scholarly journals 3:00 PM Abstract No. 190 ■ FEATURED ABSTRACT Quantifying the immune response after combined immuno-thermal ablation in a murine model of colorectal cancer

2020 ◽  
Vol 31 (3) ◽  
pp. S87
Author(s):  
R. Slovak ◽  
H. Park ◽  
W. Kamp ◽  
J. Ludwig ◽  
I. Kang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Murine Model ◽  
Thermal Ablation

scholarly journals Role of Thermal Ablation in Colorectal Cancer Lung Metastases

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 908
Author(s):  
Alexandre Delpla ◽  
Thierry de Baere ◽  
Eloi Varin ◽  
Frederic Deschamps ◽  
Charles Roux ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Thermal Ablation ◽  
Medical Oncology ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Stereotactic Ablative Radiotherapy ◽  
Chest Drainage ◽  
Results Of Surgery

Background: Consensus guidelines of the European Society for Medical Oncology (ESMO) (2016) provided recommendations for the management of lung metastases. Thermal ablation appears as a tool in the management of these secondary pulmonary lesions, in the same manner as surgical resection or stereotactic ablative radiotherapy (SABR). Methods: Indications, technical considerations, oncological outcomes such as survival (OS) or local control (LC), prognostic factors and complications of thermal ablation in colorectal cancer lung metastases were reviewed and put into perspective with results of surgery and SABR. Results: LC rates varied from 62 to 91%, with size of the metastasis (<2 cm), proximity to the bronchi or vessels, and size of ablation margins (>5 mm) as predictive factors of LC. Median OS varied between 33 and 68 months. Pulmonary free disease interval <12 months, positive carcinoembryonic antigen, absence of neoadjuvant chemotherapy and uncontrolled extra-pulmonary metastases were poor prognostic factors for OS. While chest drainage for less than 48 h was required in 13 to 47% of treatments, major complications were rare. Conclusions: Thermal ablation of a selected subpopulation of patients with colorectal cancer lung metastases is safe and can provide excellent LC and delay systemic chemotherapy.

scholarly journals Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Xu ◽  
Qing Zheng
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Validation Cohort ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Immune Checkpoints ◽  
Positive Correlation ◽  
Expression Signature ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.

scholarly journals Persimmon-derived tannin ameliorates the pathogenesis of ulcerative colitis in a murine model through inhibition of the inflammatory response and alteration of microbiota

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masahiro Kitabatake ◽  
Yoko Matsumura ◽  
Noriko Ouji-Sageshima ◽  
Tatsuki Nishioka ◽  
Atsushi Hara ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immune Response ◽  
Murine Model ◽  
Control Diet ◽  
Antimicrobial Activities ◽  
Diet Group ◽  
Chronic Inflammatory Bowel Disease ◽  
Diospyros Kaki ◽  
Colon Inflammation

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) induced by dysregulation of the immune response in the intestinal mucosa. Although the underlying mechanisms of UC development are not fully understood, disruption of gut microbiota, “dysbiosis”, is thought to lead to the development of IBD. Persimmon (Ebenaceae Diospyros kaki Thunb.)-derived tannin, which is a condensed polymeric tannin consisting of catechin groups, has antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we assessed the effect of persimmon-derived tannin on a murine model of UC established by dextran sulfate sodium-induced colitis in female mice. Dietary supplementation of tannin significantly decreased disease activity and colon inflammation. A hydrolysate of tannin directly suppressed expression of inflammatory genes in macrophages in vitro. In faecal microbiota, the relative abundance of Bacteroides was increased significantly by tannin supplementation. Alpha-diversity indices in colitis-induced mice were significantly higher in the tannin diet group compared with the control diet group. Additionally, expansion of Enterobacteriaceae and Enterococcus, which is associated with disease progression of IBD, was remarkably suppressed in the tannin diet group. These results suggest that persimmon-derived tannin ameliorates colon inflammation in UC through alteration of the microbiota composition and immune response, which may be a promising candidate for IBD therapy.

Balanced Th1/Th2 immune response induced by MSP1a functional motif coupled to multiwalled carbon nanotubes as anti-anaplasmosis vaccine in murine model

2020 ◽  
Vol 24 ◽  
pp. 102137 ◽  
Author(s):  
Leticia Santos Pimentel ◽  
Carolina Alvarenga Turini ◽  
Paula Souza Santos ◽  
Mariana Abilio de Morais ◽  
Aline Gomes Souza ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Immune Response ◽  
Multiwalled Carbon Nanotubes ◽  
Murine Model ◽  
Multiwalled Carbon ◽  
Functional Motif ◽  
Th2 Immune Response

scholarly journals Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Murine Model ◽  
Licorice Root ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Stem Cell Markers ◽  
Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

scholarly journals The features of host immune response with respect to microsatellite status of colorectal cancer

2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Responses ◽  
Continuous Production ◽  
Tumor Infiltrating Lymphocytes ◽  
Host Immune Response ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Melting Point Analysis ◽  
Peritumoral Stroma

Background: The genetic alterations in colorectal cancer (CRC) progression are determined by two separate pathways, chromosomal and microsatellite instability (MSI). The CRCs with MSI have distinct clinicopathological characteristics with pronounced tumor-associated immune responses. The aim of our study was to investigate the intensity of host immune response in CRC tissue by comparing microsatellite stable (MSS) and instable tumors. Methods: The study was performed on CRC specimens from 28 patients with MSI and compared with 30 MSS tumors. The microsatellite status was evaluated with two markers by PCR and melting point analysis. The immunostaining with anti-CD3 pan-T cell antibody was used to quantify the number of tumor infiltrating lymphocytes. The lymphocytes in peritumoral stromal and the Crohn?s-like peritumoral reaction were counted on H&E slides. Results: No significant differences were found in the average number of lymphocytes in peritumoral stroma and in clinicopathological characteristics of CRCs. The conspicuous Crohn?s-like lymphoid reactions were present in 67.86% of CRCs with MSI versus 26.66% of MSS cases. The CRCs with MSI cases carried significantly higher numbers of tumor infiltrating T-lymphocytes (13.21 versus 7.47) (p<0.0001). Conclusion: The presences of peritumoral Crohn?s-like lymphoid and intraepithelial lymphocytic reaction were intensive markers for MSI in colorectal carcinomas in our study. The peculiar genetic instability in MSI tumors may lead to a continuous production of abnormal peptides, which act as neoantigens. They could induce specific antitumor immune responses effective in limiting tumor growth and spread. Abnormal peptides are potentially promising in immunotherapy advancing and in the design of a vaccine against colorectal tumors with MSI.

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