scholarly journals Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in�vitro and in nude mice

2018 ◽  
Author(s):  
Jian Zhang ◽  
Lei Zhang ◽  
Tong Zhang ◽  
Xin‑Min Dong ◽  
Yu Zhu ◽  
...  
2021 ◽  
Vol 162 (37) ◽  
pp. 1502-1507
Author(s):  
Valéria Jósa ◽  
Krisztina Féderer ◽  
Zsombor Zrubka ◽  
Lilla Reiniger ◽  
Zsolt Baranyai

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.


Author(s):  
C.D. Bucana ◽  
R. Sanchez ◽  
R. Singh ◽  
I.J. Fidler

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.


2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>


Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Linda Bilonda Mutala ◽  
Cécile Deleine ◽  
Matilde Karakachoff ◽  
Delphine Dansette ◽  
Kathleen Ducoin ◽  
...  

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takashi Nishina ◽  
Yutaka Deguchi ◽  
Daisuke Ohshima ◽  
Wakami Takeda ◽  
Masato Ohtsuka ◽  
...  

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.


Metabolism ◽  
2001 ◽  
Vol 50 (10) ◽  
pp. 1213-1219 ◽  
Author(s):  
N. Nara-Ashizawa ◽  
T. Tsukada ◽  
K. Maruyama ◽  
Y. Akiyama ◽  
N. Kajimura ◽  
...  

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