| 1. |
- Ansari, Daniel, et al.
(författare)
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Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
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Forskningsöversikt (refereegranskat)abstract
- The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.
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| 2. |
- Ansari, Daniel, et al.
(författare)
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The hippo signaling pathway in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
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Forskningsöversikt (refereegranskat)abstract
- Hippo signaling is a key regulator of organ size, tissue hemostasis and regeneration. Dysregulation of the Hippo pathway has been recognized in a variety of human cancers, including pancreatic cancer. YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the two major downstream effectors of the Hippo pathway. YAP and TAZ have been found to promote pancreatic tumor development and progression, even in the absence of mutant Kirsten RAS (KRAS). Pancreatic cancer is associated with an abundant stromal reaction leading to tumor growth and immune escape. It has been found that YAP and TAZ modulate behavior of pancreatic stellate cells and recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. Moreover, YAP and TAZ are associated with chemoresistance and poor prognosis in pancreatic cancer. This review dissects the role of Hippo signaling in pancreatic cancer, focusing on molecular mechanisms and prospects for future intervention.
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| 3. |
- Ansari, Daniel, et al.
(författare)
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The role of PEDF in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
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Forskningsöversikt (refereegranskat)abstract
- Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.
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| 4. |
- Dimberg, Jan, et al.
(författare)
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Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:9, s. 4933-4940
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.
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| 5. |
- Hu, Dingyuan, et al.
(författare)
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The Emerging Role of Calcium-activated Chloride Channel Regulator 1 in Cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 39:4, s. 1661-1666
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Forskningsöversikt (refereegranskat)abstract
- Calcium-activated chloride channel regulator 1 (CLCA1) belongs to a group of secreted self-cleaving proteins, which activate calcium-dependent chloride channels. CLCA1 has been shown to participate in the pathogenesis of inflammatory airway diseases such as asthma. Recently, additional functions of CLCA1 have been unveiled, including its metalloprotease property and involvement in mucus homeostasis and immune modulation. Emerging evidence suggests that CLCA1 may also be involved in the pathophysiology of colorectal, pancreatic and ovarian cancer. There is growing interest in utilizing CLCA1 as a diagnostic, prognostic and predictive biomarker, as well as a potential therapeutic target. In this review, the functional role of CLCA1, with a particular focus on cancer, is described.
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| 6. |
- Shamoun, Levar, et al.
(författare)
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Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:1, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFa, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.
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| 7. |
- Song Van, Nguyen, et al.
(författare)
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Gene Polymorphism of Matrix Metalloproteinase-12 and-13 and Association with Colorectal Cancer in Swedish Patients
- 2013
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33, s. 3247-3250
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been widely reported that matrix metalloproteinases (MMPs) have fundamental roles in pathological processes in cancer through degradation of basal membranes and extracellular matrix. For MMP12 and MMP13, a functional single nucleotide polymorphism (SNP) has been detected -82A -> G (rs2276109) and -77A -> G (rs2252070), respectively. These SNPs are suggested to have an influence on different diseases. The present study evaluated the association between these SNPs in patients with colorectal cancer (CRC) patients and healthy controls. Patients and Methods: Using the TaqMan system, these SNPs were screened in 385 patients with CRC and 619 controls. Results: No significant difference in genotype distribution or in allelic frequencies was found between the two groups. However, we showed that the AA MMP-12 genotype is connected with a higher risk of disseminated CRC (Odds Ratio=1.77; 95% Confidence Interval=1.11-2.81, p=0.018). Conclusion: The results of this study suggest that the -82A -> G (rs2276109) polymorphism of the MMP12 gene reflects clinical outcome of patients with CRC.
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| 8. |
- Spelt, Lidewij, et al.
(författare)
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The prognostic role of cancer stem cell markers for long-term outcome after resection of colonic liver metastases
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:1, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. Materials and Methods: Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. Results: CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. Conclusion: CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy.
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| 9. |
- Ansari, Daniel, et al.
(författare)
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Analysis of MUC4 Expression in Human Pancreatic Cancer Xenografts in Immunodeficient Mice.
- 2014
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Ingår i: Anticancer research. - 1791-7530. ; 34:8, s. 3905-3910
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Tidskriftsartikel (refereegranskat)abstract
- Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
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| 10. |
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