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1.
Eur J Obstet Gynecol Reprod Biol ; 268: 129-134, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34915392

RESUMEN

OBJECTIVES: To evaluate the incidence of HPV infection, and the frequency of the various genotypes, using mRNA and DNA testing; to assess their relationship with the cervical lesions and women's age in the Polish patients. STUDY DESIGN: A group of 1840 women, most of whom had abnormal cytology, from the Franciszek Lukaszczyk Oncology Centre in Bydgoszcz, Poland were screened for presence of at least one of 13 high risk HPV. Following that, 545 HPV DNA positive women were tested for HPV infection using HPV mRNA with the Nucleic Acid Sequence-Based Amplification Assay (NASBA) method. RESULTS: In our study group, 70.1% had DNA HPV positive results. Only 4% of the women had normal cytology. Among 545 HPV DNA positive patients, 36.3% had HPV mRNA positive tests. Moreover, 48% of the HPV mRNA positive patients were infected with HPV 16, followed by 18 (12.6%), 31 (10.1%), 33 (8.6%%), 45 (4.5%), and 16.2% of HPV mRNA positive women were infected with more than one HPV genotype. Furthermore, we found that in women under 30, HPV DNA positivity was higher than HPV mRNA positivity, supporting the hypothesis that younger women's infections are mostly temporary. CONCLUSIONS: The differences in HPV prevalence and genotype distribution observed in our study may have an impact on the efficacy of HPV vaccinations for cervical cancer and the development of screening programs, which should be examined further in future studies.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , ADN Viral , Detección Precoz del Cáncer , Femenino , Genotipo , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Polonia/epidemiología , ARN , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología
2.
Brain Sci ; 11(11)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34827431

RESUMEN

Stereotactic biopsy of posterior fossa lesions is often regarded as hazardous due to the critical structures in that area. Therefore, the aim of the study was to evaluate the diagnostic accuracy and safety of infratentorial stereotactic biopsy of brainstem or cerebellar lesions and its associations with other clinical, laboratory, and radiological parameters. From January 2000 to May 2021, 190 infratentorial stereotactic biopsies of posterior fossa tumors, including 108 biopsies of brainstem lesions, were performed. Moreover, 63 supratentorial biopsies of cerebral peduncle lesions were analyzed to compare the safety and efficacy of both approaches. Additionally, the presence of antibodies against Toxoplasma gondii and Epstein-Barr Virus (EBV) were documented in 67 and 66 patients, respectively, and magnetic resonance imaging (MRI) scans were evaluated in 114 patients. Only 4% of patients had minor complications and 1.5% had major complications, including one patient who died from intracranial bleeding. Nine (4.7%) biopsies were non-diagnostic. Isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 29 patients, and were non-diagnostic in only 3 (10.3%) cases. Patients with high-grade gliomas (HGG) were more frequently seropositive for T. gondii than individuals with low-grade gliomas (LGG; p < 0.001). A total of 27% of HGG and 41% of LGG were non-enhancing on MRI. The infratentorial approach is generally safe and reliable for biopsy of brainstem and cerebellar lesions. In our study, the safety and efficacy of supratentorial biopsy of the cerebral peduncle and infratentorial biopsy of lesions below the cerebral peduncle were comparably high. Moreover, patients with HGG were more frequently seropositive for T. gondii than patients with LGG, and the relationship between toxoplasmosis and gliomagenesis requires further investigation.

3.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34638714

RESUMEN

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.


Asunto(s)
Biomarcadores de Tumor , Neoplasias del Sistema Nervioso Central , Glioma , Proteínas de Neoplasias , Temozolomida/uso terapéutico , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/metabolismo , Metilación de ADN/efectos de los fármacos , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Glioma/diagnóstico , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Mutación , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Pronóstico
4.
World Neurosurg ; 153: e179-e186, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34166826

RESUMEN

OBJECTIVE: To assess the quality of YouTube videos on meningioma treatment. METHODS: A search was performed on YouTube using the keywords "meningioma treatment," "meningeal tumor treatment," "meningioma brain tumor treatment," "meningioma cure," and "meningioma therapy." Sixty-one videos were independently evaluated by 2 fifth-year medical students using the DISCERN scoring system for quality analysis. Quantitative data such as video length, source of upload, and popularity and their associations with DISCERN scores were also evaluated. RESULTS: The mean total DISCERN score was 36.4. Approximately a third of YouTube videos were classified as very poor, 32.8% as poor, 11.5% as fair, 16.4% as good, and 4.9% as excellent. The question "Does the video refer to areas of uncertainty?" obtained the lowest score (2.0), and the question "Does the video describe how each treatment works?" obtained the highest score (3.0). Videos authored by a health information channel had the highest mean total DISCERN score (46.7, standard deviation = 14.6). Videos had significantly higher DISCERN scores if they included information about the symptoms of meningioma, risk factors during treatment, prognosis, or included animations and diagrams. DISCERN scores were moderately positively correlated with duration of videos and referrers and moderately negatively correlated with number of channel subscribers, video power index, and average daily views. CONCLUSION: The information content on meningioma treatment in YouTube videos was generally poor. The impact of inaccurate YouTube videos on patients' understanding of meningioma treatment must be recognized by health care professionals.


Asunto(s)
Información de Salud al Consumidor , Neoplasias Meníngeas/terapia , Meningioma/terapia , Medios de Comunicación Sociales , Humanos , Difusión de la Información , Grabación en Video
5.
Arch Immunol Ther Exp (Warsz) ; 67(6): 401-414, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31324924

RESUMEN

Poxviruses utilize multiple strategies to prevent activation of extrinsic and intrinsic apoptotic pathways for successful replication. Mitochondrial heat shock proteins (mtHsps), especially Hsp60 and its cofactor Hsp10, are engaged in apoptosis regulation; however, until now, the influence of poxviruses on mtHsps has never been studied. We used highly infectious Moscow strain of ectromelia virus (ECTV) to investigate the mitochondrial heat shock response and apoptotic potential in permissive L929 fibroblasts. Our results show that ECTV-infected cells exhibit mostly mitochondrial localization of Hsp60 and Hsp10, and show overexpression of both proteins during later stages of infection. ECTV infection has only moderate effect on the electron transport chain subunit expression. Moreover, increase of mtHsp amounts is accompanied by lack of apoptosis, and confirmed by reduced level of pro-apoptotic Bax protein and elevated levels of anti-apoptotic Bcl-2 and Bcl-xL proteins. Taken together, we show a positive relationship between increased levels of Hsp60 and Hsp10 and decreased apoptotic potential of L929 fibroblasts, and further hypothesize that Hsp60 and/or its cofactor play important roles in maintaining protein homeostasis in mitochondria for promotion of cell survival allowing efficient replication of ECTV.


Asunto(s)
Chaperonina 10/metabolismo , Chaperonina 60/metabolismo , Virus de la Ectromelia/fisiología , Ectromelia Infecciosa/inmunología , Fibroblastos/fisiología , Respuesta al Choque Térmico/inmunología , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Animales , Apoptosis , Línea Celular , Fibroblastos/virología , Regulación de la Expresión Génica , Evasión Inmune , Ratones , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Virulencia , Replicación Viral
6.
Viruses ; 10(5)2018 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-29772718

RESUMEN

Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with ectromelia virus (ECTV). We used two different cell lines and a combination of immunofluorescence techniques, confocal and electron microscopy, and flow cytometry to address subcellular changes following infection. Early in infection of L929 fibroblasts and RAW 264.7 macrophages, mitochondria gathered around viral factories. Later, the mitochondrial network became fragmented, forming punctate mitochondria that co-localized with the progeny virions. ECTV-co-localized mitochondria associated with the cytoskeleton components. Mitochondrial membrane potential, mitochondrial fission⁻fusion, mitochondrial mass, and generation of reactive oxygen species (ROS) were severely altered later in ECTV infection leading to damage of mitochondria. These results suggest an important role of mitochondria in supplying energy for virus replication and morphogenesis. Presumably, mitochondria participate in transport of viral particles inside and outside of the cell and/or they are a source of membranes for viral envelope formation. We speculate that the observed changes in the mitochondrial network organization and physiology in ECTV-infected cells provide suitable conditions for viral replication and morphogenesis.


Asunto(s)
Virus de la Ectromelia/fisiología , Fibroblastos/metabolismo , Fibroblastos/virología , Macrófagos/metabolismo , Macrófagos/virología , Mitocondrias/fisiología , Mitocondrias/ultraestructura , Animales , Autofagia/fisiología , Dinaminas/metabolismo , Virus de la Ectromelia/ultraestructura , Fibroblastos/patología , GTP Fosfohidrolasas/metabolismo , Células L , Macrófagos/patología , Potencial de la Membrana Mitocondrial/fisiología , Ratones , Centro Organizador de los Microtúbulos/metabolismo , Centro Organizador de los Microtúbulos/virología , Mitocondrias/metabolismo , Mitocondrias/virología , Proteínas Mitocondriales/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/análisis , Tubulina (Proteína)/metabolismo , Virión/metabolismo , Replicación Viral
7.
Chem Commun (Camb) ; 53(61): 8529-8532, 2017 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-28703825

RESUMEN

The future of 89Zr-based immuno-PET is reliant upon the development of new chelators with improved stability compared to the currently used deferoxamine (DFO). Herein, we report the evaluation of the octadentate molecule DFO-HOPO (3) as a suitable chelator for 89Zr and a more stable alternative to DFO. The molecule showed good potential for the future development of a DFO-HOPO-based bifunctional chelator (BFC) for the radiolabelling of biomolecules with 89Zr. This work broadens the selection of available chelators for 89Zr in search of improved successors to DFO for clinical 89Zr-immuno-PET.

8.
PLoS One ; 12(6): e0179166, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28604814

RESUMEN

Ectromelia virus (ECTV) is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV). ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV employs sophisticated and host-specific strategies to control the immune cells that are important for induction of antiviral immune response. In the present study we investigated the influence of ECTV infection on immune functions of murine GM-CSF-derived bone marrow cells (GM-BM), comprised of conventional dendritic cells (cDCs) and macrophages. Our results showed for the first time that ECTV is able to replicate productively in GM-BM and severely impaired their innate and adaptive immune functions. Infected GM-BM exhibited dramatic changes in morphology and increased apoptosis during the late stages of infection. Moreover, GM-BM cells were unable to uptake and process antigen, reach full maturity and mount a proinflammatory response. Inhibition of cytokine/chemokine response may result from the alteration of nuclear translocation of NF-κB, IRF3 and IRF7 transcription factors and down-regulation of many genes involved in TLR, RLR, NLR and type I IFN signaling pathways. Consequently, GM-BM show inability to stimulate proliferation of purified allogeneic CD4+ T cells in a primary mixed leukocyte reaction (MLR). Taken together, our data clearly indicate that ECTV induces immunosuppressive mechanisms in GM-BM leading to their functional paralysis, thus compromising their ability to initiate downstream T-cell activation events.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/virología , Virus de la Ectromelia/fisiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Animales , Antígenos/inmunología , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Línea Celular , Células Cultivadas , Citocinas/metabolismo , Endocitosis/efectos de los fármacos , Endocitosis/inmunología , Inmunofenotipificación , Interferón Tipo I/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Leucocitos/virología , Activación de Linfocitos/inmunología , Masculino , Ratones , Transducción de Señal , Linfocitos T/inmunología , Linfocitos T/metabolismo , Receptor Toll-Like 4/agonistas , Receptor Toll-Like 4/metabolismo , Replicación Viral
9.
Cytoskeleton (Hoboken) ; 73(8): 396-417, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27169394

RESUMEN

Ectromelia virus (ECTV, the causative agent of mousepox), which represents the same genus as variola virus (VARV, the agent responsible for smallpox in humans), has served for years as a model virus for studying mechanisms of poxvirus-induced disease. Despite increasing knowledge on the interaction between ECTV and its natural host-the mouse-surprisingly, still little is known about the cell biology of ECTV infection. Because pathogen interaction with the cytoskeleton is still a growing area of research in the virus-host cell interplay, the aim of the present study was to evaluate the consequences of ECTV infection on the cytoskeleton in a murine fibroblast cell line. The viral effect on the cytoskeleton was reflected by changes in migration of the cells and rearrangement of the architecture of tubulin, vimentin, and actin filaments. The virus-induced cytoskeletal rearrangements observed in these studies contributed to the efficient cell-to-cell spread of infection, which is an important feature of ECTV virulence. Additionally, during later stages of infection L929 cells produced two main types of actin-based cellular protrusions: short (actin tails and "dendrites") and long (cytoplasmic corridors). Due to diversity of filopodial extensions induced by the virus, we suggest that ECTV represents a valuable new model for studying processes and pathways that regulate the formation of cytoskeleton-based cellular structures. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Citoesqueleto/metabolismo , Virus de la Ectromelia/crecimiento & desarrollo , Fibroblastos/metabolismo , Animales , Línea Celular , Virus de la Ectromelia/metabolismo , Humanos , Ratones
10.
Gene Ther ; 23(4): 357-68, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26814609

RESUMEN

Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice.


Asunto(s)
Terapia Genética/métodos , Viroterapia Oncolítica/métodos , Neoplasias de la Próstata/terapia , Simportadores/genética , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Desnudos , Virus Oncolíticos/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/virología , Distribución Aleatoria , Simportadores/metabolismo , Transfección , Virus Vaccinia/genética , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Curr Oncol ; 21(1): e155-65, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24523614

RESUMEN

Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with a variety of mucinous tumours of varying biologic behavior. Although appendix or ovaries have usually been implicated as the primary site, cases have been reported in association with neoplastic lesions of other sites. Pseudomyxoma peritonei originating from urachal remnants is a unique entity, reported only 18 times in the English literature thus far. Considering the rarity of the lesion, we report the case of a 50-year-old man surgically treated for pmp associated with a low-grade mucinous urachal neoplasm. Unique aspects of case are the low histologic aggressiveness of the causative lesion (reported only twice worldwide) and the early stage of the disease, with a relatively small amount of intraperitoneal free mucin. Review of the literature about pmp in general and a collation of previously reported cases of pmp originating from the urachus are presented and discussed.

12.
Transl Psychiatry ; 3: e295, 2013 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-23982627

RESUMEN

ABT-384 is a potent, selective inhibitor of 11-beta-hydroxysteroid dehydrogenase type 1 (HSD-1). One milligram of ABT-384 daily fully inhibited hepatic HSD-1. Establishing the dose that fully inhibits central nervous system (CNS) HSD-1 would enable definitive clinical studies in potential CNS indications. [9,11,12,12-(2)H4] cortisol (D4 cortisol), a stable labeled tracer, was used to characterize HSD-1 inhibition by ABT-384. D4 cortisol and its products were measured in the plasma and cerebrospinal fluid (CSF) of healthy male volunteers during D4 cortisol infusions, for up to 40 h after five daily doses of 1-50 mg ABT-384. Similar procedures were conducted in control subjects who received no ABT-384. Peripheral HSD-1 inhibition was calculated from plasma levels of D4 cortisol and its products. CNS HSD-1 inhibition was characterized from plasma and CSF levels of D4 cortisol and its products. ABT-384 regimens ≥2 mg daily maintained peripheral HSD-1 inhibition ≥88%. ABT-384 1 mg daily maintained peripheral HSD-1 inhibition ≥81%. No CNS formation of D3 cortisol (the mass-labeled product of HSD-1) was detected following ABT-384 ≥2 mg daily, indicating full CNS HSD-1 inhibition by these regimens. Partial CNS HSD-1 inhibition was associated with 1 mg ABT-384 daily. CNS HSD-1 inhibition was characterized by strong hysteresis and increased with maximum post-dose plasma concentration of ABT-384 and its active metabolites. ABT-384 has a wide potential therapeutic window for potential indications including Alzheimer's disease and major depressive disorder. Stable labeled substrates may be viable tools for measuring CNS effect during new drug development for other enzyme targets.


Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Adamantano/análogos & derivados , Sistema Nervioso Central/efectos de los fármacos , Hidrocortisona/metabolismo , Piperazinas/farmacología , Adamantano/farmacología , Adulto , Sistema Nervioso Central/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Hidrocortisona/sangre , Hidrocortisona/líquido cefalorraquídeo , Hidrógeno , Isótopos , Masculino , Persona de Mediana Edad
13.
Pathog Dis ; 68(3): 105-15, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23776161

RESUMEN

During mousepox in resistant (C57BL/6) or susceptible (BALB/c) strains of mice, stimulation of Th1 or Th2 cytokine immune response, respectively, is observed. Because mechanisms of different polarization of T cells remain elusive, in this study, we quantitatively assessed the phenotype of antigen-presenting cells (APCs) involved in ectromelia virus (ECTV) antigen presentation and cluster formation with effector cells in secondary lymphoid organs of BALB/c and C57BL/6 mice. We showed that both strains of mice display similar dynamics and kinetics of viral antigen presentation by CD11c(+) , CD11b(+) , and CD19(+) cells. CD11c(+) and CD11b(+) cells highly participated in viral antigen presentation during all stages of mousepox, whereas CD19(+) cells presented viral peptides later in infection. The main population of dendritic cells (DCs) engaged in ECTV antigen presentation and cell junction formation with effector cells was a population of myeloid CD11b(+) DCs (mDCs). We suggest that, on the one hand, ECTV may differentially affect the functions of APCs depending on the strain of mice. On the other hand, we suggest that some types of APCs, such as mDCs or other DCs subsets, have different abilities to direct the shape of immune response depending on the host resistance to mousepox.


Asunto(s)
Células Presentadoras de Antígenos/clasificación , Células Presentadoras de Antígenos/virología , Virus de la Ectromelia/inmunología , Inmunofenotipificación , Animales , Células Presentadoras de Antígenos/química , Antígenos CD19/análisis , Antígeno CD11b/análisis , Antígeno CD11c/análisis , Células Dendríticas/inmunología , Ganglios Linfáticos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Bazo/inmunología
14.
Neurosci J ; 2013: 736439, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-26317098

RESUMEN

Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30 mg/kg, i.p.) showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3-10 mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor (5-HT2AR)-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

15.
Curr Med Chem ; 19(28): 4759-66, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22873662

RESUMEN

Epidermal growth factor (EGF) receptors are commonly expressed on the cell membrane of cancer cells and activity of these receptors results in accelerated cell growth and carcinogenesis. A variety of targeted molecules have been developed to block ligand binding and/or inhibit the function of these receptor tyrosine kinases, and several have proven therapeutic benefits. Along with the advent of new therapeutic agents comes a need for non-invasive tools to diagnose, characterize, and monitor tumor responsiveness to therapy. Imaging EGF receptors with radionuclides has been performed for decades. However, recently this area has advanced considerably with the development of EGF receptor-targeted optical imaging probes. Herein, we review recent advances in molecular imaging of the EGF receptor family, focusing specifically on optical imaging. Such agents provide the opportunity for earlier diagnosis, improved tumor characterization, and the ability to measure and monitor tumor responsiveness to anti-EGF receptor treatment strategies.


Asunto(s)
Receptores ErbB/metabolismo , Neoplasias/diagnóstico , Imagen Óptica , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Receptores ErbB/química , Colorantes Fluorescentes/química , Humanos , Neoplasias/metabolismo , Radiofármacos/química , Receptor ErbB-2/química , Receptor ErbB-2/metabolismo
16.
Arch Immunol Ther Exp (Warsz) ; 59(6): 463-71, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21972018

RESUMEN

Several reports have brought to light new and interesting findings on the involvement of autophagy and apoptosis in pathogenesis of viral and bacterial diseases, as well as presentation of foreign antigens. Our model studies focused on the involvement of apoptosis during replication of highly virulent Moscow strain of ectromelia virus (ECTV-MOS). Here, we show evidence that autophagy is induced during mousepox replication in a cell line. Fluorescence microscopy revealed increase of LC3 (microtubule-associated protein 1 light chain 3) aggregation in infected as opposed to non-infected control L929 cells. Furthermore, Western blot analysis showed that replication of ECTV-MOS in L929 cells led to the increase in LC3-II (marker of autophagic activity) expression. Beclin 1 strongly colocalized with extranuclear viral replication centers in infected cells, whereas expression of Bcl-2 decreased in those centers as shown by fluorescence microscopy. Loss of Beclin 1-Bcl-2 interaction may lead to autophagy in virus-infected L929 cells. To assess if Beclin 1 has a role in regulation of apoptosis during ECTV-MOS infection, we used small interfering RNA directed against beclin 1 following infection. Early and late apoptotic cells were analyzed by flow cytometry after AnnexinV and propidium iodide staining. Silencing of beclin 1 resulted in decreased percentage of early and late apoptotic cells in the late stage of ECTV-MOS infection in L929 cells. We conclude that Beclin 1 plays an important role in regulation of both, autophagy and apoptosis, during ECTV-MOS replication in L929 permissive cells.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/inmunología , Apoptosis/inmunología , Autofagia/inmunología , Virus de la Ectromelia/fisiología , Genes bcl-2/inmunología , Proteínas Asociadas a Microtúbulos/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Beclina-1 , Línea Celular , Chlorocebus aethiops , Replicación del ADN , Ectromelia Infecciosa/inmunología , Ectromelia Infecciosa/fisiopatología , Citometría de Flujo , Ratones , Microscopía Fluorescente , ARN Interferente Pequeño/farmacología , Células Vero , Replicación Viral
17.
Folia Histochem Cytobiol ; 48(2): 249-61, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20675282

RESUMEN

The prognosis in patients with pancreatic cancer is poor and some authors describe it as a lethal disease. At the time of diagnosis only 14% of patients could be surgically treated and up to 30% of them die within 12 months. Therefore, further clinical investigations on preoperative patient qualification are needed. A total of 81 patients were included into the study. The CA 19-9 concentration was measured before surgery by an automated, commercially available enzyme immunoassay in Axsym analyzer (Abott Diagnostics Laboratory). A value of 37 U/ml was used as the upper limit of normal levels. Tumors were staged according to the Union Against Cancer (UICC) of 2004 and graded during the histological evaluation according to the G0-G4 scale. All patients were monitored every three month via outpatient clinic visits. In the case of missing visit we contacted the families to establish the cause. We assessed perioperative, 12 month, 2 year and 5 year survival. Twelve moth, 2 year and 5 year survival were assessed in the whole studied population and in the group of patients with the exception of these who died during the perioperative period. The total five year survival was 6%. The median time of survival was 467 days (range: 163 - 586 days). The perioperative period was survived by 91.4% patients, 12 months were survived by 71.6% patients, 2 years were survived by 35.8% patients, 5 years were survived by 6.2% patients. The serum Ca 19-9 level was above the normal limit in 80.5% patients. ROC curve analysis revealed that CA 19-9 level of more than 106 U/ml was linked to 2 year survival with 79.3% sensitivity and 74.5% specificity. Preoperative level of CA 19-9 below 106U/ml represents a predictive factor of 2- and 5-year survival, independent of other factors, such as lower size of the tumor, absence of metastases to lymph nodes, female gender of patients. After exclusion of the patients who died in the perioperative period, no relationship could have been disclosed between preoperative CA 19-9 levels and one year survival. The observation points to the chance that patients with higher levels of CA 19-9 harbour micrometastases, the development of which is sufficiently slow to allow for a one-year survival of the patients but which increase the risk of death after two and five years.


Asunto(s)
Adenocarcinoma/sangre , Adenocarcinoma/cirugía , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Radioterapia Adyuvante , Tasa de Supervivencia
18.
Folia Histochem Cytobiol ; 48(1): 26-9, 2010 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-20529812

RESUMEN

It is not known whether in patients with breast cancer the occurrence of elevated serum tumour markers depends on its histological type. The aim of the study was to assess relationship between breast cancer histological type and the presence of increased serum levels of CEA and CA 15-3. The study population was 428 patients (all women, mean age 52.5 years), treated at The Department of Surgery of Wroclaw Medical University from 2005 to 2008 due to breast cancer. All of them had their preoperative CA 15-3 and CEA serum concentrations measured. According to the TNM system, 21% of patients were in stage I, 32.5% in stage II, 46.5% in stage III of the disease. In patients with ductal type of the cancer the elevated serum levels of CEA and CA 15-3 were observed in 48.7% and 42.2%, in lobular type in 42.4% and 52.5%, and in non-ductal/tubular types in 48.1% and 40.4% (p=N/S). Stepwise logistic regression analyses showed that ductal breast cancer is related to elevated CEA and normal CA 15-3 serum levels. The histological types of breast cancer are not significantly related to elevated serum levels of CEA and/or CA 15-3.


Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/cirugía , Antígeno Carcinoembrionario/sangre , Mucina-1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Adulto Joven
19.
Eur J Immunol ; 40(1): 113-6, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19877011

RESUMEN

Newborn higher vertebrates are largely immuno-incompetent and generally survive infections--including poxviruses--by maternal antibody protection. Here, we show that mice survived epidemics as adults only if exposed to lethal orthopoxvirus infections during infancy under the umbrella of maternal protective antibodies. This implies that both the absence of exposure to infection during early infancy or of effective vaccination renders the population highly susceptible to new or old re-emerging pathogens.


Asunto(s)
Anticuerpos Antivirales/inmunología , Ectromelia Infecciosa/inmunología , Inmunidad Materno-Adquirida , Animales , Animales Recién Nacidos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Tasa de Supervivencia
20.
Cell Tissue Bank ; 7(3): 175-82, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16933039

RESUMEN

Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries. Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.


Asunto(s)
Enfermedades de las Válvulas Cardíacas/cirugía , Válvulas Cardíacas , Bancos de Tejidos , Universidades , Adolescente , Adulto , Niño , Preescolar , Humanos , Persona de Mediana Edad , Polonia , Trasplante Homólogo
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