| 1. |
- Fath, MK, et al.
(författare)
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Current understanding of epigenetics role in melanoma treatment and resistance
- 2022
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Ingår i: Cancer cell international. - : Springer Science and Business Media LLC. - 1475-2867. ; 22:1, s. 313-
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail.
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| 2. |
- Fath, MK, et al.
(författare)
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Exosome-based strategies for diagnosis and therapy of glioma cancer
- 2022
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Ingår i: Cancer cell international. - : Springer Science and Business Media LLC. - 1475-2867. ; 22:1, s. 262-
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma belongs to the most aggressive type of cancer with a low survival rate that is characterized by the ability in forming a highly immunosuppressive tumor microenvironment. Intercellular communication are created via exosomes in the tumor microenvironment through the transport of various biomolecules. They are primarily involved in tumor growth, differentiation, metastasis, and chemotherapy or radiation resistance. Recently several studies have highlighted the critical role of tumor-derived exosomes against immune cells. According to the structural and functional properties, exosomes could be essential instruments to gain a better molecular mechanism for tumor understanding. Additionally, they are qualified as diagnostic/prognostic markers and therapeutic tools for specific targeting of invasive tumor cells such as glioblastomas. Due to the strong dependency of exosome features on the original cells and their developmental status, it is essential to review their critical modulating molecules, clinical relevance to glioma, and associated signaling pathways. This review is a non-clinical study, as the possible role of exosomes and exosomal microRNAs in glioma cancer are reported. In addition, their content to overcome cancer resistance and their potential as diagnostic biomarkers are analyzed.
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| 3. |
- Fath, MK, et al.
(författare)
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Revisiting characteristics of oncogenic extrachromosomal DNA as mobile enhancers on neuroblastoma and glioma cancers
- 2022
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Ingår i: Cancer cell international. - : Springer Science and Business Media LLC. - 1475-2867. ; 22:1, s. 200-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer can be induced by a variety of possible causes, including tumor suppressor gene failure and proto-oncogene hyperactivation. Tumor-associated extrachromosomal circular DNA has been proposed to endanger human health and speed up the progression of cancer. The amplification of ecDNA has raised the oncogene copy number in numerous malignancies according to whole-genome sequencing on distinct cancer types. The unusual structure and function of ecDNA, and its potential role in understanding current cancer genome maps, make it a hotspot to study tumor pathogenesis and evolution. The discovery of the basic mechanisms of ecDNA in the emergence and growth of malignancies could lead researchers to develop new cancer therapies. Despite recent progress, different aspects of ecDNA require more investigation. We focused on the features, and analyzed the bio-genesis, and origin of ecDNA in this review, as well as its functions in neuroblastoma and glioma cancers.
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| 4. |
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| 6. |
- Keane, Simon, et al.
(författare)
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The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma
- 2021
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Ingår i: Cancer Cell International. - : Springer Nature. - 1475-2867. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling. Methods: We evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS. Results: In neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability, with increased BAX/BCL2 ratio indicating increased apoptosis. Conclusion: We have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.
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| 7. |
- Khodakarami, A, et al.
(författare)
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The molecular biology and therapeutic potential of Nrf2 in leukemia
- 2022
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Ingår i: Cancer cell international. - : Springer Science and Business Media LLC. - 1475-2867. ; 22:1, s. 241-
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Tidskriftsartikel (refereegranskat)abstract
- NF-E2-related factor 2 (Nrf2) transcription factor has contradictory roles in cancer, which can act as a tumor suppressor or a proto-oncogene in different cell conditions (depending on the cell type and the conditions of the cell environment). Nrf2 pathway regulates several cellular processes, including signaling, energy metabolism, autophagy, inflammation, redox homeostasis, and antioxidant regulation. As a result, it plays a crucial role in cell survival. Conversely, Nrf2 protects cancerous cells from apoptosis and increases proliferation, angiogenesis, and metastasis. It promotes resistance to chemotherapy and radiotherapy in various solid tumors and hematological malignancies, so we want to elucidate the role of Nrf2 in cancer and the positive point of its targeting. Also, in the past few years, many studies have shown that Nrf2 protects cancer cells, especially leukemic cells, from the effects of chemotherapeutic drugs. The present paper summarizes these studies to scrutinize whether targeting Nrf2 combined with chemotherapy would be a therapeutic approach for leukemia treatment. Also, we discussed how Nrf2 and NF-κB work together to control the cellular redox pathway. The role of these two factors in inflammation (antagonistic) and leukemia (synergistic) is also summarized.
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| 8. |
- Kopsida, Maria, et al.
(författare)
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RhoB expression associated with chemotherapy response and prognosis in colorectal cancer
- 2024
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Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients.Materials and methods: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data.Results: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration.Conclusion: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.
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| 9. |
- Magan Barre, Mustafa, et al.
(författare)
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CAFs affect the proliferation and treatment response of head and neck cancer spheroids during co-culturing in a unique in vitro model
- 2020
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Ingår i: Cancer Cell International. - : BMC. - 1475-2867. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors for which the overall survival rate worldwide is around 60%. The tumor microenvironment, including cancer-associated fibroblasts (CAFs), is believed to affect the treatment response and migration of HNSCC. The aim of this study was to create a biologically relevant HNSCC in vitro model consisting of both tumor cells and CAFs cultured in 3D to establish predictive biomarkers for treatment response, as well as to investigate the impact of CAFs on phenotype, proliferation and treatment response in HNSCC cells. Methods Three different HNSCC patient-derived tumor cell lines were cultured with and without CAFs in a 3D model. Immunohistochemistry of the proliferation marker Ki67, epidermal growth factor receptor (EGFR) and fibronectin and a TUNEL-assay were performed to analyze the effect of CAFs on both tumor cell proliferation and response to cisplatin and cetuximab treatment in tumor spheroids (3D). mRNA expression of epithelial-mesenchymal transition (EMT) and cancer stem cells markers were analyzed using qRT-PCR. Results The results demonstrated increased cell proliferation within the tumor spheroids in the presence of CAFs, correlating with increased expression of EGFR. In spheroids with increased expression of EGFR, a potentiated response to cetuximab treatment was observed. Surprisingly, an increase in Ki67 expressing tumor cells were observed in spheroids treated with cisplatin for 3 days, correlating with increased expression of EGFR. Furthermore, tumor cells co-cultured with CAFs presented an increased EMT phenotype compared to tumor cells cultured alone in 3D. Conclusion Taken together, our results reveal increased cell proliferation and elevated expression of EGFR in HNSCC tumor spheroids in the presence of CAFs. These results, together with the altered EMT phenotype, may influence the response to cetuximab or cisplatin treatment.
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| 10. |
- Pérez-Díaz, Sergio, et al.
(författare)
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The potential role of collagen type VII in breast cancer proliferation
- 2024
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Ingår i: Cancer Cell International. - : Springer Nature. - 1475-2867. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue.Materials and methods: Screening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue.Results: Dormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6+/ ColVIIhigh compared with Int-α6-/ ColVIIlow AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVIIhigh-expressing cells were predominantly myoepithelial cells.Conclusion: ColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.
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