DigitalUM :: Browsing by Subject "Tumor"

Browsing by Subject "Tumor"

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Open Access
Are hyaluronan receptors involved in three-dimensional cell migration.
(Murcia : F. Hernández, 2000) Nehls, V.; Hayen, W.
Hyaluronan (HA), an unbranched polysaccharide consisting of repeated glucuronic acid/Nacetylglucosamine disaccharide units, is ubiquitously present in the extracellular matrix of many tissues (for a more comprehensive review see: Fraser et al., 1997). Increased amounts of hyaluronan are produced by solid tumors and tumor-associated fibroblasts, and tumorinduced HA is correlated with poor prognosis. HA is well known to stimulate the migration of a large variety of cell types. Stimulation of cell migration by HA has been explained by different mechanisms. HA was shown to specifically bind to cell surface receptors, and inhibition of HA-receptor function was demonstrated to decrease cell migration and tumor growth. On the other hand, HA as a large hydrophilic molecule is also known to modulate the extracellular packing of collagen and fibrin, leading to increased fiber size and porosity of extracellular substrates. Hence a modified matrix architecture might similarly account for increased locomotion of cells. In this review, we attempted to summarize the available data on HA-induced cell migration, with particular emphasis on the role of HA receptors in three-dimensional cell migration. Although the HA receptor CD44 has been shown to mediate migration of cells over two-dimensional hyaluronancoated surfaces in vitro, there is only little evidence that HA-binding to CD44 or other HA receptors has major impact on the locomotion of cells through threedimensional matrices in vivo. We showed recently that the promigratory effect of HA in fibrin gels is largely due to HA-mediated modulation of fibrin polymerization. By increasing the porosity of fibrin gels, HA strongly accelerates cell migration. The porosity of matrices therefore appears as an important and probably underestimated determinant of cell migration and tumor spread.
Open Access
Autophagy in the immunosuppressive perivascular microenvironment of glioblastoma
(MDPI, 2019-12-31) Molina Gallego, María Luisa; Martínez Pérez, Salvador; García Bernal, David; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.
Open Access
Chaperone-mediated autophagy ablation in pericytes reveals new glioblastoma prognostic markers and efficient treatment against tumor progression
(2022-03-18) Molina Gallego, María Luisa; Aparicio, Pedro; Moraleda, José M.; Martínez, Salvador; García Bernal, David; Rubio Pedraza, Gonzalo; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment. Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared. Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination. Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.
Open Access
Editorial: Wnt Signaling in Immune Cell Regulation During Microbial Infection and Cancer
(Frontiers, 2020-06-05) Blumenthal, Antje; Mc Bride, Jere W; Carson, Dennis A; Sen, Malini; Martín-Orozco Santiago, María Elena; Bioquímica y Biología Molecular B e Inmunología
Open Access
Expression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Tanaka, Natsuki; Izawa, Takeshi; Takenaka, Shigeo; Akiyoshi, Hideo; Yamate, Jyoji; Kuwamura, Mitsuru
Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for hemorrhagic hydrocephalus mouse which shows hydrocephalus with frequent brain hemorrhage and formation of subcortical band heterotopia. A previous study revealed that Ccdc85C protein is expressed in the systemic simple epithelial cells with proliferative activity in rats and suggested that Ccdc85C expression may be related to the cell proliferation of simple epithelial cells. To reveal the roles of Ccdc85C in the proliferative lesion, we examined the expression patterns of Ccdc85C in the mammary gland tumor of dogs, a common representative tumor derived from simple epithelial cells. In canine mammary gland tumors, Ccdc85C was expressed at the apical junctions of the luminal epithelial cells. Ccdc85C was also distributed throughout the entire cytoplasm of the myoepithelial cells. Ccdc85C expression was observed at the epithelial cells with luminal structures, but was not observed at the epithelial cells forming sheet growth pattern without luminal structure. In carcinomas, Ccdc85C expression in mammary tumor tissue tended to be weaker than that in surrounding normal mammary gland tissue. Ccdc85C is known to cause neurological diseases such as hydrocephalus, and subcortical heterotopia, and the present study is the first to demonstrate Ccdc85C expression in canine mammary tumors and a relationship between Ccdc85C expression and tumor malignancy
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Función renal a largo plazo en supervivientes de tumor de Wilms
(Sociedad Española de Cirugía Pediátrica, 2019) Sánchez-Sánchez, A.; Girón Vallejo, Óscar; Ruiz Pruneda, R.; Fernández Ibieta, M.; Villamil, V.; Giménez Aleixandre, M.C.; Montoya-Rangel, C.A.; Fuster Soler, José Luis; Pascual Gázquez, J.F.; Ortega García, Juan Antonio; Hernández Bermejo, Juan Pedro; Cirugía, Pediatría y Obstetricia y Ginecología; Facultad de Medicina
Objetivos. Evaluar la función renal y la morbimortalidad a largo plazo, en supervivientes de tumor de Wilms (TW) no sindrómico. Material y métodos. Estudio retrospectivo de pacientes con TW entre 1993-2017 tratados según protocolos SIOP. Evaluamos mortalidad, filtrado glomerular (FG), prevalencia de hipertensión arterial (HTA), necesidad de diálisis y trasplante renal. Se definió enfermedad renal crónica (ERC) como FG <90 ml/min/1,73 m2. Resultados. En los 25 años analizados se trataron 39 pacientes con edad media diagnóstica de 3,6 años (0,3-11 años). Mediana de seguimiento 6 años (0,5-21 años). El 48% (19 pacientes) debutaron con estadio I o II. Cuatro pacientes presentaron histología de alto riesgo (10%). La mortalidad fue del 10%. El 16% (6 pacientes) desarrolló ERC (grados I-II). Ningún paciente precisó terapia renal sustitutoria (TRS) o trasplante. La presencia de ERC tanto en enfermedad unilateral como bilateral fue del 16%, p>0,05; OR 1,04 (IC 95% 0,09-10,9). Se obtuvieron idénticos resultados (16%) comparando pacientes que recibieron radioterapia frente a aquellos que no. Los pacientes en estadio I, II y III presentaron una prevalencia de ERC del 11% vs. 40% en estadio IV (p=0,12); OR 5,3 (IC 95% 0,61-45). Ningún paciente asoció HTA crónica. Conclusiones. En el presente estudio la prevalencia de ERC en supervivientes de TW no sindrómico es baja pero no desdeñable, aunque ninguno precisó trasplante renal o TRS. La presencia de enfermedad bilateral y la radioterapia no se asociaron al desarrollo de ERC. La enfermedad metastásica condiciona un riesgo mayor de ERC.
Open Access
Glioblastoma progression is assisted by induction of immunosuppressive function of pericytes through interaction with tumor cells
(Impact Journals, 2017-08-02) Bueno, Carlos; Moraleda, José M.; Macián, Fernando; Martínez, Salvador; Ródenas García, Mónica; García Bernal, David; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
The establishment of immune tolerance during Glioblastoma Multiforme (GBM) progression, is characterized by high levels expression of anti-inflammatory cytokines, which suppress the function of tumor assocciated myeloid cells, and the activation and expansion of tumor antigen specific T cells. However, the mechanisms underlying the failed anti-tumor immune response around the blood vessels during GBM, are poorly understood. The consequences of possible interactions between cancer cells and the perivascular compartment might affect the tumor growth. In this work we show for the first time that GBM cells induce immunomodulatory changes in pericytes in a cell interaction-dependent manner, acquiring an immunosuppresive function that possibly assists the evasion of the anti-tumor immune response and consequently participates in tumor growth promotion. Expression of high levels of anti-inflammatory cytokines was detected in vitro and in vivo in brain pericytes that interacted with GBM cells (GBC-PC). Furthermore, reduction of surface expression of co-stimulatory molecules and major histocompatibility complex molecules in GBC-PC correlated with a failure of antigen presentation to T cells and the acquisition of the ability to supress T cell responses. In vivo, orthotopic xenotransplant of human glioblastoma in an immunocompetent mouse model showed significant GBM cell proliferation and tumor growth after the establishment of interspecific immunotolerance that followed GMB interaction with pericytes.
Open Access
Glycosylation and lectins-examples of immunesurveillance and immune evasion
(Murcia : F. Hernández, 2004) Müller, I.; Jenner, J.; Handgretinger, R.; Riberdy, J.; Kerst, G.
Cell surface proteins are posttranslationally modified by tightly regulated enzymes of glycosylation. Typical patterns of glycosylation may signal pathological situations to the immune system. Here, carbohydrate receptors on the surface of cells in the immune system are involved in regulation of effector cells. Moreover, some lectins are circulating in the plasma and take part in host defense. The code of carbohydrate modifications is impaired in malignant cells and yet they are not eliminated. In this review, we focus on recent experimental evidence for regulatory functions of lectins and carbohydrate derivatives in the immune system and tumours.
Open Access
Grading lung neuroendocrine tumors: Controversies in search of a solution
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Pelosi, Giuseppe; Pattini, Linda; Morana, Giovanni; Fabbri, Alessandra; Faccinetto, Alex; Fazio, Nicola; Valeri, Barbara; Sonzogni, Angelica
Background. Pathological grading of tumors is a way to measure biological aggressiveness. In lung neuroendocrine tumors (NET), grading is tautologically included into the current 2015 WHO histologic classification. Little is known, however, about alternative grading systems in lung NET. Methods. Through an extensive search of the English literature on lung NET (updated to April 2016), the following key questions were addressed: a) current concepts of grading; b) clinicians’ requests for grading; c) functional parameters for grading; d) Ki-67 labeling index (LI) for grading; e) towards an effective pathology grading system. Results. There is some room for inconsistency in the histologic classification of lung NET, likely due to the varying attribution of defining criteria. Innovative diffusion-weighted imaging upon magnetic resonance or molecular analysis could help separate indolent from aggressive lung NET, thus integrating a grading approach other than histology. Troubles in the clinical handling of metastatic or individual tumors when relying on morphology alone support the development of a lungspecific grading system for the more accurate prediction of prognosis and planning therapy in individual patients. To integrate the 2015 WHO classification using innovative grading based on Ki-67 LI, mitotic count and necrosis, a new proposal is emerging where three categories of lung NET are identified, namely Lu-NET G1, Lu-NET G2 and Lu-NET G3, which would allow tumors with similar behavior and therapy to be better handled according to their own biological potential. Conclusion. A new formulation of lung NET grading could have clinical relevance for the individual handling of patients. Key words:
Open Access
Hypoxia-inducible factor (HIF) in human tumorigenesis
(Murcia : F. Hernández, 2007) Mabjeesh, N.J.; Amir, S.
Hypoxia is a major event that occurs in most solid tumors. Intratumoral hypoxia is sufficient to activate the key transcription factor, hypoxia-inducible factor (HIF) that mediates the activation of the “survival machinery” in cancer cells. HIF can also be induced by oxygen-independent genetic alterations that activate a variety of oncogenic signaling pathways or inactivate tumor suppressors. Increased tumor HIF occurs at early stages of carcinogeniesis and is often correlated with increased angiogenesis, malignant progression, poor patient prognosis and chemoradio-resistance. HIF-a subunit, the oxygen-regulated subunit of HIF is overexpressed in a wide range of human solid tumors. Nuclear HIF-a protein immunostaining was restricted to tumor cells compared to normal tissues. Herein, we review and discuss the role of HIF in tumorigenesis and describe the overexpression of HIF-a proteins in human cancers and its association with overall clinical outcomes
Open Access
Lymph node lymphangiogenesis, a new concept for modulating tumor metastasis and inflammatory process
(Murcia : F. Hernández, 2009) Ji, R.C.
The proliferation of lymphatic endothelial cells (LECs) occurs not only in tumor and inflamed tissues, but also in regional draining lymph nodes (LNs). The lymph node lymphangiogenesis (LNLG) has recently emerged as a prominent area in biomedical research, because it is involved in the pathogenesis of several human diseases. The LEC functional features and lymphatic remodeling regulated by lymphangiogenic factors actively promote tumor metastasis and the inflammation process. VEGFA/ VEGFR-2 and VEGF-C/-D/VEGFR-3 have been implicated as the prime mediators in inflammation- or tumor-induced LNLG. This knowledge may provide a foundation for further understanding of specific modification in the gene expression, cell migration, and differentiation of LECs and other cells in lymphaticassociated diseases. Importantly, it should be taken into consideration that inflammation and lymphangiogenesis are strongly linked in the formation and metastasis of cancer when designing therapeutic strategies.
Open Access
MDM2 beyond cancer: podoptosis, development, inflammation, and tissue regeneration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Ebrahim, Martrez; Mulay, Shrikant R.; Anders, Hans-Joachim; Thomasova, Dana
Murine double minute (MDM)-2 is an intracellular molecule with diverse biological functions. It was first described to limit p53-mediated cell cycle arrest and apoptosis, hence, gain of function mutations are associated with malignancies. This generated a rationale for MDM2 being a potential therapeutic target in cancer therapy. Meanwhile, several additional functions and pathogenic roles of MDM2 have been identified that either enforce therapeutic MDM2 blockade or raise caution about potential side effects. MDM2 is also required for organ development and tissue homeostasis because unopposed p53 activation leads to p53-overactivation-dependent cell death, referred to as podoptosis. Podoptosis is caspaseindependent and, therefore, different from apoptosis. The mitogenic role of MDM2 is also needed for wound healing upon tissue injury, while MDM2 inhibition impairs re-epithelialization upon epithelial damage. In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. Therefore, MDM2 promotes tissue inflammation and MDM2 inhibition has potent antiinflammatory effects in tissue injury. Here we review the biology of MDM2 in the context of tissue development, homeostasis, and injury and discuss how the divergent roles of MDM2 could be used for certain therapeutic purposes. MDM2 blockade had mostly antiinflammatory and anti-mitotic effects that can be of additive therapeutic efficacy in inflammatory and hyperproliferative disorders such as certain cancers or lymphoproliferative autoimmunity, such as systemic lupus erythematosus or crescentic glomerulonephritis.
Open Access
Mesenchymal stem cell-derived microRNAs: friends or foes of tumor cells?
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Harrell, Carl Randall; Djonov, Valentin; Volarevic, Vladislav
Mesenchymal stem cell (MSC)-dependent biological effects in the tumor microenvironment mainly rely on the activity of MSC-sourced microRNAs (MSCmiRNAs) which modulate protein synthesis in target tumor cells, endothelial cells and tumor-infiltrated immune cells, regulating their phenotype and function. Several MSC-sourced miRNAs (miR-221, miR-23b, miR-21-5p, miR-222/223, miR-15a miR-424, miR-30b, miR-30c) possess tumor-promoting properties and are able to enhance viability, invasiveness and metastatic potential of malignant cells, induce proliferation and sprouting of tumor endothelial cells and suppress effector functions of cytotoxic tumor-infiltrated immune cells, crucially contributing to the rapid growth and progression of tumor tissue. On the contrary, MSCs also produce “anti-tumorigenic” miRNAs (miR-100, miR222-3p, miR-146b miR-302a, miR-338-5p, miR-100-5p and miR-1246) which suppress tumor growth and progression by: up-regulating expression of chemoresistance-related genes in tumor cells, by suppressing neo-angiogenesis and by inducing generation of tumorotoxic phenotypes in tumor-infiltrated lymphocytes. In this review article, we summarize the current knowledge about molecular mechanisms that are responsible for MSC-miRNA-dependent alterations of intracellular signaling in tumor and immune cells and we discuss different insights regarding the therapeutic potential of MSC-derived miRNAs in cancer treatment.
Open Access
Pathogenetic mechanisms of nuclear pleomorphism of tumour cells based on the mutator phenotype theory of carcinogenesis
(Murcia : F. Hernández, 2003) Bignold, L.P.
The nuclei of the cells of most solid tumours in histopathologic preparations vary in size, shape and chromatin pattern, both from normal nuclei and from each other. These features have not been explained in terms of conventional concepts of nuclear structure and theories of carcinogenesis. In recent years, the unfolded chromosomes have been shown to occupy "domains" in the nucleus during interphase, providing a relatively uniform density of fine chromatin fibres throughout the nucleus in the living state. This is in contrast to the appearances of interphase chromatin existing as coarse clumps and fibres (heterochromatin and euchromatin respectively) as are seen in histologic preparations. Additionally, the binding of chromatin to nuclear membrane, the possible existence of a nuclear matrix, the functions of nuclear pores, and the attachments of cytoskeletal structures to the outer nuclear membrane are now recognised. Studies of genetic instability of cancer cells (many random mutations are present in the genome, which vary from nucleus-to-nucleus in individual tumours) have shown that this phenomenon occurs early in tumour formation, can be present in morphologically-normal cells adjacent to tumours, and can result in thousands of genomic events per tumour cell. These observations form the basis for the mutator phenotype/clonal selection theory of carcinogenesis, which proposes that genetic instability is an essential early part of carcinogenesis. Genetic instability has been used to explain significant cell-to-cell variability of behaviour (tumour cell heterogeneity) among cells of individual tumours. This paper proposes that a high incidence of nucleus-to-nucleus-variable mutation of the genes for factors controlling nuclear morphology in tumours can explain nucleus-to-nucleus variations of histopathologic appearance of these nuclei when some additional effects of histological processing are taken into account.
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Platelet glycoprotein Ibα supports experimental lung metastasis
(National Academy of Sciences, 2007-05-22) Guerrero López, José Antonio; Jain, Shashank; Zuka, Masahiko; Liu, Jungling; Russell, Susan; Dent, Judith; Forsyth, Jane; Maruszak, Brigid; Gartner, T. Kent; Felding-Habermann, Brunhilde; Ware, Jerry; Medicina Interna; Facultad de Medicina
The platelet paradigm in hemostasis and thrombosis involves an initiation step that depends on platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. The platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process and initiates the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis paradigm is emerging with significant platelet contributions in both tumorigenesis and inflammation. We have established congenic (N10) mouse colonies (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP Ib-IX contributes to experimental metastasis because a functional absence of GP Ib-IX correlates with a 15-fold reduction in the number of lung metastatic foci using B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of the α-subunit of GP Ib is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy.
Open Access
Primary perivascular epithelioid cell tumor of the liver not related to hepatic ligaments, Hepatic PEComa as an emerging entity
(Murcia : F. Hernández, 2008) Zimmermann, Arthur; von der Brelie, Christian; Berger, Barbara; Kappeler, Andreas; Candinas, Daniel
Primary perivascular epithelioid cell tumor (PEComa) of the liver is a very rare example of an emerging family of hepatic PEC tumors. Only few cases have been described so far. We report the case of a large but benign hepatic PEComa in a 53-year-old man without signs of tuberous sclerosis. In contrast to recently described PEC-derived liver tumors in children and young adults, this neoplasm was not related to the hepatic ligaments but had developed deeply within the liver substance. The neoplastic cells displayed the complete phenotype typical for PEComas, i.e. reactivity for several melanoma markers and for smooth muscle actin. The unique relationship of myoid tumor cells to the adventitia of blood vessels prompted us, in comparison with published findings obtained with angiomyolipomas, to comment on the possible origin of the still enigmatic perivascular epithelioid cells.
Open Access
PTTG and cancer
(Murcia : F. Hernández, 2003) Hamid, T.; Kakar, S.S.
Pituitary tumor transforming gene (pttg) is a recently isolated oncogene that is expressed in most of the tumors. Overexpression of pttg results in an increase in cell proliferation, induces cell transformation in vitro, and promotes tumor formation in nude mice. The gene encodes a protein of 202 amino acids with no significant homology with other known proteins. The protein is a multi domain consisting of a transactivation domain, domain required for ubiquitin-mediated proteolysis and a DNA binding domain. pttg protein is bestowed with a multitude of functions and seems to be involved in most of the important mechanisms of cell proliferation, differentiation and signaling. Given the number of processes that are involved in the manifestation of cancer, it thus becomes mandatory to study the role of this potent oncogene in relation to the processes of cell survival, death and functioning.
Open Access
The antitumor action of cannabinoids on glioma tumorigenesis
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Zogopoulos, Panagiotis; Korkolopoulou, Penelope; Patsouris, Efstratios; Theocharis, Stamatios
Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2). Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain. Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration. We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.
Open Access
The role of TET family proteins and 5-hydroxymethylcytosine in human tumors
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Wu, Yi-Chen; Ling, Zhi-Qiang
Tumorigenesis correlates with hypermethylation of tumor suppressors and hypomethylation of oncogenes. DNA methyltransferases (DNMTs) catalyze DNA methylation, and mutations and aberrant expression in DNMT genes are found in multiple human tumors. The discovery of the DNA demethylation function of TET proteins has opened up new avenues for the study of DNA methylation regulation. TET proteins regulate the DNA demethylation pathway through oxidizing 5-mC into 5-hmC, 5-fC, and 5-aC. TET genes have been reported to be frequently mutated in hematopoietic malignancies and are associated with the malignant transformation of cells. Loss-of-function mutations in TET genes have not been reported in human solid tumors. However, 5-hmC has been found to be reduced in various solid tumors, indicating that TET genes may contribute to cellular transformation via regulation of DNA demethylation. As a new epigenetic modification, 5-hmC may be a useful biomarker for the diagnosis of cancers. To better understand the roles of TET and 5-hmC in tumors, the biological functions of TET and 5-hmC should be studied further.
Open Access
Tumor glómico de la mano: una localización extradigital poco habitual
(Thieme Gruppe, 2014-05) Albaladejo, Francisco; Sánchez Angulo, P.; Hernández Torralba, M.; Martínez Díaz, Francisco; Redondo Carazo, M. V.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Los tumores glómicos representan el 2% de los tumores de la mano. Con mayor frecuencia se trata de tumoraciones únicas, situadas a nivel subungueal, a veces periungueal o en el tejido subcutáneo del pulpejo de los dedos. es infrecuente pero pueden afectarse varios dedos en el mismo paciente. la localización extra digital es poco habitual, haciendo aún más difícil su diagnóstico. Se presenta el caso de una paciente de 45 años con una tumoración redondeada de consistencia dura, situada en la base del pulgar a nivel de la eminencia tenar, de 5 años de evolución, que presentaba dolor a la presión e intolerancia al frío. Su extirpación solucionó la clínica y el estudio anatomo-patológico confirmó el diagnóstico.