DigitalUM :: Browsing by Subject "Survival"

Browsing by Subject "Survival"

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Brain derived neurotrophic factor maintains Brn3a expression in axotomized rat retinal ganglion cells
(Elsevier, 2009-08-16) Sánchez Migallón, María del Cielo; Nadal-Nicolás, Francisco Manuel; Jiménez López, Manuel; Sobrado Calvo, Paloma; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
The transcription factor Brn3a has been reported to be a good marker for adult rat retinal ganglion cells in control and injured retinas. However, it is still unclear if Brn3a expression declines progressively by the injury itself or otherwise its expression is maintained in retinal ganglion cells that, though being injured, are still alive, as might occur when assessing neuroprotective therapies. Therefore, we have automatically quantified the whole population of surviving Brn3a positive retinal ganglion cells in retinas subjected to intraorbital optic nerve transection and treated with either brain derived neurotrophic factor or vehicle. Brain derived neurotrophic factor is known to delay retinal ganglion cell death after axotomy. Thus, comparison of both groups would inform of the suitability of Brn3a as a retinal ganglion cell marker when testing neuroprotective molecules. As internal control, retinal ganglion cells were, as well, identified in all retinas by retrogradely tracing them with fluorogold. Our data show that at all the analyzed times post-lesion, the numbers of Brn3a positive retinal ganglion cells and of fluorogold positive retinal ganglion cells are significantly higher in the brain derived neurotrophic factor-treated retinas compared to the vehicle-treated ones. Moreover, detailed isodensity maps of the surviving Brn3a positive retinal ganglion cells show that a single injection of brain derived neurotrophic factor protects retinal ganglion cells throughout the entire retina. In conclusion, Brn3a is a reliable retinal ganglion cell marker that can be used to accurately measure the potential effect of a given neuroprotective therapy.
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
Causes of death and survival in alcoholic cirrhosis patients undergoing liver transplantation: influence of the patient’s clinical variables and transplant outcome complications
(MDPI, 2021-05-27) Bolarín, J. M.; Pérez Cárceles, María Dolores; Luna, A.; Minguela, A.; Muro, Manuel; Hernández del Rincón, Juan Pedro; Legaz Pérez, Isabel; Ciencias Sociosanitarias
Background. Clinical and molecular mechanisms involved in the cause and time of death of alcoholic cirrhosis (AC) patients undergoing liver transplantation (LT) are not entirely understood. In sudden death cases, judicial autopsy practice is mandatory for determining the cause and circumstances of death. The medico-legal autopsy data are essential for helping health authorities to guide future public health activities, assess the effectiveness of health systems, and adopt the necessary preventive measures to improve and adapt the treatments in order to increase these patients’ survival. Objective. Our study aimed to determine the different clinical and sociodemographic causes that influence the different causes of death and the short- and long-term survival of AC patients undergoing liver transplantation. Methods. A total of 122 deceased AC patients undergoing LT were analyzed at different times post-transplantation. The main pre- and post-transplant complications were analyzed in relation to the cause of death and the patient’s survival, as well as the causes and time at which the patient’s death occurred. Results. A total of 53.3% of non-sudden death was observed. A large number of the deaths of AC patients undergoing transplantation were due to non-sudden death, sepsis, and graft failure (GF), the main causes of death in the sample being similar in both sexes. In non-sudden deaths, there were no significant differences between the death rates either related or not related to the liver transplant. Sepsis was the main cause, with the highest percentage (21.3%) of mortality, followed by GF (18.9%) and multiorgan failure (15.6%) at ten years. Furthermore, our results showed how pre-transplant clinical complications, such as viral infections and encephalopathy, influence the age at which multiorgan failure occurs in the transplanted patient. Conclusion. Multiorgan failure is the leading cause of sudden death, with higher mortality during the first year after transplantation, followed by sepsis and GF. Our results show the vulnerability of AC patients, both in the hospital period after the transplant and outside.
Open Access
Chemokine CCL14 affected the clinical outcome and correlated with immune infiltrates in thyroid carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Mi mi; Zhao, Yan dong; Li, Qiang; He, Yue jun
Background. As an important member of the chemokines, CCL14 plays a vital role in cancer progression. However, the role of CCL14 in THCA has not been investigated. This study aimed to reveal the clinical significance of CCL14 in THCA. Material and Methods. This study evaluated the expression and prognostic value of CCL14 in THCA. Also, the correlation between CCL14 and immune infiltrates was assessed. Enrichment analysis was finally performed to predict CCL14-associated pathways involved in THCA. Results. The mRNA and protein expressions of CCL14 in THCA tissues were down-regulated compared with normal tissues. CCL14 high expression predicted favorable DFI and PFI but did not influence the DSS and OS. Further, CCL14 showed a good prediction performance on the PFI of patients. Enrichment analysis found that CCL14 was negatively correlated with migration-related pathways such as Notch signaling, ECM-receptor interaction, and cell adhesion molecules. Further, we found that CCL14 was negatively related to immune infiltrates and their gene markers. A negative relationship was also observed between CCL14 and immune checkpoint genes. These results implied the potential effect of CCL14 on the immune response and immune therapy in THCA. Conclusions. CCL14 high expression prolonged the DFI and PFI of THCA patients. It was negatively correlated with the migration-related pathways, suggesting that CCL14 might participate in the recurrence of THCA. Further, CCL14 was also shown to be important in immune response and immune therapy in THCA.
Open Access
Clinical meaning of stromal tumor infiltrating lymphocytes (sTIL) in early luminal B breast cancer
(MDPI, 2023-05-20) García-Torralba, Esmeralda; Pérez Ramos, Miguel; Ivars Rubio, Alejandra; Navarro-Manzano, Esther; Blaya Boluda, Noel; Morena Barrio, Pilar de la; García Garre, Elisa; Martínez Díaz, Francisco; Chaves-Benito, Asunción; García-Martínez, Elena; Ayala de la Peña, Francisco; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5%(Q1–Q3range(IQR),0–10). We found thatsTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02–1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33–17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.
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Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study
(Elsevier, 2009-06-15) Parrilla Reverter, Guillermo; Agudo, Marta; Sobrado Calvo, Paloma; Villegas Pérez, María P.; Vidal Sanz, Manuel; Salinas Navarro, Manuel Ángel; Anatomía Humana y Psicobiología
We examined in adult Sprague Dawley rats the loss of retinal ganglion cells (RGCs) induced by complete intraorbital optic nerve crush (IONC) as well as the effects of several neurotrophic factors to prevent IONC-induced RGC loss. Completeness of the IONC lesion was assessed by investigating the orthograde and retrograde transport of neuronal tracers applied to the origin and termination of the retinotectal pathway. RGC survival after IONC alone or combined with intraocular injection of the neurotrophic factors NT-4, BDNF or CNTF was quantified at survival intervals ranging from 5 to 12 days post-lesion (dpl) by identifying RGCs that had been pre-labelled with fluorogold (FG). RGC loss first appeared at 7 dpl and by 12 dpl only 32% of the RGC population remained in the retina. Intraocular administration of NT-4, BDNF or CNTF resulted in almost a complete protection against IONC-induced RGC loss by 7 dpl, and the protection remained significant by 12 dpl only for NT-4 and BDNF. We have analyzed these results taking into account our previous studies on the loss of RGCs induced by intraorbital optic nerve transection (IONT) and concluded that RGC loss induced by IONC is slower and less severe than that following IONT. Moreover, as for IONT-induced RGC loss, IONC-induced RGC loss may also be prevented with administration of NT-4, BDNF or CNTF, though for NT-4 and CNTF their neuroprotective effects differ depending on the injury type. Overall this data underscore the importance of the type of ON injury on the pattern of RGC degeneration as well as in their response to neuroprotective treatments.
Open Access
Empirical research to identify early warning indicators of insolvency in small and medium-sized enterprises (SMEs)
(Universidad de Murcia, Servicio de Publicaciones, 2024) Navarro-Galera, Andrés; Gómez-Miranda, María Elena; Lara-Rubio, Juan; Buendía-Carrillo, Dionisio
En Europa, la contribución de las PYMEs es enorme en términos de creación de empleo y valor añadido, aunque en los últimos años se han producido preocupantes niveles de quiebra y desaparición de empresas. Estas circunstancias han llevado a diversos investigadores y organismos internacionales a reconocer la necesidad de contar con indicadores que permitan detectar precozmente los riesgos de insolvencia para poder adoptar medidas preventivas y correctoras. En este contexto, la Directiva (UE) 2019/1023 obliga a los Estados miembros de la Unión Europea a definir indicadores de alerta temprana de insolvencia, y en la mayoría de los casos ha sido transpuesta a las respectivas normativas NACIONALES. El objetivo del presente trabajo es identificar indicadores financieros y no financieros de riesgos de insolvencia en las pymes, para facilitar su detección temprana. Para ello, se analiza una muestra de 1.736 PYMEs españolas, estudiando su comportamiento para el periodo 2010-2020. Se identifican determinados factores financieros y no financieros como indicadores de alerta temprana de insolvencia, un resultado que resultará útil tanto para el autodiagnóstico de insolvencia como para el diseño de planes de reestructuración que mejoren las posibilidades de supervivencia de las PYMEs.
Open Access
Entrepreneurship of people with disabilities in Spain: socioeconomic aspects
(Fundación Universitaria Konrad Lorenz, 2019-02-12) Martínez-León, Inocencia; Olmedo-Cifuentes, Isabel; Nicolás Martínez, Catalina; Economía Aplicada; Facultad de Economía y Empresa
El emprendimiento es fundamental para conseguir una mayor inclusión social y laboral del colectivo de discapacitados. Este estudio tiene como principal objetivo profundizar en los aspectos socioeconómicos que influyen en el emprendimiento del individuo discapacitado. Tras un estudio cualitativo por medio de 15 entrevistas semiestructuradas, individualizadas y orales, los resultados muestran que este colectivo presenta una situación socioeconómica concreta que dificulta su emprendimiento y les diferencia del resto de individuos. Básicamente, emprenden por la necesidad de supervivencia, pues tienen menos ingresos y mayores gastos derivados de sus minusvalías, y por su necesidad de autorrealización. La disponibilidad de recursos financieros es normalmente inferior al resto de los individuos, consiguiéndolos esencialmente de su reducido entorno social, recomendándose una especial fiscalidad a medio plazo. El estatus social de reconocimiento por ser autosuficientes y generadores de riqueza es otro importante elemento socioeconómico. Finalmente, se proponen varias medidas orientadas al emprendimiento eficiente de este colectivo.
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Epidemiology, evolution, and long-term survival of alcoholic cirrhosis patients submitted to liver transplantation in southeastern Spain
(Wiley, 2016-04) Navarro Noguera, Elena; Bolarín, Jose M.; García Alonso, Ana M.; Luna Maldonado, Aurelio; Mrowiec, Anna; Campillo, José Antonio; Moya Quiles, Rosa; Álvarez López, María del Rocio; Minguela Puras, Alfredo; Miras, Manuel; Sánchez Bueno, Francisco; Muro, Manuel; Gimeno Arias, Lourdes; Legaz Pérez, Isabel; Ciencias Sociosanitarias
Background Alcoholic cirrhosis (AC) is a common cause of death among individuals abusing alcohol. In the last resort, liver transplantation (LT) is considered the only solution to save the patient's life, generating socioeconomic and public health problems. Clinical and sociodemographic characteristics, rejection frequency, and short- and long-term graft survival are not well known in end-term AC patients undergoing LT. The aim was to determine the sociodemographic and clinical characteristics, their incidence in LT, main pre- and posttransplant complications, and short- and long-term post-transplant graft survival in AC patients in southeastern Spain. Methods The medical records of 1,026 patients who underwent LT over the last 23 years were retrospectively reviewed, and demographic data and posttransplant survivals were analyzed and compared. Biochemical characteristics, major pre- and posttransplant complications and short- and long-term survivals were analyzed in a total of 398 male patients with AC undergoing LT. Results AC and viral cirrhosis are the main indications for LT in our study. Mostly represented in our study are AC men without associated viral infections with a mean age of 53.06 years. Main pretransplant complications in AC patients are ascites (78.3%) and encephalopathy (43.5%), while acute graft rejection is the most common liver posttransplant complication (26.6%), nevertheless with low graft loss frequency (1.1%). AC and autoimmune cirrhosis show the best posttransplant survival in both the short and long term. Patients with AC included on the waiting list for LT were Child-Pugh class B (52.1%) and Model for End-Stage Liver Disease score of 10 to 19 (71.2%). The highest percentage of AC patient survival was observed at 1 year posttransplant (81.2%) and progressively decreased over time up to 10 years posttransplant (69.6%). Pretransplant complications such as ascites and encephalopathy did not have an influence on the percentage of posttransplant survivals, although better survival rates were observed in nonviral AC patients. Conclusions AC without viral infections is the main indication for LT in southeastern Spain although its frequency has decreased in last decade. AC is a good indication for LT for its high survival rate and few posttransplant complications. Despite having a high percentage of pretransplant complications (ascites and encephalopathy) but does not appear to influence survivals being observed posttransplant survival rates above those expected. Conversely, viral infections in the patient with AC decrease patient survivals. The main future goals are design new strategies to detect, treat, and reduce AC frequency in our population and know alcoholic recidivism rate posttransplant in our population.
Open Access
ERCC1 (Excision repair crosscomplementing 1) expression in pT2 gallbladder cancer is a prognostic factor
(Murcia: F. Hernández, 2011) Roa, Iván; Aretxabala, Xabier de; Lantadilla, Soledad; Muñoz, Sergio
Gallbladder cancer (GBC) is the main cause of death by malignant tumour in women in Chile. There is no information regarding the role of excision repair cross-complementing group 1 (ERCC1) in GBC. Our aim is to determine the expression and significance of ERCC1 as a prognostic factor in GBC. Tissue microarrays were prepared using 200 surgically resected GBCs and 50 non-malignant gallbladders as controls. In 190 cases, ERCC1 was determined by immunohistochemistry. The correlation between ERCC1 expression and GBC pathological characteristics and patient survival were analysed. Ninety-five percent of the non-malignant gallbladder epithelia showed intense and diffuse ERCC1 expression. GBC cases showed ERCC1 expression in the tumour cells in 100/190 (53%) cases. The best differentiated tumours showed significantly greater expression than the less differentiated (p<0.05). Patients with ERCC1- positive status with subserosal carcinomas (pT2) had significantly better survival than ERCC1-negative patients at 20 and 60 months of follow-up (p=0.005), and the probability of dying was 6 times lower for ERCC1-positive than for ERCC1-negative patients. Our preliminary results show that cholecystectomised patients with GBC in stage pT2 and with ERCC1 expression have significantly better survival than patients at the same stage that did not present ERCC1 expression.
Open Access
Expression of CXCR4 and MMP-2 is associated with poor prognosis in patients with osteosarcoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Gong, Chen; Sun, Kai; Xiong, Hui-hua; Sneh, Tal; Zhang, Jing; Zhou, Xiao; Yan, Peng; Wang, Jian-hua
Backgroud. Osteosarcoma is a primary malignant tumor with a high tendency to form metastasis and poor prognosis. Consequently, finding effective early indicators of metastases is crucial for identifying and treating high-risk patients. CXCR4 and MMP-2 have been found to strongly correlate with invasion and metastasis of malignant tumors, including osteosarcoma. Materials and Methods. Our study evaluated CXCR4 in conjunction with MMP-2 as an important clinicopathological prognostic predictor for metastasis and overall survival of osteosarcoma. 73 patients’ clinical data and pathological samples were retrieved for the study. A median time of 36 months follow-up was performed to evaluate for tumor metastasis and patient survival. CXCR4 and MMP-2 proteins in tumor tissues were detected by immunohistochemistry on paraffin- embedded tissue sections. Results. The positive expression rate of CXCR4 and MMP-2 was 68.5% and 54.8% respectively, and of the 45 patients who developed distal metastasis, 33 and 28 patients had positive expression of CXCR4 and MMP-2 respectively. The median metastasis-free survival was 72.00 months in the CXCR4-negative group and 14.00 months in the CXCR4 positive group. Furthermore, median overall survival was 73.77 and 24.00 months in these same two groups. Further, the median metastasis-free survival was 66.51 months in the MMP-2 negative group and 9.00 months in the MMP-2 positive group. The median overall survival was 75.07 and 19.00 months in these same two groups. MMP2 and metastasis remained the significant and independent prognostic factors for metastasis-free survival and overall survival by using the COX regression model adjusted for the multivariate predictors of survival. Conclusion. Our results suggest that metastasis and MMP-2 are both independent prognostic indicators for metastasis-free and overall survival of osteosarcoma patients.
Open Access
Expression of γ-tubulin in non-small cell lung cancer and effect on patient survival
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Maounis, Nicoletta F.; Dráberová, Eduarda; Trakas, Nikos; Chorti, María; Riga, Dimitra; Tzannis, Kimon; Kanakis, Meletis; Voralu, Kirtanaa; Ellina, Eleni; Mahera, Eleni; Demonakou, Maria; Lioulias, Achilleas; Dráber, Pavel; Katsetos, Christos D.
Introduction. It has been reported that overexpression and altered compartmentalization of γtubulin may contribute to tumorigenesis and tumor aggressiveness in a variety of human malignancies. We have shown that γ-tubulin expression and cellular distribution pattern is also altered in non-small cell lung cancer (NSCLC) (Histol. Histopathol. 2012; 27: 1183- 1194). In the present study we examined the relationship between γ-tubulin expression and patient overall survival (OS). Material and methods. Immunohistochemistry was performed, with well-characterized anti-γ-tubulin antibodies, on 109 formalin-fixed, paraffin-embedded NSCLC specimens (p-TNM stage IIII). γ-Tubulin labeling indexes (LIs) were determined, and the association of γ-tubulin expression with clinicopathological parameters was evaluated. To analyze OS rates according to γ-tubulin LIs, patients were categorized into three groups: those with low (0- 30%), intermediate (31-69%) or high (70-100%) γtubulin LI. Association of clinicopathological parameters and γ-tubulin with survival were examined using univariate and multivariate Cox regression analysis. Results. No statistically significant association was seen between γ-tubulin overexpression and histological type, tumor differentiation, p-TNM stage and adenocarcinoma subtyping. Longer survival was observed in the high γtubulin LI group of patients with p-TNM stages II+III when compared to intermediate or low γ-tubulin LI groups, but the difference was not statistically significant (p=0.066). On the other hand, when combined low and intermediate γ-tubulin LI groups (p-TNM stages II+III) where compared to high γ-tubulin LI group, statistically significant longer survival was observed in high γtubulin group (p=0.021). Conclusion. Our findings suggest that level of γ-tubulin expression may have an impact on patient survival at more advanced NSCLC stages.
Open Access
Glucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis
(Murcia : F. Hernández, 2009) Pizzi, Sara; Porzionato, Andrea; Pasquali, Claudio; Guidolin, Diego; Sperti, Cosino; Fogar, Paola; Macchi, Verónica; De Caro, Raffaelle; Pedrazzoli, Sergio; Parenti, Anna
The purposes of this study were to evaluate the prognostic significance of Glut-1 expression in patients with pancreatic ductal adenocarcinoma, and to analyse its expression in pancreatic intraepithelial neoplasias (PanIN) and non invasive intraductal papillary mucinous neoplasms (IPMN). Glut-1 expression was studied by immunohistochemistry in 60 pancreatic ductal adenocarcinomas and scored on a 4- point scale (1: <25%; 2: 25-50%; 3: 50-75%; 4: >75%). Relationships between Glut-1 score, histological grade and MIB-1 score were evaluated by the Spearman rank correlation test. Significant correlations were found between Glut-1 expression and histological grade (P<0.001) and MIB-1 score (P<0.01). Significant prognostic factors by univariate analysis were stage (P<0.0001), histological grade (P<0.001) and Glut-1 expression (P<0.005). Independent prognostic factors after multivariate analysis were stage (P<0.001) and Glut-1 expression (P<0.05), stratified as <50% and >50%. The correlation of Glut-1 score with histological grade and MIB-1 score indicated a higher glucose uptake in poorly differentiated and highly proliferative pancreatic cancer cells. Glut-1 immunohistochemical expression provides a useful prognostic factor in pancreatic ductal adenocarcinoma. Glut-1 expression was not found in PanINs 1 but in 27.8% and 43.8% of PanINs 2 and 3, and was not found in IPMNs with lowand moderate-grade dysplasia but in 60% of IPMNs with high-grade dysplasia, indicating Glut-1 involvement in a relatively early phase of pancreatic carcinogenesis.
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Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies
(Taylor and Francis Group, 2020-03-16) Ros-Martínez, Silverio; Navas-Carrillo, Diana; Alonso-Romero, José Luis; Orenes-Piñero, Esteban; Medicina
The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is based on disease progression as a tumor cell-autonomous process, regardless the effects of the host immune response. The natural history of a tumor includes different phases of growth, migration and invasion. During these phases, tumor cells interact with their microenvironment and are influenced by signals from stromal, endothelial, inflammatory and immune cells. Indeed, tumors are often infiltrated by defensive cells such as lymphocytes, macrophages or mast cells and it has been shown extensively that lymphocytes may control cancer outcome, as evidenced in several human malignancies. Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based immunoscore (IS) has proved to be a prognostic factor in human malignancies such as colon, pancreas and lung cancer, hepatocellular carcinoma, melanoma and even brain metastases. Although the IS was initially established to evaluate the prognosis of stage I/II/III colon cancer patients, its association with clinical outcomes and survival has been shown in other malignancies. The aim of this review is to analyze the association of IS with prognosis, survival and response to therapy in different tumor types.
Open Access
Incidence trends and main features of Gastro-Intestinal Stromal Tumours in a Mediterranean region: a population-based study
(MDPI, 2023-05-30) Vaamonde Martín, Ricardo J.; Ballesta Ruiz, Mónica; Sánchez Gil, Antonia; Fernández Hernández, Juan Ángel; Martínez Barba, Enrique; Martínez García, Jerónimo; Gatta, Gemma; Chirlaque López, María Dolores; Ciencias Sociosanitarias; Facultades de la UMU::Facultad de Enfermería
Gastro-Intestinal Stromal Tumours (GISTs) are a kind of neoplasm whose diagnosis in common clinical practice just started in the current century, implying difficulties for proper registration. Staff from the Cancer Registry of Murcia, in southeastern Spain, were commissioned by the EU Joint Action on Rare Cancers into a pilot study addressing GIST registration that also yielded a population-based depiction of GISTs in the region, including survival figures. We examined reports from 2001 to 2015 from hospitals as well as cases already present in the registry. The variables collected were sex, date of diagnosis, age, vital status, primary location, presence of metastases, and risk level according to Joensuu’s Classification. In total, 171 cases were found, 54.4% occurred in males, and the mean age value was 65.0 years. The most affected organ was the stomach, with 52.6% of cases. Risk level was determined as “High” for 45.0%, with an increment of lower levels in recent years. Incidence for the year 2015 doubled that of 2001. Overall, the 5-year net survival estimation was 77.0%. The rising incidence magnitude is consistent with trends in other European countries. Survival evolution lacked statistical significance. A more interventional approach in clinical management could explain the increase in the proportion of “Low Risk GISTs” and the first occurrence of “Very Low Risk” in recent years.
Open Access
Increased expression of matrix metalloproteinase-2 -MMP-2- predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer
(Murcia : F. Hernández, 2008) Leinonen, Tero; Pirinen, Risto; Böhm, Jan; Johansson, Risto; Kosma, Veli-Matti
The purpose of this study was to analyse the expression of matrix metalloproteinase-2 (MMP-2) and its extracellular matrix metalloproteinase inducer (EMMPRIN) in non-small cell lung cancer (NSCLC), and to evaluate their significance to predict tumour behaviour. The study consists of 212 patients treated by the resection of the tumour. Tumour samples were stained immunohistochemically, and the expression of MMP-2 and EMMPRIN was evaluated both in tumour cells and in peritumoural stromal tissue. The results were compared with clinicopathological factors and survival of the patients. High expression of MMP-2 in tumour cells was found in 83 out of 191 cases (44%). Adenocarcinomas showed more often high expression of MMP-2 as compared with squamous cell or large cell carcinomas (p=0.001). High cancer cell associated MMP-2 expression was associated with increased tumour recurrence (p=0.001). Tumour stroma showed positive staining in 162 (98%) cases and was considered highly stained in 120 (72%) cases. The high stromal MMP-2 expression was noticed more often among large cell carcinomas as compared with other histological types (p=0.007). High cancer cell associated EMMPRIN expression was found in 115 (61%) cases and was associated only with high MMP-2 expression in tumour cells (p=0.006). In overall survival (OS) and disease free survival (DFS) analyses, type of tumour (p=0.001 and p=0.0004), advanced stage (p=0.001 and p=0.013) and high MMP-2 expression in tumour cells (p=0.018 and p=0.001) were associated with poor survival. Also, high stromal MMP-2 expression was related to poor outcome in both OS and DFS analyses (p=0.010 and 0.045, respectively). In multivariate analysis, stromal MMP-2 expression retained its prognostic value to predict OS and DFS (p=0.028 and p=0.039, respectively), together with tumour type and stage (p=0.017, p=0.001 and p=0.021, p=0.008, respectively). The present study shows the significant prognostic value of MMP-2 in NSCLC suggesting that the use of MMP-2 is valuable in determining the patients with more aggressive disease.
Open Access
Influence of preformed antibodies in liver transplantation
(MDPI, 2020-03-05) Boix, Francisco; López, Manuela; Alfaro, Rafael; Galián, José A.; Llorente, Santiago; Campillo, José A.; Botella, Carmen; Ramírez, Pablo; Sánchez Bueno, Francisco; Pons, José A.; Moya Quiles, María R.; Minguela, Alfredo; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
The significance of human leukocyte antigen (HLA) matching and preformed donor-specific antibodies (DSAs) in liver transplantation remains unclear. The aim of this study was to analyze the presence of DSAs in a large cohort of 810 liver recipients undergoing liver transplant to determine the influence on acute (AR) or chronic liver rejection (CR), graft loss and allograft survival. DSAs were identified using complement dependent cytotoxicity crossmatch (CDC-CM) and multiplexed solid-phase-based flow cytometry assay (Luminex). CDC-CM showed that a 3.2% of liver transplants were positive (+CDC-CM) with an AR frequency of 19.2% which was not different from that observed in negative patients (−CDC-CM, 22.3%). Only two patients transplanted with +CDC-CM (7.6%) developed CR and suffered re-transplant. +CDC-CM patients showed a significantly lower survival rate compared to −CDC-CM patients (23.1% vs. 59.1%, p = 0.0003), developing allograft failure within the first three months (p < 0.00001). In conclusion, we have demonstrated a relationship between the presence of preformed DSAs and the low graft liver survival, indicating the important role and the potential interest of performing this analysis before liver transplantation. Our results could help to detect patients with an increased risk of graft loss, a better choice of liver receptors as well as the establishment of individualized immunosuppressive regimens.
Open Access
Long non-coding RNA BRE-AS1 inhibits proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating miR-106b-5p
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zou, Gaode; Guo, Lian; Shen, Shaochen; Song, Zhen; Ouyang, Zheying; Yu, Yi
Objective. The objective of this study was to investigate the involvement of the long non-coding RNA (lncRNA) BRE-AS1 in clear cell renal cell carcinoma (ccRCC) and to explore its potential therapeutic role. Methods. The expression of BRE-AS1 and miR-106b-5p was determined by qRT-PCR. Overexpression of BRE-AS1 and miR-106b-5p were performed to study their relationship. Transwell assays were used to evaluate cell movement. Methylation-specific PCR (MSP) was performed to explore the role of BRE-AS1 in the methylation of the miR-106b-5p gene. Results. The results showed that the expression levels of BRE-AS1 were decreased, while those of miR-106b-5p were increased in ccRCC tissues. BRE-AS1 was found to be closely associated with the prognosis of patients with ccRCC. The expression of BRE-AS1 was inversely correlated with that of miR-106b-5p in tumor tissues. Overexpression of BRE-AS1 led to decreased expression levels of miR-106b-5p and increased methylation of the miR-106b-5p gene, whereas miR-106b-5p did not affect the expression of BRE-AS1. BRE-AS1 inhibited the movement and proliferation of ccRCC cell lines, while miR-106b-5p suppressed the role of BRE-AS1. Conclusion. BRE-AS1 may suppress ccRCC by downregulating the expression of miR-106b-5p.
Open Access
Modelos de Inteligencia artificial SVM-SHAP y Logísticos para identificación de factores de supervivencia y resultados clínicos en residencias de mayores en España.
Pastor Zorita, Andrea; Bote Díaz, Marcos Alonso; Pastor Seller, Enrique; Enfermería; Escuela Internacional de Doctorado
Introducción: El cuidado de personas mayores institucionalizadas representa un desafío importante en sociedades envejecidas como España. La creciente demanda de cuidados de larga duración, junto con los recursos limitados, hace necesario identificar los factores que influyen en la calidad asistencial y los resultados clínicos. Este estudio combina métodos de inteligencia artificial y análisis estadísticos para analizar las variables asociadas con la mortalidad, la supervivencia y otros resultados clínicos, proporcionando recomendaciones basadas en evidencia para mejorar la gestión de las residencias de mayores. Asimismo, esta investigación busca contribuir al desarrollo de estrategias efectivas que optimicen los recursos disponibles, promoviendo un cuidado más eficiente y humano. Métodos: Se realizó un estudio observacional en ocho residencias de la comarca Marina Alta, Alicante, con una muestra de 497 residentes. Los datos se recopilaron considerando variables demográficas, clínicas y de infraestructura, como los niveles de dependencia, ratios de personal y resultados clínicos. Los análisis se llevaron a cabo mediante regresión logística binaria y modelos de máquinas de vectores de soporte con kernel de función base radial. Para interpretar las contribuciones de cada variable para Supervivencia, se utilizó SHAP. Todos los análisis se realizaron utilizando R. Resultados: El análisis mostró que una mayor ratio enfermera/residente incrementó significativamente la supervivencia, con un OR = 8.03, IC 95% [4.45, 14.51], p < 0.05. Un incremento del 1% en habitaciones individuales disminuyó la probabilidad de mortalidad, con un OR = 0.23, IC 95% [0.15, 0.35], p < 0.05. Ratios más altas de auxiliares de enfermería redujeron las complicaciones y aumentaron la supervivencia, con un OR = 0.12, IC 95% [0.05, 0.32], p < 0.05. Un aumento en las derivaciones hospitalarias estuvo asociado con una mayor incidencia de úlceras por presión, con un OR = 1.02, IC 95% [1.01, 1.03], p < 0.05. Mayores ratios de auxiliares actuaron como un factor protector, reduciendo la prevalencia de úlceras, con un OR = 0.12, IC 95% [0.05, 0.32], p < 0.05. Discusión: Los hallazgos destacan la relevancia de los recursos humanos y la infraestructura en la mejora de los resultados clínicos y la supervivencia en residencias de mayores. La disponibilidad de habitaciones individuales y personal suficiente son factores clave para reducir la mortalidad y complicaciones. Los modelos avanzados de IA, como el SVM-SHAP, permiten analizar interacciones complejas entre variables, proporcionando información más precisa para guiar decisiones políticas y administrativas basadas en evidencia. El análisis mediante SHAP aporta una perspectiva innovadora en la gestión sanitaria, maximizando los resultados a partir de intervenciones específicas. Conclusiones: El estudio evidencia la necesidad de implementar sistemas estandarizados en España para monitorear y mejorar la calidad asistencial en residencias de mayores. Aumentar las ratios de enfermería, de auxiliares y habitaciones individuales podría traducirse en mejoras significativas en la supervivencia y calidad de vida de los residentes. Los modelos de IA, como el SVM-SHAP, son herramientas valiosas para optimizar la gestión y los cuidados en estos entornos.
Open Access
Mutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Chung, Yumin; Lee, Hyoun Wook; Park, Jung Ho; Yoo, Chang Hak; Son, Byung Ho; Kim, Kyungeun
Background. TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. Methods. Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semiquantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). Results. Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. Conclusions. Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.

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