DigitalUM :: Browsing by Subject "Cell proliferation"

Browsing by Subject "Cell proliferation"

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Open Access
A novel approach to the growth analysis of hamster secondary palate by histone 3 m RNA in situ hybridiration
(Murcia : F. Hernández, 1994) Shah, R.M.; Young, A.V.; Song, B.Z.; Wong, D.T.W.
A study was undertaken to determine the cell proliferation kinetics during the development of hamster vertical palatal shelf ad initium. Harnster embryo heads, obtained at different times between days 10 and 12 of gestation (which is the period of vertical shelf development) were processed and sectioned to localize histone 3 mRNA, a cell cycle specific gene, by in situ hybridization. Sense and antisense 35~-labelledh istone 3 riboprobes were used as hybridization probes. Percent labelled cells were determined. The results showed that a high rate of random proliferation of both epithelial and mesenchymal cells was a major component of early vertical palatal growth. Subsequently, during the latter half of vertical shelf development, the proliferation rates of the epithelial and mesenchymal cells were different in a region specific manner. It was suggested that the spatio-temporal changes in the distribution of cycling mesenchymal and epithelial cells during vertical palate development may indicate their heterogeneity for subsequent segregation into appropnate phenotypes.
Open Access
C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Li, Na; Liang, Xiao; Li, Jiawen; Li, Teng; Guo, Zuoming
Background. Colon cancer is one of the most common cancers with high incidence and high mortality. Chemokines play a crucial role in the development of cancer. Methods. Here, qRT-PCR was performed to detect gene expression. Western blot and immunohistochemistry were implemented to examine the expression of C-C motif chemokine ligand 14 (CCL14) in colon tumors. Besides, the expression of CD68 and CD206 in tumors was measured by immunohistochemistry. The percentages of M1- and M2-polarized macrophages were detected by flow cytometry. Furthermore, CCK-8 assay was performed to detect cell proliferation, and Transwell assay for cell invasion. Results. CCL14 was decreased in both colon tumors and colon cancer cells, and many tumor-associated macrophages (TAMs) infiltrated into the tumor. An increase CCL14 inhibited colon cancer cell proliferation. Importantly, CCL14 promoted THP-1 to M1 polarization induced by LPS and IFN-γ, and inhibited THP-1 to M2 polarization induced by IL-4 and IL-13. Besides, CCL14 enhanced the inhibition of M1-polarized macrophages to colon cancer cell proliferation and invasion, and reversed the promotion of M2-polarized macrophages to cell proliferation and invasion. Conclusion. Our data demonstrated that CCL14 inhibited the proliferation and invasion of colon cancer cells through suppressing the formation of M2-like TAMs
Open Access
Ccdc85C, a causative protein for hydrocephalus and subcortical heterotopia, is expressed in the systemic epithelia with proliferative activity in rats
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Tanaka, Natsuki; Izawa, Takeshi; Takenaka, Shigeo; Yamate, Jyoji; Kuwamura, Mitsuru
. Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for spontaneous mutant mouse with non-obstructive hydrocephalus and subcortical heterotopia. Detailed functions of Ccdc85C protein have not been clarified. To reveal roles of Ccdc85C, we examined the distribution and expression pattern of Ccdc85C in the systemic developing organs in rats. Ccdc85C was expressed in various simple epithelia but not stratified epithelia. In the various epithelia, Ccdc85C was localized at cell-cell junctions and its expression was strong at apical junctions. Furthermore, intense expression was seen at developing period and gradually decreased with advancing development. Distribution of Ccdc85C coincides with that of proliferating epithelial cells. These results suggest that Ccdc85C plays an important role in the proliferative property of simple epithelia.
Open Access
Cell proliferation and cancer
(Murcia : F. Hernández, 1998) Lopez-Saez, J.F.; De la Torre, C.; Pincheira, J.; Gimenez-Martin, G.
The discovery that phosphorylation of selected proteins by cyclin-dependent kinases is the engine which makes the cycle run provides a new image of the control of proliferation and of its deregulation. The high conservation of this machinery in the different eukaryotic organisms emphasizes its early origin and its importance for life. It also makes the extrapolation of findings between different species feasible. The control of proliferation relies basically on accelerating and braking mechanisms which act on the engine driving the cycle. This review particularly stresses the importance of checkpoint or tumor suppressor pathways as transduction systems of negative signals which may induce a cycle braking operation. They prevent any important cycle transition, as the initiation of proliferation, that of replication, mitosis, etc., until the DNA and other cellular conditions make such a progression safe. These checkpoint pathways are able to recognize and transduce signals about the adequacy of initiating or continuing proliferation for a cell at a particular time, under a particular set of external and internal conditions. Crucial components of these pathways are proteins encoded by some of the checkpoint genes that evaluate the final balance of mitogenic and antimitogenic pathways reaching them and, if the balance is negative, they prevent temporarily cycle inititation or its progression by inhibiting the corresponding cyclin-dependent kinases. On the other hand, when the balance becomes positive, they allow the activation of the cyclin-dependent kinases. Uncontrolled cell proliferation associated with cancer always depends on the functional abrogation of at least one of the checkpoint pathways. The checkpoint or tumor suppressor protein p53 is one of the proteins in them, and mutations in the gene encoding it are present in more than half of all human tumours. The review touches new pharmacological strategies which have been opened by the discovery of portions of some of the Offprint requests to: Prof. Dr. Jorge F. Lopez-Saez, Departamento de Biologia, Universidad Autonoma de Madrid, Canto Blanco, E-28049 Madrid, Spain *This review is dedicated to Jesljs Vazquez, a great teacher, a great histopathologist and, overall, a great man who left us prematurely. signal transduction cascades involved in the transient brake of cell proliferation. Restoration of checkpoint pathways either prevents further proliferation of cells with damaged genome until repair is over or, alternatively, the dismantling of these checkpoints induce those cells to commit suicide (apoptosis). The fact that both restoration and dismantling of checkpoint pathways sensitive to DNA damage have not disturbing effects on any other proliferating cell with undamaged DNA makes these selective strategies promissing.
Open Access
Cholecystokinin, acting through the A receptor subtype, stimulates the proliferative activity of adrenocortical cells and thymocytes in the ra
(Murcia : F. Hernández, 1999) Malendowicz, L.K.; Tretjer, M.; De Caro, Raffaelle; Jedrzejczak, N.; Brelinska, R.; Markowska, A.; Nussdorfer, G.G.; Nowak, M.
Cholecystokinin (CCK) is a multifunctional regulatory peptide, which acts through two main subtypes of receptors, named CCK-A and CCK-B. Evidence indicates that CCK modulates cell proliferation in various tissues in a paracrine manner, and proofs are available of the presence of CCK in both adrenal glands and thymus. Hence, we have investigated the possible mitogenic action of this peptide on these two tissues, by evaluating the %o of metaphase-arrested cells after vincristin injection (mitotic index). The systemic administration of CCK (three subcutaneous injections of 20 nmollkg, 28, 16 and 4 h before the sacrifice) increased the mitotic index in both the outer adrenal and thymus cortexes of immature (20-day-old) rats and the enucleated adrenal gland of adult (2-month-old) animals at day 5 and 8 of regeneration. The simultaneous administration of equimolar doses of a selective CCK-A receptor antagonist blocked the effect of CCK, while a CCK-B antagonist was ineffective. These findings indicate that CCK exerts a marked CCK-A-mediated proliferogenic effect on both adrenal cortex and thymus in the rat, the physiological relevance of which, however, remains to be demonstrated. In fact, the administration of the CCK-A antagonist alone was ineffective, thereby casting doubts on the role played by endogenous CCK in the maintenance and stimulation of adrenal and thymus growth.
Open Access
Differential distribution of transforming growth factor beta and receptors in the hyper or hypoproliferative gastric mucosa of developing and adult rats
(Murcia : F. Hernández, 2007) Alvares, E.P.; Jordão, L.R.; Gama, P.
Transforming growth factor ß (TGFß) isoforms are known for their antiproliferative effect on epithelial cells in vitro, but the role of each isoform in vivo is poorly understood, mainly when non-pathological conditions are considered. We correlated the presence and distribution of isoforms and receptors to physiological changes in gastric cell proliferation in developing and adult rats. We used fasting to induce either the hyper (14-day-old pups) or hypoproliferation (60-day-old rats) of the gastric epithelium. In 14-d-old pups fasting reduced only TGFß3 labelling in the gland. Conversely, in 60-d-old rats there was an increase of TGFß1 and TGFß3 immunolabelled cells. Receptors were detected at both ages. Therefore, the changes induced by fasting in the constitutive TGFß expression can be correlated to the differential epithelial proliferation in the stomach of developing and adult rats. These results suggest that one of the functional roles of TGFß in vivo is to locally regulate cell proliferation.
Open Access
Effects of the proapoptotic drug prodigiosin on cell cycle-related proteins in Jurkat T cells
(Murcia : F. Hernández, 2003) Pérez-Tomás, R.; Montaner, B.
Prodigiosin (PG) is a red pigment produced by Serratia marcescens with immunosuppressive and apoptotic activities. In this study, we sought to examine the effect of PG on cell cycle-related proteins. The antiproliferative activity of PG was tested using human Jurkat leukaemia T cells in culture. PG-inhibited cell proliferation was determined using thymidine incorporation assay. PG-arrested cell cycle was analysed using immunoblot analysis with specific antibodies against cell cycle-related proteins and kinase assays of cdk2. Apoptosis was determined by Hoechst staining and analysis of DNA fragmentation. PG inhibited cyclin E, cdk2, p27 and p21, the induction of the cyclin A-cdk2 and cyclin E-cdk2 kinase activity, and the phosphorylation of Rb in leukaemic Jurkat cells. We confirmed that PG induces apoptosis by the characteristic DNA laddering pattern and condensed nuclei or apoptotic bodies identified by fluorescence microscopy. These results indicate that PG and other family members form a new group of molecules with a common mechanism of action and specific molecular targets, raising the possibility of their therapeutic use as antineoplastic drugs.
Open Access
Evaluation of the impact of Momordica charantia on the testis of cisplatin-treated albino rats: Biochemical, histopathological, and ultrastructural study
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Shalaby, Fatma Mohsen; Elrefaie, Amany Omar; Abd, Kandil; Attia, El Hai; Biología Celular e Histología
Cisplatin is an antineoplastic drug that exhibits toxicity dependent on dosage and has adverse reproductive effects. Momordica charantia (Bitter melon) is a natural vegetable plant; its active ingredients possess antioxidant, apoptotic, antiproliferative, hypoglycemic, and other therapeutic properties. This study evaluates the effect of the administration of bitter melon extract, cisplatin, and cisplatin/bitter melon cotreatment on liver and kidney functions, serum and testicular oxidative status, testis histology, and sperm parameters. Adult male Wistar rats were randomly divided into four groups: Group I (Control) received normal saline, Group II received oral bitter melon extract (300 mg/kg), Group III received cisplatin (2.5 mg/kg), and Group IV received the same doses of cisplatin and bitter melon, for six successive weeks, daily. Our results showed that bitter melon extract stimulates antioxidant enzymes and has anti-lipid peroxidation properties through the significantly increased plasma levels of glutathione and significantly decreased testicular malondialdehyde. The cisplatin-treated group showed oxidative stress indicated by the significant decrease of catalase, glutathione, and superoxide dismutase levels and a significant increase in malondialdehyde levels in both serum and testis compared with the control group. In the cisplatin/bitter melon-cotreated group, there was a significant increase in superoxide dismutase and a significant decrease in malondialdehyde in both serum and testis compared with cisplatin-treated rats. The bitter melon alone or with cisplatin cotreatment resulted in reduced gonadosomatic index, sperm count, motility, and viability. These results were confirmed by histopathological examinations, apoptosis assay using flow cytometry, and immunohistochemical staining for proliferating cell nuclear antigen. In conclusion, the administration of bitter melon extract alone or in combination with cisplatin led to testicular structure disturbances and showed an anti-spermatogenic effect. These findings are likely due to a combination of inhibited cellular proliferation, increased cell death, minor decrease in testosterone levels, and localized oxidative stress that outweigh the antioxidant benefits of bitter melon extract.
Open Access
Exposure to ELF-pulse modulated X band microwaves increases in vitro human astrocytoma cell proliferation
(Murcia : F. Hernández, 2009) Pérez-Castejon, C.; Pérez-Bruzón, R.N.; Llorente, M.; Pes, N.; Lacasa, C.; Figols, T.; Lahoz, M.; Maestú, C.; Vera-Gil, A.; Del Moral, A.; Azanza, M.J.
Common concern about the biological effects of electromagnetic fields (EMF) is increasing with the expansion of X-band microwaves (MW). The purpose of our work was to determine whether exposure to MW pulses in this range can induce toxic effects on human astrocytoma cells. Cultured astrocytoma cells (Clonetics line 1321N1) were submitted to 9.6 GHz carrier, 90% amplitude modulated by extremely low frequency (ELF)-EMF pulses inside a Gigahertz Transversal Electromagnetic Mode cell (GTEM-cell). Astrocytoma cultures were maintained inside a GTEMincubator in standard culture conditions at 37±0.1°C, 5% CO2, in a humidified atmosphere. Two experimental conditions were applied with field parameters respectively of: PW 100-120 ns; PRF 100-800 Hz; PRI 10-1.25 ms; power 0.34-0.60 mW; electric field strength 1.25-1.64 V/m; magnetic field peak amplitude 41.4-54.6 μ Oe. SAR was calculated to be 4.0x10-4 W/Kg. Astrocytoma samples were grown in a standard incubator. Reaching 70-80% confluence, cells were transferred to a GTEM-incubator. Experimental procedure included exposed human astrocytoma cells to MW for 15, 30, 60 min and 24 h and unexposed shamcontrol samples. Double blind method was applied. Our results showed that cytoskeleton proteins, cell morphology and viability were not modified. Statistically significant results showed increased cell proliferation rate under 24h MW exposure. Hsp-70 and Bcl-2 antiapoptotic proteins were observed in control and treated samples, while an increased expression of connexin 43 proteins was found in exposed samples. The implication of these results on increased proliferation is the subject of our current research.
Open Access
Expression of TFF3 during multistep colon carcinogenesis
(Murcia : F. Hernández, 2007) John, R.; El-Rouby, N.M.; Tomasetto, C.; Rio, M.C.; Karam, S.M.
The pathogenesis of colon cancer is not well understood. This common type of cancer is generally believed to occur in a multistep process which involves alterations of various tumor suppressor genes and oncogenes during the progression through benign lesions towards carcinoma. TFF3 is a product of the colonic epithelium and has been implicated in colonic mucosal protection and also in the aggressiveness of colon cancer cells. The aim of this study was to analyze the expression of TFF3 during propagation towards cancer development in the human colon. Colonic tissues representing colitis, adenomatous polyposis, tubulovillous adenoma, and mucoid/adeno-carcinomas were processed for immunohistochemistry using an antibody specific for human TFF3. The results were correlated with those of PCNA-labeling, quantified, and compared with those of control tissues obtained from the safe margin of macroscopically normal colonic mucosa of patients with colon cancer. The data showed marked down-regulation of TFF3 expression in adenomatous polyposis, then TFF3 expression returns to about control level during adenoma and remains high during mucoidand adeno-carcinomas. Colonic tissues with highly invasive cancer cells were characterized by statistically significant down-regulation of TFF3 expression. The changes observed in expression of TFF3 showed an inverse correlation with cell proliferation and suggest that it might play a protective role against colon carcinogenesis. Key words:
Open Access
Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Casanova Martín, Carlos; Liviu Boaru, Diego; Fraile Martínez, Oscar; García Montero, Cielo; Leon Oliva, Diego De; Castro Martinez, Patricia De; Gimeno Longas, Maria José; Buján, Julia; García Honduvilla, Natalio; Guijarro, Luis G; Gragera, Raquel; Saez, Miguel A.; Ferrara Coppola, Connie; Baena Romero, Víctor; Diaz Pedrero, Raul; Alvarez Mon, Melchor; Toledo Lobo, M. Val; Ortega, Miguel A.; López González, Laura; Biología Celular e Histología
Penile cancer is an uncommon disease compared with other urological tumors and is more common in low- and middle-income countries. Risk factors include age, ethnicity, smoking, hygiene, and human papillomavirus infection. Although carcinoma of the penis can be cured in up to 80% of cases if detected early, late diagnosis drastically reduces survival rates, especially in metastatic cases. More than 95% of cases are squamous cell carcinomas, and the degree of cell differentiation is a key histopathological factor, distinguishing between poorly (P), moderately (M), and well-differentiated (W) carcinomas, with verrucous carcinoma (V) having the best prognosis due to its low metastatic capacity. This study analyses the differential expression of several biomarkers related to cell proliferation and cell cycle, inflammation, epigenetics, and autophagy (cell cycle (IRS-4, Ki-67, RB1, CDK4, cyclin D1, ERBB2, β-catenin, and MAGE-A), inflammation (COX2, NLRP3, and AIF-1), epigenetics (HAT-1) and autophagy (ULK-1 and ATG9A) in penile carcinoma according to the degree of differentiation. Immunohistochemical techniques were performed on 34 penile squamous cell carcinoma (PSCC) samples classified into subtype V (N=6), and groups P (N=9), M (N=9), and W (N=10). The findings suggest a differential expression of molecules according to the degree of cell differentiation, with a higher differential expression of molecules according to the degree of cell differentiation, suggesting that the proteins studied could have predictive value. The study highlights the complexity of PSCC and the need for future studies to explore translational applications and search for new biomarkers to improve clinical management and understanding of this disease
Open Access
Immunohistochemical detection of cell proliferation in gastric carcinomas with the monoclonal antibody ki-67. A study of 24 cases
(Murcia : F. Hernández, 1993) Hoang, Catherine; Polivka, Marc; Maragi, J.A.; Valleu, P.; Nemeth, J.; Galian, Annie
The proliferative activity in 24 gastric carcinomas was determined by an immunohistochemical method using monoclonal antibody Ki-67 (ABC method). Immunostained nuclei were counted by two observers through a Nachet NS 1000 image numeriser. Three grades were defined according to stained nuclei percentage (proliferation index Pi = percentage of cells engaged in cellular cycle outside Go): grade 1 (Pi < 20%); grade 2 (20% < Pi < 40%); grade 3 (Pi > 40%). About 60% of tumours were in grade 1 and 10% in grade 3. No correlations were observed between Pi and the following parameters: histological differentiation; parietal extension; presence or absence of metastasis. These results may be compared to the two other avalable studies of Ki-67 antibody in gastric cancers. Our study also showed a heterogeneous distribution of immunostained nuclei, within each single tumour and from one tumour to another, which has been noted in one previous study and in a similar one we made on colorectal carcinoma. This heterogeneity is the consequence of the variability of carcinomatous cell proliferative activity; an important biological factor in the evaluation of tumoral process. The proliferative activity in gastric carcinomas provides an estimation of tumour dynamics that might be a prospective criterium for tumoral process evaluation.
Open Access
Influence of luteinizing hormone-releasing hormone LHRH, treatment on cellular proliferation in the rat anterior pituitary
(Murcia : F. Hernández, 1994) Carbajo, S.; Gonzalez, F.; López-Muñiz, A.; Carbajo-Pérez, E.
This study was designed to gain insight into the action of LHRH on the control of cellular proliferation in the anterior pituitary. The fraction of cells labelled with bromodeoxyuridine (S-phase cells) was studied in cytospin preparations of anterior pituitary cells taken from control male and female rats and from rats treated with daily doses of 2 pg1100 g body weight of LHRH (7 days), with doses of 40 pg of LHRH given on alternate days for 14 days (7 doses) or, finally, treated with daily doses of 50 ng of busereline acetate (14 days). Treatment with LHRH for 14 days resulted in a significant increase in the fraction of S-phase cells. However, neither the blockade of gonadotrophin secretion with busereline acetate nor its stimulation with LHRH for seven days resulted in a significant change in the proliferative activity of anterior pituitary cells. This action was independent of sex. No significant changes were seen in the proportions of pituitary gonadotrops of the different study groups. Regardless of the treatmentgroup very few cells doubly-immunostained for BrdU and LH were found. It is concluded that LHRH may stimulate cellular proliferation in the anterior pituitary, but further studies are needed to define which cells are involved in this action.
Open Access
Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas
(Murcia : F. Hernández, 1992) Gottschalk, J.; Goebel, S.; Jautzke, G.; Martín, H.; Zimmer, C.; Marzheuser-Brands, S.; Cervós-Navarro, J.
We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexarnethasone may selectively inhibit the expression of PCNA in the GlISphase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.
Open Access
Maternal diabetes affects cell proliferation in developing rat placenta
(Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia, 2011) Zorn, T.M.T.; Zúñiga, M.; Madrid, E.; Tostes, R.; Fortes, Z.; Giachini, F.; San Martín, S.
Placentation starts with the formation of a spheroidal trophoblastic shell surrounding the embryo, thus facilitating both implantation into the uterine stroma and contact with maternal blood. Although it is known that diabetes increases the placental size and weight, the mechanisms responsible for this alteration are still poorly understood. In mammals, cellular proliferation occurs in parallel to placental development and it is possible that diabetes induces abnormal uncontrolled cell proliferation in the placenta similar to that seen in other organs (e.g. retina). To test this hypothesis, the objective of this work was to determine cell proliferation in different regions of the placenta during its development in a diabetic rat model. Accordingly, diabetes was induced on day 2 of pregnancy in Wistar rats by a single injection of alloxan (40 mg/kg i.v.). Placentas were collected on days 14, 17, and 20 postcoitum. Immunoperoxidase was used to identify Ki67 nuclear antigen in placental sections. The number of proliferating cells was determined in the total placental area as well as in the labyrinth, spongiotrophoblast and giant trophoblast cell regions. During the course of pregnancy, the number of Ki67 positive cells decreased in both control and diabetic rat placentas. However, starting from day 17 of pregnancy, the number of Ki67 positive cells in the labyrinth and spongiotrophoblast regions was higher in diabetic rat placentas as compared to control. The present results demonstrate that placentas from the diabetic rat model have a significantly higher number of proliferating cells in specific regions of the placenta and at defined developmental stages. It is possible that this increased cell proliferation promotes thickness of the placental barrier consequently affecting the normal maternal-fetal exchanges.
Open Access
MCM proteins as diagnostic and prognostic tumor markers in the clinical setting
(Murcia : F. Hernández, 2010) Giaginis, constantinos; Vgenopoulou, Stephanie; Vielh, Philippe; Theocharis, Stamatios
Minichromosome maintenance (MCM)proteins are essential for the process of DNA replication,functioning as license components for the S-phase ofcell-cycle initiation and further exerting weak helicaseactivity to unwind DNA from its supercoiled state atreplication forks. The requirement for MCM proteins incycling cells and their absence in quiescent onessupports evidence for their potential clinical applicationas cell proliferation markers. In the last few years, asidefrom their utility as cell proliferation markers, theassessment of MCM expression levels in diverse humanmalignancies has been the focus of extensive research inan aim to facilitate tumor diagnosis and prognosis inclinical settings. The present article aims to review theavailable data so far concerning the clinical significanceof MCM protein expression in human neoplasia incomparison to conventional proliferative markers. Areview of the literature revealed that MCM expression isassociated with important clinicopathological parametersfor patient management and also exhibits significantdiagnostic and prognostic value in several malignancies.MCMs are characterized by higher specificity andsensitivity than the conventional proliferative markers,such as Ki-67 and PCNA, and are thus considered asdiagnostic and prognostic tools of greater clinicalsignificance in several types of human malignancy.
Open Access
Melatonin promotes self-renewal and nestin expression in neural stem cells from the retina
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Gao, Yuhua; Ma, Li; Bai, Chunyu; Zhang, Xiangyang; Yang, Wancai
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promoting self-renewal in retinal stem cells remain unknown. We found that melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in retinal neural stem cells (NSCs) via melatonin receptor 1 (MT1). The ERK pathway inhibitor SCH772984 and TGF-β pathway inhibitor SB431542 were used to study the melatonin-mediated molecular mechanisms of cell proliferation in NSCs. The results revealed a novel molecular mechanism of melatonin promotion of self-renewal of NSCs in which a chain reaction in the ERK and TGF-β/Smad pathways promotes self-renewal and transcription of nestin. In addition, dual-luciferase assays revealed that Smad4 directly regulated nestin transcription after melatonin treatment in NSCs. These findings revealed novel mechanisms through which the ERK pathway cooperates with the Smad pathway to regulate self-renewal in NSCs to enhance nestin expression.
Open Access
New insights into the cytodynamics of the hamster Harderian gland as provided by the bromodeoxyuridine-labelling met hod
(Murcia : F. Hernández, 1996) Fernández-Suárez, A.; López, J. M.; Carbajo, S.; Alvarez-Uría, M.; Carbajo-Pérez, E.
The fourth week of postnatal life is a critica1 point in the development of the hamster Harderian gland. During this week, cells with large lipid vacuoles (type-11 cells) appear in the male gland, marking a morphological sex difference that is notorius in adult animals. The origin and fate of type-11 cells are controversial. To gain insight into the mechanisms by which type-11 cells become a major cell type in the gland of adult male hamsters, bromodeoxyuridine (BrdU) labelling was used to assess the proliferative activity of both types of glandular cells in 28-day-old animals. To search for possible sex differences in the proliferative activity of this gland, female animals of the same age as the males were also studied. No difference was found in the overall labelling index (BrdU-labelled cells/100 cells) between males (1.8f 0.1%) and females (1.5+0.1%). In the gland of the males, the specific labelling index of type-11 cells (3.4+0.4%) was significantly higher than that of type-1 cells (0.9+0.2%). Interestingly, the proportion of type-11 cells present in the male glands at this age (36.6%) was significantly lower than that of type-1 cells. Our results strongly suggest that the proliferation of type-11 cells, rather than a continuous differentiation of these cells from preexisting type-1 cells, is a major event in the achievement of the mature form of this gland. The results reported here counsel a reappraisal of current theories about the cytodynamics of the hamster Harderian gland.
Open Access
Proadrenomedullin-derived peptides as autocrine-paracrine regulators of cell growth
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Belloni, A. S.; Albertin, G.; Forneris, M. L.; Nussdorfer, G. G.
Proa dr e nomedullin (pADM )-d e ri ve d peptides, adrenomedullin (ADM) and pADM N-terminal 20 peptide (PAMP), are hypotensive peptides, which are expressed, along with their receptors, in several tissues and orga ns, the function of which they regulate by acting in an aut ocrin e-parac rin e mann er. Apart fr om th eir involvement in the regul ation of blood pressure and fluid and electro lyte homeostasis, pADM-deri ved peptides appear to playa role in the modulation of cell and tissue growth. Evid ence has bee n prov ided th at ADM: I) favors th e remodeling of cardiovascular system under path ologica l conditi ons, by exe rting an anti apoptotic effect on endotheli al cells and an antiproliferogeni c and antimi gratory acti on on vascul ar smooth-muscle ce lls durin g neo intimal hype rpl asia, and by dec reasin g proliferation and protein ynthesis of cardiac myoeytes and fibrobl asts. These last two effects are mediated by ca lc ito nin ge ne -re lated peptid e type 1 (CGRPI ) receptors coupled to the adenylate cycl ase (AC)/protein kin ase ( PK) A-d epe nd e nt casca de; 2) inhi bits prolife rati o n and e nh a nces apo pt osis of kidn ey mesa ngial ce lls, through the modul ation of mi togenac ti va ted PK (MAPK ) casca des; 3) stimul ates proliferation of adrenal zona glomerulosa ce lls, acting via CG RPl rece ptor coupl ed to the tyrosin e kinase - depend ent MAPK cascade, th e reby possibl y bein g involved in the maintenance and stimulation of adrenal growth ; 4) enhances proliferati on of skin and mucosa epitheli al ce lls and fibrobl asts, by ac ti va ting CGRP] receptor coupled to the AC/PKA signaling pathway; and 5) enh ances proli fe rati on of several tumor- ce ll lines through the activa ti on of the AC/PKA cascade, which suggests a pote nti a l role fo r ADM as promo te r of neopl asti c growth. The growth effects of PAMP have bee n fa r less investiga ted: findings indicate that this peptide, like ADM. enhances adrenal zona glomerulosa ce ll proliferation, and, in contrast with ADM, depresses DNA synthesis in some cancer-cell lines. Both pADMde ri ve d peptid es are th o ug ht to be invol ve d in embryoge nesis, such a contention being based on the demonstration of high pADM-gene expression during the crucial phases of organ growth and differenti ation.
Open Access
Relationship between the RB1 mRNA level and the expression of phosphorylated RB protein in human breast cancers: their relevance in cell proliferation activity and patient clinical outcome
(Murcia : F. Hernández, 2007) Derenzini, M.; Montanaro, L.; Vici, M.; Barbieri, S.; Ceccarelli, C.; Santini, D.; Taffurelli, M.; Martinelli, G.N.; Treré, D.
The aim of the present study was to ascertain the relationship between the level of RB1 mRNA and the expression of phosphorylated RB protein and the relevance of these two parameters in cancer cell proliferation and clinical outcome in human breast cancer. Sixty-eight primary human breast cancers were considered. The amount of RB1 mRNA was evaluated by quantitative RT-PCR analysis. The level of RB phosphorylation was immunohistochemical defined by measuring the phosphorylated (pp) RB labelling index (LI). Cell proliferation rate was measured by calculating the Ki67 LI. No relation was found between the RB1 mRNA level and the ppRB LI (p=0.565). Both RB1 mRNA value and ppRB LI were related (in an inverse and direct manner, respectively) to Ki67 LI. RB1 mRNA expression was more strictly associated with KI67 LI (p=0.001) than the ppRB LI (p=0.013). Regarding the patient clinical outcome, the separately considered RB parameters did not reach the prognostic significance. However, patients with low RB1 mRNA quantity and patients with high ppRB LI, taken together, had a significantly shorter disease free and overall survival than the group comprehending patients with high RB1 mRNA value and low ppRB LI, and this despite the low number of patients considered. Our results demonstrated that the ppRB LI was independent of the RB1 mRNA level; that both RB parameters are related to the cell proliferation rate and, if collectively considered, have a high informative value on breast tumour prognosis.