting effect was optimal in the medium-dose AC group, with the tumor inhibition rate of (43.43±3.71)%. Compared with the model group, 5-Fu and AC groups showed relieved pathological changes of tumor and colon tissues. Specifically, AC down-regulated the protein expression levels of SDF-1, CXCR4, and p-NF-<italic>κ</italic>B p65 in colon tissues (<italic>P</italic><0.01), and down-regulated the protein and mRNA expression levels of SDF-1, CXCR4, NF-<italic>κ</italic>B p65, Cyclin D<sub>1</sub>, and c-Myc in tumor tissues (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:AC can inhibit the growth of orthotopic transplantation tumor of colon cancer, and its intervention mechanism may be related to the regulation of related protein and mRNA expression in the SDF-1/CXCR4/NF-<italic>κ</italic>B signaling pathway.

Article in Chinese | WPRIM | ID: wpr-905864


Objective:To observe the effect of Jianpi Xiaoai prescription on long non-coding RNA Hox transcript antisense intergenic RNA (lncRNA HOTAIR)/Janus kinase 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3) signaling pathway and to explore the potential mechanism of Jianpi Xiaoai prescription in suppressing the metastasis of colon cancer. Method:The expression of lncRNA HOTAIR in different cells was analyzed. Following the treatment of HCT116 cells with 10%,15%,and 20% Jianpi Xiaoai prescription -containing serum, the invasive ability of Jianpi Xiaoai prescription on HCT116 cells was assessed by transwell assay. The mRNA expression levels of lncRNA HOTAIR,JAK2,and STAT3 were measured by Real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of JAK2, phosphorylated STAT3 (p-STAT3) and STAT3 by Western blot. Result:The highest expression of lncRNA HOTAIR was detected in HCT116 cells. Compared with the blank group, each Jianpi Xiaoai prescription group exhibited a decreased number of invasive cells (<italic>P</italic><0.05, <italic>P</italic><0.01). The relative JAK2 mRNA expression in the middle-dose Jianpi Xiaoai prescription group was down-regulated (<italic>P</italic><0.05), and the relative lncRNA HOTAIR mRNA expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative JAK2 mRNA expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated (<italic>P</italic><0.01). Compared with the blank group,the relative p-STAT3 protein expression was down-regulated in the middle-dose Jianpi Xiaoai prescription group (<italic>P</italic><0.05), and the relative JAK2 protein expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative p-STAT3 protein expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated (<italic>P</italic><0.01). Conclusion:Jianpi Xiaoai prescription effectively inhibits the metastasis of colon cancer cells, which may be related to the inhibition of lncRNA HOTAIR/JAK2/STAT3 signaling pathway.

Article in Chinese | WPRIM | ID: wpr-904752


Objective To compare the differences in the anti-tumor growth effects of organisms with different injections of CT26 tumor cell RNA loaded into nanoliposomes. Methods The extracted tumor RNA was loaded into nanoliposomes to prepare tumor RNA nanoliposome vaccines, and the related properties of nanoliposome vaccines were investigated. The particle size of nanoliposome vaccines was (120.0±12.1)nm and zeta potential was (3.39±0.56)mV. Tumor RNA nanoliposome vaccines were injected into different parts of the mice to test and analyze the influence of different injections on the growth of colon cancer transplanted tumors in mice. Results Tumor RNA nanoliposome vaccines were used to inject tumor-transplanted mice in different ways. Compared with underarm injection, intraperitoneal injection enhanced the organism's anti-tumor immune response and inhibited the growth of transplanted tumors more effectively. The H&E staining of important organs in mice was compared and no obvious organic lesions were found in the organs. Conclusion Intraperitoneal injections of nanoliposome loaded with tumor RNA can enhance the body's anti-tumor immune response more effectively than underarm injections.

Article in Chinese | WPRIM | ID: wpr-881393


@#To investigate the regulatory effects of insulin and oleic acid on serum metabolites in colon cancer, subcutaneous transplantation tumor model of colon carcinoma cell HCT116 was established. Nude mice were randomly divided into 4 groups: control (CON, vehicle); insulin treatment (INS, sc, 2.5 U/kg); oleic acid treatment (OA, ig, 2.0 g/kg); and insulin (sc, 2.5 U/kg) plus oleic acid (ig, 2.0 g/kg) treatment (IO). Non-target metabolomic analysis on the blood samples was performed by GC/MS and LC-IT-TOF/MS. Data pre-processing, including peaking, spectral deconvolution and peak alignment, was performed before data were imported to SIMCA-P for multivariate statistical analysis. Results showed that body weight of individuals in IO group was the lowest, but the tumor weight was the heaviest. Metabolic profiles of IO group were also different compared with the CON group, and the contributing metabolites were urea, arabinose, cholesterol, L-acetylcarnitine and sphingosine. There was no significant difference between OA or INS and CON. This study showed that the combination of insulin and oleic acid promoted colon cancer deterioration and caused metabolic disturbance in blood.Our study may provide theoretical foundation for the discovery of colon cancer biomarker and its early diagnosis.

China Pharmacy ; (12): 51-55, 2021.
Article in Chinese | WPRIM | ID: wpr-862265


OBJECTIVE:To study the effects of shikonin on autophagy and apoptosis of human colon cancer HCT 116 cells. METHODS:After treating HCT 116 cells for 48 h with shikonin at 0(blank control )10,20,40 μg/mL,MTT method was used to detect inhibitory rate of cell proliferation. Flow cytometry was used to detect cell apoptosis rate. RT-qPCR assay and Western blotting were respectively used to detect mRNA and protein expressions of microtubule associated protein light chain 3(LC3)and autophagy-related protein Beclin- 1 and p 62. RESULTS :Compared with blank control ,after treated with 10,20,40 μ g/mL shikonin for 48 h,proliferation inhibitory rate and apoptosis rate of HCT 116 cells were increased significantly (P<0.05 or P< 0.01). After treated with 10,20,40 μg/mL shikonin for 48 h,mRNA and protein expressions of LC 3,Beclin-1 and p 62 in HCT116 cells were increased to different extents ;except that mRNA expression of LC 3 was not increased significantly after treated with 10 μg/mL shikonin,the difference were statistically significant in other indexes ,compared with blank control (P<0.05 or P<0.01). CONCLUSIONS :Shikonin can induce the apoptosis of human colon cancer HCT 116 cells and activate its autophagy pathway.