Browsing by Subject "Chemotherapy"
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- PublicationOpen AccessAn update on the pathobiological relevance of nuclear receptors for cancers of the head and neck(Murcia : F. Hernández, 2010) Stauber, Roland H.; Wünsch, Desiree; Knauer, Shirley K.; Fetz, VerenaCancers of the head and neck are among the most common neoplasms worldwide, characterized by local tumor aggressiveness, high rate of early recurrence, development of metastasis and second primary tumors. Although disease management of head and neck cancer has improved significantly, overall survival-rates remained largely unchanged over the last decades. Thus, in addition to modern chemo-radiation treatment strategies combined with sophisticated surgery, there is still a need for molecular markers and key regulatory factors exploitable for chemoprevention and targeted therapies. A critical event in carcinogenesis is the uncontrolled modulation of genetic programs, mediated by deregulated signaling cascades, together with downstream transcriptional modulators. Hence, nuclear receptors, belonging to a superfamily of transcription factors implicated in a broad spectrum of physiological and pathophysiological processes, have also been associated with HNC. Enhanced expression of several nuclear receptors has been shown in head and neck cancer cells, and strategies targeting these molecules have been developed and tested in the clinics. In particular, the effects of retinoids targeting nuclear receptors of the thyroid hormone receptor-like receptor subfamily have been vigorously examined in large clinical chemoprevention trials. This review seeks to provide a general overview of nuclear receptors’ molecular functions and summarizes their prognostic/therapeutic relevance, as well as the (pre)clinical studies targeting nuclear receptors in HNC.
- PublicationOpen AccessCox and mesothelioma: an overview(Murcia : F. Hernández, 2005) Cardillo, I.; Spugnini, E.P.; Verdina, A.; Galati, R.; Citro, G.; Baldi, A.Cyclooxygenases catalyze the rate limiting step in the production of prostanoids. Accumulating data demonstrate that overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Malignant mesothelioma is a lethal pleural, peritoneal and pericardial neoplasia that actually lacks valid therapies and in which cyclooxygenases-2 is recognized as an important adverse prognostic factor. Hence, there is an increasing interest in the development of new treatments based on cyclooxygenases-2 inhibitors, to prolong survival and even potentially cure this neoplasia.
- PublicationOpen AccessCOX-2 overexpression in canine tumors: potential therapeutic targets in oncology(Murcia : F. Hernández, 2005) Spugnini, E.P.; Porrello, A.; Citro, G.; Baldi, A.Cyclooxygenases catalyze the initial, ratelimiting steps of prostaglandin synthesis from arachidonic acid. Two isoforms of this enzyme exist in mammalian and avian species: COX-1 and COX-2. COX-1 is constitutively expressed and is the major isoform of gastrointestinal tissue. COX-2 is induced in response to inflammatory stimuli. COX-2 has been implicated in carcinogenesis of several neoplasms. Furthermore, COX-2 over-expression has been noted in many solid tumours and has been correlated with a worse prognosis in colorectal cancer, non-small-cell lung cancer, mesothelioma and gastric cancer. In this review, the most recent findings on the mechanisms by which COX-2 promote tumorigenesis are discussed, with particular emphasis on the studies involving spontaneous canine neoplasms.
- PublicationOpen AccessIn vitro analysis of the cellular resistance to chemotherapeutic BCNU(Murcia : F. Hernández, 1992) Caballero Navarro, A.; Conde Guerri, B.; Sinués Porta, E.; Boada Apilluelo, E.; Alcalá Arellano, A.Our asays in vitro show that BCNU inhibits cell proliferation in the Ca cell line experimental glioma and is dose-dependent, starting from 0.5 pg/ml of the drug with just an hour of exposure. For every tested concentration of BCNU it is shown that, from the fifth day after exposure, cellular resistance appeared. This resistance is justified by the capacity of cell DNA reparation. A study of the clonogenic capacity of the Ca cells exposed to BCNU also shows the appearance of cellular resistance for doses of 0.5 pglml and 1 pglml. Furthermore, the exposure of Ca cell cultures to BCNU at these levels produces a cellular evolution towards more differentiated morphological patterns.
- PublicationOpen AccessIn vitro treatments for the theront stage of the ciliate protozoan Cryptocaryon irritans(Inter-Research Science Publisher, 2011-04-06) Picón-Camacho, S.M.; Ruiz de Ybáñez, M.R.; Holzer, A.S.; Arizcun Arizcun, M.; Muñoz, P.; Sanidad AnimalThe ciliate protozoan Cryptocaryon irritans Brown, 1951, the ‘marine white spot’, causes one of the most important parasitic fish diseases, with extensive losses every year in mariculture and in the ornamental fish industry. In the present study, we explore the in vitro use of 8 different com- pounds against the theront (infective) stage of C. irritans ; these compounds include extracts of natural products (epigallocatechin gallate (EGCG), L-DOPA, papain), peracetic acid-based compounds (Proxitane® 5:23 and 15% peracetic acid, PAA), quinine-based compounds (quinacrine hydrochloride and chloroquine diphosphate) and hydrogen peroxide. All of these compounds had an effect on theront survival; however, only EGCG caused significant theront mortality when applied in doses≥50 mg l–1 and over a period of 3 h; papain caused a maximum theront mortality of < 50%. We discuss the type of application and potential utility of the compounds tested as part of a management control strategy for C. irritans infections in marine aquaculture and the ornamental fish industry.
- PublicationOpen AccessIntratumoral T cells are associated with prognosis and chemotherapy benefit in gastric cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Liu, Lu; Chen, Qianwen; He, Chen; Xie, Feilan; Su, Shengyuan; Wang, Lijun; Liu, JintaoTumor-infiltrating lymphocytes (TILs) have been described in various malignancies and viewed as a sign of anti-tumor immunity, so they are frequently thought to be implicated in the prognosis of cancers. However, little information is available on the association of the distribution pattern of TILs with clinical outcomes in gastric cancer (GC). TIL densities at different regions were assessed immunohistochemically in 59 GC patients to analyze their relationship with clinicopathological characteristics. We found that GC patients in the high-density TIL group were significantly associated with reduced tumor invasion depth, absence of lymph node metastasis, earlier TNM stage, and improved progression-free survival (PFS). Both intratumoral CD3+ TILs and pathological T stage were identified as having an independent prognostic value. Additionally, GC patients with a high density of intratumoral CD3+ TILs were found to gain more benefit from chemotherapy. Overall, these results underscored the predictive power of intratumoral TILs in survival prognosis and chemotherapy benefit for GC
- PublicationRestrictedLinfomas primarios del timo(Elsevier, 2006-07) Ríos, A.; Torres, J.; Roca, M.J.; Galindo, P.J.; Alonso-Romero, José Luis; Parrilla, P.; MedicinaIntroducción. Los linfomas primarios tímicos (LPT) son infrecuentes, pero su pronóstico va ligado a un tratamiento precoz. Se realiza una revisión de esta patología en nuestro hospital con el objetivo de determinar cuál es el mejor manejo diagnóstico-terapéutico en estos pacientes. Material y métodos. Se revisan diez LPT, cuatro Hodgkin y seis no Hodgkin (4 linfomas primarios mediastínicos B [LPMB] y 2 linfomas linfoblásticos T [LLT]). La edad media fue de 23 ± 10 años, siendo la mayoría mujeres. Resultados. En los linfomas de Hodgkin la sospecha diagnóstica inicial fue de timoma en dos casos y de linfoma en los dos restantes. Todos fueron intervenidos, realizándose una biopsia intraoperatoria, completándose con una timectomía en los dos que informó de timoma. Se trataron con radioquimioterapia. En dos casos la respuesta fue parcial, completándose el tratamiento con un trasplante de médula ósea (TMO) (uno fue éxitus, y el otro presenta enfermedad activa). Los linfomas no Hodgkin (LNH) presentaban grandes tumoraciones y una evolución corta. Todos fueron intervenidos, realizándose en cuatro una biopsia y en dos una timectomía. Se trataron con quimioterapia, asociándose en dos radioterapia. La respuesta fue total en tres, recidivando dos, que tras TMO están en remisión completa. En los tres restantes la respuesta fue parcial. Conclusiones. Ante un paciente con tumoración tímica sugestiva por el estudio preoperatorio o intraoperatorio de linfoma debe realizarse una biopsia quirúrgica y no cirugía resectiva para evitar resecciones y morbilidad quirúrgica innecesaria. Los LPT son infrecuentes pero agresivos, sobre todo los LNH, siendo su principal tratamiento la radioquimioterapia, asociada a TMO en casos seleccionados.
- PublicationOpen AccessNeoplasias primarias del timo de estirpe no linfoide. Estudio de 58 casos(Elsevier, 2004) Ríos Zambudio, Antonio; Torres Lanzas, Juan; Galindo Fernández, Pedro José; Roca Calvo, María José; Alonso-Romero, José Luis; Sola Pérez, Joaquín; Parrilla Paricio, Pascual; MedicinaFundamento y objetivo: Los tumores primarios del timo de estirpe no linfoide son infrecuentes, aunque presentan una gran variedad. El objetivo de este trabajo es identificar las variables clínicas, terapéuticas e histológicas que tienen valor pronóstico. Pacientes y método: Se estudiaron 58 tumores primarios del timo de estirpe no linfoide que correspondieron a 52 neoplasias epiteliales (NEPT) (90%), 4 timolipomas (7%) y 2 tumores neuroendocrinos(3%). La clínica más frecuente fue la miastenia grave (41%) y la disnea (21%).Cabe destacar la presencia de 13 pacientes asintomáticos (24%). Para el análisis estadístico se utilizaron las curvas de supervivencia de Kaplan-Meier y el modelo de regresión de Cox. Resultados: Se intervino a todos los pacientes con timectomía, excepto en 4 casos en que se efectuó una biopsia. La mortalidad perioperatoria fue del 3% (n = 2) y la morbilidad, del 31%(n = 18), principalmente por afecciones respiratorias y de la herida. Se administró tratamiento adyuvante con quimioterapia y/o radioterapia en las 24 NEPT grados de Masaoka III y IV, y en el carcinoma linfoepitelial. Con un seguimiento medio (DE) de 13 (5) años, fallecieron 12 pacientes con NEPT y 1 con un tumor neuroendocrino, debido a evolución de la enfermedad. La supervivencia acumulada fue del 80% a los 5 años, del 71% a los 7 años y del 63% a los 10años. Actualmente existen 2 recidivas locales en 2 NEPT, tras 9 y 8 años de seguimiento, respectivamente. Los principales factores pronósticos son el tipo y subtipo histológicos, así como el estadio clínico (p < 0,001). Conclusiones: El diagnóstico precoz en los tumores primarios del timo de estirpe no linfoide es fundamental para instaurar un tratamiento correcto antes de que presenten un estadio clínico más avanzado. Los principales factores pronósticos son el tipo y subtipo histológicos, así como el estadio clínico.
- PublicationOpen AccessPembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study(BioMed Central, 2022-12-03) Cruz-Merino, L. de la; Gion, M.; Cruz, J.; Alonso-Romero, José Luis; Quiroga, V.; Andrés, R.; Santisteban, M.; Ramos, M.; Holgado, E.; Cortés, J.; López-Miranda, E.; Cortés, A.; Henao, F.; Palazón-Carrión, N.; Rodriguez, L. M.; Ceballos, I.; Soto, A.; Puertes, A.; Casas, M.; Benito, S.; Chiesa, M.; Bezares, S.; Caballero, R.; Jiménez‑Cortegana, C.; Sánchez‑Margalet, V.; Rojo, F.; MedicinaBackground: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit of.
- PublicationOpen AccessPrincipales complicaciones asociadas a la administración de quimioterapia intraperitoneal y endovenosa en pacientes con cáncer de ovario(Universidad de Murcia, 2017) Palmés Ferrera, Mercedes; Andersson Vila, Cassandra Ixena; Barrera Reyes, María del Carmen; García Gigán, María del Carmen; Graells Piqué, María Alba; Gómez Rodríguez, EstherAntecedentes: El cáncer de ovario causa más muertes que cualquier otro tipo de cáncer ginecológico. La mayoría de casos se diagnostican en una etapa avanzada de la enfermedad y el tratamiento de elección es generalmente la terapia combinada de quimioterapia intraperitoneal (IP) y endovenosa (EV). A pesar de que esta opción farmacológica ha demostrado alargar la supervivencia, se han reportado múltiples efectos adversos asociados a dicho tratamiento. Objetivo: Identificar los efectos adversos y las complicaciones derivadas del tratamiento con quimioterapia IP+EV en pacientes con carcinoma de ovario avanzado a partir de estadio IIIC, durante el periodo 2007-2015. Metodología: Se realizó un estudio descriptivo, longitudinal y retrospectivo. Un grupo de 17 mujeres diagnosticadas con cáncer de ovario a partir de estadio III fueron tratadas con quimioterapia IP+EV en el Hospital Clínic de Barcelona durante el periodo 2007-2015. Resultados: De las 17 pacientes que recibieron tratamiento con quimioterapia IP+EV, sólo 5 (29,41%) finalizaron los 6 ciclos de tratamiento. De forma notable, 12 (70,58%) pacientes no completaron el tratamiento debido a una serie de complicaciones, que fueron frecuentemente asociadas al reservorio IP y a trastornos psicológicos. Los principales efectos adversos reportados fueron astenia, neurotoxicidad y dolor abdominal. Conclusiones: La mayoría de pacientes interrumpieron la terapia debido a complicaciones relacionadas con el reservorio IP y trastornos psicológicos. Creemos que la enfermera juega un papel importante, no sólo en el manejo de los aspectos técnicos de la terapia, sino también en el soporte emocional a dichas pacientes durante esta etapa
- PublicationOpen AccessRadiation retinopathy: electron microscopy of retina and optic nerve(Murcia : F. Hernández, 1992) Krebs, Ingeborg P.; Krebs, Wolf; Merriam, John C.; Gouras, Peter; Jones, Ira S.A 4 112 year old female was treated for embryonal rhabdomyosarcoma of the left orbit in 1975 with radiation (59.5 Gy in 5 weeks), followed by chemotherapy. An electroretinogram (ERG) in March, 1988 revealed cone responses 3% of normal and no rod responses in the left eye, and normal responses in the right eye. The eye was enucleated in April 1988. In the fovea no choroidocapillaris was seen at the intact Bruch's membrane, and the pigment epithelium was preserved only in small patches. No photoreceptor cells were seen in the areas devoid of pigment epithelial cells. The parafoveal and peripheral (30° eccentricity) retina was better preserved. The thickness of the layer of rods and cones and of Henle's fiber layer was reduced. Very few outer segments were present. Macrophages had invaded the retinal tissue in moderate numbers. The retinal vessels were ensheathed by several layers of collagen fibrils. The spatial densities of pigment epithelial, cone, rod, and bipolar cells had been reduced. The optic nerve contained a total number of 1,022,000 nerve fibers
- PublicationOpen AccessTumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chaudhary, Pratima; Yadav, Pragya; Manna, Partha Pratim; Biología Celular e HistologíaLymphoma is a common type of cancer that occurs in humans. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype and is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME) in lymphoma is critical for the initiation, progression, and metastasis of tumors and influences the therapeutic efficiency of chemotherapy or immuno-therapy, including cell therapy or appropriate combinations of therapeutics. The role of effector immune cells in the development and progression of DLBCL is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators, and structural components present in the TME. Recruitment of immune cells in the TME and their distinct effects on tumor progression and therapeutic outcomes in the presence of therapy have decisive effects on the outcome of therapy. In this review, we discuss the application and implications of binary therapy involving suboptimal-dose chemotherapy and adoptive cell therapy on the basis of our recent findings on γc cytokine-aided cross-talk between dendritic cells and natural killer cells in therapy against experimental murine lymphoma. This novel therapeutic protocol induces a healing response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1. We discuss the various aspects of binary therapy covering multiple issues, including the participation of cell subsets and checkpoint inhibitors in the treatment of malignant lymphoma. These new therapies involve the induction of adoptive cell therapy through the passive transfer of immunologic effectors in addition to a suboptimal dose of adriamycin (doxorubicin hydrochloride) to increase the ability of the immune system to react against tumor antigens, inducing the destruction of tumor cells.
- PublicationOpen AccessVisual deficits and diagnostic and therapeutic strategies for neurofibromatosis type 1: bridging science and patient-centered care(MDPI, 2024-05-09) Miyagishima, Kiyoharu J.; Qiao, Fengyu; Stasheff, Steven F.; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y OptometríaNeurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. Mutations in neurofibromin, the protein encoded by the Nf1 tumor suppressor gene, result in dysregulation of the RAS/MAPK pathway leading to uncontrolled cell growth and migration. Neurofibromin is highly expressed in several cell lineages including melanocytes, glial cells, neurons, and Schwann cells. Individuals with NF1 possess a genetic predisposition to central nervous system neoplasms, particularly gliomas affecting the visual pathway, known as optic pathway gliomas (OPGs). While OPGs are typically asymptomatic and benign, they can induce visual impairment in some patients. This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. We focus on recent advancements in preclinical animal models to elucidate the underlying mechanisms of NF1 pathology and therapies targeting NF1-OPGs. Overall, our review highlights the involvement of retinal ganglion cell dysfunction and degeneration in NF1 disease, and the need for further research to transform scientific laboratory discoveries to improved patient outcomes.