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1.
BMJ Case Rep ; 17(9)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39242131

RESUMO

A woman in her 80s with a history of congestive heart failure, atrial arrhythmia treated with atrioventricular nodal ablation and permanent pacemaker (PPM) placement, mitral valve disease status post-repair and colon cancer status post-treatment was admitted for further evaluation of severe dyspnea on exertion. Imaging revealed vegetation on both the prosthetic mitral valve and the PPM lead. Blood cultures were collected without growth, so a cell-free DNA Karius test was performed, which can detect over 1000 pathogens and has a sensitivity between 87% and 93%. Testing returned positive results for Streptococcus bovis subspecies pasteurianus Given its association with colorectal cancer, abdominal imaging and an endoscopic biopsy were performed, showing recurrent colonic malignancy. The patient underwent a right colon resection prior to cardiac intervention. This report describes the clinical application of the novel cell-free DNA Karius test, which led to the diagnosis of recurrent colon cancer associated with S. pasteurianus endocarditis.


Assuntos
Endocardite Bacteriana , Streptococcus bovis , Humanos , Feminino , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Idoso de 80 Anos ou mais , Streptococcus bovis/isolamento & purificação , Infecções Estreptocócicas/diagnóstico , Neoplasias do Colo/diagnóstico , Ácidos Nucleicos Livres/sangue , Valva Mitral/diagnóstico por imagem , Valva Mitral/microbiologia
2.
Pan Afr Med J ; 47: 219, 2024.
Artigo em Francês | MEDLINE | ID: mdl-39247771
3.
Chirurgia (Bucur) ; 119(4): 359-372, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39250606

RESUMO

BACKGROUND AND OBJECTIVES: Observational studies suggest a link between D3 lymphadenectomy and improved disease-free survival in some colon cancer patients. However, high-quality randomized controlled trials are needed to confirm its advantage over D2 lymphadenectomy. Concerns about potential complications with D3 have limited its use outside of Japan. This study examines short-term outcomes following D3 lymphadenectomy for right-sided colon cancer compared to the established D2 procedure. Materials and Methods: This retrospective cohort single center study analyzed data on patients with right-sided colon cancer who underwent curative surgery within our healthcare trust between January 2019 and November 2022. Only patients treated by surgeons who routinely perform D3 lymphadenectomy were included for a homogenous study population. The decision to perform D3 was at the discretion of the operating surgeon. Data were collected from both paper charts and electronic medical records. Non-parametric statistical tests were used for data analysis. Results: A total of 214 patients met the criteria, with 170 undergoing D2 lymphadenectomy and 44 undergoing D3 lymphadenectomy. There were no significant differences between the groups in terms of surgery duration, blood loss, postoperative hemoglobin levels, or transfusion needs. Interestingly, the D3 group had a lower complication rate (25%) compared to the D2 group (41.2%). However, the D3 group also had a higher rate of lymph node spread (45.5% vs. 30.6% for D2) and more lymph nodes removed (19 [16, 25] vs. 23 [18, 28]). Importantly, both groups achieved similar complete tumour removal rates. Conclusions: This study suggests D3 lymphadenectomy for right-sided colon cancer might be safe with potential benefits, especially for younger patients with suspected lymph node involvement. However, the limited sample size necessitates larger, randomized trials to confirm these findings and potentially establish D3 lymphadenectomy as standard care.


Assuntos
Neoplasias do Colo , Estudos de Viabilidade , Excisão de Linfonodo , Humanos , Excisão de Linfonodo/métodos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Londres , Pessoa de Meia-Idade , Resultado do Tratamento , Hospitais Gerais , Hospitais de Distrito , Intervalo Livre de Doença , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais
4.
Medicine (Baltimore) ; 103(36): e39408, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252310

RESUMO

Colorectal adenocarcinoma (COAD) has a poor prognosis. Cyclin-dependent kinase inhibitor 2A (CDKN2A) significantly affects the development and progression of various human tumors. However, the significance and pathological mechanisms of CDKN2A in COAD remain to be elucidated. We assessed expression levels, clinical significance, biological function, co-expressed genes, and enrichment of related pathways of CDKN2A in COAD using various databases, including The University of Alabama at Birmingham Cancer Data Analysis Portal, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Human Protein Atlas, STRING, GeneMANIA, cBioPortal, and Linked Omics. Our investigation showed that CDKN2A was highly expressed in colon adenocarcinomas (P < .001). It is weakly expressed or not expressed in normal tissues. The survival time of patients with colon adenocarcinoma with high CDKN2A expression is significantly shorter than that of patients with low expression levels (P = .011). There was a significant positive correlation between the expression level of CDKN2A in colon adenocarcinoma tissues and the infiltration of CD4+ T cells, macrophages, and neutrophils. Moreover, there was a significant negative association between the expression level of CDKN2A in colon adenocarcinoma tissues and B cell infiltration. The ten hub genes included tumor protein 53, V-myc Avian Myelocytomatosis Viral Oncogene Homolog, AKT serine/threonine kinase 1, cyclin-dependent kinase 2, phosphatase and tensin homolog deleted on chromosome ten, cyclin D1, cyclin dependent kinase 4, cyclin dependent kinase inhibitor 1A, catenin beta 1, and B-Raf proto-oncogene, serine/threonine kinase. Mutations in the CDKN2A genome in colon adenocarcinoma reduce survival. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the differentially expressed genes were enriched in apoptotic signaling pathways and multiple pathways related to metabolic progression. Our results indicate that CDKN2A can be used as a marker of poor prognosis in patients with colon adenocarcinoma. CDKN2A may regulate the occurrence and development of colon adenocarcinomas by influencing immune cell infiltration and metabolic pathways.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Proto-Oncogene Mas , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico
5.
Medicine (Baltimore) ; 103(36): e39300, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252305

RESUMO

Pyroptosis-related genes have great potential for prognosis, an accurate prognostic model based on pyroptosis genes has not been seen in Colorectal adenocarcinoma (COAD). Furthermore, understanding the mechanisms of gene expression characteristics and the Tumor Immune Microenvironment associated with the prognosis of COAD is still largely unknown. Constructing a prognostic model based on pyroptosis-related genes, and revealing prognosis-related mechanisms associated with the gene expression characteristics and tumor microenvironment. 59 pyroptosis-related genes were collected. The gene expression data and clinical data of COAD were downloaded from The Cancer Genome Atlas. External validation datasets were downloaded from the Gene Expression Omnibus database. 10 characteristic genes with prognostic values were obtained using univariate and LASSO Cox. 10-gene Riskscore prognostic model was constructed. Both gene set enrichment analysis and network propagation methods were used to find pathways and key genes leading to different prognostic risks. The area under the ROC curves were used to evaluate the performance of the model to distinguish between high-risk and low-risk patients, the results were 0.718, 0.672, and 0.669 for 1-, 3-, and 5-year survival times. A nomogram based on Riskscore and clinical characteristics showed the probability of survival at 1, 3, and 5 years, and the calibration curves showed good agreement between the predicted and actual observations, its C-index is 0.793. The decision curves showed that the net benefit of the nomogram was significantly superior to that of the other single variables. Four key pathways leading to different prognostic risks were obtained. Six key genes with prognostic value, significant expression differences (P < .05) and significant survival differences (P < .05) between high/low risk groups were obtained from the gene set of all 4 key pathways. This study constructed a prognostic model for COAD using 10 pyroptosis-related genes with prognostic value. This study also revealed significant differences in specific pathways and the tumor immune microenvironment (TME) between the high-risk group and the low-risk group, highlighted the roles of ALDH5A1 and Wnt signaling in promoting COAD and the suppressive effects of the IL-4/IL-13 pathway and RORC on COAD. The study will be helpful for precision therapy.


Assuntos
Neoplasias do Colo , Nomogramas , Piroptose , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Piroptose/genética , Prognóstico , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/imunologia , Medição de Risco/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Masculino , Feminino , Curva ROC
6.
BMJ Case Rep ; 17(9)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39237130

RESUMO

A relatively healthy male patient in his 60s presented with chest pain and shortness of breath in addition to a history of significant weight loss over the preceding months. He was admitted to the hospital and investigated with a CT pulmonary angiogram, which did not demonstrate a pulmonary embolus, but he subsequently went on to have an ultrasound and CT scan because of abnormal findings. His CT demonstrated some thickening of the mid-transverse colon, and, in addition, large volume liver metastases described as innumerable and probably replacing most of the liver.Initially, his liver function tests were only mildly deranged at the presentation. Flexible sigmoidoscopy was performed, and a transverse colonic malignancy was identified and biopsied, which demonstrated an extrapulmonary small cell carcinoma (EPSCC). He was admitted for urgent chemotherapy for newly diagnosed metastatic small-cell colonic cancer; he developed tumour lysis syndrome following his first dose of chemotherapy. He continued to decline following this and died soon after his admission. Metastatic small-cell colonic cancer is a rare diagnosis which is challenging to manage due to the lack of trial evidence to drive treatment strategies. The management largely follows the pulmonary small cell cancer pathway. We, therefore, present a colonic EPSCC case outlining the diagnostic and treatment strategies for this disease.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Hepáticas , Humanos , Masculino , Evolução Fatal , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Pequenas/complicações , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologia
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 482-489, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39223012

RESUMO

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.


Assuntos
Apoptose , Neoplasias do Colo , Fator 2 Relacionado a NF-E2 , Estilbenos , Humanos , Estilbenos/farmacologia , Apoptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
8.
J Cancer Res Clin Oncol ; 150(9): 411, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237674

RESUMO

PURPOSE: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association. METHOD: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/ß-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3. RESULTS: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/ß-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis. CONCLUSION: NR3C2 may regulate Wnt/ß-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer.


Assuntos
Proliferação de Células , Neoplasias do Colo , Camundongos Nus , Invasividade Neoplásica , Via de Sinalização Wnt , Humanos , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Animais , Camundongos , Masculino , Prognóstico , Feminino , Movimento Celular/genética , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Receptores dos Hormônios Tireóideos/metabolismo , Receptores dos Hormônios Tireóideos/genética , Regulação Neoplásica da Expressão Gênica , Apoptose , beta Catenina/metabolismo , beta Catenina/genética , Pessoa de Meia-Idade , Receptores de Mineralocorticoides
9.
BMC Cancer ; 24(1): 1088, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223610

RESUMO

BACKGROUND: The log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy. METHOD: A total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan-Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms. RESULTS: Multivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052-3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084-2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297-2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030). CONCLUSION: The prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.


Assuntos
Neoplasias do Colo , Estadiamento de Neoplasias , Nomogramas , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Quimioterapia Adjuvante/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Linfonodos/patologia , Metástase Linfática , Adulto
10.
PLoS One ; 19(9): e0305268, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39226289

RESUMO

MOTIVATION: There exists an unexplained diverse variation within the predefined colon cancer stages using only features from either genomics or histopathological whole slide images as prognostic factors. Unraveling this variation will bring about improved staging and treatment outcomes. Hence, motivated by the advancement of Deep Neural Network (DNN) libraries and complementary factors within some genomics datasets, we aggregate atypia patterns in histopathological images with diverse carcinogenic expression from mRNA, miRNA and DNA methylation as an integrative input source into a deep neural network for colon cancer stages classification, and samples stratification into low or high-risk survival groups. RESULTS: The genomics-only and integrated input features return Area Under Curve-Receiver Operating Characteristic curve (AUC-ROC) of 0.97 compared with AUC-ROC of 0.78 obtained when only image features are used for the stage's classification. A further analysis of prediction accuracy using the confusion matrix shows that the integrated features have a weakly improved accuracy of 0.08% more than the accuracy obtained with genomics features. Also, the extracted features were used to split the patients into low or high-risk survival groups. Among the 2,700 fused features, 1,836 (68%) features showed statistically significant survival probability differences in aggregating samples into either low or high between the two risk survival groups. Availability and Implementation: https://github.com/Ogundipe-L/EDCNN.


Assuntos
Neoplasias do Colo , Genômica , Estadiamento de Neoplasias , Redes Neurais de Computação , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Genômica/métodos , Prognóstico , Metilação de DNA , Curva ROC , Aprendizado Profundo , MicroRNAs/genética
11.
Sci Rep ; 14(1): 20434, 2024 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227664

RESUMO

Cancer seems to have a vast number of deaths due to its heterogeneity, aggressiveness, and significant propensity for metastasis. The predominant categories of cancer that may affect males and females and occur worldwide are colon and lung cancer. A precise and on-time analysis of this cancer can increase the survival rate and improve the appropriate treatment characteristics. An efficient and effective method for the speedy and accurate recognition of tumours in the colon and lung areas is provided as an alternative to cancer recognition methods. Earlier diagnosis of the disease on the front drastically reduces the chance of death. Machine learning (ML) and deep learning (DL) approaches can accelerate this cancer diagnosis, facilitating researcher workers to study a vast majority of patients in a limited period and at a low cost. This research presents Histopathological Imaging for the Early Detection of Lung and Colon Cancer via Ensemble DL (HIELCC-EDL) model. The HIELCC-EDL technique utilizes histopathological images to identify lung and colon cancer (LCC). To achieve this, the HIELCC-EDL technique uses the Wiener filtering (WF) method for noise elimination. In addition, the HIELCC-EDL model uses the channel attention Residual Network (CA-ResNet50) model for learning complex feature patterns. Moreover, the hyperparameter selection of the CA-ResNet50 model is performed using the tuna swarm optimization (TSO) technique. Finally, the detection of LCC is achieved by using the ensemble of three classifiers such as extreme learning machine (ELM), competitive neural networks (CNNs), and long short-term memory (LSTM). To illustrate the promising performance of the HIELCC-EDL model, a complete set of experimentations was performed on a benchmark dataset. The experimental validation of the HIELCC-EDL model portrayed a superior accuracy value of 99.60% over recent approaches.


Assuntos
Neoplasias do Colo , Aprendizado Profundo , Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias do Colo/patologia , Neoplasias do Colo/diagnóstico , Detecção Precoce de Câncer/métodos , Redes Neurais de Computação , Masculino , Feminino
14.
J Coll Physicians Surg Pak ; 34(9): 1009-1013, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39261996

RESUMO

OBJECTIVE: To determine the outcome of awake surgery with combined spinal epidural in geriatric colon cancer patients with advanced comorbidity. STUDY DESIGN: Quasi-experimental study. Place and Duration of the Study: Department of Anaesthesiology and Reanimation, Ankara Bilkent City Hospital, Ankara, Turkiye, from April 2022 to 2023. METHODOLOGY: Twenty-four American Society of Anaesthesiologists (ASA) I-II patients, aged 25-65 years and scheduled for colon cancer surgery were included in this research. All patients were observed preoperatively, at the operation room and at the postoperative surgery service. Spinal anaesthesia was planned for Group I and general anaesthesia for Group II. Ketofol (1:1) was administered to the combined spinal-epidural group, with a Ramsay sedation score of 3 after the spinal block. Epidural analgesia was planned for all patients. Patients' age, gender, weight, comorbidities, ASA risk scores, intraoperative haemodynamic parameters, bleeding amounts, colloid, crystalloid, and blood products were collected. RESULTS: There was no significant difference between the demographic characteristics of both anaesthesia groups (p >0.05). The amount of bleeding was statistically lower in Group I than in the general anaesthesia group (p = 0.004). Oral intake, drain withdrawal, mobilisation, discharge times, and costs were similar in all groups (p >0.05). CONCLUSION: The regional anaesthesia applications facilitate compliance with routine mobilisation, discharge procedures and prevent complications in abdominal surgery and its positive perioperative effects in patients with poor respiratory parameters, poor general condition, and high comorbidity in advanced age. KEY WORDS: Regional anaesthesia, Spinal-epidural, Mobilisation, Pain, Colon cancer.


Assuntos
Anestesia Epidural , Anestesia Geral , Raquianestesia , Neoplasias do Colo , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Raquianestesia/métodos , Idoso , Adulto , Anestesia Epidural/métodos , Anestesia Geral/métodos , Neoplasias do Colo/cirurgia , Vigília , Dor Pós-Operatória , Resultado do Tratamento
15.
J Biochem Mol Toxicol ; 38(10): e23832, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39267413

RESUMO

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor-infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2-like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2-like markers (CD206, CD163, arginase1, and interleukin 10 [IL-10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage-mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL-6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL-6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2-like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL-6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo , Macrófagos , Humanos , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Prognóstico , Macrófagos/metabolismo , Macrófagos/patologia , Linhagem Celular Tumoral , Progressão da Doença , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Masculino , Feminino , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica
16.
J Clin Invest ; 134(17)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225102

RESUMO

Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy is more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor lactate efflux and enhanced glucose availability within the tumor microenvironment (TME). LDH inhibitors (LDHi) reduce glucose uptake and tumor growth in preclinical models, but their impact on tumor-infiltrating T cells is not fully elucidated. Tumor cells have higher basal LDH expression and glycolysis levels compared with infiltrating T cells, creating a therapeutic opportunity for tumor-specific targeting of glycolysis. We demonstrate that LDHi treatment (a) decreases tumor cell glucose uptake, expression of the glucose transporter GLUT1, and tumor cell proliferation while (b) increasing glucose uptake, GLUT1 expression, and proliferation of tumor-infiltrating T cells. Accordingly, increasing glucose availability in the microenvironment via LDH inhibition leads to improved tumor-killing T cell function and impaired Treg immunosuppressive activity in vitro. Moreover, combining LDH inhibition with immune checkpoint blockade therapy effectively controls murine melanoma and colon cancer progression by promoting effector T cell infiltration and activation while destabilizing Tregs. Our results establish LDH inhibition as an effective strategy for rebalancing glucose availability for T cells within the TME, which can enhance T cell function and antitumor immunity.


Assuntos
Glucose , L-Lactato Desidrogenase , Microambiente Tumoral , Animais , Camundongos , Glucose/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/imunologia , Humanos , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/imunologia , Transportador de Glucose Tipo 1/genética , Linhagem Celular Tumoral , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Glicólise/efeitos dos fármacos , Feminino , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Neoplasias do Colo/imunologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Inibidores Enzimáticos/farmacologia , Imunoterapia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico
17.
J Nanobiotechnology ; 22(1): 542, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238020

RESUMO

Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.


Assuntos
Neoplasias do Colo , Imunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Morte Celular Programada 1 , Animais , Neoplasias do Colo/terapia , Neoplasias do Colo/imunologia , Neoplasias do Colo/tratamento farmacológico , Camundongos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Polímeros/química , Linhagem Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/farmacologia , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Feminino , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Lipídeo A/análogos & derivados
18.
J Med Internet Res ; 26: e54985, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255016

RESUMO

BACKGROUND: ChatGPT (OpenAI) has shown great potential in clinical diagnosis and could become an excellent auxiliary tool in clinical practice. This study investigates and evaluates ChatGPT in diagnostic capabilities by comparing the performance of GPT-3.5 and GPT-4.0 across model iterations. OBJECTIVE: This study aims to evaluate the precise diagnostic ability of GPT-3.5 and GPT-4.0 for colon cancer and its potential as an auxiliary diagnostic tool for surgeons and compare the diagnostic accuracy rates between GTP-3.5 and GPT-4.0. We precisely assess the accuracy of primary and secondary diagnoses and analyze the causes of misdiagnoses in GPT-3.5 and GPT-4.0 according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. METHODS: We retrieved 316 case reports for intestinal cancer from the Chinese Medical Association Publishing House database, of which 286 cases were deemed valid after data cleansing. The cases were translated from Mandarin to English and then input into GPT-3.5 and GPT-4.0 using a simple, direct prompt to elicit primary and secondary diagnoses. We conducted a comparative study to evaluate the diagnostic accuracy of GPT-4.0 and GPT-3.5. Three senior surgeons from the General Surgery Department, specializing in Colorectal Surgery, assessed the diagnostic information at the Chinese PLA (People's Liberation Army) General Hospital. The accuracy of primary and secondary diagnoses was scored based on predefined criteria. Additionally, we analyzed and compared the causes of misdiagnoses in both models according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. RESULTS: Out of 286 cases, GPT-4.0 and GPT-3.5 both demonstrated high diagnostic accuracy for primary diagnoses, but the accuracy rates of GPT-4.0 were significantly higher than GPT-3.5 (mean 0.972, SD 0.137 vs mean 0.855, SD 0.335; t285=5.753; P<.001). For secondary diagnoses, the accuracy rates of GPT-4.0 were also significantly higher than GPT-3.5 (mean 0.908, SD 0.159 vs mean 0.617, SD 0.349; t285=-7.727; P<.001). GPT-3.5 showed limitations in processing patient history, symptom presentation, laboratory tests, and imaging data. While GPT-4.0 improved upon GPT-3.5, it still has limitations in identifying symptoms and laboratory test data. For both primary and secondary diagnoses, there was no significant difference in accuracy related to age, gender, or system group between GPT-4.0 and GPT-3.5. CONCLUSIONS: This study demonstrates that ChatGPT, particularly GPT-4.0, possesses significant diagnostic potential, with GPT-4.0 exhibiting higher accuracy than GPT-3.5. However, GPT-4.0 still has limitations, particularly in recognizing patient symptoms and laboratory data, indicating a need for more research in real-world clinical settings to enhance its diagnostic capabilities.


Assuntos
Neoplasias do Colo , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Idoso
19.
Immunotherapy ; 16(10): 649-657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39259508

RESUMO

Clinical evidences of neoadjuvant immunotherapy in patients with mismatch repair deficient/microsatellite instability-high status (dMMR/MSI-H) colorectal cancer have not been well received. A 36-year-old man complained of recurrent right upper quadrant pain for more than 1 year, and the symptoms were not significantly relieved after 10 days of oral Changyanning tablet. The patient was finally diagnosed as dMMR/MSI-H colon cancer. Tumor regression was achieved after seven cycles of envafolimab treatment, and the patient obtained postoperative pathological complete response (pCR). Here, we report a case of MSI-H/dMMR transverse colon cancer, who obtained pCR after neoadjuvant envafolimab (a novel subcutaneous single-domain anti-PD-L1 antibody) with a favorable safety profile, aiming to enhance the experiences of comprehensive diagnosis and treatment of colon cancer.


Immune checkpoint inhibitors (ICIs) are a type of immunotherapy which can be used in the treatment of colorectal cancer. The authors here report the functions of envafolimab (a type of ICI) used before surgery to shrink tumor volume in colorectal cancer. A 36-year-old man suffered from repeated illness of right upper quadrant for over 1 year, and the illness were not recovered after 10 days of oral Changyanning tablet. The patient was finally diagnosed with colorectal cancer. After seven cycles of envafolimab treatment, tumor volume was significantly decreased, and the patient obtained favorable surgical outcomes with tolerable safety after surgery.


Assuntos
Neoplasias do Colo , Instabilidade de Microssatélites , Terapia Neoadjuvante , Humanos , Masculino , Adulto , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Reparo de Erro de Pareamento de DNA , Inibidores de Checkpoint Imunológico/uso terapêutico
20.
Front Immunol ; 15: 1455907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247185

RESUMO

Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Hepáticas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Neoplasias Colorretais Hereditárias sem Polipose/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Pessoa de Meia-Idade , Resultado do Tratamento , Proteína 2 Homóloga a MutS/genética , Molécula de Adesão da Célula Epitelial/genética
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