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
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 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
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
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.
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
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
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.
Open Access
Chromosome instability and kinetochore dysfunction
(Murcia : F. Hernández, 2007) Tomonaga, T.; Nomura, F.
Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis. Proper chromosome segregation requires a physical connection between spindle microtubules and centromeric DNA and this attachment occurs at proteinaceous structures called kinetochore. Thus, defect in kinetochore function is a candidate source for CIN and the generation of aneuploidy. Recently, a number of kinetochore components have been shown to be mutated and/or aberrantly expressed in human cancers, which suggests an important role of kinetochore for CIN and carcinogenesis. In this article, we will discuss about how kinetochore dysfunction causes CIN and might lead to the development of cancer.
Open Access
Clinical significance of FAK expression in human neoplasia
(Murcia : F. Hernández, 2008) Chatzizacharias, Nikolaos A.; Kouraklis, Gregory P.; Theocharis, Stamatios E.
Focal Adhesion Kinase is a 119-121 kDa nonreceptor protein kinase widely expressed in various tissues and cell types. Several studies showed that FAK plays an important role in integrin signaling. Once activated by integrin and non-integrin stimuli, it binds and activates several other molecules, such as Src, p130Cas, Grb2, PI3K and paxillin, thus promoting signaling transduction. In normal cells FAK activity is under constant regulation by mechanisms such as gene amplification, alternative splicing and action of phosphatases. On the contrary, in vitro studies showed that in transformed cells unopposed FAK signaling promoted cancer cells’ malignant characteristics. FAK was held responsible for cancer cells’ uninhibited proliferation, protection from apoptosis, invasion, migration, adhesion and spreading, as well as tumor angiogenesis. Several in vivo studies supported the above observations and further correlated FAK expression with various clinicopathological parameters of several types of human malignancies. The purpose of this article is a comprehensive review of the existing data on FAK expression and signaling and their clinical significance in human malignancy.
Open Access
Correlación entre la clínica, ecografía, marcadores tumorales y bipsia intraoperatoria y definitiva en tumoraciones ováricas sospechosas de malignidad
(Universidad de Murcia, 2018-02-12) Muñoz Sánchez, Mª Jezabel; Sánchez Ferrer, María Luisa; Facultad de Medicina
Para la práctica clínica ginecológica, supone un reto mejorar la precisión del diagnóstico preoperatorio de las tumoraciones ováricas, estableciendo una correcta clasificación entre neoplasias malignas y benignas. Esta distinción es esencial para el óptimo manejo quirúrgico, y para ofrecer a la paciente la mejor opción terapéutica. La ecografía ginecológica es la prueba complementaria más empleada para determinar el grado de sospecha diagnóstica. De forma complementaria, otras pruebas de imagen (TC y/o RMN), marcadores tumorales, la clínica referida, así como factores de riesgo asociados, pueden colaborar para establecer un diagnóstico de sospecha clínico. Sin embargo, en ocasiones, resulta difícil establecer un diagnóstico preoperatorio, y es necesaria la realización de una biopsia intraoperatoria (BIO), la cual, nos proporciona gran información acerca de la naturaleza de la lesión y oferta la posibilidad de tomar decisiones durante el propio acto quirúrgico. OBJETIVOS El principal objetivo de este estudio fue valorar el grado de concordancia de la BIO con la anatomía patológica definitiva en tumoraciones anexiales sospechosas de malignidad. Además, el presente estudio se ha realizado para comprobar la precisión de las diferentes técnicas diagnósticas empleadas preoperatoriamente para la categorización de dichas tumoraciones. MATERIAL Y MÉTODOS Se realizó un estudio retrospectivo, que incluyó 375 pacientes con tumoraciones ováricas sospechosas de malignidad, sometidas a intervención quirúrgica en el Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) entre los años 2008 y 2016, y en las que se realizó BIO en el propio acto quirúrgico. Se recopilaron datos epidemiológicos, clínicos, ecográficos y de otras pruebas de imagen, bioquímicos y anatomo-patológicos. RESULTADOS La sensibilidad y especificidad global para la BIO fue del 96,3% y del 98,1%, respectivamente. Por grupos, se obtuvo una sensibilidad del 98,1% para las tumoraciones benignas, del 87,5% para las malignas y del 86,1% para las borderline. Únicamente el 9,1% de las BIO no fueron previstas pre-quirúrgicamente, y de ellas, la mayoría obtuvieron un diagnóstico definitivo de benignidad. De las biopsias previstas, el 55,4% resultaron benignas. La sensibilidad del diagnóstico ecográfico fue del 88,4% y la especificidad del 57,8%. La sensibilidad del diagnóstico clínico fue del 87,8% y la especificidad del 56,9%. DISCUSIÓN En nuestro trabajo, la sensibilidad obtenida en la BIO para tumoraciones malignas fue muy similar a la descrita en la bibliografía, sin embargo, la sensibilidad para tumoraciones borderline, así como la especificidad global fue mayor. La mayor frecuencia de discordancias en la BIO, tuvo lugar en los tumores mucinosos, de los cuales el 50% fueron borderline y la mayoría resultaron ser tumoraciones de gran tamaño. La sensibilidad ecográfica obtenida en nuestro estudio fue ligeramente superior a la esperada, sin embargo, la especificidad fue significativamente menor. Pruebas de imagen complementarias asumieron una elevada tasa de falsos positivos, mayor a la hallada en otros estudios. Únicamente el CA 125 y el algoritmo ROMA mostraron una utilidad clínica moderada en pacientes premenopáusicas y en estadios avanzados. El diagnóstico de sospecha clínico mostró una baja especificidad. CONCLUSIONES La biopsia intraoperatoria presentó una utilidad clínica excelente para el diagnóstico de tumoraciones ováricas. Resultó determinante la experiencia de patólogos especializados en patología ginecológica para alcanzar el elevado grado de precisión. La especialización en grandes centros de referencia, como es el nuestro, es de vital importancia para la categorización de tumoraciones anexiales. El diagnóstico ecográfico asumió un elevado porcentaje de diagnósticos erróneos, que resultaron benignos en el diagnóstico definitivo, condicionando un aumento de las biopsias intraoperatorias realizadas. El diagnóstico de sospecha clínico mostró menor precisión que el ecográfico, por lo que los marcadores tumorales y otras pruebas de imagen no mejoraron el rendimiento diagnóstico ecográfico. INTRODUCTION For gynecological clinical practice, it is a challenge to improve the accuracy of preoperative diagnosis of ovarian tumors, establishing a correct classification between malignant and benign neoplasms. This distinction is essential for optimal surgical management, and to offer the patient the best therapeutic option. Gynecological ultrasound is the most commonly used complementary test to determine the degree of diagnostic suspicion. In addition, other imaging tests (CT scan or MRI), tumor markers, referred symptoms, as well as associated risk factors, can collaborate to establish a diagnosis of clinical suspicion. However, it is sometimes difficult to establish a preoperative diagnosis, and it is necessary to perform an intraoperative biopsy (IOB), which gives us great information about the nature of the lesion and offers the possibility of making decisions during the surgical procedure itself. OBJECTIVES The main objective of this study was to assess the degree of concordance of IOB with the definitive pathological anatomy in adnexal tumor suspected of malignancy. In addition, the present study has been performed to verify the accuracy of the different diagnostic techniques used preoperatively for the categorization of such tumors. MATERIAL AND METHODS A retrospective study was carried out, including 375 patients with suspected malignant ovarian tumors who underwent surgery at the Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) between 2008 and 2016, and in whom IOB was performed during the operation. Epidemiological, clinical, ultrasound and other imaging test, biochemical and anatomopathological data were collected. RESULTS The overall sensitivity and specificity for IOB was 96.3% and 98.1%, respectively. By groups, a sensitivity of 98.1% was obtained for benign tumors, 87.5% for malignant tumors and 86.1% for borderline tumors. Only 9.1% of IOB's were not pre-surgically planned, and most of them obtained a definitive diagnosis of benignity. Of the predicted biopsies, 55.4% were benign. The sensitivity of the ultrasound diagnosis was 88.4% and the specificity was 57.8%. The sensitivity of the clinical diagnosis was 87.8% and the specificity was 56.9%. DISCUSSION In our study, the sensitivity obtained in IOB for malignant tumors was very similar to that described in the literature, however, the sensitivity for borderline tumors as well as the overall specificity was greater. The greatest frequency of discordance in IOB occurred in mucinous tumors, of which 50% were borderline and the majority were large tumors. The ultrasound sensitivity obtained in our study was slightly higher than expected, however, the specificity was significantly lower. Complementary imaging tests assumed a high false positive rate, higher than that found in other studies. Only CA 125 and the ROMA (Risk of Ovarian Malignancy Algorithm) showed moderate clinical utility in premenopausal and advanced stage patients. The diagnosis of clinical suspicion showed a low specificity. CONCLUSIONS The intraoperative biopsy presented an excellent clinical utility for the diagnosis of ovarian tumors. The experience of pathologists specialized in gynecological pathology was decisive in reaching the high degree of precision. Specialization in large centers of reference, such as ours, is of vital importance for the categorization of adnexal tumors. The ultrasound diagnosis assumed a high percentage of erroneous diagnoses, which were benign in the definitive diagnosis, conditioning an increase of intraoperative biopsies performed. The diagnosis of clinical suspicion showed less precision than the ultrasound, so that tumor markers and other imaging tests did not improve ultrasound diagnostic performance.
Open Access
Dehumanist resilience in Tracy Sorensen’s The vitals.
(Universidad de Murcia, Servicio de Publicaciones., 2025) O'Brien, Susie; Sin departamento asociado
This paper looks to Tracy Sorensen’s 2023 novel, The vitals, to help answer the question: what do we hope for –which bodies, which worlds– when we hope for resilience? The vitals narrates the experience of cancer from the perspective of the author’s abdominal organs and tumours. It is also, less obviously, an intervention into the cultural politics of climate change, informed by Sorensen’s many years as a climate activist. The book also reflects Sorensen’s recognition that climate change, like cancer, represents a challenge to the imagination that is partly attributable to myths of a hierarchical distinction between brain and body and between human and non-human modes of being. This paper reads The vitals as an experiment in dehumanism (Singh, 2018) that counters myths of humanist mastery with an emphasis on place-based imagination, organization and laughter.
Open Access
Desmosomes and disease
(Murcia : F. Hernández, 1997) Chidgey, M.A.J.
Considerable progress has been made in our knowledge of desmosomes and their components. Molecular cloning of the desmosomal glycoproteins has established that desmoglein 1 and desmoglein 3 are targets for autoantibodies in the blistering diseases pemphigus foliaceus and pemphigus vulgaris respectively. New evidence suggests that another desmosomal glycoprotein, desmocollin 1, is the major target antigen in the upper epidermal form of intercellular IgA dermatosis (IgA pemphigus). In human cancer there is accumulating evidence which suggests a role for desmosomes in the prevention of invasion and metastasis. The possibility exists that a mutation in a desmosomal glycoprotein gene is responsible for an inheritable human disease, the striated form of palmoplantar keratodenna.
Open Access
Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line implanted in mice: comparison between different routes of administration
(Murcia : F. Hernández, 2005) El-Salhy, M.
A human colon cancer cell line was implanted subcutaneously in nude mice. After 7 days, the animals were divided into four groups. The first group received an intraperitoneal (i.p.) continuous infusion by an osmotic pump, the second was given i.p. bolus injections, the third received continuous subcutaneous (s.c.) infusion by an osmotic pump and the fourth group was given bolus s.c. injections. Each group was divided into 2 subgroups. The first subgroup received triple treatment with octreotide, galanin, and serotonin, 40 µg/kg body weight/day of each. The second subgroup was given sterile saline solution. Treatment lasted for 14 days. The volume and wet weight of the tumours in all treated groups tended to decrease, but was statistically significant only in the group with continuous i.p. infusion. The number of viable cells tended to decrease in all the treated groups, but was not statistically significant. Proliferation index was significantly reduced in mice given triple therapy i.p. as bolus injection and as continuous infusion, as compared with their respective controls. The apoptotic index increased significantly in mice receiving triple therapy as continuous i.p. infusion as revealed by both the TUNEL method and by poly (ADP-ribose) polymerase (PARP) expression. The number of tumour blood vessels was significantly reduced in the mice given triple therapy as continuous i.p. infusion, as compared with controls. There was no statistical difference between animals treated by different routes, regarding proliferation or apoptosis of the cancer cells, or the number or mean luminal area of tumour blood vessels. The present investigation showed that regardless of the route of administration, triple therapy with octreotide, galanin and serotonin generally reduced the volumes, weights, viable cells, vascularization and proliferation of the tumours, as well as inducing apoptosis. Continuous i.p. infusion appears, however, to be the most effective route of administration.
Open Access
EPH receptors in cancer
(Murcia : F. Hernández, 2008) Castaño, Julio; Davalos, Verónica; Schwartz Jr., Simo; Arango, Diego
EPH receptors and their ephrin ligands constitute the largest sub-family of receptor tyrosine kinases (RTKs) and are components of cell signaling pathways involved in animal development. The ability of the EPH/ephrin guidance system to position cells and modulate cell morphology underlies their various roles in development. In addition, EPH signaling plays an important role in oncogenic processes observed in several organs. These receptors are involved in a wide range of processes directly related with tumorigenesis and metastasis, including cell attachment and shape, migration, and angiogenesis. Accordingly, deregulation of EPH expression and signaling activity could be crucial for the tumorigenic process. This review focuses on EPH receptors’ roles in oncogenic transformation and tumor progression.
Open Access
Epigenetic remodelling of DNA in cancer
(Murcia: F. Hernández, 2007) Lettini, A.A.; Guidoboni, M.; Fonsatti, E.; Anzalone, L.; Cortini, E.; Maio, M.
DNA methylation regulates gene expression in normal cells. This epigenetic mechanism acts in at least two different ways: at global genomic level by targeting repetitive sequences distributed among the whole genome (LINEs, SINEs, satellite DNA, transposons) and at local level by targeting CpG islands in promoter regions. Both epigenetic mechanisms are involved in the carcinogenetic process; however, different evidences suggest that promoter hypermethylation occurring in genes involved in cellcycle regulation, DNA repair, cell signalling, transcription and apoptosis likely plays a prominent role. Opposite to genetic defects DNA hypermethylation is a reversible process that can be handled through “epigenetic drugs” in a wide spectrum of tumors. Along this line, recent data have demonstrated the ability of DNA hypomethylating agents to up-regulate and/or induce the expression of genes silenced by promoter hypermethylation in cancer. Particularly relevant seems the ability of these drugs to modulate the expression of genes coding for molecules crucial for tumor immunogenicity and immune recognition of neoplastic cells by host’s immune system, such as Cancer Testis Antigens, HLA class I molecules, costimulatory molecules. These evidences, coupled to the well-known cytotoxic, pro-apoptotic, and differentiating activities of epigenetic drugs, encourage to design and to develop new therapeutic strategies able to circumvent the immune escape of neoplastic cells and to potentiate the efficacy of immunotherapy in cancer patients. This review will provide an update on the most recent information about aberrant DNA methylation in cancer and on innovative therapeutic strategies of “epigenetic remodelling” of human malignancies, with particular attention to the immunologic and immunotherapeutic potential of this approach.
Open Access
Estudio prospectivo randomizado comparando anastomosis latero-lateral isoperistáltica versus antiperistáltica tras hemicolectomia derecha laparoscópica por cáncer
(Universidad de Murcia, 2018-05-09) Ibáñez Cánovas, Noelia; Luján Mompeán, Juan Antonio; Abrisqueta Carrión, Jesús; Facultad de Medicina
La principal complejidad de la hemicolectomía derecha se encuentra en la realización de la anastomosis ileocólica debido a la escasa estandarización de la técnica. Existen multitud de artículos comparando la disposición de las asas, técnica de sutura y lugar de realización, pero no existen estudios bien diseñados acerca del papel de la peristalsis en esta anastomosis. Los objetivos de este estudio son: comparar resultados a corto y largo plazo en términos de morbimortalidad postoperatoria y comparar la calidad de vida entre ambos grupos utilizando para ello el Cuestionario de Calidad de Vida Gastrointestinal (GIQLI). Para ello se ha realizado un estudio prospectivo aleatorizado, en pacientes intervenidos de forma programada por cáncer de colon derecho con hemicolectomía derecha laparoscópica y anastomosis ileocólica iso o antiperistaltica. Se han incluido 108 pacientes, 54 por rama de tratamiento. No existieron diferencias significativas en las variables demográficas. En cuanto a las variables quirúrgicas, no se hallaron diferencias en la tasa de conversión (p=0.500) ni tampoco en el tiempo quirúrgico total (130[120-150]min. en isoperistáltica vs 140[127-160] en antiperistaltica, p=0.481)ni en el tiempo anastomótico (19[17-22] vs. 20[16-25], p=0,207). En cuanto a complicaciones posquirúrgicas: un 37,0% de pacientes en el grupo isoperistaltico y un 40,7% en el grupo en antiperistaltico presentaron algún tipo de complicación, sin diferencias entre ambos (p=0.693). Aunque no se encontraron diferencias significativas, el grupo isoperistáltico presentó una mayor tasa de ileo paralitico con respecto al antiperistaltico (14.8% vs. 5.6%). Durante el postoperatorio, el grupo antiperistaltico presentó mejores resultados con menor tiempo hasta el primer flato y hasta la primera deposición (p=0.004 y p=0.017), sin embargo, este hecho no se tradujo en una menor estancia hospitalaria (p=0.236). A largo plazo, no existen diferencias significativas en las complicaciones ni en la tasa de diarrea crónica al año de la cirugía (p=0.541). Las puntuaciones del test GIQLI fueron similares entre ambos grupos al mes, 6 meses y año, sin diferencias entre ambos grupos (p=0,154, p=0.498 y p=0.683 respectivamente). En conclusión la anastomosis ileocólica isoperistáltica y la antiperistáltica son igual de seguras y factibles no encontrándose diferencias en las variables de seguridad postoperatorias ni tampoco en los resultados del test de calidad de vida. The main complexity of the right hemicolectomy is in the performance of the ileocolic anastomosis due to the scarce standardization of the technique. There are many articles comparing the disposition of bowel loops, suture technique and place of execution, but there are no well-designed studies about the role of peristalsis in this anastomosis. A prospective randomized study was conducted in patients undergoing scheduled surgery for right colon cancer with laparoscopic right hemicolectomy and reconstruction with iso- or antiperistaltic ileocolic anastomosis. Primary endopoint was to compare short and long term results in terms of postoperative morbidity and mortality. Secondary endpoint was to compare quality of life between both groups using the Gastrointestinal Quality Life Index (GIQLI). One hundred and eight patients were included (54 per treatment branch). There were no significant differences in the demographic variables. Regarding surgical variables, no differences were found in conversion rate (p = 0.500) nor in the total surgical time (130 [120-150] min in isoperistaltic vs 140 [127-160] in antiperistaltic, p = 0.481) or anastomotic time (19 [17-22] vs. 20 [16-25], p = 0.207). Regarding postsurgical complications 37.0% of patients in the isoperistaltic group and 40.7% in the antiperistaltic group had some type of complication, without differences between them (p = 0.693). Although no significant differences were found, the isoperistaltic group presented a higher rate of paralytic ileus compared to the antiperistaltic one (14.8% vs. 5.6%). During the postoperative period, the antiperistaltic group showed better results with shorter time until first flatus and until first deposition (p = 0.004 and p = 0.017). However, this did not mean a shorter hospital stay (p = 0.236). In the term results, there are no significant differences in complications or in chronic diarrhea rates one year after surgery (p = 0.541). GIQLI scores were similar between both groups at month, 6 months and a year after surgery, without differences between both groups (p = 0.154, p = 0.498 and p = 0.683 respectively). In conclusion, isoperistaltic and antiperistaltic ileocolic anastomosis are as safe and feasible as there are no differences in the postoperative safety variables or in the results of the quality of life test.