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1.
BMC Genomics ; 25(1): 717, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049022

RESUMO

BACKGROUND: In bivalves, the rate at which organisms grow is a major functional trait underlying many aspects of their commercial production. Growth is a highly polygenic trait, which is typically regulated by many genes with small to moderate effects. Due to its complexity, growth variability in such shellfish remains poorly understood. In this study, we aimed to investigate differential gene expression among spat of the pearl oyster Pinctada margaritifera with distinct growth phenotypes. RESULTS: We selected two groups of P. margaritifera spat belonging to the same F2 cohort based on their growth performance at 5.5 months old. Transcriptome profile analysis identified a total of 394 differentially expressed genes between these Fast-growing (F) and Slow-growing (S) phenotypes. According to functional enrichment analysis, S oysters overexpressed genes associated with stress-pathways and regulation of innate immune responses. In contrast, F oysters up-regulated genes associated with cytoskeleton activity, cell proliferation, and apoptosis. Analysis of genome polymorphism identified 16 single nucleotide polymorphisms (SNPs) significantly associated with the growth phenotypes. SNP effect categorization revealed one SNP identified for high effect and annotated for a stop codon gained mutation. Interestingly, this SNP is located within a gene annotated for scavenger receptor class F member 1 (SRF1), which is known to modulate apoptosis. Our analyses also revealed that all F oysters showed up-regulation for this gene and were homozygous for the stop-codon mutation. Conversely, S oysters had a heterozygous genotype and a reduced expression of this gene. CONCLUSIONS: Altogether, our findings suggest that differences in growth among the same oyster cohort may be explained by contrasted metabolic allocation between regulatory pathways for growth and the immune system. This study provides a valuable contribution towards our understanding of the molecular components associated with growth performance in the pearl oyster P. margaritifera and bivalves in general.


Assuntos
Perfilação da Expressão Gênica , Pinctada , Polimorfismo de Nucleotídeo Único , Animais , Pinctada/genética , Pinctada/crescimento & desenvolvimento , Transcriptoma , Fenótipo
2.
J Exp Zool B Mol Dev Evol ; 342(2): 76-84, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38318922

RESUMO

Early development stages in marine bivalve are critical periods where larvae transition from pelagic free-life to sessile mature individuals. The successive metamorphosis requires the expression of key genes, the functions of which might be under high selective pressure, hence understanding larval development represents key knowledge for both fundamental and applied research. Phenotypic larvae development is well known, but the underlying molecular mechanisms such as associated gene expression dynamic and molecular cross-talks remains poorly described for several nonmodel species, such as P. margaritifera. We designed a whole transcriptome RNA-sequencing analysis to describe such gene expression dynamics following four larval developmental stages:  d-shape, Veliger, Umbo and Eye-spot. Larval gene expression and annotated functions drastically diverge. Metabolic function (gene expression related to lipid, amino acid and carbohydrate use) is highly upregulated in the first development stages, with increasing demand from  d-shape to umbo. Morphogenesis and larval transition are partly ordered by Thyroid hormones and Wnt signaling. While larvae shells show some similar characteristic to adult shells, the cause of initialization of biomineralization differ from the one found in adults. The present study provides a global overview of Pinctada margaritifera larval stages transitioning through gene expression dynamics, molecular mechanisms and ontogeny of biomineralization, immune system, and sensory perception processes.


Assuntos
Pinctada , Humanos , Animais , Pinctada/genética , Pinctada/metabolismo , Larva/genética , Transcriptoma
3.
BMC Genomics ; 20(1): 111, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30727965

RESUMO

BACKGROUND: Cultured pearls are unique gems produced by living organisms, mainly molluscs of the Pinctada genus, through the biomineralization properties of pearl sac tissue. Improvement of P. margaritifera pearl quality is one of the biggest challenges that Polynesian research has faced to date. To achieve this goal, a better understanding of the complex mechanisms related to nacre and pearl formation is essential and can now be approached through the use of massive parallel sequencing technologies. The aim of this study was to use RNA-seq to compare whole transcriptome expression of pearl sacs that had producing pearls with high and low quality. For this purpose, a comprehensive reference transcriptome of P. margaritifera was built based on multi-tissue sampling (mantle, gonad, whole animal), including different living stages (juvenile, adults) and phenotypes (colour morphotypes, sex). RESULTS: Strikingly, few genes were found to be up-regulated for high quality pearls (n = 16) compared to the up-regulated genes in low quality pearls (n = 246). Biomineralization genes up-regulated in low quality pearls were specific to prismatic and prism-nacre layers. Alternative splicing was further identified in several key biomineralization genes based on a recent P. margaritifera draft genome. CONCLUSION: This study lifts the veil on the multi-level regulation of biomineralization genes associated with pearl quality determination.


Assuntos
Biomineralização/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Pinctada/metabolismo , Animais , Feminino , Masculino , Pinctada/genética , Pinctada/fisiologia , Análise de Sequência de RNA
4.
Int J Cancer ; 138(6): 1538-44, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26501997

RESUMO

We report on a phase II clinical trial to determine the effect of a concurrent ultra-fractionated radiotherapy and temozolomide treatment in inoperable glioblastoma patients. A phase II study opened; patients over 18 years of age who were able to give informed consent and had histologically proven, newly diagnosed inoperable diagnosed and supratentorial glioblastoma were eligible. Three doses of 0.75 Gy spaced apart by at least 4 hr were delivered daily, 5 days a week for six consecutive weeks for a total of 67.5 Gy. Chemotherapy was administered during the same period, which consisted of temozolomide given at a dose of 75 mg/m(2) for 7 days a week. After a 4-week break, chemotherapy was resumed for up to six cycles of adjuvant temozolomide treatment, given every 28 days, according to the standard 5-day regimen. Tolerance and toxicity were the primary endpoints; survival and progression-free survival were the secondary endpoints. In total, 40 patients were enrolled in this study, 29 men and 11 women. The median age was 58 years, and the median Karnofsky performance status was 80. The concomitant ultra-fractionated radiotherapy and temozolomide treatment was well tolerated. Complete responses were seen in four patients, and partial responses were reported in seven patients. The median survival from the initial diagnosis was 16 months. Several long-term survivors were noted. Concurrent ultra-fractionated radiation therapy and temozolomide treatment are well accepted by the patients. The results showed encouraging survival rates for these unfavorable patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Dacarbazina/análogos & derivados , Glioblastoma/patologia , Glioblastoma/terapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Feminino , França , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Temozolomida , Resultado do Tratamento , Carga Tumoral , Proteínas Supressoras de Tumor/genética
5.
ESMO Open ; 8(5): 101626, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37713930

RESUMO

BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.


Assuntos
Glioblastoma , Humanos , Glioblastoma/cirurgia , Glioblastoma/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Biomarcadores
6.
Eur J Cancer ; 109: 129-136, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30716716

RESUMO

BACKGROUND: Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. PATIENTS AND METHODS: Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. RESULTS: Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. CONCLUSIONS: Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/mortalidade , Edema/prevenção & controle , Glioblastoma/terapia , Losartan/uso terapêutico , Prednisona/administração & dosagem , Idoso , Anti-Inflamatórios/administração & dosagem , Neoplasias Encefálicas/patologia , Método Duplo-Cego , Quimioterapia Combinada , Edema/epidemiologia , Feminino , Seguimentos , França/epidemiologia , Glioblastoma/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
7.
Anim Genet ; 39(6): 662-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18717666

RESUMO

To examine further a previously reported association between amylase gene polymorphism and growth in the Pacific oyster Crassostrea gigas, ecophysiological parameters and biochemical and molecular expression levels of alpha-amylase were studied in Pacific oysters of different amylase genotypes. Genotypes that previously displayed significantly different growth were found to be significantly different for ingestion and absorption efficiency. These estimated parameters, used in a dynamic energy budget model, showed that observed ingestion rates (unlike absorption efficiencies) allowed an accurate prediction of growth potential in these genotypes. The observed association between growth and amylase gene polymorphism is therefore more likely to be related to ingestion than to absorption efficiency. Additionally, relative mRNA levels of the two amylase cDNAs were also strongly associated with amylase gene polymorphism, possibly reflecting variation in an undefined regulatory region, although no corresponding variation was observed in specific amylase activity. Amylase gene sequences were determined for each genotype, showing the existence of only synonymous or functionally equivalent non-synonymous polymorphisms. The observed associations among growth, food consumption-related traits and amylase gene polymorphism are therefore more likely to be related to variation in the level of amylase gene expression than to functional enzymatic variants.


Assuntos
Amilases/genética , Comportamento Alimentar , Ostreidae/genética , Polimorfismo Genético , Amilases/metabolismo , Animais , Sequência de Bases , Primers do DNA , Cinética , Ostreidae/enzimologia , Ostreidae/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
8.
Aquat Toxicol ; 199: 188-198, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29653309

RESUMO

Blooms of the dinoflagellate Alexandrium spp., known as producers of paralytic shellfish toxins (PSTs), are regularly detected on the French coastline. PSTs accumulate into harvested shellfish species, such as the Pacific oyster Crassostrea gigas, and can cause strong disorders to consumers at high doses. The impacts of Alexandrium minutum on C. gigas have often been attributed to its production of PSTs without testing separately the effects of the bioactive extracellular compounds (BECs) with allelopathic, hemolytic, cytotoxic or ichthyotoxic properties, which can also be produced by these algae. The BECs, still uncharacterized, are excreted within the environment thereby impacting not only phytoplankton, zooplankton but also marine invertebrates and fishes, without implicating any PST. The aim of this work was to compare the effects of three strains of A. minutum producing either only PSTs, only BECs, or both PSTs and BECs, on the oyster C. gigas. Behavioral and physiological responses of oysters exposed during 4 days were monitored and showed contrasted behavioral and physiological responses in oysters supposedly depending on produced bioactive substances. The non-PST extracellular-compound-producing strain primarily strongly modified valve-activity behavior of C. gigas and induced hemocyte mobilization within the gills, whereas the PST-producing strain caused inflammatory responses within the digestive gland and disrupted the daily biological rhythm of valve activity behavior. BECs may therefore have a significant harmful effect on the gills, which is one of the first organ in contact with the extracellular substances released in the water by A. minutum. Conversely, the PSTs impact the digestive gland, where they are released and mainly accumulated, after degradation of algal cells during digestion process of bivalves. This study provides a better understanding of the toxicity of A. minutum on oyster and highlights the significant role of BECs in this toxicity calling for further chemical characterization of these substances.


Assuntos
Crassostrea/efeitos dos fármacos , Dinoflagellida/metabolismo , Espaço Extracelular/química , Toxinas Marinhas/toxicidade , Estruturas Animais/efeitos dos fármacos , Estruturas Animais/metabolismo , Animais , Ritmo Circadiano/efeitos dos fármacos , Crassostrea/metabolismo , Citometria de Fluxo , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/patologia , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Hemolinfa/metabolismo , Paralisia/sangue , Paralisia/induzido quimicamente , Poluentes Químicos da Água/toxicidade
9.
Ann Dermatol Venereol ; 134(6-7): 535-40, 2007.
Artigo em Francês | MEDLINE | ID: mdl-17657179

RESUMO

BACKGROUND: We examined whether serum values for proteins S100B and MIA could allow early and reliable screening of metastatic growth in melanoma. PATIENTS AND METHODS: We carried out a prospective study from 1998 to 2005 in patients presenting non-metastatic melanomas with a Breslow score>0.75 mm. Four PS00B and MIA measurements per patient were performed at regular intervals over 1 to 2 years. Blood samples were analysed for PS100B and MIA using an ELISA technique. RESULTS: Fifty patients were analysed. The maximum interval between collection of samples was 8 months. Metastatic development was noted in 15 patients. Where melanoma progressed to stage III, sensitivity was 33% for PS100B and 25% for MIA. Where it progressed to stage IV, sensitivity was 50% for PS100B and 30% for MIA. A rise in these values preceded discovery of metastasis in 3 cases for PS100B and of MIA in 1 case. Specificity of the assays was 100% for PS100B and 91% for MIA. DISCUSSION: Sensitivity and specificity were better for PS100B than for MIA regarding detection of metastasis during follow-up of thick melanomas. The ELISA technique used in our study seemed to increase the specificity of the assay but not its sensitivity compared to other techniques used previously. We may thus confirm the benefits of PS100B assay for early detection of metastasis in melanomas. However, this laboratory surveillance method is not an acceptable substitute for regular clinical follow-up due to its low sensitivity.


Assuntos
Biomarcadores Tumorais/sangue , Proteínas da Matriz Extracelular/sangue , Melanoma/sangue , Melanoma/secundário , Proteínas de Neoplasias/sangue , Proteínas S100/sangue , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/diagnóstico
10.
J Clin Oncol ; 19(11): 2778-87, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387348

RESUMO

PURPOSE: To assess the prognostic value of thymidine kinase (TK), an enzyme involved in the DNA synthesis salvage pathway, relative to other prognostic factors in primary breast cancer. PATIENTS AND METHODS: This retrospective study involved 1,692 patients with operable breast cancer treated in six institutions (median follow-up, 82 months). Among the 857 node-negative patients, 135 received adjuvant chemotherapy (fluorouracil, doxorubicin, cyclophosphamide [FAC] or fluorouracil, etoposide, and cisplatin [FEC]). TK was assayed in cytosol with a quantitative radioenzymatic technique. Disease-specific survival (DSS), local recurrence-free interval (LRI), and distant-relapse-free interval (DRI) were investigated. RESULTS: High TK levels were associated with large tumor size, high histologic grade, and steroid hormone receptor negativity. Univariate analysis of the entire data set showed that high TK levels were related to shorter DSS (P < 10(-5)), LRI (P < 10(-3)), and DRI (P < 10(-5)). In time-dependent Cox models, high TK levels remained an independent predictor of the three outcomes, both in the overall population and in node-negative patients, although its prognostic value decreased over time. In node-negative patients, the introduction of an interaction term in multivariate analysis suggested that chemotherapy was more efficacious for patients who had tumors with high TK contents. In node-positive patients, high TK levels were related only to an increased risk of LRI. CONCLUSION: High TK values are an important risk factor in node-negative patients and seem to be associated with a beneficial effect of adjuvant FAC or FEC in patients who received adjuvant chemotherapy. The rationale of chemotherapy for patients with slowly proliferating tumors has to be discussed from a risk-benefit point of view.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Timidina Quinase/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Ciclofosfamida/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
11.
Int J Oncol ; 11(3): 617-21, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21528255

RESUMO

Immunoassay of serum anti-p53 antibodies was performed in a series of 63 patients with squamous cell carcinoma of the esophagus. p53 alterations were also analyzed with DGGE to detect gene mutations (n=53) and by immunohistochemistry to assess overexpression of p53 (n=43). An immune response was observed in 16 sera (25%). The corresponding biopsies all had a p53 gene mutation or overexpression of protein p53. We were unable to demonstrate any significant relationship between habitual tumor parameters (localization, cell differentiation, TNM stage) and development of p53 alterations. However, none of the patients with a localized tumor developed an immune response, while some of them had a muted gene or overexpressed p53.

12.
Oncol Rep ; 5(6): 1561-5, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9769406

RESUMO

The tumor markers Cyfra 21-1, TPA and SCC were assayed in a series of 96 patients with squamous cell carcinoma of the esophagus. Sensitivity was 42% for Cyfra 21-1, 40% for TPA and 37% for SCC. Combining Cyfra 21-1 and SCC gave a 56% sensitivity and combining TPA and SCC a 58% sensitivity. Sensitivity varied with disease stage and was particularly good in stage IV disease. Tumor markers did not vary with tumor differentiation. SCC levels were higher in tumors in the upper third of the esophagus. Pre-treatment levels of Cyfra 21-1 correlated with histological response. Cyfra 21-1 was also the only marker which distinguished significantly different survival curves. In multivariate analysis, however, treatment was the only independent factor predictive of survival.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Serpinas , Antígeno Polipeptídico Tecidual/sangue , Análise de Variância , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Queratina-19 , Queratinas , Masculino , Análise Multivariada , Estadiamento de Neoplasias
13.
Anticancer Res ; 17(1A): 387-91, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9066682

RESUMO

The genes MAGE-1, -2, -3 and -4 are expressed in tumors of different histological types, but not in normal tissues, with the exception of testis and placenta. Short peptides derived from MAGE-1 and MAGE-3 gene products are recognized by cytolytic T lymphocytes when presented by HLA-class-I molecules, and represent potential targets for specific immunotherapy. We have determined whether esophageal carcinoma patients should be eligible for MAGE-peptide-based vaccine therapies. The expression of genes MAGE-1, -2, -3 and -4 in tumor samples was assessed by reverse-transcription and polymerase-chain-reaction amplification. Out of the 49 esophageal squa-mous-cell carcinomas studied, 53% expressed MAGE-1, 49% MAGE-2, 47% MAGE-3 and 71% MAGE-4. Eighty-four percent of the tumors expressed one or more of the four MAGE genes. Owing to the high incidence of MAGE gene expression in esophageal squamous-cell carcinoma, a large proportion of patients could be suitable candidates for immune therapies involving tumor-specific antigens encoded by MAGE genes.


Assuntos
Antígenos de Neoplasias/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Células Tumorais Cultivadas
14.
Anticancer Res ; 15(6B): 2857-63, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8669879

RESUMO

A sensitive and relatively specific tumoral marker for lung epidermoid carcinomas could be used to identify patients likely to benefit from new therapeutic protocols. The cyfra 21-1 fragment of cytokeratin 19 has raised much hope in this regard amongst both technologists and clinicians. In a study of 195 subjects, we have shown by means of a serum assay that the usual cut-off value for this marker (3.3 ng/ml) can be lowered to 1.5 ng/ml without loss of specificity, and with an increase in sensitivity. There was a good correlation between serum marker level and tumor extension, but though cyfra 21-1 was not predictive of the suitability of a patient for surgery. A decrease of cyfra-21-1 was observed after complete resection of the tumor. There was no relation between serum assay results and immunohistochemical findings.


Assuntos
Biomarcadores Tumorais/análise , Queratinas/análise , Neoplasias Pulmonares/química , Proteínas de Neoplasias/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/química , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Técnicas Imunoenzimáticas , Queratinas/sangue , Pneumopatias/sangue , Pneumopatias/complicações , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Necrose , Proteínas de Neoplasias/sangue , Estadiamento de Neoplasias , Período Pós-Operatório , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tuberculose/sangue
15.
Panminerva Med ; 38(3): 133-8, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9009675

RESUMO

Liver cell necrosis was induced in rats by a galactosamine injection. Cell death was due to an increase of Ca++ intracellular levels and was also under the control of genes. Rats were then either exposed or not to a 6 mT 100 HZ pulsed magnetic field (PMF) and they either received or not methylsilane-triol injections. Animals were sacrificed twenty-seven hours after a galactosamine injection. On the one hand it appeared from transaminase levels that the PMF increased the number of animals which were sensitized to galactosamine but decreased transaminase levels. On the other hand PMF decreased the protective effect of MST against galactosamine. We may suggest that PMF should be considered as an additional cellular signal received through genes which would determine the evolution towards or against apoptosis according to the age of the cell itself but also the Ca++ intracellular level.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Galactosamina/toxicidade , Magnetismo , Compostos de Organossilício/farmacologia , Salicilatos/farmacologia , Animais , Masculino , Ratos , Ratos Wistar
16.
Bull Cancer ; 84(11): 1047-52, 1997 Nov.
Artigo em Francês | MEDLINE | ID: mdl-9536986

RESUMO

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal model of brain tumor which was obtained by injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV beta gal resulted in the expression of the marker gene in 61% of the animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in 50% of the rats treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6, the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.


Assuntos
Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioblastoma/terapia , Simplexvirus/genética , Adenoviridae/genética , Animais , Antivirais/administração & dosagem , Neoplasias Encefálicas/patologia , Modelos Animais de Doenças , Ganciclovir/administração & dosagem , Técnicas de Transferência de Genes , Vetores Genéticos , Glioblastoma/patologia , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Simplexvirus/enzimologia , Timidina Quinase/genética , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
17.
Bull Cancer ; 88(12): 1177-206, 2001 Dec.
Artigo em Francês | MEDLINE | ID: mdl-11792611

RESUMO

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers. RESULTS: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/normas , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/diagnóstico , França , Humanos , Ácido N-Acetilneuramínico/sangue , Prognóstico , Sensibilidade e Especificidade
18.
Z Naturforsch C J Biosci ; 51(7-8): 603-6, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8810100

RESUMO

In a previous work a decrease in cholesterol and triglyceride plasma levels was observed in rats 24 hours after their exposure to a 12 Hz 6 mT pulsed magnetic field (PMF). This time, a study of intensity effects of a 12 Hz PMF for a sixty-minute exposure and of length of exposure for a 12 Hz 6 mT PMF took place. Non-linear effect-dose relationships were observed for the PMF intensity as well as for the length of exposure used. The highest decreases in cholesterol and triglyceride levels were obtained after to a sixty-minute exposure with 1.5 mT and 12 mT.


Assuntos
Colesterol/sangue , Magnetismo , Triglicerídeos/sangue , Animais , Peso Corporal , Relação Dose-Resposta à Radiação , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
19.
Ann Dermatol Venereol ; 127(1): 56-9, 2000 Jan.
Artigo em Francês | MEDLINE | ID: mdl-10717564

RESUMO

OBJECTIVE: We searched for a correlation between serum S100B protein and cutaneous malignant melanoma stage, according to the American Joint Committee on Cancer staging system, and between elevation of serum S100B protein and development of metastasis. PATIENTS AND METHODS: We conducted a prospective bicentric study for 20 months in 122 patients with malignant melanoma. LIA-mat(R) assay was used to determine serum S100B at each examination. The optimal cut-off value was determined from the ROC curve. RESULTS: The optimal cut-off value to discriminate patients with metastases from patients in remission was 0.09 microg/l. Sensitivity was 46 p. 100 in patients with stage III and 86 p. 100 in patients with stage IV disease. The positive predictive value for stage III/IV was 77 p. 100 and the negative predictive value was 89 p. 100. Serial measurements were made in 56 patients. The serum S100B protein level was elevated in 69 p. 100 of the patients disclosing disease progression (9/13). In 44 p. 100 of the patients (4/9), serum S100B protein level rose within a delay of 3 months before new metastases were detected. DISCUSSION: Our study confirms that serum S100B protein is a tumor marker for melanoma staging and follow-up. A rise in S100B protein precedes or reveals metastasis.


Assuntos
Biomarcadores Tumorais , Proteínas de Ligação ao Cálcio/sangue , Melanoma/sangue , Melanoma/patologia , Fatores de Crescimento Neural/sangue , Proteínas S100 , Neoplasias Cutâneas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Subunidade beta da Proteína Ligante de Cálcio S100 , Neoplasias Cutâneas/patologia , Fatores de Tempo
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