DigitalUM :: Browsing by Subject "Cancer"

Browsing by Subject "Cancer"

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Open Access
A comparison between double and triple therapies of octreotide, galanin and serotonin on a rat colon carcinoma
(Murcia : F. Hernández, 2003) Sitohy, B.; El-Salhy, M.
Sixty female nude mice (C578L/6jBom-nu) were injected with 100µl cell suspension containing 2x106 viable cells of an N-methyl-N-nitroguanidineinduced rat colonic adenocarcinoma. After seven days the animals were divided into five groups. The first group received only saline and served as a control group. The second group received a triple therapy of octreotide, galanin and serotonin (20 µg/kg). The last three groups received double therapies of octreotide/galanin, octreotide/serotonin or galanin/serotonin (20 µg/kg). They were treated twice a day for five days. Tumour volume and weight, relative volume density of tumourfeeding blood vessels and of tumour necrotic tissue, as well as apoptotic and proliferation indices were determined. Animal weight, food consumption, faeces weight and its water content were recorded before and after treatment. Tumour volume was significantly reduced only in the group that received the triple therapy. The volume density of the tumour-feeding blood vessels was significantly reduced in the treated groups with the exception of the group that received octreotide and serotonin. Increased relative volume density of tumour necrotic tissue occurred only in the group treated with triple therapy. Apoptotic indices were significantly increased in all treated groups. No statistical difference was found between treated animals and controls regarding proliferation indices, food consumption, faeces weight and water content or animal weight. In conclusion, double therapy using two of the gastrointestinal bioactive substances, octreotide, galanin and serotonin, has certain effects on colon cancer cells. To cause a considerable tumour necrosis, triple therapy seems to be required. Both double and triple therapy seem to lack obvious side-effects.
Open Access
A compressive review about Taxol® : history and future challenges
(MDPI, 2020-12-17) Gallego Jara, Julia; Lozano Terol, Gema; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Sola Martínez, Rosa Alba; Bioquímica y Biología Molecular B e Inmunología
Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent.
Open Access
Akt1 and Akt2: Differentiating the aktion
(Murcia: F. Hernández, 2011) Heron-Milhavet, Lisa; Khouya, Nabil; Fernandez, Anne; Lamb, Ned J.
Kinases of the Akt family are integral and essential components in growth factor signaling pathways activated downstream of the membrane bound phospho-inositol-3 kinase. In light of strong homologies in the primary amino acid sequence, the three Akt kinases were long surmised to play redundant and overlapping roles in insulin signaling across the spectra of cell and tissue types. Over the last 10 years, work using mouse knockout models, cell specific inactivation, and more recently targeted gene inactivation, has brought into question the redundancy within Akt kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. Here we concentrate on the differential roles played by Akt1 and Akt2 in a variety of cellular processes and in particular during cancer biogenesis. In this overview, we illustrate that while Akt1 and 2 are often implicated in many aspects of cellular transformation, the two isoforms frequently act in a complementary opposing manner. Furthermore, Akt1 and Akt2 kinases interact differentially with modulating proteins and are necessary in relaying roles during the evolution of cancers from deregulated growth into malignant metastatic killers. These different actions of the two isoforms point to the importance of treatments targeting isoform specific events in the development of effective approaches involving Akt kinases in human disease.
Open Access
Alcohol-related diseases and liver metastasis: role of cell-free network communication
(Baishideng Publishing Group, 2022-08-14) Muro, Manuel; Collados Ros, Aurelia; Legaz Pérez, Isabel; Ciencias Sociosanitarias
Alcohol intake is a risk factor for cancer development and metastatic disease progression. Extracellular vesicle (EV)-mediated interorgan communication is assumed to be significant in boosting tumorigenic pathways and disease progression. Recent research indicates that exosomes have a variety of roles in the development of cancer during pathophysiological conditions. The involvement of EV signaling during cancer progression in the alcohol environment is unknown. Therefore, understanding communication networks and the role of EVs as biomarkers can contribute significantly to developing strategies to address the serious public health problems associated with alcohol consumption and cancer.
Open Access
An immunohistochemical study of cyclooxygenase-2 expression in canine multicentric lymphoma
(Murcia: Servicio de Publicaciones de la Universidad de Murcia, 2011) Rodrigues, L.C.S.; Cogliati, B.; Guerra, J.L; Dagli, M.L.Z.; Lucas, S.R.R.
Cyclooxygenase-2 (COX-2) expression has been associated with development and progression in spontaneous human and dogs tumors. Studies demonstrated that non-steroidal anti-inflammatory drugs, which inhibit COX enzyme, may be used in the treatment of some tumors. Lymphoma is a systemic disease and the most common hematological malignancy in dogs. There are few studies about COX-2 expression in human and canine lymphoma. In this study, immunohistochemical evaluation for COX-2 expression was performed in 12 dogs with multicentric lymphoma. The diagnosis was confirmed by histopathological examination. Six samples of normal lymph nodes were either used in the study. No COX-2 immunoreactivity was detected in all samples from canine lymphoma and normal lymph nodes, as well previous studies in canine lymphoma.
Open Access
An optimized xylene-free protein extraction method adapted to formalin-fixed paraffin embedded tissue sections for western blot analysis
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Mansour, Anthony G.; Abou Khalil, Pamela; Bejjani, Noha; Chatila, Rajaa; Dagher Hamalian, Carole; Faour, Wissam H.
Deparaffinization of formalin-fixed paraffin embedded (FFPE) tissues with xylene currently remains a major challenge to the biomedical community. We developed an efficient xylene-free protocol to isolate proteins from archived FFPE human tissue sections. A total of 79 different types of FFPE tissue sections of 8 µm thickness were obtained from various archived FFPE specimens. Deparaffinization was conducted by gently washing each section with around 1 ml of hot distilled water (≈80°C). The deparaffinized tissues were homogenized in lysis buffer, and the isolated proteins were quantified and efficiently resolved using western blot analysis for the presence of Protein kinase B (PKB/AKT) and β-actin. Moreover, a significant amount of proteins was successfully isolated with an average of 2.31 µg/µl. The migration pattern of AKT and β-actin obtained from the specimens was similar to the positive control obtained from protein lysates prepared from in vitro cultured MDA231 cancer cell lines. AKT was successfully identified in all specimens, and β-actin protein was resolved with an efficiency higher than 80%. The entire extraction procedure requires only 20 minutes. This newly developed technique is an efficient, safe, cost-effective, and rapid method to isolate proteins from FFPE tissue sections adequate for molecular analysis.
Open Access
Annexins as disease modifiers
(Murcia : F. Hernández, 2010) Fatimathas, Lux; Moss, Stephen E.
The annexins are a family of calciumdependent phospholipid binding proteins which are present in all eukaryotes. There are currently 12 identified human annexins all of which contain unique calcium binding sites, encoded in the highly conserved annexin repeat motifs within the C terminal core. In addition to the C terminal core the annexins contain a significantly more variable N terminal head. It is this domain which endows each annexin with unique functions in a diverse range of cellular processes including; endo- and exocytosis, cytoskeletal regulation and membrane conductance and organisation. Given their involvement in such a variety of processes it is not surprising that the annexins have also been implicated in a range of disease pathologies. Although there is no singular disease state directly attributed to a dysregulation in annexin function, several pathological conditions are suggested to be modified by the annexins. In this review we shall focus on the growing evidence for the role of the annexins in the progression of cancer, diabetes and the autoimmune disorder anti-phospholipid syndrome.
Open Access
Anti-leukemic activity of Brassica-derived bioactive compounds in HL-60 myeloid leukemia cells
(MDPI, 2022-11-02) Núñez-Sánchez, María Ángeles; Martínez-Sánchez, María Antonia; Verdejo-Sánchez, Marina; García-Ibáñez, Paula; Oliva Bolarín, Alba; Ramos-Molina, Bruno; Moreno, Diego A.; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
Acute myeloid leukemia (AML) is a cancer of the myeloid blood cells mainly treated with chemotherapy for cancer remission, but this non-selective treatment also induces numerous side effects. Investigations with bioactive compounds from plant-derived foods against cancer have increased in the last years because there is an urgent need to search for new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. In this study, we analyzed the anti-leukemic activity of several phytochemicals that are representative of the major classes of compounds present in cruciferous foods (glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols, and anthocyanins) in the human acute myeloid leukemia cell line HL-60. Our results revealed that among the different Brassica-derived compounds assayed, sulforaphane (SFN) (an aliphatic isothiocyanate) showed the most potent anti-leukemic activity with an IC50 value of 6 µM in dose-response MTT assays after 48 h of treatment. On the other hand, chlorogenic acid (a hydroxycinnamic acid) and cyanidin-3-glucoside (an anthocyanin) also displayed anti-leukemic potential, with IC50 values of 7 µM and 17 µM after 48 h of incubation, respectively. Importantly, these compounds did not show significant cell toxicity in macrophages-like differentiated cells at 10 and 25 µM, indicating that their cytotoxic effects were specific to AML cancer cells. Finally, we found that these three compounds were able to induce the NRF2/KEAP1 signaling pathway in a dose-dependent manner, highlighting SFN as the most potent NRF2 activator. Overall, the present evidence shed light on the potential for using foods and ingredients rich in anticancer bioactive phytochemicals from Brassica spp.
Open Access
Antioxidant enzymes in renal cell carcinoma
(Murcia : F. Hernández, 2006) Soini, Y.; Kallio, J.P.; Hirvikoski, P.; Helin, H.; Kellokumpu-Lehtinen, P.; Tammela, T.L.J.; Peltoniemi, M.; Martikainen, P.M.; Kinnula, V.L.
The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors.
Open Access
Apoptosis in cancer: therapeutic implications
(Murcia : F. Hernández, 2000) Negoescu, A.
This review outlines the principal limitations of the mechanisms of active cell death (ACD, apoptosis) as the basis of tumorigenesis and the rationale of almost all therapies of malignancy. The concentration of cancer therapy in the directon of ACD induction is presented as both the result of progressive understanding of the mechanisms of apoptosis and that of the favourable tumor environment for ACD signal transmission. The latter property induces the by-stander killing of cancer cells, a fundamental mechanism because efficiency of all known methods of cancer treatment is far below 100%. Finally, recent results and hypotheses regarding cancer gene therapy based on final inductors of apoptosis and endogeneous ACD inhibitors in tumors are evaluated.
Restricted
Application of International Caries Detection and Assessment System (ICDAS) and Caries Management by Risk Assessment (CAMBRA) systems in child cancer patients: a clinical case report
(Springer, 2017-05-13) Hernández Fernández, Ana; Oñate Sánchez, Ricardo Elías; Fernández Miñano, Esther; Iniesta López Mantecio, P.; Ortiz Ruiz, Antonio José; Dermatología, Estomatología, Radiología y Medicina Física
Background Leukaemia represents 30–40% of all paediatric malignant tumours and is the main cause of death in patients aged <15 years. One of the main complications in these patients is infection, which may often occur in the oral cavity. Chemotherapy-related oral health problems may be reduced by oral healthcare strategies based on the International Caries Detection and Assessment System (ICDAS) and Caries Management by Risk Assessment (CABRA). Case report A case is reported of a 14-year-old girl treated for leukaemia who presented with established dental caries lesions which were classified and treated according to ICDAS and CABRA protocols. After three, no new caries was observed. Follow-up and conclusion ICDAS and CAMBRA provide useful and effective guidance for the avoidance of dental and systemic problems. Their introduction into standard practice could reduce the legal difficulties derived from dental treatment in these patients.
Open Access
Aproximación a las causas del cáncer colorrectal de intervalo en colonoscopia en el área II del Servicio Murciano de Salud
(Universidad de Murcia, 2018-06-22) Sastre Lozano, Violeta Mª; Morán Sánchez, Senador; García Solano, José; Escuela Internacional de Doctorado
Objetivos: Determinar la prevalencia de cáncer colorrectal (CCR) de intervalo o post-colonoscopia (CCR-PC) en el área II del Servicio Murciano de Salud (SMS). Conocer la sensibilidad de la colonoscopia en nuestra unidad de endoscopia mediante la Tasa de CCR-PC. Describir sus características histopatológicas y compararlas con un grupo control de CCR esporádico. Analizar los perfiles de expresión génica mediante arrays en los CCR-PC y compararlos con los de un grupo control de CCR esporádico. Evaluar los factores asociados a la aparición de CCR-PC, así como la relación entre éste y la capacidad técnica del endoscopista (Tasa de Detección de Pólipos). Material y Métodos: Se trata de un estudio observacional, descriptivo y retrospectivo, de casos y controles. La población a estudio son los mayores de 18 años diagnosticados de CCR entre el 1 de enero de 2012 y el 31 de diciembre de 2014. Se realizó el análisis histopatológico de los casos de CCR-PC y se comparó con el de un grupo control de CCR esporádico, emparejados por tipo histológico, grado de diferenciación y estadio tumoral. Del mismo modo, se realizó el estudio de funciones y perfil génico mediante arrays de los CCR-PC y se comparó igualmente con los de un grupo control de CCR esporádico. El resto de las variables registradas fueron la indicación de la colonoscopia índice, calidad de la preparación catártica, localización del tumor, comorbilidades del paciente, intubación cecal y tasa de detección de pólipos (TDP). Finalmente se estudió la relación entre la TDP de los endoscopistas agrupados en cuartiles y la aparición de CCR-PC. Resultados: Se identificaron 17 casos de CCR-PC de un total de 291 casos de CCR diagnosticados en el periodo de estudio. La tasa de CCR-PC fue del 0.0584 y la sensibilidad de la colonoscopia en el área II del SMS fue del 94.16%. La prevalencia de adenocarcinoma serrado y adenocarcinoma MSI-H fue mayor entre los casos de CCR-PC que en el CCR esporádico, pero sin alcanzar la significación estadística. Entre las características histopatológicas analizadas destaca la presencia de Infiltrado inflamatorio en todos los casos de CCR-PC y ausencia de éste en el 41.17% de los casos del grupo control de CCR esporádico (p = 0.011). El 47% de los CCR-PC presentó Respuesta Linfoide tipo Crohn frente al 5% de los casos del grupo control de CCR esporádico (p = 0.007). El diagnóstico de CCR sincrónico aumenta de forma significativa en el grupo de CCR-PC (11% frente a 0.37% en CCR esporádico). La indicación de la colonoscopia índice también varía de forma significativa para ambos grupos, siendo la anemia la indicación más habitual en CCR-PC y la rectorragia en CCR esporádico. Para comprobar si influye la calidad técnica del endoscopista en la aparición de CCR-PC se calculó la TDP del endoscopista y se agrupó a los endoscopistas por cuartiles (Q1, Q2, Q3 y Q4). Se observó que los endoscopistas con mayor TDP tenían una tasa menor de CCR-PC. Siendo éstas del 8%, 10%, 3% y 4% para Q1, Q2, Q3 y Q4 respectivamente. Conclusiones: La mayoría de los casos de CCR-PC se producen por déficits técnicos del procedimiento. Hay que prestar especial atención a la anemia como indicación en la colonoscopia índice y la TDP se relaciona en nuestro estudio con la aparición de CCR-PC. El análisis histológico muestra una mayor prevalencia de carcinoma MSI-H y adenocarcinoma serrado en el grupo de CCR-PC. Este estudio muestra diferencias histopatológicas y diferencias en la expresión génica entre el CCR-PC y el CCR esporádico, aunque son necesarios más estudios para extrapolar las conclusiones. Objectives: The main targets of the study are to determine interval colorectal cancer prevalence in the Área II of Murcia´s Health System (MHS). To know the sensibility of the colonoscopy in our endoscopy unit by means of post-colonoscopy colorectal cancer (PC-CRC) rate. To describe their histopathological features and compare them with those of a control group of sporadic CRC. To analyse the profiles of gene expression by means of arrays in the PC-CRC and to compare with those of a control group of sporadic CRC. To evaluate the factors associated with the appearance of PC-CRC, as well as its relationship with technical capacity of the endoscopist (Polyp Detection Rate). Materials and methods: It is an observational, descriptive and retrospective study, of cases and controls. People included in this study are the patients older than 18 who have a diagnosis of CRC between January 1, 2012 and December 31, 2014. The histopathological analysis of PC-CRC was realized and was compared with that of a control group of sporadic CRC, paired by histological type, differentiation grade and cancer staging. In addition, there was realized the study of functions and gene profile by means of arrays of PC-CRC and was compared too with that of a control group of sporadic CRC. The rest of the registered variables was the indication of index colonoscopy, quality of preparation, location tumour, patient comorbidities, cecum intubation and Polyp Detection Rate (PDR). Finally, the relationship between PDR of the endoscopists grouped in quartiles, and PC-CRC prevalence was studied. Results: 17 cases of PC-CRC were identified out of 291 cases of CRC diagnosed in the period of the study. PC-CRC rate was 0.0584 and colonoscopy sensibility 94.16% in the Area II of MHS. Serrated adenocarcinoma and MSI-H carcinoma prevalence were higher in PC-CRC group than sporadic CRC group, but statistical differences were not found. Among histopathological characteristics it highlights the presence of inflammatory Infiltration in all the cases of PC-CRC and absence of this one in 41.17 % of the cases of the control group of sporadic CRC (p = 0.011). 47% of PC-CRC had Lymphoid infiltration Crohn like opposite to 5% in sporadic CRC control group (p = 0.007). Synchronic PC-CRC increased significantly (11% in PC-CRC opposite to 0.37% in sporadic CRC). Index colonoscopy indication also showed some differences. Anaemia is the most frequent indication in PC-CRC group and rectal bleeding in sporadic CRC. PDR was calculated to check if the PC-CRC prevalence was influenced by technical quality of the endoscopist. The endoscopists were grouped in quartiles (Q1, Q2, Q3, Q4). It was observed that endoscopists with major TDP had a less PC-CRC rate. Being these 8 %, 10 %, 3 % and 4 % for Q1, Q2, Q3 and Q4 respectively. Conclusions: Most of the cases of PC-CRC take place because of technical deficits in procedure of colonoscopy. It is necessary to pay special attention to anaemia as indication in the index colonoscopy. PDR is related in our study to the PC-CRC appearance. Histological analysis shows a major prevalence of MSI-H carcinoma and serrated adenocarcinoma in the PC-CRC group. This study shows differences in histopathology and genic expression between PC-CRC and sporadic CRC group, although more studies are necessary to extrapolate the conclusions.
Open Access
Automated mitosis detection in stained histopathological images using Faster R-CNN and stain techniques
(De Gruyter, 2025-06-11) García-Salmerón, Jesús; García, José Manuel; Bernabé, Gregorio; González Férez, Pilar; Ingeniería y Tecnología de Computadores
Accurate mitosis detection is essential for cancer diagnosis and treatment. Traditional manual counting by pathologists is time-consuming and may cause errors. This research investigates automated mitosis detection in stained histopathological images using Deep Learning (DL) techniques, particularly object detection models. We propose a two-stage object detection model based on Faster R-CNN to effectively detect mitosis within histopathological images. The stain augmentation and normalization techniques are also applied to address the significant challenge of domain shift in histopathological image analysis. The experiments are conducted using the MIDOG++ dataset, the most recent dataset from the MIDOG challenge. This research builds on our previous work, in which two one-stage frameworks, in particular on RetinaNet using fastai and PyTorch, are proposed. Our results indicate favorable F1-scores across various scenarios and tumor types, demonstrating the effectiveness of the object detection models. In addition, Faster R-CNN with stain techniques provides the most accurate and reliable mitosis detection, while RetinaNet models exhibit faster performance. Our results highlight the importance of handling domain shifts and the number of mitotic figures for robust diagnostic tools.
Open Access
BAG3: a new therapeutic target of human cancers?
(F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Huayuan, Zhu; Peng, Liu; Jianyong, Li
Bcl-2-associated athanogene (BAG) family proteins share the BAG domain, which is characterized by their interaction with a variety of partners (heat shock proteins, steroid hormone receptors, Raf-1 and others) and is involved in regulating a number of cellular processes. BAG3, also known as CAIR-1 or Bis, mediates protein delivery to proteasome and modulates apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the cellular death program. Moreover, it takes part in the processes of cell adhesion and migration. It has been shown that, in human cancer cells, including lymphocytic and myeloblastic leukemic cells, BAG3 sustains cell survival and underlies resistance to chemotherapy, through down-modulation of apoptosis. BAG3 knocking down could enhance the effectiveness of chemotherapy. This review summarizes the physiological and pathological roles of BAG3 in cancer cells and its potential as a therapeutic target of human malignancies.
Open Access
BMI-1: a protein expressed in stem cells, specialized cells and tumors of the gastrointestinal tract
(Murcia : F. Hernández, 2006) Reinisch, C.; Kandutsch, S.; Uthman, A.; Pammer, J.
Recently, BMI-1 was identified as a protein downregulating p16ink4a and mandatory for the continued existence of several stem cell compartments like hematopoietic and neural stem cells. In this study we investigated BMI-1 expression as a potential stem cell marker of the gastrointestinal tract. We found weak expression in the isthmus region of the stomach, and moderate expression in crypts of the intestines, whereas intestinal surface epithelial cells were weakly positive or negative for BMI-1. In addition, a variety of highly differentiated cells such as parietal cells, neuroendocrine cells of the pylorus, Paneth cells and a subset of goblet cells were moderately to strongly positive for BMI-1. Furthermore, we detected strong expression in gastrointestinal neoplasias. This expression pattern indicates a correlation of BMI-1 expression with gastrointestinal stem cells as well as numerous specialized cell types and points to a role of this protein in cellular differentiation in addition to that of stem cell maintenance. Besides, our results imply a role for BMI-1 in the tumorigenesis of gastrointestinal cancer.
Open Access
Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)
(MDPI, 2022-05-15) Guevara, M; Molinuevo, A; Salmerón, D; Marcos-Gragera, R; Carulla, M; Rodríguez Camblor M; Alemán, A; Rojas, D; Vizcaíno Batllés, A; Chico, M; Jiménez Chillarón, R; López de Munain, A; de Castro, V; Sánchez, MJ; Ramalle-Gómara, E; Franch, P; Galceran, J; Ardanaz, E; Chirlaque López, María Dolores; Ciencias Sociosanitarias
The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.
Open Access
Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus, cytoplasm, endothelium, and fibroblasts of human cancers
(Murcia : F. Hernández, 2006) Saba, S.R.; Vesely, D.L.
Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) synthesized by the same gene decrease within 24 hours up to 97% the number of human breast, colon, pancreatic, and prostate adenocarcinoma cells as well as human small-cell and squamous carcinomas of the lung cells. These peptide hormones completely inhibit the growth of human pancreatic adenocarcinomas growing in athymic mice. Immunocytochemical investigations have revealed that LANP, vessel dilator, kaliuretic peptide and ANP localize to the nucleus and cytoplasm of human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer mediated by the intracellular messenger cyclic GMP. These peptide hormones also localize to the endothelium of capillaries and fibroblasts within these cancers. These are the first growth-inhibiting peptide hormones ever demonstrated to localize to the nucleus. Their ability to decrease the activation of growth promoting substances such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear Factor Kappa Beta (NFkB) suggests that in addition to inhibiting DNA synthesis their ability to decrease the activation of growth promoting substances helps to mediate their ability to inhibit the growth of human cancers.
Open Access
CD26 dipeptidyl peptidase IV and its role in cancer
(Murcia : F. Hernández, 2004) Pro, B.; Dang, N.H.
CD26/Dipeptidyl Peptidase IV (DPPIV) is a 110-kDa glycoprotein that is expressed on numerous cell types and has multiple biological functions. A key facet of CD26/DPPIV biology is its enzymatic activity and its physical and functional interaction with other molecules. The substrates of CD26/DPPIV are proline-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides. DPPIV plays an important role in immune regulation, signal transduction, and apoptosis. Furthermore, CD26 appears to play an important role in tumor progression. In the present review, we summarize key aspects of CD26/DPPIV involvement in tumor biology and its potential role in cancer development and behavior.
Open Access
CD44: functional relevance to inflammation and malignancy
(Murcia : F. Hernández, 2002) Yasuda, M.; Nakano, K.; Yasumoto, K.; Tanaka, Y.
CD44 is a principal cell surface receptor for hyaluronan, a major component of extracellular matrices. Cells are surrounded by and encounter matrix in vivo, which in turn serves a variety of cell functions through the direct adhesion via their receptors. CD44 communicates cell-matrix interactions into the cell via “outside-in signaling” and has an important role in biological activities. The interaction of CD44 with fragmented hyaluronan on rheumatoid synovial cells induces expression of VCAM-1 and Fas on the cells, which leads to Fas-mediated apoptosis of synovial cells by the interaction of T cells bearing FasL. On the other hand, engagement of CD44 on tumor cells derived from lung cancer reduces Fas expression and Fas-mediated apoptosis, resulting in less susceptibility of the cells to CTL-mediated cytotoxicity through Fas-FasL pathway. Thus, although the CD44-mediated signaling differs among cells and circumstances, we here propose the functional role of CD44 in inflammatory processes and tumor susceptibility and the rational design of future therapeutic strategies including the exploitation of CD44-mediated pathway in vivo.
Open Access
Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers
(Murcia : F. Hernández, 2005) Gallego, R.; Pintos, E.; Garcia-Caballero, Tomas; Raghay, K.; Boulanger, L.; Beiras, Andres; Gaudreau, P.; Morel, G.
Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors.