DigitalUM :: Browsing by Subject "Tumorigenesis"

Browsing by Subject "Tumorigenesis"

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Open Access
Apoptosis regulating genes in neuroendocrine tumors
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Liu, W.-H.; Wang, D.-G.
Neuroendocrine turnors (NETs) are a heterogeneous group of neoplasms. They are relatively uncommon and characterised by a relatively indolent clinical course. The indolent nature of NETs has long been enigmatic and recent advances in apoptosis research have led to speculation regarding the role of programmed cell death in NET tumorigenesis. It is hoped that a fundamental molecular understanding will help explain these variant behaviors that are so evident to the clinician, and ultimately yield novel and more effecti ve therapies. Recent studies have demonstrated that deregulation of programmed cell death may be a critical component in the multistep tumorigenesis of NETs and that the frequent expression of the BCL-2 oncoprotein in these tumors may contribute to their pathogenesis. The genetic complementation of simultaneously deregulated BCL-2 and c-MYC may be implicated in the multistep tumorigenesis of human NETs. It is also clear that numerous cellular gene products can and will be shown to impact upon apoptosis in NETs; some of these may even be molecules identified as oncoproteins or tumor suppressors. The major challenge will be to ascribe primary pathogenetic significance to tumor-associated derangements in expression of these molecules, and hopefully to then exploit our knowledge toward therapeutic benefit.
Embargo
Chronodisruption and ambulatory circadian monitoring in cancer patients: beyond the body clock
(Springer, 2022-01-21) Almaida Pagán, Pedro Francisco; Torrente, Maria; Campos Martínez, Manuel; Provencio, Mariano; Madrid, Juan A; Franco, Fabio; Rodriguez Morilla, Beatriz; Cantos, Blanca; Sousa, Pedro A; Martinez Madrid, Maria J; Pimentao, Joao; Rol, Maria A; Fisiología
Purpose of Review Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. Recent Findings In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. Summary This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the stateof-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.
Open Access
Chronodisruption and ambulatory circadian monitoring in cancer patients: beyond the body clock
(Springer, 2022-01-21) Almaida Pagan, Pedro F.; Torrente, María; Campos Martínez, Manuel; Provencio, Mariano; Madrid, Juan Antonio; Franco, Fabio; Rodríguez Morilla, Beatriz; Cantos, Blanca; Sousa, Pedro A.; Martínez Madrid, María José; Pimentao, Joao; Rol de Lama, María de los Ángeles; Fisiología
Purpose of ReviewCircadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease.Recent FindingsIn recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications.SummaryThis review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.
Open Access
Clinical significance of stem cell marker CD133 expression in colorectal cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Bin-Bin; Li, Zhi-juan; Zhang, Feng-Feng; Hou, Hai-Tao; Yu, Jing-Kui; Li, Feng
Objective: CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. Methods: A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. Results: The percentage of CD133- positive (CD133+) tumor cell population ranged between 0.84% and16.75% (mean ratio=7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133+ colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stages, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133+ colorectal cancer HCT116 cellswere sufficient to form tumor xenografts, whereas 1x105 CD133- tumor cells failed to develop tumor xenografts in nude mice. Conclusions: CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.
Open Access
Clusterin expression in elastofibroma dorsi
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Aigelsreiter, Ariane; Pichler, Martin; Pixner, Thomas; Janig, Elke; Schuller, Monika; Lackner, Carolin; Scheipl, Susanne; Beham, Alfred; Regauer, Sigrid
Background: Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. Material and methods: Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. Results: Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/ collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/11 patients, for whom clinical data were available, reported trauma to the scapular region. Conclusion: Many investigated ED were associated with trauma, which supports a reactive/ degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.
Open Access
Cytoglobin expression of rectal subepithelial myofibroblasts: Significant alterations of cytoglobin+ stromal cells in long-standing ulcerative colitis
(F. Hernández y Juan F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Okayasu, Isao; Mikami, Tetuo; Yoshida, Tsutomu; Hana, Kiyomi; Yokozawa, Yokozawa; Sada, Miwa; Fujiwara, Mutsunori; Kawada, Norifumi
Cytoglobin/stellate cell activation-associated protein (Cygb/STAP), a hemoprotein, functions as part of an O2 reservoir with protective effects against oxidative stress in hepatic stellate cells. Heterogeneous expression of the neural cell adhesion molecule (NCAM)+ and/or α-smooth muscle actin (αSMA)+ has been noted in subepithelial myofibroblasts and interstitial cells of the same lineage in the colorectum. We have demonstrated that early genomic instability of both epithelial and stromal cells in ulcerative colitis (UC) is important for colorectal tumorigenesis, as well as for mucosal remodeling. To further clarify possible roles of stromal cells in mucosal remodeling and tumor development in UC, we here focused on Cygb expression of subepithelial myofibroblasts and interstitial cells, as well as αSMA and HSP47. Noncancerous mucosa of resected rectae from UC patients with or without colorectal neoplasia (14 and 20 cases, respectively) and of sporadic rectal cancer cases (16) was analyzed immunohistochemically, as well as by immuno-fluorescence and electron microscopy. The results, heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells, corresponding to rectal stellate cells, were demonstrated. A decrease of Cygb+ subepithelial myofibroblasts and an increase of αSMA+ interstitial cells were significant in UC, as compared to normal rectal mucosa. Furthermore, a decrease of Cygb+ subepithelial myofibroblasts, correlating with αSMA+ and HSP47+ cells, was significant in long-standing UC with neoplasia. In conclusion, there are heterogeneous phenotypes of Cygb+, αSMA+ and HSP47+ subepithelial myofibroblasts and interstitial cells in the rectal mucosa. Mucosal remodeling with alterations of Cygb+ and/or αSMA+/HSP47+ stromal cells might have some relation to UC-associated tumorigenesis.
Open Access
Downregulation of nuclear ING3 expression and translocalization to cytoplasm promotes tumorigenesis and progression in head and neck squamous cell carcinoma (HNSCC)
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Li, Xiaohan; Zhang, Qun; Zhang, Mingming; Luo, Yusong
ING3 (inhibitor of growth gene 3) is a member of the ING gene family, and is considered as a candidate tumor suppressor gene. In order to explore the roles of ING3 in tumorigenesis and cancer progression of head and neck squamous cell carcinoma (HNSCC), ING3 expression was assessed in 173 cases of HNSCC by immunohistochemistry. The expression of ING3 was also compared to clinicopathological variables, and the expression of several tumorigenic markers. Nuclear expression of ING3 in HNSCC was significantly lower than that in dysplasia and normal epithelium, and was negatively correlated with a poor-differentiated status, T staging and TNM staging. In contrast, cytoplasmic expression of ING3 was significantly increased in HNSCC, and was statistically associated with lymph node metastasis and 14-3-3η expression. In addition, nuclear expression of ING3 was positively correlated with the expression of p300, p21 and acetylated p53. In conclusion, decreases in nuclear ING3 may play important roles in tumorigenesis, progression and tumor differentiation in HNSCC. Increases in cytoplasmic ING3 may be due to 14-3-3η binding and may also be involved in malignant progression. Nuclear ING3 may modulate the transactivation of target genes, promoting apoptosis through interactions with p300 and p21. Moreover, ING3 may interact with p300 to upregulate the level of acetylation of p53, and promote p53- mediated cell cycle arrest, senescence and/or apoptosis. Therefore, ING3 may be a potential tumor suppressor and a possible therapeutic target in HNSCC
Open Access
EPH receptors in cancer
(Murcia : F. Hernández, 2008) Castaño, Julio; Davalos, Verónica; Schwartz Jr., Simo; Arango, Diego
EPH receptors and their ephrin ligands constitute the largest sub-family of receptor tyrosine kinases (RTKs) and are components of cell signaling pathways involved in animal development. The ability of the EPH/ephrin guidance system to position cells and modulate cell morphology underlies their various roles in development. In addition, EPH signaling plays an important role in oncogenic processes observed in several organs. These receptors are involved in a wide range of processes directly related with tumorigenesis and metastasis, including cell attachment and shape, migration, and angiogenesis. Accordingly, deregulation of EPH expression and signaling activity could be crucial for the tumorigenic process. This review focuses on EPH receptors’ roles in oncogenic transformation and tumor progression.
Open Access
Fibroblast growth factor receptors: multifactorial-contributors to tumor initiation and progression
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Feng, Shachuan; Zhou, Li; Collins Nice, Edouard; Huang, Canhua
Fibroblast growth factor receptors (FGFRs), encoded by four genes (FGFR1, FGFR2, FGFR3, and FGFR4) are tightly associated with many biological processes such as organ development, cell proliferation and migration. Studies over the past decades have validated the pivotal roles FGFRs play in tumorigenesis due to the regulation of diverse tumorigenesis-related processes, including cell survival, proliferation, inflammation, metastasis and angiogenesis. Interestingly, FGFR mutations in somatic cells leading to tumorigenesis and those in germ cells leading to developmental disorders are identical, suggesting that FGFR mutations result in different diseases due to their spatio-temporal expression. Thus, discoveries in developmental biology may also be applicable to cancer. FGFRs regulate the expression and/or the activity of a myriad of molecules (e.g. matrix metalloproteinases (MMPs) and Snail) that are tightly linked to tumorigenesis by four main signaling pathways (RASMAPK, PI3K-AKT, PLCγ-PIP2, and STAT), as well as other minor branches. Epigenetic and genetic alteration of FGFR genes, including DNA methylation, histone remodeling, microRNA regulation, single nucleotide polymorphisms (SNPs), gene missense mutations, amplification, and fusion of FGFRs with other genes, which result in gain or loss of FGFR function, have been identified in many types of cancer. In this review, we focus in particular on recent advances in the relationship between FGFR disorders and tumorigenesis.
Open Access
Pituitary tumor transforming gene: An important gene in normal cellular functions and tumorigenesis
(Murcia : F. Hernández, 2007) Bradshaw, C.; Kakar, S.S.
Pituitary tumor transforming gene (PTTG) is an oncogene which is found to be highly expressed in proliferating cells and in most of the tumors analyzed to date. Overexpression of PTTG induces cellular transformation and promotes tumor development in nude mice. PTTG is regulated by various growth factors including insulin and IGF-1. PTTG is a multifunctional and multidomain protein. Some of the functions of PTTG include inhibition of separation of sister chromatids, expression and secretion of angiogenic and metastatic factors. In this review we focus on expression of PTTG in normal and tumor tissues, define its biological function, its role in tumorigenesis, and its interaction with other proteins that may play important role in mediating tumorigenic function of PTTG.
Open Access
Role of isocitrate dehydrogenase 1/2 (IDH 1/2) gene mutations in human tumors
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Liu, Xiang; Ling, Zhi-Qiang
In recent years, frequent isocitrate dehydrogenase 1/2 (IDH1/IDH2) gene mutations were found in a variety of tumors, which specifically alter arginine residues of catalytic active site in IDH1/IDH2 and confer new enzymatic function of directly catalyzing alpha-ketoglutarate (α-KG) to R-2-hydroxyglutarate (2- HG). 2-HG could competitively inhibit α-KG–dependent enzymes and might therefore contribute to tumorigenesis. In addition, mutation status of IDH1/IDH2 is closely related to the progress and prognosis of certain tumors. Thus IDH1/IDH2 is considered to be a promising biomarker for early diagnosis and prognosis and targeted therapy. In this study, the current research on IDH1/IDH2 mutation, especially the mechanisms and clinical characteristics related to tumor, are reviewed.
Open Access
Roles of versican in cancer biology - tumorigenesis, progression and metastasis
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Du, William Weidong; Yang, Weining; Yee, Albert J.
Versican, a large extracellular matrix proteoglycan accumulates in tumor stroma and plays a key role in both malignant transformation and tumor progression. Increased versican expression has been observed in a wide range of malignant tumors, and has been associated with both cancer relapse and poor patient outcomes in breast, prostate, and many other cancer types. Through negatively-charged chondroitin and dermatan sulfate side chains or interactions of the G1 and G3 domains, versican is able to regulate many cellular processes including cell adhesion, proliferation, apoptosis, migration, angiogenesis, invasion and metastasis. In this review, the biological roles that versican plays in cancer development are presented. Therapeutic targeting of versican in malignant tumors is also discussed.
Open Access
Telomeres and telomerase. A survey about methods and recent advances in cancer diagnostic and therapy
(Murcia : F. Hernández, 2006) Weise, J.M.; Günes, Ç.
Since the discovery that telomerase is repressed in most normal human somatic cells but strongly expressed in most human tumours, telomerase emerged as an attractive target for diagnostic, prognostic and therapeutic purposes to combat human cancer. In this review, a synopsis of methods detecting telomerase is presented evaluating their potential for diagnostic and prognostic use. Also, the most promising telomerase therapeutics are discussed in the light of recent advances in the field.
Open Access
The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis
(Murcia: F. Hernández, 2010) Zuo, Guo-Wei; Kohls, Christopher D.; He, Bai-Cheng; Chen, Liang; Zhang, Wenli; Shi, Qiong; Zhang, Bing-Qiang; Kang, Quan; Luo, Jinyong; Luo, Xiaoji; Wagner, Eric R.; Kim, Stephanie H.; Restegar, Farbod; Haydon, Rex C.; Deng, Zhong-Liang; Luu, Hue H.; He, Tong-Chuan; Luo, Qing
The CCN proteins contain six members, namely CCN1 to CCN6, which are small secreted cysteine-rich proteins. The CCN proteins are modular proteins, containing up to four functional domains. Many of the CCN members are induced by growth factors, cytokines, or cellular stress. The CCNs show a wide and highly variable expression pattern in adult and in embryonic tissues. The CCN proteins can integrate and modulate the signals of integrins, BMPs, VEGF, Wnts, and Notch. The involvement of integrins in mediating CCN signaling may provide diverse contextdependent responses in distinct cell types. CCN1 and CCN2 play an important role in development, angiogenesis and cell adhesion, whereas CCN3 is critical to skeletal and cardiac development. CCN4, CCN5 and CCN6 usually inhibit cell growth. Mutations of Ccn6 are associated with the progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia tarda. In stem cell differentiation, CCN1, CCN2, and CCN3 play a principal role in osteogenesis, chondrogenesis, and angiogenesis. Elevated expression of CCN1 is associated with more aggressive phenotypes of human cancer, while the roles of CCN2 and CCN3 in tumorigenesis are tumor type-dependent. CCN4, CCN5 and CCN6 function as tumor suppressors. Although CCN proteins may play important roles in fine-tuning other major signaling pathways, the precise function and mechanism of action of these proteins remain undefined. Understanding of the biological functions of the CCN proteins would not only provide insight into their roles in numerous cellular processes but also offer opportunities for developing therapeutics by targeting CCN functions.
Open Access
The methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Feng, Xi; Shu, Liuping; Biología Celular e Histología
Cervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC in vivo. The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.
Open Access
The role of KMT2 gene in human tumors
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zhang, Zhi Long; Yu, Peng Fei; Ling, Zhi Qiang
Histone methylation plays a crucial role in the regulation of gene transcriptional expression, and aberration of methylation-modifying enzyme genes can lead to a variety of genetic diseases, including human cancers. The histone modified protein KMT2 (lysin methyltransferase) family are involved in cell proliferation, growth, development and differentiation through regulating gene expression, and are closely related with many blood cancers and solid tumors. In recent years, several studies have shown that mutations in the KMT2 gene occur frequently in a variety of human cancers and the mutation status of the KMT2 gene may be correlated with the occurrence, development and prognosis of some tumors. Research uncovering the clinical characteristics and molecular mechanisms of KMT2 mutation in human tumors will be helpful for early diagnosis and prognosis of tumors as well as drug development for targeted therapies.
Open Access
The transcription factor E2F: a crucial switch in the control of homeostasis and tumorigenesis
(Murcia : F. Hernández, 2006) Fang, Z.H.; Han, Z.C.
The transcription factor E2F plays a crucial role in governing cell proliferation through manipulation of the expression of many genes required for cell cycle progression. As studies are exploring in depth, E2F has grown into a multimember family and has been required for the regulation of a large number of genes involved in various cellular processes. The expanding E2F membership and biological function provide us some new insights relating to the evolution of E2F. One of them is to understand the exact mechanisms by which E2F executes in these different cellular processes during ontogenesis. This review summarizes recent advances in this field, with an emphasis on a notion that E2F acts as a molecular switch in the control of both normal cell and tumor development.

Browsing by Subject "Tumorigenesis"

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