| 1. |
- Bisgin, Atil, et al.
(författare)
-
Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients
- 2019
-
Ingår i: Journal of Oncology. - : HINDAWI LTD. - 1687-8450 .- 1687-8469. ; 2019
-
Tidskriftsartikel (refereegranskat)abstract
- CD200 imparts an immunoregulatory signal through its receptor, CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain. Our aim was to investigate the expression and localization of CD200 and its receptor CD200R1 and their clinical significance in rectal cancer patients. We examined the immunohistochemical expressions and localizations of CD200 and CD200R1 in 140 rectal cancer patients. Among the patients, 79 underwent the preoperative radiotherapy and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples were evaluated. The results of immunohistochemical analysis showed a strikingly high level of CD200 in tumor cells (p=0.001) and CD200R1 expression in normal mucosal epithelium and stromal cells. Importantly, CD200R1 was overexpressed in stromal cells of the metastatic cancer patients compared to patients without metastases (p=0.002). More than that, 87% of metastatic patients had a phenotype of upregulated CD200 in tumor cells accompanied by overexpressed CD200R1 in stromal cells. In addition, low levels of CD200 were correlated with improved overall survival in untreated patients. We showed that tumor-stroma communication through CD200 and its receptor interaction is selected in patients with high risk of relapse. High levels of these molecules support instigation of the far and local metastatic nest that provides solid ground for metastasis. Our current data also disclose a mechanism by which CD200:CD200R1 affects tumor progression and may strengthen the feasibility of targeting CD200 or CD200R1 as anticancer strategy.
|
|
| 2. |
- Burocziova, Monika, et al.
(författare)
-
Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon
- 2019
-
Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889 .- 2041-4889. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in the exon 6 of the PPM1D result in production of a highly stable, C-terminally truncated PPM1D. These gain-of-function PPM1D mutations are present in various human cancers but their role in tumorigenesis remains unresolved. Here we show that truncated PPM1D impairs activation of the cell cycle checkpoints in human non-transformed RPE cells and allows proliferation in the presence of DNA damage. Next, we developed a mouse model by introducing a truncating mutation in the PPM1D locus and tested contribution of the oncogenic PPM1D(T) allele to colon tumorigenesis. We found that p53 pathway was suppressed in colon stem cells harboring PPM1D(T) resulting in proliferation advantage under genotoxic stress condition. In addition, truncated PPM1D promoted tumor growth in the colon in Apc(min) mice and diminished survival. Moreover, tumor organoids derived from colon of the Apc(min)Ppm1d(T/+) mice were less sensitive to 5-fluorouracil when compared to Apc(min)Ppm1d(+/+)and the sensitivity to 5-fluorouracil was restored by inhibition of PPM1D. Finally, we screened colorectal cancer patients and identified recurrent somatic PPM1D mutations in a fraction of colon adenocarcinomas that are p53 proficient and show defects in mismatch DNA repair. In summary, we provide the first in vivo evidence that truncated PPM1D can promote tumor growth and modulate sensitivity to chemotherapy.
|
|
| 3. |
- Han, Shuangshuang, et al.
(författare)
-
Application value of CyTOF 2 mass cytometer technology at single-cell level in human gastric cancer cells
- 2019
-
Ingår i: Experimental Cell Research. - : Elsevier. - 0014-4827 .- 1090-2422. ; 384:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy and radiotherapy are main adjuvant therapies for the treatment of gastric cancer, the treatment effects are individual difference, but the specific mechanism is unknown. CyTOF 2 mass cytometer (CyTOF) enables the detecting up to 135 parameters on single cell, the emergence of which is an opportunity for proteomics research. We first tried to apply CyTOF technique to gastric cancer cells. We verified applicability of CyTOF in gastric cancer cells, and analyzed the responses of seventeen proteins to chemoradiotherapy in human gastric cancer AGS cells. To analyze the high dimensional CyTOF data, we used two statistical and visualization tools including viSNE and Citrus. Two specific clusters were found which had differences in protein expression profiles. CyTOF technology is proved feasibility and value at single cell level of gastric cancer.
|
|
| 4. |
- Hu, Wenjun, et al.
(författare)
-
Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer
- 2019
-
Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889 .- 2041-4889. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), tumor cells can develop mechanisms to evade oxaliplatin-induced cell death and show high tolerance and acquired resistance to this drug. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) has been proved to play a critical role in DNA repair during IgH class switch recombination (CSR) in B lymphocytes, while, its role in CRC and chemotherapeutic resistance remain unknown. Our study aims to uncover an unidentified mechanism of regulating DNA double-strand breaks (DSBs) by hnRNP L in CRC cells treated by oxaliplatin. In present study, we observed that knockdown of hnRNP L enhanced the level of DNA breakage and sensitivity of CRC cells to oxaliplatin. The expression of key DNA repair factors (BRCA1, 53BP1, and ATM) was unaffected by hnRNP L knockdown, thereby excluding the likelihood of hnRNP L mediation via mRNA regulation. Moreover, we observed that phosphorylation level of ATM changed oppositely to 53BP1 and BRCA1 in the CRC cells (SW620 and HCT116) which exhibit synergistic effect by oxaliplatin plus hnRNP L impairment. And similar phenomenon was observed in the foci formation of these critical repair factors. We also found that hnRNP L binds directly with these DNA repair factors through its RNA-recognition motifs (RRMs). Analysis of cell death indicated that the RRMs of hnRNP L are required for cell survival under incubation with oxaliplatin. In conclusion, hnRNP L is critical for the recruitment of the DNA repair factors in oxaliplatin-induced DSBs. Targeting hnRNP L is a promising new clinical approach that could enhance the effectiveness of current chemotherapeutic treatment in patients with resistance to oxaliplatin.
|
|
| 5. |
- Kotti, Angeliki, et al.
(författare)
-
Survival benefit of statins in older patients with rectal cancer : A Swedish population-based cohort study
- 2019
-
Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 10:5, s. 690-697
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIncreasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.Materials and MethodsThis study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.ResultsIn the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.ConclusionStatin use was related to improved survival in older patients with rectal cancer.This observation is important given the low cost and safety of statins as a drug.
|
|
| 6. |
- Liu, Na, et al.
(författare)
-
The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer
- 2019
-
Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 104:5, s. 1153-1164
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeTo explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.Methods and MaterialsRho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.ResultsRhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry–based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.ConclusionsRhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.
|
|
| 7. |
|
|
| 8. |
- Luo, B., et al.
(författare)
-
Intratumoral polymorphism of peroxisome proliferator-activated receptor delta-87 T > C in colorectal cancer
- 2019
-
Ingår i: Neoplasma (Bratislava). - : AEPRESS SRO. - 0028-2685 .- 1338-4317. ; 66:4, s. 609-618
-
Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD -87 Tamp;gt;C (rs2016520), may play an important role in regulation of PPARD expression. However its expression patterns as well as contribution to colorectal cancer (CRC) are still controversial. In this study, the presence of the intratumoral heterogeneity of PPARD -87 Tamp;gt;C (rs2016520) polymorphism and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the tumorectomy, specimens from different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD -87 Tamp;gt;C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 Tamp;gt;C intra-tumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04 +/- 13.67 years. A total number of 808 samples (7.60 +/- 1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 Tamp;gt;C among these samples. Furthermore, intratumoral genotype of -87 Tamp;gt;C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patient age (p=0.016), tumor location (p=0.011) and the grade of differentiation (p=0.022). For patients with intratumoral heterogeneity, immunochemistry showed that the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD -87 Tamp;gt;C widely existed in CRC, and associated with patient age, tumor location and differentiation. However, the immunochemistry assay revealed that there is no significant link between heterogeneity and expression of PPARD.
|
|
| 9. |
- Pham, Tuan, et al.
(författare)
-
Deep Learning of P73 Biomarker Expression in Rectal Cancer Patients
- 2019
-
Ingår i: 2019 International Joint Conference on Neural Networks (IJCNN). - : IEEE. - 9781728119854 - 9781728119861
-
Konferensbidrag (refereegranskat)abstract
- By applying deep learning, we were able to compare p73 protein expression patterns of different tissue types including normal mucosa, primary tumor and lymph node metastasis in rectal cancer patients using immunohistochemical slides. The pair-wise pattern comparisons were automatedly carried out by considering color, edge, blobs, and other morphological information in the images. We discovered that when the pattern dissimilarity between primary tumor and lymph node metastasis is relatively low among other tissue pairs (primary tumor and distant normal, biopsy and distant normal, biopsy and primary tumor, biopsy and primary tumor, lymph node metastasis and distant normal, lymph node metastasis and biopsy), there was an implication of short-time survival. This original result suggests a novel application of advanced artificial intelligence in machine learning for clinical finding in rectal cancer and encourages relevant study of multiple biomarker expressions in cancer patients.
|
|
| 10. |
- Subramaniam, Vimala Devi, et al.
(författare)
-
Comparative study on anti-proliferative potentials of zinc oxide and aluminium oxide nanoparticles in colon cancer cells
- 2019
-
Ingår i: Acta bio-medica : Atenei Parmensis. - : Mattioli 1885. - 0392-4203. ; 90:2, s. 241-247
-
Tidskriftsartikel (refereegranskat)abstract
- Use of commercial products containing nanoparticles formulated from zinc oxide (ZnO) and aluminium oxide (Al2O-3) has increased significantly. These nanoparticles are widely used as ingredient in cosmetics, and also in food packaging industry although their toxicity status is yet to be studied. Here, we aimed to explore the effect of zinc oxide nanoparticles (ZnO-NPs) and aluminium oxide nanoparticles (ANPs) in human HT29 colon cancer cell line.
|
|
