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Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients.
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Antineoplásicos , Plasticidade Celular , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Plasticidade Celular/efeitos dos fármacos , Plasticidade Celular/genéticaRESUMO
OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
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Neoplasias Colorretais , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células , Metaloproteinase 9 da Matriz , Simulação de Acoplamento Molecular , Ciclo Celular , Receptores ErbB , Apoptose , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Linhagem Celular TumoralRESUMO
Introduction: Targetable alterations such as BRAFV600E mutation and NTRK fusion are enriched in microsatellite instability-high (MSI-H) colorectal cancer (CRC). MSI-H with targetable alterations (MSI-H altered) might present unique opportunities for both targeted therapy and immunotherapy. We systematically evaluated the molecular characteristics and immune-related features of MSI-H altered and MSI-H without targetable alterations (MSI-H wt) CRC patients in our study. Methods: Among 1938 continuously enrolled CRC patients, 126 patients with MSI-H status (6.50%) were included in this retrospective study. Genomic and transcriptomic data were investigated by next-generation sequencing (NGS) and gene expression profiling (GEP), respectively. Results: BRAFV600E, NTRK1, and FGFR2 mutations were the most frequent targetable alterations in MSI-H CRC patients. The MSI-H altered phenotype was significantly associated with older age (p< 0.001), right side (p=0.024) and females (p= 0.036). No lynch syndrome (LS) patients were identified in MSI-H altered group. The tumor mutational burden (TMB), and tumor neoantigen burden (TNB) of MSI-H altered and wt subgroups were comparable (p<0.05). Subsequently, transcriptomic study analysis further revealed MSI-H altered CRC patients were linked to an immune-active tumor microenvironment with higher levels of Teff IFN-gamma, CYT, and MERCK 18 signatures, and lower levels of the IPRES gene signature, EMT and TGF Beta signatures. In addition, case study supported MSI-H CRC patient harboring targetable alterations might also achieved a long-term disease-free survival benefit from immunotherapy. Discussion: Our study preliminary revealed MSI-H altered as a novel subtype of MSI-H CRC patients with unique molecular signatures and immune-active tumor microenvironment. Given the accessibility of immune checkpoint inhibitors (ICIs) treatment, our results might provide clinical evidence for immunotherapy in MSI-H CRC patients with targetable alterations.
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Neoplasias do Colo , Transcriptoma , Feminino , Humanos , Estudos Retrospectivos , Instabilidade de Microssatélites , Perfilação da Expressão Gênica , Imunoterapia/métodos , Genômica , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through interactions with its receptor, Angiotensin-converting enzyme 2 (ACE2), causing severe acute respiratory syndrome and death in a considerable proportion of people. Patients infected with SARS-CoV-2 experience digestive symptoms. However, the precise protein expression atlas of ACE2 in the gastrointestinal tract remains unclear. In this study, we aimed to explore the ACE2 protein expression pattern and the underlying function of ACE2 in the gastrointestinal tract, including the colon, stomach, liver, and pancreas. METHODS: We measured the protein expression of ACE2 in the gastrointestinal tract using immunohistochemical (IHC) staining with an ACE2-specific antibody of paraffin-embedded colon, stomach, liver, and pancreatic tissues. The correlation between the protein expression of ACE2 and the prognosis of patients with gastrointestinal cancers was analyzed by the log-rank (Mantel-Cox) test. The influence of ACE2 on colon, stomach, liver, and pancreatic tumor cell line proliferation was tested using a Cell Counting Kit 8 (CCK-8) assay. RESULTS: ACE2 presented heterogeneous expression patterns in the gastrointestinal tract, and it showed a punctate distribution in hepatic cells. Compared to that in parallel adjacent non-tumor tissues, the protein expression of ACE2 was significantly increased in colon cancer, stomach cancer, and pancreatic cancer tissues but dramatically decreased in liver cancer tissues. However, the expression level of the ACE2 protein was not correlated with the survival of patients with gastrointestinal cancers. Consistently, ACE2 did not affect the proliferation of gastrointestinal cancer cells in vitro. CONCLUSION: The ACE2 protein is widely expressed in the gastrointestinal tract, and its expression is significantly altered in gastrointestinal tumor tissues. ACE2 is not an independent prognostic marker of gastrointestinal cancers.
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Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disorder in the colon and rectum leading to low life-quality and high societal costs. Ursolic acid (UA) is a natural product with pharmacological and biological activities. The studies are aimed at investigating the protective and treatment effects of UA against the dextran sulfate sodium- (DSS-) induced UC mouse model and its underlying mechanism. UA was orally administered at different time points before and after the DSS-induced model. Mice body weight, colon length, and histological analysis were used to evaluate colon tissue damage and therapeutic evaluation. Intestinal transcriptome and microbe 16 s sequencing was used to analyze the mechanisms of UA in the prevention and treatment of UC. The early prevention effect of UA could effectively delay mouse weight loss and colon length shorten. UA alleviated UC inflammation and lowered serum and colon IL-6 levels. Three classical inflammatory pathways: MAPKs, IL-6/STAT3, and PI3K were downregulated by UA treatment. The proportion of macrophages and neutrophils in inflammatory cell infiltration was reduced in UA treatment groups. UA could significantly reduce the richness of intestinal flora to avoid the inflammatory response due to the destruction of the intestinal epithelial barrier. The function of UA against UC was through reducing intestinal flora abundance and regulating inflammatory and fatty acid metabolism signaling pathways to affect immune cell infiltration and cytokine expression.
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Colite Ulcerativa/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Triterpenos/administração & dosagem , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/microbiologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/imunologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Ácido UrsólicoRESUMO
BACKGROUND: To understand the biological effect of gut microbiome on the progression of colorectal cancer (CRC), we sequenced the V3-V4 region of the 16S rRNA gene to illustrate the overall structure of microbiota in the CRC patients. METHODS: In this study, a total of 66 CRC patients were dichotomized into different groups based on the following characteristics: paired tumor and adjacent normal tissues, distal and proximal CRC segments, MMR (-) and MMR (+), different TNM staging and clinic tumor staging. RESULTS: By sequencing and comparing the microbial assemblages, our results indicated that 7 microbe genus (Fusobacterium, Faecalibacterium, Akkermansia, Ruminococcus2, Parabacteroides, Streptococcus, and f_Ruminococcaceae) were significantly different between tumor and adjacent normal tissues; and 5 microbe genus (Bacteroides, Fusobacterium, Faecalibacterium, Parabacteroides, and Ruminococcus2) were significantly different between distal and proximal CRC segments; only 2 microbe genus (f_Enterobacteriaceae and Granulicatella) were significantly different between MMR (-) and MMR (+); but there was no significant microbial difference were detected neither in the TNM staging nor in the clinic tumor staging. CONCLUSION: All these findings implied a better understanding of the alteration in the gut microbiome, which may offer new insight into diagnosing and therapying for CRC patients.
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Tumor-specific CD8+T cells are exposed to persistent antigenic stimulation which induces a dysfunctional state called "exhaustion." Though functioning to limit damage caused by immune response, T cell exhaustion leads to attenuated effector function whereby cytotoxic CD8+T cells fail to control tumor progression in the late stage. This pathway is a dynamic process from activation to "progenitor exhaustion" through to "terminally exhaustion" with distinct properties. With the rapid development of immunotherapy via enhancing T cell function, new studies are dissecting the mechanisms and identifying specific biomarkers of dynamic differentiation during the process of exhaustion. Further, although immune checkpoint inhibitors (ICIs) have achieved great success in clinical practice, most patients still show limited efficacy to ICIs. The expansion and differentiation of progenitor exhausted T cells explained the success of ICIs while the depletion of the progenitor T cell pool and the transient effector function of terminally exhausted T cells accounted for the failure of immune monotherapy in the context of exorbitant tumor burden. Thus, combination strategies are urgent to be utilized based on the reduction of tumor burden or the expansion of the progenitor T cell pool. In this review, we aim to introduce the concept of homeostasis of the activated and exhausted status of CD8+T cells in the tumor immune microenvironment, and present recent findings on dynamic differentiation process during T cell exhaustion and the implications for combination strategies in immune therapy.
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Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Microambiente Tumoral/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , Humanos , Neoplasias/patologiaRESUMO
Numerous studies have revealed that the gut microbiota serves an important role in the pathogenesis of colorectal cancer (CRC). The present study aimed to investigate the populations present in the gut microbiota in patients with CRC of different stages and at different sites. Fecal samples were obtained from 67 CRC patients and 30 healthy controls, which were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Increased diversity of the fecal gut microbiota in patients with CRC was reported compared with the healthy controls. In the present study, at the genus level, the relative abundances of Prevotella, Collinsella and Peptostreptococcus in the gut microbiota of CRC patients were substantially increased compared with healthy controls, while the relative abundance of Escherichia-Shigella was significantly lower. In addition, differences in the fecal gut microbiota were also compared between patients with stage I-IV CRC and healthy controls. The results revealed that the abundances of the genera Peptostreptococcus, Collinsella and Ruminococcus were significantly increased in patients with CRC stage I compared with the healthy controls, while Alistipes was enriched in patients with stage III CRC compared with patients with stage IV. Furthermore, the present study reported that the genera Veillonella and Coprobacter were more abundant in the proximal segments than in the distal segments of the colon. In conclusion, despite the low number of samples employed in the present study, a signature of genera indicating dysbiosis of the gut microbiota of patients with stage I-IV CRC patients was proposed, which may provide insight into the mechanisms underlying the progression of CRC. These findings are also valuable for developing novel fecal diagnostic methods and therapeutic strategies for the treatment of CRC.
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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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Bactérias/patogenicidade , Neoplasias Colorretais/etiologia , Disbiose/dietoterapia , Microbioma Gastrointestinal/fisiologia , Probióticos/administração & dosagem , Antineoplásicos/efeitos adversos , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Neoplasias Colorretais/terapia , Suplementos Nutricionais , Disbiose/complicações , Disbiose/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Fatores de Virulência/metabolismoRESUMO
PURPOSE: This study aimed to analyze and evaluate the feasibility of using carbon nanoparticles (CNs) to track lymph nodes (LNs) metastases in right colon tumors, especially for patients who underwent laparoscopic-assisted radical right hemicolectomy. METHOD: A total of 99 patients were enrolled in this retrospective study between November 2015 and September 2017 (control group n = 47). One day before surgery, 1 ml of CNs suspension was injected into the submucosal layer around the site of the primary lesions by colonoscopy. Then complete mesocolic excision (CME) of laparoscopic right hemicolectomy was performed. CNs-stained LNs were identified and counted from all dissected LNs after surgery. RESULTS: The dates showed that the number of total harvested LNs and the number of positive patients in the experimental group increased significantly compared with the control group (respectively, P < 0.01 and P < 0.05). The increase of positive percentage shifted some patients toward higher stage, although the total number of positive LNs changed a little bit. In addition, the duration for pathologist to dissect LNs became shorter (26.4 vs. 31.1 min, P < 0.05). CONCLUSION: Therefore, the CNs are not only a good tattoo in laparoscopic-assisted operation, but could be regarded as a better pathological evaluating tool for tumor treatment.
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Neoplasias do Colo/diagnóstico , Metástase Linfática/diagnóstico , Nanopartículas , Estadiamento de Neoplasias , Carbono , China , Colectomia , Neoplasias do Colo/patologia , Humanos , Laparoscopia , Excisão de Linfonodo , Linfonodos , Estudos RetrospectivosRESUMO
Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration. A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms. Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide (NAD) level in aged mice. Compared to 3-month-old young controls, 2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation. Despite upregulated colonic tryptophan hydroxylases expression, serotonin release and expression of colon-predominant type IV serotonin receptor, reduced viability of interstitial cells of Cajal while enhanced aquaporins (Aqp1, 3 and 11) led to a less colonic motility and increased luminal dehydration in aged mice. Notably, this colonic degeneration was accompanied with reduced key NAD+-generating enzyme expression and lowered NAD+/NADH ratio in aged colon. Three-month continuous administration of beta nicotinamide mononucleotide, a NAD+ precursor, elevated colonic NAD+ level and improved defecation in aged mice. In contrast, pharmacological inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme for NAD+ biosynthesis, induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice. Taken together, these findings suggest the beneficial effect of NAD+ in maintaining colonic homoeostasis and reactivating NAD+ biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.
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PURPOSE: To demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers. METHODS: Patients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate. RESULTS: In total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate. CONCLUSION: The results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.
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The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.
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Clostridioides difficile/isolamento & purificação , Neoplasias Colorretais/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-OperatórioRESUMO
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered.
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BACKGROUND Dimethoxy curcumin (DMC) is a kind of lipophilic analog of curcumin with great improvement in chemical and metabolic stability. DMC has been studied in breast and renal cancer, but no research in colon cancer has been found yet. MATERIAL AND METHODS Two colon cancer cells (HT-29 and SW480) and one normal human colon mucosal epithelial cell (NCM460) were used in this study. We studied the effect of DMC on the proliferation in vitro and in vivo. Transwell migration assay was used to estimate the inhibition of DMC on invasion. Moreover, the expressions of PARP, caspase-3, survivin and E-cadherin were detected to uncover the related signaling pathways by western blotting assay both in vitro and in vivo. RESULTS DMC significantly inhibited the growth of colon cancer cells in dose-dependent manner; IC50 for DMC was calculated to be 43.4, 28.2 and 454.8µM on HT-29, SW480 and NCM460. DMC significantly increased the apoptosis in both HT-29 (p=0.0051) and SW480 (p=0.0013) cells in vitro, and significantly suppressed the growth of both cell lines in vivo. Moreover, DMC reduced the number of migrated cells in both HT-29 (p=0.007) and SW480 (p=0.004) cells. By western blotting analysis, the cleavage of pro-caspases-3 and PARP were clearly induced by DMC to their active form, while the expression of survivin was reduced and E-cadherin was enhanced in both cells in vitro and in vivo. CONCLUSIONS DMC may exert an effective anti-tumor effect in colon cancer cells by down-regulating survivin and upregulating E-cadherin.
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Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Curcumina/análogos & derivados , Proteínas Inibidoras de Apoptose/metabolismo , Animais , Antígenos CD , Antineoplásicos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Poli(ADP-Ribose) Polimerases/metabolismo , Survivina , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The aim of this study is to introduce a new technique of modified spontaneously closed defunctioning tube ileostomy after anterior resection of the rectum for rectal cancer with a low colorectal anastomosis. Patients with rectal cancer who underwent anterior resection of rectum with a low colorectal anastomosis and chose a modified defunctioning tube ileostomy between March 2012 and August 2013 were retrospectively reviewed. Data on the success of the operation procedures, post-operative hospital stay, and post-operative tube ileostomy-related complications were analyzed. One hundred fifty-two patients (87 males and 65 females; 57.1 ± 17.4 years) undergoing the modified defunctioning tube ileostomy after anterior resection for rectal cancer were included. The post-operative hospital stay was 11.9 ± 3.2 days. The tube was removed on days 22.6 ± 4.1 after operation and the ileostomy wound closed spontaneously within 13.1 ± 1.9 days. Twenty-five patients felt tube-associated pain or discomfort, which was relieved after a period of adaptation and appropriate tube adjustment. Nine patients suffered from tube blockage and were treated successfully with saline irrigation. Two patients had intestinal obstruction, which was resolved with conservative treatment. Three patients developed leakage of the distal anastomosis: two were successfully treated with conservative measures and the other completely recovered after reoperation. The modified spontaneously closed defunctioning tube ileostomy appears efficacious and safe. This technique may be used to protect the distal anastomosis and simultaneously decrease the ileostomy complications, and minimize the morbidity and mortality associated with stoma takedown.
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Colonic schwannomas are rare gastrointestinal mesenchymal tumors, and only a limited number of cases has been reported. The occurrence of these tumors is less common in the large intestine than in the stomach. The present study reports a case of colonic schwannoma in a 62-year-old female patient with no specific symptoms. The patient was diagnosed with a mass in the ascending colon by colonoscopy and abdominal computed tomography scanning. A right hemicolectomy was performed. The postoperative pathological diagnosis was ascending schwannoma. This case is noteworthy as colonic schwannomas are rare and are typically treated as colon cancer. No recurrence of the lesion was observed after 24 months of follow-up.
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Sacrococcygeal teratoma (SCT) is a sacrococcygeal neoplasm derived from more than one primitive germ layer and is only occasionally encountered in adults. The primary treatment for all primary SCTs is surgical excision. The present study reports the case of a giant SCT in a middle-aged female with a history lasting >3 decades. Multi-staged surgical treatment was performed, including ileostomy plus tumor excision, four debridement plus flap repair procedures, and closure of the ileostomy. Follow-up showed improved quality of life without evidence of local recurrence after resection. The study also presents a brief overview of the relevant literature. To the best of our knowledge, this is the first report of multi-staged surgical treatment for giant SCT in an adult patient.
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Extracolonic invasion of the duodenum and/or pancreatic head rarely occurs in patients with right hemicolon cancer. However, when necessary, combined radical operation is a challenge to the surgeon. We reported 7 patients with locally advanced right hemicolon cancer who underwent combined right hemicolectomy (RH) and pancreaticoduodenectomy (PD) due to direct involvement of the duodenum or pancreatic head. This study included four males and three females with a mean age of 66.9+/-5.9 years. Computed tomography (CT) scans revealed right hemicolon cancer with duodenal invasion (5 patients) and pancreatic invasion (2). The mean operation time was 410+/-64 minutes and the estimated blood loss was 514+/-157 mL. After the operation, the mean postoperative hospital stay was 22.1+/-7.2 days. Five patients had postoperative complications. The mean follow-up time was 16.4+/-5.9 months. During this period, three patients died from tumor recurrence, one from postoperative complications, one from pulmonary disease, and two survived until the last scheduled follow-up. Five patients survived more than one year. Combined RH and PD for locally advanced right hemicolon cancer can be performed safely, thus providing a long-term survival rate in selected patients in a high-volume center.
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Colectomia , Neoplasias do Colo/cirurgia , Duodeno/cirurgia , Pâncreas/cirurgia , Pancreaticoduodenectomia , Idoso , Perda Sanguínea Cirúrgica , Colectomia/efeitos adversos , Colectomia/mortalidade , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Duodeno/patologia , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Duração da Cirurgia , Pâncreas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Most surgeons suggest the use of fecal diversion in patients undergoing low anterior resections of rectal tumors at high risk for anastomotic leakage. We describe an exploratory study to evaluate the efficacy and safety of a new diversion method called a spontaneously closing cannula ileostomy, which was designed to protect rectal anastomoses in patients at high risk for anastomotic leakage. The outcomes of patients treated with cannula ileostomy were compared to those of patients treated with loop ileostomy. MAIN OUTCOME MEASURES: Outcomes included the rates of anastomotic leakage, reoperation and other complications, as well as length of hospital stay and cost. DESIGN AND PATIENTS: From January 2011 to December 2012, 294 patients undergoing low colorectal or coloanal anastomosis were treated with ileum diversion using cannula ileostomy or traditional loop ileostomy. Demographics, clinical features, and operational data were recorded. RESULTS: The anastomotic leakage rates were 8.1% (12/149) in the cannula ileostomy group and 8.3% (12/145) in the loop ileostomy group (p = 1.0). The reoperation rate was 3% (4/149) in patients treated with a cannula ileostomy and 3.4% (5/145) in those who underwent a loop ileostomy (p = 0.75). The median length of the hospital stay was 8.6 days in the cannula ileostomy group and 17.1 days (p < 0.01) in the loop ileostomy group, including time for the initial and reversal operations. In the cannula ileostomy group, the median time to defecation from the anus was 16.5 days after the operation. During the follow-up period, 13 patients in the loop ileostomy group retained their stoma, as compared to 2 in the cannula ileostomy group (p < 0.01). LIMITATIONS: This study was a nonrandomized design and lacked contrast enema data to identify anastomotic leaks. CONCLUSIONS: Cannula ileostomy is a safe and effective diverting technique that protects low colorectal and coloanal anastomoses. Patients receiving a cannula ileostomy had shorter hospital stays and lower rates of permanent stoma than those receiving a loop ileostomy.