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1.
Abdom Radiol (NY) ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38831072

RESUMEN

Colorectal cancer (CRC) is a significant global health concern. Prognostication of CRC traditionally relies on the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications, yet clinical outcomes often vary independently of stage. Despite similarities, rectal and colon cancers are distinct in their diagnostic methodologies and treatments, with MRI and CT scans primarily used for staging rectal and colon cancers, respectively. This paper examines the challenges in accurately assessing prognostic factors of colon cancer such as primary tumor extramural extension, retroperitoneal surgical margin (RSM) involvement, extramural vessel invasion (EMVI), and lymph node metastases through preoperative CT and MRI. It highlights the importance of these factors in risk stratification, treatment decisions, and surgical planning for colon cancer patients. Advancements in imaging techniques are crucial for improving clinical management and optimizing patient outcomes, underscoring the necessity for ongoing research to refine diagnostic methods and incorporate novel findings into practice.

2.
G Chir ; 40(1): 20-25, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30771794

RESUMEN

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.


Asunto(s)
Fuga Anastomótica/diagnóstico , Proteína C-Reactiva/análisis , Colon/cirugía , Polipéptido alfa Relacionado con Calcitonina/sangre , Recto/cirugía , Fuga Anastomótica/sangre , Biomarcadores/sangre , Diagnóstico Precoz , Procedimientos Quirúrgicos Electivos/efectos adversos , Humanos , Recuento de Leucocitos , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Factores de Riesgo , Tamaño de la Muestra , Dehiscencia de la Herida Operatoria/complicaciones
3.
Bioresour Technol ; 219: 37-44, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27475329

RESUMEN

This paper focuses on the long term operation and testing of three Microbial Fuel Cells (MFC) having three different anode materials: commercial carbon felt (C-FELT), polyaniline-deposited carbon felt (C-PANI) and carbon-coated Berl saddles (C-SADDLES). A mixed consortium from seawater was used as inoculum and acetate was used as substrate. Tests were conducted for four months under 1000Ω external load. The maximum power generation was obtained by C-SADDLES (102mWm(-2)) followed by C-FELT and C-PANI, respectively. A similar trend was obtained with the evaluation of electrical energy produced: C-SADDLES (2222J), C-PANI (2183J) and C-FELT (2114J). However, the performance of C-PANI decreased over time, most evidently due to degradation or deactivation of deposited polyaniline by the microorganisms' activity. These results provide evidence that the three-dimensional structure, C-SADDLES, offers excellent biocompatibility, high specific surface area, high conductivity and most importantly these properties are maintained for a long period of time.


Asunto(s)
Compuestos de Anilina/química , Fuentes de Energía Bioeléctrica , Carbono/química , Fibra de Carbono , Electricidad , Electrodos , Soluciones , Factores de Tiempo
4.
Ann Oncol ; 26(6): 1248-1253, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25743855

RESUMEN

BACKGROUND: A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis. PATIENTS AND METHODS: A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy. RESULTS: Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments. CONCLUSIONS: In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity. CLINICALTRIALSGOV NUMBER: NCT00869310.


Asunto(s)
Antieméticos/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Dexametasona/administración & dosificación , Metoclopramida/administración & dosificación , Morfolinas/administración & dosificación , Náusea/prevención & control , Vómitos/prevención & control , Actividades Cotidianas , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Anciano , Antieméticos/efectos adversos , Aprepitant , Dexametasona/efectos adversos , Método Doble Ciego , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Isoquinolinas/administración & dosificación , Italia , Masculino , Persona de Mediana Edad , Morfolinas/efectos adversos , Náusea/inducido químicamente , Náusea/psicología , Palonosetrón , Calidad de Vida , Quinuclidinas/administración & dosificación , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Vómitos/inducido químicamente , Vómitos/psicología , Adulto Joven
5.
Leukemia ; 29(6): 1390-401, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25533804

RESUMEN

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.


Asunto(s)
Resistencia a Antineoplásicos , Linfoma Anaplásico de Células Grandes/genética , FN-kappa B/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Factor 1 Asociado a Receptor de TNF/genética , Translocación Genética/genética , Quinasa de Linfoma Anaplásico , Animales , Western Blotting , Citometría de Flujo , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoprecipitación , Hibridación Fluorescente in Situ , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/mortalidad , Ratones , Ratones Endogámicos NOD , FN-kappa B/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Inhibidores de Proteasoma/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Factor 1 Asociado a Receptor de TNF/metabolismo , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Mol Psychiatry ; 20(2): 263-74, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24514566

RESUMEN

Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.


Asunto(s)
Encéfalo/anatomía & histología , Cognición/fisiología , Inteligencia/fisiología , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Animales , Células Cultivadas , Femenino , Estudios de Asociación Genética , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Metaanálisis como Asunto , Ratones , Ratones Transgénicos , Análisis por Micromatrices , Células-Madre Neurales/fisiología , Pruebas Neuropsicológicas
7.
Oncogenesis ; 2: e43, 2013 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-23567620

RESUMEN

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays 'ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted 'patient-specific' therapies.

8.
Water Sci Technol ; 58(8): 1623-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19001717

RESUMEN

The present study is aimed to test the effectiveness and the reproducibility of the acid pre-treatment of sewage sludge to suppress the methanogenic bacteria activity, in order to increase the hydrogen forming bacteria activity, mainly Clostridium species. The treated sludge has been tested on glucose reach medium under mesophilic conditions (35 degrees C), in batch mode to quantify the biological fermentative hydrogen production. In the whole series of experiments, the main components of biogas are hydrogen (52-60%) and carbon dioxide (40-48%); no methane and hydrogen sulphide were present in it. The rate of biogas production reached a maximum of 75 ml/lh. An overall mean hydrogen conversion efficiency was 11.20% on the assumption of maximum of 3 mol H2/mol glucose. Clostridium spp. multiplied ten times after 10 h of fermentation and over that thousand times at the end of fermentation.


Asunto(s)
Anaerobiosis , Clostridium/metabolismo , Hidrógeno/metabolismo , Aguas del Alcantarillado/microbiología , Clostridium/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Cinética , Modelos Biológicos , Oxidación-Reducción , Reproducibilidad de los Resultados
9.
Gen Comp Endocrinol ; 158(1): 138-44, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18602103

RESUMEN

There is much concern about the increasing presence in the environment of synthetic chemicals that are able to disrupt the endocrine system. Among these compounds, 4-nonylphenol (4-NP) is one of the most studied xenoestrogens, due to its widespread accumulation in water sediment and consequent presence in fatty acid of aquatic organisms. Here, we have used a zebrafish microarray representing 16,399 genes to study the effects of 4-NP and estradiol-17beta (E2) in adult male zebrafish in order to elucidate the mechanism of action of 4-NP compared with that of E2. The microarray results showed that both 4-NP and E2 induced a strong expression of vitellogenin (VTG), the sex related precursor of the yolk proteins in oviparous vertebrates. Both treatments induced elevated protein turnover upregulating genes involved in proteolysis and those that are constituents of the ribosome. Many genes regulated by 4-NP and E2 are involved in energy metabolism, oxidative stress defense mechanisms, xenobiotic metabolism, and lipid metabolism. A different pattern of expression in the two treatments was found for genes involved in oxidative stress, since E2 seems to induce the mechanism of detoxification, while 4-NP seems to inhibit this protective mechanism of the cell. Overall, these findings demonstrate that the microarray approach can contribute significantly to the understanding of expression patterns induced by E2 and 4-NP in male zebrafish. The results also demonstrate that 4-NP is able to act through an alternative pattern to that of estradiol-17beta, modulating the expression of the same genes in a different manner.


Asunto(s)
Estradiol/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Fenoles/farmacología , Pez Cebra/genética , Animales , Disruptores Endocrinos/farmacología , Perfilación de la Expresión Génica , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Contaminantes Químicos del Agua/farmacología
10.
Mol Cell Endocrinol ; 286(1-2 Suppl 1): S52-9, 2008 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-18336994

RESUMEN

Endogenous cannabinoids, through the CB1 receptor, are involved in the control of several functions including stress responses. The aim of this study was to investigate the presence of cannabinoid receptor CB1 in the sole ovary by partial cloning of brain CB1 cDNA; in a stress paradigm of disturbance by handling, which consisted in catching, netting and hand-sorting, changes of CB1 mRNA were related with those of proopiomelanocortin (POMC) mRNA; the trend and timing of stress responses and adaptation were monitored by measuring plasma cortisol levels. We characterized two forms of CB1-like receptor, termed CB1A and CB1B. The two sole CB1 (both 799bp) share 76% identity in their cDNAs, and the deduced amino acid sequences are 80% identical. The handling stress induced a sustained increase in plasma cortisol levels 1h after the handling began and decreased to low levels 12h after initiation of handling, showing the same trend of ovarian POMC mRNA expression. In addition, while CB1A mRNA did not show any significant changes during handling stress, significantly lower levels of CB1B mRNA were found in stressed fish 1h after the beginning of handling, with CB1 expression increased 24h after stress induction, both in the ovary and brain. It can be concluded that endocannabinoid system is involved in the modulation of adaptive responses to environmental conditions.


Asunto(s)
ADN Complementario/genética , Peces Planos/genética , Receptor Cannabinoide CB1/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Femenino , Regulación de la Expresión Génica , Hidrocortisona/sangre , Datos de Secuencia Molecular , Ovario/metabolismo , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Cannabinoide CB1/química , Receptor Cannabinoide CB1/metabolismo , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido
11.
Gen Comp Endocrinol ; 150(2): 263-9, 2007 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-17078952

RESUMEN

Two cannabinoid receptor-like genes (CB1-like), named CB1A and CB1B, have been isolated in teleost fish, specifically in the puffer fish, Fugu rubripes. However, information on the physiological roles, such as the control of reproduction and development in fish is still scarce. Therefore, the aim of the present study was to investigate the presence of CB1-like mRNA in the gonads of a marine teleost species, the gilthead seabream, Sparus aurata, a hermaphrodite species in which the gonadal tissues first develop as testes, and then as functional ovary. We isolated an 890 bp fragment (GenBank accession number ); that corresponded to the open reading frame of the teleost CB1 receptor gene, encoding for the central portion of the protein, which was aligned with the other bony fish sequence. Using "in situ" hybridization, CB1-like mRNA was localized in both mature and sex-reversing gonads, and relative changes in CB1-like expression levels were detected through semi-quantitative RT-PCR. In the mature testis and in the testicular part of the sex-reversing gonad, CB1 expression levels were found to be much higher compared to the ovarian portion. This suggests that the CB1 signaling is likely involved in the process of testicular regression of the S. aurata, but its actual role has yet to be determined.


Asunto(s)
Organismos Hermafroditas , Receptor Cannabinoide CB1/genética , Dorada/genética , Procesos de Determinación del Sexo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Femenino , Gónadas/fisiología , Hibridación in Situ , Masculino , Datos de Secuencia Molecular , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptor Cannabinoide CB1/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Dorada/metabolismo , Alineación de Secuencia
12.
J Hazard Mater ; 145(1-2): 296-304, 2007 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-17175099

RESUMEN

This paper is aimed to candidate the use of an ISO standard procedure (Guide to the Expression of Uncertainty in Measurement, GUM) for quantitative evaluation of uncertainty in Human Risk estimation under chronic exposure to a hazardous chemical compound. Risk was evaluated by using the usual methodologies: the deterministic reasonable maximum exposure (RME) and the statistical Monte Carlo method; in both cases the procedures to evaluate the uncertainty on risk values are detailed. The paper put in evidence that the procedure is able to single out the variables that contribute mostly to the uncertainty. The obtained results show that the application of GUM procedure is easy and straightforward to estimate the uncertainty value on the results of risk estimation. The procedure is applied to a real case concerning the ingestion of milk contaminated by dioxins in a northern part of Italy; the risk value resulted to be over the minimal threshold of 10(-6) with 20-80% confidence.


Asunto(s)
Sustancias Peligrosas/análisis , Sustancias Peligrosas/toxicidad , Modelos Teóricos , Incertidumbre , Animales , Dioxinas/análisis , Dioxinas/toxicidad , Humanos , Leche/química , Método de Montecarlo , Variaciones Dependientes del Observador , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos
13.
Mol Reprod Dev ; 73(1): 1-8, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16177984

RESUMEN

Proopiomelanocortin (POMC) is a precursor protein that contains the sequences of several bioactive peptides including adrenocorticotropin (ACTH), beta-endorphin (beta-EP), and melanocyte-stimulating-hormone (MSH). POMC is synthesized in the pituitary gland, brain, and many peripheral tissues. Immunoreactive POMC-derived peptides as well as POMC-like mRNA have been evidenced in several nonpituitary tissues, thus suggesting that POMC is actively synthesized by these tissues. The present study was aimed at evaluating if also in the case of stallion POMC-derived peptide, beta-EP, is produced locally in the testis, thus playing effects in a paracrine/autocrine fashion. To investigate this hypothesis the POMC gene expression was analyzed using 3' RACE-PCR and Northern Blot approaches in the testis and epididimys of stallion; moreover, immunocytochemical localization for beta-EP was also performed through confocal laser microscopy. The immunofluorescence results showed a positive beta-EP reaction not only in cellular nest of pituitary but also in the testis and genital tract of stallion, which function could be related with sperm mobility. Such role seem not to be no dependent on the peptide synthesized locally, because the molecular biology approach demonstrated the presence of POMC transcript in the pituitary only. In fact the Northern Blot analysis showed the presence of a single POMC transcript in the pituitary while no signal was detected in the testis and epididimys. The same results were obtained by applied 3' RACE-PCR analysis. In conclusion, opioid-derived peptide beta-EP is present in the genital tract of stallion, but is not locally produced as in other mammalian, and nonmammalian models; its possible biological function at testicular level could be linked to a long-loop feed-back mechanisms.


Asunto(s)
Epidídimo/metabolismo , Caballos/metabolismo , Hipófisis/metabolismo , Proopiomelanocortina/biosíntesis , Proopiomelanocortina/genética , Testículo/metabolismo , betaendorfina/metabolismo , Animales , Secuencia de Bases , Northern Blotting , Humanos , Masculino , Microscopía Confocal , Microscopía Fluorescente , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa
14.
Toxicol Appl Pharmacol ; 209(3): 236-43, 2005 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-15921715

RESUMEN

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17beta and different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP) on the expression of liver ERbeta-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17beta) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good "sentinel" species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10(-6) and 10(-7) M) of 4-nonylphenol (4-NP), or 10(-7) M of estradiol-17beta. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 degrees C; the gonads were fixed, then frozen and stored at -70 degrees C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 degrees C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17beta and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17beta plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERbeta-1 mRNA in the liver, demonstrating that both estradiol-17beta and 4-NP modulate the vitellogenin rate through interaction with the ERbeta-1 subtype. The present study also suggests that 4-NP at the concentration of 10(-6) M bioaccumulates in the liver.


Asunto(s)
Estradiol/farmacología , Receptor beta de Estrógeno/metabolismo , Fenoles/farmacología , Vitelogeninas/biosíntesis , Andrógenos/sangre , Animales , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Estradiol/farmacocinética , Receptor beta de Estrógeno/genética , Cromatografía de Gases y Espectrometría de Masas , Carpa Dorada , Hígado/efectos de los fármacos , Hígado/metabolismo , Fenoles/sangre , Fenoles/farmacocinética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Distribución Tisular , Vitelogeninas/sangre
15.
Ann Oncol ; 15(5): 721-5, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15111338

RESUMEN

BACKGROUND: It has been widely shown that the provision of adequate levels of information to patients does have a positive effect on quality of life by reducing anxiety and depression levels. The aim of this study was to show how Italian cancer patients rate the information they are given and whether the use of booklets and videotapes can improve their quality of life. PATIENTS AND METHODS: Cancer patients aged between 18 and 80 years who were about to receive their first chemotherapy course were randomized to fill in questionnaires on perceived quality of information, level of psychological distress, perceived severity and curability of the disease, and quality of life. The results were evaluated by means of statistical analyses. RESULTS: Out of 328 consecutive patients enrolled in 21 cancer centers, 86-93% considered the booklets either "very useful" or "useful". The videotape was regarded as "quite" or "much" more complete than the booklets (87%). According to 81%/87% of patients, the information that had been given had improved their knowledge of the disease/chemotherapy either "a lot" or "enough". CONCLUSIONS: The information patients receive from the oncologist was rated the highest, as long as they were devoted enough time. Booklets and videotapes can partially overcome the lack of oral information given by medical doctors. A better informed patient does help the oncologist save time.


Asunto(s)
Comunicación , Servicios de Información/normas , Neoplasias/psicología , Educación del Paciente como Asunto/normas , Calidad de Vida , Adulto , Anciano , Antineoplásicos/uso terapéutico , Ansiedad , Depresión , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Relaciones Médico-Paciente , Factores de Tiempo , Grabación en Video
16.
Curr Med Chem ; 11(6): 731-45, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15032727

RESUMEN

Among the known angiogenic growth factors and cytokines implicated in the modulation of normal and pathological angiogenesis, the VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D) and their corresponding receptor tyrosine kinases [VEGFR-1 (Flt-1), VEGFR-2 (Flk-1, KDR), and VEGFR-3 (Flt-4)] play a paramount and indispensable role in regulating the multiple facets of the angiogenic and lymphangiogenic processes, as well as the induction of vascular permeability and inflammation. The receptor VEGFR-2/KDR is the principal one through which VEGFs exert their mitogenic, chemotactic, and vascular permeabilizing effects on the host vasculature. Increased expression of VEGFs by tumor cells and VEGFR-2/KDR and VEGFR-1/Flt-1 by the tumor-associated vasculature are a hallmark of a variety of human and rodent tumors in vivo and correlates with tumor growth rate, micro-vessel density/proliferation, tumor metastatic potential, and poorer patient prognosis in a variety of malignancies. Approaches to disrupting the VEGF/VEGFR signaling cascade range from biological agents (soluble receptors, anti-VEGF and anti-VEGFR-2 antibodies, and VEGF transcription inhibitors) to small molecule ATP competitive VEGFR inhibitors. Examples from this latter class that are currently in clinical development include compounds from distinct chemical classes such as: indolin-2-ones, anilinoquinazolines, anilinophthalazines, isothiazoles, indolo- and indenocarbazoles. The structure activity relationships, biochemical and pharmacological profile of optimized representatives from each of these classes constitute the subject matter of this review.


Asunto(s)
Inhibidores de la Angiogénesis , Inhibidores Enzimáticos , Neoplasias/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Neoplasias/enzimología , Neoplasias/patología , Relación Estructura-Actividad
17.
Br J Dermatol ; 147(3): 481-6, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12207587

RESUMEN

BACKGROUND: In the last few years digital dermoscopy has been introduced as an additional tool to improve the clinical diagnosis of pigmented skin lesions. OBJECTIVE: To evaluate the validity of digital dermoscopy by comparing the diagnoses of a dermatologist experienced in dermoscopy (5 years of experience) with those of a clinician with minimal training in this field, and then comparing these results with those obtained using computer-aided diagnoses. METHODS: Three hundred and forty-one pigmented melanocytic and non-melanocytic skin lesions were included. All lesions were surgically excised and histopathologically examined. Digital dermoscopic images of all lesions were framed and analysed using software based on a trained artificial neural network. Cohen's kappa statistic was calculated to assess the validity with regard to the correct diagnoses of melanoma and non-melanoma. RESULTS: Sensitivity was high for the experienced dermatologist and the computer (92%) and lower for the inexperienced clinician (69%). Specificity of the diagnosis by the experienced dermatologist was higher (99%) than that of the inexperienced clinician (94%) and the computer assessment (74%). Notably, computer analysis gave a higher number of false positives (26%) compared with the experienced dermatologist (0.6%) and the inexperienced clinician (5.5%). CONCLUSIONS: Our results indicate that analysis either by a trained dermatologist or an artificial neural network-trained computer can improve the diagnostic accuracy of melanoma compared with that of an inexperienced clinician and that the computer diagnosis might represent a useful tool for the screening of melanoma, particularly at centres not experienced in dermoscopy.


Asunto(s)
Competencia Clínica , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Dermatología/educación , Diagnóstico por Computador , Diagnóstico Diferencial , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Microscopía por Video , Persona de Mediana Edad , Redes Neurales de la Computación , Nevo Pigmentado/diagnóstico , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
18.
Dig Dis Sci ; 45(3): 538-43, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10749330

RESUMEN

The CCK-A (cholecystokinin-A) receptor is selectively expressed by human pancreatic adenocarcinomas, suggesting a possible role in pancreatic tumorigenesis. In animals, pancreatic CCK receptor expression varies during ontogeny and neoplastic transformation. This study examined the temporal expression of CCK receptors in human fetal, postnatal, and adult pancreas to determine whether the appearance of CCK-A receptors in pancreatic adenocarcinomas reflected oncofetal antigen or pancreatic neoantigen expression. Messenger ribonucleic acid (mRNA) was isolated from six paraffin-embedded normal pancreatic autopsy specimens ranging in age from 17 weeks postfertilization through 26 days following full-term delivery, and samples of adult human tissues, including pancreas and pancreatic adenocarcinoma. Using reverse transcription-polymerase chain reactions, CCK-B receptor mRNA was expressed in all specimens of normal fetal and postnatal human pancreas, adult pancreas, and pancreatic adenocarcinomas. CCK-A receptor mRNA was selectively expressed only in pancreatic adenocarcinomas. These data suggest that selective CCK-A receptor expression in pancreatic adenocarcinomas reflects neoantigen expression in humans.


Asunto(s)
Adenocarcinoma/química , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/química , Receptores de Colecistoquinina/análisis , Adulto , Femenino , Feto , Humanos , Recién Nacido , Masculino , Páncreas/química , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Receptor de Colecistoquinina A , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/genética
19.
Biotechnol Prog ; 16(1): 44-51, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10662488

RESUMEN

The interactions between a strain of Saccharomyces cerevisiae and an alginate matrix are investigated to ascertain the main factors affecting the bioreaction evolution. During the tests several parameters (glucose, ethanol, calcium ion and biomass concentration, pH, and alginate bed diameter) were evaluated, coupled with microscopic investigation inside the beads to determine the spatial biomass distribution. A detailed analysis of macro parameters and a correlation among them are proposed using a fuzzy algorithm. A global two-step fuzzy model results in which biomass distribution inside the beads is represented as a hidden parameter.


Asunto(s)
Modelos Biológicos , Alginatos/metabolismo , Algoritmos , Biomasa , Biotecnología , Lógica Difusa , Cinética , Saccharomyces cerevisiae/metabolismo
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