scholarly journals Az interleukin-6-expresszió vizsgálata colorectalis adenocarcinomában szenvedő betegeken

2021 ◽  
Vol 162 (37) ◽  
pp. 1502-1507
Author(s):  
Valéria Jósa ◽  
Krisztina Féderer ◽  
Zsombor Zrubka ◽  
Lilla Reiniger ◽  
Zsolt Baranyai
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Interleukin 6 ◽  
Colorectal Adenocarcinoma ◽  
Tumor Development ◽  
Tumor Grade ◽  
Color Analysis ◽  
Potential Therapeutic Target ◽  
Complex Correlation ◽  
Advanced Stages

Összefoglaló. Bevezetés: A gyulladásos folyamatok és a tumorok kialakulása, illetve progressziója közötti összetett kapcsolat ismert. Az interleukin-6 (IL6) egy pleiotrop gyulladásos citokin, melynek tumorstimuláló és -gátló tulajdonsága is van. Célkitűzés: Kutatásunk célja az IL6-expresszió vizsgálata volt colorectalis adenocarcinoma miatt reszekción átesett betegek szövettani metszetein. Módszer: Az Uzsoki Utcai Kórházban 2004 és 2011 között reszekált 64, colorectalis tumoros beteg demográfiai, sebészeti és patológiai adatait gyűjtöttük össze. A betegek szövettani metszeteit IL6-antitesttel festettük. A digitalizált metszeteket kvantitatív színelemzéssel kiértékeltük, majd az eredményeket a betegek klinikai paramétereinek függvényében elemeztük. Eredmények: Előrehaladott stádiumú betegekben a tumorsejtek IL6-expressziója szignifikánsan magasabbnak bizonyult lineáris regresszióval. A tumorsejtek IL6-expressziója azonban nem korrelált a nemmel, az életkorral vagy a tumor differenciáltságával. Megbeszélés: Különbségek mutatkoztak a tumorsejtek és a stromasejtek IL6-kifejeződése között. Következtetés: Az IL6 hasznos marker és potenciális terápiás cél lehet az előrehaladottabb stádiumú colorectalis tumoros betegeknél. Orv Hetil. 2021; 162(37): 1502–1507. Summary. Introduction: It is well known that there is a complex correlation between inflammation and tumor development and tumor progression. Interleukin-6 (IL6) is a pleiotropic inflammatory cytokine with both tumor stimulating and inhibiting effect. Objective: The goal of our study was to evaluate the IL6 expression of histological slides from patients after resection of colorectal adenocarcinoma. Method: Demographical, surgical, and pathological findings of 64 patients with colorectal cancer operated between 2004 and 2011 in Uzsoki Teaching Hospital were evaluated. Histopathological slides were stained with IL6 antibody. The digitalized slides were assessed with quantitative color analysis, and the results were evaluated according to patients’ clinical parameters. Results: Linear regression showed significantly higher IL6 expression in the tumor cells in patients with advanced stages. However, the IL6 expression of the tumor cells did not correlate with sex, age, or tumor grade. Discussion: There were differences between the IL6 expression in tumor cells and stromal cells. Conclusion: IL6 may be a useful marker and potential therapeutic target in patients with advanced colorectal cancer. Orv Hetil. 2021; 162(37): 1502–1507.

scholarly journals Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takashi Nishina ◽  
Yutaka Deguchi ◽  
Daisuke Ohshima ◽  
Wakami Takeda ◽  
Masato Ohtsuka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Human Cancer ◽  
Tumor Development ◽  
Gene Signature ◽  
Free Survival ◽  
Expression Of Genes ◽  
Reporter Mice ◽  
Interleukin 11

AbstractInterleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

Superoxide dismutase mRNA and protein level in human colorectal cancer

2010 ◽  
Vol 5 (5) ◽  
pp. 590-599 ◽  
Author(s):  
Michał Skrzycki ◽  
Monika Majewska ◽  
Hanna Czeczot
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Liver Metastases ◽  
Tumor Cells ◽  
Protein Level ◽  
Colorectal Adenocarcinoma ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Colorectal Cancer Liver Metastases

AbstractImpairments of antioxidant enzyme expression are often concomitant with the onset of cancer. Due to epigenetic factors causing an inflammatory state the gastrointestinal tract can become exposed to reactive oxygen species. The purpose of our work was to evaluate mRNA and protein levels of superoxide dismutase isoenzymes in human colorectal adenocarcinoma due to its clinical advancement, and in colorectal cancer liver metastases. Evaluation of SOD expression in regard to CRC advancement, seems useful for clinical applications due to different tumor cells sensitivity to reactive oxygen species based treatment. Studies were conducted on a group of 27 patients: 15 diagnosed with colorectal adenocarcinoma and 12 diagnosed with colorectal cancer liver metastases. The mRNA level was determined by RT-PCR, and protein level by Western blotting. We observed significant (P≤0.05) changes of mRNA and protein level of SOD isoenzymes in subsequent stages of colorectal adenocarcinoma advancement and in colorectal cancer liver metastases. Differences in mRNA and protein level of SOD isoenzymes in colorectal adenocarcinoma and its liver metastases indicates that SOD participate in adaptation of tumor cells to oxidative stress, and maintain certain level of ROS, necessary for appropriate cell proliferation. Expression of superoxide dismutase isoenzymes seems to be regulated not only at transcriptional level, but also posttranscriptional.

scholarly journals Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4625
Author(s):  
Jimmy Stalin ◽  
Beat A. Imhof ◽  
Oriana Coquoz ◽  
Rachel Jeitziner ◽  
Philippe Hammel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Molecular Subtype ◽  
Human Cancer ◽  
Tumor Development ◽  
Tumor Grade ◽  
Tissue Expression ◽  
In Vivo Studies

The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC.

Chromogranin-A Expression in Neoplastic Neuroendocrine Cells and Prognosis in Colorectal Cancer

1996 ◽  
Vol 82 (4) ◽  
pp. 390-393 ◽  
Author(s):  
Giovanni Battista Secco ◽  
Elisabetta Campora ◽  
Roberto Fardelli ◽  
Gabriella Lapertosa ◽  
Francesca De Lucchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Chromogranin A ◽  
Colorectal Adenocarcinoma ◽  
Tumor Grade ◽  
Neuroendocrine Cells ◽  
Human Gastrointestinal Tract ◽  
Curative Surgery ◽  
Group Iii ◽  
Colorectal Cancer Patients

Aims Chromogranin-A (CG), a cytoplasmic glycoprotein, is one of the markers most frequently used to identify the presence of neuroendocrine cells in the human gastrointestinal tract. Several authors have identified a subgroup of colorectal cancer patients with a severe prognosis whose tumors contained neuroendocrine CG-positive cells. In the present study, CG expression in 100 patients with colorectal adenocarcinoma treated from January 1983 to December 1988 with potentially curative surgery was analyzed and correlated with other prognostic factors and 5-year survival rate. Methods Samples tested immunohistochemically for CG were divided into three groups: I) negative; II) less than 1 CG-positive cell/mm2; III) more than 1 CG-positive cell/mm2. Results Of 100 patients with primary colorectal adenocarcinoma, 79% had tumors comprised of CG-negative cells, 17% had rare CG-positive cells, and 4% of cases could be classified in group III. No significant relation between CG expression and location of primary tumor, bowel wall infiltration, stage of disease or tumor grade according to Broders and Jass was observed. The 5-year survival was 53% and 52% for CG-positive and CG-negative lesions, respectively. Survival of patients with Dukes-Kirklin stage C and D was comparable in patients with CG-positive (33.3%) and CG-negative (30%) tumors. Conclusions CG expression cannot, at present, be recommended as a marker to identify prognostic subgroups in colorectal cancer patients.

scholarly journals Relationship between peripheral and mesenteric serum levels of CEA and CA 242 with staging and histopathological variables in colorectal adenocarcinoma

2009 ◽  
Vol 24 (5) ◽  
pp. 405-410 ◽  
Author(s):  
Mauro Lamelas Cardoso ◽  
Luís Cesar Fernandes ◽  
Su Bong Kim ◽  
Delcio Matos
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Colorectal Adenocarcinoma ◽  
Tnm Classification ◽  
Venous Invasion ◽  
Serum Levels ◽  
Neural Invasion ◽  
Venous Involvement ◽  
Ca 242 ◽  
Advanced Stages

PURPOSE: To compare histopathological variables and staging in colorectal adenocarcinoma cases with CEA and CA 242 in peripheral and mesenteric blood. METHODS: In 169 individuals underwent surgery for colorectal cancer, CEA and CA 242 were analyzed and compared to mesenteric and peripheral blood and correlated with macroscopic tumor's morphology and size, degree of cell differentiation, venous, neural and lymphatic involvement and TNM classification. RESULTS: There was a difference between the mesenteric (M) and peripheral (P) serum levels of CEA (p=0.020). Higher levels of markers were correlated with venous invasion CEA (P) p=0.013, CEA (M) p=0.05, CA 242 (M) p=0.005 and CA 242 (P) p=0.038; with advanced staging CEA (P) < CEA (M) (p < 0.05); CA 242 (P) < CA 242 (M) (p < 0.05); and with greater dimensions CEA (P) < CEA (M) (p < 0.001); CA 242 (P) < CA 242 (M) (p < 0.001). CA 242 became higher with neural invasion (P): p=0.014, (M): p=0.003). CONCLUSIONS: There were higher mesenteric than peripheral levels of CEA. Both mesenteric and peripheral levels of CEA and CA 242 were higher in neoplasm with venous involvement, greater diameter and advanced stages. There was a correlation between CA 242 and neural invasion.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

scholarly journals The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Linda Bilonda Mutala ◽  
Cécile Deleine ◽  
Matilde Karakachoff ◽  
Delphine Dansette ◽  
Kathleen Ducoin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Explant Culture ◽  
T Cell Response ◽  
Mrna Levels ◽  
Innate And Adaptive Immunity ◽  
Caspase 1 ◽  
Culture Model

In colorectal cancer (CRC), a high density of T lymphocytes represents a strong prognostic marker in subtypes of CRC. Optimized immunotherapy strategies to boost this T-cell response are still needed. A good candidate is the inflammasome pathway, an emerging player in cancer immunology that bridges innate and adaptive immunity. Its effector protein caspase-1 matures IL-18 that can promote a T-helper/cytotoxic (Th1/Tc1) response. It is still unknown whether tumor cells from CRC possess a functional caspase-1/IL-18 axis that could modulate the Th1/Tc1 response. We used two independent cohorts of CRC patients to assess IL-18 and caspase-1 expression by tumor cells in relation to the density of TILs and the microsatellite status of CRC. Functional and multiparametric approaches at the protein and mRNA levels were performed on an ex vivo CRC explant culture model. We show that, in the majority of CRCs, tumor cells display an activated and functional caspase-1/IL-18 axis that contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Rα. Furthermore, unsupervised clustering identified three clusters of CRCs according to the caspase-1/IL-18/TIL density/interferon gamma (IFNγ) axis and microsatellite status. Together, our results strongly suggest that targeting the caspase-1/IL-18 axis can improve the anti-tumor immune response in subgroups of CRC.

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

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