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Colorectal cancer (CRC) is a lethal malignant tumor and 25-30% of CRC patients develop liver metastasis (LM) with a worse prognosis, but the metastasis mechanism is yet elucidated. To identify the potential immune regulatory mechanism of CRC liver metastasis, single-cell sequencing and multiplex immunohistochemistry were applied to identify key cell populations of the tumor microenvironment (TME) in the CRC and LM sites. We found memory CD8+ T cells, B cells, and CTSB + macrophages were enriched in the LM site, forming the memory immune hub, which was important for the anti-tumor response against LM. Therefore, our results revealed that memory immune responses were called in the LM sites and probably meditated by CTSB + macrophages.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Linfocitos T CD8-positivos/patología , Catepsina B , Neoplasias Colorrectales/patología , Humanos , Neoplasias Hepáticas/secundario , Macrófagos/patología , Microambiente TumoralRESUMEN
PURPOSE: Recent studies on hypothermia typically focused on a single anesthesia method or a particular surgical procedure. Although there are multiple risk factors leading to hypothermia, such as the use of cold solutions or nonhumidified and nonheated anesthetic gases, few studies have reported the incidence of postoperative hypothermia among patients in the postanesthesia care unit (PACU). DESIGN: This is a retrospective analysis of patients who underwent surgery and were admitted to the PACU immediately after surgery at the Fourth Affiliated Hospital, College of Medicine, Zhejiang University, from September 2018 to March 2019. METHODS: Patient data were collected and analyzed in two groups to understand the factors affecting the occurrence of hypothermia. Hypothermia was defined as a core temperature of less than 36°C. On the basis of body temperature, patients in the PACU were divided into hypothermic and nonhypothermic groups. Factors influencing hypothermia were studied by the univariate method, followed by logistic regression analysis to identify the risk factors for hypothermia onset. FINDINGS: Of a total of 1,788 patients were enrolled in the study, 113 (6.32%) exhibited hypothermia (<36°C) in the PACU. The hypothermic and nonhypothermic groups displayed significant differences (P < .05) in the anesthesia method used as well as the American Society of Anesthesiologists physical classification status. The body temperature at the time the patients were admitted to the operating room influenced the occurrence of postoperative hypothermia (P < .01). These parameters were recognized as independent risk factors for postoperative hypothermia in the PACU. CONCLUSIONS: Significant risk factors for the onset of hypothermia were general anesthesia and higher American Society of Anesthesiologists grade. However, epidural anesthesia was found to have a protective effect.
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Hipotermia , Periodo de Recuperación de la Anestesia , Temperatura Corporal , Humanos , Hipotermia/epidemiología , Hipotermia/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is recognized as one of the most common cancer globally. The association between CRC and apurinic endonuclease 1 (APE1) Asp148Glu polymorphism remains unclear; thus, this meta-analysis aimed to explore whether APE1 Asp148Glu polymorphism is related to CRC risk. METHODS: Embase, PubMed, Cochrane library, CNKI and Wanfang databases were subject to a systematic search until April, 17, 2020 to evaluate the effect of APE1 Asp148Glu polymorphism on CRC risk. The associated strength was used to evaluate with odds ratios (ORs) with 95% confidence intervals (CIs) between Asp148Glu polymorphism and CRC risk. Subgroup analyses were also performed. RESULTS: In total, 11 articles including 8,136 subjects (3,836 cases and 4,300 controls) were included. Five genetic models were analyzed, including the additive model (G vs. T), the heterozygote comparison (TG vs. TT), the homozygote comparison (GG vs. TT), the dominant model (TG+GG vs. TT), and the recessive model (GG vs. TG+TT). In these models, T refers to thymine and G refers to guanine. The APE1 Asp148Glu polymorphism in heterozygote comparison [OR (95%CI) = 1.36 (1.05, 1.75), P=0.019] and dominant model [OR (95%CI) =1.31 (1.07, 1.61), P=0.010] significantly increased CRC risk. No significant association was seen for the additive model [OR (95%CI) = 1.14 (1.00, 1.31), P=0.057], recessive model [OR (95%CI) = 0.97 (0.71, 1.31), P=0.826] or in homozygote comparison [OR (95%CI) = 1.15 (0.88, 1.52), P=0.309]. Moreover, CRC risk indicated a remarkable association with APE1 Asp148Glu polymorphism in the PCR-RFLP additive model, homozygote comparison and recessive model (PG) may be a potential risk factor for CRC.
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Neoplasias Colorrectales , ADN-(Sitio Apurínico o Apirimidínico) Liasa , Neoplasias Colorrectales/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Predisposición Genética a la Enfermedad , Humanos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
This study aimed to investigate the effects of triggering receptor expressed on myeloid cell-2 (TREM2) on the production of pro-inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2-specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre-treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF-kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF-α, IL-1ß, and the activation of AKT and NF-kB, while decreased the levels of IL-10 and TGF-ß1. However, these pro-inflammatory effects were significantly attenuated by TREM2 overexpression or pre-treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down-regulating PI3 K/AKT and NF-kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.
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Glicoproteínas de Membrana/metabolismo , Microglía/metabolismo , FN-kappa B/antagonistas & inhibidores , Inhibidores de las Quinasa Fosfoinosítidos-3 , Receptores Inmunológicos/metabolismo , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , L-Lactato Deshidrogenasa/metabolismo , Lipopolisacáridos/farmacología , Glicoproteínas de Membrana/genética , Ratones , Microglía/efectos de los fármacos , Microglía/patología , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fagocitosis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Inmunológicos/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Human guts harbor abundant microbes that regulate many aspects of host physiology. However, bacterial imbalance or dysbiosis in the gut due to the dietary or environmental changes may cause colorectal cancer (CRC). Increasing studies show that gut microbiota plays an important role in the occurrence and development of CRC, as a result of virulence factors, bacterial metabolites, or inflammatory pathways. In the future, probiotics or targeting the microbiota will probably be a powerful weapon in the battle against CRC. This review seeks to outline the relationship between gut microbiota and the development of CRC as well as the potential mechanisms of microbiota involved in treatment of CRC, so as to provide some references for research on the development, prevention, and treatment of this disease.
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Bacterias/patogenicidad , Neoplasias Colorrectales/etiología , Disbiosis/dietoterapia , Microbioma Gastrointestinal/fisiología , Probióticos/administración & dosificación , Antineoplásicos/efectos adversos , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Neoplasias Colorrectales/terapia , Suplementos Dietéticos , Disbiosis/complicaciones , Disbiosis/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Factores de Virulencia/metabolismoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is the most common cause of cancer death worldwide. Numerous studies have identified the roles of survivin -31 G/C and angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms in CRC risk; however, the results remain inconclusive. This study was to investigate associations between these two polymorphisms and CRC susceptibility. METHODS: A comprehensive literature search was conducted to collect relevant case-control studies published between 2000 and 2014. The extracted data were statistically analyzed, and the odds ratios (ORs) with 95% confidence intervals (CIs) were employed to estimate the strength of association. RESULTS: A total of 11 studies were included in the meta-analysis. For survivin G/C polymorphism, six articles reported 1,840 cases and 1,804 controls. Overall, we found the frequency of C allele is higher in CRC cases than that in the healthy controls (57.2% vs. 48.0%), and C allele significantly increased the risk of CRC compared to G allele in allele model (OR = 1.46, 95% CI = 1.33-1.60, P < 0.00001). This association was also found in other genetic models (P < 0.00001). Stratified analysis by ethnicity showed significant association in each genetic model among the Asian population. For ACE I/D polymorphism, five studies included 758 cases and 6,755 controls. No significant association was found in any genetic models. CONCLUSIONS: Our results showed that survivin -31 G/C polymorphism might contribute to risk of CRC, especially in the Asian populations. However, the ACE I/D polymorphism is not a genetic factor concerning the risk for CRC. More studies with larger sample sizes are required in the future.
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Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Proteínas Inhibidoras de la Apoptosis/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Estudios de Casos y Controles , Humanos , Pronóstico , Factores de Riesgo , SurvivinRESUMEN
BACKGROUND: This study was designed to compare the long-term surgical outcomes of patients with mid and low rectal cancer after open or hand-assisted laparoscopic surgery (HALS). METHODS: A case-matched controlled prospective analysis of 116 patients who underwent hand-assisted laparoscopic surgery (HALS) for stage I to III mid and low rectal cancer from 2005 to 2010 was performed. Contemporary patients who underwent open rectal surgery were matched to the HALS group at the ratio of 1:1. The perioperative clinical outcomes, postoperative pathology, and survival outcomes were compared between the groups. RESULTS: The patient characteristics between the two groups were comparable. Ninety patients in the open group and 85 in the HALS group received sphincter-preserving surgery. HALS resulted in less blood loss and wound infection, faster return to oral diet, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Lymph node retrieval and involvement of circumferential and distal margins were similar for both procedures. Cumulative incidences of locoregional recurrence, disease-free, or overall survival rates were statistically similar. CONCLUSIONS: This study suggests that HALS for mid and low rectal cancer is acceptable in terms of short-term clinical outcomes and long-term survival results.
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Adenocarcinoma/cirugía , Laparoscópía Mano-Asistida/métodos , Recurrencia Local de Neoplasia , Neoplasias del Recto/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIMS: To describe the initial experience of simultaneous resection of colorectal cancer and liver metastases through hand-assisted laparoscopy (HALS). METHODOLOGY: After endotracheal general anesthesia, patients were placed in the Trendelenburg with lithotomy position. A 5-cm longitudinal subumbilical port was created, and the Lap Disc device was placed and pneumoperitoneum was established. A laparoscope was inserted to explore the liver and the whole pelvic cavity. The surgeon stood on the right side or between the patient's legs, and a 10-mm trocar was placed in the abdominal wall based upon the location of the tumor. The liver and the colorectal lesion were reselected with the assisted-hand through the Lap Disc to establish the possibility of resection, the tumor margin, and metastasis. RESULTS: Simultaneous resection of colorectal cancer and liver metastases through HALS were successful in all eight patients with operating time of 2-4 h. Average intraoperative blood loss was 100-300 ml, and no severe postoperative complications were observed. The average length of postoperative hospital stay was 7.5 days. CONCLUSIONS: HALS for simultaneous resection of colorectal and metastatic liver cancer has the advantages of safety, feasibility, minimal invasion, shorter operation time, reduced operative difficulty less pain and rapid recovery.
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Colectomía/métodos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Laparoscópía Mano-Asistida , Hepatectomía/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Anciano , Pérdida de Sangre Quirúrgica , Colectomía/efectos adversos , Colectomía/instrumentación , Colonoscopía , Diseño de Equipo , Estudios de Factibilidad , Femenino , Laparoscópía Mano-Asistida/efectos adversos , Laparoscópía Mano-Asistida/instrumentación , Inclinación de Cabeza , Hepatectomía/efectos adversos , Hepatectomía/instrumentación , Humanos , Laparoscopios , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Posicionamiento del Paciente , Complicaciones Posoperatorias/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
3,5-diCQA has been shown to have anti-tumor effect by decreasing cancer cell growth. However, the molecular mechanism by which 3,5-diCQA impacts colorectal cancer (CRC) cells is unknown. This study discovered that 3,5-diCQA had a suppressive effect on CRC cells, mainly in the inhibition of proliferation, migration, and the enhancement of apoptosis in HCT116 and SW480 cells. Additionally, 3,5-diCQA was found to cause cell cycle arrest in CRC cells. Meanwhile, we found that 3,5-diCQA activates the AMPK pathway through the generation of ROS, mediates mitochondrial damage, and reduces mitochondrial aerobic glycolysis and oxidative phosphorylation levels. 3,5-diCQA promoted oxidative damage and ferroptosis in CRC cells. Hence, we added ROS inhibitor NAC and found that the NAC reversed the effects of 3,5-diCQA on proliferation, apoptosis, ROS generation, and ferroptosis in CRC cells. Moreover, 3,5-diCQA was also shown to suppress the development of CRC tumor in a tumor-forming model of nude mice. In conclusion, we found that 3,5-diCQA enhances the oxidative damage and ferroptosis while reducing proliferation and migration of CRC cells, depending on mitochondrial dysfunction caused by the ROS/AMPK/mTOR pathway.
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Neoplasias Colorrectales , Ferroptosis , Animales , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Desnudos , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Colorrectales/patología , Apoptosis , Mitocondrias/metabolismo , Proliferación Celular , Línea Celular TumoralRESUMEN
Object: Controversy remains regarding the safety and efficacy of hemorrhoid ligation and stapled hemorrhoidopexy (SH) in the treatment of hemorrhoids. The study was to explore the operative outcomes of patients underwent multiple thread ligations (MTL) with SH for the management of grade III hemorrhoids. Methods: This cohort study included patients who underwent MTL (MTL group, 128 cases) or SH (SH group, 141 cases) for grade III hemorrhoids between June 2019 and May 2021. A total of 115 patients in MTL group and 115 patients in SH group were finally included by propensity score matching with a ratio of 1:1. The primary outcome was the recurrence of prolapse within 6 months. Secondary outcomes were operative time, post-operative pain scores, hospital stay, the incidence of complications, Wexner incontinence score, and quality of life of patients with constipation at 6 months post procedure. Results: Multiple thread ligations and SH resulted in comparable recurrence within 6 months of follow-up, with five and seven cases of recurrence, respectively, (P = 0.352). The two groups had comparable outcomes in terms of post-operative pain, hospital stay, Wexner incontinence scores, and constipation-related quality of life (all P > 0.05). The median operative time was 16 min (15-18 min) in the MTL group versus 25 min (16-33 min) in the SH group (P < 0.01). Univariate analysis showed that the MTL technique had a lower risk of postoperative bleeding than that with the SH technique (P < 0.05). Conclusion: The study indicated that the MTL technique might achieve comparable operative outcomes compared with the SH technique for the management of grade III hemorrhoids, nevertheless, MTL seemed to be associated with less risk of surgical bleeding than SH.
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Colon cancer ranks third worldwide, and it has a growing incidence with urbanization and industrialization. Drug resistance in colon cancer is gradually affecting the treatment. This study focused on the mechanisms by which acriflavine (ACF) enhances the radiosensitivity of colon cancer cells. First, the expression and activation levels of tumor suppressor protein p53 were shown high in normal cells and tissues in its detection, which suggests that p53 is likely to be a key factor in colon cancer. Then, the expression of p53 ended up increasing in ACF group after SW620 cells were cultured with ACF. In addition, ACF group had some other changes. The expression of mitochondrial related antiapoptotic protein Bcl-2 increased, while the expression of proapoptotic protein Bax, Bad, cytopigment C, and apoptotic inducer AIF decreased. At the same time, the ability of apoptosis was enhanced, and the ability of proliferation and invasion was decreased. This suggests that ACF can promote p53 expression and affect mitochondrial function and the radiosensitivity of SW620. The luciferase reporting experiment showed that there was a binding site between ACF and p53. Besides, when IR treatment was applied to SW620 with high p53 expression, there was an increase in the expression of Bcl-2 in SW620 and decrease in Bax, Bad, and cytopigment C in AIF. Meanwhile, the cell apoptosis became stronger, and the proliferation and invasion became weaker. The experimental results were similar to those of SW620 cells cultured with ACF, suggesting that p53 is an intermediate factor in the regulation of SW620 by ACF. Finally, in this study, cells were cultured with ACF, and p53 was knocked down at the same time. The experimental results showed that after p53 was knocked down. ACF's ability to regulate SW620 is partially removed. This confirms the view that ACF regulates SW620 cells by regulating p53. In summary, this study found the mechanism by which ACF causes mitochondrial dysfunction and improves the radiosensitivity of colon cancer cells by activating the tumor suppressor protein p53, which may contribute to solving the drug resistance in colon cancer.
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Neoplasias del Colon , Proteína p53 Supresora de Tumor , Acriflavina/metabolismo , Acriflavina/farmacología , Acriflavina/uso terapéutico , Proteínas Reguladoras de la Apoptosis , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/radioterapia , Humanos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tolerancia a Radiación , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Background: Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma. Aims: To investigate the characteristics of intestinal microbiota in colorectal adenoma and carcinoma patients and the correlations with clinical characteristics. Methods: Fecal samples were collected from 154 colorectal carcinoma patients (CRC group), 20 colorectal adenoma patients (AD group), and 199 healthy controls (control group). The intestinal microbiota was investigated by 16S rRNA gene sequencing. Results: Compared to the healthy controls, microbial diversity was dramatically decreased in AD/CRC. At the genus level, Acidaminococcus significantly decreased with the order of control-AD-CRC (P < 0.05). Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. Combination of the top 10 most important species, including Butyricimonas synergistica, Agrobacterium larrymoorei, Bacteroides plebeius, Lachnospiraceae bacterium feline oral taxon 001, Clostridium scindens, Prevotella heparinolytica, bacterium LD2013, Streptococcus mutans, Lachnospiraceae bacterium 19gly4, and Eubacterium hallii, showed the best performance in distinguishing AD patients from CRC (AUC = 85.54%, 95% CI: 78.83%-92.25%). The clinicopathologic features, including age, sex, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC. Conclusion: Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.
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Adenoma , Carcinoma , Neoplasias Colorrectales , Microbioma Gastrointestinal , Adenoma/patología , Animales , Bacterias/genética , Gatos , Neoplasias Colorrectales/genética , Disbiosis/microbiología , Heces/microbiología , Microbioma Gastrointestinal/genética , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: The incidence of colorectal cancer (CRC) has significantly increased in adults < 50 years old who are below the screening age. OBJECTIVES: The primary objective was to evaluate the age-standardized incidence (ASI) of young-onset CRC from 1988 to 2013. The secondary objective was to assess factors associated with cancer-specific death (CSD). METHODS: We accessed data of 64,854 CRC patients (20-49 years old) from the United States Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: A gradual increase in the ASI of CRC in the study population was found: from 3.59/100,000 males in 1988 to 5.21/100,000 males in 2013, and from 3.15/100,000 females in 1988 to 4.45/100,000 females in 2013. ASI adjusted by race revealed a relatively pronounced increase in the white population compared to African American and other races, with an increase from 3.07/100,000 persons in 1988 to 4.79/100,000 persons in 2013. Males had a 19% higher likelihood of CRC-related death compared to females [hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.16-1.23], and African American had a 1.34-fold higher likelihood of CRC-related death compared to whites (95% CI: 1.28-1.39). CRC-related death was significantly higher in patients with signet ring-cell histology (HR = 1.56, 95% CI: 1.45-1.68), compared to patients with adenocarcinoma. Male gender, and advanced stage predicted a higher likelihood of CRC-related death in African Americans compared to the whole population. Signet ring-cell histology, advanced stage, and advanced grade were significantly associated with CRC-related death in African-American patients. CONCLUSION: This study corroborates emerging data that the (ASI) of young-onset CRC is increasing. It also identified factors associated with cancer-specific death in this population that may aid in targeting screening strategies for adults < 50 years old.
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Neoplasias Colorrectales/epidemiología , Programa de VERF/estadística & datos numéricos , Adulto , Distribución por Edad , Edad de Inicio , Población Negra/estadística & datos numéricos , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Incidencia , Masculino , Estado Civil/estadística & datos numéricos , Persona de Mediana Edad , Distribución por Sexo , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
Background: Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) are the main immunosuppressive cells in tumor microenvironment of gastric cancer (GC). In this prospective study, the association of prognosis with Tregs subsets and pDCs were further analyzed. Methods: pDCs, Tregs population and its expression of inducible costimulator (ICOS) were analyzed in peripheral blood from 41 GC patients by multicolor flow cytometry. These cell populations in carcinoma tissue, peritumor tissue and normal gastric mucosa from 87 GC patients were also detected by immunohistochemistry and double immunofluorescence. Results: Both ICOS+Foxp3+Treg cells (P=0.0341 and P=0.0298, respectively) and pDC (P=0.0237 and P=0.0083, respectively) in peripheral blood and tumor tissue could predict poor clinical outcome in GC patients. However, the total Foxp3+Tregs in the GC tissue didn't correlated with the outcome (P=0.4299). No correlation of CD4+ T cell or CD8+ T cell frequency could be found with clinical outcome neither in peripheral blood nor in tumor tissue. Conclusions: ICOS+Tregs and pDCs could predict poor prognosis of GC, targeting ICOS-L/ICOS costimulation axis may be a potential treatment for GC.
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Background: The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The aim of this study was to examine the role of Lgr5 in the microenvironment of gastric cancer (GC), and to explore possible immunological mechanisms influencing Lgr5 expression that are governed by regulatory T cells. Methods: Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-ß1, TGF-ß1 neutralizing antibody, or TGF-ß receptor inhibitor SB431542, and Lgr5 and ß-catenin expression were examined by qRT-PCR and western blot. Results: In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-ß1. This up-regulation was partially inhibited by the TGF-ß1 neutralizing antibody, or TGF-ß1 receptor antagonist SB431542. ß-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-ß1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival. Conclusion: Tregs promoted increased Lgr5 expression in GC cells via TGF-ß1 and TGF-ß1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-ß confer poor prognosis in gastric cancer.
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Regulación Neoplásica de la Expresión Génica/inmunología , Proteínas de Neoplasias/inmunología , Receptores Acoplados a Proteínas G/inmunología , Neoplasias Gástricas , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Linfocitos T Reguladores/patología , Microambiente Tumoral/inmunología , Vía de Señalización Wnt/inmunologíaRESUMEN
It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action. Cardamonin significantly suppressed the growth of chemotherapy-resistant colon cancer cells, induced apoptosis and promoted caspase-3/9 activity and Bax protein expression in 5-fluorouracil (5-FU)-resistant HCT-116 cells. Cardamonin significantly suppressed c-MYC, octamer-binding transcription factor 4, cyclin E, testes-specific protease 50 and nuclear factor-κB protein expression in 5-FU-resistant HCT-116 cells. The findings of the present study demonstrate that cardamonin suppresses chemotherapy-colon cancer cell via the NF-κB pathway in vitro.
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Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Bevacizumab plays an important role in the treatment of metastatic CRC (mCRC). The aim of this study was to evaluate the efficacy and safety of chemotherapy plus bevacizumab as first-line treatment in patients with mCRC. Randomized-controlled clinical trials comparing the efficacy of chemotherapy plus bevacizumab or chemotherapy alone in patients with mCRC were searched using the following electronic database of PubMed, Medline, Embase and CNKI. Total 9 trials, containing 1843 patients in chemotherapy plus bevacizumab group and 1741 patients in chemotherapy alone group, were included. Our results showed that chemotherapy plus bevacizumab statistically increased the Overall response rate (ORR) in patients with mCRC (OR = 1.57, 95% CI = 1.17-2.11, P = 0.003) in a random-effects model. The complete response rate and partial response rate were statistically increased as well (P ≤ 0.05). Subgroup analysis by bevacizumab dosage found that bevacizumab 5 mg/kg statistically increased the ORR. Significant differences were found in PFS (HR = 0.56, 95% CI = 0.46-0.69, P < 0.00001) and OS (HR = 0.83, 95% CI = 0.76-0.91, P < 0.0001) as well. No significant difference was found in adverse events. Overall, the combination of chemotherapy and bevacizumab as first-line treatment is an effective and well-tolerated regimen for patients with mCRC.
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AIM: To compare the perioperative parameters and short-term outcomes of hand-assisted laparoscopic colectomy (HALC) and open colectomy (OC) for the treatment of patients with cancer of the right hemicolon. METHODS: Patients who were scheduled to perform right hemicolectomy between August 2009 and December 2010 were randomized into either HALC or OC group. Patients were excluded if they had synchronous cancers, hepatic metastases, acute intestinal obstruction, or intestinal perforations. All the operations in the 2 groups were performed by a single surgical team. Measured outcomes included the demographic variables and perioperative parameters. The former included age, sex, body mass index, American Society of Anesthesiologists class, prior abdominal surgery, distribution of tumors, and histopathologic stage; whereas the latter included length of incision, operative time, estimated blood loss, conversion rate, number of lymph nodes retrieved, postoperative pain score, time to return of bowel function, postoperative complications, duration of hospital stay, and total cost. RESULTS: One hundred sixteen patients with cancer of the right hemicolon (HALC=59, OC=57) were recruited. The 2 groups of patients were similar in age, sex distribution, body mass index, American Society of Anesthesiologists class, and previous abdominal surgery. No significant difference was observed between the 2 groups in terms of distribution of tumors and the final histopathologic staging. HALC had a significantly shorter incision length and longer operative time than OC. Patients in the HALC group had significantly less operative blood loss, less pain and earlier passage of flatus after operation than those in the OC group. The number of lymph nodes recovered in the specimen and the overall postoperative complications was comparable in the 2 groups. The postoperative duration of hospital stay was significantly shorter in the HALC group, whereas the median overall costs in the HALC group were significantly higher than that in the OC group. CONCLUSIONS: The results from the present study demonstrate that the HALC is a valid surgical approach for cancer of the right hemicolon that retains the benefits of minimally invasive surgery. We believe that this technique is a safe, useful, and feasible method for patients with right-sided colonic cancer. If practiced more, it might be advocated as a "bridge" between traditional laparoscopic surgery and conventional open procedures.
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Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscópía Mano-Asistida/métodos , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , China , Colectomía/economía , Neoplasias del Colon/economía , Costos y Análisis de Costo , Femenino , Laparoscópía Mano-Asistida/economía , Humanos , Tiempo de Internación , Escisión del Ganglio Linfático/economía , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The relative rarity and anatomical position of retrorectal tumors may lead to difficulty in diagnosis and surgical management. METHODS: This was a retrospective review of 62 patients who had resection of retrorectal tumors between 2002 and 2010. RESULTS: All patients in this study were treated by excision of the retrorectal tumors. Surgical approach included transsacral approach (52 cases), transabdominal approach (eight cases), and combined approach (two cases). A total of 48 benign lesions (77.4%) and 14 malignant lesions (22.6%) were confirmed by histological examination. The 48 benign cases included dermoid cysts (17 cases), simple cysts (eight cases), teratomas (eight cases), neurofibromas (eight cases), fibrolipomas (four cases), neurilemmomas (two cases), and synovioma (one case). The 14 malignant cases included lymphomas (four cases), malignant teratomas (three cases), fibrosarcomas (two cases), interstitialomas (four cases) and malignant mesothelioma (one case). Complications occurred in 14.5% of patients and included intraoperative bleeding (three cases), rectal injury (three cases), and presacral infection (three cases). CONCLUSION: Primary retrorectal tumors are very rare. Successful treatment of these tumors requires extensive knowledge of pelvic anatomy and expertise in pelvic surgery.
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Multiple primary tumors (MPT) are a well-known phenomenon. Rapid advancements in diagnostics and therapeutics have contributed to a significant improvement in the survival rates of cancer patients, and also in an increase in the incidence of cases with multiple primary neoplasms, such as synchronous primary carcinomas of the rectum and prostate. We present a case history of a small number of male patients with synchronous primary carcinomas of the rectum and prostate. Two of the three cases were treated with lower anterior resection (LAR) and radical retropublic prostatectomy (RRP) during the same operation, and 1 case was treated with abdominoperineal resection (APR) and RRP during the same operation. No significant complications occurred during these operations. Our experience with these 3 cases of synchronous primary carcinomas of the rectum and prostate indicated that LAR or APR and RRP can safely be performed in a single operation.