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1.
BMJ Case Rep ; 17(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355211

RESUMO

A woman in her 70s with a medical history of recurrent ovarian carcinoma was referred to the gastroenterologist because of rectal blood loss. Colonoscopy revealed a spontaneously bleeding lesion, which was not a typical colorectal carcinoma by optical diagnosis. Biopsies confirmed the diagnosis of recurrence of the former ovarian carcinoma. The patient was not eligible for surgical resection due to former abdominal surgery and she declined chemotherapy due to severe side effects earlier. After a multidisciplinary team consultation, she was treated with endoscopic full-thickness resection (eFTR). This is a minimally invasive resection technique for removal of challenging colorectal lesions. The patient has recovered well and 2 years after the metastasis resection with eFTR there still have been no signs of recurrent malignancy.


Assuntos
Carcinoma , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma/cirurgia , Carcinoma Epitelial do Ovário , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Ressecção Endoscópica de Mucosa/métodos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Idoso
2.
Cancer Res Commun ; 4(2): 588-606, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38358352

RESUMO

Neutrophils are a highly heterogeneous cellular population. However, a thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing of human and murine datasets, both publicly available and independently generated, to identify neutrophil transcriptomic subtypes and developmental lineages in health and malignancy. Datasets of lung, breast, and colorectal cancer were integrated to establish and validate neutrophil gene signatures. Pseudotime analysis was used to identify genes driving neutrophil development from health to cancer. Finally, ligand-receptor interactions and signaling pathways between neutrophils and other immune cell populations in primary colorectal cancer and metastatic colorectal cancer were investigated. We define two main neutrophil subtypes in primary tumors: an activated subtype sharing the transcriptomic signatures of healthy neutrophils; and a tumor-specific subtype. This signature is conserved in murine and human cancer, across different tumor types. In colorectal cancer metastases, neutrophils are more heterogeneous, exhibiting additional transcriptomic subtypes. Pseudotime analysis implicates IL1ß/CXCL8/CXCR2 axis in the progression of neutrophils from health to cancer and metastasis, with effects on T-cell effector function. Functional analysis of neutrophil-tumoroid cocultures and T-cell proliferation assays using orthotopic metastatic mouse models lacking Cxcr2 in neutrophils support our transcriptional analysis. We propose that the emergence of metastatic-specific neutrophil subtypes is driven by the IL1ß/CXCL8/CXCR2 axis, with the evolution of different transcriptomic signals that impair T-cell function at the metastatic site. Thus, a better understanding of neutrophil transcriptomic programming could optimize immunotherapeutic interventions into early and late interventions, targeting different neutrophil states. SIGNIFICANCE: We identify two recurring neutrophil populations and demonstrate their staged evolution from health to malignancy through the IL1ß/CXCL8/CXCR2 axis, allowing for immunotherapeutic neutrophil-targeting approaches to counteract immunosuppressive subtypes that emerge in metastasis.


Assuntos
Neoplasias Colorretais , Neutrófilos , Animais , Camundongos , Humanos , Recidiva Local de Neoplasia/metabolismo , Transdução de Sinais/genética , Neoplasias Colorretais/genética , Análise de Célula Única
3.
Cancer Res Commun ; 4(2): 607-616, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38363145

RESUMO

Real-world data are necessitated to counsel patients about the risk for recurrent disease after curative treatment of colorectal cancer. This study provided a population-based overview of the epidemiology of recurrent disease in patients with surgically resected stage II/III colorectal cancer.Patients diagnosed with stage II/III primary colorectal cancer between July and December 2015 were selected from the Netherlands Cancer Registry (N = 3,762). Cumulative incidence of recurrent disease was estimated, and multivariable competing risk regression was used to identify risk factors for recurrent disease in patients with primary colon and rectal cancer. Moreover, overall survival (OS) after diagnosis of recurrent colorectal cancer was estimated.Median clinical follow-up was 58 months (Q1-Q3: 22-62). Five-year cumulative incidence of recurrent disease was 21.6% [95% confidence interval (CI): 20.0-23.2] and 30.0% (95% CI: 28.3-33.5) for patients with primary colon and rectal cancer, respectively. Stage III disease and incomplete resection margin in patients with primary colon cancer and extramural vascular invasion in patients with primary rectal cancer were strongly (HR ≥ 2) associated with recurrent disease. Median OS of patients with distant, locoregional, or the synchronous combination of distant and locoregional recurrent disease was 29, 27, and 13 months, respectively (P < 0.001). Patients with distant recurrences limited to liver or lung showed a median OS of 46 and 48 months, respectively. The incidence of recurrent disease was higher in patients with rectal cancer than in patients with colon cancer, predominantly due to higher rates of distant recurrences. OS after recurrent disease was impaired, but subgroups of patients diagnosed with recurrent disease limited to one site showed statistically significantly longer OS. SIGNIFICANCE: Population-based data on recurrent colorectal cancer are rare, but crucial for counseling patients and their physicians. This large nationwide, population-based study provides an up-to-date overview of the epidemiology of recurrent disease in patients with stage II and III primary colon and rectal cancer treated with surgical resection.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Incidência , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias do Colo/epidemiologia , Neoplasias Retais/tratamento farmacológico , Fatores de Risco
4.
J Exp Clin Cancer Res ; 43(1): 49, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365745

RESUMO

BACKGROUND: SMC1A is a subunit of the cohesin complex that participates in many DNA- and chromosome-related biological processes. Previous studies have established that SMC1A is involved in cancer development and in particular, is overexpressed in chromosomally unstable human colorectal cancer (CRC). This study aimed to investigate whether SMC1A could serve as a therapeutic target for CRC. METHODS: At first, we studied the effects of either SMC1A overexpression or knockdown in vitro. Next, the outcome of SMC1A knocking down (alone or in combination with bevacizumab, a monoclonal antibody against vascular endothelial growth factor) was analyzed in vivo. RESULTS: We found that SMC1A knockdown affects cell proliferation and reduces the ability to grow in anchorage-independent manner. Next, we demonstrated that the silencing of SMC1A and the combo treatment were effective in increasing overall survival in a xenograft mouse model. Functional analyses indicated that both treatments lead to atypical mitotic figures and gene expression dysregulation. Differentially expressed genes were implicated in several pathways including gene transcription regulation, cellular proliferation, and other transformation-associated processes. CONCLUSIONS: These results indicate that SMC1A silencing, in combination with bevacizumab, can represent a promising therapeutic strategy for human CRC.


Assuntos
Neoplasias Colorretais , Animais , Humanos , Camundongos , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Proteínas Cromossômicas não Histona/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inativação Gênica , Fator A de Crescimento do Endotélio Vascular/genética
5.
Drug Des Devel Ther ; 18: 425-441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370566

RESUMO

Purpose: This study aimed to investigate the effect of Salvia miltiorrhiza on colorectal cancer, as well as the mechanisms involved. Methods: The active compounds of Salvia miltiorrhiza and the associated genes in colorectal cancer were sourced from publicly available databases. Targets associated with colorectal cancer were identified by searching the GeneCards and OMIM databases. Subsequently, the Cytoscape 3.6.0 software was employed to create a regulatory network that illustrates the relationships among active ingredients, colorectal cancer, and their corresponding targets. The String database was utilized to generate a PPI network. Molecular docking studies, conducted with AutoDock Vina, verified the binding capabilities of these active components to core targets. The findings from network pharmacology analysis were corroborated through in vitro experiments. Results: In this study, we identified 39 active components derived from Salvia miltiorrhiza that are predicted to target 544 genes associated with colorectal cancer through network pharmacology. Through a combined analysis of network pharmacology, we isolated three key targets: SRC, IL6, and INS. Molecular docking results convincingly demonstrated Salvia miltiorrhiza's strong binding affinity to these targets. Additionally, in vitro experiments confirmed that Salvia miltiorrhiza effectively inhibited the progression of colorectal cancer via regulating the INS/SRC/IL6 pathway. Conclusion: Salvia miltiorrhiza emerges as a compelling herbal intervention for colorectal cancer. This study lays the foundation for potential future clinical trials assessing the efficacy of Salvia miltiorrhiza in the management of colorectal cancer.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Simulação de Acoplamento Molecular , Interleucina-6 , Farmacologia em Rede , Tecnologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Medicina Tradicional Chinesa
6.
Aging (Albany NY) ; 16(3): 2475-2493, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305787

RESUMO

OBJECTIVE: The function of Kruppel-like factor 3 (KLF3) remains largely unexplored in colorectal cancer (CRC). METHODS: KLF3 expression in CRC was assessed through qPCR, western blotting, immunohistochemical assays, and The Cancer Genome Atlas (TCGA) database. The tumor-promoting capacity of KLF3 was explored by performing in vitro functional experiments using CRC cells. A subcutaneous nude mouse tumor assay was employed to evaluate tumor growth. To further elucidate the interaction between KLF3 and other factors, luciferase reporter assay, agarose gel electrophoresis, and ChIP analysis were performed. RESULTS: KLF3 was downregulated in CRC tissue and cells. Silencing of KLF3 increased the potential of CRC cells for proliferation, migration, and invasion, while its activation decreased these processes. Downregulated KLF3 was associated with accelerated tumor growth in vivo. Mechanistically, KLF3 was discovered to target the promoter sequence of WNT1. Consequently, the diminished expression of KLF3 led to the buildup of WNT1 and the WNT/ß-catenin pathway activation, consequently stimulating the progression of CRC. CONCLUSIONS: This investigation suggests that the involvement of KLF3/WNT1 regulatory pathway contributes to the progression of CRC, thereby emphasizing its promise as an important focus for future therapies aimed at treating CRC.


Assuntos
Neoplasias Colorretais , Fatores de Transcrição , Camundongos , Animais , Fatores de Transcrição/metabolismo , beta Catenina/metabolismo , Proliferação de Células/genética , Regiões Promotoras Genéticas , Neoplasias Colorretais/patologia , Via de Sinalização Wnt/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética
7.
Chem Biodivers ; 21(2): e202301886, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38308180

RESUMO

Thymoquinone has antioxidant and anticancer effects. This study investigates the cytotoxic, genotoxic, and apoptotic effects of black seed and its active ingredient, thymoquinone on colorectal cancer cells. The antioxidant content of Black seed methanolic extracts (BSME) with different concentrations (50, 500 and 1000 µg/mL) were determined by the photometric methods. The reactive oxygen production (iROS) of BSME and thymoquinone on colorectal cancer cells (LoVo) and normal epithelial cells (CCD18Co) were analyzed by the fluorometric methods. A luminometric glutathione kit was employed to observe the changes in intracellular glutathione (GSH) levels. Cytotoxicity was determined by the ATP method, genotoxicity was determined by Comet Assay, and the apoptosis was identified by the Acridine Orange/Ethidium Bromide (AO/EB) double dye method. The cytotoxicity was increased by BSME and thymoquinone in LoVo cells in a dose-dependent manner (p<0.001). BSME and thymoquinone also increased iROS, and induced apoptosis and DNA damage (p<0.001). High doses of BSME and thymoquinone on cancer and healthy cells have cytotoxic, genotoxic and apoptotic effects with pro-oxidant effects. Colorectal cancer cells are more sensitive than healthy cells.


Assuntos
Antineoplásicos , Benzoquinonas , Neoplasias Colorretais , Humanos , Antioxidantes/farmacologia , Apoptose , Antineoplásicos/farmacologia , Glutationa , Neoplasias Colorretais/tratamento farmacológico
8.
Funct Integr Genomics ; 24(1): 24, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315263

RESUMO

This study is aimed at investigating the roles of Toll-like receptor 4 (TLR4) and microRNA-7 (miR-7) in colorectal cancer (CRC) development and progression. We assessed TLR4 and miR-7 expression in CRC cells and tissues using reverse transcription-quantitative polymerase chain reaction. The relationship between miR-7 and TLR4 was analyzed through dual luciferase reporter assays. MTT, wound healing, and cell invasion assays were conducted to examine the effects of TLR4 and miR-7 on CRC cell proliferation, migration, and invasion. Western blotting was used to explore the involvement of the TRAF6/NF-κB signaling pathway. miR-7 was underexpressed in CRC, while TLR4 levels were increased. miR-7 negatively regulated TLR4 expression and its knockdown enhanced CRC cell proliferation, migration, and invasion. TLR4 knockdown had the opposite effects. The TRAF6/NF-κB pathway was linked to TLR4's role in tumor progression. miR-7 might inhibit TRAF6/NF-κB target a signaling pathway of TLR4 and promote CRC occurrence. miR-7 may therefore be used as a sensitive biomarker in CRC patients.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , NF-kappa B/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Proliferação de Células
9.
Ann Intern Med ; 177(2): JC23, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38316002

RESUMO

SOURCE CITATION: Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA. 2023;330:1760-1768. 37870871.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Fezes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Sangue Oculto , Adenoma/diagnóstico , Adenoma/genética , Programas de Rastreamento , Colonoscopia
10.
Iran J Med Sci ; 49(1): 10-21, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38322164

RESUMO

Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalin-fixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results: Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05). Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine.


Assuntos
Relevância Clínica , Neoplasias Colorretais , Humanos , Caspase 3 , Estudos Retrospectivos , Irã (Geográfico) , Proteínas Serina-Treonina Quinases/metabolismo , Biomarcadores , Proteína 1 de Ligação a X-Box/metabolismo
11.
Medicine (Baltimore) ; 103(5): e37056, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306561

RESUMO

Colorectal cancer is a cancer that arises from the abnormal growth of cells in the colon or rectum. Osteosarcoma (OS) is a common primary bone tumor with high degree of malignancy. The configuration files for colorectal cancer dataset GSE142279 and OS datasets GSE197158 and GSE206448 were downloaded from Gene Expression Omnibus database using the platforms GPL20795, GPL20301, and GPL24676. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Construction and analysis of protein-protein interactions (PPI) network. Functional enrichment analysis, gene set enrichment analysis (GSEA) were performed. A heat map of gene expression was drawn. The Comparative Toxicogenomics Database (CTD) was used to find the diseases most associated with the core genes. TargetScan was used to screen miRNAs regulating DEGs. According to the Gene Ontology (GO) analysis, DEGs are mainly enriched in acetylcholine binding receptor activity involved in Wnt signaling pathway, cell polarity pathway, PI3K-Akt signaling pathway, receptor regulator activity, cytokine-cytokine receptor interaction, transcriptional misregulation in cancer, and inflammation-mediated regulation of tryptophan transport. In the Metascape enrichment analysis, GO enrichment items related to the regulation of Wnt signaling pathway, regulation of muscle system process, and regulation of actin filament-based movement. Eight core genes (CUX1, NES, BCL11B, PAX6, EMX1, MCOLN2, TRPA1, TRPC4) were identified. CTD showed that 4 genes (CUX1, EMX1, TRPA1, BCL11B) were associated with colorectal neoplasms, colorectal tumors, colonic diseases, multiple myeloma, OS, and inflammation. PAX6, TRPA1, BCL11B, MCOLN2, CUX1, and EMX1 are highly expressed in colorectal cancer and OS, and the higher the expression level, the worse the prognosis.


Assuntos
Neoplasias Ósseas , Neoplasias Colorretais , Proteínas de Homeodomínio , Osteossarcoma , Fator de Transcrição PAX6 , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Osteossarcoma/patologia , Neoplasias Ósseas/patologia , Neoplasias Colorretais/genética , Inflamação/genética , Proteínas Supressoras de Tumor/genética , Biologia Computacional , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Canal de Cátion TRPA1/genética , Proteínas Repressoras/metabolismo
12.
Anticancer Res ; 44(2): 511-520, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307570

RESUMO

BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer worldwide, and metastasis is strongly associated with poor prognosis in patients with CRC. We have previously found that the expression and phosphorylation of paxillin (PXN) play an important role in the metastatic potential of breast cancer. This study examined the potential role of PXN in CRC metastasis. MATERIALS AND METHODS: Resected tumor specimens from 92 patients with CRC were subjected to immunohistochemical analysis of PXN levels. Three human CRC cell lines, HCT116, LoVo, and SW480 were used for scratch and transwell invasion assays to examine the effects of PXN over-expression. RNA sequencing was performed to obtain the expression profiles under PXN over-expression. RESULTS: High levels of PXN were significantly correlated with advanced stage, higher carcinoembryonic antigen and carbohydrate antigen 19-9 levels, and poorer overall survival. The migration ability of CRC cells was enhanced by exogenous PXN over-expression, but this enhancement was not observed in cells harboring exogenously mutated PXN at Tyr31 or Tyr88 phosphorylation sites. In PXN-over-expressing cells, TNF-α signaling via NF-[Formula: see text]B was positively enriched. CONCLUSION: PXN expression and phosphorylation at Tyr31 or Tyr88 may influence the migration and invasion of CRC cells. PXN expression and phosphorylation at Tyr31 or Tyr88 are promising targets for evaluating prognosis and treating CRC.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Paxilina , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Metástase Neoplásica , Paxilina/genética , Paxilina/metabolismo , Fosforilação , Prognóstico
13.
Annu Rev Physiol ; 86: 453-478, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345904

RESUMO

Studies in preclinical models support that the gut microbiota play a critical role in the development and progression of colorectal cancer (CRC). Specific microbial species and their corresponding virulence factors or associated small molecules can contribute to CRC development and progression either via direct effects on the neoplastic transformation of epithelial cells or through interactions with the host immune system. Induction of DNA damage, activation of Wnt/ß-catenin and NF-κB proinflammatory pathways, and alteration of the nutrient's availability and the metabolic activity of cancer cells are the main mechanisms by which the microbiota contribute to CRC. Within the tumor microenvironment, the gut microbiota alter the recruitment, activation, and function of various immune cells, such as T cells, macrophages, and dendritic cells. Additionally, the microbiota shape the function and composition of cancer-associated fibroblasts and extracellular matrix components, fashioning an immunosuppressive and pro-tumorigenic niche for CRC. Understanding the complex interplay between gut microbiota and tumorigenesis can provide therapeutic opportunities for the prevention and treatment of CRC.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias do Colo/complicações , Macrófagos , Microambiente Tumoral
14.
Medicine (Baltimore) ; 103(6): e37038, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335431

RESUMO

Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Margens de Excisão , Hepatectomia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Prognóstico
15.
J Immunother Cancer ; 12(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336371

RESUMO

BACKGROUND: Immune checkpoint inhibitor (ICI) combinations represent an emerging treatment strategies in cancer. However, their efficacy in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC) is variable. Here, a multiomic characterization was performed to identify predictive biomarkers associated with patient response to ICI combinations in MSS/pMMR CRC for the further development of ICI combinations. METHODS: Whole-exome sequencing, RNA sequencing, and multiplex fluorescence immunohistochemistry of tumors from patients with MSS/pMMR CRC, who received regorafenib plus nivolumab (REGONIVO) or TAS-116 plus nivolumab (TASNIVO) in clinical trials were conducted. Twenty-two and 23 patients without prior ICI from the REGONIVO and TASNIVO trials were included in this study. A biomarker analysis was performed using samples from each of these studies. RESULTS: The epithelial-mesenchymal transition pathway and genes related to cancer-associated fibroblasts were upregulated in the REGONIVO responder group, and the G2M checkpoint pathway was upregulated in the TASNIVO responder group. The MYC pathway was upregulated in the REGONIVO non-responder group. Consensus molecular subtype 4 was significantly associated with response (p=0.035) and longer progression-free survival (p=0.006) in the REGONIVO trial. CD8+ T cells, regulatory T cells, and M2 macrophages density was significantly higher in the REGONIVO trial responders than in non-responders. Mutations in the POLE gene and patient response were significantly associated in the TASNIVO trial; however, the frequencies of other mutations or tumor mutational burden were not significantly different between responders and non-responders in either trial. CONCLUSIONS: We identified molecular features associated with the response to the REGONIVO and TASNIVO, particularly those related to tumor microenvironmental factors. These findings are likely to contribute to the development of biomarkers to predict treatment efficacy for MSS/pMMR CRC and future immunotherapy combinations for treatment.


Assuntos
Neoplasias Colorretais , Nivolumabe , Humanos , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Linfócitos T CD8-Positivos , Multiômica , Imunoterapia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Biomarcadores
16.
Medicine (Baltimore) ; 103(5): e37072, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306533

RESUMO

The purpose of the current study is to analyze whether surgical starting time affects the short-term outcomes of elective colorectal cancer (CRC) surgery. We retrospectively collected CRC patients who underwent elective surgery from Jan 2008 to Jan 2021 in a single clinical center. The effect of surgical starting time (morning surgery vs afternoon surgery, day surgery vs night surgery) on elective CRC surgery was analyzed using propensity score matching (PSM). A total of 6783 patients were included in the current study. There were 5751 patients in day surgery group and 1032 patients in night surgery group, and there were 2920 patients in morning surgery group and 2831 patients in afternoon surgery group. After 1:1 ratio PSM, there were no significant difference in terms of the baseline information (P > .05). Day surgery group had longer operation time (P = .000) and longer hospital stay (P = .029) than night surgery group after PSM. Morning surgery group had longer operation time than afternoon surgery group before PSM (P = .000) and after PSM (P = .000). Univariate and multivariate analysis of the total of 6783 patients were conducted to find predictors of complications, and found that night surgery was a predictor of major complications (P = .002, OR = 1.763, 95% CI = 1.222-2.543) but not a predictor of overall complications (P = .250, OR = 1.096, 95% CI = 0.938-1.282). Night surgery is a predictor of major complications after elective CRC surgery, therefore, surgeons should be careful when operating at night.


Assuntos
Neoplasias Colorretais , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Neoplasias Colorretais/cirurgia
17.
Aust J Gen Pract ; 53(1-2): 70-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38316485

RESUMO

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) survival in Australia differs by health insurance status, but why this occurs is uncertain. There are growing concerns about out-of-pocket healthcare costs. We examined patient experiences of referral pathways to diagnosis and treatment of CRC in Victoria, Australia, and discussions about costs, comparing public, private and mixed healthcare system users. METHOD: Semistructured telephone interviews were conducted with 16 purposively sampled, English-speaking patients aged ≥40 years with CRC. Interviews were recorded, transcribed and analysed thematically. RESULTS: Private patients described greater out-of-pocket expenses balanced by greater choice of provider and access. Public patients perceived limited choice in their diagnostic or treatment provider, although some considered switching systems. Patients trusted their general practitioner or specialist for referrals. Discussions about costs did not meet guideline recommendations. DISCUSSION: There are limited opportunities for informed decision making about public versus private care for cancer diagnosis and treatment, which could contribute to inequalities in outcomes.


Assuntos
Neoplasias Colorretais , Atenção à Saúde , Humanos , Vitória , Pesquisa Qualitativa , Encaminhamento e Consulta , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia
18.
Langenbecks Arch Surg ; 409(1): 53, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38316643

RESUMO

PURPOSE: Pringle maneuver (PM) is a double-edged sword in liver resection, which is beneficial in reducing blood loss but also causes ischemia-reperfusion injury which may stimulate the outgrowth of micrometastases. The impact of PM on tumor recurrence remains controversial. This study aimed to assess whether PM has effect on the prognosis of colorectal cancer liver metastases (CRLM) after hepatectomy. METHODS: PubMed and the Cochrane Library databases were searched. The PM is defined as the portal triad clamping for several minutes, followed by several minutes of reperfusion, repeated as needed. Prolonged PM was defined as continuous clamping ≥ 20 min or ≥ 3 cycles for maximally 15-min intermittent ischemia. RESULTS: Eleven studies encompassing 4054 patients were included in this meta-analysis. The pooled hazard ratio (HR) did not show significant differences between PM and non-PM groups for disease-free survival (DFS) (HR = 0.91, 95% confidence interval (CI) 0.76-1.11, P = 0.36) and overall survival (HR = 1.03, 95% CI 0.76-1.39, P = 0.87). Subgroup analysis revealed that prolonged PM has adverse impact on DFS (HR 1.75, 95% CI = 1.28-2.40, P = 0.0005). However, non-prolonged PM is a protective factor for DFS (HR 0.82, 95% CI = 0.73-0.92, P = 0.001). CONCLUSION: These findings suggested that prolonged PM may have an adverse impact on the DFS of patients with CRLM and non-prolonged PM is a protective factor for DFS. Further prospective multicenter studies are warranted.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Prognóstico , Neoplasias Colorretais/patologia
19.
Cancer Epidemiol Biomarkers Prev ; 33(2): 183-185, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317627

RESUMO

Implementing fecal immunochemical testing (FIT) through clinic based opportunistic screening or programmatic mailing is not as straightforward as it seems. Liu and colleagues present data for 56,980 individuals who submitted a FIT in a safety net hospital system. In 10.2% (N = 5,819), the test was deemed unsatisfactory. These data demonstrate that there is significant room for improvement in clinical practice regarding colorectal cancer screening with FIT. The high rate of 10% for unsatisfactory FIT tests is higher than the 5% benchmark suggested by the U.S. Multi-Society Task Force on colorectal cancer screening. To maximize FIT success, there needs to be a preoccupation with failure at the system level that results in reducing the number of FIT tests that are rejected. Completing a stool test independently at home is not easy. The medical system needs to help and support individuals in completing the test every step of the way. Suggestions include patient related tips such as labelling and mailing the tests. There are also suggestions for the ordering clinician including administrative tracking to notify clinicians when a FIT has not been performed or is rejected. Papers like this get us focused exactly where we need to be to improve FIT-based screening. See related article by Liu et al., p. 215.


Assuntos
Neoplasias Colorretais , Programas de Rastreamento , Humanos , Programas de Rastreamento/métodos , Sangue Oculto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Fezes
20.
Int J Nanomedicine ; 19: 1041-1054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317849

RESUMO

Purpose: The search for effective and low-risk treatment methods for colorectal cancer (CRC) is a pressing concern, given the inherent risks and adverse reactions associated with traditional therapies. Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment, offering advantages such as non-radiation, non-invasiveness, and targeted treatment. Consequently, the development of nanoparticles with high stability, biocompatibility, and photothermal effects has become a significant research focus within the field of PTT. Methods: In this study, TiO2-Ti3C2 nanocomposites were synthesized and characterized, and their photothermal conversion efficiency in the near-infrared region II (NIR-II) was determined. Then studied the in vivo and in vitro photothermal activity and anti-tumor effect of TiO2-Ti3C2 in human colorectal cancer cell lines and nude mice subcutaneous tumor model. Results: The results showed that TiO2-Ti3C2 nanocomposites have strong absorption ability in the NIR-II, and have high photothermal conversion efficiency under 1064 nm (0.5 W/cm2, 6 min) laser stimulation. In addition, in vitro experiments showed that TiO2-Ti3C2 nanocomposites significantly inhibited the invasion, migration, and proliferation of colorectal cancer cells, and induced cell apoptosis; in vivo, experiments showed that TiO2-Ti3C2 nanocomposites-mediated PTT had good biocompatibility and efficient targeted inhibition of tumor growth. Conclusion: In conclusion, TiO2-Ti3C2 nanocomposites can be used as NIR-II absorption materials in PTT to suppress the invasion, migration, and proliferation of colorectal cancer cells, induce colorectal cancer cell apoptosis, and thus inhibit the development of CRC. Therefore, TiO2-Ti3C2 nanocomposites can be used as potential anti-tumor drugs for photothermal ablation of colorectal cancer cells.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Nanocompostos , Neoplasias , Animais , Camundongos , Humanos , Camundongos Nus , Titânio , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Nanocompostos/uso terapêutico , Fototerapia , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral
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