scholarly journals Dickkopf-3 As a New Potential Marker for Neoangiogenesis in Colorectal Cancer: Expression in Cancer Tissue and Adjacent Non-Cancerous Tissue

2008 ◽  
Vol 24 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Matthias Zitt ◽  
Gerold Untergasser ◽  
Albert Amberger ◽  
Patrizia Moser ◽  
Sylvia Stadlmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tissue Microarrays ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Novel Therapies ◽  
Microvessel Count ◽  
Target Structure ◽  
Potential Marker ◽  
Tumor Endothelium ◽  
First Time

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3.Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.

scholarly journals Quantitative Image Analysis of Epithelial and Stromal Area in Histological Sections of Colorectal Cancer: An Emerging Diagnostic Tool

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
R. Rogojanu ◽  
T. Thalhammer ◽  
U. Thiem ◽  
A. Heindl ◽  
I. Mesteri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Normal Mucosa ◽  
Image Method ◽  
Cancer Tissue ◽  
The Novel ◽  
Adjacent Mucosa ◽  
Quantitative Measurements ◽  
Tumor Center ◽  
Quantitative Image ◽  
Tissue Compartments

In colorectal cancer (CRC), an increase in the stromal (S) area with the reduction of the epithelial (E) parts has been suggested as an indication of tumor progression. Therefore, an automated image method capable of discriminating E and S areas would allow an improved diagnosis. Immunofluorescence staining was performed on paraffin-embedded sections from colorectal tumors (16 samples from patients with liver metastasis and 18 without). Noncancerous tumor adjacent mucosa (n=5) and normal mucosa (n=4) were taken as controls. Epithelial cells were identified by an anti-keratin 8 (K8) antibody. Large tissue areas (5–63 mm2/slide) including tumor center, tumor front, and adjacent mucosa were scanned using an automated microscopy system (TissueFAXS). With our newly developed algorithms, we showed that there is more K8-immunoreactive E in the tumor center than in tumor adjacent and normal mucosa. Comparing patients with and without metastasis, the E/S ratio decreased by 20% in the tumor center and by 40% at tumor front in metastatic samples. The reduction of E might be due to a more aggressive phenotype in metastasis patients. The novel software allowed a detailed morphometric analysis of cancer tissue compartments as tools for objective quantitative measurements, reduced analysis time, and increased reproducibility of the data.

Differential Expression of Mimecan and Thioredoxin Domain–Containing Protein 5 in Colorectal Adenoma and Cancer: A Proteomic Study

2007 ◽  
Vol 232 (9) ◽  
pp. 1152-1159 ◽  
Author(s):  
Yinghong Wang ◽  
Yu Ma ◽  
Bingjian Lü ◽  
Enping Xu ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Normal Mucosa ◽  
Colorectal Adenomas ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Differentially Expressed Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Proteomic Study ◽  
Cancer Tissues

Adenoma is the major precursor lesion of colorectal cancer, one of the most common cancers worldwide. The elucidation of the molecular mechanism underlying adenoma is essential for early detection, prevention, and intervention of colorectal cancer. Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 27 differentially expressed proteins in adenoma, compared with matched normal mucosa and cancer tissue. Seventeen proteins were upregulated and six downregulated in adenoma when compared with the same proteins in individual-matched normal mucosa. Four were downregulated, but none upregulated in adenoma when compared with the same proteins in matched cancer tissue. Two novel proteins, mimecan and thioredoxin domain–containing protein 5 (TXNDC5), were further validated by Western blot in 8 colorectal adenomas and 19 cancers that were matched with normal mucosa. All adenoma and cancer tissues did not express mimecan, but all normal mucosa did ( P < 0.01). In contrast, TXNDC5 was significantly upregulated in colorectal adenoma and cancer tissues as compared with that in normal mucosa ( P < 0.05). This study clearly demonstrated that absence of mimecan and upregulation of TXNDC5 are involved in the early development of colorectal cancer. Thus, the differentially expressed proteins might serve as potential biomarkers for colorectal cancer detection and intervention.

scholarly journals The encounter of tumor and SARS-CoV-2: Pathological findings in a patient with colon cancer and COVID-19

2020 ◽  
Author(s):  
Weixiang Zhong ◽  
Jun Li ◽  
Mei Kong ◽  
Qiqi Gao ◽  
Xiaodong Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
T Cell ◽  
Tissue Microarrays ◽  
Cd8 T Cell ◽  
Cancer Tissue ◽  
Surgical Specimen ◽  
Positive Rate ◽  
Cancer Tumor ◽  
Cell Proportion

Abstract As coronavirus disease 2019 (COVID-19) spreads worldwide, there have been few reports of infections among the cancer population, although more than six million cases have been confirmed. Here we studied a surgical specimen from a patient with colon cancer and COVID-19 and two tissue microarrays comprising 103 colorectal cancer and 108 enterocyte cases pathologically. The results showed that, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antibody was positively expressed in colon cancer tissues. Moreover, the angiotensin converting enzyme 2 (ACE2) was overexpressed in both colorectal cancer tissue microarray and tumor tissue from this patient, with a positive rate as high as 93.2%. Finally, this case of SARS-CoV-2 infection in colon cancer tumor microenvironment (TME) is a failure of immune homeostasis, due to the decrease in TIA + and Granzyme B+ (GrB) CD8 + T cell proportion and the increase in PD-1 + CD8 + T cell proportion. In summary, we speculate that these three factors may have contributed significantly to infection risk and severity in the patient.

scholarly journals Rearrangements of Blood and Tissue Fatty Acid Profile in Colorectal Cancer - Molecular Mechanism and Diagnostic Potential

2021 ◽  
Vol 11 ◽  
Author(s):  
Adriana Mika ◽  
Katarzyna Duzowska ◽  
Lukasz P. Halinski ◽  
Alicja Pakiet ◽  
Aleksandra Czumaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Healthy Subjects ◽  
Roc Analysis ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Normal Colon Mucosa ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Ht 29

Colorectal cancer (CRC) is often diagnosed at an advanced stage due to the invasiveness of colonoscopy; thus, non-invasive CRC diagnostics are desirable. CRC is associated with lipid alterations. We aimed to verify whether fatty acid (FA) profiles in CRC patients may serve as a potential diagnostic tool for CRC diagnosis. FA profiles were assayed by GC-MS in cancer tissue, paired normal mucosa and serum from CRC patients and healthy controls. The levels of very long FAs – VLCFAs (26:0, 28:0 and 26:1) were the most highly increased FAs in cancer tissue compared to normal colon mucosa. Moreover, these FA were present in serum of CRC patients, they were absent in the serum of healthy subjects, or present in only trace amounts. To verify if cancer cells are the source of small amounts of these VLCFAs in the serum of patients we performed experiment in HT-29 CRC cells, which proved that CRC cells can produce and release VLCFAs into the blood. Most importantly, we defined a panel of FAs that may be assayed in a single analysis that definitely distinguishes CRC patients and healthy subjects, which was confirmed by PLS-DA and multivariate ROC analysis (AUC = 0.985). This study shows that selected FA panel may serve as a diagnostic marker for CRC.

196 A Sensitive Methylation Marker Panel That Discriminates Normal Mucosa from Colorectal Cancer Tissue with High Specificity

2009 ◽  
Vol 136 (5) ◽  
pp. A-36
Author(s):  
Patric Urfer ◽  
Stefan Weis ◽  
Faiza Noreen ◽  
Mirco Menigatti ◽  
Corina Kim-Fuchs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Specificity ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Marker Panel ◽  
Colorectal Cancer Tissue ◽  
Methylation Marker

Prospective study on prognostic significance of DNA ploidy and Ki-67 expression in colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21184-21184
Author(s):  
C. Saggia ◽  
A. Santagostino ◽  
G. Forti ◽  
G. Biaggi ◽  
G. Angeli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proliferative Activity ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
Normal Mucosa ◽  
Disease Stage ◽  
Cancer Tissue ◽  
Ki 67 ◽  
Number Of Patients ◽  
Immuno Histochemistry

21184 Background: The prognostic value of flow cytometry DNA ploidy and Ki-67 expression in colorectal carcinomas has not been defined yet. The study tries to correlate tumoral DNA ploidy and proliferative activity (Ki-67) with therapy response, Overall Survival (OS), Disesase Specific Survival (DSS) and Disease Free Survival (DFS). Methods: From 01/09/02 to 30/06/05, 3 samples of cancer tissue and 1 sample of normal mucosa has been collected from all operating pieces of colorectal cancer. These samples were frosen and later disgregated, treated and coloured with Propidium Iodide. DNA ploidy was evaluated by FACSCalibur cytofluorimetry. Normal mucosa tissue was our internal control. Ki-67 was evaluated by immuno-histochemistry in all tumoral samples. All the patients were cured with chemo- and/or radiotherapy in our divisions. Results: 67 patients (M/F 35/32); median age was 70; staging: 19% I, 33% II, 30% III, 18% IV. We found aneuploidy in 65,7% of carcinoma and Ki-67 median expression was 55%. DNA tumoral heterogeneity was present in 27% of patients. DNA aneuploidy correlates with advanced disease stage at diagnosis (p<0,01), with high number of metastatic lymphnodes (p<0,005) and with serological markers positivity (p<0,04). After surgery and chemotherapy 35% of the patients with aneuploid carcinoma and high proliferative activity (Ki-67>55%) do not show evident disease versus 100% of patients with DNA diploidy and lower Ki-67. Tumoral aneuploidy correlates in a significative way with lower OS (48% vs 89% of diploid patients), lower DSS (tumor death happened just in patients with aneuploid DNA in every disease stages), with lower DFS (18% vs 86% of diploid patients). Univariated analysis stated that aneuploidy determinates an Odd Ratio=5,7 to develop disease progression (p=0,033). At the moment Ki-67 expression with 55% cut-off does not seem to correlate with OS, DSS and DFS. Conclusions: Preliminar results (the study is still in progress) seem to suggest that cytofluorimetric DNA-ploidy has a prognostic and predictive significance in colo-rectal carcinomas. Ki-67 expression (immuno-histochemistry) has an uncertain significance. The small number of patients and the short follow-up do not allow us to reach any definitive conclusions, but the study is worth to go on. No significant financial relationships to disclose.

Melanoma-Associated Antigen (MAGE) Expression in the Normal Mucosa around Colorectal Cancer after Curative Resection: Presence of Undetectable Free Cancer Cells?

2011 ◽  
Vol 26 (2) ◽  
pp. 88-93 ◽  
Author(s):  
Chang-Ho Jeon ◽  
Dae-Dong Kim ◽  
Han-Il Lee ◽  
Hoon-Kyu Oh ◽  
Hyun-Dong Chae
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Curative Resection ◽  
Normal Mucosa ◽  
Clinical Findings ◽  
Cancer Tissue ◽  
Benign Diseases ◽  
Mucosal Tissues ◽  
Mucosal Site ◽  
Colorectal Diseases

Purpose Curative surgical resection is of great importance and some trials have been performed to identify free undetectable cancer cells using molecular markers. The aim of this study is to investigate melanoma-associated antigen (MAGE) expression in normal mucosa around colorectal cancer and its clinical significance. Material and method From October 2003 to June 2004, we collected 46 colorectal cancer and matched normal mucosal tissues within 20 mm, 20 to 50 mm and more than 50 mm from tumors after the curative operation. Twenty-two mucosal tissues were harvested from patients with benign colorectal diseases as controls. MAGE expression was assayed using nested RT-PCR of MAGE A1-6 mRNA. Results The MAGE expression rates in cancer tissue and adjacent normal mucosa were 65.2%, 6.5% (<20 mm), 2.2% (20–50 mm) and 0.0% (>50 mm), respectively, while MAGE was not expressed in the mucosa of benign diseases. The MAGE-positive cases in the normal mucosa around tumors were located in the left colon or rectum, and one patient showed anastomotic mucosal site recurrence. Conclusions MAGE expression in normal-appearing mucosa around colorectal cancer showed some clinical findings suggesting the presence of undetectable free cancer cells after curative resection.

Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on Colorectal Cancer HT29 Cells

2019 ◽  
Vol 35 (6) ◽  
pp. 73-79
Author(s):  
A. Turchinovich ◽  
I.M. Tsypina ◽  
V.G. Zgoda ◽  
S.V. Nikulin ◽  
D.V. Maltseva
Keyword(s):  
Colorectal Cancer ◽  
Cytotoxic Effect ◽  
Mechanisms Of Action ◽  
Ht29 Cell ◽  
Β1 Integrin ◽  
Russian Science ◽  
Apoptotic Gene ◽  
Ht29 Cells ◽  
First Time ◽  
Ht29 Cell Line

The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF)-drugs with different mechanisms of action used to treat colorectal cancer-on the HT29 cell line when cultured on plastic and laminin 521 (LM-521) has been studied. It was shown for the first time that LM-521 can increase the sensitivity of tumor cells to 5FU. Based on the analysis of the transcriptome and proteome, a possible mechanism of the observed effect of LM-521 on HT29 cell viability was proposed. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways, promote phosphorylation of the YAP transcription coactivator and its binding to a complex with the 14-3-3σ protein. The formation of such complex leads to the YAP retention in the cytoplasm, prevents its transport to the nucleus and the activation of anti-apoptotic gene transcription. apoptosis, β1 integrin, colorectal cancer, laminin 521 (laminin-11), regorafenib, 5-fluorouracil, HT29, ITGB1, LAMA5, YAP, SFN, 14-3-3σ The study was funded by the Russian Science Foundation (Project 17-14-01338).

scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

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