• BMB Reports
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• v.53 no.4
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• pp.173-180
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• 2020

Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

• BMB Reports
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• v.56 no.5
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• pp.287-295
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• 2023

The tumor microenvironment (TME) is a complex system composed of many cell types and an extracellular matrix (ECM). During tumorigenesis, cancer cells constantly interact with cellular components, biochemical cues, and the ECM in the TME, all of which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrate elasticity and biomechanical forces in tumor progression and metastasis. However, the mechanisms underlying the cell response to mechanical signals-such as extrinsic mechanical forces and forces generated within the TME-are still relatively unknown. Moreover, having a deeper understanding of the mechanisms by which cancer cells sense mechanical forces and transmit signals to the cytoplasm would substantially help develop effective strategies for cancer treatment. This review provides an overview of biomechanical forces in the TME and the intracellular signaling pathways activated by mechanical cues as well as highlights the role of mechanotransductive pathways through mechanosensors that detect the altering biomechanical forces in the TME.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4225-4231
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• 2014

Aim: To determine prognostic value of blood parameters on overall and progression-free survival in cases received adjuvant radiotherapy and chemotherapy with diagnosis of stage I-III breast cancer. Materials and Methods: We retrospectively reviewed files of 350 patients with non-metastatic breast cancer who were treated in the Radiation Oncology Department of Kayseri Teaching Hospital between 2005 and 2010. Pretreatment white blood cell (WBC), neutrophil, monocyte, basophil and eosinophil counts, and the neutrophil/lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were recorded. The relationship between clinicopathological findings and blood parameters was assessed. Results: Overall, 344 women and 6 men were recruited. Median age was $55.3{\pm}0.3$ years (range: 22-86). Of the cases, 243 (61.4%) received radiotherapy while 329 (94.3%), received chemotherapy and 215 (61.4%) received hormone therapy. Mean overall survival (OS) and progression-free survival (PFS) was 84.4 and 78.8 months, respectively. During follow-up, 48 patients died due to either disease-related or non-related causes. Local recurrence was detected in 14 cases, while distant metastasis was noted in 45 cases. In univariate analysis, age, pathology, perinodal invasion were significantly associated with overall survival, whereas gender, stage and hormone therapy were significantly associated with progression-free survival. In multivariate analysis, histopathological diagnosis (OR: 0.3; 95%: 0.1-0.7; p=0.006) and perinodal invasion (OR: 0.1; 95% CI: 0.1-1.3; p=0.026) were significantly associated with overall survival, whereas tumor stage (OR: 2.1; 95% CI: 0.0-0.7; p=0.014) and hormone therapy (OR: 2.1; 95%: 1.2-3.8; p=0.010) were significantly associated with progression-free survival. Conclusions: It was found that serum inflammatory markers including WBC, neutrophil, lymphocyte and monocyte counts, and NLR and PLR had no effect on prognosis in patients with breast cancer who underwent surgery and received adjuvant radiotherapy and chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6615-6619
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• 2015

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8047-8052
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• 2016

Proteases are important molecules that are involved in many key physiological processes. Protease signaling pathways are strictly controlled, and disorders in protease activity can result in pathological changes such as cardiovascular and inflammatory diseases, cancer and neurological disorders. Many proteases have been associated with increasing tumor metastasis in various human cancers, suggesting important functional roles in the metastatic process because of their ability to degrade the extracellular matrix barrier. Proteases are also capable of cleaving non-extracellular matrix molecules. Inhibitors of proteases to some extent can reduce invasion and metastasis of cancer cells, and slow down cancer progression. In this review, we focus on the role of a few proteases and their inhibitors in tumors as a basis for cancer prognostication and therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7015-7019
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• 2014

Metabolism lies at the heart of cell biology. The metabolism of cancer cells is significantly different from that of their normal counterparts during tumorigenesis and progression. Elevated glucose metabolism is one of the hallmarks of cancer cells, even under aerobic conditions. The Warburg effect not only allows cancer cells to meet their high energy demands and supply biological materials for anabolic processes including nucleotide and lipid synthesis, but it also minimizes reactive oxygen species production in mitochondria, thereby providing a growth advantage for tumors. Indeed, the mitochondria also play a more essential role in tumor development. As information about the numorous microRNAs has emerged, the importance of metabolic phenotypes mediated by microRNAs in cancer is being increasingly emphasized. However, the consequences of dysregulation of Warburg effect and mitochondrial metabolism modulated by microRNAs in tumor initiation and progression are still largely unclear.

• Genomics & Informatics
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• v.16 no.4
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• pp.18.1-18.9
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• 2018

Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8579-8587
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• 2016

Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$/P65) and interleukin-1 beta (IL-$1{\beta}$) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$/P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and $184.98{\pm}18.18$, respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and $171.76{\pm}7.58$, respectively) and controls ($0.70{\pm}0.02$ and $65.34{\pm}6.41$, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$/P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$, $0.79{\pm}0.03$ and $247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ( $139.14{\pm}5.83$, $0.34{\pm}0.02$ and $184.23{\pm}37.75$, respectively) and controls ($33.95{\pm}3.11$, $0.11{\pm}0.02$ and $7.83{\pm}0.92$, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2023-2028
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• 2013

A number of studies have indicated that Nurr1, which belongs to a novel class of orphan nuclear receptors (the NR4A family), is important for carcinogenesis. Here we investigated expression of Nurr1 protein in benign and malignant human prostate tissues and association with clinicopathologic features using immunohistochemical techniques. Moreover, we also investigated the ability of Nurr1 to influence proliferation, migration, invasion and apoptosis of human prostate cancer cells using small interfering RNA silencing. Immunohistochemical analysis revealed that the expression of Nurr1 protein was higher in prostate cancer tissues than in benign prostate tissue (P<0.001), levels being positively correlated with tumor T classification (P = 0.003), N classification (P = 0.017), M classification (P = 0.011) and the Gleason score (P = 0.020) of prostate cancer patients. In vitro, silencing of endogenous Nurr1 attenuated cell proliferation, migration and invasion, and induced apoptosis of prostate cancer cells. These results suggest that Nurr1 may be used as an indicator for prostate cancer progression and be useful for novel potential therapeutic strategies.

• BMB Reports
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• v.53 no.3
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• pp.125-132
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• 2020

Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca²⁺ distribution. The resulting dysregulation of multiple downstream effectors, depending on Ca²⁺ homeostasis, is associated with hallmarks of cancer pathophysiology, including enhanced proliferation, survival and invasion of cancer cells. These findings indicate that TRP channels affect multiple events that control cellular fate and play a key role in cancer progression. This review discusses the accumulating evidence supporting the role of TRP channels in tumorigenesis, with emphasis on prostate cancer.