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1.
Hum Vaccin Immunother ; 19(3): 2288282, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38037900

RESUMEN

Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Neoplasias , Humanos , Herpesvirus Humano 3 , Proyectos Piloto , Estudios Prospectivos , Herpes Zóster/prevención & control , Adyuvantes Inmunológicos , Neoplasias/tratamiento farmacológico , Glicoproteínas , Vacunación , Vacunas Sintéticas/efectos adversos
2.
Front Oncol ; 12: 1003494, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36313689

RESUMEN

Introduction: Radiotherapy represents a major treatment option for patients with pancreatic cancer, however, its benefits remain limited also due to the ability of cancer cells to migrate to the surrounding tissues. Low-LET ionizing radiation is well known to promote tumor cell migration and invasion, nevertheless, little data provided by studies using high-LET radiation has led to ambiguous findings. What is hypothesized to be fundamental in the modulation of migration of tumor cells exposed to ionizing radiation is the influence of the microenvironment. Therefore, the properties of cells that populate the tumor stroma cannot be ignored when studying the influence of radiation on the migratory and invasive capacity of cancer cells. This is especially important in the case of pancreatic malignancies that are characterized by an abundance of stromal cells, including cancer-associated fibroblasts, which are known to orchestrate the cross-talk with tumor cells. Aim: The current study aims to investigate whether the presence of factors released by irradiated fibroblasts affects the migratory and invasive capacity of pancreatic cancer cells exposed to different doses of photons or C-ions. Materials and methods: AsPC-1 and AG01522 cells were irradiated with the same dose of photons or C-ions at room temperature. Through Boyden chamber assay, we tested whether factors secreted by irradiated fibroblasts may influence tumor cell migration, while the invasiveness of AsPC-1 cells was assessed using matrigel precoated inserts in which medium collected from non-irradiated (0 Gy), photon and C-ion irradiated fibroblasts, was added. Data were analyzed by Student t-test using GraphPad software. The mean ± s.d. was determined with a significance level of p<0.05. Results: In the presence of conditioned medium collected from 1 Gy and 2 Gy photon irradiated fibroblasts, the number of migrated tumor cells increased (P<0.0360, P<0.0001) but decreased at 4 Gy dose (P<0.002). There was a trend of reduction in migration (P<0.0460, P<0.038, P<0.0024, P<0.0002), as well as a decrease in invasiveness (P<0.0525, P<0.0035, P<0.0868, P<0.0310) after exposure to 0.5 Gy, 1 Gy, 2 Gy and 4 Gy of C-ions. Conclusions: The presence of irradiated fibroblasts affected the invasiveness capability of pancreatic cancer cells, probably by the reciprocal release of soluble factors whose production is differently modulated after high or low-LET radiation. Understanding the effects of irradiation on the metastatic potential of pancreatic cancer cells is of utmost importance for improving the outcome and tailoring the therapeutic approach. This challenging scenario requires a continuous and multidisciplinary approach that involves clinicians together with researcher experts in oncological and radiation treatment. In the last years, including preclinical experiences in a multidisciplinary approach has proved to be a winning strategy in clinical oncological research.

3.
Int J Antimicrob Agents ; 59(6): 106594, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35483624

RESUMEN

Carbapenemase-producing Enterobacterales (CPE) represent a serious threat to public health worldwide. Elderly patients are at increased risk of colonisation/infection with CPE. This study aimed to evaluate the persistence of CPE colonisation and the genotypic characteristics of persistent strains in elderly people discharged from Italian hospitals. A longitudinal study was conducted in two Italian cities (March 2018 to September 2020) enrolling 137 patients aged ≥65 years with CPE intestinal colonisation at hospital discharge. CPE colonisation was evaluated after 4, 8 and 12 months. Competing risk analysis was used to explore the association between baseline characteristics and persistence at 4 months. For all isolates, carbapenemase typing and multilocus sequence typing were performed. Persistent isolates underwent whole-genome sequencing. Of 137 patients, 91% carried carbapenemase-producing Klebsiella pneumoniae (CP-KP) and 8.8% carried carbapenemase-producing Escherichia coli. Although a large number of patients were lost to follow-up owing to death or withdrawal, 28/65 patients (43.1%) remained colonised at Month 4; 16/42 (38.1%) and 5/28 (17.9%) were found colonised up to Months 8 and 12, respectively. Colonisation persistence was more frequent in patients with bacteraemia or complicated urinary tract infection while in hospital and in those staying in long-term care facilities (LTCFs). Clonal characteristics of CP-KP isolates did not appear to influence persistence. Isolates obtained from each persistent carrier were identical or highly related by SNP phylogenetic analysis. Identification of patients at higher risk of persistent intestinal carriage after hospital discharge can prompt control measures to limit the transmission of CPE in the community, especially in LTCF settings.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae , Anciano , Proteínas Bacterianas/genética , Infecciones por Enterobacteriaceae/epidemiología , Escherichia coli , Hospitales , Humanos , Klebsiella pneumoniae , Estudios Longitudinales , Alta del Paciente , Filogenia , beta-Lactamasas/genética
4.
Front Neurosci ; 14: 589924, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33281548

RESUMEN

The differential diagnosis between brain tumors recurrence and early neuroinflammation or late radionecrosis is still an unsolved problem. The new emerging magnetic resonance imaging, computed tomography, and positron emission tomography diagnostic modalities still lack sufficient accuracy. In the last years, a great effort has been made to develop radiotracers able to detect specific altered metabolic pathways or tumor receptor markers. Our research project aims to evaluate irradiation effects on radiopharmaceutical uptake and compare the kinetic of the fluorinate tracers. T98G glioblastoma cells were irradiated at doses of 2, 10, and 20 Gy with photons, and 18F-DOPA and 18F-FET tracer uptake was evaluated. Activity and cell viability at different incubation times were measured. 18F-FET and 18F-DOPA are accumulated via the LAT-1 transporter, but 18F-DOPA is further incorporated, whereas 18F-FET is not metabolized. Therefore, time-activity curves (TACs) tend to plateau with 18F-DOPA and to a rapid washout with 18F-FET. After irradiation, 18F-DOPA TAC resembles the 18F-FET pattern. 18F-DOPA activity peak we observed at 20 min might be fictitious, because earlier time points have not been evaluated, and a higher activity peak before 20 min cannot be excluded. In addition, the activity retained in the irradiated cells remains higher in comparison to the sham ones at all time points investigated. This aspect is similar in the 18F-FET TAC but less evident. Therefore, we can hypothesize the presence of a second intracellular compartment in addition to the amino acidic pool one governed by LAT-1, which could explain the progressive accumulation of 18F-DOPA in unirradiated cells.

5.
Radiat Environ Biophys ; 59(2): 237-244, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32040721

RESUMEN

In recent years, scientists have found evidence confirming the aberrant expression of miRNAs in cancer patients compared to healthy individuals. The growing interest in the identification of non-invasive and specific diagnostic and prognostic molecular markers has identified microRNAs as potential candidates in cancer diagnosis, prognosis and treatment response. In the present study, we have analyzed the expression profile of circulating miR-21, -191 and -421 in peripheral blood of head and neck cancer patients (HNC) to investigate a possible modulation of mRNA levels by radiation and to identify the role of mRNA as biomarkers of cancer prognosis. Results showed a modulation of the microRNA expression at different time points after radiotherapy, suggesting that treatment may influence the release of circulating miRNAs depending also on the time interval elapsed since radiotherapy. The expression levels of miR-21, -191 and -421 were higher in blood of patients treated with radiotherapy alone after 6 months from the end of therapy and high levels of them seemed to correlate with the remission of the disease. The trends shown in this study confirmed that miRNAs could be useful prognosis markers and could provide preliminary data for further evaluation in predicting patients' response to radiotherapy by developing miRNA-based treatments to improve the sensitivity of cancer cells to radiotherapy.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/genética , MicroARNs/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Aceleradores de Partículas , Pronóstico , Rayos X
6.
Anticancer Res ; 39(1): 119-125, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30591448

RESUMEN

BACKGROUND/AIM: Glioblastoma is the most malignant and widespread brain tumor in adults, with a rapid clinical course. Recently, it has been hypothesized that L-DOPA plays a role in the diagnosis and treatment of glioblastoma. The aim of this study was to assess the effects of pretreatment with L-DOPA on the biological behavior of human T98G cells in vitro. MATERIALS AND METHODS: T98G cells were treated with 50 µg/ml or 100 µg/ml of L-DOPA for 4 h and their morphology, growth rate, clonogenic survival and migratory capacity in basal conditions and after carbon ion irradiation were evaluated using standard methods. RESULTS: Treated cells showed a lower growth rate and an increased migratory capacity that correlated with the dose of tested L-DOPA. Treatment with L-DOPA increased the growth rate of carbon ion irradiated T98G cells compared to control non-treated cells exposed to the same radiation dose. CONCLUSION: Our results open further questions about the overall advantage of L-DOPA treatment of glioblastoma.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Levodopa/farmacología , Adulto , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Glioblastoma/patología , Radioterapia de Iones Pesados , Humanos , Cinética
7.
Anticancer Res ; 38(8): 4585-4591, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30061225

RESUMEN

BACKGROUND/AIM: Cell migration and invasion are fundamental components of tumor cell metastasis that represent the biggest threat to the survival and quality of life of cancer patients. There is clear evidence that ionizing radiation can differently modulate migration and invasiveness of cancer cells depending on the cell lines, the doses and the radiation types investigated. This suggests that motile cells are able to adopt different migration strategies according to their molecular characteristics and external signals. MATERIALS AND METHODS: In this study, a morphological analysis was performed on pancreatic cancer Aspc-1 cells to evaluate the amoeboid-mesenchymal mobility transition in several experimental conditions considering the role played by factors released by normal and tumor cells, in basal conditions and after low and high Linear Energy Transfer (LET) irradiation. RESULTS AND CONCLUSION: The migratory behavior of Aspc-1 cells is modulated by factors released by normal fibroblasts and tumor cells, and this is in turn modulated by both the radiation dose and the radiation quality.


Asunto(s)
Movimiento Celular/fisiología , Transición Epitelial-Mesenquimal/fisiología , Transferencia Lineal de Energía/fisiología , Invasividad Neoplásica/patología , Neoplasias Pancreáticas/patología , Línea Celular Tumoral , Fibroblastos/patología , Humanos , Neoplasias Pancreáticas/radioterapia , Calidad de Vida , Radiación Ionizante
8.
Leuk Lymphoma ; 59(3): 702-709, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28679326

RESUMEN

hTERT component is the key regulator of telomerase. Alternatively spliced variants of hTERT generate different telomerase activity. The goal of the study was to determine the role of different hTERT isoforms in the regulation of telomerase expression in AML patients. Among the 97 studied patients, 45 had a complex karyotype and 52 a normal karyotype. hTERT isoforms expression was determined in bone marrow samples by q-RT-PCR, using SYBR Green I. hTERT expression was lower in AML patients than controls (median 2.5 vs. 10.1, p = .003), though no difference was observed between the complex and normal karyotype (median 3.2 vs. 2.3, p = .37). High trans-dominant negative isoform expression increased the response rate by two. High expression of inactive product (-α - ß) was shown to increase the risk of relapse by about three times. In conclusion, our data suggest an intriguing link between the control of hTERT isoforms expression and AML outcome.


Asunto(s)
Empalme Alternativo , Médula Ósea/patología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Leucemia Mieloide Aguda/genética , Recurrencia Local de Neoplasia/genética , Telomerasa/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Médula Ósea/metabolismo , Estudios de Casos y Controles , Aberraciones Cromosómicas , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/enzimología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tasa de Supervivencia , Telomerasa/metabolismo
9.
Contrast Media Mol Imaging ; 2017: 6491674, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29097931

RESUMEN

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our data suggest that both FCH and FET could be useful to analyze the metabolic pathways of glioblastoma cells before and after radiotherapy. Physicians will have to consider the different kinetics pathways of uptake concerning the two radiopharmaceuticals.


Asunto(s)
Colina/análogos & derivados , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Tirosina/análogos & derivados , Carbono , Línea Celular Tumoral , Colina/farmacocinética , Diagnóstico Diferencial , Glioblastoma/patología , Glioblastoma/radioterapia , Humanos , Iones , Metástasis de la Neoplasia/diagnóstico por imagen , Fotones , Tirosina/farmacocinética
10.
Anticancer Res ; 37(2): 645-649, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28179312

RESUMEN

In myelodysplatic syndromes and acute myeloid leukemia (MDS/AML) deletion of the 11q14 region is a rare chromosomal defect (incidence: 0.6-1.0%), included within the intermediate risk criteria by the International Prognostic Scoring System. No fluorescence in situ hybridization (FISH) study has yet been performed to identify a common breakpoint region (CBR). In our study through FISH with bacterial artificial chromosomes and commercial probes, we analyzed seven patients with MDS/AML harboring 11q14 deletion on conventional cytogenetic analysis. FISH revealed deletions in five patients and amplifications in two. Three patients with deletion carried a CBR, two had a deletion involving a more centromeric breakpoint. These five patients exhibited multilineage dysplasia, blast cells with large round nuclei, loose chromatin, small and abundant nucleoli, and vacuolated cytoplasm with very thin Auer bodies. In conclusion, the morphological features which occur independently of the extent of the deletion are of multilineage dysplasia in MDS and leukemic blasts strongly reactive to peroxidase in AML; despite the variable size of the deleted area, some patients harbor a CBR.


Asunto(s)
Puntos de Rotura del Cromosoma , Deleción Cromosómica , Cromosomas Humanos Par 11/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicos/genética , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana Edad
11.
Anticancer Res ; 36(11): 5719-5730, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27793893

RESUMEN

223Ra prolongs overall survival in symptomatic patients affected by multiple bone-metastatic castration-resistant prostatic cancer, without visceral or nodal involvement. However, many questions remain about its mechanisms of action, and its use in clinical practice is still unresolved. First of all, what is the main target of alpha-particle emission, that is, in what way does it influences the tumor microenvironment? When is the best timing in the course of the disease, extending its use to asymptomatic low-volume or even to the micrometastatic phase? What are suitable biomarkers to be employed as prognostic factors and response indicators? Which associations with other drugs and their sequence can offer the best results, and is their effect additive or synergistic? Ultimately, in the current climate of spending review, what is the optimal cost and benefit ratio regarding available treatments? In this review, we tried to answer these questions by analyzing the available scientific literature.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/uso terapéutico , Neoplasias Óseas/radioterapia , Economía Farmacéutica , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/patología
12.
Anticancer Res ; 36(11): 5821-5826, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27793904

RESUMEN

Treatment with pulsed electromagnetic fields (PEMFs) is emerging as an interesting therapeutic option for patients with cancer. The literature has demonstrated that low-frequency/low-energy electromagnetic fields do not cause predictable effects on DNA; however, they can epigenetically act on gene expression. The aim of the present work was to study a possible epigenetic effect of a PEMF, mediated by miRNAs, on a human glioblastoma cell line (T98G). We tested a PEMF (maximum magnetic induction, 2 mT; frequency, 75 Hz) that has been demonstrated to induce autophagy in glioblastoma cells. In particular, we studied the effect of PEMF on the expression of genes involved in cancer progression and a promising synergistic effect with temozolomide, a frequently used drug to treat glioblastoma multiforme. We found that electromagnetic stimulation in combination with temozolomide can elicit an epigenetic pro-apoptotic effect in the chemo- and radioresistant T98G glioblastoma cell line.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Apoptosis/efectos de los fármacos , Dacarbazina/análogos & derivados , Campos Electromagnéticos , Epigénesis Genética/efectos de los fármacos , Glioblastoma/patología , Apoptosis/genética , Reactores Biológicos , Proliferación Celular/efectos de los fármacos , Dacarbazina/farmacología , Humanos , MicroARNs/genética , Temozolomida
13.
Electromagn Biol Med ; 35(4): 343-52, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27254779

RESUMEN

Extremely low-frequency electromagnetic fields (ELF-EMFs) applied in magnetotherapy have frequency lower than 100 Hz and magnetic field intensity ranging from 0.1 to 20 mT. For many years, the use of magnetotherapy in clinics has been increasing because of its beneficial effects in many processes, e.g., skin diseases, inflammation and bone disorders. However, the understanding of the microscopic mechanisms governing such processes is still lacking and the results of the studies on the effects of ELF-EMFs are controversial because effects derive from different conditions and from intrinsic responsiveness of different cell types.In the present study, we studied the biological effects of 1.5 h exposure of human dermal fibroblasts to EMFs with frequencies of 5 and 50 Hz and intensity between 0.25 and 1.6 mT. Our data showed that the magnetic treatment did not produce changes in cell viability, but gave evidence of a sizeable decrease in proliferation at 24 h after treatment. In addition, immunofluorescence experiments displayed an increase in tubulin expression that could foreshadow changes in cell motility or morphology. The decrease in proliferation with unchanged viability and increase in tubulin expression could be consistent with the triggering of a transdifferentiation process after the exposure to ELF-EMFs.


Asunto(s)
Campos Electromagnéticos , Fibroblastos/citología , Fibroblastos/efectos de la radiación , Piel/citología , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Citoesqueleto/metabolismo , Citoesqueleto/efectos de la radiación , Humanos
14.
Radiol Oncol ; 50(2): 153-8, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-27247547

RESUMEN

BACKGROUND: Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. (18)F-methyl-choline ((18)F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The (18)F-ethyl-tyrosine ((18)F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. (18)F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate (18)F-FCH and (18)F-FET uptake by human glioblastoma T98G cells. MATERIAL AND METHODS: Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10(5) cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for (18)F-FCH and (18)F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 10(5) cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. RESULTS: A significant uptake of (18)F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of (18)F-FET in comparison to (18)F-FCH was lower by a factor of more than 3, with different kinetic curves.(18)F-FET showed a more rapid initial uptake up to 40 minutes and (18)F-FCH showed a progressive rise reaching a maximum after 90 minutes. CONCLUSIONS: (18)F-FCH and (18)F-FET are candidates for neuro-oncological PET imaging. (18)F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of (18)F-FCH to inflammatory cells makes it more difficult to discriminate between tumour persistence and non-neoplastic changes. Additional studies on the influence of inflammatory tissue and radionecrotic cellular components on radiopharmaceutical uptake are necessary.

15.
Anticancer Res ; 35(12): 6439-43, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26637854

RESUMEN

AIM: Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional morphological imaging. (18)F-FCH was compared against (18)F-FDG in the T98G glioblastoma cell line with regard to their radiopharmaceutical uptake, in order to test its diagnostic power on brain tumor lesions. MATERIALS AND METHODS: Equimolar amounts of (18)F-FCH and (18)F-FDG were added to human glioblastoma T98G cells and human dermal fibroblasts for 20, 40, 60, 90 and 120 min of incubation. Radiopharmaceutical uptake was expressed as a percentage of the administered dose. Cold choline was used for binding competition experiments. RESULTS: In T98G cells (18)F-FCH was taken-up in higher amounts than 18F-FDG after 60 min. In fibroblasts, uptake was lower than 1% for both radiopharmaceuticals. Cold choline reduced the uptake of FCH to 1% similarly to fibroblasts. CONCLUSION: Our results prove the efficacy of (18)F-FCH as a promising tracer, better than (18)F-FDG in establishing the tumor-to-background ratio in brain tumors.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Colina/análogos & derivados , Fluorodesoxiglucosa F18/farmacocinética , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Radiofármacos/farmacocinética , Línea Celular Tumoral , Colina/farmacocinética , Humanos , Cintigrafía
16.
Int J Oncol ; 46(4): 1491-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25646699

RESUMEN

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adulthood, characterized by very high recurrence. Following the limited results for conventional therapies, novel therapeutic agents are under investigation. Among the putative new molecules, gallic acid (GA) represents a promising new anticancer drug. The anticancer effect of this drug has been based on its antioxidant effects. The aim of the present study was to investigate the toxic effects of GA on the T98G human glioblastoma cell line and its capacity to modulate the expression of microRNAs targeting the genes involved in tumor growth and invasion. Cytotoxicity, clonogenic ability and cell migration after GA treatment were tested. Moreover, the expression of miRNAs that target genes for antioxidant mitochondrial enzymes (mir-17-3p), p-21 protein (mir-21-5p) and ATM (mir-421-5p) was determined by qRT-PCR. The results confirmed in the T98G cells the anti-proliferative effect of GA reported for other glioma cell lines and showed that the miRNA expression changes depending on GA concentrations. Different GA concentrations can determine a protective or a toxic effect on tumor cells. Thus, the key for GA to induce a specific anticancer action is to use an optimal concentration that avoids these twin effects.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Ácido Gálico/farmacología , Glioblastoma/tratamiento farmacológico , MicroARNs/genética , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Humanos , Proteínas Mitocondriales/genética
17.
Biomed Res Int ; 2014: 453497, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25097859

RESUMEN

The success of chemo- and radiotherapy in glioblastoma multiforme, the most common and lethal primary brain tumour, could rely on the induction of immunogenic tumour cell death and on the induction of anticancer immune response. In this study we investigated cell survival to single treatments or combination of X-rays and temozolomide in glioblastoma cell lines (T98G and U251MG) and we attempted to identify danger signals (HMGB1 and HSP70) released by dying cells in the microenvironment that could activate antitumour immunity contributing to the therapeutic efficacy of conventional treatments. Our data suggest that HSP70 translocates from cytoplasm to extracellular environment after an increase in radiation dose and HMGB1 translocates from the nucleus to the cytoplasm and subsequently is released into the extracellular space, confirming a role of these proteins as signals released after radiation-induced damage in glioblastoma cells. We also could state that TMZ had limited effectiveness in activating HMGB1 and HSP70 signalling and, instead, an adjuvant effect was observed in some combined treatments, depending on schedule, cell line, and timing. A big challenge in tumour therapy is, therefore, to identify the most beneficial combination and chronology of multiple treatment options to contribute to the improvement of the therapeutic outcome.


Asunto(s)
Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Microambiente Tumoral/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Terapia Combinada , Dacarbazina/administración & dosificación , Glioblastoma/patología , Proteína HMGB1/biosíntesis , Proteínas HSP70 de Choque Térmico/biosíntesis , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Temozolomida
18.
Nano Lett ; 14(7): 3959-65, 2014 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-24913622

RESUMEN

Advanced nanostructured materials, such as gold nanoparticles, magnetic nanoparticles, and multifunctional materials, are nowadays used in many state-of-the-art biomedical application. However, although the engineering in this field is very advanced, there remain some fundamental problems involving the interaction mechanisms between nanostructures and cells or tissues. Here we show the potential of (1)H NMR in the investigation of the uptake of two different kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed experimental protocol provides a new way to investigate the general problem of cellular uptake for a variety of biocompatible nanostructures and drugs.


Asunto(s)
Compuestos Férricos/metabolismo , Oro/metabolismo , Espectroscopía de Resonancia Magnética , Nanopartículas/metabolismo , Antineoplásicos Alquilantes/farmacocinética , Línea Celular Tumoral , Dacarbazina/análogos & derivados , Dacarbazina/farmacocinética , Glioblastoma/tratamiento farmacológico , Humanos , Espectroscopía de Resonancia Magnética/métodos , Ramnosa/metabolismo , Temozolomida
19.
Anticancer Res ; 34(2): 837-44, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24511020

RESUMEN

AIM: Late oral mucosa changes after radiotherapy for head and neck cancer have been poorly studied. This study aimed to determine long-term effects of radiotherapy on oral mucosa using exfoliative oral cytology. PATIENTS AND METHODS: Fifty patients with cancer were enrolled, five of whom in order to validate microscopic analysis. Smears were collected at programmed visit; a score was used to rank possible cytological alterations. Presence of inflammation was also microscopically described and compared to blood count tests. RESULTS: Epithelial cells revealed a peculiar 'folding' phenotype, not related to chemotherapy, total dose, or to the effective dose delivered to mucosa. Inflammation described was related to the score for 'folding' cells; moreover, score decreased in the presence of a higher lymphocyte count, while it was not altered by neutrophil count. CONCLUSION: We suggest application of exfoliative cytology to study radiation injury and the variability of individual response of oral mucosa to radiation.


Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Mucosa Bucal/patología , Mucosa Bucal/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Citodiagnóstico/métodos , Humanos , Persona de Mediana Edad , Cintigrafía , Coloración y Etiquetado/métodos
20.
Anticancer Res ; 32(7): 2755-8, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22753735

RESUMEN

Glioblastoma multiforme, the most common type of primary brain tumour, remains an unsolved clinical problem. A great deal of work has been done in an effort to understand the biology and genetics of glioblastoma multiforme, but clinically effective treatments remain elusive. It is well known that malignant gliomas develop resistance to chemo- and radiotherapy. In this review we evaluated the literature data regarding therapeutic progress for the treatment of astrocytic tumours, focusing our attention on new frontiers for glioblastoma. The research studies performed in in vitro and in vivo models show that the application of hyperthermia using magnetic nanoparticles is safe and could be a promising tool in the treatment of glioblastoma patients. Our efforts are focused towards new fields of research, for example nanomedicine and the study of the uptake and cytotoxic effects of magnetic nanoparticles. The improvement of the quality of life of patients, by increasing their survival rate is the best result to be pursued, since these tumours are considered as ineradicable.


Asunto(s)
Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Astrocitoma/patología , Neoplasias Encefálicas/patología , Glioblastoma/patología , Humanos , Hipertermia Inducida/métodos , Magnetismo/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico
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